Modeling circadian clocks: From equations to oscillations

2011 ◽  
Vol 6 (5) ◽  
pp. 699-711 ◽  
Author(s):  
Didier Gonze
Keyword(s):  
Genetic Network ◽  
Cellular Level ◽  
Circadian Clocks ◽  
Subsequent Paper ◽  
Molecular Models ◽  
Response Curves ◽  
Sustained Oscillations ◽  
Higher Eukaryotes ◽  
The Right ◽  
Selection Of

AbstractCircadian rhythms are generated at the cellular level by a small but tightly regulated genetic network. In higher eukaryotes, interlocked transcriptional-translational feedback loops form the core of this network, which ensures the activation of the right genes (proteins) at the right time of the day. Understanding how such a complex molecular network can generate robust, self-sustained oscillations and accurately responds to signals from the environment (such as light and temperature) is greatly helped by mathematical modeling. In the present paper we review some mathematical models for circadian clocks, ranging from abstract, phenomenological models to the most detailed molecular models. We explain how the equations are derived, highlighting the challenges for the modelers, and how the models are analyzed. We show how to compute bifurcation diagrams, entrainment, and phase response curves. In the subsequent paper, we discuss, through a selection of examples, how modeling efforts have contributed to a better understanding of the dynamics of the circadian regulatory network.

Ridogrel Inhibits Systemic and Renal Formation of Thromboxane A2 and Antagonizes Platelet Thromboxane A2/Prostaglandin Endoperoxide Receptors upon Chronic Administration to Man

1992 ◽  
Vol 68 (02) ◽  
pp. 214-220 ◽  
Author(s):  
C Weber ◽  
J R Beetens ◽  
F Tegtmeier ◽  
P Van Rooy ◽  
E Vercammen ◽  
...  
Keyword(s):  
Uric Acid ◽  
Potent Inhibitor ◽  
Ex Vivo ◽  
Thromboxane A2 ◽  
Chronic Administration ◽  
Response Curves ◽  
Clinically Significant ◽  
Synthase Inhibitor ◽  
The Right ◽  
Steady State Plasma Level

SummaryThe effects of ridogrel, a dual thromboxane A2 (TXA2) synthase inhibitor and TXA2/prostaglandin (PG) endoperoxide receptor antagonist, on systemic and renal production of prostaglandins and on platelet TXA2/PG endoperoxide receptors was evaluated upon chronic administration (300 mg b. i. d. orally, for 8 and 29 days) to man. Such a medication with ridogrel inhibits the systemic as well as the renal production of TXA2 as measured by the urinary excretion of 2,3-dinor-TXB2 and TXB2 respectively without inducing significant changes in systemic or renal PGI2 production. Simultaneously with the latter effects, the production of TXB2 by spontaneously coagulated whole blood ex vivo is inhibited (>99%) while that of PGE2 and PGF2α is largely increased. Administration of ridogrel causes a three- to five-fold shift to the right of concentration-response curves for U46619 in eliciting platelet aggregation; no tachyphylaxis is observed after 29 days of treatment in this respect. Apart from a reduction of serum uric acid levels with a concomitant increase in urinary uric acid excretion during the first days of treatment, no clinically significant changes in hematological, biochemical, hemodynamic and coagulation parameters occur during the 8 days or 29 days study. The study demonstrates that ridogrel is a potent inhibitor of the systemic as well as renal TXA2 synthase and an antagonist of platelet TXA2/PG endoperoxide receptor in man, covering full activity during 24 h at steady-state plasma level conditions without tachyphylaxis during 29 days of medication. The compound is well tolerated, at least during 1 month of administration.

PROBLEM ASPECTS OF THE IMPLEMENTATION OF CRIMINAL PROCEDURAL NORMS OF PROTECTION OF THE VICTIMS FROM CRIME

2020 ◽  
pp. 72-76
Author(s):  
Яна Валерьевна Самиулина
Keyword(s):  
Preventive Measure ◽  
Criminal Procedure ◽  
Legal Rights ◽  
Criminal Proceedings ◽  
Effective Mechanism ◽  
The Russian Federation ◽  
The Individual ◽  
The Right ◽  
To Receive ◽  
Selection Of

В настоящей статье предпринята попытка исследовать отдельные проблемные аспекты института потерпевшего в российском уголовном процессе. В этих целях подвергнуты анализу правовые нормы, регламентирующие его процессуальный статус. Раскрываются отдельные пробелы уголовно-процессуального законодательства в сфере защиты законных прав и интересов потерпевшего. Автор акцентирует внимание на том, что совершенствование уголовно-процессуального законодательства в части расширения правомочий потерпевшего по отстаиванию своих нарушенных преступлением прав следует продолжить. На основании проведенного исследования действующего законодательства в части регламентации прав потерпевшего от преступления предлагается расширить перечень получаемых им копий постановлений, указанных в п. 13 ч. 2 ст. 42 УПК РФ. Автор предлагает включить в перечень указанной законодательной нормы право получения потерпевшим копии постановления об избрании конкретного вида меры пресечения, избранного в отношении подозреваемого (обвиняемого). Для создания действенного механизма защиты интересов потерпевших от преступления юридических лиц предлагаем ч. 9 ст. 42 УПК РФ изложить в следующей редакции: «в случае признания потерпевшим юридического лица его процессуальное право в уголовном процессе осуществляет представляющий его профессиональный адвокат». This article attempts to investigate certain problematic aspects of the institution of the victim in the Russian criminal process. For this purpose, analyzed the individual norms governing his procedural status. Separate gaps of the criminal procedure legislation in the sphere of protection of the legal rights and interests of the victim are disclosed. The author emphasizes that the improvement of the criminal procedure legislation in terms of the extension of the victim’s authority to defend his rights violated by the crime should be continued. On the basis of the study of the current legislation regarding the regulation of the rights of the victim of a crime, it is proposed to expand the list of decisions received by him, referred to in paragraph 13, part 2 of article 42 Code of Criminal Procedure. The author proposes to include in the list of the indicated legislative norm the right to receive the victim a copy of the decision on the selection of a specific type of preventive measure, selected in relation to the suspect (accused). To create an effective mechanism for protecting the interests of legal entities victims of a crime, we offer part 9 of art. 42 of the Code of Criminal Procedure of the Russian Federation shall be reworded as follows: «if a legal entity is recognized as a victim, his procedural right in criminal proceedings is exercised by the professional lawyer representing him».

scholarly journals The Impact of Alkaloid-Producing Epichloë Endophyte on Forage Ryegrass Breeding: A New Zealand Perspective

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 158
Author(s):  
Colin Eady
Keyword(s):  
Seed Production ◽  
Health Issues ◽  
Abiotic Stressors ◽  
Livestock Health ◽  
The Right ◽  
The Impact ◽  
The Relationship ◽  
And Storage ◽  
Selection Of ◽  
Epichloë Endophyte

For 30 years, forage ryegrass breeding has known that the germplasm may contain a maternally inherited symbiotic Epichloë endophyte. These endophytes produce a suite of secondary alkaloid compounds, dependent upon strain. Many produce ergot and other alkaloids, which are associated with both insect deterrence and livestock health issues. The levels of alkaloids and other endophyte characteristics are influenced by strain, host germplasm, and environmental conditions. Some strains in the right host germplasm can confer an advantage over biotic and abiotic stressors, thus acting as a maternally inherited desirable ‘trait’. Through seed production, these mutualistic endophytes do not transmit into 100% of the crop seed and are less vigorous than the grass seed itself. This causes stability and longevity issues for seed production and storage should the ‘trait’ be desired in the germplasm. This makes understanding the precise nature of the relationship vitally important to the plant breeder. These Epichloë endophytes cannot be ‘bred’ in the conventional sense, as they are asexual. Instead, the breeder may modulate endophyte characteristics through selection of host germplasm, a sort of breeding by proxy. This article explores, from a forage seed company perspective, the issues that endophyte characteristics and breeding them by proxy have on ryegrass breeding, and outlines the methods used to assess the ‘trait’, and the application of these through the breeding, production, and deployment processes. Finally, this article investigates opportunities for enhancing the utilisation of alkaloid-producing endophytes within pastures, with a focus on balancing alkaloid levels to further enhance pest deterrence and improving livestock outcomes.

Evaluation of β-Adrenerglc Blocking Agents in Presence of Adrenergic Tone

1972 ◽  
Vol 50 (5) ◽  
pp. 381-388
Author(s):  
Victor Elharrar ◽  
Reginald A. Nadeau
Keyword(s):  
Dose Response ◽  
Sinus Node ◽  
Stellate Ganglion ◽  
Sodium Pentobarbital ◽  
Response Curves ◽  
Chronotropic Response ◽  
Blocking Agents ◽  
Sinus Node Artery ◽  
Anesthetized Dogs ◽  
The Right

The importance of the level of adrenergic tone in the determination of the dose–response curve to noradrenaline (NA) and in the evaluation of β-adrenergic blocking agents was studied in open-chest sodium pentobarbital anesthetized dogs by injecting drugs directly into the sinus node artery. Changes in the level of adrenergic tone by stimulating the right stellate ganglion resulted in variation of the observed chronotropic response to NA and of its ED50. The chronotropic responses were corrected by taking into account the underlying adrenergic tone. The negative chronotropic effect of dl-propranolol (1 and 10 μg) appeared to be related to its β-blocking properties and not to its quinidine-like effects as shown by the lack of effect of d-propranolol injected at the same doses. The magnitude of the negative chronotropic effects of 10 μg of propranolol and 100 μg of practolol, oxprenolol, and sotalol was shown to be related to the initial heart rate and consequently to the level of adrenergic tone. The comparison of these four β-blocking agents was carried out on corrected dose-response curves to NA. Their relative potencies were found to be: propranolol > oxprenolol > practolol > sotalol, corresponding to ratios of 1, [Formula: see text], [Formula: see text], and [Formula: see text]

Antagonist properties of arylaminopyridazine GABA derivatives at the Ascaris muscle GABA receptor

1991 ◽  
Vol 159 (1) ◽  
pp. 149-164
Author(s):  
A. H. Duittoz ◽  
R. J. Martin
Keyword(s):  
Gabaa Receptor ◽  
Binding Sites ◽  
Gaba Receptor ◽  
Dissociation Constants ◽  
Ascaris Suum ◽  
Antagonistic Activity ◽  
Maximal Response ◽  
Response Curves ◽  
Gaba Derivatives ◽  
The Right

1. In a previous study, it was shown that the potency order for two arylamino-pyridazine derivatives, SR95531 and SR95103, was different in Ascaris suum when compared to vertebrate preparations. SR95531, the most potent analogue at the vertebrate GABAA receptor, was found to be very weak at antagonizing GABA responses in Ascaris, but SR95103, approximately 20 times less potent than SR95531 in vertebrate preparations, was more potent than SR95531 in Ascaris. These results suggested the existence of different accessory binding sites at the Ascaris GABA receptor. 2. To test this hypothesis, the effects of a series of arylaminopyridazine derivatives of GABA on the GABA response in Ascaris suum muscle were investigated using a two-microelectrode current-clamp technique. 3. The results showed that SR42627, a potent antagonist at the GABAA receptor, was one of the weakest analogues in Ascaris muscle. In contrast, SR95132, virtually inactive in vertebrate preparations, was equipotent to SR95103, the most potent analogue of the series in Ascaris muscle. 4. The three most potent analogues in Ascaris, SR95103, SR95132 and SR42666, displace GABA dose-response curves to the right without decreasing the maximal response. The modified Schild plots for these compounds are consistent with a competitive mechanism involving two molecules of GABA and only one molecule of antagonist interacting with the receptor. The estimated dissociation constants for SR95103, SR95132 and SR42666 are, respectively, 64, 65 and 105 mumol l-1. 5. Structure-activity relationships for this series of compounds were examined in Ascaris and compared to those in vertebrates. Substitution on the pyridazine ring in the 4-position, while detrimental for the antagonist potency at the vertebrate GABAA receptor, appears to be a prerequisite for antagonistic activity on the Ascaris muscle GABA receptor. These results are interpreted in terms of the accessory binding site theory of Ariens, and suggest the existence of different accessory binding sites on the Ascaris GABA receptor.

Compressed acoustic sealing foam optimization investigation using statistical approach

2021 ◽  
Vol 263 (1) ◽  
pp. 4955-4961
Author(s):  
Mathieu Gontier ◽  
Barbara Romeyns
Keyword(s):  
Porous Materials ◽  
Statistical Approach ◽  
Complete System ◽  
Statistical Techniques ◽  
Industrial Equipment ◽  
Acoustic Performance ◽  
Material Characteristics ◽  
Sealing Performance ◽  
The Right ◽  
Selection Of

In industry segments such as automotive and industrial equipment the use of compressed porous materials is well known to improve the global acoustic performance of the complete system. Such porous materials should be designed in a specific way in order to reach a significant acoustic sealing performance at different compression rates. Unfortunately, there are no standard measurement procedures nor predefined material characteristics that allow the selection of the right material with the optimal acoustic performance. The main goal of this research is to link acoustic performance of compressed porous materials with intrinsic material characteristics using statistical techniques.

A Spectral Optimization Algorithm for Multi-Objective Prototype Selection

1995 ◽  
Author(s):  
Andy Dong ◽  
Alice M. Agogino
Keyword(s):  
Optimization Algorithm ◽  
Parametric Design ◽  
Selection Process ◽  
Objective Evaluation ◽  
Design Synthesis ◽  
Multi Objective ◽  
Trade Offs ◽  
Spectral Optimization ◽  
The Right ◽  
Selection Of

Abstract In design synthesis, engineering prototypes make an ideal representation medium for preliminary designs. Unlike parametric design wherein a pre-specified design is parametrically varied, design synthesis demands artistic creativity and engineering experience to transform the previously known components, relationships and designs into a new form. The process compels the designer to ascertain which prototypes will, in some sense, best satisfy the design task. The challenge in this assignment lies in selecting the “right” design prototype. This selection process typically entails an objective evaluation of different designs that perform the same functions or have similar intended behavior and comparing trade-offs between alternate designs. This paper introduces a multi-objective spectral optimization algorithm for the selection of design prototypes based upon their functional representations. The optimization algorithm returns an index of rank, scoring the functional similarity of the proposed design to the goal design. Two illustrative examples apply the algorithm to the selection of a heat fin and beam.

Prophylaxis of obstetric and perinatal pathology at women with pathological increase of body weight during pregnancy

2018 ◽  
pp. 7-79
Author(s):  
S.Yu. Vdovichenko ◽  
◽  
T.D. Fakhrutdinova ◽  
Keyword(s):  
Health Care ◽  
Body Weight ◽  
Pregnant Women ◽  
Key Words ◽  
Perinatal Outcomes ◽  
Perinatal Complications ◽  
Perinatal Pathology ◽  
Fetoplacental Complex ◽  
The Right ◽  
Selection Of

The objective: depression of obstetric and perinatal complications at pregnant women with pathological increase of body weight during pregnancy on the basis of studying of clinical-functional, endocrinologic, metabolic, morphological features of condition of fetoplacental complex and development of advanced algorithm of treatment-and-prophylactic actions. Materials and methods. We conducted examination of 264 patients who consisted on the account concerning pregnancy in female consultations of Kiev. By a method of selection of 178 women were included in retrospective research and 86 – in prospective. The main group was made by 39 pregnant women with whom led individual discussions, control – 142 women, that received traditional references in female consultation. Results. Use of the algorithm improved by us allows to improve obstetric (decrease of frequency of a preeclampsia by 12.3%; anomalies of a patrimonial deyalnost for 8.4%) and perinatal outcomes (depression of level of an asphyxia at a delivery for 9.4% and post-natal adaptation for 7.8%) deliveries of women with an excessive increase of body weight during pregnancy. Conclusion. The received results grant the right to recommend the algorithm improved by us for wide use in practical health care. Key words: obstetric and perinatal pathology, pathological increase of body weight, prophylaxis.

scholarly journals Pharmacologically mechanistic basis for the traditional uses of Rumex acetosa in gut motility disorders and emesis

2015 ◽  
Vol 10 (3) ◽  
pp. 548 ◽  
Author(s):  
Musaddique Hussain ◽  
Shahid Masood Raza ◽  
Khalid Hussain Janbaz
Keyword(s):  
Rumex Acetosa ◽  
Response Curves ◽  
Motility Disorders ◽  
Traditional Uses ◽  
Antiemetic Activity ◽  
Rabbit Jejunum ◽  
Mechanistic Basis ◽  
The Right

<p class="Abstract"><em>In vitro</em> and<em> in vivo</em> studies were undertaken to evaluate the pharmacologically mechanistic background to validate the traditional uses of <em>Rumex acetosa</em> in the treatment of emesis and gastrointestinal motility disorders such as constipation and diarrhea. In rabbit jejunum preparation, methanolic extract of <em>R. acetosa</em> (0.01-1.0 mg/mL) caused a transient spasmogenic effect, followed by the spasmolytic effect (3-10 mg/mL). In presence of atropine, spasmogenic effect was blocked while spasmolytic effect was emerged, suggesting that spasmogenic effect was mediated through activation of muscarinic receptors. Extract inhibited the K<sup>+ </sup>(80 mM)-induced contraction, suggesting Ca<sup>2+</sup>-cha-nnel blockade, which was further confirmed when pretreatment of tissue with extract shifted the Ca<sup>2+ </sup>concentration-response curves to the right, similarly as verapamil.<em> R. acetosa</em> also exhibited the significant antiemetic activity (p&lt;0.05) against different emetogenic stimuli, when compared with chlorpromazine. This study confirms the presence of gut modulator (spasmogenic and spasmolytic) and antiemetic activates, validating its traditional uses.</p><p> </p>

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