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Michael Porter

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https://www.readbyqxmd.com/read/29241011/silver-free-palladium-catalyzed-c-sp3-h-arylation-of-saturated-bicyclic-amine-scaffolds
#1
Charlotte E Coomber, Laure Benhamou, Dejan-Krešimir Bučar, Peter D Smith, Michael J Porter, Tom David Sheppard
Herein we report a silver-free Pd(II)-catalyzed C(sp3)-H arylation of saturated bicyclic and tricyclic amine scaffolds. The reaction provides good yields using a range of aryl iodides and aryl bromides including functionalized examples bearing aldehydes, ketones, esters, free phenols and heterocycles. The methodology has been applied to medicinally relevant scaffolds. Two of the intermediate palladium complexes in the catalytic cycle have been prepared and characterized, and a mechanism proposed. Removal of the directing group proceeded with good yield under relatively mild conditions...
December 14, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29213124/the-ra-map-consortium-a-working-model-for-academia-industry-collaboration
#2
REVIEW
Andrew P Cope, Michael R Barnes, Alexandra Belson, Michael Binks, Sarah Brockbank, Francisco Bonachela-Capdevila, Claudio Carini, Benjamin A Fisher, Carl S Goodyear, Paul Emery, Michael R Ehrenstein, Neil Gozzard, Ray Harris, Sally Hollis, Sarah Keidel, Marc Levesque, Catharina Lindholm, Michael F McDermott, Iain B McInnes, Christopher M Mela, Gerry Parker, Simon Read, Ayako Wakatsuki Pedersen, Frederique Ponchel, Duncan Porter, Ravi Rao, Anthony Rowe, Peter Schulze-Knappe, Matthew A Sleeman, Deborah Symmons, Peter C Taylor, Brian Tom, Wayne Tsuji, Denny Verbeeck, John D Isaacs
Collaboration can be challenging; nevertheless, the emerging successes of large, multi-partner, multi-national cooperatives and research networks in the biomedical sector have sustained the appetite of academics and industry partners for developing and fostering new research consortia. This model has percolated down to national funding agencies across the globe, leading to funding for projects that aim to realise the true potential of genomic medicine in the 21st century and to reap the rewards of 'big data'...
December 7, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/29183129/synthesis-of-4-5-diazaspiro-2-3-hexanes-and-1-2-diazaspiro-3-3-heptanes-as-hexahydropyridazine-analogues
#3
Alpa K Pancholi, Gregory P Iacobini, Guy J Clarkson, David W Porter, Michael Shipman
4,5-Diazaspiro[2.3]hexanes are made by dihalocarbene addition across the exocyclic double bond of readily accessible 3-alkylidene-1,2-diazetidines. Using difluorocarbene, generated from TMSCF3/NaI, these spirocycles were produced in yields up to 97% by stereospecific addition across the alkene. Lower yields (up to 64%) were observed using more reactive dichlorocarbene, due to competitive insertion of the carbene into the N-N bond. Larger 1,2-diazaspiro[3.3]heptanes are produced by [2+2] cycloaddition of 3-alkylidene-1,2-diazetidines with tetracyanoethylene (TCNE) in up to 99% yield...
November 28, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29182501/radiolar-eyes-of-serpulid-worms-annelida-serpulidae-structures-function-and-phototransduction
#4
Michael J Bok, Megan L Porter, Harry A Ten Hove, Richard Smith, Dan-Eric Nilsson
Fan worms, represented by sabellid and serpulid polychaetes, have an astonishing array of unusual eyes and photoreceptors located on their eponymous feeding appendages. Here we organize the previous descriptions of these eyes in serpulids and report new anatomical, molecular, and physiological data regarding their structure, function, and evolution and the likely identity of their phototransduction machinery. We report that, as in sabellids, serpulids display a broad diversity of radiolar eye arrangements and ocellar structures...
August 2017: Biological Bulletin
https://www.readbyqxmd.com/read/29179292/bringing-value-based-perspectives-to-care-including-patient-and-family-members-in-decision-making-processes
#5
Graeme Kohler, Tara Sampalli, Ashley Ryer, Judy Porter, Les Wood, Lisa Bedford, Irene Higgins-Bowser, Lynn Edwards, Erin Christian, Susan Dunn, Rick Gibson, Shannon Ryan Carson, Michael Vallis, Joanna Zed, Barna Tugwell, Colin Van Zoost, Carolyn Canfield, Eleanor Rivoire
BACKGROUND: Recent evidence shows that patient engagement is an important strategy in achieving a high performing healthcare system. While there is considerable evidence of implementation initiatives in direct care context, there is limited investigation of implementation initiatives in decision-making context as it relates to program planning, service delivery and developing policies. Research has also shown a gap in consistent application of system-level strategies that can effectively translate organizational policies around patient and family engagement into practice...
March 6, 2017: International Journal of Health Policy and Management
https://www.readbyqxmd.com/read/29171289/preclinical-biomarker-qualification
#6
John-Michael Sauer, Amy C Porter
Biomarkers are ubiquitously used within drug development programs in both nonclinical species and in humans to assess safety and efficacy of novel compounds. To routinely apply such novel biomarkers with certainty, a well-defined data package is necessary for review and endorsement by regulatory agencies including the US Food and Drug Administration, European Medicines Agency, and Japanese Pharmaceuticals and Medical Devices Agency. This type of endorsement is known as regulatory qualification. Novel approaches are being applied to speed the process, lower the resource intensity, and increase the accessibility of biomarker qualification data and it is likely that consortia will continue to play a fundamental role in the qualification process by bringing together like-minded stakeholders focused on specific tools to accelerate drug development...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29171092/oral-keratinocytes-synthesize-ctack-a-new-insight-into-the-pathophysiology-of-the-oral-mucosa
#7
Alison Marshall, Antonio Celentano, Nicola Cirillo, Michael McCullough, Stephen Porter
The skin-associated chemokine CTACK plays a key role in many inflammatory conditions and could be instrumental in the pathophysiology of tissue-specific immunological diseases such as oral lichen planus (OLP). In the present study, we investigated by RT-PCR, ELISA, chemotaxis assays, and fluorescence-activated cell sorting (FACS) the production of CTACK in oral keratinocytes, its expression in tissues from normal and OLP patients, and its role in T cell recruitment. CTACK was produced by the oral epithelium and it affects chemotaxis of memory CLA+ cells to the oral epithelium...
November 24, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/29166655/how-well-do-you-know-your-mutation-complex-effects-of-genetic-background-on-expressivity-complementation-and-ordering-of-allelic-effects
#8
Christopher H Chandler, Sudarshan Chari, Alycia Kowalski, Lin Choi, David Tack, Michael DeNieu, William Pitchers, Anne Sonnenschein, Leslie Marvin, Kristen Hummel, Christian Marier, Andrew Victory, Cody Porter, Anna Mammel, Julie Holms, Gayatri Sivaratnam, Ian Dworkin
For a given gene, different mutations influence organismal phenotypes to varying degrees. However, the expressivity of these variants not only depends on the DNA lesion associated with the mutation, but also on factors including the genetic background and rearing environment. The degree to which these factors influence related alleles, genes, or pathways similarly, and whether similar developmental mechanisms underlie variation in the expressivity of a single allele across conditions and among alleles is poorly understood...
November 22, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29165004/person-directed-care-planning-in-nursing-homes-resident-family-and-staff-perspectives
#9
Kezia Scales, Michael Lepore, Ruth A Anderson, Eleanor S McConnell, Yuting Song, Bada Kang, Kristie Porter, Trini Thach, Kirsten N Corazzini
Empowering individuals to direct their own care is central to person-centered care and health care policy. However, there is limited knowledge of how "person-directed care planning" (PDCP) can be achieved in particular settings. This study identifies key structures and processes for operationalizing and implementing PDCP in nursing homes. Using participatory inquiry, we convened "stakeholder engagement sessions" with residents, families, nursing staff, and managers/administrators in two North Carolina nursing homes ( N = 24 sessions; N = 67 unique participants)...
September 1, 2017: Journal of Applied Gerontology: the Official Journal of the Southern Gerontological Society
https://www.readbyqxmd.com/read/29164205/theory-of-sers-enhancement-general-discussion
#10
Duncan Graham, Roy Goodacre, Heike Arnolds, Jean-Francois Masson, George Schatz, Jeremy Baumberg, Dong-Ho Kim, Javier Aizpurua, William Lum, Alessandro Silvestri, Bart de Nijs, Yikai Xu, Giuliana Di Martino, Michael Natan, Sebastian Schlücker, Pieter Wuytens, Ian Bruzas, Christian Kuttner, Mike Hardy, Rohit Chikkaraddy, Natalia Martín Sabanés, Ines Delfino, Paul Dawson, Sylwester Gawinkowski, Nicolò Bontempi, Sumeet Mahajan, Stephanie Reich, Ben Hourahine, Steven Bell, Agata Królikowska, Marc Porter, Alex Keeler, Marlous Kamp, Augustus Fountain, Claudia Fasolato, Fabrizio Giorgis, Juan C Otero, Cristiano Matricardi, Richard Van Duyne, John Lombardi, Volker Deckert, Leonora Velleman
No abstract text is available yet for this article.
November 22, 2017: Faraday Discussions
https://www.readbyqxmd.com/read/29162340/effects-of-intensive-blood-pressure-treatment-on-acute-kidney-injury-events-in-the-systolic-blood-pressure-intervention-trial-sprint
#11
Michael V Rocco, Kaycee M Sink, Laura C Lovato, Dawn F Wolfgram, Thomas B Wiegmann, Barry M Wall, Kausik Umanath, Frederic Rahbari-Oskoui, Anna C Porter, Roberto Pisoni, Cora E Lewis, Julia B Lewis, James P Lash, Lois A Katz, Amret T Hawfield, William E Haley, Barry I Freedman, Jamie P Dwyer, Paul E Drawz, Mirela Dobre, Alfred K Cheung, Ruth C Campbell, Udayan Bhatt, Srinivasan Beddhu, Paul L Kimmel, David M Reboussin, Glenn M Chertow
BACKGROUND: Treating to a lower blood pressure (BP) may increase acute kidney injury (AKI) events. STUDY DESIGN: Data for AKI resulting in or during hospitalization or emergency department visits were collected as part of the serious adverse events reporting process of the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS: 9,361 participants 50 years or older with 1 or more risk factors for cardiovascular disease...
November 18, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29160893/sers-in-biology-biomedical-sers-general-discussion
#12
Jeremy Baumberg, Steven Bell, Alois Bonifacio, Rohit Chikkaraddy, Malama Chisanga, Stella Corsetti, Ines Delfino, Olga Eremina, Claudia Fasolato, Karen Faulds, Holly Fleming, Roy Goodacre, Duncan Graham, Mike Hardy, Lauren Jamieson, Tia Keyes, Agata Królikowska, Christian Kuttner, Judith Langer, Carin Lightner, Sumeet Mahajan, Jean-Francois Masson, Howbeer Muhamadali, Michael Natan, Fay Nicolson, Evelina Nikelshparg, Konstantinos Plakas, Jürgen Popp, Marc Porter, Daniel Prezgot, Nathalie Pytlik, Sebastian Schlücker, Alessandro Silvestri, Nick Stone, Zhong-Qun Tian, Ashish Tripathi, Marjorie Willner, Pieter Wuytens
No abstract text is available yet for this article.
November 21, 2017: Faraday Discussions
https://www.readbyqxmd.com/read/29142109/the-ndc80-complex-targets-bod1-to-human-mitotic-kinetochores
#13
Katharina Schleicher, Michael Porter, Sara Ten Have, Ramasubramanian Sundaramoorthy, Iain M Porter, Jason R Swedlow
Regulation of protein phosphatase activity by endogenous protein inhibitors is an important mechanism to control protein phosphorylation in cells. We recently identified Biorientation defective 1 (Bod1) as a small protein inhibitor of protein phosphatase 2A containing the B56 regulatory subunit (PP2A-B56). This phosphatase controls the amount of phosphorylation of several kinetochore proteins and thus the establishment of load-bearing chromosome-spindle attachments in time for accurate separation of sister chromatids in mitosis...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29094619/acute-in-vitro-and-in-vivo-toxicity-of-a-commercial-grade-boron-nitride-nanotube-mixture
#14
Vamsi K Kodali, Jenny R Roberts, Mohammad Shoeb, Michael G Wolfarth, Lindsey Bishop, Tracy Eye, Mark Barger, Katherine A Roach, Sherri Friend, Diane Schwegler-Berry, Bean T Chen, Aleksandr Stefaniak, Kevin C Jordan, Roy R Whitney, Dale W Porter, Aaron D Erdely
Boron nitride nanotubes (BNNTs) are an emerging engineered nanomaterial attracting significant attention due to superior electrical, chemical and thermal properties. Currently, the toxicity profile of this material is largely unknown. Commercial grade BNNTs are composed of a mixture (BNNT-M) of ∼50-60% BNNTs, and ∼40-50% impurities of boron and hexagonal boron nitride. We performed acute in vitro and in vivo studies with commercial grade BNNT-M, dispersed by sonication in vehicle, in comparison to the extensively studied multiwalled carbon nanotube-7 (MWCNT-7)...
October 2017: Nanotoxicology
https://www.readbyqxmd.com/read/29092930/developing-cancer-informatics-applications-and-tools-using-the-nci-genomic-data-commons-api
#15
Shane Wilson, Michael Fitzsimons, Martin Ferguson, Allison Heath, Mark Jensen, Josh Miller, Mark W Murphy, James Porter, Himanso Sahni, Louis Staudt, Yajing Tang, Zhining Wang, Christine Yu, Junjun Zhang, Vincent Ferretti, Robert L Grossman
The NCI Genomic Data Commons (GDC) was launched in 2016 and makes available over 4 petabytes (PB) of cancer genomic and associated clinical data to the research community. This dataset continues to grow and currently includes over 14,500 patients. The GDC is an example of a biomedical data commons, which collocates biomedical data with storage and computing infrastructure and commonly used web services, software applications, and tools to create a secure, interoperable, and extensible resource for researchers...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/29076741/correlating-in-vitro-solubilization-and-supersaturation-profiles-with-in-vivo-exposure-for-lipid-based-formulations-of-the-cetp-inhibitor-cp-532-623
#16
Claire L McEvoy, Natalie L Trevaskis, Orlagh M Feeney, Glenn A Edwards, Michael E Perlman, Catherine M Ambler, Christopher J H Porter
Lipid based formulations (LBFs) are a promising formulation strategy for many poorly water-soluble drugs and have been shown previously to enhance the oral exposure of CP-532,623, an oral cholesteryl ester transfer protein inhibitor. In the current study, an in vitro lipid digestion model was used to probe the relationship between drug solubilization and supersaturation on in vitro dispersion and digestion of LBF containing long chain (LC) lipids and drug absorption in vivo. After in vitro digestion of LBF based on LC lipids, the proportion of CP-532,623 maintained in the solubilized state in the aqueous phase of the digest was highest in formulations containing Kolliphor RH 40, and in most cases outperformed equivalent formulations based on MC lipids...
November 9, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29066434/ride-report-mobile-app-user-guide
#17
Anna K Porter, Michael Schwartz
No abstract text is available yet for this article.
October 24, 2017: British Journal of Sports Medicine
https://www.readbyqxmd.com/read/29063834/what-s-in-a-name
#18
Michael D Schaller, Gary McDowell, André Porter, Dorothy Shippen, Katherine L Friedman, Matthew S Gentry, Tricia R Serio, Wesley I Sundquist
Numerous concerns have been raised about the sustainability of the biomedical research enterprise in the United States. Improving the postdoctoral training experience is seen as a priority in addressing these concerns, but even identifying who the postdocs are is made difficult by the multitude of different job titles they can carry. Here, we summarize the detrimental effects that current employment structures have on training, compensation and benefits for postdocs, and argue that academic research institutions should standardize the categorization and treatment of postdocs...
October 24, 2017: ELife
https://www.readbyqxmd.com/read/29059523/conversion-of-alcohols-to-phosphorothiolates-using-a-thioiminium-salt-as-coupling-agent
#19
Helen Grounds, Kristaps Ermanis, Sophie A Newgas, Michael J Porter
We report a method for the direct and rapid conversion of primary and secondary alcohols to the corresponding phosphorothiolates in yields ranging from 64% to 97%, using as a coupling agent the iminium salt prepared from N,N-dimethylthioformamide and Meerwein's salt. Selective reaction of primary alcohols in the presence of secondary alcohols is possible. The reaction of secondary alcohols proceeds stereospecifically with inversion of configuration.
October 31, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29055813/amyloid-%C3%AE-synaptotoxicity-is-wnt-pcp-dependent-and-blocked-by-fasudil
#20
Katherine J Sellers, Christina Elliott, Joshua Jackson, Anshua Ghosh, Elena Ribe, Ana I Rojo, Heledd H Jarosz-Griffiths, Iain A Watson, Weiming Xia, Mikhail Semenov, Peter Morin, Nigel M Hooper, Rod Porter, Jane Preston, Raya Al-Shawi, George Baillie, Simon Lovestone, Antonio Cuadrado, Michael Harte, Paul Simons, Deepak P Srivastava, Richard Killick
INTRODUCTION: Synapse loss is the structural correlate of the cognitive decline indicative of dementia. In the brains of Alzheimer's disease sufferers, amyloid β (Aβ) peptides aggregate to form senile plaques but as soluble peptides are toxic to synapses. We previously demonstrated that Aβ induces Dickkopf-1 (Dkk1), which in turn activates the Wnt-planar cell polarity (Wnt-PCP) pathway to drive tau pathology and neuronal death. METHODS: We compared the effects of Aβ and of Dkk1 on synapse morphology and memory impairment while inhibiting or silencing key elements of the Wnt-PCP pathway...
October 19, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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