1980 Preface * 1999 Preface * 1999 Acknowledgements * Introduction * 1 Circular Logic * 2 Phase Singularities (Screwy Results of Circular Logic) * 3 The Rules of the Ring * 4 Ring Populations * 5 Getting Off the Ring * 6 Attracting Cycles and Isochrons * 7 Measuring the Trajectories of a Circadian Clock * 8 Populations of Attractor Cycle Oscillators * 9 Excitable Kinetics and Excitable Media * 10 The Varieties of Phaseless Experience: In Which the Geometrical Orderliness of Rhythmic Organization Breaks Down in Diverse Ways * 11 The Firefly Machine 12 Energy Metabolism in Cells * 13 The Malonic Acid Reagent ('Sodium Geometrate') * 14 Electrical Rhythmicity and Excitability in Cell Membranes * 15 The Aggregation of Slime Mold Amoebae * 16 Numerical Organizing Centers * 17 Electrical Singular Filaments in the Heart Wall * 18 Pattern Formation in the Fungi * 19 Circadian Rhythms in General * 20 The Circadian Clocks of Insect Eclosion * 21 The Flower of Kalanchoe * 22 The Cell Mitotic Cycle * 23 The Female Cycle * References * Index of Names * Index of Subjects

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/596B270197FE27DE5FABB598B6210622/S0025557200150892a.pdf/div-class-title-span-class-italic-the-geometry-of-biological-time-span-by-a-t-winfree-pp-544-dm68-corrected-second-printing-1990-isbn-3-540-52528-9-springer-div.pdf

The geometry of biological time , by A. T. Winfree. Pp 544. DM68. Corrected Second Printing 1990. ISBN 3-540-52528-9 (Springer)

The emergence of publications on extracellular RNA (exRNA) and extracellular vesicles (EV) has highlighted the potential of these molecules and vehicles as biomarkers of disease and therapeutic targets. These findings have created a paradigm shift, most prominently in the field of oncology, prompting expanded interest in the field and dedication of funds for EV research. At the same time, understanding of EV subtypes, biogenesis, cargo and mechanisms of shuttling remains incomplete. The techniques that can be harnessed to address the many gaps in our current knowledge were the subject of a special workshop of the International Society for Extracellular Vesicles (ISEV) in New York City in October 2012. As part of the “ISEV Research Seminar: Analysis and Function of RNA in Extracellular Vesicles (evRNA)”, 6 round-table discussions were held to provide an evidence-based framework for isolation and analysis of EV, purification and analysis of associated RNA molecules, and molecular engineering of EV for therapeutic intervention. This article arises from the discussion of EV isolation and analysis at that meeting. The conclusions of the round table are supplemented with a review of published materials and our experience. Controversies and outstanding questions are identified that may inform future research and funding priorities. While we emphasize the need for standardization of specimen handling, appropriate normative controls, and isolation and analysis techniques to facilitate comparison of results, we also recognize that continual development and evaluation of techniques will be necessary as new knowledge is amassed. On many points, consensus has not yet been achieved and must be built through the reporting of well-controlled experiments. Keywords: extracellular vesicle; exosome; microvesicle; standardization; isolation (Published: 27 May 2013) Citation: Journal of Extracellular Vesicles 2013, 2 : 20360 - http://dx.doi.org/10.3402/jev.v2i0.20360

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Standardization of sample collection, isolation and analysis methods in extracellular vesicle research

To determine whether the onset of myocardial infarction occurs randomly throughout the day, we analyzed the time of onset of pain in 2999 patients admitted with myocardial infarction. A marked circadian rhythm in the frequency of onset was detected, with a peak from 6 a.m. to noon (P<0.01). In 703 of the patients, the time of the first elevation in the plasma creatine kinase MB (CK-MB) level could be used to time the onset of myocardial infarction objectively. CK-MB—estimated timing confirmed the existence of a circadian rhythm, with a threefold increase in the frequency of onset of myocardial infarction at peak (9 a.m.) as compared with trough (11 p.m.) periods. The circadian rhythm was not detected in patients receiving beta-adrenergic blocking agents before myocardial infarction but was present in those not receiving such therapy. If coronary arteries become vulnerable to occlusion when the intima covering an atherosclerotic plaque is disrupted, the circadian timing of myocardial infarction ma...

Circadian variation in the frequency of onset of acute myocardial infarction

Three experience-sampling studies explored the distributions of Big-Five-relevant states (behavior) across 2 to 3 weeks of everyday life. Within-person variability was high, such that the typical individual regularly and routinely manifested nearly all levels of all traits in his or her everyday behavior. Second, individual differences in central tendencies of behavioral distributions were almost perfectly stable. Third, amount of behavioral variability (and skew and kurtosis) were revealed as stable individual differences. Finally, amount of within-person variability in extraversion was shown to reflect individual differences in reactivity to extraversion-relevant situational cues. Thus, decontextualized and noncontingent Big-Five content is highly useful for descriptions of individuals' density distributions as wholes. Simultaneously, contextualized and contingent personality units (e.g., conditional traits, goals) are needed for describing the considerable within-person variation.

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Toward a structure- and process-integrated view of personality: Traits as density distributions of states.

This article updates the ethical standards and methods for the conduct of high-quality animal and human biological rhythm research, which should be especially useful for new investigators of the rhythms of life. The editors of Chronobiology International adhere to and endorse the Code of Conduct and Best Practice Guidelines of the Committee On Publication Ethics (COPE), which encourages communication of such updates at regular intervals in the journal. The journal accepts papers representing original work, no part of which was previously submitted for publication elsewhere, except as brief abstracts, as well as in-depth reviews. The majority of research papers published in Chronobiology International entails animal and human investigations. The editors and readers of the journal expect authors of submitted manuscripts to have made an important contribution to the research of biological rhythms and related phenomena using ethical methods/procedures and unbiased, accurate, and honest reporting of findings. Authors of scientific papers are required to declare all potential conflicts of interest. The journal and its editors endorse compliance of investigators to the Guide for the Care and Use of Laboratory Animals of the Institute for Laboratory Animal Research of the National Research Council, relating to the conduct of ethical research on laboratory and other animals, and the principles of the Declaration of Helsinki of the World Medical Association, relating to the conduct of ethical research on human beings. The peer review of manuscripts by Chronobiology International thus includes judgment as to whether or not the protocols and methods conform to ethical standards. Authors are expected to show mastery of the basic methods and procedures of biological rhythm research and proper statistical assessment of data, including the appropriate application of time series data analyses, as briefly reviewed in this article. The journal editors strive to consistently achieve high standards for the research of original and review papers reported in Chronobiology International, and current examples of expectations are presented herein.

Ethics and methods for biological rhythm research on animals and human beings

Differing paradecadal cycles, semidecadal/decadal amplitude ratios and vascular variability anomalies in the physiology of a physician-scientist

Increased sleep debt associated with more math errors in residents during on-call rotations

BACKGROUND Tumor markers such as CA130 can be determined in human whole saliva. Saliva represents an attractive body fluid for longitudinal studies. MATERIALS AND METHODS CA130 was determined in parotid saliva from 8 rats fed different diets, with or without autonomic denervation. RESULTS CA130 could be determined in parotid saliva of rats, irrespective of diet and/or autonomic denervation. Whether the numerical decrease in CA130 observed after autonomic denervation is statistically significant requires further work. CONCLUSIONS Since salivary CA130 has been shown to decrease following treatment with anti-cancer drugs in humans, the ability to determine this tumor marker in rat saliva opens new opportunities for optimizing cancer chronotherapy in the experimental laboratory.

Salivary CA130 with and without unilateral autonomic parotid denervation of rats fed different diets.

Chronomics, the mapping of broad time structures (chronomes), provides the indispensable control whether studies aim at examining the effect of a given intervention such as dietary restriction, at optimizing the timing of administration of treatment, or at assessing an elevated risk of developing a disease such as cancer. An increase in circadian amplitude exceeding any effect on the mean is likely to yield controversial results from single spot checks. An analog of the adrenocorticotropic hormone (ACTH 1–17), administered in the evening may help patients with rheumatoid arthritis, but may be ineffective when given around awakening. A daytime single sample of prolactin may not be discriminatory in assessing breast cancer risk when large differences are found during the rest span. The merits of assessing peptide chronomics are perhaps best illustrated by the facts that a peptide drug may have a major effect at one circadian stage but not at another, that a major effect on a polypeptide may be exerted again at one circadian stage but not at another, and that, by the design and the software of chronomics, relatively small numbers of patients are needed to validate such effects by inferential statistics.

CHAPTER 213 – Peptide Chronomics

To introduce the study of physiologic urinary rhythms into secondary education, six girls and 11 boys, 14-18 years of age, collected urine at about 3-hr intervals for 24 hr. The volume and the excretion in urine of creatinine, potassium, and sodium were determined. Blood pressure was measured during the same 24-hr span to teach the students some elements of chronobiologic sampling and analysis in the context of evaluating the risk of developing a high blood pressure later in life. Herein, we examine on urinary excretory rates whether dynamic chronobiologic endpoints such as the amplitude (A) and/or acrophase (phi) may complement the more static mesor (M) in distinguishing groups of adolescents. In a comparison of the two sexes, dynamic characteristics of the urinary excretion of sodium and of the ratio of sodium/potassium do not separate the two groups, while the M does so. The reverse holds true for the excretion of potassium. In the case of urinary creatinine, the circadian A in itself is an index suggesting a "sex" difference; whereas in urinary volume, the M alone, and to a lesser extent the combination of (M, A, phi), yields a P value below the 5% level. The groups are rather small and heterogeneous; a study of ethnicity is beyond our scope. These qualifications notwithstanding, results indicate the need for testing multiple chronobiologic characteristics in comparing groups whether one's interest in the future relates to ethnicity, sex, or other factors. Such studies of urinary rhythms of high-school students serve for instruction and research and to instill responsibility for self-help in preventive health care.

Erhard Haus

Papers

Differing paradecadal cycles, semidecadal/decadal amplitude ratios and vascular variability anomalies in the physiology of a physician-scientist

Increased sleep debt associated with more math errors in residents during on-call rotations

Salivary CA130 with and without unilateral autonomic parotid denervation of rats fed different diets.

CHAPTER 213 – Peptide Chronomics

Circadian urinary characteristics of adolescents: sensitive dynamic indices complement mean values as new physiologic endpoints.