scholarly journals Joint epitope selection and spacer design for string-of-beads vaccines

2020 ◽  
Vol 36 (Supplement_2) ◽  
pp. i643-i650
Author(s):  
Emilio Dorigatti ◽  
Benjamin Schubert

Abstract Motivation Conceptually, epitope-based vaccine design poses two distinct problems: (i) selecting the best epitopes to elicit the strongest possible immune response and (ii) arranging and linking them through short spacer sequences to string-of-beads vaccines, so that their recovery likelihood during antigen processing is maximized. Current state-of-the-art approaches solve this design problem sequentially. Consequently, such approaches are unable to capture the inter-dependencies between the two design steps, usually emphasizing theoretical immunogenicity over correct vaccine processing, thus resulting in vaccines with less effective immunogenicity in vivo. Results In this work, we present a computational approach based on linear programming, called JessEV, that solves both design steps simultaneously, allowing to weigh the selection of a set of epitopes that have great immunogenic potential against their assembly into a string-of-beads construct that provides a high chance of recovery. We conducted Monte Carlo cleavage simulations to show that a fixed set of epitopes often cannot be assembled adequately, whereas selecting epitopes to accommodate proper cleavage requirements substantially improves their recovery probability and thus the effective immunogenicity, pathogen and population coverage of the resulting vaccines by at least 2-fold. Availability and implementation The software and the data analyzed are available at https://github.com/SchubertLab/JessEV. Supplementary information Supplementary data are available at Bioinformatics online.

2020 ◽  
Author(s):  
Emilio Dorigatti ◽  
Benjamin Schubert

AbstractMotivationConceptually, epitope-based vaccine design poses two distinct problems: (1) selecting the best epitopes eliciting the strongest possible immune response, and (2) arranging and linking the selected epitopes through short spacer sequences to string-of-beads vaccines so as to increase the recovery likelihood of each epitope during antigen processing. Current state-of-the-art approaches solve this design problem sequentially. Consequently, such approaches are unable to capture the inter-dependencies between the two design steps, usually emphasizing theoretical immunogenicity over correct vaccine processing and resulting in vaccines with less effective immunogencity.ResultsIn this work, we present a computational approach based on linear programming that solves both design steps simultaneously, allowing to weigh the selection of a set of epitopes that have great immunogenic potential against their assembly into a string-of-beads construct that provides a high chance of recovery. We conducted Monte-Carlo cleavage simulations to show that, indeed, a fixed set of epitopes often cannot be assembled adequately, whereas selecting epitopes to accommodate proper cleavage requirements substantially improves their recovery probability and thus the effective immunogenicity, pathogen, and population coverage of the resulting vaccines by at least two fold.AvailabilityThe software and the data analyzed are available at https://github.com/SchubertLab/JessEV


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yangfan Xu ◽  
Xianqun Fan ◽  
Yang Hu

AbstractEnzyme-catalyzed proximity labeling (PL) combined with mass spectrometry (MS) has emerged as a revolutionary approach to reveal the protein-protein interaction networks, dissect complex biological processes, and characterize the subcellular proteome in a more physiological setting than before. The enzymatic tags are being upgraded to improve temporal and spatial resolution and obtain faster catalytic dynamics and higher catalytic efficiency. In vivo application of PL integrated with other state of the art techniques has recently been adapted in live animals and plants, allowing questions to be addressed that were previously inaccessible. It is timely to summarize the current state of PL-dependent interactome studies and their potential applications. We will focus on in vivo uses of newer versions of PL and highlight critical considerations for successful in vivo PL experiments that will provide novel insights into the protein interactome in the context of human diseases.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shreeya Sriram ◽  
Shitij Avlani ◽  
Matthew P. Ward ◽  
Shreyas Sen

AbstractContinuous multi-channel monitoring of biopotential signals is vital in understanding the body as a whole, facilitating accurate models and predictions in neural research. The current state of the art in wireless technologies for untethered biopotential recordings rely on radiative electromagnetic (EM) fields. In such transmissions, only a small fraction of this energy is received since the EM fields are widely radiated resulting in lossy inefficient systems. Using the body as a communication medium (similar to a ’wire’) allows for the containment of the energy within the body, yielding order(s) of magnitude lower energy than radiative EM communication. In this work, we introduce Animal Body Communication (ABC), which utilizes the concept of using the body as a medium into the domain of untethered animal biopotential recording. This work, for the first time, develops the theory and models for animal body communication circuitry and channel loss. Using this theoretical model, a sub-inch$$^3$$ 3 [1″ × 1″ × 0.4″], custom-designed sensor node is built using off the shelf components which is capable of sensing and transmitting biopotential signals, through the body of the rat at significantly lower powers compared to traditional wireless transmissions. In-vivo experimental analysis proves that ABC successfully transmits acquired electrocardiogram (EKG) signals through the body with correlation $$>99\%$$ > 99 % when compared to traditional wireless communication modalities, with a 50$$\times$$ × reduction in power consumption.


Author(s):  
Weixiang Xu ◽  
Xiangyu He ◽  
Tianli Zhao ◽  
Qinghao Hu ◽  
Peisong Wang ◽  
...  

Large neural networks are difficult to deploy on mobile devices because of intensive computation and storage. To alleviate it, we study ternarization, a balance between efficiency and accuracy that quantizes both weights and activations into ternary values. In previous ternarized neural networks, a hard threshold Δ is introduced to determine quantization intervals. Although the selection of Δ greatly affects the training results, previous works estimate Δ via an approximation or treat it as a hyper-parameter, which is suboptimal. In this paper, we present the Soft Threshold Ternary Networks (STTN), which enables the model to automatically determine quantization intervals instead of depending on a hard threshold. Concretely, we replace the original ternary kernel with the addition of two binary kernels at training time, where ternary values are determined by the combination of two corresponding binary values. At inference time, we add up the two binary kernels to obtain a single ternary kernel. Our method dramatically outperforms current state-of-the-arts, lowering the performance gap between full-precision networks and extreme low bit networks. Experiments on ImageNet with AlexNet (Top-1 55.6%), ResNet-18 (Top-1 66.2%) achieves new state-of-the-art.


Parasitology ◽  
2009 ◽  
Vol 137 (3) ◽  
pp. 589-603 ◽  
Author(s):  
J. KEISER

SUMMARYSchistosomiasis and food-borne trematodiases are chronic parasitic diseases affecting millions of people mostly in the developing world. Additional drugs should be developed as only few drugs are available for treatment and drug resistance might emerge. In vitro and in vivo whole parasite screens represent essential components of the trematodicidal drug discovery cascade. This review describes the current state-of-the-art of in vitro and in vivo screening systems of the blood fluke Schistosoma mansoni, the liver fluke Fasciola hepatica and the intestinal fluke Echinostoma caproni. Examples of in vitro and in vivo evaluation of compounds for activity are presented. To boost the discovery pipeline for these diseases there is a need to develop validated, robust high-throughput in vitro systems with simple readouts.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Fayçal Ait Aoudia ◽  
Matthieu Gautier ◽  
Olivier Berder

Opportunistic forwarding has emerged as a promising technique to address the problem of unreliable links typical in wireless sensor networks and improve energy efficiency by exploiting multiuser diversity. Timer-based solutions, such as timer-based contention, form promising schemes to allow opportunistic next hop relay selection. However, they can incur significant idle listening and thus reduce the lifetime of the network. To tackle this problem, we propose to exploit emerging wake-up receiver technologies that have the potential to considerably reduce the power consumption of wireless communications. A careful design of MAC protocols is required to efficiently employ these new devices. In this work, we propose Opportunistic Wake-Up MAC (OPWUM), a novel multihop MAC protocol using timer-based contention. It enables the opportunistic selection of the best receiver among its neighboring nodes according to a given metric (e.g., the remaining energy), without requiring any knowledge about them. Moreover, OPWUM exploits emerging wake-up receivers to drastically reduce nodes power consumption. Through analytical study and exhaustive networks simulations, we show the effectiveness of OPWUM compared to the current state-of-the-art protocols using timer-based contention.


2021 ◽  
Vol 7 ◽  
Author(s):  
Priyanka Rao ◽  
Quentin Peyron ◽  
Sven Lilge ◽  
Jessica Burgner-Kahrs

Tendon actuation is one of the most prominent actuation principles for continuum robots. To date, a wide variety of modelling approaches has been derived to describe the deformations of tendon-driven continuum robots. Motivated by the need for a comprehensive overview of existing methodologies, this work summarizes and outlines state-of-the-art modelling approaches. In particular, the most relevant models are classified based on backbone representations and kinematic as well as static assumptions. Numerical case studies are conducted to compare the performance of representative modelling approaches from the current state-of-the-art, considering varying robot parameters and scenarios. The approaches show different performances in terms of accuracy and computation time. Guidelines for the selection of the most suitable approach for given designs of tendon-driven continuum robots and applications are deduced from these results.


2021 ◽  
Author(s):  
Gema Vera Gonzalez ◽  
Phatsimo Kgwarae ◽  
Luca Annecchino ◽  
Simon Schultz

A review paper on the current state of the art in robotic automation of in vivo patch-clamp electrophysiology


1984 ◽  
Vol 6 (4) ◽  
pp. 349-395 ◽  
Author(s):  
J. Ophir ◽  
T. H. Shawker ◽  
N. F. Maklad ◽  
J. G. Miller ◽  
S. W. Flax ◽  
...  

This monograph presents a tutorial review of the current state-of-the-art in ultrasonic attenuation estimation in reflection. Clinical indications which provide the motivation for attempting in vivo attenuation estimation are discussed. Frequency and time domain techniques and their respective tradeoffs and problems are presented. Finally, current clinical results obtained with the various techniques are summarized and further areas of study are suggested.


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