263 research outputs found
Proton transport and torque generation in rotary biomotors
We analyze the dynamics of rotary biomotors within a simple
nano-electromechanical model, consisting of a stator part and a ring-shaped
rotor having twelve proton-binding sites. This model is closely related to the
membrane-embedded F motor of adenosine triphosphate (ATP) synthase, which
converts the energy of the transmembrane electrochemical gradient of protons
into mechanical motion of the rotor. It is shown that the Coulomb coupling
between the negative charge of the empty rotor site and the positive stator
charge, located near the periplasmic proton-conducting channel (proton source),
plays a dominant role in the torque-generating process. When approaching the
source outlet, the rotor site has a proton energy level higher than the energy
level of the site, located near the cytoplasmic channel (proton drain). In the
first stage of this torque-generating process, the energy of the
electrochemical potential is converted into potential energy of the
proton-binding sites on the rotor. Afterwards, the tangential component of the
Coulomb force produces a mechanical torque. We demonstrate that, at low
temperatures, the loaded motor works in the shuttling regime where the energy
of the electrochemical potential is consumed without producing any
unidirectional rotation. The motor switches to the torque-generating regime at
high temperatures, when the Brownian ratchet mechanism turns on. In the
presence of a significant external torque, created by ATP hydrolysis, the
system operates as a proton pump, which translocates protons against the
transmembrane potential gradient. Here we focus on the F motor, even though
our analysis is applicable to the bacterial flagellar motor.Comment: 24 pages, 5 figure
Effects of Cardiac Structural Remodelling During Heart Failure on Cardiac Excitation – Insights from a Heterogeneous 3D Model of the Rabbit Atria
Heart failure is a leading cause of morbidity and mortality in the western world. One of the effects of heart failure is the structural remodelling of cardiac tissue, including tissue dilation and development of fibrosis. It is therefore important to study these changes and their effect on cardiac activity, in order to gain a better understanding of the underlying mechanisms in arrhythmogenesis, which will hopefully enable us to develop better treatments for heart failure. In this study we developed biophysically detailed models of the rabbit atria for normal and heart failure conditions. These models were used to study the effects of structural remodelling of heart failure on cardiac excitation wave conduction. Anatomical reconstructions of the control and heart failure hearts were based on contrast enhanced micro-CT imaging. Fibre orientation was extracted from the control and heart failure datasets. Effects of heart failure geometry on the activation pattern of atrial excitation waves were analyzed. It was found that atrial activation time increased from the control to the heart failure case in both isotropic and anisotropic conditions, which is attributed primarily to the dilation of tissue caused by heart failure
Bayesian semiparametric modeling for stochastic precedence, with applications in epidemiology and survival analysis
A Master equation approach to modeling an artificial protein motor
Linear bio-molecular motors move unidirectionally along a track by
coordinating several different processes, such as fuel (ATP) capture,
hydrolysis, conformational changes, binding and unbinding from a track, and
center-of-mass diffusion. A better understanding of the interdependencies
between these processes, which take place over a wide range of different time
scales, would help elucidate the general operational principles of molecular
motors. Artificial molecular motors present a unique opportunity for such a
study because motor structure and function are a priori known. Here we describe
use of a Master equation approach, integrated with input from Langevin and
molecular dynamics modeling, to stochastically model a molecular motor across
many time scales. We apply this approach to a specific concept for an
artificial protein motor, the Tumbleweed.Comment: Submitted to Chemical Physics; 9 pages, 7 figure
Fluctuations of company yearly profits versus scaled revenue: Fat tail distribution of Levy type
We analyze annual revenues and earnings data for the 500 largest-revenue U.S.
companies during the period 1954-2007. We find that mean year profits are
proportional to mean year revenues, exception made for few anomalous years,
from which we postulate a linear relation between company expected mean profit
and revenue. Mean annual revenues are used to scale both company profits and
revenues. Annual profit fluctuations are obtained as difference between actual
annual profit and its expected mean value, scaled by a power of the revenue to
get a stationary behavior as a function of revenue. We find that profit
fluctuations are broadly distributed having approximate power-law tails with a
Levy-type exponent , from which we derive the associated
break-even probability distribution. The predictions are compared with
empirical data.Comment: 6 pages, 6 figure
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LIVAS: A 3-D multi-wavelength aerosol/cloud database based on CALIPSO and EARLINET
We present LIVAS (LIdar climatology of Vertical Aerosol Structure for space-based lidar simulation studies), a 3-D multi-wavelength global aerosol and cloud optical database, optimized to be used for future space-based lidar end-to-end simulations of realistic atmospheric scenarios as well as retrieval algorithm testing activities. The LIVAS database provides averaged profiles of aerosol optical properties for the potential spaceborne laser operating wavelengths of 355, 532, 1064, 1570 and 2050 nm and of cloud optical properties at the wavelength of 532 nm. The global database is based on CALIPSO observations at 532 and 1064 nm and on aerosol-type-dependent backscatter- and extinction-related Ångström exponents, derived from EARLINET (European Aerosol Research Lidar Network) ground-based measurements for the UV and scattering calculations for the IR wavelengths, using a combination of input data from AERONET, suitable aerosol models and recent literature. The required spectral conversions are calculated for each of the CALIPSO aerosol types and are applied to CALIPSO backscatter and extinction data corresponding to the aerosol type retrieved by the CALIPSO aerosol classification scheme. A cloud optical database based on CALIPSO measurements at 532 nm is also provided, neglecting wavelength conversion due to approximately neutral scattering behavior of clouds along the spectral range of LIVAS. Averages of particle linear depolarization ratio profiles at 532 nm are provided as well. Finally, vertical distributions for a set of selected scenes of specific atmospheric phenomena (e.g., dust outbreaks, volcanic eruptions, wild fires, polar stratospheric clouds) are analyzed and spectrally converted so as to be used as case studies for spaceborne lidar performance assessments. The final global data set includes 4-year (1 January 2008–31 December 2011) time-averaged CALIPSO (Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations) data on a uniform grid of 1° × 1° with the original high vertical resolution of CALIPSO in order to ensure realistic simulations of the atmospheric variability in lidar end-to-end simulations
Sinteza backstepping regulatora za praćenje maksimalne proizvodnje energije u fotonaponskim sustavima
This work presents a new control method to track the maximum power point of a grid-connected photovoltaic (PV) system. A backstepping controller is designed to be applied to a buck-boost DC-DC converter in order to achieve an optimal PV array output voltage. This nonlinear control is based on Lyapunov functions assuring the local stability of the system. Control reference voltages are initially estimated by a regression plane, avoiding local maximum and adjusted with a modified perturb and observe method (P&O). Thus, the maximum power extraction of the generating system is guaranteed. Finally, a DC-AC converter is controlled to supply AC current in the point of common coupling (PCC) of the electrical network. The performance of the developed system has been analyzed by means a simulation platform in Matlab/Simulink helped by SymPowerSystem Blockset. Results testify the validity of the designed control method.Ovaj rad predstavlja novu metodu upravljanja za slije.enje točke maksimalne snage fotonaponskog (PV) sustava. Dana je sinteza backstepping regulatora za primjenu u silazno-uzlaznom DC-DC pretvaraču za postizanje optimalnog izlaznog napona PV-a. Ova je nelinearna metoda upravljanja zasnovana na Ljapunovim funkcijama osiguravajući tako lokalnu stabilnost sustava. Upravljačke reference napona prvo su estimirane korištenjem regresijske ravnine izbjegavajući lokalne maksimume, a zatim podešene tzv. modificiranom perturbiraj i uoči metodom (P&O). Prema tome, zagarantirano je maksimalno izvlačenje energije iz sustava proizvodnje. Naposlijetku, DC-AC pretvaračem upravlja se na način da osigurava željena izmjenična struja u točki zajedničkog spoja (PCC) elektroenergetske mreže. Ponašanje razvijenog sustava analizirano je kroz simulacije provedene u Matlab/Simulink okruženju uz korištenje SymPowerSystem biblioteke
Retroviral Integration Process in the Human Genome: Is It Really Non-Random? A New Statistical Approach
Retroviral vectors are widely used in gene therapy to introduce therapeutic genes into patients' cells, since, once delivered to the nucleus, the genes of interest are stably inserted (integrated) into the target cell genome. There is now compelling evidence that integration of retroviral vectors follows non-random patterns in mammalian genome, with a preference for active genes and regulatory regions. In particular, Moloney Leukemia Virus (MLV)–derived vectors show a tendency to integrate in the proximity of the transcription start site (TSS) of genes, occasionally resulting in the deregulation of gene expression and, where proto-oncogenes are targeted, in tumor initiation. This has drawn the attention of the scientific community to the molecular determinants of the retroviral integration process as well as to statistical methods to evaluate the genome-wide distribution of integration sites. In recent approaches, the observed distribution of MLV integration distances (IDs) from the TSS of the nearest gene is assumed to be non-random by empirical comparison with a random distribution generated by computational simulation procedures. To provide a statistical procedure to test the randomness of the retroviral insertion pattern, we propose a probability model (Beta distribution) based on IDs between two consecutive genes. We apply the procedure to a set of 595 unique MLV insertion sites retrieved from human hematopoietic stem/progenitor cells. The statistical goodness of fit test shows the suitability of this distribution to the observed data. Our statistical analysis confirms the preference of MLV-based vectors to integrate in promoter-proximal regions
Infinite mixture-of-experts model for sparse survival regression with application to breast cancer
BACKGROUND: We present an infinite mixture-of-experts model to find an unknown number of sub-groups within a given patient cohort based on survival analysis. The effect of patient features on survival is modeled using the Cox's proportionality hazards model which yields a non-standard regression component. The model is able to find key explanatory factors (chosen from main effects and higher-order interactions) for each sub-group by enforcing sparsity on the regression coefficients via the Bayesian Group-Lasso. RESULTS: Simulated examples justify the need of such an elaborate framework for identifying sub-groups along with their key characteristics versus other simpler models. When applied to a breast-cancer dataset consisting of survival times and protein expression levels of patients, it results in identifying two distinct sub-groups with different survival patterns (low-risk and high-risk) along with the respective sets of compound markers. CONCLUSIONS: The unified framework presented here, combining elements of cluster and feature detection for survival analysis, is clearly a powerful tool for analyzing survival patterns within a patient group. The model also demonstrates the feasibility of analyzing complex interactions which can contribute to definition of novel prognostic compound markers
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