8,281 research outputs found
Modelling cytoskeletal traffic: an interplay between passive diffusion and active transport
We introduce the totally asymmetric exclusion process with Langmuir kinetics
(TASEP-LK) on a network as a microscopic model for active motor protein
transport on the cytoskeleton, immersed in the diffusive cytoplasm. We discuss
how the interplay between active transport along a network and infinite
diffusion in a bulk reservoir leads to a heterogeneous matter distribution on
various scales. We find three regimes for steady state transport, corresponding
to the scale of the network, of individual segments or local to sites. At low
exchange rates strong density heterogeneities develop between different
segments in the network. In this regime one has to consider the topological
complexity of the whole network to describe transport. In contrast, at moderate
exchange rates the transport through the network decouples, and the physics is
determined by single segments and the local topology. At last, for very high
exchange rates the homogeneous Langmuir process dominates the stationary state.
We introduce effective rate diagrams for the network to identify these
different regimes. Based on this method we develop an intuitive but generic
picture of how the stationary state of excluded volume processes on complex
networks can be understood in terms of the single-segment phase diagram.Comment: 5 pages, 7 figure
Reset and switch protocols at Landauer limit in a graphene buckled ribbon
Heat produced during a reset operation is meant to show a fundamental bound
known as Landauer limit, while simple switch operations have an expected
minimum amount of produced heat equal to zero. However, in both cases,
present-day technology realizations dissipate far beyond these theoretical
limits. In this paper we present a study based on molecular dynamics
simulations, where reset and switch protocols are applied on a graphene buckled
ribbon, employed here as a nano electromechanical switch working at the
thermodynamic limit
Motor proteins traffic regulation by supply-demand balance of resources
In cells and in vitro assays the number of motor proteins involved in
biological transport processes is far from being unlimited. The cytoskeletal
binding sites are in contact with the same finite reservoir of motors (either
the cytosol or the flow chamber) and hence compete for recruiting the available
motors, potentially depleting the reservoir and affecting cytoskeletal
transport. In this work we provide a theoretical framework to study,
analytically and numerically, how motor density profiles and crowding along
cytoskeletal filaments depend on the competition of motors for their binding
sites. We propose two models in which finite processive motor proteins actively
advance along cytoskeletal filaments and are continuously exchanged with the
motor pool. We first look at homogeneous reservoirs and then examine the
effects of free motor diffusion in the surrounding medium. We consider as a
reference situation recent in vitro experimental setups of kinesin-8 motors
binding and moving along microtubule filaments in a flow chamber. We
investigate how the crowding of linear motor proteins moving on a filament can
be regulated by the balance between supply (concentration of motor proteins in
the flow chamber) and demand (total number of polymerised tubulin
heterodimers). We present analytical results for the density profiles of bound
motors, the reservoir depletion, and propose novel phase diagrams that present
the formation of jams of motor proteins on the filament as a function of two
tuneable experimental parameters: the motor protein concentration and the
concentration of tubulins polymerized into cytoskeletal filaments. Extensive
numerical simulations corroborate the analytical results for parameters in the
experimental range and also address the effects of diffusion of motor proteins
in the reservoir.Comment: 31 pages, 10 figure
The meaning of different forms of structural myocardial injury, immune response and timing of infarct necrosis and cardiac repair
Although a decline in the all-cause and cardiac mortality rates following myocardial infarction (MI) during the past 3 decades has been reported, MI is a major cause of death and disability worldwide. From a pathological point of view MI consists in a particular myocardial cell death due to prolonged ischemia. After the onset of myocardial ischemia, cell death is not immediate, but takes a finite period of time to develop. Once complete myocytes’ necrosis has occurred, a process leading to a healed infarction takes place. In fact, MI is a dynamic process that begins with the transition from reversible to irreversible ischemic injury and culminates in the replacement of dead myocardium by a fibrous scar. The pathobiological mechanisms underlying this process are very complex, involving an inflammatory response by several pathways, and pose a major challenge to ability to improve our knowledge. An improved understanding of the pathobiology of cardiac repair after MI and further studies of its underlying mechanisms provide avenues for the development of future strategies directed toward the identification of novel therapies. The chronologic dating of MI is of great importance both to clinical and forensic investigation, that is, the ability to create a theoretical timeline upon which either clinicians or forensic pathologists may increase their ability to estimate the time of MI. Aging of MI has very important practical implications in clinical practice since, based on the chronological dating of MI, attractive alternatives to solve therapeutic strategies in the various phases of MI are developing
Cardiac oxidative stress and inflammatory cytokines response after myocardial infarction
Oxidative stress in heart failure or during ischemia/reperfusion occurs as a result of the excessive generation or accumulation of free radicals or their oxidation products. Free radicals formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks. Oxidative stress is a condition in which oxidant metabolites exert toxic effects because of their increased production or an altered cellular mechanism of protection. In the early phase of acute heart ischemia cytokines have the feature to be functional pleiotropy and redundancy, moreover, several cytokines exert similar and overlapping actions on the same cell type and one cytokine shows a wide range of biological effects on various cell types. Activation of cytokine cascades in the infarcted myocardium was established in numerous studies. In experimental models of myocardial infarction, induction and release of the pro-inflammatory cytokines like TNF-&alpha (Tumor Necrosis Factor &alpha), IL-1&beta (Interleukin- 1&beta) and IL-6 (Interleukin-6) and chemokines are steadily described. The current review examines the role of oxidative stress and pro-inflammatory cytokines response following acute myocardial infarction and explores the inflammatory mechanisms of cardiac injur
Confocal laser scanning microscope, raman microscopy and western blotting to evaluate inflammatory response after myocardial infarction
Cardiac muscle necrosis is associated with inflammatory cascade that clears the infarct from dead
cells and matrix debris, and then replaces the damaged tissue with scar, through three overlapping phases: the
inflammatory phase, the proliferative phase and the maturation phase.
Western blotting, laser confocal microscopy, Raman microscopy are valuable tools for studying the inflammatory
response following myocardial infarction both humoral and cellular phase, allowing the identification and
semiquantitative analysis of proteins produced during the inflammatory cascade activation and the topographical distribution
and expression of proteins and cells involved in myocardial inflammation. Confocal laser scanning microscopy
(CLSM) is a relatively new technique for microscopic imaging, that allows greater resolution, optical sectioning of the
sample and three-dimensional reconstruction of the same sample. Western blotting used to detect the presence of a specific
protein with antibody-antigen interaction in the midst of a complex protein mixture extracted from cells, produced
semi-quantitative data quite easy to interpret. Confocal Raman microscopy combines the three-dimensional optical resolution
of confocal microscopy and the sensitivity to molecular vibrations, which characterizes Raman spectroscopy.
The combined use of western blotting and confocal microscope allows detecting the presence of proteins in the sample
and trying to observe the exact location within the tissue, or the topographical distribution of the same. Once demonstrated
the presence of proteins (cytokines, chemokines, etc.) is important to know the topographical distribution, obtaining in this
way additional information regarding the extension of the inflammatory process in function of the time stayed from the
time of myocardial infarction. These methods may be useful to study and define the expression of a wide range of inflammatory
mediators at several different timepoints providing a more detailed analysis of the time course of the infarct
Exclusion processes on networks as models for cytoskeletal transport
We present a study of exclusion processes on networks as models for complex
transport phenomena and in particular for active transport of motor proteins
along the cytoskeleton. We argue that active transport processes on networks
spontaneously develop density heterogeneities at various scales. These
heterogeneities can be regulated through a variety of multi-scale factors, such
as the interplay of exclusion interactions, the non-equilibrium nature of the
transport process and the network topology.
We show how an effective rate approach allows to develop an understanding of
the stationary state of transport processes through complex networks from the
phase diagram of one single segment. For exclusion processes we rationalize
that the stationary state can be classified in three qualitatively different
regimes: a homogeneous phase as well as inhomogeneous network and segment
phases.
In particular, we present here a study of the stationary state on networks of
three paradigmatic models from non-equilibrium statistical physics: the totally
asymmetric simple exclusion process, the partially asymmetric simple exclusion
process and the totally asymmetric simple exclusion process with Langmuir
kinetics. With these models we can interpolate between equilibrium (due to
bi-directional motion along a network or infinite diffusion) and
out-of-equilibrium active directed motion along a network. The study of these
models sheds further light on the emergence of density heterogeneities in
active phenomena.Comment: 55 pages, 26 figure
Patterns of Filipino Migration to Guam: United States Military Colonialism and its Aftermath
In the context of US military colonialism, this research note examines patterns of migrant Filipino employment in Guam using US census data. While Chamorros were in the majority in various occupational categories in 1920, by 1950 Filipinos dominated many categories, except in professional, technical, and managerial positions in which whites had preponderance. The surge of Filipino male migration to Guam owed to the need for skilled labor in postwar reconstruction. From 1970 onwards, Filipino migration to Guam increased, but so did other Asians, resulting in a labor situation in which no ethnic group was dominant in any one occupational category.Keywords: Guam • Filipinos • overseas migration • skilled migrants • US militar
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