61 results
361 WDR5 represents a therapeutically exploitable target for cancer stem cells in glioblastoma
- Part of
- Christopher Hubert, Kelly Mitchell, Samuel Sprowls, Sajina Shakya, Sonali Arora, Daniel J. Silver, Christopher M. Goins, Lisa Wallace, Gustavo Roversi, Rachel Schafer, Kristen Kay, Tyler E. Miller, Adam Lauko, John Bassett, Anjali Kashyap, J. D’Amato Kass, Erin E. Mulkearns-Hubert, Sadie Johnson, Joseph Alvarado, Jeremy N. Rich, Patrick J. Paddison, Anoop P. Patel, Shaun R. Stauffer, Christopher G. Hubert, Justin D. Lathia
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue s1 / April 2023
- Published online by Cambridge University Press:
- 24 April 2023, p. 107
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OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.
9 - Considerations for First-Generation Students in Graduate School
- from Part II - Beginning your Career
- Edited by Mitchell J. Prinstein, University of North Carolina, Chapel Hill
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- Book:
- The Portable Mentor
- Published online:
- 21 July 2022
- Print publication:
- 04 August 2022, pp 166-178
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Summary
Many graduate programs are sincerely invested in fostering diversity and increasing the number of students from underrepresented backgrounds who will contribute to our discipline.But increasing representation is only one step needed to address inequities, disparities, and injustices.Helping all students thrive, and have an equal opportunity to achieve their educational goals requires the creation of “safe spaces” in which demographic differences are understood, appreciated, and considered in larger educational systems.This chapter discusses a frequently overlooked identity characteristic that can significantly impact the graduate school experience:being a first-generation college student.
Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The Challenge of Managing Patients Suffering from TBI: The Utility of Multiparametric MRI
- John L. Sherman, Laurence J. Adams, Christen F. Kutz, Deborah York, Mitchell S. Szymczak
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- Journal:
- CNS Spectrums / Volume 26 / Issue 2 / April 2021
- Published online by Cambridge University Press:
- 10 May 2021, pp. 178-179
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Traumatic brain injury (TBI) is a complex phenomenon affecting multiple areas of the brain in multiple ways. Both right and left hemispheres are affected as well as supratentorial and infratentorial compartments. These multifocal injuries are caused by many factors including acute mechanical injury, focal intracranial hemorrhage, blunt and rotational forces, epidural and subdural hematoma, hypoxemia, hypotension, edema, axonal damage, neuronal death, gliosis and blood brain barrier disruption. Clinicians and patients benefit by precise information about the neuroanatomical areas that are affected macroscopically, microscopically and biochemically in an individual patient.
Standard imaging studies are frequently negative or grossly underestimate the severity of TBI and may exacerbate and prolong patient suffering with an imaging result of “no significant abnormality”. Specifically, sophisticated imaging tools have been developed which reveal significant damage to the brain structure including atrophy, MRI spectroscopy showing variations in neuronal metabolite N-acetyl-aspartate, elevations of membrane related Choline, and the glial metabolite myo-inositol is often observed to be increased post injury. In addition, susceptibility weighted imaging (SWI) has been shown to be more reliable for detecting microbleeds versus calcifications.
We have selected two TBI patients with diffuse traumatic brain injury.
The first patient is a 43-year-old male who suffered severe traumatic brain injury from a motorcycle accident in 2016. Following the accident, the patient was diagnosed with seizures, major depression, and intermittent explosive disorder. He has attempted suicide and has neurobehavioral disinhibition including severe anger, agitation and irritability. He denies psychiatric history prior to TBI and has negative family history. Following the TBI, he became physically aggressive and assaultive in public with minimal provocation. He denies symptoms of thought disorder and mania. He is negative for symptoms of cognitive decline or encephalopathy.
The second patient is a 49-year-old male who suffered at least 3 concussive blasts in the Army and a parachute injury. Following the last accident, the patient was diagnosed with major depressive disorder, panic disorder, PTSD and generalized anxiety disorder. He denies any psychiatric history prior to TBI including negative family history of psychiatric illness. In addition, he now suffers from nervousness, irritability, anger, emotional lability and concurrent concentration issues, problems completing tasks and alterations in memory.
Both patients underwent 1.5T multiparametric MRI using standard T2, FLAIR, DWI and T1 sequences, and specialized sequences including susceptibility weighted (SWAN/SWI), 3D FLAIR, single voxel MRI spectroscopy (MRS), diffusion tensor imaging (DTI), arterial spin labeling perfusion (ASL) and volumetric MRI (NeuroQuant). Importantly, this exam can be performed in 30–45 minutes and requires no injections other than gadolinium in some patients. We will discuss the insights derived from the MRI which detail the injured areas, validate the severity of the brain damage, and provide insight into the psychological, motivational and physical disabilities that afflict these patients. It is our expectation that this kind of imaging study will grow in value as we link specific patterns of injury to specific symptoms and syndromes resulting in more targeted therapies in the future.
A Multiparametric MRI Protocol for Evaluation of Cognitive Insufficiency, Dementia and Traumatic Brain Injury (TBI): A Case Series
- John L. Sherman, Christen F. Kutz, Mitchell S. Szymczak, Deborah York, Laurence J. Adams
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- Journal:
- CNS Spectrums / Volume 26 / Issue 2 / April 2021
- Published online by Cambridge University Press:
- 10 May 2021, p. 179
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Background
The purpose of this work was to determine the extent to which a multiparametric magnetic resonance imaging (MRI) approach to patients with dementia and/or traumatic brain injury (TBI) can help to determine the most likely diagnosis and the prognosis of these patients.
ObjectiveVolumetric brain MRI alone is recognized as a useful imaging tool to differentiate behavioral variant frontotemporal dementia (bvFTD) from the more common Alzheimer’s disease (AD). Our objective is to create a protocol that will provide additional non-standard, objective imaging data that can be utilized clinically to distinguish common and uncommon forms of dementia and TBI. As patients with these diseases are increasingly presenting to clinical practice, our ability to combine multiple parameters within the standard 30-minute or 45-minute (pre- and post-contrast) MRI exams has high potential to affect current and future clinical practice.
MethodsAll MRI studies were performed on 1.5 T MRI GE 450w or GE HDx imagers. All patients were seen clinically in outpatient practices. All techniques are FDA approved. The 30 minute protocol utilized T2w FSE 3 mm, 2.5 mm SWAN, 3D T1 sagittal 1.2 mm, DWI 5 mm, 3D FLAIR 1.2 mm, 2.5 mm SWAN (susceptibility sensitive), 3D T1 sagittal 1.2 mm, arterial spin labeling perfusion, posterior cingulate single voxel PRESS MR spectroscopy and NeuroQuant automated volumetric analysis and LesionQuant automated lesion detection and measurement. The 45-minute TBI protocol added diffusion tensor imaging, MR spectroscopy (MRS) of normal appearing frontal white matter and 3D gadolinium enhanced technique.
ResultsThe combination of multiparametric data together with standard imaging and clinical information allowed radiologic interpretation that was able to focus on 1–2 specific diagnoses and to indicate those patients in which a combination of pathologies was most likely. Neurologists, gerontologists, neuropsychologists and psychiatric specialists used these data and our summary conclusions to develop more specific diagnoses, treatments and prognoses.
ConclusionsReadily available MRI techniques can be added to standard imaging to markedly improve the usefulness of the radiologic opinion in cases of subjective cognitive insufficiency, clinical mild cognitive insufficiency, behavioral pathologies, dementia and post-traumatic brain syndromes.
The impact of tandem redundant/sky-based calibration in MWA Phase II data analysis
- Part of
- Zheng Zhang, Jonathan C. Pober, Wenyang Li, Bryna J. Hazelton, Miguel F. Morales, Cathryn M. Trott, Christopher H. Jordan, Ronniy C. Joseph, Adam Beardsley, Nichole Barry, Ruby Byrne, Steven J. Tingay, Aman Chokshi, Kenji Hasegawa, Daniel C. Jacobs, Adam Lanman, Jack L. B. Line, Christene Lynch, Benjamin McKinley, Daniel A. Mitchell, Steven Murray, Bart Pindor, Mahsa Rahimi, Keitaro Takahashi, Randall B. Wayth, Rachel L. Webster, Michael Wilensky, Shintaro Yoshiura, Qian Zheng
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 37 / 2020
- Published online by Cambridge University Press:
- 04 November 2020, e045
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Precise instrumental calibration is of crucial importance to 21-cm cosmology experiments. The Murchison Widefield Array’s (MWA) Phase II compact configuration offers us opportunities for both redundant calibration and sky-based calibration algorithms; using the two in tandem is a potential approach to mitigate calibration errors caused by inaccurate sky models. The MWA Epoch of Reionization (EoR) experiment targets three patches of the sky (dubbed EoR0, EoR1, and EoR2) with deep observations. Previous work in Li et al. (2018) and (2019) studied the effect of tandem calibration on the EoR0 field and found that it yielded no significant improvement in the power spectrum (PS) over sky-based calibration alone. In this work, we apply similar techniques to the EoR1 field and find a distinct result: the improvements in the PS from tandem calibration are significant. To understand this result, we analyse both the calibration solutions themselves and the effects on the PS over three nights of EoR1 observations. We conclude that the presence of the bright radio galaxy Fornax A in EoR1 degrades the performance of sky-based calibration, which in turn enables redundant calibration to have a larger impact. These results suggest that redundant calibration can indeed mitigate some level of model incompleteness error.
David Johnson. Buying Gay: How Physique Entrepreneurs Sparked a Movement. New York: Columbia University Press, 2019. 328 pp. ISBN 978-0-2311-8910-1, $32.00 (cloth).
- Christopher Adam Mitchell
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- Journal:
- Enterprise & Society / Volume 21 / Issue 4 / December 2020
- Published online by Cambridge University Press:
- 14 July 2020, pp. 993-997
- Print publication:
- December 2020
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EROS AT JUNNAR: RECONSIDERING A PIECE OF MEDITERRANEAN ART
- Matthew Adam Cobb, Fiona Mitchell
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- Journal:
- Greece & Rome / Volume 66 / Issue 2 / October 2019
- Published online by Cambridge University Press:
- 19 September 2019, pp. 203-226
- Print publication:
- October 2019
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In 1969 on a riverside near the Lenyardi caves (about 5 kilometres from present-day Junnar, in the Indian state of Maharashtra), Dr Satish Deshmukh discovered an alabaster object in the form of half an egg (longitudinally cut) with a young male child lying inside it (with small traces of red paint on the right side of the object). This high-quality oval object (figures 1 and 2) measures about 5 cm × 3.4 cm and is usually interpreted as an item that was originally manufactured in the Mediterranean world before being brought to India, rather than a piece of artwork produced in India itself. One possible, and largely accepted, interpretation is that this figure represents the birth of the god Eros. However, identification of the figure within the egg-like structure is not easily made. While the figure does bear similarities to the putto-style representation of Eros in instances of Greek and Roman art, it does not possess any clear identifying features (such as the wings with which Eros is often depicted). The figure's resemblance to Eros in some of his other iconographic depictions and the egg-like structure around him suggest a possible identification of this infant with Eros and the myth of his birth from an egg. However, without evidence from other iconography of a more clearly identifiable Eros in similar contexts, the figure cannot be said to be him with any certainty. As Dhavalikar notes, this object ‘is the only one of its kind among the classical antiquities so far found in the Indian subcontinent and perhaps has no parallel in the classical world’. Thus the identification of this sculpture as a depiction of Eros in the egg is possible, but not certain.
48 - Qantas Skybed
- from The Digital Now
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- By Mitchell Adams, Mitchell Adams is a Research Associate at Swinburne Law School, and the Research Centre Manager of the Centre for Transformative Innovation at Swinburne University
- Edited by Claudy Op den Kamp, Bournemouth University, Dan Hunter
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- Book:
- A History of Intellectual Property in 50 Objects
- Published online:
- 12 June 2019
- Print publication:
- 20 June 2019, pp 392-399
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Summary
A LOT OF thought goes into what we sit on. From the design of the office chair to the cafe bench, kitchen stool, or couch where we watch television. For consumers, even more thought goes into what we sit on when we fly. Either domestic or international, we all have ourpreferences. Starting with which airline, then the location within the aeroplane—either up front or behind the wing. Finally, our preference for aisle or window, but never choosing a middle seat. Choice matters and can influence passengers to pay more than an economy fare. Design also plays a part and can affect a consumer's experience when flying. Good design can also play a role in linking innovation and the commercial success of products and services. Airplane seating is no exception.
Less thought goes into understanding the importance of design. Qantas Airlines Australia, however, recognized the importance of design and equally its protection and with the inception of the Skybed, it changed the perception of international business-class travel and what it means to fly. Design played a key role and created a consumer experience that was more functionally efficient and more aesthetically pleasing. The Qantas Skybed is an illustrative example of the unseen connections between industry, designer, consumer experience and design law.
In 2001, Qantas approached Marc Newson, a designer famous for his Lockheed Lounge and Embryo chair, to create a new business-class seat. The seat would need to recline and produce a flat bed. Qantas knew what drove customers to choose business class: comfort, privacy, and flexibility. The Newson seat would achieve all this, but also create a new sense of space for passengers either while working, relaxing, sleeping, or being entertained. Newson designed a retro-futuristic business-class seat with a sculpted carbon fibre back shell. Although not the first flatbed business-class seat—British Airways introduced the first in 1999—the Skybed was the longest at two meters fully reclined. The innovative design went on to win the Good Design Award from the Chicago Athenaeum Museum in 2003 and, a year later, an Australian Design Award. Following the successful launch and acclaim of the Skybed, Qantas asked Marc Newson back to redesign the entire cabin interior of Qantas’ new A380 fleet. To Qantas, the Skybed was the crown jewel of a $385 million modernization process.
6 - Global Configuration and Seasonal Variations of Saturn’s Magnetosphere
- Edited by Kevin H. Baines, University of Wisconsin, Madison, F. Michael Flasar, NASA-Goddard Space Flight Center, Norbert Krupp, Tom Stallard, University of Leicester
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- Book:
- Saturn in the 21st Century
- Published online:
- 13 December 2018
- Print publication:
- 06 December 2018, pp 126-165
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Summary
Our understanding of Saturn’s magnetosphere has been drastically changed over the last decade, since the arrival of Cassini, the first spacecraft to go into orbit around the planet. The trajectory of Cassini allowed the Saturnian magnetosphere to be studied both in the equatorial plane and at high latitudes, in a wide range of radial distances and local time sectors. This chapter reviews the current picture of Saturn’s global magnetospheric configuration and describes the local fields and particle properties in key regions like the radiation belts and the inner, middle and outer magnetosphere. The moon Enceladus, deep in the magnetosphere, is the major source of neutrals and charged particles in the magnetosphere, and in this chapter we describe how the particles are generated, transported and lost within the highly dynamic magnetosphere. We also describe how both particles and fields in the Saturnian magnetosphere vary with time, both on shorter timescales and with Saturn’s seasons. We highlight some of the most recent findings and discoveries, including a formerly unknown electric field oriented in the noon-midnight direction. Finally, we discuss magnetospheric measurements planned for the final sequence of the Cassini mission in 2017, called the “Grand Finale,” along with a list of open questions to be solved by future missions.
2173 RNA-nanoparticles to enhance and track dendritic cell migration
- Adam J. Grippin, Elias J. Sayour, Brandon Wummer, Adam Monsalve, Tyler Wildes, Kyle Dyson, Jon Dobson, Duane A. Mitchell
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- Journal:
- Journal of Clinical and Translational Science / Volume 2 / Issue S1 / June 2018
- Published online by Cambridge University Press:
- 21 November 2018, p. 26
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OBJECTIVES/SPECIFIC AIMS: Despite aggressive chemotherapy, surgical resection, and radiation therapy, glioblastoma remains almost universally fatal. In a pilot, randomized, and blinded clinical trial, we recently demonstrated that administration of RNA-loaded DC vaccines was associated with significantly improved progression-free and overall survival in patients with glioblastoma (Mitchell et al., Nature, 2015). Furthermore, clinical outcomes correlated with DC migration to vaccine-site draining lymph nodes measured by Indium-111 labeling of RNA-loaded DCs and SPECT/CT imaging. Although these studies demonstrated that tracking DC migration may be an important clinical biomarker for response to DC vaccination, the complexity and regulatory requirements associated with nuclear labelling to track DC migration limits widespread application of this technique. We have therefore developed RNA-loaded magnetic nanoparticles (RNA-NPs) to enhance DC migration to LNs and track that migration with a widely available imaging modality (i.e., MRI). METHODS/STUDY POPULATION: Cationic liposomes were loaded with iron oxide nanoparticles with or without cholesterol. The resulting nanoparticles were complexed with RNA and used to transfect DCs ex vivo. RNA-NP-loaded DsRed+ DCs were then injected intradermally into mice and tracked noninvasively with T2-weighted 11T MRI before excision and quantification with flow cytometry. RESULTS/ANTICIPATED RESULTS: In vitro experiments demonstrate that iron oxide loading does not reduce RNA-NP-mediated transfection of DCs. Additionally, replacement of cationic lipids with cholesterol increased RNA-NP transfection of the DC2.4 cell line and enhanced the T cell stimulatory capacity of treated bone marrow-derived dendritic cells (BMDCs). Compared to electroporation, RNA-NPs enhanced DC migration to lymph nodes and reduced T2 MRI intensity in DC-bearing lymph nodes. DISCUSSION/SIGNIFICANCE OF IMPACT: This data suggests that iron oxide-loaded RNA-NPs enable noninvasive cell tracking with MRI and enhance DC migration to lymph nodes. We have further shown that inclusion of cholesterol in RNA-NPs augments the stimulatory capacity of transfected DCs. Future work will consider effects of RNA-NPs on antitumor immune responses and the utility of MRI-detected DC migration as a biomarker of vaccine efficacy.
2422: Magnetic nanoparticles facilitate tracking of dendritic cells for treatment of malignant brain tumors
- Adam Grippin, Elias Sayour, Jon Dobson, Duane A. Mitchell
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- Journal:
- Journal of Clinical and Translational Science / Volume 1 / Issue S1 / September 2017
- Published online by Cambridge University Press:
- 10 May 2018, p. 9
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OBJECTIVES/SPECIFIC AIMS: Immune-based therapies hold great promise for treatment of refractory tumors. However, development is limited by a lack of identified immune correlates to vaccination. We recently showed that dendritic cells (DCs) prolong progression-free survival (PFS) and overall survival (OS) in patients with glioblastoma, and that DC migration to site draining lymph nodes robustly correlates with both PFS and OS. While this appears to be a reliable immune correlate, the complexity of routine labeling for PET and SPECT prohibits validation in a large clinical study. We therefore seek to develop a safe, translatable reporter that can be imaged with a widely available imaging modality. METHODS/STUDY POPULATION: The cationic liposome 1,2-doleoyl-3-trimethylammonium-propane (DOTAP) was loaded with MRI-imageable iron oxide nanoparticles (IONPs) with or without the neutral molecules PEG and cholesterol. The resulting nanoparticles were loaded with RNA to form RNA-NPs that were characterized with transmission electron microscopy (TEM) and used to transfect DCs in vitro; 4.7 T MRI was then used to image particles or cells in agarose gel phantoms. RESULTS/ANTICIPATED RESULTS: TEM images of RNA-NPs indicate the presence of IONP-loaded liposomes. In vitro transfection experiments demonstrate that iron oxide does not reduce RNA-NP-mediated transfection of DCs. Additionally, small amounts of either PEG or cholesterol within RNA-NPs increased transfection of DC2.4s and enhanced T-cell priming by bone marrow-derived dendritic cells. A series of 4.7 T MRI images of particles in cells, spleens, and LNs demonstrated quantifiable differences in particle density between groups. DISCUSSION/SIGNIFICANCE OF IMPACT: This data suggests that IONP-loaded RNA-NPs can be imaged with MRI and manipulated to augment DC function. Future work will include in vivo imaging in mice and safety studies to facilitate translation into first-in-human studies. Successful completion of this project would provide a powerful clinical tool to improve and track patient responses to immune therapy.
Summary of the Snowmastodon Project Special Volume A high-elevation, multi-proxy biotic and environmental record of MIS 6–4 from the Ziegler Reservoir fossil site, Snowmass Village, Colorado, USA
- Ian M. Miller, Jeffrey S. Pigati, R. Scott Anderson, Kirk R. Johnson, Shannon A. Mahan, Thomas A. Ager, Richard G. Baker, Maarten Blaauw, Jordon Bright, Peter M. Brown, Bruce Bryant, Zachary T. Calamari, Paul E. Carrara, Michael D. Cherney, John R. Demboski, Scott A. Elias, Daniel C. Fisher, Harrison J. Gray, Danielle R. Haskett, Jeffrey S. Honke, Stephen T. Jackson, Gonzalo Jiménez-Moreno, Douglas Kline, Eric M. Leonard, Nathaniel A. Lifton, Carol Lucking, H. Gregory McDonald, Dane M. Miller, Daniel R. Muhs, Stephen E. Nash, Cody Newton, James B. Paces, Lesley Petrie, Mitchell A. Plummer, David F. Porinchu, Adam N. Rountrey, Eric Scott, Joseph J.W. Sertich, Saxon E. Sharpe, Gary L. Skipp, Laura E. Strickland, Richard K. Stucky, Robert S. Thompson, Jim Wilson
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- Journal:
- Quaternary Research / Volume 82 / Issue 3 / November 2014
- Published online by Cambridge University Press:
- 20 January 2017, pp. 618-634
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In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.
Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance
- Ming Li, Xiong-jian Luo, Mikael Landén, Sarah E. Bergen, Christina M. Hultman, Xiao Li, Wen Zhang, Yong-Gang Yao, Chen Zhang, Jiewei Liu, Manuel Mattheisen, Sven Cichon, Thomas W. Mühleisen, Franziska A. Degenhardt, Markus M. Nöthen, Thomas G. Schulze, Maria Grigoroiu-Serbanescu, Hao Li, Chris K. Fuller, Chunhui Chen, Qi Dong, Chuansheng Chen, Stéphane Jamain, Marion Leboyer, Frank Bellivier, Bruno Etain, Jean-Pierre Kahn, Chantal Henry, Martin Preisig, Zoltán Kutalik, Enrique Castelao, Adam Wright, Philip B. Mitchell, Janice M. Fullerton, Peter R. Schofield, Grant W. Montgomery, Sarah E. Medland, Scott D. Gordon, Nicholas G. Martin, MooDS Consortium, The Swedish Bipolar Study Group, Marcella Rietschel, Chunyu Liu, Joel E. Kleinman, Thomas M. Hyde, Daniel R. Weinberger, Bing Su
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- Journal:
- The British Journal of Psychiatry / Volume 208 / Issue 2 / February 2016
- Published online by Cambridge University Press:
- 02 January 2018, pp. 128-137
- Print publication:
- February 2016
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Background
Bipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.
AimsWe sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.
MethodTo detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.
ResultsIntegrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10–5). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54×10–8). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.
ConclusionsOur findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.
Contributors
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- The Cambridge Dictionary of Philosophy
- Published online:
- 05 August 2015
- Print publication:
- 27 April 2015, pp ix-xxx
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Photo-modulated dynamic competition between metallic and insulating phases in a layered manganite
- Yuelin Li, Donald Walko, Qing’an Li, Yaohua Liu, Stephan Rosenkranz, Hong Zheng, J. F Mitchell, Haidan Wen, Eric Dufresne, Bernhard Adams
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- MRS Online Proceedings Library Archive / Volume 1636 / 2014
- Published online by Cambridge University Press:
- 09 January 2014, mrsf13-1636-u6.09
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- 2014
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We show evidence that the competition between the antiferromagnetic metallic phase and the charge- and orbital-ordered insulating phase at the reentrant phase boundary of a layered manganite, LaSr2Mn2O7, can be manipulated using ultrafast optical excitation. The time-dependent evolution of the Jahn-Teller superlattice reflection, the indicator of the formation of charge and orbital order, was measured at different laser fluences. The laser-induced change in the Jahn-Teller reflection intensity shows a reversal of sign between earlier (∼10 ns) and later (∼150 ns) times during the relaxation of the sample. This is consistent with a physics picture whereby the laser excitation modulates the local competition between the metallic and the insulating phases.
Science with the Murchison Widefield Array
- Part of
- Judd D. Bowman, Iver Cairns, David L. Kaplan, Tara Murphy, Divya Oberoi, Lister Staveley-Smith, Wayne Arcus, David G. Barnes, Gianni Bernardi, Frank H. Briggs, Shea Brown, John D. Bunton, Adam J. Burgasser, Roger J. Cappallo, Shami Chatterjee, Brian E. Corey, Anthea Coster, Avinash Deshpande, Ludi deSouza, David Emrich, Philip Erickson, Robert F. Goeke, B. M. Gaensler, Lincoln J. Greenhill, Lisa Harvey-Smith, Bryna J. Hazelton, David Herne, Jacqueline N. Hewitt, Melanie Johnston-Hollitt, Justin C. Kasper, Barton B. Kincaid, Ronald Koenig, Eric Kratzenberg, Colin J. Lonsdale, Mervyn J. Lynch, Lynn D. Matthews, S. Russell McWhirter, Daniel A. Mitchell, Miguel F. Morales, Edward H. Morgan, Stephen M. Ord, Joseph Pathikulangara, Thiagaraj Prabu, Ronald A. Remillard, Timothy Robishaw, Alan E. E. Rogers, Anish A. Roshi, Joseph E. Salah, Robert J. Sault, N. Udaya Shankar, K. S. Srivani, Jamie B. Stevens, Ravi Subrahmanyan, Steven J. Tingay, Randall B. Wayth, Mark Waterson, Rachel L. Webster, Alan R. Whitney, Andrew J. Williams, Christopher L. Williams, J. Stuart B. Wyithe
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 30 / 2013
- Published online by Cambridge University Press:
- 16 April 2013, e031
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Significant new opportunities for astrophysics and cosmology have been identified at low radio frequencies. The Murchison Widefield Array is the first telescope in the southern hemisphere designed specifically to explore the low-frequency astronomical sky between 80 and 300 MHz with arcminute angular resolution and high survey efficiency. The telescope will enable new advances along four key science themes, including searching for redshifted 21-cm emission from the EoR in the early Universe; Galactic and extragalactic all-sky southern hemisphere surveys; time-domain astrophysics; and solar, heliospheric, and ionospheric science and space weather. The Murchison Widefield Array is located in Western Australia at the site of the planned Square Kilometre Array (SKA) low-band telescope and is the only low-frequency SKA precursor facility. In this paper, we review the performance properties of the Murchison Widefield Array and describe its primary scientific objectives.
Contributors
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- By Alaine Auger, Kathleen Brager, Christopher M. Buddle, Jaret Daniels, Thomas A. Delamere, Adam Dodd, Crystal M. Ernst, Brian D. Farrell, Adrian Franklin, Donna J. Giberson, C. Michael Hall, Yupa Hanboonsong, Glen T. Hvenegaard, Kelsey Johansen, Akito Y. Kawahara, Raynald Harvey Lemelin, Jeff Lockwood, Forrest L. Mitchell, Tim R. New, David L. Pearson, Robert M. Pyle, Jessica J. Rykken, Michael J. Samways, Matt Shardlow, Edward M. Spevak, Arnold van Huis, Ko Veltman, Kristen M. Vinke, Alan L. Yen
- Edited by Raynald Harvey Lemelin, Lakehead University, Ontario
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- The Management of Insects in Recreation and Tourism
- Published online:
- 05 December 2012
- Print publication:
- 22 November 2012, pp x-xiv
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Archaic Period Shell Middens, Sea-Level Fluctuation, and Seasonality: Archaeology along the Northern Gulf of California Littoral, Sonora, Mexico
- Michael S. Foster, Douglas R. Mitchell, Gary Huckleberry, David Dettman, Karen R. Adams
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- American Antiquity / Volume 77 / Issue 4 / October 2012
- Published online by Cambridge University Press:
- 20 January 2017, pp. 756-772
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- October 2012
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Five recent radiocarbon assays on wood charcoal within archaeological sites from the Puerto Peñasco area, Sonora, Mexico indicate use of the marine resources of the northern Gulf of California area during the Middle Archaic through the Late Archaic periods, ca. 3800 B.C.–A.D. 100. The archaeological shell middens of the region are generally thought of as remains associated with Ceramic period Hohokam marine shell collecting forays with there being little consideration given to the likelihood of an Archaic period component being present. The importance of these age estimates is that they are derived from carbonized botanical remains rather than shell. Because of considerable variability in the carbon reservoir effect, age estimates derived from marine shell from the northern Gulf of California have limited reliability. The seasonality of collection is also considered through a preliminary study of stable oxygen isotope ratios in two shell samples. The results suggests that these shellfish were collected in the late fall, winter, and perhaps very early spring.
Frontmatter
- Edited by Paul Butler, Adam Mitchell, Jeremiah C. Healy
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- Applied Radiological Anatomy
- Published online:
- 05 November 2012
- Print publication:
- 05 July 2012, pp i-iv
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