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Robert Langer

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https://www.readbyqxmd.com/read/28409544/hypoxia-and-the-hypoxia-regulated-transcription-factor-hif-1%C3%AE-suppress-the-host-defence-of-airway-epithelial-cells
#1
Markus Polke, Frederik Seiler, Philipp M Lepper, Andreas Kamyschnikow, Frank Langer, Dominik Monz, Christian Herr, Robert Bals, Christoph Beisswenger
Chronic diseases of the respiratory tract, such as cystic fibrosis, are associated with mucosal and systemic hypoxia. Innate immune functions of airway epithelial cells are required to prevent and control infections of the lung parenchyma. The transcription factor hypoxia-inducible factor 1α (HIF-1α) regulates cellular adaptation to low oxygen conditions. Here, we show that hypoxia and HIF-1α regulate innate immune mechanisms of cultured human bronchial epithelial cells (HBECs). Exposure of primary HBECs to hypoxia or the prolyl hydroxylase inhibitor dimethyloxaloylglycine (DMOG) resulted in a significantly decreased expression of inflammatory mediators (IL-6, IFN-γ-induced protein 10) in response to ligands for TLRs (flagellin, polyI:C) and Pseudomonas aeruginosa, whereas the expression of inflammatory mediators was not affected by hypoxia or DMOG in the absence of microbial factors...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28377441/percutaneous-transfemoral-tricuspid-valve-edge-to-edge-repair-a-case-series
#2
Karin Müller, Rezo Jorbenadze, Tobias Walker, Robert Schüler, Christoph Hammerstingl, Christian Schlensak, Meinrad Gawaz, Harald F Langer, Peter Seizer
No abstract text is available yet for this article.
April 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28353188/feasibility-of-standardized-methods-to-specify-behavioral-pediatric-obesity-prevention-interventions
#3
Meghan M JaKa, Simone A French, Julian Wolfson, Robert W Jeffery, Fabianna Lorencatto, Susan Michie, Shelby L Langer, Rona L Levy, Nancy E Sherwood
Standardized methods are needed to evaluate what occurs within the 'black box' of behavioral interventions to prevent pediatric obesity. The purpose of this research is to evaluate methods to specify the behavior change techniques used and the amount of time spent discussing target weight-related behaviors in an intervention for parents of children at risk for becoming overweight or obese. Independent coders were trained to identify behavior change techniques and time spent discussing weight-related behaviors in audio recordings and transcripts of intervention sessions from 100 randomly selected participants...
March 28, 2017: Journal of Behavioral Medicine
https://www.readbyqxmd.com/read/28333908/tuberculosis-united-states-2016
#4
Kristine M Schmit, Zimy Wansaula, Robert Pratt, Sandy F Price, Adam J Langer
In 2016, a total of 9,287 new tuberculosis (TB) cases were reported in the United States; this provisional* count represents the lowest number of U.S. TB cases on record and a 2.7% decrease from 2015 (1). The 2016 TB incidence of 2.9 cases per 100,000 persons represents a slight decrease compared with 2015 (-3.4%) (Figure). However, epidemiologic modeling demonstrates that if similar slow rates of decline continue, the goal of U.S. TB elimination will not be reached during this century (2). Although current programs to identify and treat active TB disease must be maintained and strengthened, increased measures to identify and treat latent TB infection (LTBI) among populations at high risk are also needed to accelerate progress toward TB elimination...
March 24, 2017: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/28332061/tutorial-assistance-for-board-certification-in-surgery-frequency-associated-time-and-cost
#5
Robert Mechera, Salome Dell-Kuster, Marco von Strauss Und Torney, Igor Langer, Markus Furrer, Heiner C Bucher, Rachel Rosenthal
BACKGROUND: Tutorial assistance is related to extra time and cost, and the hospitals' financial compensation for this activity is under debate. We therefore aimed at quantifying the extra time and resulting cost required to train one surgical resident in the operating theatre for board certification in Switzerland as an example of a training curriculum involving several surgical subspecialties. Additionally, we intended to quantify the percentage of tutorial assistance. METHODS: We analysed 200,700 operations carried out between 2008 and 2012...
March 22, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/28327460/comprehensive-proteomic-characterization-of-stem-cell-derived-extracellular-matrices
#6
Héloïse Ragelle, Alexandra Naba, Benjamin L Larson, Fangheng Zhou, Miralem Prijić, Charles A Whittaker, Amanda Del Rosario, Robert Langer, Richard O Hynes, Daniel G Anderson
In the stem-cell niche, the extracellular matrix (ECM) serves as a structural support that additionally provides stem cells with signals that contribute to the regulation of stem-cell function, via reciprocal interactions between cells and components of the ECM. Recently, cell-derived ECMs have emerged as in vitro cell culture substrates to better recapitulate the native stem-cell microenvironment outside the body. Significant changes in cell number, morphology and function have been observed when mesenchymal stem cells (MSC) were cultured on ECM substrates as compared to standard tissue-culture polystyrene (TCPS)...
March 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28319612/colony-stimulating-factor-1-receptor-is-a-central-component-of-the-foreign-body-response-to-biomaterial-implants-in-rodents-and-non-human%C3%A2-primates
#7
Joshua C Doloff, Omid Veiseh, Arturo J Vegas, Hok Hei Tam, Shady Farah, Minglin Ma, Jie Li, Andrew Bader, Alan Chiu, Atieh Sadraei, Stephanie Aresta-Dasilva, Marissa Griffin, Siddharth Jhunjhunwala, Matthew Webber, Sean Siebert, Katherine Tang, Michael Chen, Erin Langan, Nimit Dholokia, Raj Thakrar, Meirigeng Qi, Jose Oberholzer, Dale L Greiner, Robert Langer, Daniel G Anderson
Host recognition and immune-mediated foreign body response to biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not. Macrophages, via CXCL13, lead to downstream B cell recruitment, which further potentiated fibrosis, as confirmed by B cell knockout and CXCL13 neutralization...
March 20, 2017: Nature Materials
https://www.readbyqxmd.com/read/28317839/polymeric-mechanical-amplifiers-of-immune-cytokine-mediated-apoptosis
#8
Michael J Mitchell, Jamie Webster, Amanda Chung, Pedro P G Guimarães, Omar F Khan, Robert Langer
Physical forces affect tumour growth, progression and metastasis. Here, we develop polymeric mechanical amplifiers that exploit in vitro and in vivo physical forces to increase immune cytokine-mediated tumour cell apoptosis. Mechanical amplifiers, consisting of biodegradable polymeric particles tethered to the tumour cell surface via polyethylene glycol linkers, increase the apoptotic effect of an immune cytokine on tumour cells under fluid shear exposure by as much as 50% compared with treatment under static conditions...
March 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28316241/investigating-the-cellular-specificity-in-tumors-of-a-surface-converting-nanoparticle-by-multimodal-imaging
#9
Francois Fay, Line Hansen, Stefanie J C G Hectors, Brenda L Sanchez-Gaytan, Yiming Zhao, Jun Tang, Jazz Munitz, Amr Alaarg, Mounia S Braza, Anita Gianella, Stuart A Aaronson, Thomas Reiner, Jørgen Kjems, Robert Langer, Freek J M Hoeben, Henk M Janssen, Claudia Calcagno, Gustav J Strijkers, Zahi A Fayad, Carlos Perez-Medina, Willem J M Mulder
Active targeting of nanoparticles through surface functionalization is a common strategy to enhance tumor delivery specificity. However, active targeting strategies tend to work against long polyethylene glycol's shielding effectiveness and associated favorable pharmacokinetics. To overcome these limitations, we developed a matrix metalloproteinase-2 sensitive surface-converting polyethylene glycol coating. This coating prevents nanoparticle-cell interaction in the bloodstream but once exposed to matrix metalloproteinase-2, i...
March 19, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28295624/mixed-reversible-covalent-crosslink-kinetics-enable-precise-hierarchical-mechanical-tuning-of-hydrogel-networks
#10
Volkan Yesilyurt, Andrew M Ayoob, Eric A Appel, Jeffrey T Borenstein, Robert Langer, Daniel G Anderson
Hydrogels play a central role in a number of medical applications and new research aims to engineer their mechanical properties to improve their capacity to mimic the functional dynamics of native tissues. This study shows hierarchical mechanical tuning of hydrogel networks by utilizing mixtures of kinetically distinct reversible covalent crosslinks. A methodology is described to precisely tune stress relaxation in PEG networks formed from mixtures of two different phenylboronic acid derivatives with unique diol complexation rates, 4-carboxyphenylboronic acid, and o-aminomethylphenylboronic acid...
March 15, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28273716/lipid-nanoparticle-assisted-mrna-delivery-for-potent-cancer-immunotherapy
#11
Matthias A Oberli, Andreas M Reichmuth, J Robert Dorkin, Michael J Mitchell, Owen S Fenton, Ana Jaklenec, Daniel G Anderson, Robert Langer, Daniel Blankschtein
The induction of a strong cytotoxic T cell response is an important prerequisite for successful immunotherapy against many viral diseases and tumors. Nucleotide vaccines, including mRNA vaccines with their intracellular antigen synthesis, have been shown to be potent activators of a cytotoxic immune response. The intracellular delivery of mRNA vaccines to the cytosol of antigen presenting immune cells is still not sufficiently well understood. Here, we report on the development of a lipid nanoparticle formulation for the delivery of mRNA vaccines to induce a cytotoxic CD 8 T cell response...
March 8, 2017: Nano Letters
https://www.readbyqxmd.com/read/28267733/us-immigration-order-strikes-against-biotech
#12
Jeremy M Levin, Steven H Holtzman, John Maraganore, Paul J Hastings, Ron Cohen, Bassil Dahiyat, Julian Adams, Chris Adams, Brett Ahrens, Jeff Albers, Mara G Aspinall, James E Audia, Martin Babler, Peter Barrett, Zoe Barry, Nessan Bermingham, Stephen Bloch, Robert I Blum, Paul B Bolno, Michael W Bonney, Bruce Booth, Daniel M Bradbury, Steven K Brauer, Brook Byers, Pablo J Cagnoni, Brian M Cali, Isaac Ciechanover, Chip Clark, Michael D Clayman, Jeff L Cleland, Paula Cobb, Ron Cooper, Mark G Currie, John Diekman, Eric L Dobmeier, Doug Doerfler, Elizabeth Lr Donley, Deborah Dunsire, Matthew During, Jens W Eckstein, Eric Elenko, Neil A Exter, Jonathan J Fleming, Gregory J Flesher, Jean-Francois Formela, Robert Forrester, Cedric Francois, Heather Franklin, Mason W Freeman, Howard Furst, Leonard Patrick Gage, Nicholas Galakatos, Brian M Gallagher, James A Geraghty, Simba Gill, David V Goeddel, Mark A Goldsmith, Maxine Gowen, Vikas Goyal, Tom Graney, David Grayzel, Barry Greene, Paul Grint, J C Gutierrez-Ramos, Bill Haney, Tuan Ha-Ngoc, Tim Harris, Faheem Hasnain, Yujiro Steve Hata, Peter Hecht, Leslie Henshaw, Rich Heyman, Herve Hoppenot, H Robert Horvitz, Thomas E Hughes, Wende S Hutton, Stephen T Isaacs, Annalisa Jenkins, Jeff Jonker, Jeff Kaplan, Perry Karsen, Jeb Keiper, Jean Kim, Jeff Kindler, Rachel King, Vanessa King, Nina Kjellson, Scott Koenig, Gerhard Koenig, Peter Kolchinsky, Paul Laikind, Robert Bob Langer, John J Lee, Jonathan S Leff, Bruce A Leicher, Nick Leschly, Andrew Levin, Mark Levin, Arnold J Levine, Alan Levy, David R Liu, Harvey F Lodish, Uri Lopatin, Ted W Love, Guy Macdonald, Gail J Maderis, Ankit Mahadevia, Nagesh K Mahanthappa, Joel F Martin, Alex Martin, W Eddie Martucci, James G McArthur, Corey M McCann, Sean A McCarthy, C Geoffrey McDonough, John Mendlein, Larry Miller, Diego Miralles, Kenneth I Moch, Bob More, Andrew G Myers, Michael A Narachi, Amir Nashat, Wendy Nelson, William J Newell, Bernat Olle, John E Osborn, Julia C Owens, Atul Pande, Stelios Papadopoulos, H Stewart Parker, Kush M Parmar, Matthew R Patterson, Steve M Paul, Rob Perez, Matthew Perry, Cary G Pfeffer, Mike Powell, Mark Pruzanski, Dennis J Purcell, Amit Rakhit, Kartik Ramamoorthi, William Rastetter, Adrian Ad Rawcliffe, Laurence E Reid, Ron C Renaud, Jason P Rhodes, William J Rieflin, Chad Robins, Scott M Rocklage, Michael Rosenblatt, Jonathan G Rosin, William J Rutter, Saurabh Saha, Camille Samuels, Vicki L Sato, George Scangos, John A Scarlett, David Schenkein, Stuart L Schreiber, Andrew Schwab, Paul Sekhri, Rajeev Shah, Thomas Shenk, Clay B Siegall, Nick J Simon, Nancy Simonian, Jeff Stein, Michael Su, Mary T Szela, Marco Taglietti, Nina Tandon, Henri Termeer, Nancy A Thornberry, Martin Tolar, Richard Ulevitch, Akshay K Vaishnaw, Anne VanLent, Martin Varsavsky, George P Vlasuk, Michel Vounatsos, Samuel G Waksal, Neil Warma, Ryan J Watts, Yaron Werber, Christoph Westphal, Wendell Wierenga, Doug E Williams, Lewis Rusty Williams, Kleanthis G Xanthopoulos, Daphne Zohar, Sandford Sandy Zweifach
No abstract text is available yet for this article.
March 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28251176/bioprinting-the-cancer-microenvironment
#13
Yu Shrike Zhang, Margaux Duchamp, Rahmi Oklu, Leif W Ellisen, Robert Langer, Ali Khademhosseini
Cancer is intrinsically complex, comprising both heterogeneous cellular compositions and microenvironmental cues. During the various stages of cancer initiation, development, and metastasis, cell-cell interactions (involving vascular and immune cells besides cancerous cells) as well as cell-extracellular matrix (ECM) interactions (e.g., alteration in stiffness and composition of the surrounding matrix) play major roles. Conventional cancer models both two- and three-dimensional (2D and 3D) present numerous limitations as they lack good vascularization and cannot mimic the complexity of tumors, thereby restricting their use as biomimetic models for applications such as drug screening and fundamental cancer biology studies...
October 10, 2016: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/28228258/clonal-expansion-of-lgr5-positive-cells-from-mammalian-cochlea-and-high-purity-generation-of-sensory-hair-cells
#14
Will J McLean, Xiaolei Yin, Lin Lu, Danielle R Lenz, Dalton McLean, Robert Langer, Jeffrey M Karp, Albert S B Edge
Death of cochlear hair cells, which do not regenerate, is a cause of hearing loss in a high percentage of the population. Currently, no approach exists to obtain large numbers of cochlear hair cells. Here, using a small-molecule approach, we show significant expansion (>2,000-fold) of cochlear supporting cells expressing and maintaining Lgr5, an epithelial stem cell marker, in response to stimulation of Wnt signaling by a GSK3β inhibitor and transcriptional activation by a histone deacetylase inhibitor...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28167778/barcoded-nanoparticles-for-high-throughput-in-vivo-discovery-of-targeted-therapeutics
#15
James E Dahlman, Kevin J Kauffman, Yiping Xing, Taylor E Shaw, Faryal F Mir, Chloe C Dlott, Robert Langer, Daniel G Anderson, Eric T Wang
Nucleic acid therapeutics are limited by inefficient delivery to target tissues and cells and by an incomplete understanding of how nanoparticle structure affects biodistribution to off-target organs. Although thousands of nanoparticle formulations have been designed to deliver nucleic acids, most nanoparticles have been tested in cell culture contexts that do not recapitulate systemic in vivo delivery. To increase the number of nanoparticles that could be tested in vivo, we developed a method to simultaneously measure the biodistribution of many chemically distinct nanoparticles...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28167393/biodegradable-scaffolds-promote-tissue-remodeling-and-functional-improvement-in-non-human-primates-with-acute-spinal-cord-injury
#16
Jonathan R Slotkin, Christopher D Pritchard, Brian Luque, Janice Ye, Richard T Layer, Mathew S Lawrence, Timothy M O'Shea, Roland R Roy, Hui Zhong, Isabel Vollenweider, V Reggie Edgerton, Grégoire Courtine, Eric J Woodard, Robert Langer
Tissue loss significantly reduces the potential for functional recovery after spinal cord injury. We previously showed that implantation of porous scaffolds composed of a biodegradable and biocompatible block copolymer of Poly-lactic-co-glycolic acid and Poly-l-lysine improves functional recovery and reduces spinal cord tissue injury after spinal cord hemisection injury in rats. Here, we evaluated the safety and efficacy of porous scaffolds in non-human Old-World primates (Chlorocebus sabaeus) after a partial and complete lateral hemisection of the thoracic spinal cord...
January 25, 2017: Biomaterials
https://www.readbyqxmd.com/read/28154902/guidelines-for-the-diagnosis-and-management-of-hirschsprung-associated-enterocolitis
#17
REVIEW
Ankush Gosain, Philip K Frykman, Robert A Cowles, John Horton, Marc Levitt, David H Rothstein, Jacob C Langer, Allan M Goldstein
BACKGROUND: Patients with Hirschsprung disease are at risk for Hirschsprung-associated enterocolitis (HAEC), an inflammatory disorder of the bowel that represents the leading cause of serious morbidity and death in these patients. The diagnosis of HAEC is made based on clinical signs and symptoms which are often non-specific, making it difficult to establish a definitive diagnosis in many patients. The purpose of this guideline is to present a rational, expert-based approach to the diagnosis and management of HAEC...
May 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28152774/quality-of-life-qol-in-patients-pts-with-squamous-scc-nsclc-treated-with-nab-paclitaxel-with-carboplatin-nab-p-c-induction-therapy-interim-analysis-of-the-phase-iii-abound-sqm-study
#18
Corey J Langer, Robert M Jotte, Edward S Kim, Amy Ko, Teng Jin Ong, Mark A Socinski, Peter Staib, Nataliya Trunova, David R Spigel
64 Background: Recent data on QoL in pts with advanced NSCLC treated with platinum-doublets are limited. This interim analysis evaluated QoL in pts with SCC NSCLC treated with nab-P/C during the induction part of the ABOUND.sqm study. METHODS: In the ongoing phase III ABOUND.sqm study, pts with advanced SCC NSCLC are treated with first-line nab-P 100 mg/m(2) d 1, 8, 15 and C AUC 6 mg•min/mL d 1 (21-d cycles) for 4 cycles (induction). Pts not progressing after 4 cycles are randomized 2:1 to maintenance nab-P 100 mg/m(2)d 1 and 8 of each 21-d cycle + best supportive care (BSC) or BSC alone until progression...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28107282/early-posthepatoportoenterostomy-predictors-of-native-liver-survival-in-biliary-atresia
#19
Scott Nightingale, Michael O Stormon, Edward V O'Loughlin, Albert Shun, Gordon Thomas, Eric I Benchimol, Andrew S Day, Susan Adams, Edward Shi, Chee Y Ooi, Binita M Kamath, Annie Fecteau, Jacob C Langer, Eve A Roberts, Simon C Ling, Vicky L Ng
OBJECTIVES: Most infants with biliary atresia (BA) require liver transplantation (LT) after hepatoportoenterostomy (HPE), including those who initially clear jaundice. The aim of the present study was to identify clinical and routine laboratory factors in infants with BA post-HPE that predict native liver survival at 2 years. METHODS: A retrospective cohort study was conducted in 217 patients with BA undergoing HPE in Sydney, Australia and Toronto, Canada between January 1986 and July 2009...
February 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28088460/ultrasound-mediated-delivery-of-rna-to-colonic-mucosa-of-live%C3%A2-mice
#20
Carl M Schoellhammer, Gregory Y Lauwers, Jeremy A Goettel, Matthias A Oberli, Cody Cleveland, June Y Park, Daniel Minahan, Yiyun Chen, Daniel G Anderson, Ana Jaklenec, Scott B Snapper, Robert Langer, Giovanni Traverso
BACKGROUND & AIMS: It is a challenge to deliver nucleic acids to gastrointestinal (GI) tissues due to their size and need for intracellular delivery. They are also extremely susceptible to degradation by nucleases, which are ubiquitous in the GI tract. We investigated whether ultrasound, which can permeabilize tissue through a phenomenon known as transient cavitation, can be used to deliver RNA to the colonic mucosa of living mice. METHODS: We investigated delivery of fluorescently labeled permeants to colon tissues of Yorkshire pigs ex vivo and mice in vivo...
April 2017: Gastroenterology
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