scholarly journals Computation-guided optimization of split protein systems

2019 ◽  
Author(s):  
Taylor B. Dolberg ◽  
Anthony T. Meger ◽  
Jonathan D. Boucher ◽  
William K. Corcoran ◽  
Elizabeth E. Schauer ◽  
...  
Keyword(s):  
Protein Design ◽  
New Technology ◽  
Computational Design ◽  
Fluorescent Reporters ◽  
High Propensity ◽  
Biochemical Systems ◽  
Split Protein ◽  
Protein Biophysics ◽  
Context Specific ◽  
And Control

ABSTRACTSplitting bioactive proteins, such as enzymes or fluorescent reporters, into conditionally reconstituting fragments is a powerful strategy for building tools to study and control biochemical systems. However, split proteins often exhibit a high propensity to reconstitute even in the absence of the conditional trigger, which limits their utility. Current approaches for tuning reconstitution propensity are laborious, context-specific, or often ineffective. Here, we report a computational design-driven strategy that is grounded in fundamental protein biophysics and which guides the experimental evaluation of a focused, sparse set of mutants—which vary in the degree of interfacial destabilization while preserving features such as stability and catalytic activity—to identify an optimal functional window. We validate our method by solving two distinct split protein design challenges, generating both broad insights and new technology platforms. This method will streamline the generation and use of split protein systems for diverse applications.

A Review of Switched Inertance Hydraulic Converter Technology

2018 ◽  
Author(s):  
Chenggang Yuan ◽  
Min Pan ◽  
Andrew Plummer
Keyword(s):  
Power Management ◽  
Energy Efficient ◽  
Control Strategies ◽  
New Technology ◽  
High Energy ◽  
Management Systems ◽  
Hydraulic Power ◽  
Controlled Systems ◽  
Hydraulic Machines ◽  
And Control

Digital hydraulics is a new technology providing an alternative to conventional proportional or servovalve-controlled systems in the area of fluid power. Research is driven by the need for highly energy efficient hydraulic machines but is relatively immature compared to other energy-saving technologies. Digital hydraulic applications, such as digital pumps, digital valves and actuators, switched inertance hydraulic converters (SIHCs) and digital hydraulic power management systems, all promise high energy efficiency. This review introduces the development of SIHCs and evaluates the device configurations, performance and control strategies that are found in current SIHC research, particularly focusing on the work being undertaken in last 15 years. The designs for highspeed switching valves are evaluated, and their advantages and limitations are discussed. This article concludes with some suggestions for the future development of SIHCs.

scholarly journals Protein structure prediction and design in a biologically-realistic implicit membrane

2019 ◽  
Author(s):  
Rebecca F. Alford ◽  
Patrick J. Fleming ◽  
Karen G. Fleming ◽  
Jeffrey J. Gray
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Protein Structure Prediction ◽  
Protein Design ◽  
Structure Prediction ◽  
De Novo ◽  
Computational Design ◽  
Amino Acid Distribution

ABSTRACTProtein design is a powerful tool for elucidating mechanisms of function and engineering new therapeutics and nanotechnologies. While soluble protein design has advanced, membrane protein design remains challenging due to difficulties in modeling the lipid bilayer. In this work, we developed an implicit approach that captures the anisotropic structure, shape of water-filled pores, and nanoscale dimensions of membranes with different lipid compositions. The model improves performance in computational bench-marks against experimental targets including prediction of protein orientations in the bilayer, ΔΔG calculations, native structure dis-crimination, and native sequence recovery. When applied to de novo protein design, this approach designs sequences with an amino acid distribution near the native amino acid distribution in membrane proteins, overcoming a critical flaw in previous membrane models that were prone to generating leucine-rich designs. Further, the proteins designed in the new membrane model exhibit native-like features including interfacial aromatic side chains, hydrophobic lengths compatible with bilayer thickness, and polar pores. Our method advances high-resolution membrane protein structure prediction and design toward tackling key biological questions and engineering challenges.Significance StatementMembrane proteins participate in many life processes including transport, signaling, and catalysis. They constitute over 30% of all proteins and are targets for over 60% of pharmaceuticals. Computational design tools for membrane proteins will transform the interrogation of basic science questions such as membrane protein thermodynamics and the pipeline for engineering new therapeutics and nanotechnologies. Existing tools are either too expensive to compute or rely on manual design strategies. In this work, we developed a fast and accurate method for membrane protein design. The tool is available to the public and will accelerate the experimental design pipeline for membrane proteins.

scholarly journals Developing a theory-based behavior change intervention to improve the prescription of surgical prophylaxis in an Egyptian University Hospital.

2021 ◽  
Author(s):  
Anna-Leena Lohiniva ◽  
Iman Heweidy ◽  
Samiha Abdu ◽  
Abouelata Omar ◽  
Caroline Ackley ◽  
...  
Keyword(s):  
Behaviour Change ◽  
Prevention And Control ◽  
Infection Prevention ◽  
Theoretical Domains Framework ◽  
Control Measures ◽  
World Health ◽  
Infection Prevention And Control ◽  
Surgical Prophylaxis ◽  
Context Specific ◽  
And Control

Abstract Background: Antimicrobial resistance (AMR) is increasingly pervasive due to multiple, complex prescribing and consuming behaviours. Accordingly, behaviour change is an important component of response to AMR. Little is known about the best approaches to change antibiotic use practices and behaviours. This project aims to develop a context-specific behaviour change strategy focusing on promoting appropriate prescription practices following the World Health Organization recommendations for surgical prophylaxis in an orthopaedic surgery unit in Egypt.Methods: The project included a formative qualitative research study was based on the Theoretical Domains Framework (TDF) to explore the determinants for inappropriate prescription of surgical antibiotic prophylaxis at an orthopaedic unit. The intervention was developed to following the Behaviour Change Wheel (BCW) in a knowledge co-production workshop with infection prevention and control experts that ensured that the theory based intervention was a culturally acceptable, practical and implementable intervention. Results: The prescription of surgical prophylaxis was influenced by five TDF domains including, knowledge, belief in consequences (mistrust towards infection prevention and control measures), environmental factors (lack of prescription guidelines) , professional role and reinforcement (a lack of appropriate follow up actions influenced prescription of surgical prophylaxis). The appropriate set of behaviour change functions of BCW and related activities to improve the current practices included education, enablement, persuasion, environmental restructuring and restriction. Conclusions The study showed that a theory based and context specific intervention can be created by using the TDF and BCW together with knowledge-co creation to improve the prescription of surgical prophylaxis in and Egyptian orthopaedic unit. The intervention need to piloted and scaled up.

Technology-Driven Convergence of Business Processes in the Acquisition Cycle: Implications for Accountants and Educators

2011 ◽  
Vol 8 (1) ◽  
pp. 65-87
Author(s):  
Richard J. Palmer ◽  
Mahendra R. Gupta
Keyword(s):  
Business Processes ◽  
New Technology ◽  
Organizational Structures ◽  
Regulatory Compliance ◽  
Accounting Education ◽  
Student Preparation ◽  
Business Applications ◽  
And Control ◽  
The Impact ◽  
Acquisition Cycle

ABSTRACT Organizations have sought competitive cost advantage in the acquisition cycle through software associated with e-procurement, expense management, payment technology, data mining, ERP “bolt-ons,” and regulatory compliance. The net effect of advancing technology has been a convergence of the different business processes operating within the acquisition cycle such that the potential exists for one basic procurement process and payment tool to support multiple business applications, greatly improving organizational efficiency. Thus, this paper examines (1) processes within the traditional acquisition cycle and the technological and control drivers that sustain them, (2) how emerging technologies (in particular, card-based payment technologies) are disrupting the acquisition cycle, and (3) how new technology represents a paradigm shift for accountants and educators that requires a significant reconsideration of the nature of and balance between key controls, risks, and efficiency. The paper also examines the impact of acquisition cycle change on organizational structures, the role of accountants, accounting education, and student preparation for the competitive market.

Principles of Protein Stability and Their Application in Computational Design

2018 ◽  
Vol 87 (1) ◽  
pp. 105-129 ◽  
Author(s):  
Adi Goldenzweig ◽  
Sarel J. Fleishman
Keyword(s):  
Thermal Stability ◽  
Phylogenetic Analysis ◽  
Protein Design ◽  
Biomedical Research ◽  
Design Methodology ◽  
Computational Design ◽  
Marginal Stability ◽  
Computational Stability ◽  
Rational Engineering ◽  
The Past

Proteins are increasingly used in basic and applied biomedical research. Many proteins, however, are only marginally stable and can be expressed in limited amounts, thus hampering research and applications. Research has revealed the thermodynamic, cellular, and evolutionary principles and mechanisms that underlie marginal stability. With this growing understanding, computational stability design methods have advanced over the past two decades starting from methods that selectively addressed only some aspects of marginal stability. Current methods are more general and, by combining phylogenetic analysis with atomistic design, have shown drastic improvements in solubility, thermal stability, and aggregation resistance while maintaining the protein's primary molecular activity. Stability design is opening the way to rational engineering of improved enzymes, therapeutics, and vaccines and to the application of protein design methodology to large proteins and molecular activities that have proven challenging in the past.

scholarly journals Positive multistate protein design

2019 ◽  
Vol 36 (1) ◽  
pp. 122-130
Author(s):  
Jelena Vucinic ◽  
David Simoncini ◽  
Manon Ruffini ◽  
Sophie Barbe ◽  
Thomas Schiex
Keyword(s):  
Protein Design ◽  
Critical Role ◽  
Average Energy ◽  
Computational Design ◽  
Amino Acid Sequences ◽  
Supplementary Information ◽  
Backbone Flexibility ◽  
Identify Amino Acid ◽  
Design Software ◽  
Protein Redesign

Abstract Motivation Structure-based computational protein design (CPD) plays a critical role in advancing the field of protein engineering. Using an all-atom energy function, CPD tries to identify amino acid sequences that fold into a target structure and ultimately perform a desired function. The usual approach considers a single rigid backbone as a target, which ignores backbone flexibility. Multistate design (MSD) allows instead to consider several backbone states simultaneously, defining challenging computational problems. Results We introduce efficient reductions of positive MSD problems to Cost Function Networks with two different fitness definitions and implement them in the Pompd (Positive Multistate Protein design) software. Pompd is able to identify guaranteed optimal sequences of positive multistate full protein redesign problems and exhaustively enumerate suboptimal sequences close to the MSD optimum. Applied to nuclear magnetic resonance and back-rubbed X-ray structures, we observe that the average energy fitness provides the best sequence recovery. Our method outperforms state-of-the-art guaranteed computational design approaches by orders of magnitudes and can solve MSD problems with sizes previously unreachable with guaranteed algorithms. Availability and implementation https://forgemia.inra.fr/thomas.schiex/pompd as documented Open Source. Supplementary information Supplementary data are available at Bioinformatics online.

New technology for electrical metering monitoring and control instrumentation

1984 ◽  
Vol 24 (3) ◽  
pp. 177-180
Author(s):  
B.L. Capehart
Keyword(s):  
New Technology ◽  
Monitoring And Control ◽  
And Control

A Review of Switched Inertance Hydraulic Converter Technology1

2020 ◽  
Vol 142 (5) ◽  
Author(s):  
Chenggang Yuan ◽  
Min Pan ◽  
Andrew Plummer
Keyword(s):  
Energy Efficient ◽  
High Speed ◽  
Control Strategies ◽  
New Technology ◽  
High Energy ◽  
Hydraulic Power ◽  
Controlled Systems ◽  
Hydraulic Machines ◽  
And Control ◽  
High Speed Switching

Abstract Digital hydraulics is a new technology providing an alternative to conventional proportional or servovalve-controlled systems in the area of fluid power. Digital hydraulic applications, such as digital pumps, digital valves and actuators, switched inertance hydraulic converters (SIHCs), and digital hydraulic power management systems, promise high-energy efficiency and less contamination sensitivity. Research on digital hydraulics is driven by the need for highly energy efficient hydraulic machines but is relatively immature compared to other energy-saving technologies. This review introduces the development of SIHCs particularly focusing on the work being undertaken in the last 15 years and evaluates the device configurations, performance, and control strategies that are found in the current SIHC research. Various designs for high-speed switching valves are presented, and their advantages and limitations are compared and discussed. The current limitations of SIHCs are discussed and suggestions for the future development of SIHCs are made.

Predictable policing: New technology, old bias, and future resistance in big data surveillance

2020 ◽  
Vol 26 (5-6) ◽  
pp. 1108-1124
Author(s):  
Xerxes Minocher ◽  
Caelyn Randall
Keyword(s):  
Big Data ◽  
Science And Technology Studies ◽  
New Technology ◽  
The United States ◽  
Surveillance Network ◽  
Predictive Policing ◽  
Sociotechnical System ◽  
Power And Control ◽  
Data Surveillance ◽  
And Control

Within this article, we explore the rise of predictive policing in the United States as a form of big data surveillance. Bringing together literature from communication, criminology, and science and technology studies, we use a case study of Milwaukee, Wisconsin, USA to outline that predictive policing, rather than being a novel development, is in fact part of a much larger, historical network of power and control. By examining the mechanics of these policing practices: the data inputs, behavioral outputs, as well as the key controllers of these systems, and the individuals who influenced their adoption, we show that predictive policing as a form of big data surveillance is a sociotechnical system that is wholly human-constructed, biases and all. Identifying these elements of the surveillance network then allows us to turn our attention to the resistive practices of communities who historically and presently live under surveillance – pointing to the types of actions and imaginaries required to combat the myth and allure that swirls around the rhetoric of big data surveillance today.

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