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2. Investigating Local Parity Violation in Heavy-Ion Collisions Using Lambda Helicity

Author

Finch, L. Evan and Murray, Stephen J.

Subjects
High Energy Physics - Phenomenology, Nuclear Experiment
Abstract

We propose the measurement of net $\Lambda$ and $\bar{\Lambda}$ helicity, correlated event-by-event with the magnitude and sign of charge separation along the event's magnetic field direction, as a probe to investigate the Chiral Magnetic Effect in Heavy-Ion Collisions. With a simple simulation model of heavy-ion events that includes effects of Local Parity Violation, we estimate the experimental correlation signal that could be expected at RHIC given the results of previous measurements that are sensitive to the CME., Comment: 10 pages, 1 figure

Published
2018
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3. Production of Stable and Unstable Nuclei and Hyperfragments in 11.5 A GeV/c Au+Pb collisions

Author

The E864 Collaboration and Finch, L. Evan

Subjects
Nuclear Experiment
Abstract

We present measurements of the production of stable light nuclei for mass number A<=7, of strongly decaying states He(5) and Li(5) and of the hypernucleus H(3,lambda). We also examine trends in the production of these multibaryon states as a function of kinematic variables and properties of these states including strangeness content., Comment: Quark Matter '99 Conference

Published
1999
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5. Basal cell carcinomas in mice arise from hair follicle stem cells and multiple epithelial progenitor populations

Author

Grachtchouk, Marina, Pero, Joanna, Yang, Steven H., Ermilov, Alexandre N., Michael, L. Evan, Wang, Aiqin, Wilbert, Dawn, Patel, Rajiv M., Ferris, Jennifer, Diener, James, Allen, Mary, Lim, Seokchun, Syu, Li-Jyun, Verhaegen, Monique, and Dlugosz, Andrzej A.

Subjects
Stem cells -- Physiological aspects -- Research, Epithelial cells -- Physiological aspects -- Research, Basal cell carcinoma -- Development and progression -- Research, Health care industry
Abstract

Uncontrolled Hedgehog (Hh) signaling leads to the development of basal cell carcinoma (BCC), the most common human cancer, but the cell of origin for BCC is unclear. While Hh pathway [...]

Published
2011
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6. The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold

Author

Selyunin, Andrey S., Sutton, Sarah E., Weigele, Bethany A., Reddick, L. Evan, Orchard, Robert C., Bresson, Stefan M., Tomchick, Diana R., and Alto, Neal M.

Subjects
Bacterial proteins -- Properties -- Physiological aspects -- Research -- Health aspects, Cellular signal transduction -- Research -- Health aspects -- Physiological aspects, DNA binding proteins -- Physiological aspects -- Health aspects -- Research, Guanosine triphosphatase -- Physiological aspects -- Health aspects -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The fidelity and specificity of information flow within a cell is controlled by scaffolding proteins that assemble and link enzymes into signalling circuits (1,2). These circuits can be inhibited by bacterial effector proteins that post-translationally modify individual pathway components (3-6). However, there is emerging evidence that pathogens directly organize higher-order signalling networks through enzyme scaffolding (7,8), and the identity of the effectors and their mechanisms of action are poorly understood. Here we identify the enterohaemorrhagic Escherichia coli O157:H7 type III effector EspG as a regulator of endomembrane trafficking using a functional screen, and report ADP-ribosylation factor (ARF) GTPases and p21-activated kinases (PAKs) as its relevant host substrates. The 2.5 A crystal structure of EspG in complex with ARF6 shows how EspG blocks GTPase-activating-protein-assisted GTP hydrolysis, revealing a potent mechanism of GTPase signalling inhibition at organelle membranes. In addition, the 2.8 Å crystal structure of EspG in complex with the autoinhibitory Iα3-helix of PAK2 defines a previously unknown catalytic site in EspG and provides an allosteric mechanism of kinase activation by a bacterial effector. Unexpectedly, ARF and PAKs are organized on adjacent surfaces of EspG, indicating its role as a 'catalytic scaffold' that effectively reprograms cellular events through the functional assembly of GTPase-kinase signalling complex., To identify new signalling pathways targetedby bacterial pathogens, we used a human growth hormone (hGH) secretion assay (9) to measure the ability of type III and type IV effector proteins [...]

Published
2011
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7. Judicial ethics.

Author

Van Gorder, L. Evan

Subjects
Judicial ethics -- Surveys
Published
2008

8. Sustained hedgehog signaling is required for basal cell carcinoma proliferation and survival: Conditional skin tumor genesis recapitulates the hair growth cycle

Author

Hutchin, Mark E., Kariapper, Muhammed S.T., Grachtchouk, Marina, Aiqin Wang, Lebing Wei, Cummings, Donelle, Jianhong Liu, Glick, Adam, Dlugosz, Andrzej A., and Michael, L. Evan

Subjects
Epithelium -- Research, Hair follicles -- Research, Skin tumors -- Research, Biological sciences
Abstract

The temporally and spatially constrained Hedgehog (Hh) signaling regulates the cyclic growth of hair follicle epithelium whereas the constitutive Hh signaling drives the development of basal cell carcinomas (BCCs). The study carried out on the Hh signaling reveals that continued Hh signaling is required for proliferation and survival of established BCCs.

Published
2005

9. Concurrent nonavalent human papillomavirus (HPV) vaccination and immune stimulation with imiquimod to treat recalcitrant HPV-associated high grade vaginal intra-epithelial neoplasia

Author

R. Farrell, J. Zaunders, IM. Poynten, L. Anderson, and L. Evans

Subjects
Human papillomavirus (HPV), Vaginal intraepitheial neoplasia (VAIN), Imiquimod, HPV vaccine, Gynecology and obstetrics, RG1-991, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

This is the first report describing detailed T cell responses to viral-like proteins contained in an HPV specific vaccine given in combination with Imiquimod for treatment of persistent VAIN2/3. We postulate that stimulation of the innate immune system with Imiquimod and the specific CD4 and CD8T cell responses following HPV vaccination with Gardasil9@ combined to induce clinical remission in a woman with treatment-refractory disease.

Published
2024
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11. Practitioner approaches to trade‐off decision‐making in marine conservation development

Author

M. Fortnam, T. Chaigneau, L. Evans, and L. Bastian

Subjects
conservation development, decision‐making, justice, marine governance, trade‐offs, Human ecology. Anthropogeography, GF1-900, Ecology, QH540-549.5
Abstract

Abstract Mounting evidence suggests that win‐wins are elusive and trade‐offs are the norm in marine conservation development practice. The status quo involves trade‐offs, and any change brought to ecosystems, economies and societies will alter the distribution of costs and benefits, creating other winners and losers among ecosystem services, sectors and people. While studies are increasingly acknowledging the prevalence of trade‐offs, this article analyses how practitioners working for conservation development agencies consider, facilitate and make trade‐off decisions a priori and post hoc when designing and implementing marine conservation development programmes in Southeast Asia. We find that these practitioners recognize both substantive trade‐offs, which are diverse social and ecological trade‐offs resulting from their programmes, and process trade‐offs, related to how they design programmes, including between their prioritization of different locations; between strategic relationships; and between the efficacy, equity and sustainability of projects. Existing decision support tools only capture a limited range of substantive (mainly ecological) trade‐offs, however, and are not widely used. Typically, social trade‐offs are not systematically assessed. Instead, they are implicitly identified by participants and beneficiaries voicing their concerns during consultation processes. Importantly, whether a trade‐off is then deemed acceptable is not determined through transparent assessment of trade‐offs and principles of equity or justice but by the uneven political power of stakeholders to project their values in decision‐making processes. The article concludes that practitioners should facilitate inclusive, transparent and systematic identification and deliberation of the social acceptability of multidimensional trade‐offs, and formulate response options to avoid or minimize adverse consequences. Tackling trade‐offs in this way has the potential to make invisible trade‐offs visible and improve the sustainability and legitimacy of marine conservation development programmes while promoting the interests of the most marginalized in efforts to achieve the sustainable development goals. Read the free Plain Language Summary for this article on the Journal blog.

Published
2023
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13. Functional Analysis of Semi-conserved Transit Peptide Motifs and Mechanistic Implications in Precursor Targeting and Recognition

Author

Huixia Zhang, Chitra Subramanian, Kristen Holbrook, Lily Moncrief, L. Evan Reddick, Prakitchai Chotewutmontri, Barry D. Bruce, and Sarah J Wright

Subjects
0301 basic medicine, Toc complex, Chloroplasts, Functional analysis, Plant Science, Computational biology, Biology, Chloroplast, Chloroplast Proteins, Protein Transport, 03 medical and health sciences, 030104 developmental biology, Biochemistry, Transit Peptide, Organelle, Plastid, Peptides, Molecular Biology, Function (biology), Ferredoxin, Plant Proteins
Abstract

Over 95% of plastid proteins are nuclear-encoded as their precursors containing an N-terminal extension known as the transit peptide (TP). Although highly variable, TPs direct the precursors through a conserved, posttranslational mechanism involving translocons in the outer (TOC) and inner envelope (TOC). The organelle import specificity is mediated by one or more components of the Toc complex. However, the high TP diversity creates a paradox on how the sequences can be specifically recognized. An emerging model of TP design is that they contain multiple loosely conserved motifs that are recognized at different steps in the targeting and transport process. Bioinformatics has demonstrated that many TPs contain semi-conserved physicochemical motifs, termed FGLK. In order to characterize FGLK motifs in TP recognition and import, we have analyzed two well-studied TPs from the precursor of RuBisCO small subunit (SStp) and ferredoxin (Fdtp). Both SStp and Fdtp contain two FGLK motifs. Analysis of large set mutations (∼85) in these two motifs using in vitro, in organello, and in vivo approaches support a model in which the FGLK domains mediate interaction with TOC34 and possibly other TOC components. In vivo import analysis suggests that multiple FGLK motifs are functionally redundant. Furthermore, we discuss how FGLK motifs are required for efficient precursor protein import and how these elements may permit a convergent function of this highly variable class of targeting sequences.

Published
2016

14. Myristoylome Profiling Reveals a Concerted Mechanism of ARF GTPase Deacylation by the Bacterial Protease IpaJ

Author

Neal M. Alto, Howard C. Hang, Tao Peng, Nikolay Burnaevskiy, and L. Evan Reddick

Subjects
Models, Molecular, ADP ribosylation factor, Protein Conformation, medicine.medical_treatment, Molecular Sequence Data, GTPase, Plasma protein binding, Crystallography, X-Ray, Myristic Acid, Article, Shigella flexneri, Escherichia coli, medicine, Humans, Amino Acid Sequence, Protein myristoylation, Molecular Biology, Myristoylation, Antigens, Bacterial, Protease, biology, ADP-Ribosylation Factors, Effector, Cell Biology, biology.organism_classification, Recombinant Proteins, Protein Structure, Tertiary, Cell biology, Biochemistry, ADP-Ribosylation Factor 6, ADP-Ribosylation Factor 1, lipids (amino acids, peptides, and proteins), Hydrophobic and Hydrophilic Interactions, Protein Processing, Post-Translational, HeLa Cells, Protein Binding, Signal Transduction
Abstract

Summary N -myristoylation is an essential fatty acid modification that governs the localization and activity of cell signaling enzymes, architectural proteins, and immune regulatory factors. Despite its importance in health and disease, there are currently no methods for reversing protein myristoylation in vivo. Recently, the Shigella flexneri protease IpaJ was found to cleave myristoylated glycine of eukaryotic proteins, yet the discriminatory mechanisms of substrate selection required for targeted demyristoylation have not yet been evaluated. Here, we performed global myristoylome profiling of cells treated with IpaJ under distinct physiological conditions. The protease is highly promiscuous among diverse N- myristoylated proteins in vitro but is remarkably specific to Golgi-associated ARF/ARL family GTPases during Shigella infection. Reconstitution studies revealed a mechanistic framework for substrate discrimination based on IpaJ's function as a GTPase "effector" of bacterial origin. We now propose a concerted model for IpaJ function that highlights its potential for programmable demyristoylation in vivo.

Published
2015

15. Convergence criteria analysis for thermal conductance measurements of building walls: A case study

Author

L. Evangelisti, C. Guattari, E. De Lieto Vollaro, and F. Asdrubali

Subjects
Non-destructive technique, Heat-flow meter method, Thermal conductance, Experimental test, Convergence criteria, Engineering (General). Civil engineering (General), TA1-2040
Abstract

The significance of on-site measurements for the thermal characterization of building components is widely recognized. Walls thermal performance can be identified through the widely used Heat-Flow Meter (HFM) method, which has been frequently applied in literature. However, only a few scientific works have examined the convergence criteria suggested by the ISO 9869–1. Starting from this, the aim of this work is evaluating the convergence criteria in a case study using the progressive average method. Thermal conductance (C-value) measurements were carried out in a small-scale building, placed in the external area of a building school site near Rome (Italy). The building is internally equipped with an electric heating system. Heat-flux sensor and surface temperature probes were applied to assess the C-value of the envelope. The different switching-on of the heater characterized by different power levels and the reaching of regular thermal conditions after initial transients were considered to evaluate the acquired data and their influence on the results. The known walls stratigraphy allowed to compute and compare theoretical and experimental C-values. Based on the examined data, it is possible to assert that the convergence conditions are very strict, mainly due to the third criterion.

Published
2023
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16. Bacteria Fighting Back: How Pathogens Target and Subvert the Host Innate Immune System

Author

Neal M. Alto and L. Evan Reddick

Subjects
Innate immune system, Bacteria, Antimicrobial peptides, Models, Immunological, Pattern recognition receptor, Cell Biology, Biology, Immunity, Innate, Article, Microbiology, Toll-Like Receptor 4, Classical complement pathway, Immune system, Immunity, Receptors, Pattern Recognition, Host-Pathogen Interactions, Antigenic variation, Signal transduction, Molecular Biology, Immune Evasion, Signal Transduction
Abstract

The innate immune system has evolved under selective pressure since the radiation of multicellular life approximately six hundred million years ago. Because of this long history, innate immune mechanisms found in modern eukaryotic organisms today are highly complex, yet are built from common molecular strategies. It is now clear that evolution has selected a conserved set of anti-microbial peptides as well as Pattern Recognition Receptors (PRRs) that initiate cellular-based signals as a first line of defense against invading pathogens. Conversely, microbial pathogens employ their own strategies to evade, inhibit, or otherwise manipulate the innate immune response. Here, we discuss recent discoveries that have changed our view of immune modulatory mechanisms employed by bacterial pathogens, focusing specifically on the initial sites of microbial recognition and extending to host cellular signal transduction, pro-inflammatory cytokine production, and alteration of protein trafficking and secretion.

Published
2014

18. In Vitro Comparative Kinetic Analysis of the Chloroplast Toc GTPases

Author

Ian M. Campbell, Sarah J Wright, Michael Vaughn, L. Evan Reddick, and Barry D. Bruce

Subjects
Models, Molecular, Toc complex, Chloroplasts, Arabidopsis, GTPase, Buffers, Biology, Biochemistry, Chloroplast membrane, GTP Phosphohydrolases, Substrate Specificity, GTP-binding protein regulators, Enzyme Stability, Molecular Biology, Ions, Cell Biology, Translocon, Protein Structure, Tertiary, Transport protein, Enzyme Activation, Chloroplast, Kinetics, Metals, Structural Homology, Protein, Mutation, Guanosine Triphosphate, Guanine nucleotide exchange factor, Protein Binding
Abstract

A unique aspect of protein transport into plastids is the coordinate involvement of two GTPases in the translocon of the outer chloroplast membrane (Toc). There are two subfamilies in Arabidopsis, the small GTPases (Toc33 and Toc34) and the large acidic GTPases (Toc90, Toc120, Toc132, and Toc159). In chloroplasts, Toc34 and Toc159 are implicated in precursor binding, yet mechanistic details are poorly understood. How the GTPase cycle is modulated by precursor binding is complex and in need of careful dissection. To this end, we have developed novel in vitro assays to quantitate nucleotide binding and hydrolysis of the Toc GTPases. Here we present the first systematic kinetic characterization of four Toc GTPases (cytosolic domains of atToc33, atToc34, psToc34, and the GTPase domain of atToc159) to permit their direct comparison. We report the KM, Vmax, and Ea values for GTP hydrolysis and the Kd value for nucleotide binding for each protein. We demonstrate that GTP hydrolysis by psToc34 is stimulated by chloroplast transit peptides; however, this activity is not stimulated by homodimerization and is abolished by the R133A mutation. Furthermore, we show peptide stimulation of hydrolytic rates are not because of accelerated nucleotide exchange, indicating that transit peptides function as GTPase-activating proteins and not guanine nucleotide exchange factors in modulating the activity of psToc34. Finally, by using the psToc34 structure, we have developed molecular models for atToc33, atToc34, and atToc159G. By combining these models with the measured enzymatic properties of the Toc GTPases, we provide new insights of how the chloroplast protein import cycle may be regulated.

Published
2007

19. Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle

Author

Andrzej A. Dlugosz, Muhammed S.T. Kariapper, Lebing Wei, Jianhong Liu, L. Evan Michael, Marina Grachtchouk, Aiqin Wang, Mark E. Hutchin, Adam B. Glick, and Donelle Cummings

Subjects
medicine.medical_specialty, Skin Neoplasms, Cellular differentiation, Mesenchyme, Kruppel-Like Transcription Factors, Apoptosis, Mice, Transgenic, Zinc Finger Protein Gli2, Biology, Mice, Internal medicine, GLI2, Genetics, medicine, Animals, Hedgehog Proteins, Hedgehog, Cell Proliferation, Stem Cells, Cell Differentiation, Epithelial Cells, Hair follicle, Research Papers, Hedgehog signaling pathway, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Endocrinology, Carcinoma, Basal Cell, Trans-Activators, Cancer research, Signal transduction, Stem cell, Hair Follicle, Signal Transduction, Transcription Factors, Developmental Biology
Abstract

Temporally and spatially constrained Hedgehog (Hh) signaling regulates cyclic growth of hair follicle epithelium while constitutive Hh signaling drives the development of basal cell carcinomas (BCCs), the most common cancers in humans. Using mice engineered to conditionally express the Hh effector Gli2, we show that continued Hh signaling is required for growth of established BCCs. Transgene inactivation led to BCC regression accompanied by reduced tumor cell proliferation and increased apoptosis, leaving behind a small subset of nonproliferative cells that could form tumors upon transgene reactivation. Nearly all BCCs arose from hair follicles, which harbor cutaneous epithelial stem cells, and reconstitution of regressing tumor cells with an inductive mesenchyme led to multilineage differentiation and hair follicle formation. Our data reveal that continued Hh signaling is required for proliferation and survival of established BCCs, provide compelling support for the concept that these tumors represent an aberrant form of follicle organogenesis, and uncover potential limitations to treating BCCs using Hh pathway inhibitors.

Published
2004

20. Integration of Photosynthetic Protein Molecular Complexes in Solid-State Electronic Devices

Author

Francesco Stellacci, A. Amy Yu, Leyu Wang, Marc A. Baldo, Nikolai Lebedev, Patrick Kiley, R. Das, Rajay Kumar, Barry D. Bruce, L. Evan Reddick, Shuguang Zhang, Joel M. Schnur, Michael Segal, Julie E. Norville, and Scott A. Trammell

Subjects
Biophotovoltaic, Chemistry, Mechanical Engineering, Energy conversion efficiency, Analytical chemistry, Quantum yield, Bioengineering, General Chemistry, engineering.material, Condensed Matter Physics, Photosynthesis, Organic semiconductor, Coating, Chemical engineering, Monolayer, engineering, General Materials Science, Photosynthetic bacteria
Abstract

Plants and photosynthetic bacteria contain protein−molecular complexes that harvest photons with nearly optimum quantum yield and an expected power conversion efficiency exceeding 20%. In this work, we demonstrate the integration of electrically active photosynthetic protein−molecular complexes in solid-state devices, realizing photodetectors and photovoltaic cells with internal quantum efficiencies of approximately 12%. Electronic integration of devices is achieved by self-assembling an oriented monolayer of photosynthetic complexes, stabilizing them with surfactant peptides, and then coating them with a protective organic semiconductor.

Published
2004

21. Delaware Follows Suit, Joins Number Of Jurisdictions Banning Salary History Inquiries

Author

Gorder, L. Evan Van

Subjects
Labor law -- Interpretation and construction, Wages and salaries -- Laws, regulations and rules, Compensation (Business) -- Laws, regulations and rules, Government regulation, Salary, Business, international
Abstract

On June 14, 2017, Delaware's governor signed a measure enacting a pay history inquiry ban similar to those enacted recently in Massachusetts, New York City, Philadelphia, and Puerto Rico. Specifically, [...]

Published
2017

22. Evaluating the performance of temporal pattern discovery: new application using statins and rhabdomyolysis in OMOP databases

Author

M. Lavallee, T. Yu, L. Evans, M. Van Hemelrijck, C. Bosco, A. Golozar, and A. Asiimwe

Subjects
Temporal pattern discover, Adverse events, Statins, Rhabdomyolysis, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Background Temporal pattern discovery (TPD) is a method of signal detection using electronic healthcare databases, serving as an alternative to spontaneous reporting of adverse drug events. Here, we aimed to replicate and optimise a TPD approach previously used to assess temporal signals of statins with rhabdomyolysis (in The Health Improvement Network (THIN) database) by using the OHDSI tools designed for OMOP data sources. Methods We used data from the Truven MarketScan US Commercial Claims and the Commercial Claims and Encounters (CCAE). Using an extension of the OHDSI ICTemporalPatternDiscovery package, we ran positive and negative controls through four analytical settings and calculated sensitivity, specificity, bias and AUC to assess performance. Results Similar to previous findings, we noted an increase in the Information Component (IC) for simvastatin and rhabdomyolysis following initial exposure and throughout the surveillance window. For example, the change in IC was 0.266 for the surveillance period of 1–30 days as compared to the control period of − 180 to − 1 days. Our modification of the existing OHDSI software allowed for faster queries and more efficient generation of chronographs. Conclusion Our OMOP replication matched the we can account forwe can account for of the original THIN study, only simvastatin had a signal. The TPD method is a useful signal detection tool that provides a single statistic on temporal association and a graphical depiction of the temporal pattern of the drug outcome combination. It remains unclear if the method works well for rare adverse events, but it has been shown to be a useful risk identification tool for longitudinal observational databases. Future work should compare the performance of TPD with other pharmacoepidemiology methods and mining techniques of signal detection. In addition, it would be worth investigating the relative TPD performance characteristics using a variety of observational data sources.

Published
2022
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25. Express Your LOV: An Engineered Flavoprotein as a Reporter for Protein Expression and Purification

Author

John M. Christie, Andrew J. Roe, L. Evan Reddick, Mads Gabrielsen, Neal M. Alto, Jayde A. Gawthorne, Katherine S. H. Beckham, and Snezhana Akpunarlieva

Subjects
Proteases, Applied Microbiology, lcsh:Medicine, Gene Expression, Golgi Apparatus, Biology, medicine.disease_cause, Kidney, Biochemistry, Microbiology, Green fluorescent protein, 03 medical and health sciences, Viral Proteins, Plasmid, medicine, Genetics, Escherichia coli, Animals, Cloning, Molecular, lcsh:Science, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Cell fusion, Flavoproteins, 030306 microbiology, Effector, Escherichia coli Proteins, lcsh:R, 3C Viral Proteases, Kidney metabolism, Proteins, Bacteriology, Recombinant Proteins, Cell biology, Rats, Luminescent Proteins, Cysteine Endopeptidases, Cell culture, lcsh:Q, Gene Function, Genetic Engineering, Research Article, Biotechnology
Abstract

In this work, we describe the utility of Light, Oxygen, or Voltage-sensing (LOV) flavoprotein domains from plant phototropins as a reporter for protein expression and function. Specifically, we used iLOV, an enhanced and more photostable variant of LOV. A pET-based plasmid for protein expression was constructed, encoding a C terminal iLOV-octahistidine (His8)-tag and a HRV 3C protease cleavage recognition site. Ten different proteins, with various sub-cellular locations, were cloned into the plasmid, creating iLOV-His8 tag fusions. To test protein expression and how iLOV could be used as a reporter, the proteins were expressed in three different cell lines, in four different culture media, at two different temperatures. To establish whether the presence of the iLOV tag could have an impact on the functionality, one of the proteins, EspG, was over-expressed and purified. EspG is an "effector" protein normally produced by enterohemorrhagic E. coli strains and "injected" into host cells via the T3SS. We tested functionality of EspG-iLOV fusion by performing functional studies of EspG in mammalian host cells. When EspG-iLOV was microinjected into the host cell, the Golgi apparatus was completely disrupted as had previously been observed for EspG.

Published
2012

26. Differential transit peptide recognition during preprotein binding and translocation into flowering plant plastids

Author

Ian M. Campbell, L. Evan Reddick, Prakitchai Chotewutmontri, Barry D. Bruce, and David R. McWilliams

Subjects
Models, Molecular, Chloroplasts, Protein subunit, Recombinant Fusion Proteins, Ribulose-Bisphosphate Carboxylase, Molecular Sequence Data, Sequence alignment, Plant Science, Plasma protein binding, Biology, Magnoliopsida, Protein structure, Transit Peptide, Tobacco, Amino Acid Sequence, Plastids, Protein Precursors, Peptide sequence, Research Articles, Preprotein binding, Plant Proteins, Hydrolysis, Peas, food and beverages, Computational Biology, Cell Biology, Translocon, Cell biology, Protein Structure, Tertiary, Protein Transport, Biochemistry, Ferredoxins, Carrier Proteins, Peptides, Sequence Alignment, Protein Binding
Abstract

Despite the availability of thousands of transit peptide (TP) primary sequences, the structural and/or physicochemical properties that determine TP recognition by components of the chloroplast translocon are not well understood. By combining a series of in vitro and in vivo experiments, we reveal that TP recognition is determined by sequence-independent interactions and vectorial-specific recognition domains. Using both native and reversed TPs for two well-studied precursors, small subunit of ribulose-1,5-bis-phosphate carboxylase/oxygenase, and ferredoxin, we exposed these two modes of recognition. Toc34 receptor (34-kD subunit of the translocon of the outer envelope) recognition in vitro, preprotein binding in organellar, precursor binding in vivo, and the recognition of TPs by the major stromal molecular motor Hsp70 are specific for the physicochemical properties of the TP. However, translocation in organellar and in vivo demonstrates strong specificity to recognition domain organization. This organization specificity correlates with the N-terminal placement of a strong Hsp70 recognition element. These results are discussed in light of how individual translocon components sequentially interact with the precursor during binding and translocation and helps explain the apparent lack of sequence conservation in chloroplast TPs.

Published
2012

27. Correlative light and electron microscopy (CLEM) as a tool to visualize microinjected molecules and their eukaryotic sub-cellular targets

Author

L. Evan Reddick and Neal M. Alto

Subjects
Microinjections, Confocal, General Chemical Engineering, Biology, Kidney, General Biochemistry, Genetics and Molecular Biology, law.invention, Cell Line, Microscopy, Electron, Transmission, Confocal microscopy, law, Microscopy, Fluorescence microscope, Animals, Humans, Ultrasonography, Microscopy, Confocal, General Immunology and Microbiology, General Neuroscience, Resolution (electron density), Subcellular localization, Cell biology, Rats, Cellular Biology, Eukaryotic Cells, Microscopy, Fluorescence, Ultrastructure, Electron microscope, HeLa Cells, Subcellular Fractions
Abstract

The eukaryotic cell relies on complex, highly regulated, and functionally distinct membrane bound compartments that preserve a biochemical polarity necessary for proper cellular function. Understanding how the enzymes, proteins, and cytoskeletal components govern and maintain this biochemical segregation is therefore of paramount importance. The use of fluorescently tagged molecules to localize to and/or perturb subcellular compartments has yielded a wealth of knowledge and advanced our understanding of cellular regulation. Imaging techniques such as fluorescent and confocal microscopy make ascertaining the position of a fluorescently tagged small molecule relatively straightforward, however the resolution of very small structures is limited. On the other hand, electron microscopy has revealed details of subcellular morphology at very high resolution, but its static nature makes it difficult to measure highly dynamic processes with precision. Thus, the combination of light microscopy with electron microscopy of the same sample, termed Correlative Light and Electron Microscopy (CLEM), affords the dual advantages of ultrafast fluorescent imaging with the high-resolution of electron microscopy. This powerful technique has been implemented to study many aspects of cell biology. Since its inception, this procedure has increased our ability to distinguish subcellular architectures and morphologies at high resolution. Here, we present a streamlined method for performing rapid microinjection followed by CLEM (Fig. 1). The microinjection CLEM procedure can be used to introduce specific quantities of small molecules and/or proteins directly into the eukaryotic cell cytoplasm and study the effects from millimeter to multi-nanometer resolution (Fig. 2). The technique is based on microinjecting cells grown on laser etched glass gridded coverslips affixed to the bottom of live cell dishes and imaging with both confocal fluorescent and electron microscopy. Localization of the cell(s) of interest is facilitated by the grid pattern, which is easily transferred, along with the cells of interest, to the Epon resin used for immobilization of samples and sectioning prior to electron microscopy analysis (Fig. 3). Overlay of fluorescent and EM images allows the user to determine the subcellular localization as well as any morphological and/or ultrastructural changes induced by the microinjected molecule of interest (Fig. 4). This technique is amenable to time points ranging from ≤5 s up to several hours, depending on the nature of the microinjected sample.

Published
2012

28. The performance simulation of multilayer reflectors in soft X-ray and EUV regions

Author

B L Evan and Shi Xu

Subjects
Materials science, Mathematical model, business.industry, Extreme ultraviolet lithography, Condensed Matter Physics, Computer Science Applications, Metal, Wavelength, Optics, Mechanics of Materials, Position (vector), Modeling and Simulation, visual_art, visual_art.visual_art_medium, Optoelectronics, General Materials Science, Thermal stability, Diffusion (business), business, Matrix method
Abstract

Mathematical models of interfacial roughness and interlayer diffusion and reaction, incorporated into the multilayer matrix method, in multilayer reflectors used in soft X-ray and EUV regions are created and discussed. Simulations on typical multilayers (e.g. Pt/a-Si, Pt/a-C and Ni/a-C) have revealed that the interfacial roughness reduces the peak reflectivity of a multilayer without a change of peak position, while the interlayer diffusion and reaction not only reduce the peak reflectivity sometimes (especially when diffusion occurs) but also shift the peak position. The interlayer diffusion causes more drastic change in multilayer performance than the interlayer reaction. The simulations on 'ideal' multilayer reflectors of commonly used materials (Pt, Mo, W, Ni, Cu) in conjunction with a-Si or a-C have also led to a recommended selection guide for material combinations over the wavelengths 3

Published
1994

29. Basal cell carcinomas in mice arise from hair follicle stem cells and multiple epithelial progenitor populations

Author

Joanna Pero, Monique Verhaegen, Alexandre N. Ermilov, Andrzej A. Dlugosz, L. Evan Michael, Seokchun Lim, Rajiv M. Patel, Li Jyun Syu, Jennifer Ferris, D. Wilbert, Mary A. Allen, Marina Grachtchouk, Aiqin Wang, Steven H. Yang, and James Diener

Subjects
Pathology, medicine.medical_specialty, Skin Neoplasms, Hamartoma, Kruppel-Like Transcription Factors, Mice, Transgenic, Biology, Zinc Finger Protein Gli2, medicine.disease_cause, Mice, GLI2, medicine, Animals, Humans, Basal cell carcinoma, Hedgehog Proteins, Hedgehog, Alleles, Progenitor, Hyperplasia, integumentary system, Stem Cells, Epithelial Cells, General Medicine, Hair follicle, medicine.disease, Protein Structure, Tertiary, medicine.anatomical_structure, Phenotype, Carcinoma, Basal Cell, Commentary, Stem cell, Epidermis, Carcinogenesis, Hair Follicle, Signal Transduction
Abstract

Uncontrolled Hedgehog (Hh) signaling leads to the development of basal cell carcinoma (BCC), the most common human cancer, but the cell of origin for BCC is unclear. While Hh pathway dysregulation is common to essentially all BCCs, there exist multiple histological subtypes, including superficial and nodular variants, raising the possibility that morphologically distinct BCCs may arise from different cellular compartments in skin. Here we have shown that induction of a major mediator of Hh signaling, GLI2 activator (GLI2ΔN), selectively in stem cells of resting hair follicles in mice, induced nodular BCC development from a small subset of cells in the lower bulge and secondary hair germ compartments. Tumorigenesis was markedly accelerated when GLI2ΔN was induced in growing hair follicles. In contrast, induction of GLI2ΔN in epidermis led to the formation of superficial BCCs. Expression of GLI2ΔN at reduced levels in mice yielded lesions resembling basaloid follicular hamartomas, which have previously been linked to low-level Hh signaling in both mice and humans. Our data show that the cell of origin, tissue context (quiescent versus growing hair follicles), and level of oncogenic signaling can determine the phenotype of Hh/Gli-driven skin tumors, with high-level signaling required for development of superficial BCC-like tumors from interfollicular epidermis and nodular BCC-like tumors from hair follicle stem cells.

Published
2011

30. The assembly of a GTPase–kinase signalling complex by a bacterial catalytic scaffold

Author

L. Evan Reddick, Diana R. Tomchick, Robert C. Orchard, Bethany A. Weigele, Sarah E. Sutton, Andrey S. Selyunin, Stefan Bresson, and Neal M. Alto

Subjects
Scaffold protein, Models, Molecular, ADP ribosylation factor, Protein Conformation, Golgi Apparatus, Plasma protein binding, GTPase, Biology, Crystallography, X-Ray, Endoplasmic Reticulum, Escherichia coli O157, Article, Cell Line, Mice, Allosteric Regulation, Catalytic Domain, Two-Hybrid System Techniques, Protein Interaction Mapping, Animals, Humans, Endomembrane system, p21-activated kinases, Protein Unfolding, Multidisciplinary, Effector, ADP-Ribosylation Factors, Escherichia coli Proteins, Hydrolysis, Biological Transport, Intracellular Membranes, Transport protein, Cell biology, Rats, Enzyme Activation, p21-Activated Kinases, Biocatalysis, Guanosine Triphosphate, Protein Binding, Signal Transduction
Abstract

Pathogenic strains of Escherichia coli translocate many proteins into the host cell to promote virulence. The structure of one of these proteins, EspG from E. coli O157:H7, has been determined in a complex with two host enzymes and its mechanism dissected. These structures reveal how EspG disrupts endomembrane trafficking pathways by specifically recognizing the GTP-bound active state of the host's ARF6 enzyme during the vesicle budding reaction at membrane organelles. EspG directly activates PAK kinase by trapping an unfolded transition state in the kinase activation cascade. Pathogenic Escherichia coli translocate many proteins into the host cell to promote virulence. It is now shown that one of these proteins, EspG, which is present in enterohaemorrhagic E. coli, interferes with the host signalling network. The fidelity and specificity of information flow within a cell is controlled by scaffolding proteins that assemble and link enzymes into signalling circuits1,2. These circuits can be inhibited by bacterial effector proteins that post-translationally modify individual pathway components3,4,5,6. However, there is emerging evidence that pathogens directly organize higher-order signalling networks through enzyme scaffolding7,8, and the identity of the effectors and their mechanisms of action are poorly understood. Here we identify the enterohaemorrhagic Escherichia coli O157:H7 type III effector EspG as a regulator of endomembrane trafficking using a functional screen, and report ADP-ribosylation factor (ARF) GTPases and p21-activated kinases (PAKs) as its relevant host substrates. The 2.5 A crystal structure of EspG in complex with ARF6 shows how EspG blocks GTPase-activating-protein-assisted GTP hydrolysis, revealing a potent mechanism of GTPase signalling inhibition at organelle membranes. In addition, the 2.8 A crystal structure of EspG in complex with the autoinhibitory Iα3-helix of PAK2 defines a previously unknown catalytic site in EspG and provides an allosteric mechanism of kinase activation by a bacterial effector. Unexpectedly, ARF and PAKs are organized on adjacent surfaces of EspG, indicating its role as a ‘catalytic scaffold’ that effectively reprograms cellular events through the functional assembly of GTPase-kinase signalling complex.

Published
2010

33. Nano-scale characterization of the dynamics of the chloroplast Toc translocon

Author

L Evan, Reddick, Prakitchai, Chotewutmontri, Will, Crenshaw, Ashita, Dave, Michael, Vaughn, and Barry D, Bruce

Subjects
Inclusion Bodies, Models, Molecular, Chloroplasts, Microscopy, Confocal, Hydrolysis, Ribulose-Bisphosphate Carboxylase, Blotting, Western, Molecular Sequence Data, Peas, Fluorescence, Recombinant Proteins, GTP Phosphohydrolases, Protein Structure, Tertiary, Protein Transport, Solubility, Guanine Nucleotide Exchange Factors, Nanotechnology, Biological Assay, Electrophoresis, Polyacrylamide Gel, Amino Acid Sequence, Peptides, Plant Proteins
Abstract

Translocons are macromolecular nano-scale machines that facilitate the selective translocation of proteins across membranes. Although common in function, different translocons have evolved diverse molecular mechanisms for protein translocation. Subcellular organelles of endosymbiotic origin such as the chloroplast and mitochondria had to evolve/acquire translocons capable of importing proteins whose genes were transferred to the host genome. These gene products are expressed on cytosolic ribosomes as precursor proteins and targeted back to the organelle by an N-terminal extension called the transit peptide or presequence. In chloroplasts the transit peptide is specifically recognized by the Translocon of the Outer Chloroplast membrane (Toc) which is composed of receptor GTPases that potentially function as gate-like switches, where GTP binding and hydrolysis somehow facilitate preprotein binding and translocation. Compared to other translocons, the dynamics of the Toc translocon are probably more complex and certainly less understood. We have developed biochemical/biophysical, imaging, and computational techniques to probe the dynamics of the Toc translocon at the nanoscale. In this chapter we provide detailed protocols for kinetic and binding analysis of precursor interactions in organeller, measurement of the activity and nucleotide binding of the Toc GTPases, native electrophoretic analysis of the assembly/organization of the Toc complex, visualization of the distribution and mobility of Toc apparatus on the surface of chloroplasts, and conclude with the identification and molecular modeling Toc75 POTRA domains. With these new methodologies we discuss future directions of the field.

Published
2009

34. Chapter 16 Nano‐scale Characterization of the Dynamics of the Chloroplast Toc Translocon

Author

Barry D. Bruce, Will Crenshaw, Prakitchai Chotewutmontri, Ashita Dave, Michael Vaughn, and L. Evan Reddick

Subjects
Toc complex, Chloroplast, Transit Peptide, lipids (amino acids, peptides, and proteins), GTPase, Biology, Translocon, environment and public health, Ribosome, Chloroplast membrane, Preprotein binding, Cell biology
Abstract

Translocons are macromolecular nano-scale machines that facilitate the selective translocation of proteins across membranes. Although common in function, different translocons have evolved diverse molecular mechanisms for protein translocation. Subcellular organelles of endosymbiotic origin such as the chloroplast and mitochondria had to evolve/acquire translocons capable of importing proteins whose genes were transferred to the host genome. These gene products are expressed on cytosolic ribosomes as precursor proteins and targeted back to the organelle by an N-terminal extension called the transit peptide or presequence. In chloroplasts the transit peptide is specifically recognized by the Translocon of the Outer Chloroplast membrane (Toc) which is composed of receptor GTPases that potentially function as gate-like switches, where GTP binding and hydrolysis somehow facilitate preprotein binding and translocation. Compared to other translocons, the dynamics of the Toc translocon are probably more complex and certainly less understood. We have developed biochemical/biophysical, imaging, and computational techniques to probe the dynamics of the Toc translocon at the nanoscale. In this chapter we provide detailed protocols for kinetic and binding analysis of precursor interactions in organeller, measurement of the activity and nucleotide binding of the Toc GTPases, native electrophoretic analysis of the assembly/organization of the Toc complex, visualization of the distribution and mobility of Toc apparatus on the surface of chloroplasts, and conclude with the identification and molecular modeling Toc75 POTRA domains. With these new methodologies we discuss future directions of the field.

Published
2008

35. Applications of the Zero-Group-Velocity Lamb Mode for Air-Coupled Ultrasonic Imaging

Author

Junho Song, Stephen D. Holland, Victoria L. Evan, and Dale E. Chimenti

Subjects
Honeycomb structure, Materials science, Transmission (telecommunications), business.industry, Nondestructive testing, Acoustics, Ultrasound, Mode (statistics), Group velocity, Sensitivity (control systems), Classification of discontinuities, business
Abstract

Airborne ultrasound couples particularly well into plates at the zero‐group‐velocity point of the first order symmetric (S1) Lamb mode. Applications of this mode to ultrasonic imaging of plate‐like structures are discussed. The sensitivity and high Q of this mode makes it ideal for imaging. Images from a wide variety of materials and samples, including composites and honeycomb structures are presented. Transmission at the zero‐group‐velocity frequency is shown to be particularly sensitive to nearby flaws and discontinuities, and is therefore suitable for wide‐area scanning for cracks or manufacturing flaws.

Published
2005

36. HIP1 and HIP1r stabilize receptor tyrosine kinases and bind 3-phosphoinositides via epsin N-terminal homology domains

Author

Djenann Saint-Dic, Theodora S. Ross, Teresa S. Hyun, Priti D. Kumar, Dinesh S. Rao, Katherine Oravecz-Wilson, Ikuko F. Mizukami, Sarah V. Bradley, and L. Evan Michael

Subjects
Epsin, Vesicular Transport Proteins, Biology, Phosphatidylinositols, Biochemistry, Receptor tyrosine kinase, chemistry.chemical_compound, Protein structure, Animals, Humans, Inositol, Phosphatidylinositol, ENTH domain, Molecular Biology, Adaptor Proteins, Signal Transducing, Binding Sites, Cell Death, Microfilament Proteins, Neuropeptides, Signal transducing adaptor protein, Antibodies, Monoclonal, Receptor Protein-Tyrosine Kinases, Cell Biology, Huntingtin-interacting protein 1, Clathrin, Endocytosis, Cell biology, Protein Structure, Tertiary, DNA-Binding Proteins, ErbB Receptors, Adaptor Proteins, Vesicular Transport, Kinetics, Protein Transport, chemistry, Mutagenesis, COS Cells, biology.protein, Carrier Proteins, HeLa Cells
Abstract

Huntingtin-interacting protein 1-related (HIP1r) is the only known mammalian relative of huntingtin-interacting protein 1 (HIP1), a protein that transforms fibroblasts via undefined mechanisms. Here we demonstrate that both HIP1r and HIP1 bind inositol lipids via their epsin N-terminal homology (ENTH) domains. In contrast to other ENTH domain-containing proteins, lipid binding is preferential to the 3-phosphate-containing inositol lipids, phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,5-bisphosphate. Furthermore, the HIP1r ENTH domain, like that of HIP1, is necessary for lipid binding, and expression of an ENTH domain-deletion mutant, HIP1r/deltaE, induces apoptosis. Consistent with the ability of HIP1r and HIP1 to affect cell survival, full-length HIP1 and HIP1r stabilize pools of growth factor receptors by prolonging their half-life following ligand-induced endocytosis. Although HIP1r and HIP1 display only a partially overlapping pattern of protein interactions, these data suggest that both proteins share a functional homology by binding 3-phosphorylated inositol lipids and stabilizing receptor tyrosine kinases in a fashion that may contribute to their ability to alter cell growth and survival.

Published
2004

38. Supersymmetric proton decay revisited

Author

John Ellis, L. Evans, Natsumi Nagata, Keith A. Olive, and Liliana Velasco-Sevilla

Subjects
Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

Abstract Encouraged by the advent of a new generation of underground detectors – JUNO, DUNE and Hyper-Kamiokande – that are projected to improve significantly on the present sensitivities to various baryon decay modes, we revisit baryon decay in the minimal supersymmetric SU(5) GUT. We discuss the phenomenological uncertainties associated with hadronic matrix elements and the value of the strong coupling $$\alpha _s$$ αs – which are the most important – the weak mixing angle $$\theta _W$$ θW , quark masses including one-loop renormalization effects, quark mixing and novel GUT phases that are not visible in electroweak interaction processes. We apply our analysis to a variety of CMSSM, super- and sub-GUT scenarios in which soft supersymmetry-breaking parameters are assumed to be universal at, above and below the GUT scale, respectively. In many cases, we find that the next generation of underground detectors should be able to probe models with sparticle masses that are $${{\mathcal {O}}}(10)$$ O(10) TeV, beyond the reach of the LHC.

Published
2020
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39. Mining for natural product antileishmanials in a fungal extract library

Author

A.J. Mbekeani, R.S. Jones, M. Bassas Llorens, J. Elliot, C. Regnault, M.P. Barrett, J. Steele, B. Kebede, S.K. Wrigley, L. Evans, and P.W. Denny

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Leishmaniasis is a Neglected Tropical Disease caused by the insect-vector borne protozoan parasite, Leishmania species. Infection affects millions of the World's poorest, however vaccines are absent and drug therapy limited. Recently, public-private partnerships have developed to identify new modes of controlling leishmaniasis. Most of these collaborative efforts have relied upon the small molecule synthetic compound libraries held by industry, but the number of New Chemical Entities (NCE) identified and entering development as antileishmanials has been very low. In light of this, here we describe a public-private effort to identify natural products with activity against Leishmania mexicana, a causative agent of cutaneous leishmanaisis (CL). Utilising Hypha Discovery's fungal extract library which is rich in small molecule (

Published
2019
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44. Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle

Author

Hutchin, Mark E., primary, Kariapper, Muhammed S.T., additional, Grachtchouk, Marina, additional, Wang, Aiqin, additional, Wei, Lebing, additional, Cummings, Donelle, additional, Liu, Jianhong, additional, Michael, L. Evan, additional, Glick, Adam, additional, and Dlugosz, Andrzej A., additional

Published
2004
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45. Integration of Photosynthetic Protein Molecular Complexes in Solid-State Electronic Devices

Author

Das, Rupa, primary, Kiley, Patrick J., additional, Segal, Michael, additional, Norville, Julie, additional, Yu, A. Amy, additional, Wang, Leyu, additional, Trammell, Scott A., additional, Reddick, L. Evan, additional, Kumar, Rajay, additional, Stellacci, Francesco, additional, Lebedev, Nikolai, additional, Schnur, Joel, additional, Bruce, Barry D., additional, Zhang, Shuguang, additional, and Baldo, Marc, additional

Published
2004
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48. Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry

Author

Jitendra PS. Sawhney, Veerappa A. Kothiwale, Vikas Bisne, Rajashekhar Durgaprasad, Praveen Jadhav, Manoj Chopda, Velam Vanajakshamma, Ramdhan Meena, Govindan Vijayaraghavan, Kamaldeep Chawla, Jagan Allu, Karen S. Pieper, A. John Camm, Ajay K. Kakkar, Jean-Pierre Bassand, David A. Fitzmaurice, Samuel Z. Goldhaber, Shinya Goto, Sylvia Haas, Werner Hacke, Lorenzo G. Mantovani, Frank Misselwitz, Alexander G.G. Turpie, Martin van Eickels, Freek W.A. Verheugt, Gloria Kayani, Keith A.A. Fox, Bernard J. Gersh, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Frank Cools, Antonio Carlos Pereira Barretto, Stuart J. Connolly, Alex Spyropoulos, John Eikelboom, Ramon Corbalan, Dayi Hu, Petr Jansky, Jørn Dalsgaard Nielsen, Hany Ragy, Pekka Raatikainen, Jean-Yves Le Heuzey, Harald Darius, Matyas Keltai, Sanjay Kakkar, Jitendra Pal Singh Sawhney, Giancarlo Agnelli, Giuseppe Ambrosio, Yukihiro Koretsune, Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan Atar, Janina Stepinska, Elizaveta Panchenko, Toon Wei Lim, Barry Jacobson, Seil Oh, Xavier Viñolas, Marten Rosenqvist, Jan Steffel, Pantep Angchaisuksiri, Ali Oto, Alex Parkhomenko, Wael Al Mahmeed, David Fitzmaurice, D.Y. Hu, K.N. Chen, Y.S. Zhao, H.Q. Zhang, J.Z. Chen, S.P. Cao, D.W. Wang, Y.J. Yang, W.H. Li, Y.H. Yin, G.Z. Tao, P. Yang, Y.M. Chen, S.H. He, Ying Wang, Yong Wang, G.S. Fu, X. Li, T.G. Wu, X.S. Cheng, X.W. Yan, R.P. Zhao, M.S. Chen, L.G. Xiong, P. Chen, Y. Jiao, Y. Guo, L. Xue, F.Z. Wang, H. Li, Z.M. Yang, C.L. Bai, J. Chen, J.Y. Chen, X. Chen, S. Feng, Q.H. Fu, X.J. Gao, W.N. Guo, R.H. He, X.A. He, X.S. Hu, X.F. Huang, B. Li, J. Li, L. Li, Y.H. Li, T.T. Liu, W.L. Liu, Y.Y. Liu, Z.C. Lu, X.L. Luo, T.Y. Ma, J.Q. Peng, X. Sheng, X.J. Shi, Y.H. Sun, G. Tian, K. Wang, L. Wang, R.N. Wu, Q. Xie, R.Y. Xu, J.S. Yang, L.L. Yang, Q. Yang, Y. Ye, H.Y. Yu, J.H. Yu, T. Yu, H. Zhai, Q. Zhan, G.S. Zhang, Q. Zhang, R. Zhang, Y. Zhang, W.Y. Zheng, B. Zhou, Z.H. Zhou, X.Y. Zhu, S. Kakkar, J.P.S. Sawhney, P. Jadhav, R. Durgaprasad, A.G. Ravi Shankar, R.K. Rajput, K. Bhargava, R. Sarma, A. Srinivas, D. Roy, U.M. Nagamalesh, M. Chopda, R. Kishore, G. Kulkarni, P. Chandwani, R.A. Pothiwala, M. Padinhare Purayil, S. Shah, K. Chawla, V.A. Kothiwale, B. Raghuraman, G. Vijayaraghavan, V.M. Vijan, G. Bantwal, V. Bisne, A. Khan, J.B. Gupta, S. Kumar, D. Jain, S. Abraham, D. Adak, A. Barai, H. Begum, P. Bhattacharjee, M. Dargude, D. Davies, B. Deshpande, P. Dhakrao, V. Dhyani, S. Duhan, M. Earath, A. Ganatra, S. Giradkar, V. Jain, R. Karthikeyan, L. Kasala, S. Kaur, S. Krishnappa, A. Lawande, B. Lokesh, N. Madarkar, R. Meena, P. More, D. Naik, K. Prashanth, M. Rao, N.M. Rao, N. Sadhu, D. Shah, M. Sharma, P. Shiva, S. Singhal, S. Suresh, V. Vanajakshamma, S.G. Panse, Y. Koretsune, S. Kanamori, K. Yamamoto, K. Kumagai, Y. Katsuda, K. Sadamatsu, F. Toyota, Y. Mizuno, I. Misumi, H. Noguchi, S. Ando, T. Suetsugu, M. Minamoto, Hiroshi Oda, K. Shiraishi, S. Adachi, K. Chiba, H. Norita, M. Tsuruta, T. Koyanagi, H. Ando, T. Higashi, K. Okada, S. Azakami, S. Komaki, K. Kumeda, T. Murayama, J. Matsumura, Y. Oba, R. Sonoda, K. Goto, K. Minoda, Y. Haraguchi, H. Suefuji, H. Miyagi, H. Kato, Tadashi Nakamura, Tsugihiro Nakamura, H. Nandate, R. Zaitsu, Yoshihisa Fujiura, A. Yoshimura, H. Numata, J. Ogawa, H. Tatematsu, Y. Kamogawa, K. Murakami, Y. Wakasa, M. Yamasawa, H. Maekawa, S. Abe, H. Kihara, S. Tsunoda, Katsumi Saito, Kazuyuki Saito, T. Fudo, K. Obunai, H. Tachibana, I. Oba, T. Kuwahata, S. Higa, M. Gushiken, T. Eto, H. Yoshida, D. Ikeda, Yoshitake Fujiura, M. Ishizawa, M. Nakatsuka, K. Murata, C. Ogurusu, M. Shimoyama, M. Akutsu, I. Takamura, F. Hoshino, N. Yokota, T. Iwao, K. Tsuchida, M. Takeuchi, Y. Hatori, Y. Kitami, Yoichi Nakamura, R. Oyama, M. Ageta, Hiroyuki Oda, Y. Go, K. Mishima, T. Unoki, S. Morii, Yuhei Shiga, H. Sumi, T. Nagatomo, K. Sanno, K. Fujisawa, Y. Atsuchi, T. Nagoshi, T. Seto, T. Tabuchi, M. Kameko, K. Nii, K. Oshiro, H. Takezawa, S. Nagano, N. Miyamoto, M. Iwaki, Yuichiro Nakamura, M. Fujii, M. Okawa, Masahiko Abe, Masatake Abe, Mitsunori Abe, T. Saito, T. Mito, K. Nagao, J. Minami, T. Mita, I. Sakuma, T. Taguchi, S. Marusaki, H. Doi, M. Tanaka, T. Fujito, M. Matsuta, T. Kusumoto, S. Kakinoki, K. Ashida, N. Yoshizawa, J. Agata, O. Arasaki, M. Manita, M. Ikemura, S. Fukuoka, H. Murakami, S. Matsukawa, Y. Hata, T. Taniguchi, T. Ko, H. Kubo, M. Imamaki, M. Akiyama, M. Inagaki, H. Odakura, T. Ueda, Y. Katsube, A. Nakata, H. Watanabe, M. Techigawara, M. Igarashi, K. Taga, T. Kimura, S. Tomimoto, M. Shibuya, M. Nakano, K. Ito, T. Seo, S. Hiramitsu, H. Hosokawa, M. Hoshiai, M. Hibino, K. Miyagawa, Hajime Horie, N. Sugishita, Yukio Shiga, A. Soma, K. Neya, Tetsuro Yoshida, Tomoki Yoshida, M. Mizuguchi, M. Ishiguro, T. Minagawa, M. Wada, H. Mukawa, F. Okuda, S. Nagasaka, Y. Abe, Sen Adachi, Susumu Adachi, T. Adachi, K. Akahane, T. Amano, K. Aoki, T. Aoyama, H. Arai, S. Arima, T. Arino, H. Asano, T. Asano, J. Azuma, T. Baba, T. Betsuyaku, H. Chibana, H. Date, J. Doiuchi, Y. Emura, M. Endo, Y. Fujii, R. Fujiki, A. Fujisawa, Y. Fujisawa, T. Fukuda, T. Fukui, N. Furukawa, T. Furukawa, W. Furumoto, T. Goto, M. Hamaoka, N. Hanazono, K. Hasegawa, T. Hatsuno, Y. Hayashi, K. Higuchi, K. Hirasawa, H. Hirayama, M. Hirose, S. Hirota, M. Honda, Hideki Horie, T. Ido, O. Iiji, H. Ikeda, K. Ikeda, K. Ikeoka, M. Imaizumi, H. Inaba, T. Inoue, F. Iseki, A. Ishihara, N. Ishioka, N. Ito, T. Iwase, H. Kakuda, J. Kamata, H. Kanai, H. Kanda, M. Kaneko, H. Kano, T. Kasai, T. Kato, Y. Kato, Y. Kawada, K. Kawai, K. Kawakami, S. Kawakami, T. Kawamoto, S. Kawano, J. Kim, T. Kira, H. Kitazawa, H. Kitazumi, T. Kito, T. Kobayashi, T. Koeda, J. Kojima, H. Komatsu, I. Komatsu, Y. Koshibu, T. Kotani, T. Kozuka, Y. Kumai, T. Kumazaki, I. Maeda, K. Maeda, Y. Maruyama, S. Matsui, K. Matsushita, Y. Matsuura, K. Mineoi, H. Mitsuhashi, N. Miura, S. Miyaguchi, S. Miyajima, H. Miyamoto, A. Miyashita, S. Miyata, I. Mizuguchi, A. Mizuno, T. Mori, O. Moriai, K. Morishita, O. Murai, Sho Nagai, Shunichi Nagai, E. Nagata, H. Nagata, A. Nakagomi, S. Nakahara, M. Nakamura, R. Nakamura, N. Nakanishi, T. Nakayama, R. Nakazato, T. Nanke, J. Nariyama, Y. Niijima, H. Niinuma, Y. Nishida, Y. Nishihata, K. Nishino, H. Nishioka, K. Nishizawa, I. Niwa, K. Nomura, S. Nomura, M. Nozoe, T. Ogawa, N. Ohara, M. Okada, K. Okamoto, H. Okita, M. Okuyama, H. Ono, T. Ono, Y. Onuki Pearce, S. Oriso, A. Ota, E. Otaki, Y. Saito, H. Sakai, N. Sakamoto, Y. Sakamoto, Y. Samejima, Y. Sasagawa, H. Sasaguri, A. Sasaki, T. Sasaki, Kazuki Sato, Kiyoharu Sato, M. Sawano, S. Seki, Y. Sekine, Y. Seta, K. Sezaki, N. Shibata, Y. Shiina, H. Shimono, Y. Shimoyama, T. Shindo, H. Shinohara, R. Shinohe, T. Shinozuka, T. Shirai, T. Shiraiwa, Y. Shozawa, T. Suga, C. Sugimoto, Kazuo Suzuki, Keita Suzuki, Shu Suzuki, Shunji Suzuki, Susumu Suzuki, Y. Suzuki, M. Tada, A. Taguchi, T. Takagi, Y. Takagi, K. Takahashi, S. Takahashi, H. Takai, C. Takanaka, S. Take, H. Takeda, K. Takei, K. Takenaka, T. Tana, G. Tanabe, K. Taya, H. Teragawa, S. Tohyo, S. Toru, Y. Tsuchiya, T. Tsuji, K. Tsuzaki, H. Uchiyama, O. Ueda, Y. Ueyama, N. Wakaki, T. Wakiyama, T. Washizuka, M. Watanabe, T. Yamada, T. Yamagishi, H. Yamaguchi, Kenichi Yamamoto, Kentaro Yamamoto, Kunihiko Yamamoto, T. Yamamoto, M. Yamaura, M. Yamazoe, K. Yasui, Y. Yokoyama, K. Yoshida, T.W. Lim, C.K. Ching, C.G. Foo, J.H. Chow, D.D. Chen, F.R. Jaufeerally, Y.M. Lee, G. Lim, W.T. Lim, S. Thng, S.Y. Yap, C. Yeo, S. Oh, H.N. Pak, J.-B. Kim, J.H. Kim, S.-W. Jang, D.H. Kim, D.R. Ryu, S.W. Park, D.-K. Kim, D.J. Choi, Y.S. Oh, M.-C. Cho, S.-H. Kim, H.-K. Jeon, D.-G. Shin, J.S. Park, H.K. Park, S.-J. Han, J.H. Sung, J.-G. Cho, G.-B. Nam, Y.K. On, H.E. Lim, J.J. Kwak, T.-J. Cha, T.J. Hong, S.H. Park, J.H. Yoon, N.-H. Kim, K.-S. Kim, B.C. Jung, G.-S. Hwang, C.-J. Kim, D.B. Kim, J.J. Ahn, H.J. An, H. Bae, A.L. Baek, W.J. Chi, E.A. Choi, E.H. Choi, H.K. Choi, H.S. Choi, S. Han, E.S. Heo, K.O. Her, S.W. Hwang, E.M. Jang, H.-S. Jang, S. Jang, H.-G. Jeon, S.R. Jeon, Y.R. Jeon, H.K. Jeong, I.-A. Jung, Hyeon Jeong Kim, Hyun Ju Kim, Ji Seon Kim, Jung Sook Kim, J.A. Kim, K.T. Kim, M.S. Kim, Sang Hee Kim, Sang Hyun Kim, Y.-I. Kim, C.S. Lee, E.H. Lee, G.H. Lee, H.Y. Lee, H.-Y. Lee, K.H. Lee, K.R. Lee, M.S. Lee, M.-Y. Lee, R.W. Lee, S.E. Lee, S.H. Lee, S. Lee, W.Y. Lee, I.K. Noh, A.R. Park, B.R. Park, H.N. Park, J.H. Park, M. Park, Y. Park, S.-Y. Seo, J. Shim, J.H. Sim, Y.M. Sohn, W.S. Son, Y.S. Son, H.J. Song, H.K. Wi, J.J. Woo, S. Ye, K.H. Yim, K.M. Yoo, E.J. Yoon, S.Y. Yun, P. Angchaisuksiri, S. Chawanadelert, P. Mongkolwongroj, K. Kanokphatcharakun, S. 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Nathani, M. Ibrahim, E.M. Esheiba, R. Singh, A. Naguib, M. Abu-Mahfouz, M. Al Omairi, A. Al Naeemi, R. Maruthanayagam, N. Bazargani, A. Wassef, R. Gupta, M. Khan, B. Subbaraman, A. Abdul, A. Al Mulla, S. El Bardisy, P. Haridas, S. Jadhav, K. Magdaluyo, M. Makdad, I. Maqsood, R. Mohamed, N. Sharma, R. Sharma, M. Thanzeel, S.Z. Goldhaber, R. Canosa, P. Rama, E. Blumberg, J. Garcia, P. Mullen, V. Wilson, A. Quick, K. Ferrick, W.M. Kutayli, M. Cox, M. Franco, S. Falkowski, R. Mendelson, M. Williams, S. Miller, S. Beach, A. Alfieri, T. Gutowski, I. Haque, R. Reddy, W. Ahmed, P. Delafontaine, D. Diercks, D. Theodoro, K. Remmel, M. Alberts, R. Ison, H. Noveck, P. Duffy, S. Pitta, D. Nishijima, C. Treasure, N. Asafu-Adjaye, K. Ball, M. Bartlett, M. Bentley, S. Bowers, A. Brown, A. Browne, J. Cameron-Watts, M. Canova, D. Cassidy, K. Cervellione, S. Congal, J. DePauw, A. Dickerson, M. Eley, L. Evans, S. Felpel, K. Ferdinand, D. Fielder, P. Gentry, A. Haideri, F. Hakimi, T. Harbour, E. Hartranft, B. Hawkins, M. Headlee, L. Henson, C. Herrick, T. Hicks, S. Jasinski, A. Jones, L. Jones, P. Jones, S. Karl, M. Keeling, J. Kerr, P. Knowles, J. Langdon, M. Lay, J.A. Lee, T. Lincoln, E. Malone, A. Merliss, D. Merritt, J. Minardo, B. Mooso, C. Orosco, V. Palumbo, M. Parker, T. Parrott, S. Paserchia, G. Pearl, J. Peterson, N. Pickelsimer, T. Purcell, J. Raynor, S. Raziano, C. Richard, T. Richardson, C. Robertson, A. Sage, T. Sanghera, P. Shaw, J. Shoemaker, K. Smith, B. Stephanie, A. Thatcher, H. Theobald, N. Thompson, L. Treasure, T. Tripti, C. Verdi, and V. Worthy

Subjects
Surgery, RD1-811, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

Published
2018
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49. The world without language

Author

L., Evan

Abstract

"Ah noo," said the seer as she looked into her crystal ball. "What is it?" asked the customer, who had asked her what the world would be like in ten […]

Published
2009

50. Fracture Behaviour of Concrete with Reactive Magnesium Oxide as Alternative Binder

Author

J. A. Forero, M. Bravo, J. Pacheco, J. de Brito, and L. Evangelista

Subjects
reactive magnesium oxide, fracture energy, wedge splitting test, alternative binder, concrete, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

This research evaluates the fracture behavior of concrete with reactive magnesium oxide (MgO). Replacing cement with MgO is an attractive option for the concrete industry, mainly due to sustainability benefits and reduction of shrinkage. Four different MgO’s from Australia, Canada, and Spain were used in the concrete mixes, as a partial substitute of cement, at 5%, 10%, and 20% (by weight). The fracture toughness (KI) intensity factor and the stress–strain softening parameters of the wedge split test were evaluated after 28 days. The experimental results showed that the replacement of cement with MgO reduced the fracture energy between 13% and 53%. Moreover, the fracture energy was found to be correlated with both compressive strength and modulus of elasticity. A well-defined relationship between these properties is important for an adequate prediction of the non-linear behavior of reinforced concrete structures made with partial replacement of cement with MgO.

Published
2021
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