scholarly journals Application of transport-based metric for continuous interpolation between cryo-EM density maps

2021 ◽  
Vol 7 (1) ◽  
pp. 986-999
Author(s):  
Arthur Ecoffet ◽  
◽  
Geoffrey Woollard ◽  
Artem Kushner ◽  
Frédéric Poitevin ◽  
...  

<abstract><p>Cryogenic electron microscopy (cryo-EM) has become widely used for the past few years in structural biology, to collect single images of macromolecules "frozen in time". As this technique facilitates the identification of multiple conformational states adopted by the same molecule, a direct product of it is a set of 3D volumes, also called EM maps. To gain more insights on the possible mechanisms that govern transitions between different states, and hence the mode of action of a molecule, we recently introduced a bioinformatic tool that interpolates and generates morphing trajectories joining two given EM maps. This tool is based on recent advances made in optimal transport, that allow efficient evaluation of Wasserstein barycenters of 3D shapes. As the overall performance of the method depends on various key parameters, including the sensitivity of the regularization parameter, we performed various numerical experiments to demonstrate how MorphOT can be applied in different contexts and settings. Finally, we discuss current limitations and further potential connections between other optimal transport theories and the conformational heterogeneity problem inherent with cryo-EM data.</p></abstract>

Symmetry ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1363
Author(s):  
Damilare Peter Oyinloye ◽  
Je Sen Teh ◽  
Norziana Jamil ◽  
Moatsum Alawida

Blockchain networks are based on cryptographic notions that include asymmetric-key encryption, hash functions and consensus protocols. Despite their popularity, mainstream protocols, such as Proof of Work or Proof of Stake still have drawbacks. Efforts to enhance these protocols led to the birth of alternative consensus protocols, catering to specific areas, such as medicine or transportation. These protocols remain relatively unknown despite having unique merits worth investigating. Although past reviews have been published on popular blockchain consensus protocols, they do not include most of these lesser-known protocols. Highlighting these alternative consensus protocols contributes toward the advancement of the state of the art, as they have design features that may be useful to academics, blockchain practitioners and researchers. In this paper, we bridge this gap by providing an overview of alternative consensus protocols proposed within the past 3 years. We evaluate their overall performance based on metrics such as throughput, scalability, security, energy consumption, and finality. In our review, we examine the trade-offs that these consensus protocols have made in their attempts to optimize scalability and performance. To the best of our knowledge, this is the first paper that focuses on these alternative protocols, highlighting their unique features that can be used to develop future consensus protocols.


1973 ◽  
Vol 12 (2) ◽  
pp. 181-188
Author(s):  
Rafiq Ahmad

Like nations and civilizations, sciences also pass through period of crises when established theories are overthrown by the unpredictable behaviour of events. Economics is passing through such a crisis. The challenge thrown by the Great Depression of early 1930s took a decade before Keynes re-established the supremacy of economics. But this supremacy has again been upset by the crisis of poverty in the vast under-developed world which attained political independence after the Second World War. Poverty had always existed but never before had it been of such concern to economists as during the past twenty five years or so. Economic literature dealing with this problem has piled up but so have the agonies of poverty. No plausible and well-integrated theory of economic development or under-development has emerged so far, though brilliant advances have been made in isolated directions.


Author(s):  
Rocco J. Rotello ◽  
Timothy D. Veenstra

: In the current omics-age of research, major developments have been made in technologies that attempt to survey the entire repertoire of genes, transcripts, proteins, and metabolites present within a cell. While genomics has led to a dramatic increase in our understanding of such things as disease morphology and how organisms respond to medications, it is critical to obtain information at the proteome level since proteins carry out most of the functions within the cell. The primary tool for obtaining proteome-wide information on proteins within the cell is mass spectrometry (MS). While it has historically been associated with the protein identification, developments over the past couple of decades have made MS a robust technology for protein quantitation as well. Identifying quantitative changes in proteomes is complicated by its dynamic nature and the inability of any technique to guarantee complete coverage of every protein within a proteome sample. Fortunately, the combined development of sample preparation and MS methods have made it capable to quantitatively compare many thousands of proteins obtained from cells and organisms.


Author(s):  
John Hunsley ◽  
Eric J. Mash

Evidence-based assessment relies on research and theory to inform the selection of constructs to be assessed for a specific assessment purpose, the methods and measures to be used in the assessment, and the manner in which the assessment process unfolds. An evidence-based approach to clinical assessment necessitates the recognition that, even when evidence-based instruments are used, the assessment process is a decision-making task in which hypotheses must be iteratively formulated and tested. In this chapter, we review (a) the progress that has been made in developing an evidence-based approach to clinical assessment in the past decade and (b) the many challenges that lie ahead if clinical assessment is to be truly evidence-based.


2021 ◽  
pp. 088506662199232
Author(s):  
Xiaojuan Zhang ◽  
Xin Li

Septic shock with multiple organ failure is a devastating situation in clinical settings. Through the past decades, much progress has been made in the management of sepsis and its underlying pathogenesis, but a highly effective therapeutic has not been developed. Recently, macromolecules such as histones have been targeted in the treatment of sepsis. Histones primarily function as chromosomal organizers to pack DNA and regulate its transcription through epigenetic mechanisms. However, a growing body of research has shown that histone family members can also exert cellular toxicity once they relocate from the nucleus into the extracellular space. Heparin, a commonly used anti-coagulant, has been shown to possess life-saving capabilities for septic patients, but the potential interplay between heparin and extracellular histones has not been investigated. In this review, we summarize the pathogenic roles of extracellular histones and the therapeutic roles of heparin in the development and management of sepsis and septic shock.


Author(s):  
Arthur Ecoffet ◽  
Frédéric Poitevin ◽  
Khanh Dao Duc

Abstract Motivation Cryogenic electron microscopy (cryo-EM) offers the unique potential to capture conformational heterogeneity, by solving multiple three-dimensional classes that co-exist within a single cryo-EM image dataset. To investigate the extent and implications of such heterogeneity, we propose to use an optimal-transport-based metric to interpolate barycenters between EM maps and produce morphing trajectories. Results While standard linear interpolation mostly fails to produce realistic transitions, our method yields continuous trajectories that displace densities to morph one map into the other, instead of blending them. Availability and implementation Our method is implemented as a plug-in for ChimeraX called MorphOT, which allows the use of both CPU or GPU resources. The code is publicly available on GitHub (https://github.com/kdd-ubc/MorphOT.git), with documentation containing tutorial and datasets. Supplementary information Supplementary data are available at Bioinformatics online.


1939 ◽  
Vol 17 (2) ◽  
pp. 69-82 ◽  
Author(s):  
D. W. Fenwick

Numerous attempts have been made in the past to induce the eggs of Ascaris suum to hatch outside the body of the host. Extra-corporeal hatching has been observed under a variety of conditions by different workers. Kondo (1920, 1922), Asada (1921) and others record hatching in water, charcoal and sand cultures. Wharton (1915) states that hatching will occur in alkaline digestive juices, while Martin (1913) records a similar phenomenon in pancreatic fluid. Many different explanations have been offered to explain this hatching. Wharton suggested that the interaction of algae and sand might have some effect. Ohba (1923), who found that hatching would occur in 0·2% hydrochloric acid and 0·2% sodium carbonate believed that extra-corporeal hatching was limited to very old cultures of eggs. Many workers are of the opinion that some stimulus normally present in the digestive tract is necessary for hatching.


2015 ◽  
Vol 370 (1681) ◽  
pp. 20140267 ◽  
Author(s):  
Paul J. Ferraro ◽  
Merlin M. Hanauer

To develop effective protected area policies, scholars and practitioners must better understand the mechanisms through which protected areas affect social and environmental outcomes. With strong evidence about mechanisms, the key elements of success can be strengthened, and the key elements of failure can be eliminated or repaired. Unfortunately, empirical evidence about these mechanisms is limited, and little guidance for quantifying them exists. This essay assesses what mechanisms have been hypothesized, what empirical evidence exists for their relative contributions and what advances have been made in the past decade for estimating mechanism causal effects from non-experimental data. The essay concludes with a proposed agenda for building an evidence base about protected area mechanisms.


1995 ◽  
Vol 347 (1319) ◽  
pp. 21-25 ◽  

Over the past three or four years, great strides have been made in our understanding of the proteins involved in recombination and the mechanisms by which recombinant molecules are formed. This review summarizes our current understanding of the process by focusing on recent studies of proteins involved in the later steps of recombination in bacteria. In particular, biochemical investigation of the in vitro properties of the E. coli RuvA, RuvB and RuvC proteins have provided our first insight into the novel molecular mechanisms by which Holliday junctions are moved along DNA and then resolved by endonucleolytic cleavage.


Author(s):  
Wei Chen ◽  
S.L. Yuen ◽  
R.H.Y. So

This paper summarizes the progress made in the quest to establish a Cybersickness Dose Value (CSDV). The Motion Sickness Dose Value (MSDV), reported in the British Standard BS6841, has been used to predict the severity of seasickness since 1987. In 1999, the authors of this paper proposed a CSDV formulation with a structure similar to that of the MSDV (So, 1999). Since then, several experiments and simulation studies have been conducted to modify and develop the proposed CSDV formula. In particular, progress has been made in (i) the methods to measure CSDV, (ii) the determination of a frequency weighting curve to equalize the non-linear relationship between the navigation velocity and levels of cybersickness, and (iii) the detailed formulation of CSDV. This paper summarizes the past progress and reports on the current effort in developing a CSDV.


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