343 research outputs found

    Familial hypercholesterolemia in a healthy elderly population

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    Abstract not availablePaul Lacaze, Robert Sebra, Moeen Riaz, Amanda J. Hooper, Jane Tiller, Andrew Baksh ... et al

    DNA sequencing at ultra-high fidelity

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    Heterogeneity of mutated tumor antigens in a single high grade ovarian serous carcinoma

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    Abstract: Patient PT189 presented with stage IIIC high grade papillary serous ovarian cancer in 2012. She was originally treated with carboplatin/paclitaxel. Having failed this original doublet chemotherapy, she has received a total of five additional chemotherapy regimens, all with recurrence of her disease. We performed exome and RNA sequencing on normal PBMC as well as nine tumor samples collected over a two year period during the course of her treatment.Choice of variant calling algorithm yields significantly different results in each sample. Low overlap between epitope predictions for primary vs. recurrent sample sets using “confident” variants. Greater concordance between samples from the primary time point compared with later recurrences.Presented at: 13th Cancer Immunotherapy (CIMT) annual meeting 2015Authors: Alex Rubinsteyn, John Martignetti , Elena Pereira, Tim O'Donnell , Arun Ahuja , Leo Garnar-Wortzel , Robert Sebra , Peter Dottino , Jeff Hammerbacher , Eric Schadt<br

    Use of multiple sequencing technologies to produce a high-quality genome of the fungus pseudogymnoascus destructans, the causative agent of bat white-nose syndrome

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    White-nose syndrome has recently emerged as one of the most devastating wildlife diseases recorded, causing widespread mortality in numerous bat species throughout eastern North America. Here, we present an improved reference genome of the fungal pathogen Pseudogymnoascus destructans for use in comparative genomic studies

    NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer

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    Single-cell RNA sequencing data used in the following article:NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancerhttps://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00369-5Authors:Bérengère Salomé, John P. Sfakianos, Daniel Ranti, Jorge Daza, Christine Bieber, Andrew Charap, Christian Hammer, Romain Banchereau, Adam M. Farkas, Dan Fu Ruan, Sudeh Izadmehr, Daniel Geanon, Geoffrey Kelly, Ronaldo M. de Real, Brian Lee, Kristin G. Beaumont, Sanjana Shroff, Yuan Shuo A. Wang, Ying-chih Wang, Tin Htwe Thin, Monica Garcia-Barros, Everardo Hegewisch-Solloa, Emily M. Mace, Li Wang, Timothy O’Donnell, Diego Chowell, Ruben Fernandez-Rodriguez, Mihaela Skobe, Nicole Taylor, Seunghee Kim-Schulze, Robert P. Sebra, Doug Palmer, Eleanor Clancy-Thompson, Scott Hammond, Alice O. Kamphorst, Karl-Johan Malmberg, Emanuela Marcenaro, Pedro Romero, Rachel Brody, Mathias Viard, Yuko Yuki, Maureen Martin, Mary Carrington, Reza Mehrazin, Peter Wiklund, Ira Mellman, Sanjeev Mariathasan, Jun Zhu, Matthew D. Galsky, Nina Bhardwaj*, Amir Horowitz*SummaryPD-1/PD-L1-blockade immunotherapies have limited efficacy in the treatment of bladder cancer. Here,we show that NKG2A associates with improved survival and responsiveness to PD-L1 blockadeimmunotherapy in bladder tumors that have high abundance of CD8+ T cells. In bladder tumors, NKG2Ais acquired on CD8+ T cells later than PD-1 as well as other well-established immune checkpoints.NKG2A+ PD-1+ CD8+ T cells diverge from classically defined exhausted T cells through their ability toreact to HLA class I-deficient tumors using TCR-independent innate-like mechanisms. HLA-ABCexpression by bladder tumors is progressively diminished as disease progresses, framing the importanceof targeting TCR-independent anti-tumor functions. Notably, NKG2A+ CD8+ T cells are inhibited whenHLA-E is expressed by tumors and partly restored upon NKG2A blockade in an HLA-E-dependentmanner. Overall, our study provides a framework for subsequent clinical trials combining NKG2Ablockade with other T cell-targeted immunotherapies, where tumors express higher levels of HLA-E

    Robust Polymer Microfluidic Device Fabrication via Contact Liquid Photolitographic Polymerization (CLiPP)

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    Microfluidic devices are commonly fabricated in silicon or glass using micromachining technology or elastomers using soft lithography methods; however, invariable bulk material properties, limited surface modification methods and difficulty in fabricating high aspect ratio devices prevent these materials from being utilized in numerous applications and/or lead to high fabrication costs. Contact Liquid Photolithographic Polymerization (CLiPP) was developed as an alternative microfabrication approach that uniquely exploits living radical photopolymerization chemistry to facilitate surface modification of device components, fabrication of high aspect ratio structures from many different materials with numerous covalently-adhered layers and facile construction of three-dimensional devices. This contribution describes CLiPP and demonstrates unique advantages of this new technology for microfabrication of polymeric microdevices. Specifically, the procedure for fabricating devices with CLiPP is presented, the living radical photopolymerization chemistry which enables this technology is described, and examples of devices made using CLiPP are shown.</p

    3D Polymeric Microfluidic Device Fabrication via Contact Liquid Photolithographic Polymerization (CLiPP)

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    In this contribution, a new method for the fabrication of complex polymeric microfluidic devices is presented. The technology, contact liquid photolithographic polymerization (CLIPP). overcomes many of the draw backs associated kith other rapid prototyping schemes, such as limited materials choices and time-consuming microassembly protocols. CUPP shares many traits with other photolithographic methods, but three distinct features: (i) liquid photoresists in contact with the photomask. (ii) readily removed sacrificial Materials. and (iii) living radical processes, enable multiple polymeric chemistries and mechanical properties while simultaneously enabling facile fabrication of 3D geometries and surface chemistry control. This contribution details fabrication techniques and methods for the fabrication of high aspect ratio posts covalently bonded to a polymeric substrate, an array of independently stacked bars on top of perpendicular bars, multiple undercut structures fabricated simultaneously, and a complex 3D geometry with intertwined channels.</p
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