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| 1 | Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis显示文摘AIM: To evaluate the effect of orally administeredplecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models.METHODS: The cyclic guanosine monophosphate(cG MP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cellbased assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid(5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium(DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic(TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout(TCRα-/-) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity.RESULTS: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C(GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cG MP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs(0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity(P < 0.05) and disease activity index(P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα-/- mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUSION: This is the first-ever study reporting the therapeutic utility of GC-C agonists as a new class of orally delivered and mucosally active drug candidates for the treatment of inflammatory bowel diseases. | Kunwar Shailubhai Vaseem Palejwala Krishna Priya Arjunan Sayali Saykhedkar Bradley Nefsky John A Foss Stephen Comiskey Gary S Jacob Scott E Plevy | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 5 |
| 2 | Pushing the boundaries of diode-pumped solid-state lasers for high-energy applications显示文摘We report on the successful demonstration of a 150 J nanosecond pulsed cryogenic gas cooled,diode-pumped multi-slab Yb:YAG laser operating at 1 Hz.To the best of our knowledge,this is the highest energy ever recorded for a diodepumped laser system. | Saumyabrata Banerjee Paul Mason Jonathan Phillips Jodie Smith Thomas Butcher Jacob Spear Mariastefania De Vido Gary Quinn Danielle Clarke Klaus Ertel Cristina Hernez-Gomez Chris Edwards John Collier | 2020 | High Power Laser Science and Engineering2020，8，2： | 4 |
| 3 | Flight control design using robust dynamic inversion and time-scale separation显示文摘 | Jacob Reiner Gary J. Balas William L. Garrard | 1996 | Automatica1996，，11： | 2 |
| 4 | Low temperature water-gas shift: in situ DRIFTS-reaction study of ceria surface area on the evolution of formats on Pt/CeO2 fuel processing catalysts for fuel cell applications 显示文摘 | Gary Jacobs Leann Williams Uschi Graham Gerald A Pennis E Burtron H D | 2003 | Applied Catalysis A: General2003，252，： | 1 |
| 5 | Flight control design using robust dynamic inversion and time- scale separation显示文摘 | Jacob Reiner Gary J Balas William L Garrard | 1994 | IEEE Transactions on Automatic Control1994，32，11： | 1 |
| 6 | The interaction of stressful life events and chronic strains on community mental health显示文摘 | Gary W. Evans Stephen V. Jacobs David Dooley Ralph Catalano | 1987 | American Journal of Community Psychology1987，，1： | 1 |
| 7 | Upper limb bilateral symmetric training with robotic assistance and clinical outcomes for stroke A pilot study显示文摘Purpose–The purpose of this paper is to evaluate the physiotherapeutic benefits of bilateral symmetric training(BST)for stroke survivors affected by hemiparesis.Design/methodology/approach–Other studies have investigated symmetric physiotherapy.A key difficulty in previous work is in maintaining mirror-imaged trajectories between the affected and less-affected limbs.This obstacle was overcome in this work by using a two-armed robotic exoskeleton to enforce symmetry.In total,15 subjects,W6 months post stroke were,randomly assigned to bilateral symmetric robotic training,unilateral robotic training,and standard physical therapy.Findings–After 12 training sessions(90 minutes/session),the bilateral training group had the greatest intensity of movement training.They also had the greatest improvement in range of motion at the shoulder.The unilateral training group showed the greatest reduction in spasticity.Research limitations/implications–The rationale for symmetric physiotherapy is that it might promote connections from the undamaged brain hemisphere.The robot generated copious amounts of detailed kinematic data.Even though these data provided insights into the human to machine interface using different training modalities,it proved difficult to draw neurological conclusions.It is recommended that future research along these lines should include measures of neurophysiological change and/or changes in neurological activity.Practical implications–This research suggests that the advantage of bilateral symmetric movement over other modalities is slight,and that robotic training has comparable results with standard care.If BSTis used,care is potentially needed toavoid exacerbation of spasticity.Finally,this research includes a novel quantitative approach for evaluating robotic training.Originality/value–This study is of value to therapeutic researchers interested in new physiotherapy techniques,roboticists interested in developing rehabilitation devices,or for rehabilitation game designers interested in using virtual reality. | Matt Simkins Nancy Byl Hyunchul Kim Gary Abrams Jacob Rosen | 2016 | International Journal of Intelligent Computing and Cybernetics2016，9，1： | 1 |
| 8 | Sleep-related problems in pediatric obsessive-compulsive disorder显示文摘 | Eric A. Storch Tanya K. Murphy Caleb W. Lack Gary R. Geffken Marni L. Jacob Wayne K. Goodman | 2007 | Journal of Anxiety Disorders2007，，5： | 1 |
| 9 | Plecanatide, an Oral Guanylate Cyclase C Agonist Acting Locally in the Gastrointestinal Tract, Is Safe and Well-Tolerated in Single Doses显示文摘 | Kunwar Shailubhai Stephen Comiskey John A. Foss Rong Feng Laura Barrow Gail M. Comer Gary S. Jacob | 2013 | Digestive Diseases and Sciences2013，，9： | 1 |
| 10 | 925g Plecanatide, a Novel Guanylate Cyclase-C (GC-C) Receptor Agonist, is Efficacious and Safe in Patients with Chronic Idiopathic Constipation (CIC): Results from a 951 Patient, 12 Week, Multi-Center Trial显示文摘 | Philip B. Miner Ron Surowitz Ron Fogel William Koltun Douglas A. Drossman Michael Camilleri Allen Mangel Laura Barrow Gary S. Jacob Kunwar Shailubhai | 2013 | Gastroenterology2013，，5： | 1 |
| 11 | Appropriateness of Coronary Revascularization for Patients Without Acute Coronary Syndromes显示文摘 | Edward L. Hannan Kimberly Cozzens Zaza Samadashvili Gary Walford Alice K. Jacobs David R. Holmes Nicholas J. Stamato Samin Sharma Ferdinand J. Venditti Icilma Fergus Spencer B. King | 2012 | Journal of the American College of Cardiology2012，，21： | 1 |
| 12 | Fischer–Tropsch synthesis: support, loading, and promoter effects on the reducibility of cobalt catalysts显示文摘 | Gary Jacobs Tapan K Das Yongqing Zhang Jinlin Li Guillaume Racoillet Burtron H Davis | 2002 | Applied Catalysis A General2002，，1： | 1 |
| 13 | Robust dynamic inversion for control of highly maneuverable aircraft显示文摘 | Jacob Reiner Gary J Balas | 1995 | Journal of Guidance Control and Dynamics1995，18，1： | 1 |
| 14 | Five-year Analysis of Operative Mortality and Neonatal Outcomes in Congenital Heart Disease显示文摘 | James R. Padley Andrew D. Cole Victoria E. Pye Richard B. Chard Ian A. Nicholson Stephen Jacobe David Baines Nadia Badawi Karen Walker Gabbie Scarfe Karen Leclair Gary F. Sholler David S. Winlaw | 2011 | Heart, Lung and Circulation2011，，7： | 1 |
| 15 | Fischer-Tropsch synthesis : Support, loading, and promoter effects on the reducibility of cobalt catalysts 显示文摘 | Gary Jacobs Tapan K Das Zhang Yongqing | 2002 | Applied Catalysis A: General2002，233，12： | 1 |
| 16 | Increased sulfur tolerance of Pt/KL catalysts prepared by vapor-phase Impregnation and containing a Tm promoter 显示文摘 | Gary Jacob s Firoz Ghadiall Adriana Pi sanu | 2000 | Journal of Catalysis2000，191，： | 1 |
| 17 | Study of preparation parameters of powder and pelletized PtKL catalyst for n-hexane aromatization显示文摘 | Gary Jacobs Walter E Alvarez | 2001 | Applied Catalysis2001，206，： | 1 |
| 18 | 显示文摘 | Gary Jacobs Patricia M Patterson Zhang Yongqing | 2002 | Applied Catalysis A:General2002，233，： | 1 |
| 19 | Air Pollution and Human Behavior显示文摘 | Gary W Evans Stephen V Jacobs | 1981 | Journal of Social Issues1981，37，1： | 1 |
| 20 | Evaluation of the performance of Ni/La 2 O 3 catalyst prepared from LaNiO 3 perovskite-type oxides for the production of hydrogen through steam reforming and oxidative steam reforming of ethanol显示文摘 | Sania M. de Lima Adriana M. da Silva Lídia O.O. da Costa José M. Assaf Gary Jacobs Burtron H. Davis Lisiane V. Mattos Fábio B. Noronha | 2010 | Applied Catalysis A General2010，，1： | 1 |
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