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Full-Text Articles in Life Sciences

Single-Cell Analysis Of Proxy Reporter Allele-Marked Epthelial Cells Establishes Intestinal Stem Cell Hierarchy, Ning Li, Maryam Yousefi, Angela Nakauka-Ddamba, Rajan Jain, John Tobias, Jonathan A. Epstein, Shane T. Jensen, Christopher J. Lengner Nov 2014

Single-Cell Analysis Of Proxy Reporter Allele-Marked Epthelial Cells Establishes Intestinal Stem Cell Hierarchy, Ning Li, Maryam Yousefi, Angela Nakauka-Ddamba, Rajan Jain, John Tobias, Jonathan A. Epstein, Shane T. Jensen, Christopher J. Lengner

Statistics Papers

The recent development of targeted murine reporter alleles as proxies for intestinal stem cell activity has led to significant advances in our understanding of somatic stem cell hierarchies and dynamics. Analysis of these reporters has led to a model in which an indispensable reserve stem cell at the top of the hierarchy (marked by Bmi1 and Hopx reporters) gives rise to active intestinal stem cells (marked by an Lgr5 reporter). Despite these advances, controversy exists regarding the specificity and fidelity with which these alleles distinguish intestinal stem cell populations. Here, we undertake a comprehensive comparison of widely used proxy reporters ...


Characterization Of A Computationally Designed Water-Soluble Human Μ Opioid Receptor Variant Using X-Ray Structural Information, Xuelian Zhao, Jose Manuel Perez Aguilar, Felipe Matsunaga, Mitchell Bryant Lerner, Jin Xi, Bernard Selling, A. T. Charlie Johnson, Jeffery G. Saven, Renyu Liu Oct 2014

Characterization Of A Computationally Designed Water-Soluble Human Μ Opioid Receptor Variant Using X-Ray Structural Information, Xuelian Zhao, Jose Manuel Perez Aguilar, Felipe Matsunaga, Mitchell Bryant Lerner, Jin Xi, Bernard Selling, A. T. Charlie Johnson, Jeffery G. Saven, Renyu Liu

Departmental Papers (Chemistry)

Background

The recent X-ray crystal structure of the murine μ opioid receptor (MUR) allowed us to reengineer a previously designed water-soluble variant of the transmembrane portion of the human MUR (wsMUR-TM).

Methods

The new variant of water soluble MUR (wsMUR-TM_v2) was engineered based upon the murine MUR crystal structure. This novel variant was expressed in E. coliand purified. The properties of the receptor were characterized and compared with those of wsMUR-TM.

Results

Seven residues originally included for mutation in the design of the wsMUR-TM, were reverted to their native identities. wsMUR-TM_v2 contains 16% mutations of the total sequence. It ...


Variable Selection For Bart: An Application To Gene Regulation, Justin Bleich, Adam Kapelner, Edward I. George, Shane T. Jensen Oct 2014

Variable Selection For Bart: An Application To Gene Regulation, Justin Bleich, Adam Kapelner, Edward I. George, Shane T. Jensen

Statistics Papers

We consider the task of discovering gene regulatory networks, which are defined as sets of genes and the corresponding transcription factors which regulate their expression levels. This can be viewed as a variable selection problem, potentially with high dimensionality. Variable selection is especially challenging in high-dimensional settings, where it is difficult to detect subtle individual effects and interactions between predictors. Bayesian Additive Regression Trees [BART, Ann. Appl. Stat. 4 (2010) 266–298] provides a novel nonparametric alternative to parametric regression approaches, such as the lasso or stepwise regression, especially when the number of relevant predictors is sparse relative to the ...


Aiding Decision Making To Reduce The Impacts Of Climate Change, Howard Kunreuther Sep 2014

Aiding Decision Making To Reduce The Impacts Of Climate Change, Howard Kunreuther

Operations, Information and Decisions Papers

Utilizing theory and empirical insights from psychology and behavioural economics, this paper examines individuals’ cognitive and motivational barriers to adopting climate change adaptation and mitigation measures that increase consumer welfare. We explore various strategies that take into account the simplified decision-making processes used by individuals and resulting biases. We make these points by working through two examples: (1) investments in energy efficiency products and new technology and (2) adaptation measures to reduce property damage from future floods and hurricanes. In both cases there is a reluctance to undertake these measures due to high and certain upfront costs, delayed and probabilistic ...


Metastatic Tumor Evolution And Organoid Modeling Implicate Tgfbr2 As A Cancer Driver In Diffuse Gastric Cancer, Lincoln Nadauld, Sarah Garcia, Georges Natsoulis, John M. Bell, Laura Miotke, Erik S. Hopmans, Hua Xu, Reetesh K. Pai, Curt Palm, John F. Regan, Hao Chen, Patrick Flaherty, Akifumi Ootani, Nancy R. Zhang, James M. Ford, Calvin J. Kuo, Hanlee P. Ji Aug 2014

Metastatic Tumor Evolution And Organoid Modeling Implicate Tgfbr2 As A Cancer Driver In Diffuse Gastric Cancer, Lincoln Nadauld, Sarah Garcia, Georges Natsoulis, John M. Bell, Laura Miotke, Erik S. Hopmans, Hua Xu, Reetesh K. Pai, Curt Palm, John F. Regan, Hao Chen, Patrick Flaherty, Akifumi Ootani, Nancy R. Zhang, James M. Ford, Calvin J. Kuo, Hanlee P. Ji

Statistics Papers

Background: Gastric cancer is the second-leading cause of global cancer deaths, with metastatic disease representing the primary cause of mortality. To identify candidate drivers involved in oncogenesis and tumor evolution, we conduct an extensive genome sequencing analysis of metastatic progression in a diffuse gastric cancer. This involves a comparison between a primary tumor from a hereditary diffuse gastric cancer syndrome proband and its recurrence as an ovarian metastasis.

Results: Both the primary tumor and ovarian metastasis have common biallelic loss-of-function of both the CDH1 and TP53 tumor suppressors, indicating a common genetic origin. While the primary tumor exhibits amplification of ...


Anesthesia Technique, Mortality, And Length Of Stay After Hip Fracture Surgery, Mark Neuman, Paul R. Rosenbaum, Justin Ludwig, Jose Zubizarreta, Jeffrey H. Silber Jun 2014

Anesthesia Technique, Mortality, And Length Of Stay After Hip Fracture Surgery, Mark Neuman, Paul R. Rosenbaum, Justin Ludwig, Jose Zubizarreta, Jeffrey H. Silber

Statistics Papers

Importance: More than 300 000 hip fractures occur each year in the United States. Recent practice guidelines have advocated greater use of regional anesthesia for hip fracture surgery.

Objective: To test the association of regional (ie, spinal or epidural) anesthesia vs general anesthesia with 30-day mortality and hospital length of stay after hip fracture.


Scalable Production Of Highly Sensitive Nanosensors Based On Graphene Functionalized With A Designed G Protein-Coupled Receptor, Mitchell Bryant Lerner, Felipe Matsunaga, Gang Hee Han, Sung Ju Hong, Jin Xi, Alexander Crook, Jose Manuel Perez Aguilar, Yung Woo Park, Jeffery G. Saven, Renyu Liu, A. T. Charlie Johnson Apr 2014

Scalable Production Of Highly Sensitive Nanosensors Based On Graphene Functionalized With A Designed G Protein-Coupled Receptor, Mitchell Bryant Lerner, Felipe Matsunaga, Gang Hee Han, Sung Ju Hong, Jin Xi, Alexander Crook, Jose Manuel Perez Aguilar, Yung Woo Park, Jeffery G. Saven, Renyu Liu, A. T. Charlie Johnson

Departmental Papers (Chemistry)

We have developed a novel, all-electronic biosensor for opioids that consists of an engineered μ-opioid receptor protein, with high binding affinity for opioids, chemically bonded to a graphene field-effect transistor to read out ligand binding. A variant of the receptor protein that provided chemical recognition was computationally redesigned to enhance its solubility and stability in an aqueous environment. A shadow mask process was developed to fabricate arrays of hundreds of graphene transistors with average mobility of ∼1500 cm2 V–1 s–1 and yield exceeding 98%. The biosensor exhibits high sensitivity and selectivity for the target naltrexone, an opioid receptor ...


Minimal Animal: Surveillance, Simulation, And Stochasticity In Wildlife Biology, Etienne S. Benson Jan 2014

Minimal Animal: Surveillance, Simulation, And Stochasticity In Wildlife Biology, Etienne S. Benson

Departmental Papers (HSS)

This article discusses the problematics and potentialities proposed by the "minimal animal" an animal that is nothing but a stochastic pattern across a blank page. The minimal animal was not an invention of the 1960s, but the tracking systems and digital computers that first became available during that period both broadened its reach and changed its character in significant ways.