23 research outputs found
On the dynamics of the adenylate energy system: homeorhesis vs homeostasis.
Biochemical energy is the fundamental element that maintains both the adequate turnover of the biomolecular structures and the functional metabolic viability of unicellular organisms. The levels of ATP, ADP and AMP reflect roughly the energetic status of the cell, and a precise ratio relating them was proposed by Atkinson as the adenylate energy charge (AEC). Under growth-phase conditions, cells maintain the AEC within narrow physiological values, despite extremely large fluctuations in the adenine nucleotides concentration. Intensive experimental studies have shown that these AEC values are preserved in a wide variety of organisms, both eukaryotes and prokaryotes. Here, to understand some of the functional elements involved in the cellular energy status, we present a computational model conformed by some key essential parts of the adenylate energy system. Specifically, we have considered (I) the main synthesis process of ATP from ADP, (II) the main catalyzed phosphotransfer reaction for interconversion of ATP, ADP and AMP, (III) the enzymatic hydrolysis of ATP yielding ADP, and (IV) the enzymatic hydrolysis of ATP providing AMP. This leads to a dynamic metabolic model (with the form of a delayed differential system) in which the enzymatic rate equations and all the physiological kinetic parameters have been explicitly considered and experimentally tested in vitro. Our central hypothesis is that cells are characterized by changing energy dynamics (homeorhesis). The results show that the AEC presents stable transitions between steady states and periodic oscillations and, in agreement with experimental data these oscillations range within the narrow AEC window. Furthermore, the model shows sustained oscillations in the Gibbs free energy and in the total nucleotide pool. The present study provides a step forward towards the understanding of the fundamental principles and quantitative laws governing the adenylate energy system, which is a fundamental element for unveiling the dynamics of cellular life
OPTOGENETIC GUIDE RNA PRODUCTION FOR SPATIOTEMPORAL REGULATION OF CRISPR/CAS SYSTEMS
OPTOGENETIC GUIDE RNA PRODUCTION FOR SPATIOTEMPORAL REGULATION OF CRISPR/CAS SYSTEM
Hanging in there: Prenatal origins of antigravity homeostasis in humans
All life on Earth must find a way to manage the continuous perturbation of
gravity. From birth, and even before, humans exhibit effortful antigravity work
to enact bodily, postural and behavioural form despite gravity. Indeed,
observable antigravity behaviour is a standard diagnostic indicator of neonatal
sensorimotor health. Antigravity behaviour has been investigated extensively in
its biomechanical details. Yet its motivational structure has not been a focus
of research. What drives the human body to expend energy on this effortful
behaviour? It is widely understood that thermic homeostasis in humans is
organised around conserving core body temperature at a set-point of
36.5-37.5oC. There is currently no equivalent concept of a general homeostatic
set-point driving antigravity effort. In this theoretical paper, we aim to
establish such a concept. We make the case that the core developmental
set-point for human antigravity homeostasis is neutral buoyancy (gravity and
buoyant force are balanced), which is afforded to the foetus by its
approximately equi-dense amniotic fluid medium in utero. We argue that
postnatally, the general task of human antigravity balance is to emulate the
conditions of neutral buoyancy, based upon prenatal experience thereof. Our aim
in this paper is to sketch a high-level outline of a novel characterisation of
antigravity balance as conservative homeostasis, and lay out some implications
and predictions of this model, with the intention of spurring wider research
and discussion on this hitherto little explored topic.
Keywords: antigravity, posture, homeostasis, prenatal, buoyancy, density,
fetus, foetusComment: 19 pages (including references) Zero figure
Quantitative analyses in basic, translational and clinical biomedical research: metabolism, vaccine design and preterm delivery prediction
2 t.There is nothing more important than preserving life, and the thesis here presented is framed in the field of quantitative biomedicine (or systems biomedicine), which has as objective the application of physico-mathematical techniques in biomedical research in order to enhance the understanding of life's basis and its pathologies, and, ultimately, to defend human health.
In this thesis, we have applied physico-mathematical methods in the three fundamental levels of Biomedical Research: basic, translational and clinical.
At a basic level, since all pathologies have their basis in the cell, we have performed two studies to deepen in the understanding of the cellular metabolic functionality. In the first work, we have quantitatively analyzed for the first time calcium-dependent chloride currents inside the cell, which has revealed the existence of a dynamical structure characterized by highly organized data sequences, non-trivial long-term correlation that last in average 7.66 seconds, and "crossover" effect with transitions between persistent and anti-persistent behaviors.
In the second investigation, by the use of delay differential equations, we have modeled the adenylate energy system, which is the principal source of cellular energy. This study has shown that the cellular energy charge is determined by an oscillatory non-stationary invariant function, bounded from 0.7 to 0.95.
At a translational level, we have developed a new method for vaccine design that, besides obtaining high coverages, is capable of giving protection against viruses with high mutability rates such as HIV, HCV or Influenza.
Finally, at a clinical level, first we have proven that the classic quantitative measure of uterine contractions (Montevideo Units) is incapable of predicting preterm labor immediacy. Then, by applying autoregressive techniques, we have designed a novel tool for premature delivery forecasting, based only in 30 minutes of uterine dynamics.
Altogether, these investigations have originated four scientific publications, and as far as we know, our work is the first European thesis which integrates in the same framework the application of mathematical knowledge to biomedical fields in the three main stages of Biomedical Research: basic, translational and clinical
An Approach for the Development of Complex Systems Archetypes
The purpose of this research is to explore the principles and concepts of systems theory in pursuit of a collection of complex systems archetypes that can be used for system exploration and diagnostics. The study begins with an examination of the archetypes and classification systems that already exist in the domain of systems theory. This review includes a critique of their purpose, structure, and general applicability. The research then develops and employs a new approach to grounded theory, using a visual coding model to explore the origins, relationships, and meanings of the principles of systems theory. The goal of the visual grounded theory approach is to identity underlying, recurrent imagery in the systems literature that will form the basis for the archetypes.
Using coding models derived from the literature, the study then examines the interrelationships between system principles. These relationships are used to clearly define the environment where the archetypes are found in terms of energy, entropy and time. A collection of complex system archetypes is then derived which are firmly rooted in the literature, as well as being demonstrably manifested in the real world. The definitions of the emerging complex systems archetypes are consistent with the environmental definition and are governed by the system’s behavior related to energy collection, entropy displacement, and the pursuit of viability.
Once the archetypes have been identified, this study examines the similarities and differences that distinguish them. The individual system principles that either define or differentiate each of the archetypes are described, and real-world manifestations of the archetypes are discussed. The collection of archetypes is then examined as a continuum, where they are related to one another in terms of energy use, entropy accumulation, self-modification and external-modification.
To illustrate the applicability of these archetypes, a case study is undertaken which examines a medium-sized organization with multiple departments in an industrial setting. The individual departments are discussed in detail, and their archetypical forms are identified and described. Finally, the study examines future applications for the archetypes and other research that might enhance their utility for complex systems governance
Quantitative analyses in basic, translational and clinical biomedical research: metabolism, vaccine design and preterm delivery prediction
2 t.There is nothing more important than preserving life, and the thesis here presented is framed in the field of quantitative biomedicine (or systems biomedicine), which has as objective the application of physico-mathematical techniques in biomedical research in order to enhance the understanding of life's basis and its pathologies, and, ultimately, to defend human health.
In this thesis, we have applied physico-mathematical methods in the three fundamental levels of Biomedical Research: basic, translational and clinical.
At a basic level, since all pathologies have their basis in the cell, we have performed two studies to deepen in the understanding of the cellular metabolic functionality. In the first work, we have quantitatively analyzed for the first time calcium-dependent chloride currents inside the cell, which has revealed the existence of a dynamical structure characterized by highly organized data sequences, non-trivial long-term correlation that last in average 7.66 seconds, and "crossover" effect with transitions between persistent and anti-persistent behaviors.
In the second investigation, by the use of delay differential equations, we have modeled the adenylate energy system, which is the principal source of cellular energy. This study has shown that the cellular energy charge is determined by an oscillatory non-stationary invariant function, bounded from 0.7 to 0.95.
At a translational level, we have developed a new method for vaccine design that, besides obtaining high coverages, is capable of giving protection against viruses with high mutability rates such as HIV, HCV or Influenza.
Finally, at a clinical level, first we have proven that the classic quantitative measure of uterine contractions (Montevideo Units) is incapable of predicting preterm labor immediacy. Then, by applying autoregressive techniques, we have designed a novel tool for premature delivery forecasting, based only in 30 minutes of uterine dynamics.
Altogether, these investigations have originated four scientific publications, and as far as we know, our work is the first European thesis which integrates in the same framework the application of mathematical knowledge to biomedical fields in the three main stages of Biomedical Research: basic, translational and clinical
Endogenous development: a model for the process of man-environment transaction
Iran is currently subject to a number of adverse factors affecting good development in the built
environment: population explosion, oil- dependent economy, finite resources, war and natural
disasters, etc. The object of the study is to research a development model appropriate to the
Country's needs for a proactive system of building environment. This model is not specific to
Iran and, as the case studies and the discourse of the thesis indicate, is universal. However,
the author suggests that the validity of development approaches will not be determined as a result of theoretical and ideological debate but in the realm of practice. Therefore, he has
explored diverse ways in which professionals in the built environment can provide an
analytical survey of the problems that beset them. An attempt has been made to bring these
various elements into perspective and offer a model of 'endogenous development'.The process for achieving a viable, exciting and humane built environment is very complex
and calls for contributions from many individuals and small multi -disciplinary groups. Beside
professionals contributions (which is accomplished by deduction inference), there is a need
for people's participation in design process (which is accomplished either by deduction or by
abduction inferences). This participatory approach can also help shifting the process of design
towards a wider domain that of the 'production process' (which is accomplished by abduction
and induction inferences). Production process is the first paradigm of the model of
endogenous development and is a manifestation of a feedback mechanism and acts as an open - ended living system. The second is 'supply- demand' paradigm which shows the relationships
between the components of a system or between different systems in surface- structuresThis model is directed at society's development, not just its economic growth, but it does not
preclude the possibility of such growth. The reduction of the problems' effect in an
endogenous development is viewed more as a way of improving the quality of life than of
increasing the standard of living. Nowadays, people are passive recipients in the consumer
society and are totally dependent on others for their survival. This style of living is assumed
to project an image of economic development and higher productivity, but there is a confrontation of preadjusted commodities which are the products of others. That is because
the process of production is not natural (i.e. a closed loop cyclic process via feedback
control). It is artificial (i.e. an open -loop linear process via a feed -forward control) which may
not help satisfying the user's needs and wants entirely. In the built environment, the great
majority have no say in the planning and design of their homes or places of work.Accordingly, endogenous development offers a framework within which the necessity of
employing the people's creative power in building their environment is explained. It is based
on the assumption that each individual and society's knowledge and experiences play a central
and mediating role between professionals' perceptions of the environment and a series of
preferences judgements or choices they might make towards and within that environment.
Indigenous knowledge and cultural attributes of traditional societies and the organizational
capabilities of traditional polities are essential in qualification of the development plans, which
are also evaluated and assessed by this proposed framework
Everything Flows
This collection of essays explores the metaphysical thesis that the living world is not ontologically made up of substantial particles or things, as has often been assumed, but is rather constituted by processes. The biological domain is organized as an interdependent hierarchy of processes, which are stabilized and actively maintained at different timescales. Even entities that intuitively appear to be paradigms of things, such as organisms, are actually better understood as processes. Unlike previous attempts to articulate processual views of biology, which have tended to use Alfred North Whitehead’s panpsychist metaphysics as a foundation, this book takes a naturalistic approach to metaphysics. It submits that the main motivations for replacing an ontology of substances with one of processes are to be looked for in the empirical findings of science. Biology provides compelling reasons for thinking that the living realm is fundamentally dynamic and that the existence of things is always conditional on the existence of processes. The phenomenon of life cries out for theories that prioritize processes over things, and it suggests that the central explanandum of biology is not change but rather stability—or, more precisely, stability attained through constant change. This multicontributor volume brings together philosophers of science and metaphysicians interested in exploring the consequences of a processual philosophy of biology. The contributors draw on an extremely wide range of biological case studies and employ a process perspective to cast new light on a number of traditional philosophical problems such as identity, persistence, and individuality
Centrality in the structure of built environment: a study in the structural transformation of society and space
Born out of a long term interest in thought and social values and nearly ten years of involvement in space and design as a student of architecture and urban design, this dissertation aims to make a contribution to both the structural theory of the transformation of society and space and to our knowledge of the principle of centrality in the structure of built environment. It looks at the concept of centrality in the Iranian city of Meshed. However, this is not intended as a study of a unique experience. Rather the spatial and temporal co- ordinates of the text, Islam and Iran, and the historical period of Modernist thought, offer a framework within which theoretical and principal questions of a more general nature concerning the structural character of society and space can be explored.The emphasis throughout is on the concept of the social production of the built environment at the centre of which lies the ideal process, understood in its most general sense as purposeful human activity. The dissertation seeks to show how changes in the relations between the elements and actors of production, the physical and mental means by which the built environment is created, and the relation between moment and totality within which the production process occurs, are central to an understanding of the structural transformation of human society, the form of city and the organization of space