scholarly journals Immuno-Detection by sequencing (ID-seq) enables large-scale high-dimensional phenotyping in cells

2017 ◽  
Author(s):  
Jessie A.G. van Buggenum ◽  
Jan P. Gerlach ◽  
Sabine E.J. Tanis ◽  
Mark Hogeweg ◽  
Jesse Middelwijk ◽  
...  
Keyword(s):  
Large Scale ◽  
Kinase Inhibitor ◽  
Protein Detection ◽  
High Dimensional ◽  
Small Molecule Screening ◽  
Large Numbers ◽  
Tremendous Progress ◽  
Screening Assays ◽  
Cellular Phenotypes

AbstractCell-based small molecule screening is an effective strategy leading to new medicines. Scientists in the pharmaceutical industry as well as in academia have made tremendous progress in developing both large-scale and smaller-scale screening assays. However, an accessible and universal technology for measuring large numbers of molecular and cellular phenotypes in many samples in parallel is not available. Here, we present the Immuno-Detection by sequencing (ID-seq) technology that combines antibody-based protein detection and DNA-sequencing via DNA-tagged antibodies. We used ID-seq to simultaneously measure 84 (phospho-)proteins in hundreds of samples and screen the effects of ~300 kinase inhibitor probes on primary human epidermal stem cells to characterise the role of 225 kinases. Our work highlighted a previously unrecognized downregulation of mTOR signaling during differentiation and uncovered 13 kinases regulating epidermal renewal through distinct mechanisms.

scholarly journals MHD simulations of star-disk magnetospheres and the formation of outflows and jets

2007 ◽  
Vol 3 (S243) ◽  
pp. 265-276
Author(s):  
Christian Fendt
Keyword(s):  
Numerical Simulation ◽  
Stellar Wind ◽  
Large Scale ◽  
Disk Surface ◽  
Time Dependent ◽  
Mhd Simulations ◽  
Tremendous Progress ◽  
Stellar Magnetospheres ◽  
Scale Evolution

AbstractIn this review the recent development concerning the large-scale evolution of stellar magnetospheres in interaction with the accretion disk is discussed. I put emphasis on the generation of outflows and jets from the disk and/or the star. In fact, tremendous progress has occurred over the last decade in the numerical simulation of the star-disk interaction. The role of numerical simulations is essential in this area because the processes involved are complex, strongly interrelated, and often highly time-dependent. Recent MHD simulations suggest that outflows launched from a very concentrated region tend to be un-collimated. I present preliminary results of simulations of large-scale star-disk magnetospheres loaded with matter from the stellar, resp. the disk surface demonstrating how a disk jet collimates the wind from the star and also how the stellar wind lowers the collimation degree of the disk outflow.

scholarly journals Shaping of intraplate mountain patterns: The Cantabrian orocline legacy in Alpine Iberia

Lithosphere ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 708-721 ◽  
Author(s):  
J. Fernández-Lozano ◽  
G. Gutiérrez-Alonso ◽  
E. Willingshofer ◽  
D. Sokoutis ◽  
G. de Vicente ◽  
...  
Keyword(s):  
Large Scale ◽  
Sedimentary Basins ◽  
Surface Velocity ◽  
Mantle Evolution ◽  
Large Numbers ◽  
Subsequent Response ◽  
Geodynamic Processes ◽  
Analogue Experiments ◽  
Fault Displacement

Abstract The present-day topography in Iberia is related to geodynamic processes dealing with lithospheric-scale deformation. However, little attention has been paid to the role of inherited crustal- or lithospheric-scale structures involved in the recent observed large-scale topographic patterns. Whereas the analysis of brittle structures focuses on the evolution of Mesozoic sedimentary basins and their subsequent response to tectonic inversion, their contribution to mountain building has been underestimated. Large numbers of structures, from ductile to brittle, which affected the whole lithosphere, were developed during the evolution of the Cantabrian orocline (ca. 310–300 Ma). The contribution of these Paleozoic post-Variscan structures, together with lithospheric mantle evolution and replacement during orocline development in the Mesozoic and Cenozoic geological evolution of Iberia, remains unexplored. To explore the role of these inherited structures on the final configuration of topography during N-S Pyrenean shortening, we carried out a series of analogue experiments complemented by surface velocity field analyses. Our experiments indicate that strain was concentrated along preexisting crustal- to lithospheric-scale discontinuities, and they show several reactivation events marked by differences in the velocity vector field. Differences in fault displacement were also observed in the models depending upon preexisting fault trends. The obtained results may explain the different amount of displacement observed during the reactivation of some of the post-orocline structures in Iberia during the Cenozoic, indicating the key role of unveiled structures, which probably have accommodated most of the Alpine shortening.

scholarly journals Role of genomic instability in human carcinogenesis

2019 ◽  
Vol 244 (3) ◽  
pp. 227-240 ◽  
Author(s):  
Jung Joo Moon ◽  
Alexander Lu ◽  
Chulso Moon
Keyword(s):  
Dna Repair ◽  
Cell Line ◽  
Genomic Instability ◽  
Large Scale ◽  
Kinase Inhibitor ◽  
Initial Study ◽  
Repair Gene ◽  
Hereditary Cancers ◽  
Dna Repair Gene

Genomic instability has been an area of active area of research in the last two decades. Based on the initial study for hereditary cancers, DNA repair gene family mutations have been identified. In sporadic (non-hereditary) cancers, several large-scale DNA sequencing studies suggest that mutations in DNA repair genes are less frequent, suggesting the complexity of tumorigenesis of sporadic cancers. So far, several important genes have been identified, by using mostly cell line models and mice studies. These include DNA damage response modifier like ataxia telangiectasia mutated (ATM), conventional tumor suppressor genes like TP53 and cyclin-dependent kinase inhibitor 2A (CDKN2A; which encodes p16INK4A and p14ARF). Various hypotheses for sporadic tumorigenesis have been developed, and so far, “oncogene-induced DNA replication stress model” has been gaining widespread interests. In this review, we will first describe some of the important concepts of genomic instability. Then, we will outline oncogene-induced genomic instability and discuss the role of the MYC gene during this process, which will be followed by detailed reviews of mutation data. We hope that this review can outline the overall perspectives of genomic instability. Impact statement This review provides various genetic and cell line data previously published in a way to explain how cellular stress can lead into genetic instability.

scholarly journals “Poor” archeological levels not to be forgotten: units of Middle and early Upper Magdalenian age in El Mirón Cave (Ramales de la Victoria, Cantabria, Spain)

2021 ◽  
Author(s):  
undefined Lawrence Guy STRAUS ◽  
undefined Manuel R. GONZÁLEZ MORALES
Keyword(s):  
Coastal Zone ◽  
Significant Role ◽  
Large Scale ◽  
Late Glacial ◽  
Short Term ◽  
Large Numbers ◽  
Portable Art ◽  
Early Upper

This succinct contribution focuses on description and preliminary interpretation of “minor” occupations of the large, strategically located El Mirón Cave on the edge of the Cantabrian Cordillera in eastern Cantabria (Spain) during the Middle and early Upper Magalenian that followed upon the massive, culturally rich, faunally dense, functionally complex deposits of the Initial and Lower Magdalenian. The ten levels analyzed here date to the Late Glacial, c. 15.5-12.5 uncal kya BP. At a time when the classic Middle Magdalenian of the nearby French Pyrenees developed and major residential sites with clear social links to it (via the key site of Isturitz) were occupied in the lowland coastal zone of Cantabria and Asturias (e.g. La Garma, Llonín, La Viña), El Mirón had reverted for the most part to the role of a short-term, special-purpose, perhaps logistical campsite, rather than as a long-term, large-scale hub residential base. It is tempting (and indeed traditional) to focus on levels with large numbers of lithic and osseous artifacts, as well as works of portable art and personal ornaments, which are so characteristic of the most famous Magdalenian occupations. However, in hunter-gatherer subsistence systems, the “minor” locations played a significant role in the human exploitation of territories (especially ones with such complex, high relief as Cantabrian Spain). The levels in question here include some that can be interpreted as hunting camps (suggested by high percentages of worked and unworked bladelets and some antler points within the small assemblages), partially reminiscent of the use to which the cave may have been put during pre-Initial Magdalenian times, notably during the Solutrean, which was relatively rich in stone points.

Localization of Intracisternal a Particle Antigens in Neoplastic Cells and Preimplantation Mouse Embryos

1980 ◽  
Vol 38 ◽  
pp. 696-697
Author(s):  
Thomas T.F. Huang ◽  
Patricia G. Calarco
Keyword(s):  
Endoplasmic Reticulum ◽  
Normal Development ◽  
Mouse Embryos ◽  
Neoplastic Cells ◽  
Large Numbers ◽  
Preimplantation Mouse Embryos ◽  
Preimplantation Mouse ◽  
Intracisternal A Particle ◽  
Normal Feature

The stage specific appearance of a retravirus, termed the Intracisternal A particle (IAP) is a normal feature of early preimplantation development. To date, all feral and laboratory strains of Mus musculus and even Asian species such as Mus cervicolor and Mus pahari express the particles during the 2-8 cell stages. IAP form by budding into the endoplasmic reticulum and appear singly or as groups of donut-shaped particles within the cisternae (fig. 1). IAP are also produced in large numbers in several neoplastic cells such as certain plasmacytomas and rhabdomyosarcomas. The role of IAP, either in normal development or in neoplastic behavior, is unknown.

DNA methylation in satellite repeats disorders

2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Repetitive Dna ◽  
Dna Sequences ◽  
Satellite Repeats ◽  
Tremendous Progress ◽  
Genes Encoding ◽  
Dna Elements ◽  
Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

The Role of Sense of Direction and Other Factors During Navigation in a Large-Scale, Unconstrained Environment

2013 ◽  
Author(s):  
Elisabeth J. Ploran ◽  
Ericka Rovira ◽  
James C. Thompson ◽  
Raja Parasuraman
Keyword(s):  
Large Scale ◽  
Sense Of Direction

Computer Analyses in Preventive Health Research

1967 ◽  
Vol 06 (01) ◽  
pp. 8-14 ◽  
Author(s):  
M. F. Collen
Keyword(s):  
Medical Research ◽  
Preventive Medicine ◽  
Health Research ◽  
Large Scale ◽  
Preventive Health ◽  
New Era ◽  
Large Numbers ◽  
Normal Test ◽  
Computer Analyses

The utilization of an automated multitest laboratory as a data acquisition center and of a computer for trie data processing and analysis permits large scale preventive medical research previously not feasible. Normal test values are easily generated for the particular population studied. Long-term epidemiological research on large numbers of persons becomes practical. It is our belief that the advent of automation and computers has introduced a new era of preventive medicine.

Magnetic Properties of xCeO2•(50 − x) PbO•50B2O3 Glasses and Glass Ceramics

2017 ◽  
Vol 13 (1) ◽  
pp. 4486-4494 ◽  
Author(s):  
G.El Damrawi ◽  
F. Gharghar
Keyword(s):  
Magnetic Properties ◽  
Large Scale ◽  
Glass Ceramics ◽  
Magnetic Behavior ◽  
Crystal Formation ◽  
Dual Roles ◽  
Effective Agent ◽  
Ordered Structures ◽  
Essential Change

Cerium oxide in borate glasses of composition xCeO2·(50 − x)PbO·50B2O3 plays an important role in changing both microstructure and magnetic behaviors of the system. The structural role of CeO2 as an effective agent for cluster and crystal formation in borate network is clearly evidenced by XRD technique. Both structure and size of well-formed cerium separated clusters have an effective influence on the structural properties. The cluster aggregations are documented to be found in different range ordered structures, intermediate and long range orders are the most structures in which cerium phases are involved. The nano-sized crystallized cerium species in lead borate phase are evidenced to have magnetic behavior.  The criteria of building new specific borate phase enriched with cerium as ferrimagnetism has been found to keep the magnetization in large scale even at extremely high temperature. Treating the glass thermally or exposing it to an effective dose of ionized radiation is evidenced to have an essential change in magnetic properties. Thermal heat treatment for some of investigated materials is observed to play dual roles in the glass matrix. It can not only enhance alignment processes of the magnetic moment but also increases the capacity of the crystallite species in the magnetic phases. On the other hand, reverse processes are remarked under the effect of irradiation. The magnetization was found to be lowered, since several types of the trap centers which are regarded as defective states can be produced by effect of ionized radiation. 

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