scholarly journals Top-down engineering of complex communities by directed evolution

2020 ◽  
Author(s):  
Chang-Yu Chang ◽  
Jean C.C. Vila ◽  
Madeline Bender ◽  
Richard Li ◽  
Madeleine C. Mankowski ◽  
...  
Keyword(s):  
Directed Evolution ◽  
Microbial Consortia ◽  
Selection Strategy ◽  
Top Down ◽  
Modeling Framework ◽  
Theoretical Understanding ◽  
Fundamental Limits ◽  
Flexible Modeling ◽  
Wide Range ◽  
Selected Functions

AbstractDirected evolution has been used for decades to engineer biological systems from the top-down. Generally, it has been applied at or below the organismal level, by iteratively sampling the mutational landscape in a guided search for genetic variants of higher function. Above the organismal level, a small number of studies have attempted to artificially select microbial communities and ecosystems, with uneven and generally modest success. Our theoretical understanding of artificial ecosystem selection is still limited, particularly for large assemblages of asexual organisms, and we know little about designing efficient methods to direct their evolution. To address this issue, we have developed a flexible modeling framework that allows us to systematically probe any arbitrary selection strategy on any arbitrary set of communities and selected functions, in a wide range of ecological conditions. By artificially selecting hundreds of in-silico microbial metacommunities under identical conditions, we examine the fundamental limits of the two main breeding methods used so far, and prescribe modifications that significantly increase their power. We identify a range of directed evolution strategies that, particularly when applied in combination, are better suited for the top-down engineering of large, diverse, and stable microbial consortia. Our results emphasize that directed evolution allows an ecological structure-function landscape to be navigated in search for dynamically stable and ecologically and functionally resilient high-functioning communities.

scholarly journals International Sex Survey: Study protocol of a large, cross-cultural collaborative study in 45 countries

2021 ◽  
Author(s):  
Beáta Bőthe ◽  
Mónika Koós ◽  
Léna Nagy ◽  
Shane W. Kraus ◽  
Marc N. Potenza ◽  
...  
Keyword(s):  
Large Scale ◽  
Latent Profile Analysis ◽  
Self Report ◽  
Screening Tools ◽  
Sexuality Research ◽  
Equation Modeling ◽  
Modeling Framework ◽  
Theoretical Understanding ◽  
Empirically Supported ◽  
Wide Range

Abstract Background and aims Limitations of research into sexuality and compulsive sexual behavior disorder (CSBD) include the use of simplistic methodological designs and the absence of quality and unified measurements, empirically supported theoretical models, and large, collaborative studies between laboratories. We aim to fill these gaps with the International Sex Survey (ISS, http://internationalsexsurvey.org/). Methods The ISS is a large-scale, international, multi-lab, multi-language study using cross-sectional survey methods, involving more than 40 countries. Participants responding to advertisements complete a self-report, anonymous survey on a secure online platform. Collaborators from each country collect a community sample of adults with a minimum sample size of 2,000 participants with a gender ratio of approximately 50–50% men and women, including diverse individuals with respect to sexuality and gender. The ISS includes a wide range of sociodemographic questions and scales assessing a diverse set of sexual behaviors, pornography use, psychological characteristics, and potential comorbid disorders. Analyses are conducted within a structural equation modeling framework, including variable (e.g., measurement invariance tests) and person-centered approaches (e.g., latent profile analysis). Discussion and conclusions The ISS will provide well-validated, publicly available screening tools, helping to eliminate significant measurement issues in the field of sexuality research and health care. It will provide important insights to improve the theoretical understanding of CSBD as well as help to identify empirically supported treatment targets for prevention and intervention programs. Following open-science practices and making study materials open-access, the ISS may serve as a blueprint for future large-scale research in addiction and sexuality research.

scholarly journals Fundamental limits of electron and nuclear spin qubit lifetimes in an isolated self-assembled quantum dot

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
George Gillard ◽  
Ian M. Griffiths ◽  
Gautham Ragunathan ◽  
Ata Ulhaq ◽  
Callum McEwan ◽  
...  
Keyword(s):  
Quantum Dot ◽  
Spin Relaxation ◽  
Nuclear Spin ◽  
Operating Conditions ◽  
External Control ◽  
Spin Qubits ◽  
Fundamental Limits ◽  
Trade Offs ◽  
Wide Range ◽  
Spin Qubit

AbstractCombining external control with long spin lifetime and coherence is a key challenge for solid state spin qubits. Tunnel coupling with electron Fermi reservoir provides robust charge state control in semiconductor quantum dots, but results in undesired relaxation of electron and nuclear spins through mechanisms that lack complete understanding. Here, we unravel the contributions of tunnelling-assisted and phonon-assisted spin relaxation mechanisms by systematically adjusting the tunnelling coupling in a wide range, including the limit of an isolated quantum dot. These experiments reveal fundamental limits and trade-offs of quantum dot spin dynamics: while reduced tunnelling can be used to achieve electron spin qubit lifetimes exceeding 1 s, the optical spin initialisation fidelity is reduced below 80%, limited by Auger recombination. Comprehensive understanding of electron-nuclear spin relaxation attained here provides a roadmap for design of the optimal operating conditions in quantum dot spin qubits.

scholarly journals EXPRESS: Overcoming the Cold Start Problem of CRM using a Probabilistic Machine Learning Approach

2021 ◽  
pp. 002224372110329
Author(s):  
Nicolas Padilla ◽  
Eva Ascarza
Keyword(s):  
Machine Learning ◽  
Cold Start ◽  
Customer Relationship ◽  
Exponential Families ◽  
Modeling Framework ◽  
Wide Range ◽  
The Moment ◽  
Probabilistic Machine Learning ◽  
Marketing Actions ◽  
Cold Start Problem

The success of Customer Relationship Management (CRM) programs ultimately depends on the firm's ability to identify and leverage differences across customers — a very diffcult task when firms attempt to manage new customers, for whom only the first purchase has been observed. For those customers, the lack of repeated observations poses a structural challenge to inferring unobserved differences across them. This is what we call the “cold start” problem of CRM, whereby companies have difficulties leveraging existing data when they attempt to make inferences about customers at the beginning of their relationship. We propose a solution to the cold start problem by developing a probabilistic machine learning modeling framework that leverages the information collected at the moment of acquisition. The main aspect of the model is that it exibly captures latent dimensions that govern the behaviors observed at acquisition as well as future propensities to buy and to respond to marketing actions using deep exponential families. The model can be integrated with a variety of demand specifications and is exible enough to capture a wide range of heterogeneity structures. We validate our approach in a retail context and empirically demonstrate the model's ability at identifying high-value customers as well as those most sensitive to marketing actions, right after their first purchase.

scholarly journals Protein Engineering Approaches to Enhance Fungal Laccase Production in S. cerevisiae

2021 ◽  
Vol 22 (3) ◽  
pp. 1157
Author(s):  
Pablo Aza ◽  
Felipe de Salas ◽  
Gonzalo Molpeceres ◽  
David Rodríguez-Escribano ◽  
Iñigo de la Fuente ◽  
...  
Keyword(s):  
Protein Engineering ◽  
Directed Evolution ◽  
Signal Peptide ◽  
Laccase Activity ◽  
Laccase Production ◽  
Wide Range ◽  
Mating Factor ◽  
Conserved Amino Acids ◽  
Basidiomycete Fungi

Laccases secreted by saprotrophic basidiomycete fungi are versatile biocatalysts able to oxidize a wide range of aromatic compounds using oxygen as the sole requirement. Saccharomyces cerevisiae is a preferred host for engineering fungal laccases. To assist the difficult secretion of active enzymes by yeast, the native signal peptide is usually replaced by the preproleader of S. cerevisiae alfa mating factor (MFα1). However, in most cases, only basal enzyme levels are obtained. During directed evolution in S. cerevisiae of laccases fused to the α-factor preproleader, we demonstrated that mutations accumulated in the signal peptide notably raised enzyme secretion. Here we describe different protein engineering approaches carried out to enhance the laccase activity detected in the liquid extracts of S. cerevisiae cultures. We demonstrate the improved secretion of native and engineered laccases by using the fittest mutated α-factor preproleader obtained through successive laccase evolution campaigns in our lab. Special attention is also paid to the role of protein N-glycosylation in laccase production and properties, and to the introduction of conserved amino acids through consensus design enabling the expression of certain laccases otherwise not produced by the yeast. Finally, we revise the contribution of mutations accumulated in laccase coding sequence (CDS) during previous directed evolution campaigns that facilitate enzyme production.

scholarly journals A modeling study to inform screening and testing interventions for the control of SARS-CoV-2 on university campuses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ben Lopman ◽  
Carol Y. Liu ◽  
Adrien Le Guillou ◽  
Andreas Handel ◽  
Timothy L. Lash ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Disease Surveillance ◽  
Control Strategies ◽  
Transmission Model ◽  
University Administrators ◽  
Modeling Framework ◽  
University Campuses ◽  
School Year ◽  
Flexible Modeling ◽  
Resource Requirements

AbstractUniversity administrators face decisions about how to safely return and maintain students, staff and faculty on campus throughout the 2020–21 school year. We developed a susceptible-exposed-infectious-recovered (SEIR) deterministic compartmental transmission model of SARS-CoV-2 among university students, staff, and faculty. Our goals were to inform planning at our own university, Emory University, a medium-sized university with around 15,000 students and 15,000 faculty and staff, and to provide a flexible modeling framework to inform the planning efforts at similar academic institutions. Control strategies of isolation and quarantine are initiated by screening (regardless of symptoms) or testing (of symptomatic individuals). We explored a range of screening and testing frequencies and performed a probabilistic sensitivity analysis. We found that among students, monthly and weekly screening can reduce cumulative incidence by 59% and 87%, respectively, while testing with a 2-, 4- and 7-day delay between onset of infectiousness and testing results in an 84%, 74% and 55% reduction in cumulative incidence. Smaller reductions were observed among staff and faculty. Community-introduction of SARS-CoV-2 onto campus may be controlled with testing, isolation, contract tracing and quarantine. Screening would need to be performed at least weekly to have substantial reductions beyond disease surveillance. This model can also inform resource requirements of diagnostic capacity and isolation/quarantine facilities associated with different strategies.

Actual Challenges, Risks and Security Safety

2020 ◽  
Vol 1 (1) ◽  
pp. 65-83
Author(s):  
Božidar Forca ◽  
Dragoljub Sekulović ◽  
Igor Vukonjanski
Keyword(s):  
National Security ◽  
Modern World ◽  
Security Strategy ◽  
Theoretical Understanding ◽  
National Security Strategy ◽  
Security Challenges ◽  
Wide Range ◽  
The Subject ◽  
Almost All ◽  
The Relationship

Security is one of the most common terms in the modern world. This statement is supported by the fact that the term security is used in a wide range of areas. The subject of this paper is national security and the challenges, risks and threats to that security in contemporary international relations. The purpose of the work is twofold. First, to show the diversity of theoretical understanding of the term challenge, risk and threat by various authors. On the other hand, the overriding goal is to analyze the relationship to the challenges, risks and threats in different countries. When it comes to national security, challenges, risks and threats, most often, are identified in a document called the national security strategy. This document, as one of the highest in the hierarchy of political acts of every state, when it comes to security, is passed by almost all modern states of the world. The analysis of numerous national security strategies has revealed that it is possible to identify: 1) the challenges, risks and threats that appear in all strategies, 2) the challenges, risks and threats of security that appear in most strategies, and 3) the challenges, risks and threats of security which are country specific.

CONCEPTUAL DIRECTIONS OF THE TAXATION THEORIES DEVELOPMENT THROUGH THE REALIZING PRISM INTERESTS OF THE STATE AND TAXPAYERS

2021 ◽  
Vol 7 (1) ◽  
pp. 188-204
Author(s):  
Yulia G. TYURINA ◽  
Kristina A. BANNOVA
Keyword(s):  
Income Tax ◽  
The State ◽  
Personal Income ◽  
Point Of View ◽  
Theoretical Point ◽  
Personal Income Tax ◽  
State Budget ◽  
Theoretical Understanding ◽  
Direct Taxation ◽  
Wide Range

Nowadays, direct taxation of personal income is used in almost all countries of the world, and to this day there are various changes that shift the share of revenue from these taxes towards increasing the state budget. The significance of the personal income tax in economic policy is also due to the fact that it affects the interests of almost the entire population of the country. A variety of disputes constantly arise around the personal income tax, which can be explained by a wide range of taxpayers in various social strata. The ongoing transformations in the tax area predetermine the construction of the individuals taxation fair system as the fulfillment of one of the conditions for improving the living standards of the population. The relevance of the study lies in the need to reform the tax system in Russia, namely, the taxation of personal income, in order to implement the principle of social justice, as well as to satisfy the fiscal component of this tax, respectively, to fulfill the interests of participants in tax relations. The purpose of the article is a theoretical understanding of the conceptual directions of the taxation theories development through the prism of realizing the interests of the state and taxpayers in the taxation system of personal income. The subject of this research is the set of economic relations between the state and individuals, formed in the process of taxation of personal income in Russia. The methodological basis was the conceptual provisions of the theories of taxation, scientific methods and methods of analysis. The scientific novelty of the work lies in the fact that the results of the methodological analysis of the taxation theories development through the prism of realizing the state interests and taxpayers will make it possible to solve from a theoretical point of view the issue of interests balance achieving of all parties, which will contribute to the development of practical measures to achieve a decent standard of living for the population.

Modeling framework for IoT integration of building automation systems

2017 ◽  
Vol 65 (9) ◽  
Author(s):  
Daniel Schachinger ◽  
Andreas Fernbach ◽  
Wolfgang Kastner
Keyword(s):  
Web Services ◽  
Web Service ◽  
Building Automation ◽  
Modeling Framework ◽  
Seamless Integration ◽  
Automation Systems ◽  
Wide Range ◽  
Machine To Machine Communication ◽  
Machine Communication ◽  
The Internet Of Things

AbstractAdvancements within the Internet of Things are leading to a pervasive integration of different domains including also building automation systems. As a result, device functionality becomes available to a wide range of applications and users outside of the building automation domain. In this context, Web services are identified as suitable solution for machine-to-machine communication. However, a major requirement to provide necessary interoperability is the consideration of underlying semantics. Thus, this work presents a universal framework for tag-based semantic modeling and seamless integration of building automation systems via Web service-based technologies. Using the example of the KNX Web services specification, the applicability of this approach is pointed out.

scholarly journals BEAR-FP: A ROBUST FRAMEWORK FOR FLOORPLANNING

1992 ◽  
Vol 03 (01) ◽  
pp. 137-170 ◽  
Author(s):  
MASSOUD PEDRAM ◽  
ERNEST S. KUH
Keyword(s):  
Shape Function ◽  
Optimization Procedure ◽  
University Of California ◽  
Global Routing ◽  
Top Down ◽  
Function Computation ◽  
Wide Range ◽  
The University ◽  
Linear Assignment ◽  
Selection Of

This paper presents a hierarchical floorplanning approach for macrocell layouts which is based on the bottom-up clustering, shape function computation, and top-down floorplan optimization with integrated global routing and pin assignment. This approach provides means for specifying and techniques for satisfying a wide range of constraints (physical, topological, timing) and is, therefore, able to generate floorplans for a number of different layout styles. A systematic and efficient optimization procedure during the selection of suitable floorplan patterns that integrates floorplanning, global routing and pin assignment, a new pin assignment technique based on linear assignment and driven by the global routing solution and floorplan topology, and an effective timing-driven floorplanning scheme are among the other novel features of the floorplanner. These techniques have been incorporated in BEAR-FP, a macrocell layout system developed at the University of California, Berkeley. Results on various placement and floorplanning benchmarks are quite good.

scholarly journals Abundance and Sources of Atmospheric Halocarbons in the Eastern Mediterranean

2017 ◽  
Author(s):  
Fabian Schoenenberger ◽  
Stephan Henne ◽  
Matthias Hill ◽  
Martin K. Vollmer ◽  
Giorgos Kouvarakis ◽  
...  
Keyword(s):  
Western Europe ◽  
Atmospheric Transport ◽  
Eastern Mediterranean ◽  
Stratospheric Ozone ◽  
Regional Scale ◽  
Top Down ◽  
Inversion Domain ◽  
Hfc 134A ◽  
Wide Range ◽  
Hfc 152A

Abstract. A wide range of anthropogenic halocarbons is released to the atmosphere, contributing to stratospheric ozone depletion and global warming. Using measurements of atmospheric abundances for the estimation of halocarbon emissions on the global and regional scale has become an important top-down tool for emission validation in the recent past, but many populated and developing areas of the world are only poorly covered by the existing atmospheric halocarbon measurement network. Here we present six months of continuous halocarbon observations from Finokalia on the island of Crete in the Eastern Mediterranean. The gases measured are the hydrofluorocarbons (HFCs), HFC-134a (CH2FCF3), HFC-125 (CHF2CF3), HFC-152a (CH3CHF2) and HFC-143a (CH3CF3), and the hydrochlorofluorocarbons (HCFCs), HCFC-22 (CHClF2) and HCFC-142b (CH3CClF2). The Eastern Mediterranean is home to 250 million inhabitants, consisting of a number of developed and developing countries, for which different emission regulations exist under the Kyoto and Montreal Protocols. Regional emissions of halocarbons were estimated with Lagrangian atmospheric transport simulations and a Bayesian inverse modelling system, using measurements at Finokalia in conjunction with those from Advanced Global Atmospheric Gases Experiment (AGAGE) sites at Mace Head (Ireland), Jungfraujoch (Switzerland) and Monte Cimone (Italy). Measured peak mole fractions at Finokalia showed generally smaller amplitudes for HFCs than at the European AGAGE sites, except periodic peaks of HFC-152a, indicating strong upwind sources. Higher peak mole fractions were observed for HCFCs, suggesting continued emissions from nearby developing regions such as Egypt and the Middle East. For 2013, the Eastern Mediterranean inverse emission estimates for the four analysed HFCs and the two HCFCs were 14.7 (6.7–23.3) Tg CO2eq yr-1 and 9.7 (4.3–15.7) Tg CO2eq yr-1, respectively. These emissions contributed 17.3 % (7.9–27.4 %) and 53 % (23.5–86%) to the total inversion domain, which covers the Eastern Mediterranean as well as Central and Western Europe. Greek bottom-up HFC emissions reported to the UNFCCC were much smaller than our top-down estimates, whereas for Turkey our estimates agreed with UNFCCC-reported values for HFC-125 and HFC-143a, but were much and slightly smaller for HFC-134a and HFC-152a, respectively. Sensitivity estimates suggest an improvement of the a posteriori emission estimates, i.e. a reduction of the uncertainties by 40–80 %, compared to an inversion using only the existing Central European AGAGE observations.

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