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Mapping uncharted territory in ice from zeolite networks to ice structures

Edgar A. Engel, Andrea Anelli, Michele Ceriotti, Chris J. Pickard, Richard J. Needs
2018 Nature Communications  
Ice is one of the most extensively studied condensed matter systems. Yet, both experimentally and theoretically several new phases have been discovered over the last years. Here we report a large-scale density-functional-theory study of the configuration space of water ice. We geometry optimise 74,963 ice structures, which are selected and constructed from over five million tetrahedral networks listed in the databases of Treacy, Deem, and the International Zeolite Association. All prior
more » ... e of ice is set aside and we introduce "generalised convex hulls" to identify configurations stabilised by appropriate thermodynamic constraints. We thereby rediscover all known phases (I-XVII, i, 0 and the quartz phase) except the metastable ice IV. Crucially, we also find promising candidates for ices XVIII through LI. Using the "sketch-map" dimensionality-reduction algorithm we construct an a priori, navigable map of configuration space, which reproduces similarity relations between structures and highlights the novel candidates. By relating the known phases to the tractably small, yet structurally diverse set of synthesisable candidate structures, we provide an excellent starting point for identifying formation pathways.
doi:10.1038/s41467-018-04618-6 pmid:29872048 pmcid:PMC5988809 fatcat:pxhai7cxlncxnmatal4hr6yzfe

Reactive oxygen species signalling in the diabetic heart: emerging prospect for therapeutic targeting

Adam J Wilson, Eleanor K Gill, Rawan A Abudalo, Kevin S Edgar, Chris J Watson, David J Grieve
2017 Heart  
Despite being first described 45 years ago, the existence of a distinct diabetic cardiomyopathy remains controversial. Nonetheless, it is widely accepted that the diabetic heart undergoes characteristic structural and functional changes in the absence of ischaemia and hypertension, which are independently linked to heart failure progression and are likely to underlie enhanced susceptibility to stress. A prominent feature is marked collagen accumulation linked with inflammation and extensive
more » ... acellular matrix changes, which appears to be the main factor underlying cardiac stiffness and subclinical diastolic dysfunction, estimated to occur in as many as 75% of optimally controlled diabetics. Whether this characteristic remodelling phenotype is primarily driven by microvascular dysfunction or alterations in cardiomyocyte metabolism remains unclear. Although hyperglycaemia regulates multiple pathways in the diabetic heart, increased reactive oxygen species (ROS) generation is thought to represent a central mechanism underlying associated adverse remodelling. Indeed, experimental and clinical diabetes are linked with oxidative stress which plays a key role in cardiomyopathy, while key processes underlying diabetic cardiac remodelling, such as inflammation, angiogenesis, cardiomyocyte hypertrophy and apoptosis, fibrosis and contractile dysfunction, are redox sensitive. This review will explore the relative contributions of the major ROS sources (dysfunctional nitric oxide synthase, mitochondria, xanthine oxidase, nicotinamide adenine dinucleotide phosphate oxidases) in the diabetic heart and the potential for therapeutic targeting of ROS signalling using novel pharmacological and nonpharmacological approaches to modify specific aspects of the remodelling phenotype in order to prevent and/or delay heart failure development and progression.
doi:10.1136/heartjnl-2017-311448 pmid:28954833 fatcat:xtnzw2wznvebdj73jsulw5xupi

The role of human cognitive neuroscience in drug discovery for the dementias

Keith A Wesnes, Chris J Edgar
2014 Current opinion in pharmacology (Print)  
Drug discovery for the dementias Wesnes and Edgar 63 Table 1 Summary of non-industry sponsored upcoming and current prevention trials in Alzheimer's disease Target engagement at two years; a subsequent  ...  Drug discovery for the dementias Wesnes and Edgar 67 With appropriate design and standardization, tests can be developed which properly characterize the quality of performance over repeated assessments  ... 
doi:10.1016/j.coph.2013.12.001 pmid:24565014 fatcat:tcm6bkj6wzd27lguopuqcithv4

Histopathological diagnoses on pleural biopsy specimens over a 15-year period at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa: A retrospective review

J R Edgar, M L Wong, M Hale, C N Menezes
2018 South African Medical Journal  
Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, Johannesburg, is the largest hospital in SA, and indeed in the southern hemisphere, but there have been no studies investigating pleural biopsies  ...  Primary lung adeno- carcnoma Primary lung SCC Large cell Poorly differentiated Adeno- carcinoma SCC Poorly differentiated Acute Chronic Suppurative HIV + 10 S Afr Med J  ... 
doi:10.7196/samj.2018.v109i1.13400 fatcat:oztkwwpc3vfahpcszdv3qh6w6u

Psychometric evaluation of the Work Readiness Questionnaire in schizophrenia

Steven G. Potkin, Dragana Bugarski-Kirola, Chris J. Edgar, Sherif Soliman, Stephanie Le Scouiller, Jelena Kunovac, Eugenio Miguel Velasco, George M. Garibaldi
2014 CNS Spectrums  
Objective/Introduction Unemployment can negatively impact quality of life among patients with schizophrenia. Employment status depends on ability, opportunity, education, and cultural influences. A clinician-rated scale of work readiness, independent of current work status, can be a valuable assessment tool. A series of studies were conducted to create and validate a Work Readiness Questionnaire (WoRQ) for clinicians to assess patient ability to engage in socially useful activity, independent
more » ... work availability. Methods Content validity, test–retest and inter-rater reliability, and construct validity were evaluated in three separate studies. Results Content validity was supported. Cronbach's α was 0.91, in the excellent range. Clinicians endorsed WoRQ concepts, including treatment adherence, physical appearance, social competence, and symptom control. The final readiness decision showed good test–retest reliability and moderate inter-rater reliability. Work readiness was associated with higher function and lower levels of negative symptoms. Low positive and high negative predictive values confirmed the concept validity. Discussion The WoRQ has suitable psychometric properties for use in a clinical trial for patients with a broad range of symptom severity. The scale may be applicable to assess therapeutic interventions. It is not intended to assess eligibility for supported work interventions. Conclusions The WoRQ is suitable for use in schizophrenia clinical trials to assess patient work functional potential.
doi:10.1017/s1092852914000352 pmid:25269787 pmcid:PMC4825104 fatcat:a4n5wdc26ffprnrvqw7x4zrobu

Cell Cycle-controlled Interaction of Nucleolin with the Retinoblastoma Protein and Cancerous Cell Transformation

Edgar Grinstein, Ying Shan, Leonid Karawajew, Peter J. F. Snijders, Chris J. L. M. Meijer, Hans-Dieter Royer, Peter Wernet
2006 Journal of Biological Chemistry  
Retinoblastoma protein (Rb) is a multifunctional tumor suppressor, frequently inactivated in certain types of human cancer. Nucleolin is an abundant multifunctional phosphoprotein of proliferating and cancerous cells, recently identified as cell cycle-regulated transcription activator, controlling expression of human papillomavirus type 18 (HPV18) oncogenes in cervical cancer. Here we find that nucleolin is associated with Rb in intact cells in the G 1 phase of the cell cycle, and the complex
more » ... rmation is mediated by the growth-inhibitory domain of Rb. Association with Rb inhibits the DNA binding function of nucleolin and in consequence the interaction of nucleolin with the HPV18 enhancer, resulting in Rb-mediated repression of the HPV18 oncogenes. The intracellular distribution of nucleolin in epithelial cells is Rb-dependent, and an altered nucleolin localization in human cancerous tissues results from a loss of Rb. Our findings suggest that deregulated nucleolin activity due to a loss of Rb contributes to tumor development in malignant diseases, thus providing further insights into the molecular network for the Rb-mediated tumor suppression.
doi:10.1074/jbc.m513335200 pmid:16698799 fatcat:xg6vyamjnfas5pj5s3suizmqvi

Generalized convex hull construction for materials discovery

Andrea Anelli, Edgar A. Engel, Chris J. Pickard, Michele Ceriotti
The fingerprints identify the structures X i according to additive, data-driven features Φ j , which encode the full structural diversity of the dataset.  ...  Day and J. Yang for sharing the W99 optimized configurations of pentacene and 5A crystals, and for insightful discussion. Methods Structural Features.  ... 
doi:10.1103/physrevmaterials.2.103804 fatcat:62kluue4gnayjoughkedbfnsni

Molecular Mechanisms of Disease Pathogenesis Differ in Krabbe Disease Variants

Samantha J. Spratley, Chris H. Hill, Agnete H. Viuff, James R. Edgar, Karsten Skjødt, Janet E. Deane
2016 Traffic : the International Journal of Intracellular Transport  
doi:10.1111/tra.12404 pmid:27126738 pmcid:PMC4949656 fatcat:ahrbsllhlnedppi53jvyu4puba

Quantifying the impact of the COVID ‐19 pandemic on gastrointestinal cancer care delivery

Nicholas R. Perkons, Casey Kim, Chris Boedec, Luke J. Keele, Charles Schneider, Ursina R. Teitelbaum, Edgar Ben‐Josef, Peter E. Gabriel, John P. Plastaras, Lawrence N. Shulman, Andrzej P. Wojcieszynski
2021 Cancer Reports  
Column 2 (B, D, F, H, J) includes graphical representations of the difference in the number of patients with a recorded encounter subtype within a given week as compared between 2019 and 2020.  ... 
doi:10.1002/cnr2.1427 pmid:34137216 pmcid:PMC8420475 fatcat:mbq44is5rnep5cp4atb36w4a7y

Pilot Evaluation of the Unsupervised, At-Home Cogstate Brief Battery in ADNI-2

Chris J. Edgar, Eric Siemers, Paul Maruff, Ronald C. Petersen, Paul S. Aisen, Michael W. Weiner, Bruce Albala, for the Alzheimer's Disease Neuroimaging Initiative, Montse Alegret
2021 Journal of Alzheimer's Disease  
There is a need for feasible, scalable assessments to detect cognitive impairment and decline. The Cogstate Brief Battery (CBB) is validated for Alzheimer's disease (AD) and in unsupervised and bring your own device contexts. The CBB has shown usability for self-completion in the home but has not been employed in this way in a multisite clinical trial in AD. Objective: The objective of the pilot was to evaluate feasibility of at-home, self-completion of the CBB in the Alzheimer's Disease
more » ... aging Initiative (ADNI) over 24 months. Methods: The CBB was included as a pilot for cognitively normal (CN) and mild cognitive impairment (MCI) participants in ADNI-2, invited to take the assessment in-clinic, then at at-home over a period of 24 months follow-up. Data were analyzed to explore acceptability/usability, concordance of in-clinic and at-home assessment, and validity. Results: Data were collected for 104 participants (46 CN, 51 MCI, and 7 AD) who consented to provide CBB data. Subsequent analyses were performed for the CN and MCI groups only. Test completion rates were 100%for both the first in-clinic supervised and first at-home unsupervised assessments, with few repeat performances required. However, availability follow-up data declined sharply over time. Good concordance was seen between in-clinic and at-home assessments, with non-significant and small effect size differences (Cohen's d between -0.04 and 0.28) and generally moderate correlations (r = 0.42 to 0.73). Known groups validity was also supported (11/16 comparisons with Cohen's d≥0.3). Conclusion: These data demonstrate the feasibility of use for the CBB for unsupervised at-home, testing, including MCI groups. Optimal approaches to the application of assessments to support compliance over time remain to be determined.
doi:10.3233/jad-210201 pmid:34366337 pmcid:PMC8543269 fatcat:54zb74gsavethg54n7v7kktxry

Ambipolar ion acceleration in an expanding magnetic nozzle

Benjamin W Longmier, Edgar A Bering, Mark D Carter, Leonard D Cassady, William J Chancery, Franklin R Chang Díaz, Tim W Glover, Noah Hershkowitz, Andrew V Ilin, Greg E McCaskill, Chris S Olsen, Jared P Squire
2011 Plasma Sources Science & Technology  
The helicon plasma stage in the Variable Specific Impulse Magnetoplasma Rocket (VASIMR ® ) VX-200i device was used to characterize an axial plasma potential profile within an expanding magnetic nozzle region of the laboratory based device. The ion acceleration mechanism is identified as an ambipolar electric field produced by an electron pressure gradient, resulting in a local axial ion speed of Mach 4 downstream of the magnetic nozzle. A 20 eV argon ion kinetic energy was measured in the
more » ... n source, which had a peak magnetic field strength of 0.17 T. The helicon plasma source was operated with 25 mg s −1 argon propellant and 30 kW of RF power. The maximum measured values of plasma density and electron temperature within the exhaust plume were 1 × 10 20 m −3 and 9 eV, respectively. The measured plasma density is nearly an order of magnitude larger than previously reported steady-state helicon plasma sources. The exhaust plume also exhibits a 95% to 100% ionization fraction. The size scale and spatial location of the plasma potential structure in the expanding magnetic nozzle region appear to follow the size scale and spatial location of the expanding magnetic field. The thickness of the potential structure was found to be 10 4 to 10 5 λ De depending on the local electron temperature in the magnetic nozzle, many orders of magnitude larger than typical laboratory double layer structures. The background plasma density and neutral argon pressure were 10 15 m −3 and 2 × 10 −5 Torr, respectively, in a 150 m 3 vacuum chamber during operation of the helicon plasma source. The agreement between the measured plasma potential and plasma potential that was calculated from an ambipolar ion acceleration analysis over the bulk of the axial distance where the potential drop was located is a strong confirmation of the ambipolar acceleration process.
doi:10.1088/0963-0252/20/1/015007 fatcat:kr6z5f7yvrbpnhxu5ksqgwgeyi

Cognitive performance in relapsing remitting multiple sclerosis: A longitudinal study in daily practice using a brief computerized cognitive battery

Chris Edgar, Peter J Jongen, Evert Sanders, Christian Sindic, Sophie Goffette, Michel Dupuis, Philippe Jacquerye, Daniel Guillaume, Regine Reznik, Keith Wesnes
2011 BMC Neurology  
Edgar has a PhD in Cognitive Competing interests Dr.  ...  Edgar is an expert in computerized cognitive assessment and a former Scientific Director at CDR Ltd, developers of the CDR System computerized cognitive test battery. Dr.  ...  -1 Day 30 Month 3 Month 6 Month 12 Month 18 Month 24 Z-score +/-sem -1.0 -0.8 -0.6 -0.4 -0.2 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 DSST Timed 25-FWT 9HPT PASAT 3" MSFC Edgar  ... 
doi:10.1186/1471-2377-11-68 pmid:21649910 pmcid:PMC3128855 fatcat:n4b2as4xvjey5eiz3mkpthiizu

Defining therapeutic benefit for people with schizophrenia: Focus on negative symptoms

Nina R. Schooler, Robert W. Buchanan, Thomas Laughren, Stefan Leucht, Henry A. Nasrallah, Steven G. Potkin, Danielle Abi-Saab, Carmen Galani Berardo, Dragana Bugarski-Kirola, Thomas Blaettler, Chris J. Edgar, Anna-Lena Nordstroem (+2 others)
2015 Schizophrenia Research  
It should be noted that Contents lists available at ScienceDirect Schizophrenia Research j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / s c h r e s negative symptoms  ... 
doi:10.1016/j.schres.2014.12.001 pmid:25579053 fatcat:mn5y3pt5ajhvfgzbdoskel67c4

Cognitive Performance by Humans During a Smoked Cocaine Binge-Abstinence Cycle

Edward F. Pace-Schott, Robert Stickgold, Amir Muzur, Pia E. Wigren, Amie S. Ward, Carl L. Hart, Matthew Walker, Chris Edgar, J. Allan Hobson
2005 The American Journal of Drug and Alcohol Abuse  
Five cocaine-dependent individuals completed a 22-day inpatient study of sleep and cognition. Following 3 days of drug-free baseline, participants underwent 3 days of twice-daily smoked cocaine base self-administration (6 50-mg doses, 14 minutes apart), followed by 15 days of abstinence. Each morning and afternoon, the CDR repeatable, multiple-version, computerized cognitive battery (whose stability following practice has been documented) was administered. During abstinence, performance
more » ... ated on vigilance tasks (especially reaction time) as well as on immediate and delayed verbal recognition tasks but not on working memory tasks. Declines were most evident in the afternoon. Data suggest that abstinence can unmask cognitive deficits induced by chronic cocaine use and circadian factors may mediate their severity.
doi:10.1081/ada-200068120 pmid:16320435 fatcat:qdqecsmz4rg37daa7gr2ynqjrq

Clinical Implications for the Timely Diagnosis of Mycobacterium marinum in the Age of Biologic Therapy: A Case Report and Review of the Literature

Chris J. Lata, Kelle Edgar, Stephen Vaughan
2017 Case Reports in Infectious Diseases  
Mycobacterium marinum infections typically present as cutaneous nodular lesions with a sporotrichoid lymphatic spread on extensor surfaces of extremities. The natural history of this infection can be altered if the host is immunosuppressed, leading to disseminated presentations. A detailed exposure history and high degree of suspicion for this indolent pathogen are often required for the correct diagnosis of this disease. We present a case of a 67-year-old male misdiagnosed with seronegative
more » ... umatoid arthritis presenting with rheumatic nodules. Initiation of chronic immunosuppressant therapy including biologic monoclonal antibodies resulted in the exacerbation of initially localized disease to broadly disseminated lymphatic, joint, and myotendinous granulomatous disease and led to delay in the correct diagnosis. Cessation of immunosuppressants, with a prolonged course of antimicrobial therapy and multiple surgical debridements were required for cure.
doi:10.1155/2017/5274302 pmid:28392952 pmcid:PMC5368394 fatcat:r5qlilqpk5formc2bjlzjyssby
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