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CRT-504 A Pilot Study of the Effect of Niacin on Pulmonary Arterial Pressure

Jason Sayanlar, Martin McNamara, Daniel Dooley, Allen Taylor
2014 JACC: Cardiovascular Interventions  
Niacin, a compound primarily used for its lipid altering properties, has been shown to improve endothelial function with short term administration, via the release of prostaglandins. We hypothesized that via these effects, niacin could lead to reductions in pulmonary artery pressures. Methods: Pilot study involving 32 subjects with known tricuspid regurgitation (TR) and a Doppler jet velocity of 2.7 m/s or greater. Subjects were randomized in a 1:2:2 ratio to receive a single dose of either
more » ... ebo, niacin 100mg or niacin 500mg respectively in a double blinded, acute provocation study. Following baseline assessment of TR jet velocity, blinded study drug was administered. At peak absorption of niacin and maximal flushing triggered by prostaglandin release (1 hour postadministration), TR jet velocity was re-assessed. The study was powered to detect a difference of 0.2 AE 0.2 m/s in TR jet velocity between groups. Results: Baseline TR jet velocity was 2.89 AE 0.30 m/s. The mean change in Doppler jet velocity was -0.024 AE 0.15 m/s in the placebo group, compared to -0.041 AE 0.27 m/s with niacin 100 mg, and -0.065 AE 0.17 m/s with niacin 500 mg. This trend was not statistically significant (ANOVA). The overall reduction in TR jet velocity observed with niacin, (2.93 AE 0.32 m/s to 2.87 AE 0.42 m/s) was small and not statistically significant (P ¼ 0.26). There was no observed effect among subgroups with above or below median baseline TR Doppler jet velocities. Conclusion: Single dose administration of immediate-release niacin 100 mg or 500 mg has no significant effect on PA pressures at 1 hour post administration.
doi:10.1016/j.jcin.2014.01.118 fatcat:yspabtqnlbgb7i7gqe7qrce3iu

A randomized pilot study on the effect of niacin on pulmonary arterial pressure

Martin J. McNamara, Jason J. Sayanlar, Daniel J. Dooley, Monvadi B. Srichai, Allen J. Taylor
2015 Trials  
Niacin induces the release of vasodilating prostaglandins, for which receptors are present within the pulmonary arterial circulation. We hypothesized that immediate-release niacin would reduce right ventricular systolic pressure in patients with pulmonary hypertension in a randomized, double-blinded, single-dose provocation study. Methods: We recruited inpatient subjects with a Doppler echocardiogram showing a peak tricuspid regurgitation (TR) jet velocity of 2.7 m/s or greater, and who were
more » ... e of known pulmonary vascular disease. Subjects were randomized in a 1:2:2 ratio to receive a single dose of either placebo, niacin 100 mg or niacin 500 mg, respectively. TR jet velocities were measured immediately before, and 1 hour post dose, corresponding to peak niacin absorption and prostaglandin release. The primary endpoint was the change in mean TR jet velocity measured over ten successive cardiac cycles. Results: The baseline mean estimated right ventricular systolic pressure (RVSP) for all 49 subjects (25 male) was 51.9 ± 12.1 mm Hg. The primary endpoint of mean change in TR jet velocity was 0.016 ± 0.065 m/s in the placebo group, compared to −0.017 ± 0.065 m/s with niacin 100 mg, and −0.063 ± 0.038 m/s with niacin 500 mg (P = 0.63). The change in maximum estimated RVSP across the three drug groups was 0.2 ± 1.6 mm Hg, −1.3 ± 1.8 mm Hg and −2.2 ± 1.2 mm Hg (P = 0.62). In exploratory pairwise analysis in the high-dose niacin group (500 mg), the reduction in mean RVSP was from 50.9 ± 9.4 mm Hg to 48.7 ± 10.0 mm Hg (P = 0.09).
doi:10.1186/s13063-015-1013-6 pmid:26590128 pmcid:PMC4654874 fatcat:ste3xezxazdgli66ottvubcm3y

Genetic Tools for Studying Adaptation and the Evolution of Behavior

Christine R. B. Boake, Stevan J. Arnold, Felix Breden, Lisa M. Meffert, Michael G. Ritchie, Barbara J. Taylor, Jason B. Wolf, Allen J. Moore
2002 American Naturalist  
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doi:10.1086/342902 pmid:18707473 fatcat:kbkinegrw5b4rnxmchhfrd23qq

Oseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape

Friederike Feldmann, Darwyn Kobasa, Carissa Embury-Hyatt, Allen Grolla, Tracy Taylor, Maki Kiso, Satoshi Kakugawa, Jason Gren, Steven M. Jones, Yoshihiro Kawaoka, Heinz Feldmann, Diane E. Griffin
2019 mBio  
The 1918 influenza virus, subtype H1N1, was the causative agent of the most devastating pandemic in the history of infectious diseases. In vitro studies have confirmed that extreme virulence is an inherent property of this virus. Here, we utilized the macaque model for evaluating the efficacy of oseltamivir phosphate against the fully reconstructed 1918 influenza virus in a highly susceptible and relevant disease model. Our findings demonstrate that oseltamivir phosphate is effective in
more » ... ng severe disease in macaques but vulnerable to virus escape through emergence of resistant mutants, especially if given in a treatment regimen. Nevertheless, we conclude that oseltamivir would be highly beneficial to reduce the morbidity and mortality rates caused by a highly pathogenic influenza virus although it would be predicted that resistance would likely emerge with sustained use of the drug. IMPORTANCE Oseltamivir phosphate is used as a first line of defense in the event of an influenza pandemic prior to vaccine administration. Treatment failure through selection and replication of drug-resistant viruses is a known complication in the field and was also demonstrated in our study with spread of resistant 1918 influenza virus in multiple respiratory tissues. This emphasizes the importance of early treatment and the possibility that noncompliance may exacerbate treatment effectiveness. It also demonstrates the importance of implementing combination therapy and vaccination strategies as soon as possible in a pandemic situation.
doi:10.1128/mbio.02059-19 pmid:31641086 pmcid:PMC6805992 fatcat:leudk3wmtjcjtdxexc7waoydnu

Ubiquitin Proteasome Pathway–Mediated Degradation of Proteins: Effects Due to Site-Specific Substrate Deamidation

Edward J. Dudek, Kirsten J. Lampi, Jason A. Lampi, Fu Shang, Jonathan King, Yongting Wang, Allen Taylor
2010 Investigative Ophthalmology and Visual Science  
PURPOSE. The accumulation, aggregation, and precipitation of proteins is etiologic for age-related diseases, particularly cataract, because the precipitates cloud the lens. Deamidation of crystallins is associated with protein precipitation, aging, and cataract. Among the roles of the ubiquitin proteasome pathway (UPP) is protein surveillance and maintenance of protein quality. The purpose of this study was to determine whether deamidation can alter clearance of crystallins by the UPP. METHODS.
more » ... Wild-type (WT) and deamidated crystallins were expressed and 125 I-radiolabeled. Ubiquitination and degradation were monitored separately. RESULTS. For ␤B2 crystallins, rates of ubiquitination and adenosine triphosphate-dependent degradation, both indicators of active UPP, occurred in the order Q70E/Q162EϾQ162EϾ Q70EϭWT ␤B2 using reticulocyte lysate as the source of degradation machinery. Human lens epithelial cell lysates and lens fiber cell lysates also catalyzed ubiquitination but only limited degradation. Supplementation with proteasome failed to enhance degradation. Rates of ubiquitination and degradation of WT and deamidated ␤B1 crystallins were rapid and showed little relationship to the site of deamidation using N157D and Q204E mutants. ␥D-Crystallins were not degraded by the UPP. Deamidation altered amine reactivity, circular dichroism spectra, surface hydrophobicity, and thermal stability. CONCLUSIONS. These data demonstrate for the first time that, like mild oxidative stress, deamidation of some proteins makes them preferred substrates for ubiquitination and, in some cells, for UPP-dependent degradation. Failure to properly execute ubiquitination and degrade the ubiquitin-conjugates may ex-From the
doi:10.1167/iovs.09-4087 pmid:20592226 pmcid:PMC2910644 fatcat:jpvomptkgfe7dh3bliv4vfr6tq

The Thermal Infrared Sensor on the Landsat Data Continuity Mission

Dennis Reuter, Cathy Richardson, James Irons, Rick Allen, Martha Anderson, Jason Budinoff, Gordon Casto, Craig Coltharp, Paul Finneran, Betsy Forsbacka, Taylor Hale, Tom Jennings (+13 others)
2010 2010 IEEE International Geoscience and Remote Sensing Symposium  
Figure 2 shows an example of the evapotranspiration data product derived from Landsat 5 using the University of Idaho METRIC process (Allen et al, 2007) .  ...  Bibliography Allen, R.G., Tasumi, M. and Trezza, R., 2007. Satellite-based energy balance for mapping evapotranspiration with internalized calibration (METRIC) -Model. ASCE J.  ... 
doi:10.1109/igarss.2010.5653746 dblp:conf/igarss/ReuterRIAABCCFFHJJLMMMORSSTTUW10 fatcat:jhyyut3j7fchher3mf2e3z7uea

Genomic evolutionary patterns of leiomyosarcoma and liposarcoma

Ali Amin-Mansour, Suzanne George, Stefano Sioletic, Scott L. Carter, Mara Rosenberg, Amaro Taylor-Weiner, Chip Stewart, Aaron Chevalier, Sara Seepo, Adam Tracy, Gad Getz, Jason L. Hornick (+7 others)
2019 Clinical Cancer Research  
From a genomic perspective, leiomyosarcoma metastases contain genetic alterations that are also found in primary tumors. WDLPS and DDLPS, however, appear to divergently evolve from a common precursor harboring 12q amplification, rather than as a transformation to a higher-grade tumor. Further efforts to identify specific drivers of these distinct evolutionary patterns may inform future translational and clinical research in STS.
doi:10.1158/1078-0432.ccr-19-0271 pmid:31164371 pmcid:PMC7341441 fatcat:hmibtwtqjrawhocgijwleodd3y

Preparing For Hyperseed MAC: An Observing Campaign To Monitor The Entry Of The Genesis Sample Return Capsule

2005 Earth, moon, and planets  
The imminent return of the Genesis Sample Return Capsule (SRC) from the Earth's L1 point on September 8, 2004, represents the first opportunity since the Apollo era to study the atmospheric entry of a meter-sized body at or above the Earth's escape speed. Until now, reentry heating models are based on only one successful reentry with an instrumented vehicle at higher than escape speed, the 22 May 1965 NASA "FIRE 2" experiment. In preparation of an instrumented airborne and ground-based
more » ... campaign, we examined the expected bolide radiation for the reentry of the Genesis SRC. We find that the expected emission spectrum consists mostly of blackbody emission from the SRC surface (T ~ 2630 K @ peak heating), slightly skewed in shape because of a range of surface temperatures. At high enough spectral resolution, shock emission from nitrogen and oxygen atoms, as well as the first positive and first negative bands of N 2 + , will stand out above this continuum. Carbon atom lines and the 389-nm CN band emission may also be detected, as well as the mid-IR 4.6-micron CO band. The ablation rate can be studied from the signature of trace sodium in the heat shield material, calibrated by the total amount of matter lost from the recovered shield. A pristine collection of the heat shield would also permit the sampling of products of ablation.
doi:10.1007/s11038-005-9021-2 fatcat:zk5o3pdmhvd7xcg5n5aa7gwi2i

Biomarker significance of plasma and tumor miR-21, miR-221, and miR-106a in osteosarcoma

Manjula Nakka, Wendy Allen-Rhoades, Yiting Li, Aaron J. Kelly, Jianhe Shen, Aaron M. Taylor, Donald A. Barkauskas, Jason T. Yustein, Irene L. Andrulis, Jay S. Wunder, Richard Gorlick, Paul S. Meltzer (+3 others)
2017 OncoTarget  
Osteosarcoma is the most common malignant bone tumor in children and young adults. Despite the use of surgery and multi-agent chemotherapy, osteosarcoma patients who have a poor response to chemotherapy or develop relapses have a dismal outcome. Identification of biomarkers for active disease may help to monitor tumor burden, detect early relapses, and predict prognosis in these patients. In this study, we examined whether circulating miRNAs can be used as biomarkers in osteosarcoma patients.
more » ... performed genome-wide miRNA profiling on a discovery cohort of osteosarcoma and control plasma samples. A total of 56 miRNAs were upregulated and 164 miRNAs were downregulated in osteosarcoma samples when compared to control plasma samples. miR-21, miR-221 and miR-106a were selected for further validation based on their known biological importance. We showed that all three circulating miRNAs were expressed significantly higher in osteosarcoma samples than normal samples in an independent cohort obtained from the Children's Oncology Group. Furthermore, we demonstrated that miR-21 was expressed significantly higher in osteosarcoma tumors compared with normal bone controls. More importantly, lower expressions of miR-21 and miR-221, but not miR-106a, significantly correlated with a poor outcome. In conclusion, our results indicate that miR-21, miR-221 and miR-106a were elevated in the circulation of osteosarcoma patients, whereas tumor expressions of miR-21 and miR-221 are prognostically significant. Further investigation of these miRNAs may lead to a better prognostic method and potential miRNA therapeutics for osteosarcoma.
doi:10.18632/oncotarget.18236 pmid:29228567 pmcid:PMC5722519 fatcat:3477xe74mnck7gpnpdz5hhtjv4

Budget impact analysis of robotic exoskeleton use for locomotor training following spinal cord injury in four SCI Model Systems

Daniel Pinto, Mauricio Garnier, Jason Barbas, Shuo-Hsiu Chang, Susan Charlifue, Edelle Field-Fote, Catherine Furbish, Candy Tefertiller, Chaithanya K. Mummidisetty, Heather Taylor, Arun Jayaraman, Allen W. Heinemann
2020 Journal of NeuroEngineering and Rehabilitation  
We know little about the budget impact of integrating robotic exoskeleton over-ground training into therapy services for locomotor training. The purpose of this study was to estimate the budget impact of adding robotic exoskeleton over-ground training to existing locomotor training strategies in the rehabilitation of people with spinal cord injury. A Budget Impact Analysis (BIA) was conducted using data provided by four Spinal Cord Injury (SCI) Model Systems rehabilitation hospitals. Hospitals
more » ... rovided estimates of therapy utilization and costs about people with spinal cord injury who participated in locomotor training in the calendar year 2017. Interventions were standard of care walking training including body-weight supported treadmill training, overground training, stationary robotic systems (i.e., treadmill-based robotic gait orthoses), and overground robotic exoskeleton training. The main outcome measures included device costs, training costs for personnel to use the device, human capital costs of locomotor training, device demand, and the number of training sessions per person with SCI. Robotic exoskeletons for over-ground training decreased hospital costs associated with delivering locomotor training in the base case analysis. This analysis assumed no difference in intervention effectiveness across locomotor training strategies. Providing robotic exoskeleton overground training for 10% of locomotor training sessions over the course of the year (range 226-397 sessions) results in decreased annual locomotor training costs (i.e., net savings) between $1114 to $4784 per annum. The base case shows small savings that are sensitive to parameters of the BIA model which were tested in one-way sensitivity analyses, scenarios analyses, and probability sensitivity analyses. The base case scenario was more sensitive to clinical utilization parameters (e.g., how often devices sit idle and the substitution of high cost training) than device-specific parameters (e.g., robotic exoskeleton device cost or device life). Probabilistic sensitivity analysis simultaneously considered human capital cost, device cost, and locomotor device substitution. With probabilistic sensitivity analysis, the introduction of a robotic exoskeleton only remained cost saving for one facility. Providing robotic exoskeleton for over-ground training was associated with lower costs for the locomotor training of people with SCI in the base case analyses. The analysis was sensitive to parameter assumptions.
doi:10.1186/s12984-019-0639-0 pmid:31924224 pmcid:PMC6954546 fatcat:zkkvunhelrc4dg4wyoh7sn5y5i

Epigenetic control of Cdkn2a.Arf protects tumor-infiltrating lymphocytes from metabolic exhaustion

Brian Koss, Bradley D. Shields, Erin M. Taylor, Aaron J. Storey, Stephanie D. Byrum, Allen J. Gies, Charity L. Washam, Samrat Roy Choudhury, Jeong Hyun Ahn, Hidetaka Uryu, Jason B. Williams, Kimberly J. Krager (+7 others)
2020 Cancer Research  
T cell exhaustion in cancer is linked to poor clinical outcomes and evidence suggests T cell metabolic changes precede functional exhaustion. Direct competition between tumor-infiltrating lymphocytes (TIL) and cancer cells for metabolic resources often renders T cells dysfunctional. Here, we report an epigenetic mechanism contributing to the development of metabolic exhaustion in TILs. Environmental stress produces epigenome remodeling events within tumor-infiltrating lymphocytes resulting from
more » ... loss of the histone methyltransferase EZH2. Using a multi-omics approach, we have defined a Cdkn2a.Arf-mediated, p53-independent mechanism by which EZH2 inhibition leads to mitochondrial dysfunction and the resultant exhaustion. Reprogramming T cells to express a gain-of-function EZH2 mutant resulted in an enhanced ability of T cells to inhibit tumor growth in vitro and in vivo. Our data suggest manipulation of T cell EZH2 within the context of cellular therapies may yield lymphocytes which are able to withstand harsh tumor metabolic environments and collateral pharmacologic insults.
doi:10.1158/0008-5472.can-20-0524 pmid:33004350 fatcat:knewqzy2enew5e5ecz2lzn23sm

Ground water and climate change

Richard G. Taylor, Bridget Scanlon, Petra Döll, Matt Rodell, Rens van Beek, Yoshihide Wada, Laurent Longuevergne, Marc Leblanc, James S. Famiglietti, Mike Edmunds, Leonard Konikow, Timothy R. Green (+14 others)
2012 Nature Climate Change  
Allen, D. M., Whitfield, P. H. & Werner, A. Groundwater level responses in temperate 453 mountainous terrain: regime classification, and linkages to climate and streamflow. 454 Hydrol.  ...  Owor, M., Taylor, R. G., Tindimugaya, C. & Mwesigwa, D. Rainfall intensity and 437 groundwater recharge: evidence from the Upper Nile Basin. Environ. Res. Lett. Small, E. E.  ... 
doi:10.1038/nclimate1744 fatcat:wbcszlt3a5gajmehkksu4ihthu

The construction, alignment, and installation of the VIRUS spectrograph

Sarah E. Tuttle, Gary J. Hill, Hanshin Lee, Brian Vattiat, Eva Noyola, Niv Drory, Mark Cornell, Trent Peterson, Taylor Chonis, Richard Allen, Gavin Dalton, Darren DePoy (+16 others)
2014 Ground-based and Airborne Instrumentation for Astronomy V  
VIRUS is the massively replicated fiber-fed spectrograph being built for the Hobby-Eberly Telescope to support HETDEX (the Hobby-Eberly Telescope Dark Energy Experiment). The instrument consists of 156 identical channels, fed by 34,944 fibers contained in 78 integral field units, deployed in the 22 arcminute field of the upgraded HET. VIRUS covers 350-550nm at R ⇡ 700 and is built to target Lyman ↵ emitters at 1.9 < z < 3.5 to measure the evolution of dark energy. Here we present the assembly
more » ... ne construction of the VIRUS spectrographs, including their alignment and plans for characterization. We briefly discuss plans for installation on the telescope. The spectrographs are being installed on the HET in several stages, and the instrument is due for completion by the end of 2014. Downloaded From: on 09/26/2014 Terms of Use: Proc. of SPIE Vol. 9147 91470R-2 Downloaded From: on 09/26/2014 Terms of Use: Proc. of SPIE Vol. 9147 91470R-5 Downloaded From: on 09/26/2014 Terms of Use: Proc. of SPIE Vol. 9147 91470R-6 Downloaded From: on 09/26/2014 Terms of Use: Proc. of SPIE Vol. 9147 91470R-11 Downloaded From: on 09/26/2014 Terms of Use:
doi:10.1117/12.2056503 fatcat:llkokbvou5g3zfzzxrvnn6xneu

VIRUS early installation and commissioning

Sarah E. Tuttle, Gary J. Hill, Brian L. Vattiat, Hanshin Lee, Niv Drory, Andreas Kelz, Jason Ramsey, Trent Peterson, Eva Noyola, Darren L. DePoy, Jennifer L. Marshall, Taylor S. Chonis (+20 others)
2016 Ground-based and Airborne Instrumentation for Astronomy VI  
VIRUS is a massively replicated spectrograph built for HETDEX, the Hobby Eberly Telescope Dark Energy Experiment. It consists of 156 channels within 78 units fed by 34944 fibers over the 22 arcminute field of the upgraded HET. VIRUS covers a relatively narrow bandpass (350-550nm) at low resolution (R ⇠ 700) to target the emission of Lyman-alpha emitters (LAEs) for HETDEX. VIRUS is a first demonstration of industrial style assembly line replication in optical astronomy. Installation and testing
more » ... f VIRUS units began in November of 2015. This winter we celebrated the first on sky instrument activity of the upgraded HET, using a VIRUS unit and LRS2-R (the upgraded facility Low Resolution Spectrograph for the HET). Here we describe progress in VIRUS installation and commissioning through June 2016. We include early sky data obtained to characterize spectrograph performance and on sky performance of the newly upgraded HET. As part of the instrumentation for first science light at the HET, the IFU fed spectrographs were used to test a full range of telescope system functionality including the field calibration unit (FCU). We also use placement of strategic IFUs to map the new HET field to the fiber placement, and demonstrate actuation of the dithering mechanism key to HETDEX observations. Please verify that (1) all pages are present, (2) all figures are correct, (3) all fonts and special characters are correct, and (4) all text and figures fit within the red margin lines shown on this review document. Complete formatting information is available at Return to the Manage Active Submissions page at and approve or disapprove this submission. Your manuscript will not be published without this approval. Please contact with any questions or concerns. Return to the Manage Active Submissions page at and approve or disapprove this submission. Your manuscript will not be published without this approval. Please contact with any questions or concerns. Please verify that (1) all pages are present, (2) all figures are correct, (3) all fonts and special characters are correct, and (4) all text and figures fit within the red margin lines shown on this review document. Complete formatting information is available at Return to the Manage Active Submissions page at and approve or disapprove this submission. Your manuscript will not be published without this approval. Please contact with any questions or concerns.
doi:10.1117/12.2231253 fatcat:4siuljs46rhihp5mu37mk7iem4

MYC regulates ductal-neuroendocrine lineage plasticity in pancreatic ductal adenocarcinoma associated with poor outcome and chemoresistance

Amy S. Farrell, Meghan Morrison Joly, Brittany L. Allen-Petersen, Patrick J. Worth, Christian Lanciault, David Sauer, Jason Link, Carl Pelz, Laura M. Heiser, Jennifer P. Morton, Nathiya Muthalagu, Megan T. Hoffman (+13 others)
2017 Nature Communications  
Intratumoral phenotypic heterogeneity has been described in many tumor types, where it can contribute to drug resistance and disease recurrence. We analyzed ductal and neuroendocrine markers in pancreatic ductal adenocarcinoma, revealing heterogeneous expression of the neuroendocrine marker Synaptophysin within ductal lesions. Higher percentages of Cytokeratin-Synaptophysin dual positive tumor cells correlate with shortened disease-free survival. We observe similar lineage marker heterogeneity
more » ... n mouse models of pancreatic ductal adenocarcinoma, where lineage tracing indicates that Cytokeratin-Synaptophysin dual positive cells arise from the exocrine compartment. Mechanistically, MYC binding is enriched at neuroendocrine genes in mouse tumor cells and loss of MYC reduces ductalneuroendocrine lineage heterogeneity, while deregulated MYC expression in KRAS mutant mice increases this phenotype. Neuroendocrine marker expression is associated with chemoresistance and reducing MYC levels decreases gemcitabine-induced neuroendocrine marker expression and increases chemosensitivity. Altogether, we demonstrate that MYC facilitates ductal-neuroendocrine lineage plasticity in pancreatic ductal adenocarcinoma, contributing to poor survival and chemoresistance.
doi:10.1038/s41467-017-01967-6 pmid:29170413 pmcid:PMC5701042 fatcat:fzlwdbrdjnh7hbuoomeu6d3soy
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