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Michael Acker

David Capper, David T W Jones, Martin Sill, Volker Hovestadt, Daniel Schrimpf, Dominik Sturm, Christian Koelsche, Felix Sahm, Lukas Chavez, David E Reuss, Annekathrin Kratz, Annika K Wefers, Kristin Huang, Kristian W Pajtler, Leonille Schweizer, Damian Stichel, Adriana Olar, Nils W Engel, Kerstin Lindenberg, Patrick N Harter, Anne K Braczynski, Karl H Plate, Hildegard Dohmen, Boyan K Garvalov, Roland Coras, Annett Hölsken, Ekkehard Hewer, Melanie Bewerunge-Hudler, Matthias Schick, Roger Fischer, Rudi Beschorner, Jens Schittenhelm, Ori Staszewski, Khalida Wani, Pascale Varlet, Melanie Pages, Petra Temming, Dietmar Lohmann, Florian Selt, Hendrik Witt, Till Milde, Olaf Witt, Eleonora Aronica, Felice Giangaspero, Elisabeth Rushing, Wolfram Scheurlen, Christoph Geisenberger, Fausto J Rodriguez, Albert Becker, Matthias Preusser, Christine Haberler, Rolf Bjerkvig, Jane Cryan, Michael Farrell, Martina Deckert, Jürgen Hench, Stephan Frank, Jonathan Serrano, Kasthuri Kannan, Aristotelis Tsirigos, Wolfgang Brück, Silvia Hofer, Stefanie Brehmer, Marcel Seiz-Rosenhagen, Daniel Hänggi, Volkmar Hans, Stephanie Rozsnoki, Jordan R Hansford, Patricia Kohlhof, Bjarne W Kristensen, Matt Lechner, Beatriz Lopes, Christian Mawrin, Ralf Ketter, Andreas Kulozik, Ziad Khatib, Frank Heppner, Arend Koch, Anne Jouvet, Catherine Keohane, Helmut Mühleisen, Wolf Mueller, Ute Pohl, Marco Prinz, Axel Benner, Marc Zapatka, Nicholas G Gottardo, Pablo Hernáiz Driever, Christof M Kramm, Hermann L Müller, Stefan Rutkowski, Katja von Hoff, Michael C Frühwald, Astrid Gnekow, Gudrun Fleischhack, Stephan Tippelt, Gabriele Calaminus, Camelia-Maria Monoranu, Arie Perry, Chris Jones, Thomas S Jacques, Bernhard Radlwimmer, Marco Gessi, Torsten Pietsch, Johannes Schramm, Gabriele Schackert, Manfred Westphal, Guido Reifenberger, Pieter Wesseling, Michael Weller, Vincent Peter Collins, Ingmar Blümcke, Martin Bendszus, Jürgen Debus, Annie Huang, Nada Jabado, Paul A Northcott, Werner Paulus, Amar Gajjar, Giles W Robinson, Michael D Taylor, Zane Jaunmuktane, Marina Ryzhova, Michael Platten, Andreas Unterberg, Wolfgang Wick, Matthias A Karajannis, Michel Mittelbronn, Till Acker, Christian Hartmann, Kenneth Aldape, Ulrich Schüller, Rolf Buslei, Peter Lichter, Marcel Kool, Christel Herold-Mende, David W Ellison, Martin Hasselblatt, Matija Snuderl, Sebastian Brandner, Andrey Korshunov, Andreas von Deimling, Stefan M Pfister
Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting...
March 14, 2018: Nature
Edo Y Birati, Thomas C Hanff, Dawn Maldonado, E Wilson Grandin, Peter J Kennel, Jeremy A Mazurek, Esther Vorovich, Matthew Seigerman, Jessica L L Howard, Michael A Acker, Yoshifumi Naka, Joyce Wald, Lee R Goldberg, Mariell Jessup, Pavan Atluri, Kenneth B Margulies, P Christian Schulze, J Eduardo Rame
BACKGROUND: Predicting which patients are unlikely to benefit from continuous flow left ventricular assist device (LVAD) treatment is crucial for the identification of appropriate patients. Previously developed scoring systems are limited to past eras of device or restricted to specific devices. Our objective was to create a risk model for patients treated with continuous flow LVAD based on the preimplant variables. METHODS AND RESULTS: We performed a retrospective analysis of all patients implanted with a continuous flow LVAD between 2006 and 2014 at the University of Pennsylvania and included a total of 210 patients (male 78%; mean age, 56±15; mean follow-up, 465±486 days)...
March 7, 2018: Journal of the American Heart Association
Benoit C Mouzon, Corbin Bachmeier, Joseph O Ojo, Christopher M Acker, Scott Ferguson, Daniel Paris, Ghania Ait-Ghezala, Gogce Crynen, Peter Davies, Michael Mullan, William Stewart, Fiona Crawford
Objective: Exposure to repetitive concussion, or mild traumatic brain injury (mTBI), has been linked with increased risk of long-term neurodegenerative changes, specifically chronic traumatic encephalopathy (CTE). To date, preclinical studies largely have focused on the immediate aftermath of mTBI, with no literature on the lifelong consequences of mTBI in these models. This study provides the first account of lifelong neurobehavioral and histological consequences of repetitive mTBI providing unique insight into the constellation of evolving and ongoing pathologies with late survival...
January 2018: Annals of Clinical and Translational Neurology
Higinio Dopeso, Hui-Ke Jiao, Angel M Cuesta, Anne-Theres Henze, Liane Jurida, Michael Kracht, Amparo Acker-Palmer, Boyan K Garvalov, Till Acker
Lung cancer is the leading cause of cancer-related death worldwide, in large part due to its high propensity to metastasize and develop therapy resistance. Adaptive responses to hypoxia and epithelial-mesenchymal transition (EMT) are linked to tumor metastasis and drug resistance, but little is known about how oxygen sensing and EMT intersect to control these hallmarks of cancer. Here we show that the oxygen sensor PHD3 links hypoxic signaling and EMT regulation in the lung tumor microenvironment. PHD3 was repressed by signals that induce EMT and acted as a negative regulator of EMT, metastasis and therapeutic resistance...
January 16, 2018: Cancer Research
Michelle Fodor, Edmund Price, Ping Wang, Hengyu Lu, Andreea Argintaru, Zhouliang Chen, Meir Glick, Huai-Xiang Hao, Mitsunori Kato, Robert Koenig, Jonathan R LaRochelle, Gang Liu, Eric McNeill, Dyuti Majumdar, Gisele A Nishiguchi, Lawrence B Perez, Gregory Paris, Christopher M Quinn, Timothy Ramsey, Martin Sendzik, Michael David Shultz, Sarah L Williams, Travis Stams, Stephen C Blacklow, Michael G Acker, Matthew J LaMarche
SHP2 is a cytoplasmic protein tyrosine phosphatase encoded by the PTPN11 gene and is involved in cell proliferation, differentiation, and survival. Recently, we reported an allosteric mechanism of inhibition that stabilizes the auto-inhibited conformation of SHP2. SHP099 (1) was identified and characterized as a moderately potent, orally bioavailable, allosteric small molecule inhibitor, which binds to a tunnel-like pocket formed by the confluence of three domains of SHP2. In this report, we describe further screening strategies that enabled the identification of a second, distinct small molecule allosteric site...
January 18, 2018: ACS Chemical Biology
Jaroslav G Vostal, Paul W Buehler, Monique P Gelderman, Abdu I Alayash, Alan Doctor, James C Zimring, Simone A Glynn, John R Hess, Harvey Klein, Jason P Acker, Philip C Spinella, Angelo D'Alessandro, Bernhard Palsson, Thomas J Raife, Michael P Busch, Timothy J McMahon, Marcos Intaglietta, Harold M Swartz, Michael A Dubick, Sylvain Cardin, Rakesh P Patel, Charles Natanson, John W Weisel, Jennifer A Muszynski, Philip J Norris, Paul M Ness
The US Food and Drug Administration (FDA) held a workshop on red blood cell (RBC) product regulatory science on October 6 and 7, 2016, at the Natcher Conference Center on the National Institutes of Health (NIH) Campus in Bethesda, Maryland. The workshop was supported by the National Heart, Lung, and Blood Institute, NIH; the Department of Defense; the Office of the Assistant Secretary for Health, Department of Health and Human Services; and the Center for Biologics Evaluation and Research, FDA. The workshop reviewed the status and scientific basis of the current regulatory framework and the available scientific tools to expand it to evaluate innovative and future RBC transfusion products...
December 15, 2017: Transfusion
Patrick T O'Gara, Thoralf M Sundt, Michael A Acker, Tirone E David, Robert E Michler, Michael A Borger, Gorav Ailawadi, Vinod H Thourani, A Marc Gillinov, Ralph J Damiano, Michael J Mack, Richard Lee, Eric A Rose, Timothy J Gardner, Marissa A Miller, Richard D Weisel, Annetine C Gelijns
No abstract text is available yet for this article.
December 2017: Journal of Thoracic and Cardiovascular Surgery
Ali M Abbas, Andrew T Strong, David L Diehl, Brian C Brauer, Iris H Lee, Rebecca Burbridge, Jaroslav Zivny, Jennifer T Higa, Marcelo Falcão, Ihab I El Hajj, Paul Tarnasky, Brintha K Enestvedt, Alexander R Ende, Adarsh M Thaker, Rishi Pawa, Priya Jamidar, Kartik Sampath, Eduardo Guimarães Hourneaux de Moura, Richard S Kwon, Alejandro L Suarez, Murad Aburajab, Andrew Y Wang, Mohammad H Shakhatreh, Vivek Kaul, Lorna Kang, Thomas E Kowalski, Rahul Pannala, Jeffrey Tokar, A Aziz Aadam, Demetrios Tzimas, Mihir S Wagh, Peter V Draganov, M D The LA-Ercp Research Group Jeffrey Ponsky, Bruce D Greenwald, Lance T Uradomo, Alyson A McGhan, Shahrad Hakimian, Andrew Ross, Stuart Sherman, Benjamin L Bick, Christopher E Forsmark, Dennis Yang, Anand Gupte, Shailendra Chauhan, Steven J Hughes, Karen Saks, Gennadiy Bakis, Adam W Templeton, Michael Saunders, Alireza Sedarat, John A Evans, Thiruvengadam Muniraj, Timothy B Gardner, Almino C Ramos, Marco Aurelio Santo, Andrew Nett, Gregory A Coté, B Joseph Elmunzer, Kulwinder S Dua, Michael J Nosler, Daniel S Strand, Paul Yeaton, Shivangi Kothari, Asad Ullah, Pushpak Taunk, Patrick Brady, Haim Pinkas, Ashley L Faulx, Haroon Shahid, Jordan Holmes, Davinderbir Pannu, Srinadh Komanduri, Juan Carlos Bucobo, Harry Dhaliwal, Alaa Rostom, Brent W Acker
BACKGROUND AND AIMS: The obesity epidemic has led to increased use of Roux-en-Y gastric bypass (RYGB). These patients have an increased incidence of pancreaticobiliary diseases yet standard ERCP is not possible due to surgically altered gastroduodenal anatomy. Laparoscopic-ERCP (LA-ERCP) has been proposed as an option but supporting data are derived from single center small case-series. Therefore, we conducted a large multicenter study to evaluate the feasibility, safety, and outcomes of LA-ERCP...
November 9, 2017: Gastrointestinal Endoscopy
Adriana Galvan, William R Stauffer, Leah Acker, Yasmine El-Shamayleh, Ken-Ichi Inoue, Shay Ohayon, Michael C Schmid
Optogenetics is the use of genetically coded, light-gated ion channels or pumps (opsins) for millisecond resolution control of neural activity. By targeting opsin expression to specific cell types and neuronal pathways, optogenetics can expand our understanding of the neural basis of normal and pathological behavior. To maximize the potential of optogenetics to study human cognition and behavior, optogenetics should be applied to the study of nonhuman primates (NHPs). The homology between NHPs and humans makes these animals the best experimental model for understanding human brain function and dysfunction...
November 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jonathan R LaRochelle, Michelle Fodor, Jana M Ellegast, Xiaoxi Liu, Vidyasiri Vemulapalli, Morvarid Mohseni, Travis Stams, Sara J Buhrlage, Kimberly Stegmaier, Matthew J LaMarche, Michael G Acker, Stephen C Blacklow
The PTPN11 oncogene encodes the cytoplasmic protein tyrosine phosphatase SHP2, which, through its role in multiple signaling pathways, promotes the progression of hematological malignancies and other cancers. Here, we employ high-throughput screening to discover a lead chemical scaffold, the benzothiazolopyrimidones, that allosterically inhibits this oncogenic phosphatase by simultaneously engaging the C-SH2 and PTP domains. We improved our lead to generate an analogue that better suppresses SHP2 activity in vitro...
December 15, 2017: Bioorganic & Medicinal Chemistry
Dipika J Gopal, Thomas C Hanff, Jeremy A Mazurek, Wilson E Grandin, Jessica Howard, Rhondalyn Forde-McLean, Joyce Wald, Kathie King, Michael A Acker, Lee R Goldberg, Mariell Jessup, Pavan Atluri, Kenneth B Margulies, Eduardo J Rame, Edo Y Birati
Mechanical assist devices have emerged as an established therapeutic option for patients with end-stage heart failure. Because preimplant hypoalbuminemia is a known risk factor for adverse outcomes, we hypothesized that change in albumin may be a prognostic indicator in patients with continuous-flow left ventricular assist devices (cfLVADs). This is a retrospective single-center study of patients who underwent cfLVAD implantation (HeartMate II and HeartWare HVAD) at an academic center from 2008 to 2014. After excluding those who died, were transplanted, or hospitalized during the first 3 months post-implant, albumin values were obtained and stratified by an increase or a decrease from pre-implant to 3 months post-implant on 171 (81% male, mean age 57 ± 16 years) patients (139 for the survival analysis and 90 for the hospitalization analysis)...
December 1, 2017: American Journal of Cardiology
Carlo R Bartoli, David Zhang, Jooeun Kang, Samson Hennessy-Strahs, David Restle, Jessica Howard, Gretchen Redline, Christian Bermudez, Pavan Atluri, Michael A Acker
BACKGROUND: Recent data suggest that hemolysis contributes to left ventricular assist device (LVAD) thrombosis, but the mechanism is unknown. In a clinical study, we measured plasma free hemoglobin (pfHgb) and the incidence of LVAD thrombosis. In an in vitro study, we examined biophysical relationships between shear stress, pfHgb and von Willebrand factor (vWF) metabolism toward understanding mechanisms of LVAD thrombosis. METHODS: In the clinical study, blood samples were obtained from continuous-flow LVAD patients (n = 30)...
September 21, 2017: Annals of Thoracic Surgery
Jason J Han, Jennifer Chung, Carol W Chen, Ann C Gaffey, Alex Sotolongo, Christyna Justice, Alyse E Ameer, J Eduardo Rame, Christian Bermudez, Michael A Acker, Pavan Atluri
Extracorporeal membrane oxygenation (ECMO) as a bridge to left ventricular assist device (LVAD) implantation has shown promise in improving end-organ function and optimizing outcomes in some critically ill patients, but the practice remains controversial. Retrospective review of patients who received LVADs from May 2008 to September 2016 at a high-volume, tertiary care cardiovascular center was performed. Subjects were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) class 1 patients divided into ECMO bridge and non-ECMO bridge cohorts...
September 21, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
Ronen R Leker, Steven R Messé, Guray Erus, Michel Bilello, Molly Fanning, Michael Acker, Allie Massaro, Scott E Kasner, Thomas Floyd
BACKGROUND: Acute cerebral infarctions on diffusion-weighted magnetic resonance imaging (MRI) are common after cardiothoracic surgery. However, most are asymptomatic and we aimed to identify features associated with clinical stroke symptoms. METHODS: Patients over 65 years of age undergoing surgical aortic valve replacement (AVR) for calcific stenosis were prospectively recruited (N = 196). All patients underwent neurological evaluation preoperatively and on postoperative days 1, 3, and 7, and MRI on planned postoperative day 5...
August 24, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Ann C Gaffey, Carol W Chen, Jennifer J Chung, Emily Phillips, Joyce Wald, Matthew L Williams, David W Low, Michael A Acker, Pavan Atluri
BACKGROUND: The HeartMate II (St. Jude Medical, Inc, St. Paul, MN [previously Thoratec]) left ventricular assist device (LVAD) exchange has traditionally involved a redo sternotomy. Alternate minimally invasive subcostal approaches have the advantage of avoiding sternal reentry, excessive bleeding, and prolonged recovery. METHODS: This retrospective review included patients who underwent an exchange from May 2009 to March 2016. The patients were divided into three cohorts: (1) redo sternotomy, (2) subcostal approach involving cardiopulmonary bypass (CPB) (ON-CPB SC), and (3) subcostal approach off the CPB pump (OFF-CPB SC)...
November 2017: Annals of Thoracic Surgery
Timothy M Acker, Jonathan E Gable, Markus-Frederik Bohn, Priyadarshini Jaishankar, Michael C Thompson, James S Fraser, Adam R Renslo, Charles S Craik
Targeting of cryptic binding sites represents an attractive but underexplored approach to modulating protein function with small molecules. Using the dimeric protease (Pr) from Kaposi's sarcoma-associated herpesvirus (KSHV) as a model system, we sought to dissect a putative allosteric network linking a cryptic site at the dimerization interface to enzyme function. Five cryogenic X-ray structures were solved of the monomeric protease with allosteric inhibitors bound to the dimer interface site. Distinct coordinated movements captured by the allosteric inhibitors were also revealed as alternative states in room-temperature X-ray data and comparative analyses of other dimeric herpesvirus proteases...
August 17, 2017: Journal of the American Chemical Society
Jooeun Kang, Samson Hennessy-Strahs, Pawel Kwiatkowski, Christian A Bermudez, Michael A Acker, Pavan Atluri, Patrick I McConnell, Carlo R Bartoli
RATIONALE: The objective of this autopsy study was to determine whether gastrointestinal angiodysplasia develops during continuous-flow left ventricular assist device (LVAD) support. OBJECTIVE: LVAD support causes pathologic degradation of von Willebrand factor (vWF) and bleeding from gastrointestinal angiodysplasia at an alarming rate. It has been speculated that LVAD support itself may cause angiodysplasia. The relationship to abnormal vWF metabolism is unknown...
September 29, 2017: Circulation Research
Kevin T Ebata, Kathryn Mesh, Shichong Liu, Misha Bilenky, Alexander Fekete, Michael G Acker, Martin Hirst, Benjamin A Garcia, Miguel Ramalho-Santos
BACKGROUND: Histone methylation patterns regulate gene expression and are highly dynamic during development. The erasure of histone methylation is carried out by histone demethylase enzymes. We had previously shown that vitamin C enhances the activity of Tet enzymes in embryonic stem (ES) cells, leading to DNA demethylation and activation of germline genes. RESULTS: We report here that vitamin C induces a remarkably specific demethylation of histone H3 lysine 9 dimethylation (H3K9me2) in naïve ES cells...
2017: Epigenetics & Chromatin
Kevin T Ebata, Kathryn Mesh, Shichong Liu, Misha Bilenky, Alexander Fekete, Michael G Acker, Martin Hirst, Benjamin A Garcia, Miguel Ramalho-Santos
BACKGROUND: Histone methylation patterns regulate gene expression and are highly dynamic during development. The erasure of histone methylation is carried out by histone demethylase enzymes. We had previously shown that vitamin C enhances the activity of Tet enzymes in embryonic stem (ES) cells, leading to DNA demethylation and activation of germline genes. RESULTS: We report here that vitamin C induces a remarkably specific demethylation of histone H3 lysine 9 dimethylation (H3K9me2) in naïve ES cells...
July 12, 2017: Epigenetics & Chromatin
Rifat Atun, Justine I Davies, Edwin A M Gale, Till Bärnighausen, David Beran, Andre Pascal Kengne, Naomi S Levitt, Florence W Mangugu, Moffat J Nyirenda, Graham D Ogle, Kaushik Ramaiya, Nelson K Sewankambo, Eugene Sobngwi, Solomon Tesfaye, John S Yudkin, Sanjay Basu, Christian Bommer, Esther Heesemann, Jennifer Manne-Goehler, Iryna Postolovska, Vera Sagalova, Sebastian Vollmer, Zulfiqarali G Abbas, Benjamin Ammon, Mulugeta Terekegn Angamo, Akhila Annamreddi, Ananya Awasthi, Stéphane Besançon, Sudhamayi Bhadriraju, Agnes Binagwaho, Philip I Burgess, Matthew J Burton, Jeanne Chai, Felix P Chilunga, Portia Chipendo, Anna Conn, Dipesalema R Joel, Arielle W Eagan, Crispin Gishoma, Julius Ho, Simcha Jong, Sujay S Kakarmath, Yasmin Khan, Ramu Kharel, Michael A Kyle, Seitetz C Lee, Amos Lichtman, Carl P Malm, Maïmouna N Mbaye, Marie A Muhimpundu, Beatrice M Mwagomba, Kibachio Joseph Mwangi, Mohit Nair, Simon P Niyonsenga, Benson Njuguna, Obiageli L O Okafor, Oluwakemi Okunade, Paul H Park, Sonak D Pastakia, Chelsea Pekny, Ahmed Reja, Charles N Rotimi, Samuel Rwunganira, David Sando, Gabriela Sarriera, Anshuman Sharma, Assa Sidibe, Elias S Siraj, Azhra S Syed, Kristien Van Acker, Mahmoud Werfalli
No abstract text is available yet for this article.
July 5, 2017: Lancet Diabetes & Endocrinology
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