Miracle-dz/UniFAR-FTUs huggingface dataset:
QuASAR-MPRA: Accurate allele-specific analysis for massively parallel reporter assays

Motivation The majority of the human genome is composed of non-coding regions containing regulatory elements such as enhancers, which are crucial for controlling gene expression. Many variants associated with complex traits are in these regions, and may disrupt gene regulatory sequences. Consequently, it is important to not only identify true enhancers but also to test if a variant within an enhancer affects gene regulation. Recently, allele-specific analysis in high-throughput reporter assays, such as massively parallel reporter assays (MPRA), have been used to functionally validate non-coding variants. However, we are still missing high-quality and robust data analysis tools for these datasets. Results We have further developed our method for allele-specific analysis QuASAR (quantitative allele-specific analysis of reads) to analyze allele-specific signals in barcoded read counts data from MPRA. Using this approach, we can take into account the uncertainty on the original plasmid proportions, over-dispersion, and sequencing errors. The provided allelic skew estimate and its standard error also simplifies meta-analysis of replicate experiments. Additionally, we show that a beta-binomial distribution better models the variability present in the allelic imbalance of these synthetic reporters and results in a test that is statistically well calibrated under the null. Applying this approach to the MPRA data by Tewhey et al. (2016), we found 602 SNPs with significant (FDR 10%) allele-specific regulatory function in LCLs. We also show that we can combine MPRA with QuASAR estimates to validate existing experimental and computational annotations of regulatory variants. Our study shows that with appropriate data analysis tools, we can improve the power to detect allelic effects in high throughput reporter assays. Availability http://github.com/piquelab/QuASAR/tree/master/mpra Contact fluca@wayne.edu; rpique@wayne.edu
Anti-natural octyl disaccharide-leprosy IDRI diagnostic (NDO-LID) antibodies as indicators of leprosy reactions and neuritis

Background Leprosy is a complex infectious and neurological disease caused by Mycobacterium leprae. Nerve damage is related to immunological hypersensitivity responses known as leprosy reactions (LRs). Diagnostic tools to predict LRs are not available. We hypothesized that natural octyl disaccharide-leprosy IDRI diagnostic (NDO-LID) would be helpful as an indicator of LRs and neuritis. Methods To assess the utility of NDO-LID in indicating reactions, ELISA were used to detect specific antibodies in serum samples from 80 Colombian leprosy patients (40 with and 40 without history of LRs). Responses were detected using a range of detection reagents detecting IgG, IgM or both isotypes. Results Patients with a history of LRs had an increased seropositivity rate for anti-NDO-LID antibodies compared to patients without (anti-NDO-LID protein A [p=0.02], IgG anti-NDO-LID [p=0.01] and IgM anti-NDO-LID [p=0.01]). Further analyses of patients with a history of LRs indicated that both seropositivity rate and magnitude of responses were elevated among patients with neuritis versus those without neuritis (anti-NDO-LID protein A [p=0.03], IgG anti-NDO-LID [p=0.001] and IgM anti-NDO-LID [p=0.06]). Conclusions Our data indicate that testing for serum anti-NDO-LID antibodies can be a useful screen to identify patients at risk of developing LRs and neuritis.
TGF-β1 Suppresses the Type I IFN Response and Induces Mitochondrial Dysfunction in Alveolar Macrophages

TGF-β1 is a pleiotropic cytokine with an established role in fibrosis; however, the immunosuppressive effects of TGF-β1 are less characterized. Elevated levels of TGF-β1 are found in patients with acute and chronic lung diseases, and the underlying disease processes are exacerbated by respiratory viral infections. The alveolar macrophage is the first line of cellular defense against respiratory viral infections, and its response to infections is dependent on environmental cues. Using the mouse alveolar macrophage line, MH-S, and human CD14+ monocyte-derived macrophages, we examined the effects of TGF-β1 on the type I IFN antiviral response, macrophage polarization, and mitochondrial bioenergetics following a challenge with human respiratory syncytial virus (RSV). Our results showed that TGF-β1 treatment of macrophages decreased the antiviral and proinflammatory response, and suppressed basal, maximal, spare mitochondrial respiration, and mitochondrial ATP production. Challenge with RSV following TGF-β1 treatment further exacerbated mitochondrial dysfunction. The TGF-β1 and TGF-β1+RSV–treated macrophages had a higher frequency of apoptosis and diminished phagocytic capacity, potentially through mitochondrial stress. Disruption of TGF-β1 signaling or rescue of mitochondrial respiration may be novel therapeutically targetable pathways to improve macrophage function and prevent secondary bacterial infections that complicate viral respiratory infections.
Flow in Information Systems Research: Review, Integrative Theoretical Framework, and Future Directions

As information systems (IS) are increasingly able to create highly engaging and interactive experiences, the phenomenon of flow is considered a promising vehicle to understand pre-adoptive and post-adoptive IS user behavior. However, despite a strong interest of researchers and practitioners in flow, the reliability, validity, hypothesized relationships, and measurement of flow constructs in current IS literature remain challenging. By reviewing extant literature in top IS outlets, this paper develops an integrative theoretical framework of flow antecedents, flow constructs, and flow consequences within IS research. In doing so, we identify and discuss four major flow streams in IS research and indicate future research directions.
Numerical And Experimental Studies Of Three-Dimensional Crack Evolution In Aluminum Alloys: Macroscale To Microscale

EDUCATION M.S./Ph.D. Civil Engineering, Cornell University 2014 Structural Engineering Option Minor: Theoretical and Applied Mechanics Dissertation: Numerical and Experimental Studies of Three-Dimensional Crack Evolution in Aluminum Alloys: Macroscale to Microscale Advisor: Anthony Ingraffea B.S. Architectural Engineering, summa cum laude, University of Wyoming 2007 Structural Design Option Minor: Honors Program
The Response to 2-Aminoacrylate Differs in Escherichia coli and Salmonella enterica, despite Shared Metabolic Components

ABSTRACT The metabolic network of an organism includes the sum total of the biochemical reactions present. In microbes, this network has an impeccable ability to sense and respond to perturbations caused by internal or external stimuli. The metabolic potential (i.e., network structure) of an organism is often drawn from the genome sequence, based on the presence of enzymes deemed to indicate specific pathways. Escherichia coli and Salmonella enterica are members of the Enterobacteriaceae family of Gram-negative bacteria that share the majority of their metabolic components and regulatory machinery as the “core genome. ” In S. enterica, the ability of the enamine intermediate 2-aminoacrylate (2AA) to inactivate a number of pyridoxal 5′-phosphate (PLP)-dependent enzymes has been established in vivo. In this study, 2AA metabolism and the consequences of its accumulation were investigated in E. coli. The data showed that despite the conservation of all relevant enzymes, S. enterica and E. coli differed in both the generation and detrimental consequences of 2AA. In total, these findings suggest that the structure of the metabolic network surrounding the generation and response to endogenous 2AA stress differs between S. enterica and E. coli. IMPORTANCE This work compared the metabolic networks surrounding the endogenous stressor 2-aminoacrylate in two closely related members of the Enterobacteriaceae. The data showed that despite the conservation of all relevant enzymes in this metabolic node, the two closely related organisms diverged in their metabolic network structures. This work highlights how a set of conserved components can generate distinct network architectures and how this can impact the physiology of an organism. This work defines a model to expand our understanding of the 2-aminoacrylate stress response and the differences in metabolic structures and cellular milieus between S. enterica and E. coli.
Sodium pump organization in dendritic spines

Abstract. Advancement in fluorescence imaging with the invention of several super-resolution microscopy modalities (e.g., PALM/STORM and STED) has opened up the possibility of deciphering molecular distributions on the nanoscale. In our quest to better elucidate postsynaptic protein distribution in dendritic spines, we have applied these nanoscopy methods, where generated results could help improve our understanding of neuronal functions. In particular, we have investigated the principal energy transformer in the brain, i.e., the Na+,K+-ATPase (or sodium pump), an essential protein responsible for maintaining resting membrane potential and a major controller of intracellular ion homeostasis. In these investigations, we have focused on estimates of protein amount, giving assessments of how variations may depend on labeling strategies, sample analysis, and choice of nanoscopic imaging method, concluding that all can be critical factors for quantification. We present a comparison of these results and discuss the influences this may have for homeostatic sodium regulation in neurons and energy consumption.
Separability and aggregate shocks in the life-cycle model of consumption: evidence from Spain

The purpose of this paper is to test the life-cycle permanent income hypothesis using an unbalanced panel from the Spanish family expenditure survey. Our model accounts for aggregate shocks and non-separability in the Euler equation among consumption goods, contrary to most of the Literature in this area. Our results do not indicate excess sensitivity of consumption growth to income.
National Diabetes Month — November 2014

Rui Li, PhD1, Sundar S. Shrestha, PhD1, Ruth Lipman, PhD2, Nilka R. Burrows, MPH1, Leslie E. Kolb, MBA2, Stephanie Rutledge, PhD1 (Author affiliations at end of text) Diabetes is a complex chronic disease that requires active involvement of patients in its management (1). Diabetes selfmanagement education and training (DSMT), “the ongoing process of facilitating the knowledge, skill, and ability necessary for prediabetes and diabetes self-care,” is an important component of integrated diabetes care (2). It is an intervention in which patients learn about diabetes and how to implement the self-management that is imperative to control the disease.
Effectiveness of Optional Videoconferencing-Based Treatment of Alcohol Use Disorders: Randomized Controlled Trial

Background Treatment of alcohol use disorders (AUDs) is characterized by an adherence rate below 50%. Clinical research has found that patient adherence enhances treatment effect; hence, health authorities, clinicians, and researchers strive to explore initiatives contributing to patients receiving treatment. Concurrently, videoconferencing-based treatment is gaining ground within other addiction and psychiatric areas. Objective The aim of this study was to test whether optional videoconferencing increases adherence to and effectiveness of AUD treatment in a randomized controlled trial (RCT). We hypothesized that the intervention would decrease premature dropout (the primary outcome), as well as increase successful treatment termination, treatment duration, and treatment outcome (secondary outcomes). Methods We conducted this study in the public outpatient alcohol clinic in Odense, Denmark, between September 2012 and April 2013. It was an RCT with 2 groups: treatment as usual (TAU) and treatment as usual with add-on intervention (TAU+I). The TAU+I group had the option, from session to session, to choose to receive treatment as usual via videoconferencing. Data consisted of self-reported responses to the European version of the Addiction Severity Index (EuropASI). We collected data at baseline, at follow-up at 3, 6, and 12 months, and at discharge. Results Among consecutive patients attending the clinic, 128 met the inclusion criteria, and 71 of them were included at baseline. For the primary outcome, after 180 days, 2 of 32 patients (6%) in the TAU+I group and 12 of 39 patients (31%) in the TAU group had dropped out prematurely. The difference is significant (P=.008). After 365 days, 8 patients (25%) in the TAU+I group and 17 patients (44%) in the TAU group had dropped out prematurely. The difference is significant (P=.02). For the secondary outcomes, significantly more patients in the TAU+I group were still attending treatment after 1 year (P=.03). We found no significant differences between the 2 groups with regard to successful treatment termination and treatment outcome. Conclusions The results indicate that offering patients optional videoconferencing may prevent premature dropouts from treatment and prolong treatment courses. However, the small sample size precludes conclusions regarding the effect of the intervention, which was not detectable in the patients’ use of alcohol and severity of problems. Trial Registration The Regional Health Research Ethics Committee System in Denmark: S-20110052; https://komite.regionsyddanmark. dk/wm258128 (Archived by WebCite at http://www.webcitation.org/6tTL3CO6u)
A 0.8‐V supply bulk‐driven operational transconductance amplifier and Gm‐C filter in 0.18 µm CMOS process

A low voltage bulk‐driven operational transconductance amplifier (OTA) and its application to implement a tunable Gm‐C filter are presented. The linearity of the proposed OTA is achieved by nonlinear terms cancelation technique, using two paralleled differential topologies with opposite signs in the third‐order harmonic distortion term of the differential output current. The proposed OTA uses 0.8 V supply voltage and consumes 31.2 μW. The proposed OTA shows a total harmonic distortion of better than −40 dB over the tuning range of the transconductance, by applying 800 mVppd sine wave input signal with 1 MHz frequency. The OTA has been used to implement a third‐order low‐pass Gm‐C filter, which can be used for wireless sensor network applications. The filter can operate as the channel select filter and variable gain amplifier, simultaneously. The gain of the filter can be tuned from −1 to 23 dB, which results in power consumptions of 187.2 to 450.6 μW, respectively. The proposed OTA and filter have been simulated in a 0.18 µm CMOS technology. Simulations of process corners and temperature variations are also included in the paper. Copyright © 2014 John Wiley & Sons, Ltd.
iTRAQ-Based Proteomic Analysis of Neonatal Kidney from Offspring of Protein Restricted Rats Reveals Abnormalities in Intraflagellar Transport Proteins

Background: It is well recognized that adverse events in utero can impair fetal development and lead to the development of kidney injury and hypertension in adulthood. We previously reported a lower kidney index, glomeruli number, and decreased glomerular filtration rate in intrauterine growth restriction (IUGR) offspring induced by maternal protein malnutrition. To explore the molecular mechanisms linking impaired fetal growth to renal diseases, we investigated differentially expressed proteins (DEPs) in the IUGR neonatal kidneys by isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Methods: We induced IUGR through maternal protein malnutrition. Neonatal kidneys were collected; the protein was extracted; pooled before iTRAQ labeling, and subjected to mass spectrometric analysis. Mass spectrometry results were then further confirmed by assessing five representative proteins in individual specimens with quantitative PCR (qPCR), immunohistochemical (IHC) and / or western blot analysis. Results: A total of 367DEPs (263 up-regulated, 104 down-regulated.) with a threshold of a 1.2-fold change and a P value ≤ 0.05 between IUGR kidneys and control kidneys were identified. Further bioinformatics analysis revealed that these proteins play important roles in oxidative phosphorylation, purine metabolism, pyrimidine metabolism, RNA small body, spliceosome assembly and intraflagellar transport (IFT). IFT family proteins (IFT80, 88,144) and PKD2 were shown to be up-regulated in IUGR kidneys, confirmed by western blotting, IHC and Q-PCR. Epigenetic modulating factors SET and MYND domain containing 3 (SMYD3), a histone-lysine N-methyltransferase, and H3K4me3 level were also remarkably enhanced in IUGR neonatal kidneys. Conclusions: This first comprehensive analysis of the neonatal kidney proteome reveals new insights in nephridial development, and may make a valuable contribution towards the identification of the pathological mechanisms involved in the developmental origins of adult disease.
Global patterns of phytoplankton nutrient and light colimitation inferred from an optimality‐based model

The widely used concept of constant ”Redfield” phytoplankton stoichiometry is often applied for estimating which nutrient limits phytoplankton growth in the surface ocean. Culture experiments, in contrast, show strong relations between growth conditions and cellular stoichiometry with often substantial deviations from Redfield stoichiometry. Here we investigate to what extent both views agree by analyzing remote sensing and in situ data with an optimality‐based model of nondiazotrophic phytoplankton growth in order to infer seasonally varying patterns of colimitation by light, nitrogen (N), and phosphorus (P) in the global ocean. Our combined model‐data analysis suggests strong N and N‐P colimitation in the tropical ocean, seasonal light, and N‐P colimitation in the Northern Hemisphere, and strong light limitation only during winter in the Southern Ocean. The eastern equatorial Pacific appears as the only ocean area that is essentially not limited by N, P, or light. Even though our optimality‐based approach specifically accounts for flexible stoichiometry, inferred patterns of N and P limitation are to some extent consistent with those obtained from an analysis of surface inorganic nutrients with respect to the Redfield N:P ratio. Iron is not part of our analysis, implying that we cannot accurately predict N cell quotas in high‐nutrient, low‐chlorophyll regions. Elsewhere, we do not expect a major effect of iron on the relative distribution of N, P, and light colimitation areas. The relative importance of N, P, and light in limiting phytoplankton growth diagnosed here by combining observations and an optimal growth model provides a useful constraint for models used to predict future marine biological production under changing environmental conditions. © 2014. American Geophysical Union. All Rights Reserved.
The effect of glazing and aging on the surface properties of CAD/CAM resin blocks

PURPOSE To investigate the effect of accelerated aging on surface properties of glazed CAD/CAM resin blocks using a 2D surface profilometer and a 3D non-contact optical profilometer. MATERIALS AND METHODS Three types of CAD/CAM resin restorative materials, LAVA Ultimate (3M ESPE, St Paul, MN, USA), VITA Enamic (Vita Zahnfabrik H. Rauter, Bad Säckingen, Germany), and Cerasmart (GC Corparation, Tokyo, Japan) were used for this study. CAD/CAM blocks were cut in 3-mm thickness slabs and divided into three groups; Group 1: control group (specimens polished with 600 grit SCI paper); Group 2: specimens sandblasted, silanized, and glazed with Optiglaze Color (GC); Group 3: glazed specimens subjected to 5000 thermocycles (n=15). The surface roughness (Ra and Rz) was evaluated using a profilometer and a 3D scanning instrument. Data were analyzed using two-way ANOVA and Tukey's post-hoc test (P<.05). RESULTS LAVA, VITA, and Cerasmart exhibited statistically similar Ra and Rz values for each group (P>.05). For VITA and Cerasmart, the specimens in Group 1 exhibited significantly higher Ra values than Group 2 (P<.05). Group 1 (0.502 Ra), Group 2 (0.384 Ra), and Group 3 (0.431 Ra) exhibited statistically similar Ra values for LAVA (P=.062). After 5000 thermocycles, surface roughness values did not change significantly for glazed LAVA, VITA, and Cerasmart (P>.05). CONCLUSION Glaze material Optiglaze Color makes CAD/CAM resin surfaces smooth and glazed CAD/CAM surfaces seem resistant to deterioration under 5000 thermocycles.
A Study of the Effects of Laser Shock Peening on Residual Stress, Microstructure and Local Properties of IN718 Ni-Base Superalloy

In this project effects of Laser shock peening (LSP) on two aero engine alloys, IN718 and IN718 SPF were studied. The primary goal of the program was to secure required fundamental knowledge of e impact of LSP process parameters on these two aero engine alloys and thereby advance the science and application base of this process to other materials and parts. The research program designed accordingly includes the following key elements: 1) Developing LSP process parameters for typical Ni base aero engine alloys; (2) characterization of surface and sub-surface macro and micro residual strains/stresses a function of LSP process parameters (3) characterization of microstructural changes as a function of LSP process parameters and; (4) Study Thermal relaxation of residual stresses and understand the underlying kinetics. Firstly, different LSP process parameters including: Power density, impact overlaps, ablative overlays and coverage were studied to impart deep compressive residual stresses to the near surface regions of peened coupons. A host of different techniques were then used to characterize distribution of residual stresses/strains, roughness, hardness, plastic strains and microstructure. Role of ablative layer was also investigated. Samples were peened using an ablative layer different ablative layers (black vinyl tape, aluminum tape) and without an ablative layer and compared in terms of topography, residual stress fields and microstructure. Two different diffraction based techniques were used to characterize residual stress fields: conventional X-ray diffraction and Synchrotron X-ray diffraction (SXRD). Conventional X-ray coupled with electro polishing offers a fast means of analyzing residual stresses, while SXRD enables high resolution, non-destructive characterization of strains/stresses. Experiments showed that higher power density lead to compressive residual stresses which were higher in magnitude in near surface regions. There is a saturation power density, after which any increase in power density did not result in further increase in magnitude and depth residual stresses. Plastic deformation introduced by LSP was characterized using a variety of tools including hardness measurements (micro hardness with a knoop’s indenter and nano indentation), analyzing full width half maximum of diffraction peaks, micro pillar compression tests and electron back scattered diffraction. Results indicated that LSP does not introduce high plastic strain in the material. This was evident in moderate increase in hardness (~20%), a small increase in FWHM of diffraction peaks and a small increase in low angle misorientations (obtained using EBSD). Using all these techniques it was determined that the plastic deformation introduced by peening extended 300- 500µm from the peened surface. Microstructure of as-received and peened samples was studied using optical microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Electron back scattered Diffraction (EBSD). Peened…