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Linking uplift and mineralisation at the Mount Novit Zn-Pb-Ag Deposit,Northern Australia:Evidence from geology,U-Pb geochronology and sphalerite geochemistry

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Geoscience Frontiers 2022年第2期13卷 333-350页

作者： Bradley Cave William Perkins richard lilly Department of Earth Sciences University of AdelaideAdelaideSAAustralia Geological Survey of Queensland BrisbaneQLDAustralia

The subeconomic Mount Novit Zn-Pb-Ag deposit is located approximately 20 km south of Mount Isa,*** contrast to the nearby Mount Isa,Hilton and George Fisher Zn-Pb-Ag deposits,mineralisation at Mount Novit is situated to the west of the regional-scale Mount Isa Fault and is hosted in the Moondarra Siltstone as opposed to the Urquhart ***-grade(10 wt.%Zn+Pb)mineralisation occurs as a matrix supported breccia dominated by sphalerite and pyrrhotite with galena,pyrite,and ***-situ U-Pb geochronology was completed on apatite and two textural varieties of ***-grained(10 ppm),possibly reflecting the leaching of the metals from an underlying basement *** GGIMFis geothermometer(Frenzel et al.,2016)produced a mean formation temperature of 345±52℃.The timing and temperature of Zn-Pb-Ag mineralisation is consistent with the age and cooling temperature of apatite presented in this *** on these correlations,we

关键词： Mount Isa Mount Novit Zn-Pb-Ag mineralisation Monazite Apatite Geochronology

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Redefinition of Fatty Liver Disease from NAFLD to MAFLD through the Lens of Drug Development and Regulatory Science

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Journal of Clinical and Translational Hepatology 2022年第2期10卷 374-382页

作者： Yasser Fouad Melissa Palmer Minjun Chen Arie Regev Rajarshi Banerjee Rob Myers Robert Riccio richard Torstenson Ramy Younes Puneet SArora Henrik Landgren Morten A.Karsdal Martin Blake David A.Shapiro Hans-Juergen Gruss Muhammad Y.Sheikh Dina Attia Steven Bollipo Alastair D.Smith Bradley Freilich Robert G.Gish Detlef Schuppan Department of Gastroenterology Hepatologyand Endemic MedicineFaculty of MedicineMinia UniversityMiniaEgypt Gan-nex/Ascletis Pharma Co Ltd BeijingChina Liver Consulting LLC New YorkNYUSA Division of Bioinformatics and Biostatis-tics National Center for Toxicological ResearchUS Food and Drug AdministrationJeffersonARUSA Eli lilly and Company IndianapolisINUSA Perspectum Diagnostics Ltd OxfordUK Gilead Sciences Inc Foster CityCAUSA Syneos Health LLC MorrisvilleNCUSA Allergan Marlow International BuckinghamshireUKAstraZenecaCambridgeUK Boehringer Ingel-heim International GmbHIngelheimGermany Genentech IncSouth San FranciscoCAUSA AbbVie MarlowBuck-inghamshireUK Nordic Bioscience A/S HerlevDenmark Resonance Health BurswoodWAAustralia Intercept Phar-maceuticals Inc San DiegoCAUSA Fresno Clinical Research Center FresnoCAUSA Gastroenterology and Hepatology Department Beni-Suef UniversityBeni SuefEgypt Department of Gastroenterology and Endoscopy John Hunter HospitalNewcastleNSWAustralia School of Medicine and Public Health University of NewcastleNewcastleNSWAustralia Kan-sas City Research Institute Kansas CityMOUSA Division of Gastroenterology and Hepatology Loma Linda UniversityLoma LindaCAUSA Institute of Translational Immunology and Research Center for Immune Therapy University Medical CenterMainzGermany Division of Gastroenterology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA

Metabolic(dysfunction)-associated fatty liver disease(MAFLD)affects a third of the population and is a leading cause of liver-related *** no effective treatments exist,novel approaches to drug development are ***,outdated terminology and definitions of the disease are hampering efforts to develop new drugs and *** international consensus panel has put forth an influential proposal for the disease to be renamed from nonalcoholic fatty liver disease(NAFLD)to MAFLD,includ-ing a proposal for how the disease should be *** allies with the many stakeholders in MAFLD care―including patients,patients’advocates,clinicians,researchers,nurse and allied health groups,regional societies,and others―we are aware of the negative consequences of the NAFLD term and *** share the sense of urgency for change and will act in new ways to achieve our *** there is much work to be done to overcome clinical inertia and reverse worrisome recent trends,the MAFLD initiative provides a firm foundation to build *** provides a roadmap for moving for-ward toward more efficient care and affordable,sustainable drug and device innovation in MAFLD *** hope it will bring promising new opportunities for a brighter future for MAFLD care and improve care and outcomes for patients of one of the globe’s largest and costliest public health *** this viewpoint,we have revisited this initiative through the perspectives of drug development and regulatory science.

关键词： NAFLD MAFLD NASH Fatty liver disease Liver Fibrosis

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Bisarylmaleimides & the Corresponding Indolocarbazoles as Kinase Inhibitors

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合成化学 2004年第z1期12卷 11-11页

作者： Scott E. Conner Harold B. Brooks Eileen Considine Jack A. Dempsey Margaret M. Faul Cathy Ogg Bharvin Patel richard M. Schultz Charles D. Spencer Beverly Teicher Scott A. Watkins lilly Research Laboratories A Division of Eli Lilly & Company Lilly Corporate Center Indianapolis Indiana 46285 USA

Cyclin dependent kinases (CDKs) have recently raised considerable attention because of their central role in the regulation of cell cycle progression. A high incidence of genetic mutation of CDK substrates and deregulaton of CDK modulators were found in a number of disease states,particularly in cancer. A novel series of unsymmetrical substituted indolocarbazoles were synthesized and their kinase inhibitory capability was evaluated in vitro. 6-Substtuted indolocarbazoles were found to be highly potent and selective D1/CDK4 inhibitors. These indolocarbazoles exhibited ATP competitive D1/CDK4 activity and inhibited tumor cell growth,arrested tumor cell at G1 phase. These molecules demonstrated potent anti-tumor activity and inhibited pRb phosphorylation at S780 in the human lung carcinoma (Calu6) and non-small cell lung carcinoma (NCI-H460) xenograft models. The results indicate that these small molecules have potential as therapeutic agents in cancer chemotherapeutc agents.

关键词： Bisarylmaleimides the Corresponding Indolocarbazoles as Kinase Inhibitors CDK

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