A functional context for heterogeneity of the circadian clock in cells

Characterization of circadian systems at the organism level—a top-down approach—has led to definition of unifying properties, a hallmark of the science of chronobiology. The next challenge is to use a bottom-up approach to show how the molecular workings of the cellular circadian clock work as building blocks of those properties. We review new studies, including a recently published PLOS Biology paper by Nikhil and colleagues, that show how programmed but also stochastic generation of variation in cellular circadian period explain important adaptive features of entrained circadian phase.

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Integracja w dezintegracji i dezintegracja w integracji: determinanty mechanizmów integracyjnych w Unii Europejskiej

10.31338/1641-2478pe.3.17.1 ◽

2018 ◽

pp. 10-37

Author(s):

Barbara Curyło

Keyword(s):

European Union ◽

The European Union ◽

Top Down ◽

Modus Operandi ◽

Bottom Up ◽

Differentiated Integration ◽

Integration Mechanisms ◽

Strategic Issue ◽

Definition Of ◽

The Eu

In the discussion on the future of the EU, the topic of differentiated integration has become a strategic issue, with different variants beginning to appear as modus operandi of the European Union, which has become a subject of controversy among Member States. Significantly, the debate on differentiated integration began to be accompanied by reflections on disintegration. This article attempts to define disintegration on the assumption that it should be defined through the prism of integration, and that such a defining process can not be limited to concluding a one-way contrast between disintegration versus integration and vice versa. This is due to the assumption that the European Union is a dichotomous construct in which integration and disintegration mutually exclude and complement each other. This dichotomy is most evident in the definition of integration and disintegration through the prism of Europeanisation top-down and bottom-up processes that generate, reveal, visualize, stimulate integration mechanisms what allows to diagnose their determinants.

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Ambivalences of populism: The case of Catalan independentism

Social Science Information ◽

10.1177/0539018418811685 ◽

2018 ◽

Vol 57 (4) ◽

pp. 573-587 ◽

Cited By ~ 3

Author(s):

Daniel Gamper Sachse

Keyword(s):

Social Mobilization ◽

Top Down ◽

Bottom Up ◽

Democratic Experience ◽

Procedural Safeguards

Most of the Spanish media have portrayed Catalan independentism as nationalism and populism. This article argues that this political and social mobilization does not fit into the usual definitions of populism as anti-elitist, anti-liberal and anti-pluralistic movement. Catalan independentism is here interpreted by stressing its democratic features, namely as a form of democratic populism: horizontally organized, and critical of procedural safeguards and counter-majoritarian powers. The popular organization of the referendum on 1 October 2017 and the vigorous democratic experience by almost half of the population of Catalonia allow for a characterization of this populism as a hybrid phenomenon that includes bottom-up and top-down dynamics, thereby contrasting with the usual leader-centred understanding of populism.

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Comparative Environmental Law

The Oxford Handbook of Comparative Environmental Law ◽

10.1093/law/9780198790952.003.0001 ◽

2019 ◽

pp. 2-34

Author(s):

Jorge E. Viñuales

Keyword(s):

Environmental Law ◽

Comparative Method ◽

Comparative Law ◽

Building Blocks ◽

Top Down ◽

Conceptual Approach ◽

Research Project ◽

Bottom Up ◽

Present Volume ◽

Functionalist Approach

This volume examines the building blocks of environmental law across different jurisdictions. More specifically, it provides a cartography of environmental law, with a focus on its underlying logic, main arrangements and their variations, and how it is embedded within the broader legal arrangements developed to tackle other questions. In this context, this preliminary chapter provides an overview of the comparative method as it applies to the overall research project leading to the present volume. It discusses descriptive and evolutionary approaches, the conceptual approach, the functionalist approach, the factual approach, legal formants, the contextualist approach, and legal transplants. It then considers a range of methodologies proposed by comparative law experts, including the bottom-up functionalism and top-down functionalism, before explaining the methodology used for the organization of this book. The chapter concludes by summarizing a tentative structure of comparative environmental law as a single overall technology.

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Characterization of Human Sperm Protamine Proteoforms through a Combination of Top-Down and Bottom-Up Mass Spectrometry Approaches

Journal of Proteome Research ◽

10.1021/acs.jproteome.9b00499 ◽

2019 ◽

Vol 19 (1) ◽

pp. 221-237 ◽

Cited By ~ 3

Author(s):

Ada Soler-Ventura ◽

Marina Gay ◽

Meritxell Jodar ◽

Mar Vilanova ◽

Judit Castillo ◽

...

Keyword(s):

Mass Spectrometry ◽

Human Sperm ◽

Top Down ◽

Bottom Up

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0433 Targeting Light Sensitivity Parameters to Optimize Circadian Phase Predictions

SLEEP ◽

10.1093/sleep/zsaa056.430 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A166-A166

Author(s):

J E Stone ◽

E M McGlashan ◽

S W Cain ◽

A J Phillips

Keyword(s):

Sensitivity Analysis ◽

Circadian Clock ◽

Mean Absolute Error ◽

Light Response ◽

Absolute Error ◽

Light Sensitivity ◽

Model Parameters ◽

Circadian Period ◽

Individual Level ◽

Circadian Phase

Abstract Introduction Existing models of the human circadian clock accurately predict phase at group-level but not at individual-level. Interindividual variability in light sensitivity is not currently accounted for in these models and may be a practical approach to improving individual-level predictions. Using the gold-standard predictive model, we (i) identified whether varying light sensitivity parameters produces meaningful changes in predicted phase in field conditions; and (ii) tested whether optimizing parameters can significantly improve accuracy of circadian phase prediction. Methods Healthy participants (n=12, 7 women, aged 18-26) underwent continuous light and activity monitoring for 3 weeks (Actiwatch Spectrum). Salivary dim light melatonin onset (DLMO) was measured each week. A model of the human circadian clock and its response to light was used to predict the three weekly DLMO times using the individual’s light data. A sensitivity analysis was performed varying three model parameters within physiological ranges: (i) amplitude of the light response [p]; (ii) advance vs. delay bias of the light response [K]; and (iii) intrinsic circadian period [tau]. These parameters were then fitted using least squares estimation to obtain optimal predictions of DLMO for each individual. Accuracy was compared between optimized parameters and default parameters. Results The default model predicted DLMO with mean absolute error of 1.02h. Sensitivity analysis showed the average range of variation in predicted DLMOs across participants was 0.65h for p, 4.28h for K and 3.26h for tau. Fitting parameters independently, we found mean absolute error of 0.85h for p, 0.71h for K and 0.75h for tau. Fitting p and K together reduced mean absolute error to 0.57h. Conclusion Light sensitivity parameters capture similar or greater variability in phase as intrinsic circadian period, indicating they are a viable option for individualising circadian phase predictions. Future prospective work is needed using measures of light sensitivity to validate this approach. Support N/A

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Characterization of Mustard 2S Albumin Allergens by Bottom-up, Middle-down, and Top-down Proteomics: A Consensus Set of Isoforms of Sin a 1

Journal of Proteome Research ◽

10.1021/pr5012262 ◽

2015 ◽

Vol 14 (3) ◽

pp. 1547-1556 ◽

Cited By ~ 19

Author(s):

Marlene Hummel ◽

Tina Wigger ◽

Jens Brockmeyer

Keyword(s):

Top Down ◽

2S Albumin ◽

Bottom Up

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Perspective: Validation—What Does It Mean?

Journal of Fluids Engineering ◽

10.1115/1.3077134 ◽

2009 ◽

Vol 131 (3) ◽

Cited By ~ 35

Author(s):

Patrick J. Roache

Keyword(s):

Fluid Dynamics ◽

Computational Fluid Dynamics ◽

Top Down ◽

Bottom Up ◽

Definition Of ◽

Journal Policies

Ambiguities, inconsistencies, and recommended interpretations of the commonly cited definition of validation for computational fluid dynamics codes/models are examined. It is shown that the definition-deduction approach is prone to misinterpretation, and that bottom-up descriptions rather than top-down legalistic definitions are to be preferred for science-based engineering and journal policies, though legalistic definitions are necessary for contracts.

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Visual Illusions?

10.1093/acprof:oso/9780199794607.003.0008 ◽

2017 ◽

Cited By ~ 1

Author(s):

Jan Koenderink

Keyword(s):

Partial Order ◽

Visual Illusions ◽

Formal Structure ◽

Top Down ◽

Bottom Up ◽

Biological Approach ◽

Definition Of

The very definition of “illusion” is elusive. Various distinct ontologies are considered. The concept is tightly bound to the understanding of reality, awareness, “God’s eye,” objectivity, subjectivity, emphatic relations, and several others. Here the distinctions between “illusion,” “ambiguity, “delusion,” and “deception,” are clarified. The very notion of illusion is closely tied to conceptual approaches to mind. Especially the dichotomy between a top-down “controlled hallucination” and a bottom-up “inverse physics” approach accounts for much confusion in the literature. It is suggested that a thoroughly biological approach might be preferable. In such an approach, experimental psychobiology would be a special sub-branch—devoted to the genus homo—of ethology. Does this help to impose a formal structure, such as a partial order, on the zoo of illusions as we know them? Unfortunately, not really. At this moment in history, we are still far from such a reasoned inventory.

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