bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping tissue waterT1in the liver using the MOLLIT1method in the presence of fat, iron andB0inhomogeneity
Authors: Mozes Ferenc E. , Tunnicliffe Elizabeth M. , Moolla Ahmad , Marjot Thomas , Levick Christina K. , Pavlides Michael , Robson Matthew D.
Published: November 2018

Modified Look‐Locker inversion recovery (MOLLI)T1mapping sequences can be useful in cardiac and liver tissue characterization, but determining underlying waterT1is confounded by iron, fat and frequency offsets. This article proposes an algorithm that provides an independent water MOLLIT1(referred to as on‐resonance waterT1) that would have been measured if a subject had no fat and normal iron, and imaging had been done on resonance. Fifteen NiCl2‐doped agar phantoms with different peanut oil concentrations and 30 adults with various liver diseases, nineteen (63.3%) with liver steatosis, were scanned at 3 T using the shortened MOLLI (shMOLLI)T1mapping, multiple‐echo spoiled gradient‐recalled echo and1H MR spectroscopy sequences. An algorithm based on Bloch equations was built in MATLAB, and water shMOLLIT1values of both phantoms and human participants were determined. The quality of the algorithm's result was assessed by Pearson's correlation coefficient between shMOLLIT1values and spectroscopically determinedT1values of the water, and by linear regression analysis. Correlation between shMOLLI and spectroscopy‐basedT1values increased, fromr = 0.910 (P < 0.001) tor = 0.998 (P < 0.001) in phantoms and fromr = 0.493 (for iron‐only correction;P = 0.005) tor = 0.771 (for iron, fat and off‐resonance correction;P < 0.001) in patients. Linear regression analysis revealed that the determined water shMOLLIT1values in patients were independent of fat and iron. It can be concluded that determination of on‐resonance water (sh)MOLLIT1independent of fat, iron and macroscopic field inhomogeneities was possible in phantoms and human subjects.
Rapid Synthesis of N‐Tosylhydrazones under Solvent‐Free Conditions and Their Potential Application Against Human Triple‐Negative Breast Cancer
Authors: Xie Zengyang , Song Yuying , Xu Lujia , Guo Yukun , Zhang Min , Li Limei , Chen Kai , Liu Xue
Published: November 2018

Some N‐tosylhydrazone derivatives were effectively synthesized under solvent‐free conditions by using a grinding method at room temperature. The short reaction time, clean and mild process with simple workup and easy purification of the target compounds were salient features of the present protocol, which enables straightforward access to N‐tosylhydrazones. Among the tosylhydrazone derivatives evaluated, compound 3 l exhibits excellent apoptosis‐promoting and anticancer potential against triple‐negative breast cancer (TNBC) cell lines. This research shows that our synthesized compound 3 l may be a desirable and effective therapeutic drug against TNBC.
ANGPTL4 gene E40K variation protects against obesity‐associated dyslipidemia in participants with obesity
Authors: Bailetti D. , Bertoccini L. , Mancina R. M. , Barchetta I. , Capoccia D. , Cossu E. , Pujia A. , Lenzi A. , Leonetti F. , Cavallo M. G. , Romeo S. , Baroni M. G.
Published: November 2018

Objective

ANGPTL4 inhibits lipoprotein lipase in adipose tissue, regulating plasma triglycerides levels. In persons with obesity plasma ANGPTL4 levels have been positively correlated with body fat mass, TG levels and low HDL. A loss‐of‐function E40K mutation in ANGPTL4 prevents LPL inhibition, resulting in lower TGs and higher HDLc in the general population. Since obesity determines metabolic alterations and consequently is a major risk factor for cardiovascular disease, the aim was to explore if obesity‐related metabolic abnormalities are modified by the ANGPTL4‐E40K mutation.

Methods

ANGPTL4‐E40K was screened in 1206 Italian participants, of which 863 (71.5%) with obesity. All subjects without diabetes underwent OGTT with calculation of indices of insulin‐sensitivity.

Results

Participants with obesity carrying the E40K variant had significantly lower TG (p = 0.001) and higher HDLc levels (p = 0.024). Also in the whole population low TGs and high HDLc were confirmed in E40K carriers. In the obese subpopulation it was observed that almost all E40K carriers were within the lowest quartile of TGs (p = 1.1 × 10−9). E40K had no substantial effect of on glucose metabolism. Finally, none of the obese E40K carriers had T2D, and together with the favourable lipid profile, they resemble a metabolically healthy obese (MHO) phenotype, compared to 38% of E40E wild‐type obese that had diabetes and/or dyslipidaemia (p = 0.0106).

Conclusions

In participants with obesity the ANGPTL4‐E40K variant protects against dyslipidemia. The phenotype of obese E40K carriers is that of a patient with obesity without metabolic alterations, similar to the phenotype described as metabolic healthy obesity.
In situ characterization of surface‐layer structure evolution in γ‐irradiated carbon fibers by X‐ray photoelectron spectroscopy combined with argon‐ion sputtering
Authors: Liu Liangsen , Wang Haibo , Zhao Lihuan , Xu Zhiwei , Sui Xianhang , Feng Tingting , Li Nan , Li Jing , Chen Cheng , Lv Hanming
Published: November 2018

In this article, the surface‐layer structure evolution of carbon fibers along the cross‐section γ‐irradiated in epoxy chloropropane has been estimated by X‐ray photoelectron spectroscopy combined with in situ argon‐ion sputtering that is different from argon‐ion cleaning. In argon‐ion (Ar‐ion) sputtering, the detection and sputtering were alternately in situ carried out. The penetration depth of irradiation medium on the surface of carbon fibers was accurately verified (13 nm) according to the absence of chlorine element and the change of O/C atomic ratio on γ‐irradiated carbon fiber surface. Such characterization technology has opened up a meaningful method to analyze the heterogeneous structure of materials. POLYM. COMPOS., 40:E832–E834, 2019. © 2018 Society of Plastics Engineers
Modeling a bivariate residential‐workplace neighborhood effect when estimating the effect of proximity to fast‐food establishments on body mass index
Authors: O'Malley A. James , James Peter , MacKenzie Todd A. , Byun Jinyoung , Subramanian S. V. , Block Jason P.
Published: November 2018

Hierarchical modeling is the preferred approach of modeling neighborhood effects. When both residential and workplace neighborhoods are known, a bivariate (residential‐workplace) neighborhood random effect that quantifies the extent that a neighborhood's residential and workplace effects are correlated may be modeled. However, standard statistical software for hierarchical models does not easily allow correlations between the random effects of distinct clustering variables to be incorporated. To overcome this challenge, we develop a Bayesian model and an accompanying estimation procedure that allows for correlated bivariate neighborhood effects and allows individuals to reside or work in multiple neighborhoods, cross‐sectional and longitudinal heterogeneity between individuals, and serial correlation between repeated observations over time. Simulation studies that vary key model parameters evaluate how well each aspect of the model is identified by the data. We apply the model to the motivating Framingham Heart Study linked food establishment data to examine whether (i) proximity to fast‐food establishments is associated with body mass index, (ii) workplace neighborhood exposure associations are larger than those for residential neighborhood exposure, and (iii) residential neighborhood exposure associations correlate with workplace neighborhood exposure. Comparisons of the full model to models with restricted versions of the covariance structure illustrate the impact of including each feature of the covariance structure.
Uniform Lithium Nucleation Guided by Atomically Dispersed Lithiophilic CoNx Sites for Safe Lithium Metal Batteries
Authors: Liu He , Chen Xiang , Cheng Xin‐Bing , Li Bo‐Quan , Zhang Rui , Wang Bin , Chen Xiao , Zhang Qiang
Published: November 2018

The mossy lithium dendrite growth during repeated lithium plating/stripping induces low Coulombic efficiency, poor lifespan, and safety concerns of working lithium metal batteries. Herein, atomically dispersed CoNx‐doped graphene is exploited as a host to accommodate dendrite‐free lithium deposits. The coordination between Co and N in the conductive matrix can effectively regulate the local electronic structure, and thereby enhance the adsorption of lithium ions and promote the following nucleation process. Meanwhile, the doped N facilitates high dispersion of Co atoms into graphene through the CoN coordination bond. The strong lithiophilicity provided by N coordinated with Co promises a uniform lithium nucleation behavior, further contributing to the smooth lithium deposition morphology. These characteristics afford a superhigh Coulombic efficiency of 99.2% at 2.0 mA cm−2 (≈400 cycles) and 5.0 mA cm−2 (350 cycles), and 98.2% at 10.0 mA cm−2 (200 cycles) with a capacity of 2.0 mAh cm−2. LiFePO4|CoNC–Li full cells deliver a long lifespan of 340 cycles at 1.0 C (240 cycles for routine cells). This offers fresh insights into effectively regulating the lithiophilic chemistry of lithium metal host toward uniform nucleation and growth of lithium deposits in working high‐energy‐density batteries.
Combined analysis of 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and cotinine in urine by heart cutting two‐dimensional LC‐MS/MS
Authors: Lin Huaqing , Wang Yangzhong , Wang Tiannan , Wu Da , Li Gang , Deng Chunhui
Published: November 2018

4‐(Methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and cotinine are valuable biomarkers of tobacco smoke exposure. It is crucial to detect them for evaluating the health impact of exposure and the understanding of detoxification mechanism in humans. Considering the huge difference concentration in smoker's urine, they are always detected separately rather than simultaneously. In this work, we have developed an effective system of two‐dimensional liquid chromatography coupled with tandem mass spectrometry for high‐throughput simultaneous determination of 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and cotinine in smoker's urine. The strong cation‐exchange and the reversed‐phase chromatography were chosen as the first and second dimensional studies. The orthogonality of this two‐dimensional system was evaluated through the separation of 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and cotinine. Compared with traditional methodologies, the limits of detection of the method were 0.24 pg/mL and 0.054 ng/mL for 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and cotinine respectively. The recoveries of the spiked samples were 99.8‐105.1 and 111.9‐114.2% for 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and cotinine respectively in urine. The precisions of the method were 0.43‐3.07 and 0.73‐2.11%. The method is useful for monitoring 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and cotinine in smoking and satisfying to evaluate the tobacco exposure.
Freshwater Tidal Forests and Estuarine Wetlands May Confer Early Life Growth Advantages for Delta‐Reared Chinook Salmon
Authors: Davis Melanie J. , Woo Isa , Ellings Christopher S. , Hodgson Sayre , Beauchamp David A. , Nakai Glynnis , De La Cruz Susan E. W.
Published: November 2018

Large river deltas are complex ecosystems that are believed to play a pivotal role in promoting the early marine growth and survival of threatened Chinook Salmon Oncorhynchus tshawytscha. We used a fish bioenergetics model to assess the functional role of multiple delta habitats across a gradient of salinities and vegetation types, where consumption and growth rate potential (GRP) were considered as proxies for habitat quality. We subsequently compared our model output to empirical, or realized, growth estimates from scale circuli. In terms of consumption, prey energy density (EDprey) was 46–86% higher in tidal freshwater forest than in any other habitat type, while estimated consumption rates (expressed as proportion of maximum daily consumption; Pcmax) were positively correlated with FL. These size‐related differences in Pcmax led to a noticeable increase along a freshwater‐to‐saline gradient from roughly 0.25 in tidal freshwater forest to 0.55 in the offshore subtidal zone, yet despite higher observed Pcmax values in nearshore and offshore habitats, the tidal freshwater forest and emergent salt marsh demonstrated the highest modeled GRP values. Similarly, realized growth rates for fish caught in tidal freshwater forest were up to 0.5% higher per day than for fish caught in the offshore area, but habitat‐level differences were overshadowed by allometry and rearing origin. Scales from unmarked fish (assumed to be of wild origin) indicated that they grew, on average, 11% faster than did hatchery fish; however, these differences were subtle and were more obvious at fork lengths <100 mm. Our results suggest that tidal forests and emergent marshes may offer early life growth advantages for wild Chinook Salmon, but that wild and hatchery fish can compensate as they move seaward by opportunistically consuming greater quantities of low‐energy density prey, taking advantage of pulses of larval forage fish, or by spending time in multiple interconnected habitat types.
Blade imbalance fault diagnosis of doubly fed wind turbine based on current coordinate transformation
Authors: Yang Dong , Tang Ju , Zeng Fuping
Published: November 2018

A stator current characteristic analysis method based on coordinate transformation is proposed to address the issue of the double‐fed induction generator (DFIG) blade imbalance. Based on the DFIG and the wind turbine transmission chain model, the stator current expression of DFIG under blade imbalance failure was derived in detail, and the corresponding fault characteristic frequency was analyzed, which shows that the blade imbalance fault causes the stator current of the DFIG to generate the fault feature component with frequency fm on the d‐axis and q‐axis components. Then, the stator current characteristic analysis method based on coordinate transformation was proposed. Finally, a simulation model of DFIG with blade imbalance was established, and the fault characteristics of the turbine under different wind speeds and imbalance coefficients are simulated and analyzed. The results show that the stator current characteristic analysis method based on coordinate transformation can extract the characteristics of imbalanced fault and can be effective in determining the severity of the fault by monitoring the changes in the amplitude of the characteristic frequency compared with direct spectrum analysis of stator current and blade speed. © 2018 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Managing Religion and Morality Within the Abortion Experience: Qualitative Interviews With Women Obtaining Abortions in the U.S.
Authors: Frohwirth Lori , Coleman Michele , Moore Ann M.
Published: November 2018

Most women in the United States are religious, and most major religions in the United States doctrinally disapprove of abortion. A substantial proportion of U.S. women have abortions. Although relationships among religious beliefs, abortion attitudes, behaviors, and stigma have been found in previous research, the relationship between stigma and religion is understudied. In‐depth interviews conducted with 78 women having abortions at nine sites in the United States found religion to permeate abortion stigma manifestations and management strategies identified in previous research, for religious and religiously affiliated respondents as well as those who did not claim a religious affiliation. Health‐care providers, religious leaders, researchers, and advocates need to recognize the influence religion has on the experience of obtaining an abortion for all women in the United States.
Sozial interagierende Roboter in der Pflege
Authors: Janowski Kathrin , Ritschel Hannes , Lugrin Birgit , André Elisabeth
Published: November 2018

In naher Zukunft werden Roboter immer häufiger in den Lebensbereichen von Alltagsnutzerinnen und -nutzern anzutreffen sein. Sehr deutlich wird dies am Beispiel von Haushalts- und Pflegerobotern, denen im Hinblick auf eine alternde Gesellschaft verstärkt die Rolle des Mitbewohners und Weggefährten zukommen wird. Damit einher geht der Wunsch, die Mensch-Roboter-Kommunikation menschzentrierter zu gestalten. Es geht nicht mehr lediglich um die effiziente Durchführung von Aufgaben, sondern auch darum, für den Menschen ein angenehmes Interaktionserlebnis zu schaffen und ein Vertrauensverhältnis zu dem Roboter herzustellen. Der nachfolgende Artikel diskutiert den aktuellen Stand in Forschung und Entwicklung im Bereich sozial interagierender Roboter, die über multimodale soziale Hinweisreize mit pflegebedürftigen Menschen kommunizieren.
Pflegeroboter aus Sicht der Geriatrie
Authors: Gisinger Christoph
Published: November 2018

Im Rahmen von zwei großen EU-Forschungsprojekten (HOBBIT und STRANDS) wurden Feldstudien über den Langzeiteinsatz von Robotersystemen in der geriatrischen Pflege- und Rehabilitationseinrichtung Haus der Barmherzigkeit und in Privatwohnungen von alleine lebenden Menschen im Alter über 75 Jahre durchgeführt. Die geriatrischen Patienten reagierten im Allgemeinen offen und aufgeschlossen, wesentlich zurückhaltender waren – vor allem anfangs – die Mitarbeiterinnen und Mitarbeiter. Die technischen Projektpartner bewerteten den Langzeiteinsatz unter Alltagsbedingungen äußerst positiv, weil die Assistenzrobotersysteme außerhalb des Labors unter Real-Life-Bedingungen überhaupt langfristig und weitgehend autonom funktionsfähig waren. Die Nutzer (Pflegepatienten, deren Angehörige und Mitarbeiter) reagierten eher enttäuscht, weil die eingesetzten Prototypen nicht ausreichend robust, rasch und verlässlich funktionierten und dadurch zu wenig Unterstützung im Alltag und praktischer Nutzen erlebbar war. Im weiteren Projektverlauf konnten Ängste der Mitarbeiter entkräftet werden, dass Pflegepersonen durch Roboter in absehbarer Zeit ersetzt werden könnten. Für Teilaufgaben oder unterstützend bzw. im Tandem wird jedoch ein großes Potenzial für intelligente technische Lösungen begrüßt. Seitens der Nutzer bzw. Pflegepatienten zeigte sich keine grundsätzliche Ablehnung von robust und sicher funktionierenden Robotern und sogar eine Präferenz für technische Hilfe statt Personenhilfe, wenn es um den Intimbereich (z. B. Körperpflege, Ausscheidung) geht und dadurch Autonomie und Selbstständigkeit erhalten werden können. Hier gibt es allerdings technische, wirtschaftliche, Sicherheits- und ethische Probleme, die noch gelöst werden müssen. „Pflegeroboter“ werden kommen, auch wenn noch ein langer Weg vor uns liegt und die genaue Funktionalität noch einer Klärung bedarf.
Webs of W-algebras
Authors: Procházka Tomáš , Rapčák Miroslav
Published: November 2018

Abstract

We associate vertex operator algebras to (p, q)-webs of interfaces in the topologically twisted

$$ \mathcal{N}=4 $$

N
=
4

super Yang-Mills theory. Y-algebras associated to trivalent junctions are identified with truncations of

$$ \mathcal{W} $$

W

1+∞ algebra. Starting with Y-algebras as atomic elements, we describe gluing of Y-algebras analogous to that of the topological vertex. At the level of characters, the construction matches the one of counting D0-D2-D4 bound states in toric Calabi-Yau threefolds. For some configurations of interfaces, we propose a BRST construction of the algebras and check in examples that both constructions agree. We define generalizations of

$$ \mathcal{W} $$

W

1+∞ algebra and identify a large class of glued algebras with their truncations. The gluing construction sheds new light on the structure of vertex operator algebras conventionally constructed by BRST reductions or coset constructions and provides us with a way to construct new algebras. Many well-known vertex operator algebras, such as U(N)
k
affine Lie algebra,

$$ \mathcal{N}=2 $$

N
=
2

superconformal algebra,

$$ \mathcal{N}=2 $$

N
=
2

super-

$$ {\mathcal{W}}_{\infty } $$

W
∞

, Bershadsky-Polyakov

$$ {\mathcal{W}}_3^{(2)} $$

W
3

2

, cosets and Drinfeld-Sokolov reductions of unitary groups can be obtained as special cases of this construction.
Planar two-loop five-parton amplitudes from numerical unitarity
Authors: Abreu S. , Febres Cordero F. , Ita H. , Page B. , Sotnikov V.
Published: November 2018

Abstract

We compute a complete set of independent leading-color two-loop five-parton amplitudes in QCD. These constitute a fundamental ingredient for the next-to-next-to-leading order QCD corrections to three-jet production at hadron colliders. We show how to consistently consider helicity amplitudes with external fermions in dimensional regularization, allowing the application of a numerical variant of the unitarity method. Amplitudes are computed by exploiting a decomposition of the integrand into master and surface terms that is independent of the parton type. Master integral coefficients are numerically computed in either finite-field or floating-point arithmetic and combined with known analytic master integrals. We recompute leading-color two-loop four-parton amplitudes as a check of our implementation. Results are presented for all independent four- and five-parton processes including contributions with massless closed fermion loops.
2336 Novel PGF2a synthesis pathway in epithelial ovarian cancer
Authors: Hu Muhan , Tiwary Ekta , Arend Rebecca , Miller Michael
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: To understand the role of PGF2a and to characterize a novel cyclooxyrgenase (COX)-independent prostaglandin synthesis pathway in epithelial ovarian cancer. METHODS/STUDY POPULATION: We used high grade epithelial ovarian cancer cell line (OVCAR3) as a model to study our pathway. Our main mode of PGF2a detection is through mass spectrometry. RESULTS/ANTICIPATED RESULTS: Our current results suggest the OVCAR3 cells may synthesize PGF2a independently of COX enzymes. We anticipate this novel pathway may be dependent on the TGFb pathway. DISCUSSION/SIGNIFICANCE OF IMPACT: Understanding the role and synthesis pathway of PGF2a may allow us to uncover a novel therapeutic pathway for high grade ovarian cancer.
2126 Optimizing a technique for visualizing retinal and choroidal blood flow noninvasively
Authors: Vora Paras , Bell Nicholas , Albuquerque Romulo , Cho Jooyoung , Botzet Gregory
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Diabetic retinopathy is an increasingly prevalent disease, difficult to screen for across the globe. We have developed and began optimizing an innovative technique to visualize and quantify retinal blood flow, to elucidate the role of the choroid in retinal pathologies such as diabetic retinopathy or choroidopathy. METHODS/STUDY POPULATION: Preliminary retinal was obtained from a surgical retina video library (Truvision, Goleta, CA, USA). Videos of different organs were recorded while vessels were occluded via a blood pressure cuff, using consumer-grade digital video cameras (NEX-5T, a7sii; Sony, New York, NY, USA). All other retinal videos were taken using a fundus camera (50×; Topcon, Oxland, NJ, USA) modified to support the above digital video cameras. All videos were processed using experimental software (MATLAB, Mathworks, Natick, MA, USA). RESULTS/ANTICIPATED RESULTS: Video imaging of the retina was optimized for lighting conditions and software requirements. Parameters were defined for the software imaging pipeline, such as frequency range of interest, sampling rate, and noise minimization. Software was developed to stabilize frames, accounting for eye saccades. Use of a biosensor enabled accurate measurement of pulse waveform, increasing signal-to-noise ratio. The optimal light requirements were determined such that adequate exposure of the retina is reproducible yet still comfortable for use in human subjects. DISCUSSION/SIGNIFICANCE OF IMPACT: This novel technique allows for an inexpensive, noninvasive, and reproducible ocular blood flow imaging platform. By optimizing this technique, we can proceed with our future plans for a pilot study to compare our imaging technique with the current standard, paving the way for future clinical studies.
2566 Personalized models of distal airway epithelial-stromal unit in COPD
Authors: Mahjour Seyed B. , Gomi Kazunori , Lee Busub , Elemento Olivier , Randell Scott , Shaykhiev Renat
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The objective of this study is to develop patient-derived “personalized” organotypic models of human distal airways, in which basal stem cells (BCs) isolated from the pre-/terminal conducting airway region are co-cultured with autologous stromal cells from the same region to reproduce patient-specific distal airway epithelial-stromal units and their remodeling in COPD. METHODS/STUDY POPULATION: We established a protocol to isolate and propagate epithelial BCs, fibroblasts, and endothelial cells from the distal airways of normal and COPD lung donors. Heterogeneous cellular and molecular phenotypes in the human distal airways were characterized using immunofluorescence and single-cell RNA sequencing. Patient-specific distal airway epithelial-stromal units were reconstructed by co-culturing BCs and autologous stromal cells using an air-liquid interface-based airway wall model and a bronchosphere-based 3D distal airway organoid assay. RESULTS/ANTICIPATED RESULTS: Histologic analysis of derived epithelial-stromal units revealed heterogeneous patient-specific phenotypes characterized by hypo-/hyper-/metaplastic lesions (hypo-regenerative phenotype, mucous cell hyperplasia, squamous metaplasia, distal-to-proximal repatterning) in the epithelial compartment, accompanied, in some samples, by stromal remodeling. Candidate epithelial-stromal cross-talk mechanisms were identified using quantitative real-time RT-PCR analysis of autologous epithelial and stromal compartments of established patient-specific distal airway unit models. DISCUSSION/SIGNIFICANCE OF IMPACT: Epithelial and stromal cells isolated from distal airways of subjects with and without COPD can be assembled into functional, organ-level tissue which mimics the architecture of human distal airways and, in patients with COPD, reproduces several distal airway remodeling phenotypes. Patient-specific models of distal airway epithelial-stromal cross-talk established in this study can be used to identify candidate pathways that mediate disease-relevant airway remodeling and potentially utilized as pre-clinical platforms for developing personalized therapeutic approaches to suppress the progression of distal airway remodeling in chronic lung diseases, including COPD.
2375 Pharmacokinetics of phosphatidylethanol 16:0/20:4 homolog in human blood after consumption of 0.4 and 0.8 g/kg alcohol in a laboratory clinical study
Authors: Lopez-Cruzan Marisa , Hill-Kapturczak Nathalie S. , Sanchez Jesus J. , Roache John D. , Wright Tara , Dougherty Donald , Javors Martin
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The purpose of this study was to characterize the pharmacokinetics of phosphatidylethanol (PEth) 16:0/20:4 homolog in uncoagulated, human blood samples taken from 18 participants in a clinical laboratory setting after consumption of 2 doses of ethanol. METHODS/STUDY POPULATION: Male and female participants received either 0.4 or 0.8 g/kg oral doses of ethanol during a 15-minute period. Blood samples were collected before and throughout 6 hours immediately after alcohol administration, then after 2, 4, 7, 11, and 14 days of administration day. PEth 16:0/20:4 levels were quantified by liquid mass spectrometry. Breath ethanol concentrations were measure concurrently with each blood collection during the administration day, as well as transdermal ethanol concentrations monitored constantly before, during and after ethanol administration day. RESULTS/ANTICIPATED RESULTS: (1) Single doses of 0.4 and 0.8 g ethanol/kg produced proportional increases in BrAC and PEth 16:0/20:4 levels; (2) the increase of Peth 16:0/20:4 from base line to Cmax was less than either PEth 16:0/18:1 or PEth 16:0/18:2 during the 6-hour period after ethanol administration; (3) the mean rate of formation of PEth 16:0/20:4 was lower than those of the other 2 homologs; (4) the mean half-life of PEth 16:0/20:4 was 2.18 days, which was shorter than that of either PEth 16:0/18:1 and PEth 16:0/18:2, which were 6.80 and 6.62, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: The results of this study further confirm that PEth homologs are a sensitive biomarker for ethanol consumption. The measurement of three PEth homologs appears to provide additional information about the level and time frame of drinking.
2342 Protein production as an early pharmacodynamics biomarker for RNA-targeting therapies
Authors: Self Wade K. , Schoch Kathleen , Bollinger James , Cole Tracy , Kordasiewicz Holly , Bateman Randall , Miller Timothy
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: We aimed to develop an assay to measure new protein synthesis after Antisense Oligonucleotide treatment, which we hypothesized to be the earliest biochemical identification of RNA-targeting therapy efficacy. METHODS/STUDY POPULATION: We treated 2 transgenic animal models expressing proteins implicated in neurodegenerative disease: human tau protein (hTau) and human superoxide dismutase 1 (hSOD1), with ASO against these mRNA transcripts. Animals received isotope-labeled 13C6-Leucine via drinking water to label newly synthesized proteins. We assayed target protein synthesis and concentration after ASO treatment to determine the earliest identification of ASO target engagement. RESULTS/ANTICIPATED RESULTS: hTau ASO treatment in transgenic mice lowered hTau protein concentration 23 days post-treatment in cortex (95% CI: 0.05%–64.0% reduction). In the same tissue, we observed lowering of hTau protein synthesis as early as 13 days (95% CI: 29.4%–123%). In hSOD1 transgenic rats, we observed lowering of 13C6-leucine-labeled hSOD1 in the cerebrospinal fluid 30 days after ASO treatment compared with inactive ASO control (95% CI: 12.0%–48.4%). DISCUSSION/SIGNIFICANCE OF IMPACT: In progressive neurodegenerative diseases, it is crucial to develop measurements that identify treatment efficacy early to improve patient outcomes. These data support the use of stable isotope labeling of amino acids to measure new protein synthesis as an early pharmacodynamics measurement for therapies that target RNA and inhibit the translation of proteins.
2121 Quantitative structural knee measurements improve classification of accelerated knee osteoarthritis: Data from the osteoarthritis initiative
Authors: Price Lori L. , McAlindon Timothy E. , Amin Mamta , Eaton Charles B. , Davis Julie E. , Lu Bing , Lo Grace H. , DeBakey Michael E. , Duryea Jeffrey , Barbe Mary F. , Driban Jeffrey B.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The aim of this study is to determine whether quantitative measures of knee structures including effusion, bone marrow lesions, cartilage, and meniscal damage can improve upon an existing model of demographic and clinical characteristics to classify accelerated knee osteoarthritis (AKOA). METHODS/STUDY POPULATION: We conducted a case-control study using data from baseline and four annual follow-up visits from the osteoarthritis initiative. Participants had no radiographic knee osteoarthritis (KOA) at baseline. AKOA is defined as progressing from no KOA to advance-stage KOA in at least 1 knee within 48 months. AKOA knees were matched 1:1 based on sex to (1) participants who did not develop KOA within 48 months and (2) participants who developed KOA but not AKOA. Analyses were person based. Classification and regression tree analysis was used to determine the important variables and percent of variance explained. RESULTS/ANTICIPATED RESULTS: A previous classification and regression tree analysis found that age, BMI, serum glucose, and femorotibial angle explained 31% of the variability between those who did and did not develop AKOA. Including structural measurements as candidate variables yielded a model that included effusion, BMI, serum glucose, cruciate ligament degeneration and coronal slope and explained 39% of the variability. DISCUSSION/SIGNIFICANCE OF IMPACT: Knee structural measurements improve classification of participants who developed AKOA Versus those who did not. Further research is needed to better classify patients at risk for AKOA.
2267 Radiofrequency renal denervation attenuates kidney fibrosis in spontaneously hypertensive rats
Authors: Gao Juan , Denys Ian B. , Del Valle Luis , Naljayan Mihran V. , Kapusta Daniel R.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The goal of this study was to investigate whether RF-RDN attenuates renal fibrosis and inflammation in SHR with established hypertension. METHODS/STUDY POPULATION: Twenty-two-week-old SHR received bilateral RF-RDN or Sham-RDN (Biosense Webster Stockert 70 generator and RF-probe). Four weeks later, SHR were sacrificed and paraffin sections of kidneys were stained for fibrosis by Masson’s trichrome staining. Kidney tissue were homogenized for measurement of cytokines levels by ELISA. RESULTS/ANTICIPATED RESULTS: The results showed that Sham-RDN treated SHR had extensive fibrosis as demonstrated by moderate thickening of Bowman’s capsule, collagen deposition in glomerulus, extensive tubulointerstitial fibrosis, and segmental glomerulosclerosis. In contrast, RF-RDN significantly reduced each of these pathological components of fibrosis in kidney cortex and medulla as compared with Sham-RDN treated kidneys. In other studies, RF-RDN decreased B cells, CD4+ T cells, and CD8+ T cells in the kidney of SHR as measured by flow cytometry. Meanwhile, kidney tissue levels of IL-17, INF-γ, MIP-3a, TNF-α, and TGF-β were decreased as compared with respective levels in Sham-RDN. DISCUSSION/SIGNIFICANCE OF IMPACT: Together, these findings demonstrate that removal of the influence of heightened renal sympathetic activity by RF-RDN decreases kidney inflammatory markers and attenuates renal fibrosis in hypertensive SHR.
2559 Role of tissue non-specific alkaline phosphatase (TNAP) in promoting the survival of acute myeloid leukemia (AML) cells within the bone marrow microenvironment
Authors: Bowles Bradley , Sterner Rosalie M. , Kremer Kimberly N. , Dudakovic Amel , Westendorf Jennifer J. , Van Wijnen Andre J. , Hedin Karen E.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Treatment of acute myeloid leukemia (AML) is challenging, as apoptosis-resistant AML cells often persist within the bone marrow microenvironment despite chemotherapy. The overall goal of our laboratory is to identify and ultimately target the bone marrow factors that protect AML cells. METHODS/STUDY POPULATION: Using cell cultures, we previously reported that SDF-1 (CXCL12), an abundant bone marrow chemokine, induces apoptosis of isolated CXCR4+ AML cells, including freshly isolated bone marrow-derived AML cells from approximately one-third of AML patients. However, co-culture of AML cells with differentiating osteoblasts protected AML cells from apoptosis. RESULTS/ANTICIPATED RESULTS: Histone deacetylase inhibitors (HDACi) abrogated the ability of osteoblasts to protect AML cells and altered expression of matrix mineralization genes including tissue nonspecific alkaline phosphatase (TNAP). A different drug, cyclosporine A (CSA), similarly inhibited osteoblast-mediated protection of AML cells and reduced TNAP expression. Specifically targeting osteoblast TNAP via siRNA was sufficient to prevent osteoblasts from protecting AML cells in co-cultures. In addition, we are targeting TNAP enzymatically. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that targeting TNAP may be useful in AML treatment to render the bone marrow microenvironment more hostile to leukemic cell survival.
2029 Surface display of chimeric proteins for exosome imaging and capturing in mammalians
Authors: Do Mai A. , Levy Daniel H. , Lim Stacie , Duong Natalie , Curley Kevin , Ling Grace , Lu Biao
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Exosomes are living nanoscale vesicles that can shuttle large amounts of bioactive cargo for intercellular communication. The potential of these nanovesicles to serve as both biomarkers for disease diagnosis and vehicles for delivery of therapeutics has only begun to be explored. To realize these potentials, molecular tools for effective exosome tracking and capturing must be invented in order to advance basic research and clinical translation. METHODS/STUDY POPULATION: We utilize a surface display strategy that enables exosome modification in living mammalian systems. By reconfiguring the surface protein CD63 or viral envelope glycoprotein VSV-G, we generate 3 topologically distinctive protein chimeras for exosome imaging and capture in mammalian systems. RESULTS/ANTICIPATED RESULTS: We have shown that these genetically encoded protein chimeras have the ability to correctly target and integrate into exosomes in cultured human cells. Furthermore, we have demonstrated that the secreted exosomes could be successfully captured by an affinity peptide intentionally displayed on the outer surface of exosomes. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study highlights the potential of these fusion proteins for exosome tracking and provides novel genetic tools for exosome research and translation, one of which is loading protein therapeutics for targeted delivery.
2041 The cell-cell adhesion component PLEKHA7 regulates the pro-tumorigenic MIR17HG long non-coding RNA in colon epithelial cells
Authors: Bridges Mary C. , Nair-Menon Joyce , Kourtidis Antonis
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The goal of this study is to test the hypothesis that the adherens junctions of colon epithelial cells regulate lncRNAs levels and function via the microprocessor and RISC complexes to suppress expression of pro-tumorigenic markers and aberrant cell behavior. METHODS/STUDY POPULATION: To test this hypothesis, we used colon epithelial cancer cell lines. We performed RNA-seq following knockdown of PLEKHA7, a key component of the adherens junctions, to identify changes in lncRNA expression and downstream mRNA levels. We confirmed junctional localization of affected lncRNAs from the RNA-seq and those that we found in our preliminary study by using in situ hybridization (ISH). RESULTS/ANTICIPATED RESULTS: RNA-seq identified junction-associated lncRNAs whose expression levels are regulated by PLEKHA7. The top upregulated lncRNA upon PLEKHA7 depletion was MIR17HG, an oncogenic host transcript of a cluster of miRNAs. These mature miRNAs also co-precipitate with PLEKHA7. PLEKHA7 knockdown results in increased levels of MIR17HG, but only a subset of its hosted miRNAs (miR-19a,b). Notably, miR-19a and mir-19b are highly upregulated in colon cancer. Our data suggest that 2 PLEKHA7-associated miRNAs, miR-203a and miR-372, mediate suppression MIR17HG. Re-expression of PLEKHA7 in aggressive colon cancer cells that lack PLEKHA7 suppressed expression of MIR17HG, as well as anchorage independent growth of these cells. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data point towards a novel mechanism of lncRNA regulation that tethers epithelial tissue integrity with pro-tumorigenic cell transformation. Reducing elevated MIR17HG levels, is a potential therapeutic approach to suppress the tumorigenic behavior of cells that have lost their junctional integrity and homeostasis. identify a network of miRNA-mRNA-lncRNA interactions that could be exploited for further mechanistic studies, as well as for diagnostic and therapeutic purposes in the future.
2483 The Empower Lab: An innovative model for research experience and training for undergraduate, graduate, and medical students
Authors: Ades Veronica , Chessky Anna , Vasquez Ydelsie , Rabinowitz Emily
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The Empower Lab was established in 2015 with the goal of providing students with hands-on research experience in sexual and gender-based violence and health. METHODS/STUDY POPULATION: The Empower Lab consists of 10–12 undergraduate, graduate, and medical students at a time. Students undergo a rigorous application process, and agree to volunteer 8 hours per week for at least 1 year. Students are assigned to teams, and learn research skills such as literature searches, systematic reviews, research question generation, study design, IRB procedures, database creation and management, data collection and analysis, oral and poster presentation, manuscript preparation, team collaboration and communication, advocacy, and leadership. Students start as research assistants, and can be promoted to team leader, and associate director of research. Students mentor and teach each other, and are supervised by the principal investigator (PI). A survey skill self-assessment is administered to lab members on entry to the lab, every 4–6 months, and upon exit. RESULTS/ANTICIPATED RESULTS: In total, 20 students have participated in the lab to date, and 12 are currently enrolled. Eighty percent of the lab members are women. The students are 45% undergraduates, 15% graduate (nursing, social work, public health), 20% medical students, and 10% not currently enrolled in school (gap year). Twenty students completed entry surveys, 11 students have completed interim surveys, and 5 students have completed exit surveys. Examination of current surveys indicates that students are gaining skills throughout the lab experience. Free-text feedback provided further insight. Currently, the lab has 5 IRB-approved studies actively recruiting participants, 4 manuscripts being written, and 3 studies in the development phase. Students have presented at three local and 2 national meetings to date. Changes have been made to the lab structure over time in order to provide clear expectations and feedback, and strengthen student performance. DISCUSSION/SIGNIFICANCE OF IMPACT: The Empower Lab is an innovative public health lab that provides opportunities for real-world research experience for students. The teamwork, collaboration, and structure of the lab permit mentoring, support, and teaching from peers, as well as from the PI. The Lab increases the PI’s productivity. Students are encouraged to develop and implement their own research ideas, further encouraging independence and initiative. Although the number of surveys is limited to date, they indicate improvement in skills and confidence among lab members. The predominance of women in the lab suggests that this is a strong model for recruitment and retention of women in STEM.
2323 Large patient volume is associated with adverse patient outcomes among those requiring maintenance renal replacement therapy
Authors: Reule Scott , Foley Robert , Ishani Areef , Rosenberg Mark
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: We set out to describe important associations and outcomes among those requiring maintenance renal replacement therapy with the patient volume per provider. METHODS/STUDY POPULATION: Through the combination of several large administrative datasets, including the United States Renal Data System (n=237,485), the American Medical Association Master file (n=6249), and Medicare data limited to 2012, we compared characteristics of patients, by quintile of patient/provider volume. χ2 and logistic regression, adjusted for various patient and provider factors for categorical and continuous variables, was used for baseline comparisons, respectively. Cox regression, adjusted for patient, provider, and socioeconomic variables, was used to calculate risks for important clinical outcomes such as kidney transplant listing, transplant receipt, and all-cause mortality. RESULTS/ANTICIPATED RESULTS: There is a threshold patient volume at which important clinical outcomes, including kidney transplantation and all-cause mortality, may be influenced. Higher patient volume is associated with adverse patient outcome. Those receiving care from providers with the highest patient volumes are less likely to receive kidney transplantation, live in a more rural area, and be non-White. DISCUSSION/SIGNIFICANCE OF IMPACT: There is a need to identify novel and potentially modifiable factors associated with patient outcome among those with end-stage kidney disease on maintenance renal replacement therapy. Provider level variables, such as patient volume, is one such variable. As nephrologists are often tasked with the care of variable numbers of patients on dialysis, a better understanding of this association is an unmet need.
2481 A collaborative neurology-emergency medicine rapid outpatient clinic for the management of TIA and minor stroke in the emergency department
Authors: Chang Bernard P. , Mehendale Rachel , Miller Eliza , Kummer Benjamin , Willey Joshua , Elkind Mitchell
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Current practice frequently dictates hospitalization for TIA and minor stroke (TIAMS) in order to obtain comprehensive evaluation of stroke risk factors and mechanism. Inpatient hospitalization is often done to expedite workup and to coordinate care although may be associated with nosocomial risks and increased healthcare cost. However, a subset of these patients who do not have debilitating deficits may not require inpatient hospitalization. We conducted a pilot study to assess the feasibility of conducting rapid outpatient stroke evaluations in low risk patients with TIAMS without disabling deficits. METHODS/STUDY POPULATION: The rapid access clinic was initiated at a single-site urban tertiary care facility for outpatient evaluation of TIAMS within 24 hours of emergency department (ED) evaluation. Patients were selected using a decision tool identifying presumed low-risk TIAMS seen in the ED. Criteria included medical (e.g., no disabling deficit, no thrombolytic agent given, negative CT for hemorrhagic stroke) as well as social criteria (e.g., patient ability to follow-up as an outpatient). We evaluated rates of noncompliance with post-ED follow-up, need for hospitalization from clinic, and 90 day stroke and health outcome data. RESULTS/ANTICIPATED RESULTS: Between December 2016 and December 2017 a total of 93 TIAMS patients seen in the ED were recommended for the rapid access clinic utilizing the decision tool. Of these patients, 94.5% (86) were evaluated within 24 hours of ED discharge. Only 2 patients (2.4%) who received outpatient evaluation required hospitalization; 61 (71.8%) patients had TIAMS on final evaluation in clinic. DISCUSSION/SIGNIFICANCE OF IMPACT: Our pilot data suggests that for a subset of patients, rapid outpatient evaluation may be a feasible and safe strategy for TIAMS management. Future work exploring such strategies may help improve TIAMS outcomes and reduce ED crowding and unnecessary hospital admissions.