We present a theoretical technique for quantifying the cellular copy-number of fluorophores that relies on the random nature of the photobleaching process. Our approach does not require single-molecule sensitivity, and therefore can be used with commonly used epifluorescence microscopes. Fluctuations arising from photobleaching can be used to estimate the proportionality between fluorescence intensity and copy-number, which can then be used with subsequent intensity measurements to estimate copy-number. We calculate the statistical errors of our approach and verify them with stochastic simulations. By using fluctuations over the entire photobleaching process, we obtain significantly smaller errors than previous approaches that have used fluctuations arising from cytoplasmic proteins partitioning during cellular division. From the time-dependence of the fluctuations as photobleaching proceeds, we can discriminate between desired photobleach fluctuations and background noise or photon shot noise. Our approach does not require cellular division and the photobleaching rate sets a timescale that is adjustable with respect to cellular processes. We hope that our approach will now be applied experimentally.
We investigate the effect of the phase difference of applied fields on the dynamics of mutually coupled Josephson junction. The system desynchronizes for any value of applied phase difference and the dynamics even changes from chaotic to periodic motion for some values of applied phase difference. We report that by keeping the value of phase difference as π, the system continues to be in periodic motion for a wide range of system parameter values which might be of great practical applications.
Many signaling pathways act through shared components, where different ligand molecules bind the same receptors or activate overlapping sets of response regulators downstream. Nevertheless, different ligands acting through cross-wired pathways often lead to different outcomes in terms of the target cell behavior and function. Although a number of mechanisms have been proposed, it still largely remains unclear how cells can reliably discriminate different molecular ligands under such circumstances. Here we show that signaling via ligand-induced receptor dimerization-a very common motif in cellular signaling-naturally incorporates a mechanism for the discrimination of ligands acting through the same receptor.
This paper presents a plausible solution using brain based learning principles as instructional delivery protocols to address the issue of lack of academic engagement among the upper level engineering students. The study was conducted at Tuskegee University, an HBCU and can be implemented universally in other institutes due to its foundation on brain based learning principles. Although student engagement issues inside engineering classrooms have several components, we focus our attention in this paper mainly on two issues: the dis-engagement arising due to the lack of understanding of pre-requisites and insufficient mathematical skills of students reaching junior and senior engineering classes. A previous pilot study confirmed that a large fraction of students who reach junior and senior level classes require repeated review of pre-requisite concepts and need assistance in reviewing their basic and essential mathematical skills before they can successfully engage in their classes. To address these issues, an instructional delivery framework titled "Tailored Instructions and Engineered Delivery Using PROTOCOLs" (TIED-UP) has been designed and explored, where mandatory brain-based learning procedures were used along with a media rich online delivery strategy. This paper summarizes the efforts currently undertaken to develop this framework based on brain-based learning theories to address some of these issues. In this framework, each course concept is broken down to interconnected sub-concepts. Short conceptual videos that use a number of mandatory instructional protocols were developed for the instruction of each of these concept and sub-concept. The study shows that such an intervention has significantly increased students' academic success as measured by grades and caused a substantial decline in their failure rate, when compared against a control group.
The Type I Interferon family of cytokines all act through the same cell surface receptor and induce phosphorylation of the same subset of response regulators of the STAT family. Despite their shared receptor, different Type I Interferons have different functions during immune response to infection. In particular, they differ in the potency of their induced anti-viral and anti-proliferative responses in target cells. It remains not fully understood how these functional differences can arise in a ligand-specific manner both at the level of STAT phosphorylation and the downstream function. We use a minimal computational model of Type I Interferon signaling, focusing on Interferon-α and Interferon-β. We validate the model with quantitative experimental data to identify the key determinants of specificity and functional plasticity in Type I Interferon signaling. We investigate different mechanisms of signal discrimination, and how multiple system components such as binding affinity, receptor expression levels and their variability, receptor internalization, short-term negative feedback by SOCS1 protein, and differential receptor expression play together to ensure ligand specificity on the level of STAT phosphorylation. Based on these results, we propose phenomenological functional mappings from STAT activation to downstream anti-viral and anti-proliferative activity to investigate differential signal processing steps downstream of STAT phosphorylation. We find that the negative feedback by the protein USP18, which enhances differences in signaling between Interferons via ligand-dependent refractoriness, can give rise to functional plasticity in Interferon-α and Interferon-β signaling, and explore other factors that control functional plasticity. Beyond Type I Interferon signaling, our results have a broad applicability to questions of signaling specificity and functional plasticity in signaling systems with multiple ligands acting through a bottleneck of a small number of shared receptors.
Systems of coupled oscillators have been seen to exhibit chimera states, i.e. states where the system splits into two groups where one group is phase locked and the other is phase randomized. In this work, we report the existence of chimera states in a system of two interacting populations of sine circle maps. This system also exhibits the clustered chimera behavior seen earlier in delay coupled systems. Rich spatio-temporal behavior is seen in different regimes of the phase diagram. We carry out a detailed analysis of the stability regimes and map out the phase diagram using numerical and analytic techniques.
since 2008. His primary interest is in the area of solid mechanics and manufacturing as well as the integration of best practices in engineering education.
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