scholarly journals A combined transcriptional and dynamic roadmap of single human pancreatic endocrine progenitors reveals proliferative capacity and differentiation continuum

2021 ◽  
Author(s):  
Belin Selcen Beydag-Tasöz ◽  
Joyson Verner D'Costa ◽  
Lena Hersemann ◽  
Federica Luppino ◽  
Yung Hae Kim ◽  
...  

Basic helix-loop-helix genes, particularly proneural genes, are well-described triggers of cell differentiation, yet limited information exists on their dynamics, notably in human development. Here, we focus on Neurogenin 3 (NEUROG3), which is crucial for pancreatic endocrine lineage initiation. Using a double reporter to monitor endogenous NEUROG3 transcription and protein expression in single cells in 2D and 3D models of human pancreas development, we show peaks of expression for the RNA and protein at 22 and 11 hours respectively, approximately two-fold slower than in mice, and remarkable heterogeneity in peak expression levels all triggering differentiation. We also reveal that some human endocrine progenitors proliferate once, mainly at the onset of differentiation, rather than forming a subpopulation with sustained proliferation. Using reporter index-sorted single-cell RNA-seq data, we statistically map transcriptome to dynamic behaviors of cells in live imaging and uncover transcriptional states associated with variations in motility as NEUROG3 levels change, a method applicable to other contexts.

2015 ◽  
Vol 1 (6) ◽  
pp. 276
Author(s):  
Maria Rashid ◽  
Wardah Mehmood ◽  
Aliya Ashraf

Eye movement tracking is a method that is now-a-days used for checking the usability problems in the contexts of Human Computer Interaction (HCI). Firstly we present eye tracking technology and key elements.We tend to evaluate the behavior of the use when they are using the interace of eye gaze. Used different techniques i.e. electro-oculography, infrared oculography, video oculography, image process techniques, scrolling techniques, different models, probable approaches i.e. shape based approach, appearance based methods, 2D and 3D models based approach and different software algorithms for pupil detection etc. We have tried to compare the surveys based on their geometric properties and reportable accuracies and eventually we conclude this study by giving some prediction regarding future eye-gaze. We point out some techniques by using various eyes properties comprising nature, appearance and gesture or some combination for eye tracking and detection. Result displays eye-gaze technique is faster and better approach for selection than a mouse selection. Rate of error for all the matters determines that there have been no errors once choosing from main menus with eye mark and with mouse. But there have been a chance of errors when once choosing from sub menus in case of eye mark. So, maintain head constantly in front of eye gaze monitor.


Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4288
Author(s):  
Fernanda Malhão ◽  
Ana Catarina Macedo ◽  
Carla Costa ◽  
Eduardo Rocha ◽  
Alice Abreu Ramos

Fucoxanthin (Fx) is a carotenoid derived from marine organisms that exhibits anticancer activities. However, its role as a potential drug adjuvant in breast cancer (BC) treatment is still poorly explored. Firstly, this study investigated the cytotoxic effects of Fx alone and combined with doxorubicin (Dox) and cisplatin (Cis) on a panel of 2D-cultured BC cell lines (MCF7, SKBR3 and MDA-MB-231) and one non-tumoral cell line (MCF12A). Fucoxanthin induced cytotoxicity against all the cell lines and potentiated Dox cytotoxic effects towards the SKBR3 and MDA-MB-231 cells. The combination triggering the highest cytotoxicity (Fx 10 µM + Dox 1 µM in MDA-MB-231) additionally showed significant induction of cell death and genotoxic effects, relative to control. In sequence, the same combination was tested on 3D cultures using a multi-endpoint approach involving bioactivity assays and microscopy techniques. Similar to 2D cultures, the combination of Fx and Dox showed higher cytotoxic effects on 3D cultures compared to the isolated compounds. Furthermore, this combination increased the number of apoptotic cells, decreased cell proliferation, and caused structural and ultrastructural damages on the 3D models. Overall, our findings suggest Fx has potential to become an adjuvant for Dox chemotherapy regimens in BC treatment.


2021 ◽  
Vol 7 (8) ◽  
pp. eabe3610
Author(s):  
Conor J. Kearney ◽  
Stephin J. Vervoort ◽  
Kelly M. Ramsbottom ◽  
Izabela Todorovski ◽  
Emily J. Lelliott ◽  
...  

Multimodal single-cell RNA sequencing enables the precise mapping of transcriptional and phenotypic features of cellular differentiation states but does not allow for simultaneous integration of critical posttranslational modification data. Here, we describe SUrface-protein Glycan And RNA-seq (SUGAR-seq), a method that enables detection and analysis of N-linked glycosylation, extracellular epitopes, and the transcriptome at the single-cell level. Integrated SUGAR-seq and glycoproteome analysis identified tumor-infiltrating T cells with unique surface glycan properties that report their epigenetic and functional state.


2014 ◽  
Vol 532 ◽  
pp. 249-252
Author(s):  
Ying Hua Liao ◽  
Gao Jun Liu ◽  
Xiang Guo Sun

An intelligent CAD system for Involute cylindrical gear cutting tools is developed by VC++ and SQL server, and it includes four modules, such as user interface, instance query, intelligent gear tool design and database. The intelligent gear tool design is the key to the intelligent CAD system, and it is based on the forward reasoning production system, and as the Intelligent reasoning technology is used for gear tool design, a lots of expert knowledge could be made full use of. The design results by the developed intelligent CAD system are more reasonable than those by a traditional CAD system, and the efficiency and quality of the gear tool design also could be improved. The developed intelligent CAD system supports both 2D and 3D models, which can lay foundation for CAD/CAE/CAM integration of gear cutting tools.


Author(s):  
Wenbin Ye ◽  
Tao Liu ◽  
Hongjuan Fu ◽  
Congting Ye ◽  
Guoli Ji ◽  
...  

Abstract Motivation Alternative polyadenylation (APA) has been widely recognized as a widespread mechanism modulated dynamically. Studies based on 3′ end sequencing and/or RNA-seq have profiled poly(A) sites in various species with diverse pipelines, yet no unified and easy-to-use toolkit is available for comprehensive APA analyses. Results We developed an R package called movAPA for modeling and visualization of dynamics of alternative polyadenylation across biological samples. movAPA incorporates rich functions for preprocessing, annotation and statistical analyses of poly(A) sites, identification of poly(A) signals, profiling of APA dynamics and visualization. Particularly, seven metrics are provided for measuring the tissue-specificity or usages of APA sites across samples. Three methods are used for identifying 3′ UTR shortening/lengthening events between conditions. APA site switching involving non-3′ UTR polyadenylation can also be explored. Using poly(A) site data from rice and mouse sperm cells, we demonstrated the high scalability and flexibility of movAPA in profiling APA dynamics across tissues and single cells. Availability and implementation https://github.com/BMILAB/movAPA. Supplementary information Supplementary data are available at Bioinformatics online.


2021 ◽  
Vol 8 (1) ◽  
pp. 11
Author(s):  
Sorel E. De Leon ◽  
Lana Cleuren ◽  
Zay Yar Oo ◽  
Paul R. Stoddart ◽  
Sally L. McArthur

Three-dimensional (3D) cell cultures have recently emerged as tools for biologically modelling the human body. As 3D models make their way into laboratories there is a need to develop characterisation techniques that are sensitive enough to monitor the cells in real time and without the need for chemical labels. Impedance spectroscopy has been shown to address both of these challenges, but there has been little research into the full impedance spectrum and how the different components of the system affect the impedance signal. Here we investigate the impedance of human fibroblast cells in 2D and 3D collagen gel cultures across a broad range of frequencies (10 Hz to 5 MHz) using a commercial well with in-plane electrodes. At low frequencies in both 2D and 3D models it was observed that protein adsorption influences the magnitude of the impedance for the cell-free samples. This effect was eliminated once cells were introduced to the systems. Cell proliferation could be monitored in 2D at intermediate frequencies (30 kHz). However, the in-plane electrodes were unable to detect any changes in the impedance at any frequency when the cells were cultured in the 3D collagen gel. The results suggest that in designing impedance measurement devices, both the nature and distribution of the cells within the 3D culture as well as the architecture of the electrodes are key variables.


2021 ◽  
Author(s):  
Ruizi Zhang ◽  
Ian Frigaard

Abstract Many numerical studies have been conducted regarding laminar miscible displacement flow in narrow, vertical, eccentric annuli. For the next decade it is likely that primary cementing flows on the scale of the well will continue to be simulated predominantly with 2D gap-averaged (2DGA) models. However, 3D simulations are less common due to the computational cost. The comparison between 2D and 3D models needs further attention, to understand the main discrepancies and thus help to understand primary cementing flows better. In this paper, comparisons of 3D against 2DGA model results show a range of interesting different phenomena, e.g. static layers, dispersive spikes, and instabilities. The predictions of the 2DGA model are the same as the 3D results to a degree. In particular, they are consistent with each other regarding the evolving process, interface shape, etc. However, the main difference with the 2DGA concentration arises from dispersion on the scale of the annular gap. From the recent research of Renteria and Frigaard (J. Fluid Mech., vol. 905, 2020) [1], a variety of dispersive effects are the main discrepancy between experiments and 2DGA results as well. We give representative examples of these flows in surface casing geometries and suggest methods for improvement of the 2DGA model.


2022 ◽  
Vol 14 (4) ◽  
pp. 139-148
Author(s):  
Aleksandr Poluektov ◽  
Konstantin Zolnikov ◽  
V. Antsiferova

The mathematical model and algorithms of oscillatory movements are considered. Various factors affecting the oscillatory process are considered. Oscillatory movements are constructed in the MVSTUDIUM modeling environment. The schemes of three computer models demonstrating oscillatory processes are determined: a model of a pendulum with a non-movable suspension point, a model of a pushing pendulum with friction force and a model of a breaking pendulum. Classes are being built to execute models with embedded properties, as well as with the ability to export the created classes to other models, and embed classes created by the program developer into the model. Creation of 2D and 3D models of oscillatory processes, an experiment behavior map and a virtual stand.


2018 ◽  
Vol 203 ◽  
pp. 04011
Author(s):  
Ong Yin Hoe ◽  
Hisham Mohamad

There is a trend in Malaysia and Singapore, engineers tend to model the effect of TBM tunneling or deep excavation to the adjacent piles in 2D model. In the 2D model, the pile is modelled using embedded row pile element which is a 1-D element. The user is allowed to input the pile spacing in out-of-plane direction. This gives an impression to engineers the embedded pile row element is able to model the pile which virtually is a 3D problem. It is reported by Sluis (2014) that the application of embedded pile row element is limited to 8D of pile length. It is also reported that the 2D model overestimates the axial load in pile and the shear force and bending moment at pile top and it is not realistic in comparison to 3D model. In this paper, the centrifuge results of single pile and 6-pile group - tunneling problem carried out in NUS (National University of Singapore) are back-analysed with Midas GTS 3D and a 2D program. In a separate case study, pile groups adjacent to a deep excavation is modelled by 3D and 2D program. This paper compares the deflection and forces in piles in 2D and 3D models.


2019 ◽  
Author(s):  
Ning Wang ◽  
Andrew E. Teschendorff

AbstractInferring the activity of transcription factors in single cells is a key task to improve our understanding of development and complex genetic diseases. This task is, however, challenging due to the relatively large dropout rate and noisy nature of single-cell RNA-Seq data. Here we present a novel statistical inference framework called SCIRA (Single Cell Inference of Regulatory Activity), which leverages the power of large-scale bulk RNA-Seq datasets to infer high-quality tissue-specific regulatory networks, from which regulatory activity estimates in single cells can be subsequently obtained. We show that SCIRA can correctly infer regulatory activity of transcription factors affected by high technical dropouts. In particular, SCIRA can improve sensitivity by as much as 70% compared to differential expression analysis and current state-of-the-art methods. Importantly, SCIRA can reveal novel regulators of cell-fate in tissue-development, even for cell-types that only make up 5% of the tissue, and can identify key novel tumor suppressor genes in cancer at single cell resolution. In summary, SCIRA will be an invaluable tool for single-cell studies aiming to accurately map activity patterns of key transcription factors during development, and how these are altered in disease.


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