bluuebunny/crossref_metadata_2025 huggingface dataset:
Clock bias prediction algorithm for navigation satellites based on a supervised learning long short-term memory neural network
Authors: Huang Bohua , Ji Zengxi , Zhai Renjian , Xiao Changfu , Yang Fan , Yang Bohang , Wang Yupu
Published: March 2021

In a satellite navigation system, high-precision prediction of satellite clock bias directly determines the accuracy of navigation, positioning, and time synchronization and is the key to realizing autonomous navigation. To further improve satellite clock bias prediction accuracy, we establish a satellite clock bias prediction model by using long short-term memory (LSTM) that can accurately express the nonlinear characteristics of the navigation satellite clock bias. Outliers in the original clock bias should be preprocessed before using the clock bias for prediction. By analyzing the working principle of the traditional median absolute deviations method, the ambiguity of the mathematical model of that method was improved. Experimental results show that the improved method is better than the traditional method at detecting gross errors. The single difference sequence of the preprocessed satellite clock bias was taken as the research object. First, a quadratic polynomial model was fit to the trend term of the single difference sequence. Second, based on the LSTM neural network model and the basic principles of supervised learning, a supervised learning LSTM network model (SL-LSTM) was proposed that models cyclic and random terms. Finally, the prediction function of the satellite clock bias was realized by extrapolating the model by adding a trend term. We adopt the GPS precision satellite clock bias of International GNSS Service data forecast experiments and apply wavelet neural network (WNN), autoregressive integrated moving average (ARIMA), and quadratic polynomial (QP) models to compare their prediction effects. The average prediction RMSE for 3 h, 6 h, 12 h, 1 d, and 3 d based on the SL-LSTM improved by approximately −21.80, −1.85, 8.57, 2.27, and 40.79%, respectively, compared with the results of the WNN. The average prediction RMSE based on the SL-LSTM improved by approximately 38.23, 65.48, 80.22, 85.18, and 94.51% compared with the ARIMA results. The average prediction RMSE based on the SL-LSTM improved by approximately 82.37, 75.88, 67.24, 45.71, and 58.22% compared with the QP results. Compared with the WNN, the SL-LSTM method has no obvious advantages in the prediction accuracy and stability in short-term prediction but achieves a better long-term prediction accuracy and stability. With an increased prediction duration, the SL-LSTM method is clearly better than the other three methods in terms of the prediction accuracy and stability. The results indicated that the quality of satellite clock bias prediction by the SL-LSTM method is better than that of the above three methods and is more suitable for the middle- and long-term prediction of satellite clock bias.
The role of P53 up-regulated modulator of apoptosis (PUMA) in ovarian development, cardiovascular and neurodegenerative diseases
Authors: Li Mei
Published: March 2021

P53 up-regulated modulator of apoptosis (PUMA), a pro-apoptotic BCL-2 homology 3 (BH3)-only member of the BCL-2 family, is a direct transcriptional target of P53 that elicits mitochondrial apoptosis under treatment with radiation and chemotherapy. It also induces excessive apoptosis in cardiovascular and/or neurodegenerative diseases. PUMA has been found to play a critical role in ovarian apoptosis. In the present paper, we review the progress of the study in PUMA over the past two decades in terms of its inducement and/or amplification of programmed cell death and describe recent updates to the understanding of both P53-dependent and P53-independent PUMA-mediated apoptotic pathways that are implicated in physiology and pathology, including the development of the ovary and cardiovascular and neurodegenerative diseases. We propose that PUMA may be a key regulator during ovary development, provide a model for PUMA-mediated apoptotic pathways, including intrinsic and extrinsic apoptotic pathways.
Dynamic Movement Primitives: Volumetric Obstacle Avoidance Using Dynamic Potential Functions
Authors: Ginesi Michele , Meli Daniele , Roberti Andrea , Sansonetto Nicola , Fiorini Paolo
Published: March 2021

Obstacle avoidance for Dynamic Movement Primitives (DMPs) is still a challenging problem. In our previous work, we proposed a framework for obstacle avoidance based on superquadric potential functions to represent volumes. In this work, we extend our previous work to include the velocity of the system in the definition of the potential. Our formulations guarantee smoother behavior with respect to state-of-the-art point-like methods. Moreover, our new formulation allows obtaining a smoother behavior in proximity of the obstacle than when using a static (i.e. velocity independent) potential. We validate our framework for obstacle avoidance in a simulated multi-robot scenario and with different real robots: a pick-and-place task for an industrial manipulator and a surgical robot to show scalability; and navigation with a mobile robot in a dynamic environment.
Natural radioactivity and radiological risks of common building materials used in Semnan Province dwellings, Iran
Authors: Imani Morteza , Adelikhah Mohammademad , Shahrokhi Amin , Azimpour Ghazaleh , Yadollahi Ali , Kocsis Erika , Toth-Bodrogi Edit , Kovács Tibor
Published: March 2021

Impact assessment of building materials is a focused topic in the field of radioecology. A radiological survey has conducted to monitor radioactivity of most common building materials in Semnan Province, Iran, and assess the radiation risk. Activity concentrations of 226Ra, 232Th, and 40K were measured in 29 samples including nine commonly used building materials that were collected from local suppliers and manufacturers, using a high purity germanium gamma-ray detector. The activity concentrations of 226Ra, 232Th, and 40K varied from 6.7±1 to 43.6±9, 5.9±1 to 60±11, and 28.5±3 to 1085±113 Bq kg−1 with averages of 26.8±5, 22.7±4, and 322.4±4 Bq kg−1, respectively. By applying multivariate statistical approach (Pearson correlation, cluster, and principal component analyses (PCA)), the radiological health hazard parameters were analyzed to obtain similarities and correlations between the various samples. The Pearson correlation showed that the 226Ra distribution in the samples is controlled by changing the 232Th concentration. The variance of 95.58% obtained from PCA resulted that the main radiological health hazard parameters exist due to the concentration of 226Ra and 232Th. The resulting dendrogram of cluster analysis also shows a well coincidence with the correlation analysis.
Optimization of the CCT Curves for Steels Containing Al, Cu and B
Authors: Miettinen Jyrki , Koskenniska Sami , Somani Mahesh , Louhenkilpi Seppo , Pohjonen Aarne , Larkiola Jari , Kömi Jukka
Published: March 2021

New continuous cooling transformation (CCT) equations have been optimized to calculate the start temperatures and critical cooling rates of phase formations during austenite decomposition in low-alloyed steels. Experimental CCT data from the literature were used for applying the recently developed method of calculating the grain boundary soluble compositions of the steels for optimization. These compositions, which are influenced by solute microsegregation and precipitation depending on the heating/cooling/holding process, are expected to control the start of the austenite decomposition, if initiated at the grain boundaries. The current optimization was carried out rigorously for an extended set of steels than used previously, besides including three new solute elements, Al, Cu and B, in the CCT-equations. The validity of the equations was, therefore, boosted not only due to the inclusion of new elements, but also due to the addition of more low-alloyed steels in the optimization. The final optimization was made with a mini-tab tool, which discarded statistically insignificant parameters from the equations and made them prudently safer to use. Using a thermodynamic-kinetic software, IDS, the new equations were further validated using new experimental CCT data measured in this study. The agreement is good both for the phase transformation start temperatures as well as the final phase fractions. In addition, IDS simulations were carried out to construct the CCT diagrams and the final phase fraction diagrams for 17 steels and two cast irons, in order to outline the influence of solute elements on the calculations and their relationship with literature recommendations.
Fire Behavior of 3D-Printed Polymeric Composites
Authors: Babu Karthik , Das Oisik , Shanmugam Vigneshwaran , Mensah Rhoda Afriye , Försth Michael , Sas Gabriel , Restás Ágoston , Berto Filippo
Published: March 2021

3D printing or additive manufacturing (AM) is considered as a flexible manufacturing method with the potential for substantial innovations in fabricating geometrically complicated structured polymers, metals, and ceramics parts. Among them, polymeric composites show versatility for applications in various fields, such as constructions, microelectronics and biomedical. However, the poor resistance of these materials against fire must be considered due to their direct relation to human life conservation and safety. In this article, the recent advances in the fire behavior of 3D-printed polymeric composites are reviewed. The article describes the recently developed methods for improving the flame retardancy of 3D-printed polymeric composites. Consequently, the improvements in the fire behavior of 3D-printed polymeric materials through the change in formulation of the composites are discussed. The article is novel in the sense that it is one of the first studies to provide an overview regarding the flammability characteristics of 3D-printed polymeric materials, which will further incite research interests to render AM-based materials fire-resistant.
Virtuelle Planung der chirurgischen Korrektur einer Kraniosynostose
Authors: Raith S. , Lautner N. , Clusmann H. , Hölzle F. , Modabber A.
Published: March 2021

Kraniosynostosen sind schwerwiegende kongenitale Komplikationen, die das physiologische Schädelwachstum behindern. Um die dadurch entstehenden Fehlstellungen zu therapieren und eine normale Entwicklung der Schädelform zu ermöglichen, ist oftmals die chirurgische Korrektur unausweichlich. Da Formen und Ausprägungen bei diesem Krankheitsbild sehr stark variieren, ist eine patientenindividuelle Operationsplanung notwendig. Bei dem vorgestellten Fall handelt es sich um die Operationsplanung und -durchführung bei einem 6 Monate alten Mädchen, das mit einer Verknöcherung sowohl der mediofrontalen als auch beider koronalen Suturen geboren wurde, was zu einer Fehlbildung der Schädelform mit flacher, enger Stirn und stark ausgeprägtem Turmschädel führte. Basierend auf computertomographischen Daten wurde eine digitale Planung erstellt, bei der diverse Varianten virtueller Osteotomien vorab am Computer erprobt und beurteilt werden konnten. Dabei lassen sich die Abstände zwischen den Segmenten quantifizieren, um zu große Spaltmaße zu verhindern, die zu Komplikationen führen könnten. Des Weiteren kann mit einem eigens entwickelten Algorithmus die Vergrößerung des Schädelinnenvolumens als Zielgröße berechnet werden. Schließlich wurde eine 3‑D-gedruckte Osteotomieschablone aus Polyamid hergestellt, die intraoperativ eine passgenaue Überführung der geplanten Schnittführung ermöglichte. Die Segmente konnten nach Vorgabe platziert werden, sodass sich harmonische Proportionen ergaben. Das gemessene Schädelinnenvolumen wurde gemäß der digitalen Planung um 5,5 % erhöht. Die erfolgreiche Umsetzung der Methode zeigt, dass computergestützte Planung einen relevanten Mehrwert für die patientenindividuelle Behandlung von Kraniosynostosen haben kann.
Correction to: Comparison of biomass estimates from multiple stratification approaches in a swept area method for Pacific saury Cololabis saira in the western North Pacific
Authors: Hashimoto Midori , Kidokoro Hideaki , Suyama Satoshi , Fuji Taiki , Miyamoto Hiroomi , Naya Miyako , Vijai Dharmamony , Ueno Yasuhiro , Kitakado Toshihide
Published: March 2021

A correction to this paper has been published: https://doi.org/10.1007/s12562-021-01506-9
Unterschiede zwischen Schüler*innen im Sportunterricht in der Wahrnehmung von Lehrkräften
Authors: Wagner Ingo , Bartsch Fabienne , Rulofs Bettina
Published: March 2021

Ein Ziel des vom BMBF geförderten Projektes „Schulsport 2020“ (FKZ: 01JA1622) ist die Unterstützung von (zukünftigen) Sportlehrkräften beim Umgang mit der Heterogenität von Schüler*innen und der Förderung von Inklusion im Sportunterricht. Der Beitrag untersucht, welche Unterschiede Sportlehrkräfte zwischen Schüler*innen wahrnehmen und welche dieser Unterscheidungen sie als relevant für das Fach Sport erachten. Dazu wurden zunächst bestehende Erkenntnisse zu Heterogenität und Differenzen im Sportunterricht systematisiert und darauf aufbauend im Rahmen einer Fragebogenstudie mit 958 Sportlehrkräften verschiedener Schulformen aus Nordrhein-Westfalen Wahrnehmungen der Lehrkräfte von Unterschieden zwischen Schüler*innen erhoben und analysiert. Die Ergebnisse zeigen für 30 Items die jeweilige Relevanzattribuierung. Durch eine explorative Faktorenanalyse hat sich eine 6‑dimensionale Faktorstruktur herauskristallisiert. Diese Faktoren umfassen in abnehmender Relevanzzuschreibung durch die Sportlehrkräfte 1. Unterschiede in Bezug auf personale Merkmale (u. a. Motivation, Selbstvertrauen), 2. in Bezug auf Förderbedarfe, 3. körperbezogene Unterschiede (Geschlecht, Alter), 4. kognitiv-sprachliche (u. a. Intelligenz, Sprachverständnis), 5. organisational-strukturelle (u. a. Zugehörigkeit zu schulsportlichen Talentfördermaßnahmen) und 6. soziokulturell-ökonomische (u. a. Herkunftskultur, Besitz) Unterschiede, die von Sportlehrkräften bei Schüler*innen wahrgenommen werden. Insgesamt bieten die Ergebnisse eine Grundlage für einen systematischen Rahmen, der zur Sensibilisierung von (angehenden) Lehrkräften und zum reflektierten Umgang mit Unterschieden im Fach Sport beitragen kann.
Hamster numbers: biopolitics and animal agency in the Dutch fields, circa 1870-present
Authors: De Bont Raf
Published: March 2021

Numbers of European hamsters (Cricetus cricetus) in the Dutch Province of Limburg have been subject to much scrutiny and controversy. In the late nineteenth century, policymakers who considered them too numerous (and invasive) set up eradication programs. In the second half of the twentieth century, even when its domestic relative (Mesocricetus auratus) increasingly circulated as a pet in urban spaces, the numbers of European hamsters in the rural areas collapsed. Large-scale preservation campaigns and reintroduction programs ensued. According to some media, all this has turned the European hamster into the most expensive undomesticated animal of the Netherlands. A whole network of institutions became involved to save the species – ranging from local activist organizations, over zoos and universities, to federal ministries and international organizations. The interactions between the Dutch and ‘their’ hamsters, this article argues, were inscribed in various forms of biopolitics. The article highlights the changing discursive framings and spatial practices that have shaped the management ofCricetus cricetusover time and calls attention to the diversity of living and non-living agents that produced the multispecies choreographies of the present-day Limburg landscape. Finally, it alerts us to the (sometimes-paradoxical) kinds of agency that reside in the numbers of non-human animals.
High dimensional feature data reduction of multichannel sEMG for gesture recognition based on double phases PSO
Authors: Jie Jing , Liu Kairui , Zheng Hui , Wang Beibei , Dai Rui
Published: March 2021

Surface electromyography (sEMG) is a kind of valuable bioelectric signal and very potential in the field of human–machine interaction. Ideal interactions require sEMG based patterns recognition not only with high accuracy but also with good rapidity. However, too much real-time feature-related computation will greatly slow down the interaction, especially for multichannel sEMG. To decrease the feature-related time consumption, the paper formulates the feature reduction as an optimization problem, and develops a double-phases particle swarm optimization (PSO) with hybrid coding to solve the problem. In the research, the initial feature data set with 31 kinds of feature is built firstly based on eight subjects’ 16 channels forearm sEMG signals, then PSO is introduced to conduct the feature reduction of 31 × 16 dimensions through the feature and channel optimization in double phases. During the optimization, two improved k-nearest neighbor (KNN) methods such as weighted representation based KNN (WRKNN) and weighted local mean representation based KNN (WLMRKNN) are introduced to classify the gestures, and the classification accuracy is used to evaluate the particles of PSO. Experimental results and comparison analysis show that PSO based feature reduction methods outperform genetic algorithm (GA), ant colony optimization (ACO) and principal component analysis (PCA) based feature reduction methods. With the optimized feature data subset by PSO, WRKNN and WLMRKNN are superior to KNN, quadratic discriminant analysis (QDA), and naive bayes (NB) greatly. The proposed method can be applied in the pattern recognition of high dimensional sEMG with multichannel or high-density channels for the purpose of rapidity and without a decline of accuracy in real-time control. Further, it can be used to reduce the economic cost of the personalized customization equipment through the optimal channels for any subjects in the future.
Lower limb movement intention recognition for rehabilitation robot aided with projected recurrent neural network
Authors: Liu Mei , Peng Bo , Shang Mingsheng
Published: March 2021

For the lower limb rehabilitation robot, how to better realize intention recognition is the key issue in the practical application. Recognition of the patient’s movement intention is a challenging research work, which needs to be studied from the shallow to the deep. Specifically, it is necessary to ensure that the movement intention of the normal person can be accurately recognized, and then improve the model to realize the recognition of the movement intention of the patients. Therefore, before studying the patient’s movement intention, it is essential to consider the normal person first, which is also for safety considerations. In recent years, a new Hill-based muscle model has been demonstrated to be capable of directly estimating the joint angle intention in an open-loop form. On this basis, by introducing a recurrent neural network (RNN), the whole prediction process can achieve more accuracy in a closed-loop form. However, for the traditional RNN algorithms, the activation function must be convex, which brings some limitations to the solution of practical problems. Especially, when the convergence speed of the traditional RNN model is limited in the practical applications, as the error continues to decrease, the convergence performance of the traditional RNN model will be greatly affected. To this end, a projected recurrent neural network (PRNN) model is proposed, which relaxes the condition of the convex function and can be used in the saturation constraint case. In addition, the corresponding theoretical proof is given, and the PRNN method with saturation constraint has been successfully applied in the experiment of intention recognition of lower limb movement compared with the traditional RNN model.
Motives and Laterality: Exploring the Links
Authors: Schultheiss Oliver C. , Schwemmer Olivia S. , Khalaidovski Ksenia
Published: March 2021

Objectives

We explored associations between the needs for power, achievement, and affiliation and functional cerebral asymmetries (FCAs), guided by three established hypotheses about the nature of these associations.

Methods

One-hundred-and-seven participants completed picture-story measures of dispositional motives and activity inhibition (AI), a frequent moderator of motive-behavior associations, tasks measuring FCAs (line bisection, chimeric emotional face judgments, turning bias, perceptual and response asymmetries on the Poffenberger task), self-reported laterality preferences (handedness, footedness, ear and eye preference), and interhemispheric interaction (crossed-uncrossed difference). They also completed an experiment manipulating hand contractions (left, right, both, neither) while they worked on a second picture-story motive measure.

Results

Dispositional power motivation was associated with stronger rightward asymmetry and less interhemispheric transfer in high-AI and stronger leftward asymmetry and more interhemispheric transfer in low-AI individuals. For the affiliation motive, findings were fewer and in the opposite direction of those for the power motive. These findings emerged for men, but not for women. Left- or right-hand contractions led to increases in power and achievement motivation, but not affiliation motivation. Only left-hand contractions led to decreased AI.

Conclusions

We discuss these findings in the context of sex-dimorphic organizing and activating effects of steroids on motives and laterality.
From Micropores to Ultra-micropores inside Hard Carbon: Toward Enhanced Capacity in Room-/Low-Temperature Sodium-Ion Storage
Authors: Yang Jinlin , Wang Xiaowei , Dai Wenrui , Lian Xu , Cui Xinhang , Zhang Weichao , Zhang Kexin , Lin Ming , Zou Ruqiang , Loh Kian Ping , Yang Quan-Hong , Chen Wei
Published: March 2021

Highlights

Hard-carbon anode dominated with ultra-micropores (< 0.5 nm) was synthesized for sodium-ion batteries via a molten diffusion–carbonization method.

The ultra-micropores dominated carbon anode displays an enhanced capacity, which originates from the extra sodium-ion storage sites of the designed ultra-micropores.

The thick electrode (~ 19 mg cm−2) with a high areal capacity of 6.14 mAh cm−2 displays an ultrahigh cycling stability and an outstanding low-temperature performance.

Pore structure of hard carbon has a fundamental influence on the electrochemical properties in sodium-ion batteries (SIBs). Ultra-micropores (< 0.5 nm) of hard carbon can function as ionic sieves to reduce the diffusion of slovated Na+ but allow the entrance of naked Na+ into the pores, which can reduce the interficial contact between the electrolyte and the inner pores without sacrificing the fast diffusion kinetics. Herein, a molten diffusion–carbonization method is proposed to transform the micropores (> 1 nm) inside carbon into ultra-micropores (< 0.5 nm). Consequently, the designed carbon anode displays an enhanced capacity of 346 mAh g−1 at 30 mA g−1 with a high ICE value of ~ 80.6% and most of the capacity (~ 90%) is below 1 V. Moreover, the high-loading electrode (~ 19 mg cm−2) exhibits a good temperature endurance with a high areal capacity of 6.14 mAh cm−2 at 25 °C and 5.32 mAh cm−2 at − 20 °C. Based on the in situ X-ray diffraction and ex situ solid-state nuclear magnetic resonance results, the designed ultra-micropores provide the extra Na+ storage sites, which mainly contributes to the enhanced capacity. This proposed strategy shows a good potential for the development of high-performance SIBs.
Post-tensioning of glass beams: Analytical determination of the allowable pre-load
Authors: Cupać Jagoda , Louter Christian , Nussbaumer Alain
Published: March 2021

The effectiveness of post-tensioning in enhancing the fracture resistance of glass beams depends on the level of compressive pre-stress introduced at the glass edge surface that will in service be exposed to tensile stresses induced by bending. Maximum pre-load that can be applied in a post-tensioned glass beam system, yielding maximum compressive pre-stress, is limited by various failure mechanisms which might occur during post-tensioning. In this paper, failure mechanisms are identified for a post-tensioned glass beam system with a flat stainless steel tendon adhesively bonded at the bottom glass edge, including the rupture of the tendon, glass failure in tension and adhesive/glass failure in the load introduction zone. Special attention is given to the load introduction failure given that the transparent nature of glass limits the use of vertical confinement usually applied in concrete. An analytical model for determination of the allowable pre-load in post-tensioned glass beams is proposed, based on the model applied for externally post-tensioned concrete beams. The model is verified with the results of a numerical model, showing good correlation, and applied in a parametric study to determine the influence of various beam parameters on the effectiveness of post-tensioning glass beams.
Maintaining High Eudaimonic Wellbeing Despite Ambiguity Intolerance Among Three Employment Status Groups: Examining the Buffering Effects of Positive Psychological Attributes
Authors: Baluku Martin Mabunda , Bantu Edward , Namale Betty , Otto Kathleen
Published: March 2021

The unemployed, as well as individuals in self and salaried employment, face several work-related risks and uncertainties which can result in diminished psychological wellbeing especially for individuals with high ambiguity intolerance. However, positive psychology literature suggests that individuals with strong psychological resources can be resilient in difficult circumstances. Using a sample of 922 individuals (including 240 unemployed, 391 salary-employed, and 291 self-employed) from Uganda and Kenya, we investigated the moderating effects of locus of control and psychological capital on the association between ambiguity intolerance and eudaimonic wellbeing, comparing the unemployed with individuals in salaried and self-employment. Our findings indicated that ambiguity intolerance and external locus of control are negatively associated with eudaimonic wellbeing. Conversely, internal locus of control and psychological capital were positively associated with eudaimonic wellbeing. The moderation analysis revealed that whereas an external locus of control boosts the negative effects of ambiguity intolerance on eudaimonic wellbeing, internal locus of control and psychological capital buffer against the negative effects of ambiguity intolerance on eudaimonic wellbeing. Differences between employment status groups and implications are discussed.
21746 Antigen discovery in membranous glomerulopathy using laser capture microdissection and mass spectrometry
Authors: Fede Jacquelyn , Kogut Stephen , Heyward Anthony , Stevenson John F. , Nunn Amy , Plaut Julie , Kimberly Judy A.
Published: March 2021

ABSTRACT IMPACT: Identifying the causative antigen in membranous glomerulopathy cohorts enables the development of serum assays to detect and monitor disease progression without the need for invasive kidney biopsies. OBJECTIVES/GOALS: Primary membranous glomerulopathy is caused by the formation of autoantibody immune complexes which deposit in the glomerulus and obstruct kidney function. Causative antigens remain to be identified in roughly 20% of cases. Our goal is to identify the antigen in these cohorts, so that non-invasive assays can be developed for disease monitoring. METHODS/STUDY POPULATION: Renal biopsy tissue from known antigen cases (PLA2R, THSD7A), and unknown cases were included in the analysis. Renal biopsy tissue from formalin fixed paraffin embedded tissue was cut at a thickness of 10 µm onto Leica PET-membrane frame slides. These slides were then stained with hematoxylin. The glomeruli were microdissected into microcentrifuge tubes using a Leica DM6000B microscope. The microdissected glomeruli were lysed in 2% SDS and 0.1M DTT at 99 degrees Celsius for 1 hour and processed by filter assisted sample preparation (FASP). Digested peptides were analyzed by liquid chromatography-mass spectrometry using an Orbitrap Fusion Lumos using data-dependent acquisition. RESULTS/ANTICIPATED RESULTS: Mass spectrometry data collected from the laser captured glomeruli was searched against the human proteome fasta database from Uniprot using MaxQuant. IBAQ values were used for quantitation and statistical analysis. Null hypothesis significance testing was performed for each protein by comparing each sample group to the rest of the samples in the data set. In the control groups, the causative antigens PLA2R and THSD7A were detected and quantified with the largest magnitude fold change in their respective category, validating the experimental design. Using this approach, the proteins SAP, NELL1, and NCAM1 were identified and subsequently validated as causative antigens in distinct patient cohorts. DISCUSSION/SIGNIFICANCE OF FINDINGS: Here, we share the results of our efforts to comprehensively identify the spectrum of causative antigens in membranous glomerulopathy. In this context, antigen discovery is an essential first step for the development of non-invasive assays to inform prognosis, monitor response to treatment, and better understand disease etiology.
66108 Central Cholinergic Synapse Formation in Optimized Primary Septal “Hippocampal Co” cultures
Authors: Djemil Sarra , Ressel Claire R. , Schneeweisi Amanda K. , Abdel-Ghani S. , Pak Daniel T.S.
Published: March 2021

ABSTRACT IMPACT: Optimization of primary septal-hippocampal co-cultures facilitates studying central cholinergic synapse formation and dysfunction OBJECTIVES/GOALS: Septal cholinergic innervation to the hippocampus is critical for normal learning and memory and is severely degenerated in Alzheimer’s disease. To understand the molecular events underlying this loss, we optimized a primary septal-hippocampal co-culture system that facilitates the study of central cholinergic synapses. METHODS/STUDY POPULATION: We developed an optimized in vitro septal-hippocampal co-culture system modified from previously published protocols. Briefly, hippocampal and septal tissue were harvested from embryonic day 19 (E19) Sprague-Dawley rats, digested with 0.1% trypsin, and an equal number of cells from each region plated onto coverslips coated with poly-D-lysine and laminin at a final density of 300 cells/mm2. We use immunostaining with validated primary antibodies and a fluorescent binding assay, together with confocal microscopy, to determine the structure of cholinergic synapses that are 1) native, 2) mammalian, 3) CNS derived, 4) comprised of physiological synaptic partners, and 5) developmentally mature. RESULTS/ANTICIPATED RESULTS: After DIV21, co-cultures maintained a healthy morphology. A subpopulation of neurons strongly expressed the cholinergic markers vesicular ACh transporter (vAChT), choline acetyltransferase (ChAT), and the high-affinity choline transporter (ChT1), whereas most neurons lacked vAChT expression and were presumably glutamatergic or GABAergic. The percentage of cholinergic neurons attained in the co-culture is ˜5-7%. The size of these cholinergic neurons is strikingly similar to that reported for BFCNs in the intact brain (mean 30μm, range 18-43μm). All sampled cholinergic neurons (28/28 neurons) also expressed molecular machinery necessary for GABA release. Staining for a cholinergic postsynaptic marker shows that 63% of the contacts made with are synaptic. DISCUSSION/SIGNIFICANCE OF FINDINGS: Primary septal-hippocampal co-cultured neurons have not been exploited extensively in the field, perhaps due to the difficulty in maintaining such cultures for extended periods. Here, we optimized an in vitro septal-hippocampal co-culture system, a powerful tool to comprehensively analyze central cholinergic synapse formation and dysfunction.
82125 Multiple epidemics of multidrug-resistant tuberculosis revealed by spatial disease mapping and whole-genome sequencing analysis in urban China
Authors: Yang Chongguang , Zhang Yangyi , Jiang Yuan , Wu Zheyuan , Shen Xin , Warren Joshua L. , Cohen Ted
Published: March 2021

ABSTRACT IMPACT: Our study will integrate state-of-the-art methods in pathogen genomics, epidemiology, and geospatial analysis to identify both host- and pathogen-factors driving the MDR-TB transmission and the study outcome can inform the design of targeted interventions OBJECTIVES/GOALS: The emergence of multidrug-resistant tuberculosis (MDR-TB) poses serious challenges for the global eradication of tuberculosis. Recent research has shown that transmission is now the dominant driver of MDR-TB. However, our limited understanding of where and among whom MDR-TB is transmitted hampers efforts to control person-to-person spread. METHODS/STUDY POPULATION: We used several analytic approaches to characterize the dynamics of MDR-TB transmission in Shanghai, China. We identified all culture-confirmed MDR cases between 2009-2016 in the city and 1) estimated individual-level risk factors for MDR disease; 2) mapped the TB cases by their home addresses and used a Bayesian spatial disease mapping method to identify regions with an elevated risk of MDR-TB; and 3) we sequenced all MDR isolates to understand whether transmission explained variance in risk that was not attributable to the distribution of individual or location-specific risk variates. RESULTS/ANTICIPATED RESULTS: There were 1034 MDR-TB cases among 16,315 culture-confirmed TB cases during the study period. Bayesian disease mapping identified spatial heterogeneity of MDR-TB and determined four hotspots with an elevated risk of MDR-TB, none of which were fully explained by individual or regional-covariates (Figure 1). Sequencing revealed that more than 40% of the MDR-TB strains were in genomic clusters, indicating recent MDR-TB transmission. Most importantly, MDR-TB cases in three of the four large clades (>8 isolates) were spatially concentrated in three strain-specific hotspots (Figure 2). DISCUSSION/SIGNIFICANCE OF FINDINGS: With the combination of traditional epidemiological tools, geographical, and genomic methods, this study revealed multiple loci of transmission of specific MDR-TB clades within a single city. Identification of where and among whom MDR-TB is transmitted can inform the design of targeted interventions.
27558 Obeticholic acid (OCALIVA ®) protects against 2,8-dihydroxyadenine nephropathy in mice
Authors: Jones Bryce , Benitez Carlos , Cruz Idalia , Myakala Komuraiah , Wang Xiaoxin , Libby Andrew , Rowland Emma , Kurtz Ryan , Rosenberg Avi , Levi Moshe
Published: March 2021

ABSTRACT IMPACT: This work may lead to new treatments for crystalline nephropathies. OBJECTIVES/GOALS: This study investigated obeticholic acid (OCALIVA ®) as a potential treatment for 2,8-dihydroxyadenine (2,8-DHA) nephropathy using a mouse model. The treatment was investigated in both sexes at two timepoints. METHODS/STUDY POPULATION: Male and female C57BL/6J mice (12 weeks of age) were fed chow (Research Diets D19120401i) or chow admixed with adenine (0.2% w/w) ad lib for either 3.5 or 7 weeks. Mice were treated with either vehicle (corn oil) or obeticholic acid (10 mg/kg BW) by gavage 5 days per week. Each of the 16 combinations of sex/diet/timepoint/treatment groups had an n = 6 (96 mice in total). Food and body weights were measured twice per week, and 24-hour urines were collected prior to euthanasia. Serum and organs were collected and processed for biochemical and histopathological analyses. RESULTS/ANTICIPATED RESULTS: At both the 3.5-week and 7-week timepoints, dietary adenine robustly increased BUN and serum creatinine compared to control diet in vehicle-treated male and female mice (P < .01, all comparisons). At the 3.5-week timepoint, obeticholic acid reduced BUN in male (P < .05) but not female adenine mice. Obeticholic acid did not affect serum creatinine at this timepoint. At the 7-week timepoint, obeticholic acid reduced BUN in female (P < .05) but not male adenine mice. At the 7-week timepoint, obeticholic acid reduced serum creatinine in both male (P < .05) and female (P < .01) mice. Biochemical and histopathological analyses are ongoing, and we anticipate that the results will agree with the serum chemistries. DISCUSSION/SIGNIFICANCE OF FINDINGS: Obeticholic acid is FDA-approved for primary biliary cholangitis, and it is in clinical trials for several other hepatobiliary diseases. Although currently untested in humans, it is nephroprotective in many preclinical models of kidney disease. This study is the first to investigate obeticholic acid in a model of crystalline nephropathy.
32329 A novel mouse model of Ataxia Telangiectasia for testing small molecule readthrough compounds
Authors: Mathews Paul
Published: March 2021

ABSTRACT IMPACT: Small molecule readthrough compounds are a promising therapeutic with the potential to overcome nonsense mutations thereby enabling the production of functional ATM protein in patients with Ataxia Telangiectasia OBJECTIVES/GOALS: To generate a novel mouse model of Ataxia-Telangiectasia for testing small molecule readthrough compounds that both expresses a clinically relevant nonsense mutation and recapitulates the major symptoms of the disease, including a progressive loss of motor coordination not previously observed in prior A-T animal models. METHODS/STUDY POPULATION: Using a double-hit strategy to increase genotoxic stress, we generated a novel A-T mouse model that expresses a clinically relevant (c.103C>T) mutation in the Atm gene and a knockout of the functionally related Aptx gene. We then characterized the mouse across multiple domains related to the various symptoms related to the disease. This includes examination of survivability, immunologic function, cancer prevalence, and motor behavior and its associated cerebellar dysfunction and atrophy. Lastly, we tested the ability of small molecule readthrough compounds to enable production of ATM from tissue explants extracted from these ATM deficient mice. RESULTS/ANTICIPATED RESULTS: The double mutant mice display reduced survivability compared to control mice (53% vs. 97%; p<0.0001), dying at a clinically relevant rate of about 30% from thymomas. At postnatal day 400 (P400), only AtmR35X/R35X; Aptx-/- mice, and none of the controls expressing at least one wildtype Atm or Aptx gene develop a motor behavioral deficits that are associate with reduced Purkinje neuron diameter (8.0 ±0.4 µm vs. 9.92 ±0.5; p<0.01) and density (4.3 ±0.2 vs. 6.0 ±0.3 per 100 µm; p<0.05) as well as cerebellar atrophy (cerebellum/forebrain area 0.26 ±0.01 vs. 0.31 ±0.01; p<0.001). ATM deficient mice also display disrupted thymocyte development and metabolic function. When exposed to small molecular readthrough compounds, greater than 50% of the ATM protein is restored. DISCUSSION/SIGNIFICANCE OF FINDINGS: We have created a novel, clinically relevant A-T mouse model that develops a severe ataxia associated with changes in cerebellar function and atrophy as well as demonstrate the potential of SMRT compounds as an A-T therapeutic.
73565 Defining tp53 tumor suppressor functions in zebrafish embryonal rhabdomyosarcoma
Authors: Baxi Kunal , Chen Jiangfei , Lipsitt Amanda , Hensch Nicole , Wang Long , Bandopadhyay Abhik , Sugalski Aaron , Gilbert Andrea , Chen Eleanor , Houghton Peter , Tomlinson Gail , Ignatius Myron
Published: March 2021

ABSTRACT IMPACT: By assessing function of mutant (patient-specific) tp53 in zebrafish embryonal rhabdomyosarcoma will inform clinicians of the severity of mutant tp53 alleles. OBJECTIVES/GOALS: This study aims to define loss- and gain-of-function TP53 mutations by comparing effects in tp53-null and wild-type tumors. In addition, it aims to generate a rapid in vivo analysis platform to assign function to patient specific TP53 mutations in the clinic METHODS/STUDY POPULATION: To define tp53 function in ERMS pathogenesis, we previously generated a new tp53-null mutant (tp53-/-) in zebrafish by deleting the entire tp53 genomic locus using TALEN mutagenesis. tp53-/- zebrafish spontaneously develop a spectrum of tumors including sarcomas, leukemia and germ cell tumors (Ignatius…Baxi et. al., eLife) reminiscent of tumors observed in Trp53-null mice. Using the tp53-/- mutants to generate kRASG12D-induced ERMS, we discovered that tp53 is a potent repressor of metastases but rather surprisingly had no effect on self-renewal (Ignatius…Baxi et. al., eLife). Here, using tp53-/- zebrafish, we assessed effects of wild-type and mutant (patient specific) tp53 on tumor initiation, proliferation and apoptosis. RESULTS/ANTICIPATED RESULTS: ERMS tumor initiation in the tp53-/- background is observed in > 97% of animals whereas only <40% of wild-type animals develop ERMS. Additionally, tp53 is a potent suppressor of ERMS proliferation and its effect on apoptosis is minor. Next, we expressed either WT zebrafish or human TP53 in tp53-/- animals along with kRASG12D and both genes suppressed tumor initiation and growth. We co-expressed TP53C176F (found in two ERMS patients) and TP53P153del (identified in a patient with osteosarcoma in our clinic) in zebrafish ERMS, and find that the TP53C176F allele significantly suppressed tumor initiation with effects predominantly on enhanced apoptosis. However, the TP53P153del allele initiated tumors at similar frequency compared to tp53-/- animals but increased the initiation of tumors in the head musculature. DISCUSSION/SIGNIFICANCE OF FINDINGS: Different TP53 alleles identified in patient tumors have very different effects on tumorigenesis in vivo and can respond differently to potentially therapeutic compounds. Thus, the type of precision modeling demonstrated here promises to help further define patient-specific TP53 biology and improve clinical strategies in the future.
11791 Gray matter volume differences in bilingual compared to monolingual children
Authors: Schug Alison K. , Brignoni-Perez Edith , Jamal Nasheed , Eden Guinevere F.
Published: March 2021

ABSTRACT IMPACT: This study examines gray matter volume differences resulting from the bilingual experience in children and adults allowing us to better understand the brains of over half of the world’s population that speaks more than one language. OBJECTIVES/GOALS: Literature is mixed regarding a bilingual advantage in executive control (EC). While it has been shown that young adult bilinguals have greater gray matter volume (GMV) than monolinguals in EC regions, there is behavioral evidence that suggests such difference would be more pronounced in children. METHODS/STUDY POPULATION: Using SPM12 to test this hypothesis, we used a whole-brain t-test to compare GMV in 35 English-speaking monolingual and 20 Spanish-English early (learned both languages before 6 years old) bilingual children. Next, we submitted both groups of children to an ANOVA with 42 English speaking monolingual and 26 Spanish-English bilingual adults to test for an interaction of Language Experience by Age Group at the level of the whole brain. RESULTS/ANTICIPATED RESULTS: e between-group comparison of bilingual and monolingual children, revealed more GMV in bilingual compared to monolingual children in regions associated with EC (right middle and inferior frontal gyri, superior parietal lobule, and precuneus). Our second analysis, an ANOVA comparing bilingual and monolingual children and adults, revealed an interaction in which bilingual>monolingual GMV in children was greater than any bilingual>monolingual GMV (or bilingual=monolingual GMV) in the adult groups in the right superior parietal lobule (BA1). No regions indicated that bilingual>monolingual GMV was more pronounced in adults. DISCUSSION/SIGNIFICANCE OF FINDINGS: These results provide further evidence for GMV differences in early bilinguals in regions associated with EC and indicate that more GMV differences exist between bilingual and monolingual children than adults.
45852 Parenting stress predicts fast food intake in an urban community sample of overweight parents of toddlers
Authors: Bautista Tara , Fogelman Nia , Lartigue Schan , Silverman Wendy K. , Jastreboff Ania M. , Sinha Rajita
Published: March 2021

ABSTRACT IMPACT: The findings suggest that targeting parenting stress in combination with psychoeducation on nutrition and physical activity may have positive effects in improving healthy food choices such as reduction of fast food intake, which may in turn impact the health of toddlers and their families. OBJECTIVES/GOALS: Parent stress is associated with a myriad of unhealthy behaviors including overeating, decreased physical activity, which contribute to increased weight. Several programs have aimed to increase education of nutrition, but few have focused on parent stress to improve healthy food intake. The present study assessed parent stress and fast food intake. METHODS/STUDY POPULATION: Parents who have obesity and had a toddler in the age group of 2-5 years were enrolled for a preventive intervention study to assess the effect of a parent-based intervention to improve family health choices and reduce childhood obesity risk. The sample included 105 participants, mean age 34.80 (6.27) years old, mean body mass index (BMI) 35.51 kg/m2, 39.0% Non-Hispanic White, 20.0% Non-Hispanic Black, 22.9% multiracial, 12.4% Hispanic, and 5.7% other. Stress was assessed using the Perceived Stress Scale (PSS) to assess overall general stress and the Parenting Stress Index (PSI) to assess parent-specific stress. Chaos in the home and fast food intake were also assessed using self-report surveys. RESULTS/ANTICIPATED RESULTS: Preliminary results are based on available data as of October 2020, data collection and recruitment are still in progress. There was a significant correlation between fast food intake with PSS (r=.18, p=.04), chaos (r=.24, p=.02), and PSI (r=.25, p=.01). Using a hierarchical regression model, we entered home chaos in the first block which explained a significant amount of the variability (R2= .06, p=.04). PSS was entered in the second block, which was not significant (R2 change=.01, p=.50), and in the final block PSI was entered and was significant (R2 change=.13, p <.01). DISCUSSION/SIGNIFICANCE OF FINDINGS: The data indicate that parenting stress uniquely predicts fast food intake above and beyond what could be explained by home chaos and general perceived stress. Future analyses will assess a parent-based intervention targeting stress reduction to improve weight and health for the parent and their toddlers in order to reduce childhood obesity risk.