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A Yaroshchuk, E E Licón, E K Zholkovskiy, M P Bondarenko, T Heldal
To have non-zero net flow in AC electroosmotic pumps, the electroosmosis (EO) has to be non-linear and asymmetric. This can be achieved due to ionic concentration polarization. This is known to occur close to micro-/nano-interfaces provided that the sizes of the nanopores are not too large compared to the Debye screening length. However, operation of the corresponding EO pumps can be quite sensitive to the solution concentration and, thus, unstable in practical applications. Concentration polarization of ion-exchange membranes is much more robust...
April 21, 2017: Faraday Discussions
John Paul Shen, Dongxin Zhao, Roman Sasik, Jens Luebeck, Amanda Birmingham, Ana Bojorquez-Gomez, Katherine Licon, Kristin Klepper, Daniel Pekin, Alex N Beckett, Kyle Salinas Sanchez, Alex Thomas, Chih-Chung Kuo, Dan Du, Assen Roguev, Nathan E Lewis, Aaron N Chang, Jason F Kreisberg, Nevan Krogan, Lei Qi, Trey Ideker, Prashant Mali
We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies...
March 20, 2017: Nature Methods
I Sancho, E Licon, C Valderrama, N de Arespacochaga, S López-Palau, J L Cortina
The integration of up-concentration processes to increase the efficiency of primary sedimentation, as a solution to achieve energy neutral wastewater treatment plants, requires further post-treatment due to the missing ammonium removal stage. This study evaluated the use of zeolites as a post-treatment step, an alternative to the biological removal process. A natural granular clinoptilolite zeolite was evaluated as a sorbent media to remove low levels (up to 100mg-N/L) of ammonium from treated wastewater using batch and fixed bed columns...
April 15, 2017: Science of the Total Environment
Michael H Kramer, Jean-Claude Farré, Koyel Mitra, Michael Ku Yu, Keiichiro Ono, Barry Demchak, Katherine Licon, Mitchell Flagg, Rama Balakrishnan, J Michael Cherry, Suresh Subramani, Trey Ideker
We have developed a general progressive procedure, Active Interaction Mapping, to guide assembly of the hierarchy of functions encoding any biological system. Using this process, we assemble an ontology of functions comprising autophagy, a central recycling process implicated in numerous diseases. A first-generation model, built from existing gene networks in Saccharomyces, captures most known autophagy components in broad relation to vesicle transport, cell cycle, and stress response. Systematic analysis identifies synthetic-lethal interactions as most informative for further experiments; consequently, we saturate the model with 156,364 such measurements across autophagy-activating conditions...
February 16, 2017: Molecular Cell
A Licon, J Ford, D Defoor, R Crownover, Y Li, C Ha, T Eng, W Jones, N Papanikolaou, S Stathakis, P Mavroidis
PURPOSE: To create an IMRT treatment plan quantitative score using QUANTEC dose/volume parameters to assess plan quality. METHODS: 132 IMRT patient plans of various treatment sites were evaluated. The optimized plan's dose volume histogram (DVH) was exported to Velocity for evaluation. The proposed scoring was based on calculating the shortest distance from the QUANTEC objective to the DVH line of each organ. Each plan was normalized against the "perfect" plan where the organs at risk (OAR) received no dose and hence the distance between the QUANTEC objective and the DVH line was maximized...
June 2016: Medical Physics
Marie H Foss, Sovitj Pou, Patrick M Davidson, Jennifer L Dunaj, Rolf W Winter, Sovijja Pou, Meredith H Licon, Julia K Doh, Yuexin Li, Jane X Kelly, Rozalia A Dodean, Dennis R Koop, Michael K Riscoe, Georgiana E Purdy
New treatments for tuberculosis infection are critical to combat the emergence of multidrug- and extensively drug-resistant Mycobacterium tuberculosis (Mtb). We report the characterization of a diphenylether-modified adamantyl 1,2-diamine that we refer to as TBL-140, which has a minimal inhibitory concentration (MIC99) of 1.2 μg/mL. TBL-140 is effective against drug-resistant Mtb and nonreplicating bacteria. In addition, TBL-140 eliminates expansion of Mtb in cell culture infection assays at its MIC. To define the mechanism of action of this compound, we performed a spontaneous mutant screen and biochemical assays...
July 8, 2016: ACS Infectious Diseases
Rohith Srivas, John Paul Shen, Chih Cheng Yang, Su Ming Sun, Jianfeng Li, Andrew M Gross, James Jensen, Katherine Licon, Ana Bojorquez-Gomez, Kristin Klepper, Justin Huang, Daniel Pekin, Jia L Xu, Huwate Yeerna, Vignesh Sivaganesh, Leonie Kollenstart, Haico van Attikum, Pedro Aza-Blanc, Robert W Sobol, Trey Ideker
An emerging therapeutic strategy for cancer is to induce selective lethality in a tumor by exploiting interactions between its driving mutations and specific drug targets. Here we use a multi-species approach to develop a resource of synthetic lethal interactions relevant to cancer therapy. First, we screen in yeast ∼169,000 potential interactions among orthologs of human tumor suppressor genes (TSG) and genes encoding drug targets across multiple genotoxic environments. Guided by the strongest signal, we evaluate thousands of TSG-drug combinations in HeLa cells, resulting in networks of conserved synthetic lethal interactions...
August 4, 2016: Molecular Cell
Jose A Bazan, Amy S Peterson, Robert D Kirkcaldy, Elizabeth C Briere, Courtney Maierhofer, Abigail Norris Turner, Denisse B Licon, Nicole Parker, Amanda Dennison, Melissa Ervin, Laura Johnson, Barbara Weberman, Pamela Hackert, Xin Wang, Cecilia B Kretz, A Jeanine Abrams, David L Trees, Carlos Del Rio, David S Stephens, Yih-Ling Tzeng, Mary DiOrio, Mysheika Williams Roberts
Neisseria meningitidis (Nm) urogenital infections, although less common than infections caused by Neisseria gonorrhoeae (Ng), have been associated with urethritis, cervicitis, proctitis, and pelvic inflammatory disease. Nm can appear similar to Ng on Gram stain analysis (gram-negative intracellular diplococci) (1-5). Because Nm colonizes the nasopharynx, men who receive oral sex (fellatio) can acquire urethral Nm infections (1,3,5). This report describes an increase in Nm-associated urethritis in men attending sexual health clinics in Columbus, Ohio, and Oakland County, Michigan...
June 3, 2016: MMWR. Morbidity and Mortality Weekly Report
Andrew M Gross, Philipp A Jaeger, Jason F Kreisberg, Katherine Licon, Kristen L Jepsen, Mahdieh Khosroheidari, Brenda M Morsey, Susan Swindells, Hui Shen, Cherie T Ng, Ken Flagg, Daniel Chen, Kang Zhang, Howard S Fox, Trey Ideker
HIV-infected individuals are living longer on antiretroviral therapy, but many patients display signs that in some ways resemble premature aging. To investigate and quantify the impact of chronic HIV infection on aging, we report a global analysis of the whole-blood DNA methylomes of 137 HIV+ individuals under sustained therapy along with 44 matched HIV- individuals. First, we develop and validate epigenetic models of aging that are independent of blood cell composition. Using these models, we find that both chronic and recent HIV infection lead to an average aging advancement of 4...
April 21, 2016: Molecular Cell
Michael Ku Yu, Michael Kramer, Janusz Dutkowski, Rohith Srivas, Katherine Licon, Jason Kreisberg, Cherie T Ng, Nevan Krogan, Roded Sharan, Trey Ideker
Accurately translating genotype to phenotype requires accounting for the functional impact of genetic variation at many biological scales. Here we present a strategy for genotype-phenotype reasoning based on existing knowledge of cellular subsystems. These subsystems and their hierarchical organization are defined by the Gene Ontology or a complementary ontology inferred directly from previously published datasets. Guided by the ontology's hierarchical structure, we organize genotype data into an "ontotype," that is, a hierarchy of perturbations representing the effects of genetic variation at multiple cellular scales...
February 24, 2016: Cell Systems
Adriana Leticia Perales-Torres, Octelina Castillo-Ruíz, María Teresa Castañeda Licón, Sanjuana E Alemán-Castillo, Juan Miguel Jiménez Andrade
The purpose of this review is to analyze the biochemical progression of atherosclerotic plaque and its association with diet and diabetes. This study shows the scientific evidence of demonstrating that diabetic patients present high levels of fatty acids like palmitic acid and linoleic acid in their atheroma plaques in comparison with non-diabetic patients. This study also establishes how patients with diabetes mellitus have a higher prevalence of atherosclerotic heart diseases in the form of Coronary Thrombosis and have different anatomopathological appearance like higher necrotic core and thin fibrotic layer than the general population...
October 2016: Archivos de Cardiología de México
John Paul Shen, Rohith Srivas, Andrew Gross, Jianfeng Li, Eric J Jaehnig, Su Ming Sun, Ana Bojorquez-Gomez, Katherine Licon, Vignesh Sivaganesh, Jia L Xu, Kristin Klepper, Huwate Yeerna, Daniel Pekin, Chu Ping Qiu, Haico van Attikum, Robert W Sobol, Trey Ideker
Chemical inhibitors of the checkpoint kinases have shown promise in the treatment of cancer, yet their clinical utility may be limited by a lack of molecular biomarkers to identify specific patients most likely to respond to therapy. To this end, we screened 112 known tumor suppressor genes for synthetic lethal interactions with inhibitors of the CHEK1 and CHEK2 checkpoint kinases. We identified eight interactions, including the Replication Factor C (RFC)-related protein RAD17. Clonogenic assays in RAD17 knockdown cell lines identified a substantial shift in sensitivity to checkpoint kinase inhibition (3...
November 3, 2015: Oncotarget
Alik S Widge, Ernesto Licon, Samuel Zorowitz, Andrew Corse, Amanda R Arulpragasam, Joan A Camprodon, Cristina Cusin, Emad N Eskandar, Thilo Deckersbach, Darin D Dougherty
Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is a novel therapy for neuropsychiatric disorders. Hypomania is a known complication of VC/VS DBS, but who is at risk is less understood. Factors such as family history, combined with details of DBS programming, might quantify that risk. The authors performed an iterative modeling procedure on a VC/VS DBS patient registry to identify key predictors. Hypomania was less common for men and for patients stimulated on the ventral right contact...
2016: Journal of Neuropsychiatry and Clinical Neurosciences
Tsung-Han Chou, Jared A Delmar, Catherine C Wright, Nitin Kumar, Abhijith Radhakrishnan, Julia K Doh, Meredith H Licon, Jani Reddy Bolla, Hsiang-Ting Lei, Kanagalaghatta R Rajashankar, Chih-Chia Su, Georgiana E Purdy, Edward W Yu
Mycobacterium tuberculosis is a pathogenic bacterial species, which is neither Gram positive nor Gram negative. It has a unique cell wall, making it difficult to kill and conferring resistance to antibiotics that disrupt cell wall biosynthesis. Thus, the mycobacterial cell wall is critical to the virulence of these pathogens. Recent work shows that the mycobacterial membrane protein large (MmpL) family of transporters contributes to cell wall biosynthesis by exporting fatty acids and lipidic elements of the cell wall...
December 2015: Protein Science: a Publication of the Protein Society
José Alejandro Martínez-Ibarra, Benjamín Nogueda-Torres, Ángel Licón-Trillo, Ricardo Alejandre-Aguilar, Paz María Salazar-Schettino, Mauro Omar Vences-Blanco
The degree of reproductive isolation between Triatoma recurva (Stål) (Hemiptera: Reduviidae: Triatominae) and the six species of the genus Meccus plus T. mexicana (Herrich-Schaeffer) (Hemiptera: Reduviidae) was examined. Fertility and the segregation of morphological characteristics were examined in two generations of hybrids from crosses between these species. The percentage of couples with offspring (fertile) was low in the vast majority of sets of crosses, with the exception of that between T. recurva female and M...
June 2015: Journal of Vector Ecology: Journal of the Society for Vector Ecology
Claudia P Herrera, Meredith H Licon, Catherine S Nation, Samuel B Jameson, Dawn M Wesson
BACKGROUND: Chagas disease is an anthropozoonosis caused by the protozoan parasite Trypanosoma cruzi that represents a major public health problem in Latin America. Although the United States is defined as non-endemic for Chagas disease due to the rarity of human cases, the presence of T. cruzi has now been amply demonstrated as enzootic in different regions of the south of the country from Georgia to California. In southeastern Louisiana, a high T. cruzi infection rate has been demonstrated in Triatoma sanguisuga, the local vector in this area...
2015: Parasites & Vectors
Claudia P Herrera, Meredith H Licon, Catherine S Nation, Samuel B Jameson, Dawn M Wesson
BACKGROUND: Chagas disease is an anthropozoonosis caused by the protozoan parasite Trypanosoma cruzi that represents a major public health problem in Latin America. Although the United States is defined as non-endemic for Chagas disease due to the rarity of human cases, the presence of T. cruzi has now been amply demonstrated as enzootic in different regions of the south of the country from Georgia to California. In southeastern Louisiana, a high T. cruzi infection rate has been demonstrated in Triatoma sanguisuga, the local vector in this area...
December 2015: Parasites & Vectors
Jesse Stombaugh, Abel Licon, Žaklina Strezoska, Joshua Stahl, Sarah Bael Anderson, Michael Banos, Anja van Brabant Smith, Amanda Birmingham, Annaleen Vermeulen
RNA interference screening using pooled, short hairpin RNA (shRNA) is a powerful, high-throughput tool for determining the biological relevance of genes for a phenotype. Assessing an shRNA pooled screen's performance is difficult in practice; one can estimate the performance only by using reproducibility as a proxy for power or by employing a large number of validated positive and negative controls. Here, we develop an open-source software tool, the Power Decoder simulator, for generating shRNA pooled screening experiments in silico that can be used to estimate a screen's statistical power...
September 2015: Journal of Biomolecular Screening
Ryong Nam Kim, Yoon-La Choi, Mi-Sook Lee, Maruja E Lira, Mao Mao, Derrick Mann, Joshua Stahl, Abel Licon, So Jung Choi, Michael Van Vrancken, Joungho Han, Iwona Wlodarska, Jhingook Kim
Anaplastic lymphoma kinase (ALK) fusion is a common mechanism underlying pathogenesis of non-small cell lung carcinoma (NSCLC) where these rearrangements represent important diagnostic and therapeutic targets. In this study, we found a new ALK fusion gene, SEC31A-ALK, in lung carcinoma from a 53-year-old Korean man. The conjoined region in the fusion transcript was generated by the fusion of SEC31A exon 21 and ALK exon 20 by genomic rearrangement, which contributed to generation of an intact, in-frame open reading frame...
January 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Abel Licon, Michela Taufer, Ming-Ying Leung, Kyle L Johnson
In this paper, we present a dynamic programming algorithm that runs in polynomial time and allows us to achieve the optimal, non-overlapping segmentation of a long RNA sequence into segments (chunks). The secondary structure of each chunk is predicted independently, then combined with the structures predicted for the other chunks, to generate a complete secondary structure prediction that is thus a combination of local energy minima. The proposed approach not only is more efficient and accurate than other traditionally used methods that are based on global energy minimizations, but it also allows scientists to overcome computing and storage constraints when trying to predict the secondary structure of long RNA sequences...
March 2010: International Conference on Bioinformatics and Computational Biology 2010: BICoB-2010
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