219 research outputs found
The interplay of intrinsic and extrinsic bounded noises in genetic networks
After being considered as a nuisance to be filtered out, it became recently
clear that biochemical noise plays a complex role, often fully functional, for
a genetic network. The influence of intrinsic and extrinsic noises on genetic
networks has intensively been investigated in last ten years, though
contributions on the co-presence of both are sparse. Extrinsic noise is usually
modeled as an unbounded white or colored gaussian stochastic process, even
though realistic stochastic perturbations are clearly bounded. In this paper we
consider Gillespie-like stochastic models of nonlinear networks, i.e. the
intrinsic noise, where the model jump rates are affected by colored bounded
extrinsic noises synthesized by a suitable biochemical state-dependent Langevin
system. These systems are described by a master equation, and a simulation
algorithm to analyze them is derived. This new modeling paradigm should enlarge
the class of systems amenable at modeling.
We investigated the influence of both amplitude and autocorrelation time of a
extrinsic Sine-Wiener noise on: the Michaelis-Menten approximation of
noisy enzymatic reactions, which we show to be applicable also in co-presence
of both intrinsic and extrinsic noise, a model of enzymatic futile cycle
and a genetic toggle switch. In and we show that the
presence of a bounded extrinsic noise induces qualitative modifications in the
probability densities of the involved chemicals, where new modes emerge, thus
suggesting the possibile functional role of bounded noises
From Retinal Waves to Activity-Dependent Retinogeniculate Map Development
A neural model is described of how spontaneous retinal waves are formed in infant mammals, and how these waves organize activity-dependent development of a topographic map in the lateral geniculate nucleus, with connections from each eye segregated into separate anatomical layers. The model simulates the spontaneous behavior of starburst amacrine cells and retinal ganglion cells during the production of retinal waves during the first few weeks of mammalian postnatal development. It proposes how excitatory and inhibitory mechanisms within individual cells, such as Ca2+-activated K+ channels, and cAMP currents and signaling cascades, can modulate the spatiotemporal dynamics of waves, notably by controlling the after-hyperpolarization currents of starburst amacrine cells. Given the critical role of the geniculate map in the development of visual cortex, these results provide a foundation for analyzing the temporal dynamics whereby the visual cortex itself develops
Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.
A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions" of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides
Fault-tolerant aggregation: Flow-Updating meets Mass-Distribution
Flow-Updating (FU) is a fault-tolerant technique that has proved to be efficient in practice for the distributed computation of aggregate functions in communication networks where individual processors do not have access to global information. Previous distributed aggregation protocols, based on repeated sharing of input values (or mass) among processors, sometimes called Mass-Distribution (MD) protocols, are not resilient to communication failures (or message loss) because such failures yield a loss of mass. In this paper, we present a protocol which we call Mass-Distribution with Flow-Updating (MDFU). We obtain MDFU by applying FU techniques to classic MD. We analyze the convergence time of MDFU showing that stochastic message loss produces low overhead. This is the first convergence proof of an FU-based algorithm. We evaluate MDFU experimentally, comparing it with previous MD and FU protocols, and verifying the behavior predicted by the analysis. Finally, given that MDFU incurs a fixed deviation proportional to the message-loss rate, we adjust the accuracy of MDFU heuristically in a new protocol called MDFU with Linear Prediction (MDFU-LP). The evaluation shows that both MDFU and MDFU-LP behave very well in practice, even under high rates of message loss and even changing the input values dynamically.- A preliminary version of this work appeared in [2]. This work was partially supported by the National Science Foundation (CNS-1408782, IIS-1247750); the National Institutes of Health (CA198952-01); EMC, Inc.; Pace University Seidenberg School of CSIS; and by Project "Coral - Sustainable Ocean Exploitation: Tools and Sensors/NORTE-01-0145-FEDER-000036" financed by the North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, and through the European Regional Development Fund (ERDF).info:eu-repo/semantics/publishedVersio
Three-dimensional studies of pathogenic peptides from the c-terminal of Trypanosoma cruzi ribosomal P proteins and their interaction with a monoclonal antibody structural model
The acidic C-terminal peptides from Trypanosoma cruzi ribosomal P proteins are the major target of the antibody response in patients suffering Chagas chronic heart disease. It has been proposed that the disease is triggered by the cross-reaction of these antibodies with the second extra cellular loop of the β1-adrenoreceptor, brought about by the molecular mimicry between the acidic C-terminal peptides and the receptor's loop. To improve the understanding of the structural basis of the autoimmune response against heart receptors, the 3-dimensional structure of the C-terminal peptides of Trypanosoma cruzi ribosomal proteins P0 (EDDDDDFGMGALF) and P2β (EEEDDDMGFGLFD) were solved using the Electrostaticaly Driven MonteCarlo method. Their structures were compared with the second extra-cellular loop of our homology model of human rhodopsin and the existing experimental NMR structures of the C-terminal peptides from human P0 (EESDDDMGFGLFD) and from Leishmania braziliensis P0 (EEADDDMGFGLFD). Docking of Trypanosoma cruzi peptides P0, P2β and human rhodopsin loop into our anti-P2β monoclonal antibody homology model allowed to explore their interactions
Quantum dynamics in strong fluctuating fields
A large number of multifaceted quantum transport processes in molecular
systems and physical nanosystems can be treated in terms of quantum relaxation
processes which couple to one or several fluctuating environments. A thermal
equilibrium environment can conveniently be modelled by a thermal bath of
harmonic oscillators. An archetype situation provides a two-state dissipative
quantum dynamics, commonly known under the label of a spin-boson dynamics. An
interesting and nontrivial physical situation emerges, however, when the
quantum dynamics evolves far away from thermal equilibrium. This occurs, for
example, when a charge transferring medium possesses nonequilibrium degrees of
freedom, or when a strong time-dependent control field is applied externally.
Accordingly, certain parameters of underlying quantum subsystem acquire
stochastic character. Herein, we review the general theoretical framework which
is based on the method of projector operators, yielding the quantum master
equations for systems that are exposed to strong external fields. This allows
one to investigate on a common basis the influence of nonequilibrium
fluctuations and periodic electrical fields on quantum transport processes.
Most importantly, such strong fluctuating fields induce a whole variety of
nonlinear and nonequilibrium phenomena. A characteristic feature of such
dynamics is the absence of thermal (quantum) detailed balance.Comment: review article, Advances in Physics (2005), in pres
A semiparametric Bayesian proportional hazards model for interval censored data with frailty effects
<p>Abstract</p> <p>Background</p> <p>Multivariate analysis of interval censored event data based on classical likelihood methods is notoriously cumbersome. Likelihood inference for models which additionally include random effects are not available at all. Developed algorithms bear problems for practical users like: matrix inversion, slow convergence, no assessment of statistical uncertainty.</p> <p>Methods</p> <p>MCMC procedures combined with imputation are used to implement hierarchical models for interval censored data within a Bayesian framework.</p> <p>Results</p> <p>Two examples from clinical practice demonstrate the handling of clustered interval censored event times as well as multilayer random effects for inter-institutional quality assessment. The software developed is called survBayes and is freely available at CRAN.</p> <p>Conclusion</p> <p>The proposed software supports the solution of complex analyses in many fields of clinical epidemiology as well as health services research.</p
Aspects of coverage in medical DNA sequencing
<p>Abstract</p> <p>Background</p> <p>DNA sequencing is now emerging as an important component in biomedical studies of diseases like cancer. Short-read, highly parallel sequencing instruments are expected to be used heavily for such projects, but many design specifications have yet to be conclusively established. Perhaps the most fundamental of these is the redundancy required to detect sequence variations, which bears directly upon genomic coverage and the consequent resolving power for discerning somatic mutations.</p> <p>Results</p> <p>We address the medical sequencing coverage problem via an extension of the standard mathematical theory of haploid coverage. The expected diploid multi-fold coverage, as well as its generalization for aneuploidy are derived and these expressions can be readily evaluated for any project. The resulting theory is used as a scaling law to calibrate performance to that of standard BAC sequencing at 8× to 10× redundancy, i.e. for expected coverages that exceed 99% of the unique sequence. A differential strategy is formalized for tumor/normal studies wherein tumor samples are sequenced more deeply than normal ones. In particular, both tumor alleles should be detected at least twice, while both normal alleles are detected at least once. Our theory predicts these requirements can be met for tumor and normal redundancies of approximately 26× and 21×, respectively. We explain why these values do not differ by a factor of 2, as might intuitively be expected. Future technology developments should prompt even deeper sequencing of tumors, but the 21× value for normal samples is essentially a constant.</p> <p>Conclusion</p> <p>Given the assumptions of standard coverage theory, our model gives pragmatic estimates for required redundancy. The differential strategy should be an efficient means of identifying potential somatic mutations for further study.</p
Frontiers of open quantum system dynamics
We briefly examine recent developments in the field of open quantum system
theory, devoted to the introduction of a satisfactory notion of memory for a
quantum dynamics. In particular, we will consider a possible formalization of
the notion of non-Markovian dynamics, as well as the construction of quantum
evolution equations featuring a memory kernel. Connections will be drawn to the
corresponding notions in the framework of classical stochastic processes, thus
pointing to the key differences between a quantum and classical formalization
of the notion of memory effects.Comment: 15 pages, contribution to "Quantum Physics and Geometry", Lecture
Notes of the Unione Matematica Italiana 25,E. Ballico et al. (eds.
Insights into pathogenic events of HIV-associated Kaposi sarcoma and immune reconstitution syndrome related Kaposi sarcoma
A decrease in the incidence of human immune deficiency virus-associated Kaposi sarcoma (HIV-KS) and regression of some established HIV-KS lesions is evident after the introduction of highly active anti-retroviral treatment (HAART), and is attributed to generalized immune restoration, to the reconstitution of human herpesvirus (HHV)-8 specific cellular immune responses, and to the decrease in HIV Tat protein and HHV-8 loads following HAART. However, a small subset of HIV-seropositive subjects with a low CD4+ T cell count at the time of introduction of HAART, may develop HIV-KS as immune reconstitution inflammatory syndrome (IRIS) within 8 weeks thereafter
- …