scholarly journals Single-molecule binding experiments on long time scales

2010 ◽  
Vol 81 (8) ◽  
pp. 083705 ◽  
Author(s):  
Mark P. Elenko ◽  
Jack W. Szostak ◽  
Antoine M. van Oijen
2018 ◽  
Author(s):  
Mayuri Rege ◽  
Ji Hun Kim ◽  
Jacqueline Valeri ◽  
Margaret C. Dunagin ◽  
Aryeh Metzger ◽  
...  

AbstractMammalian genomes are folded into tens of thousands of long-range looping interactions1,2. The cause and effect relationship between looping and genome function is poorly understood, and the extent to which chromatin loops are dynamic on short time scales remains a fundamental unanswered question. Currently available strategies for loop engineering involve synthetic transcription factors tethered to dCas93,4 or zinc fingers5,6, which are constitutively expressed5,6 or induced on long time scales by the presence of a small molecule3. Here we report a new class of 3-D optoepigenetic tools for the directed rearrangement of 3-D chromatin looping on short time scales using blue light. We create synthetic architectural proteins by fusing the CIBN protein subunit from Arabidopsis thaliana with enzymatically dead Cas9 (dCas9). We target our light-activated dynamic looping system (LADL) to two genomic anchors with CRISPR guide RNAs and engineer their spatial co-localization via light-induced heterodimerization of the cryptochrome 2 (CRY2) protein with dCas9-CIBN. We apply LADL to redirect a stretch enhancer (SE) away from its endogenous Klf4 target gene and to the Zfp462 promoter. Looping changes occur as early as four hours after light induction. Using single molecule RNA FISH, we observe a LADL-induced increase in the total nascent Zfp462 transcripts and the number of Zfp462 alleles expressing simultaneously per cell. Moreover, LADL also increased synchronous Sox2 expression after reinforcement of a known Sox2-SE looping interaction. LADL facilitates loop synchronization across a large population of cells without exogenous chemical cofactors and can enable future efforts to engineer reversible and oscillatory looping on short time scales.


2012 ◽  
Vol 19 (02) ◽  
pp. 1250011 ◽  
Author(s):  
F. Giraldi ◽  
F. Petruccione

A model multilevel molecule described by two sets of rotational internal energy levels of different parity and degenerate ground states, coupled by a constant interaction, is considered, by assuming that the random collisions in a gas of identical molecules, provoke transitions between adjacent energy levels of the same parity. The prescriptions of the continuous time quantum random walk is applied to the single molecule, interpreted as an open quantum system, and the master equation driving its internal dynamics is built for a general distribution of random collision times. Over estimated long time scales, the dynamics of the coherence terms and the populations of the energy levels is evaluated analytically for relevant classes of non-Poissonian distributions of the collision times. Inverse power law relaxations and the inverse Zeno effect emerge over estimated long time scales and the stable asymptotic equilibrium configuration results to be independent of the distribution of the collision times.


1984 ◽  
Vol 16 (3-4) ◽  
pp. 623-633
Author(s):  
M Loxham ◽  
F Weststrate

It is generally agreed that both the landfill option, or the civil techniques option for the final disposal of contaminated harbour sludge involves the isolation of the sludge from the environment. For short time scales, engineered barriers such as a bentonite screen, plastic sheets, pumping strategies etc. can be used. However for long time scales the effectiveness of such measures cannot be counted upon. It is thus necessary to be able to predict the long term environmenttal spread of contaminants from a mature landfill. A model is presented that considers diffusion and adsorption in the landfill site and convection and adsorption in the underlaying aquifer. From a parameter analysis starting form practical values it is shown that the adsorption behaviour and the molecular diffusion coefficient of the sludge, are the key parameters involved in the near field. The dilution effects of the far field migration patterns are also illustrated.


2005 ◽  
Vol 9 (5) ◽  
pp. 523-533 ◽  
Author(s):  
S. M. Vicente-Serrano ◽  
J. I. López-Moreno

Abstract. At present, the Standardized Precipitation Index (SPI) is the most widely used drought index to provide good estimations about the intensity, magnitude and spatial extent of droughts. The main advantage of the SPI in comparison with other indices is the fact that the SPI enables both determination of drought conditions at different time scales and monitoring of different drought types. It is widely accepted that SPI time scales affect different sub-systems in the hydrological cycle due to the fact that the response of the different water usable sources to precipitation shortages can be very different. The long time scales of SPI are related to hydrological droughts (river flows and reservoir storages). Nevertheless, few analyses empirically verify these statements or the usefulness of the SPI time scales to monitor drought. In this paper, the SPI at different time scales is compared with surface hydrological variables in a big closed basin located in the central Spanish Pyrenees. We provide evidence about the way in which the longer (>12 months) SPI time scales may not be useful for drought quantification in this area. In general, the surface flows respond to short SPI time scales whereas the reservoir storages respond to longer time scales (7–10 months). Nevertheless, important seasonal differences can be identified in the SPI-usable water sources relationships. This suggests that it is necessary to test the drought indices and time scales in relation to their usefulness for monitoring different drought types under different environmental conditions and water demand situations.


2017 ◽  
Vol 123 (2) ◽  
pp. 344-351 ◽  
Author(s):  
Luiz Eduardo Virgilio Silva ◽  
Renata Maria Lataro ◽  
Jaci Airton Castania ◽  
Carlos Alberto Aguiar Silva ◽  
Helio Cesar Salgado ◽  
...  

Heart rate variability (HRV) has been extensively explored by traditional linear approaches (e.g., spectral analysis); however, several studies have pointed to the presence of nonlinear features in HRV, suggesting that linear tools might fail to account for the complexity of the HRV dynamics. Even though the prevalent notion is that HRV is nonlinear, the actual presence of nonlinear features is rarely verified. In this study, the presence of nonlinear dynamics was checked as a function of time scales in three experimental models of rats with different impairment of the cardiac control: namely, rats with heart failure (HF), spontaneously hypertensive rats (SHRs), and sinoaortic denervated (SAD) rats. Multiscale entropy (MSE) and refined MSE (RMSE) were chosen as the discriminating statistic for the surrogate test utilized to detect nonlinearity. Nonlinear dynamics is less present in HF animals at both short and long time scales compared with controls. A similar finding was found in SHR only at short time scales. SAD increased the presence of nonlinear dynamics exclusively at short time scales. Those findings suggest that a working baroreflex contributes to linearize HRV and to reduce the likelihood to observe nonlinear components of the cardiac control at short time scales. In addition, an increased sympathetic modulation seems to be a source of nonlinear dynamics at long time scales. Testing nonlinear dynamics as a function of the time scales can provide a characterization of the cardiac control complementary to more traditional markers in time, frequency, and information domains. NEW & NOTEWORTHY Although heart rate variability (HRV) dynamics is widely assumed to be nonlinear, nonlinearity tests are rarely used to check this hypothesis. By adopting multiscale entropy (MSE) and refined MSE (RMSE) as the discriminating statistic for the nonlinearity test, we show that nonlinear dynamics varies with time scale and the type of cardiac dysfunction. Moreover, as complexity metrics and nonlinearities provide complementary information, we strongly recommend using the test for nonlinearity as an additional index to characterize HRV.


2020 ◽  
Author(s):  
Minzhen Yin ◽  
Shanshan Chu ◽  
Tingyu Shan ◽  
Liangping Zha ◽  
Huasheng Peng

Abstract Background: Astragalus mongholicus Bunge is an important medicinal plant and has been used in traditional Chinese medicine for a long history, which is rich in isoflavonoids and triterpenoid saponins. Although these active constituents in A. mongholicus have been discovered for a long time, the molecular genetic basis of the isoflavonoid and triterpenoid saponin biosynthesis pathways is virtually unknown due to the lack of a reference genome. The combination of next-generation sequencing (NGS) and single-molecule real-time (SMRT) sequencing to analyze genes involved in the biosynthetic pathways of secondary metabolites in medicinal plants has been widely recognized.Results: In this study, NGS, SMRT sequencing, and targeted compounds were combined to investigate the association between isoflavonoids and triterpenoid saponins and gene expression in roots, stems and leaves of A. mongholicus. A total of four main isoflavonoids and four astragalosides (belong to triterpenoid saponins) were measured, and 44 differentially expressed genes (DEGs) of nine gene families, 44 DEGs of 16 gene families that encode for enzymes involved in isoflavonoid and triterpenoid saponin biosynthesis were identified, separately. Additionally, transcription factors (TFs) associated with isoflavonoid and triterpenoid saponin biosynthesis were analyzed, including 72 MYBs, 53 bHLHs, 64 AP2-EREBPs and 11 bZIPs. The above transcripts exhibit different expression trends in different organs.Conclusions: Our study provides important genetic information for the essential genes of isoflavonoid and triterpenoid saponin biosynthesis in A. mongholicus, and provides a basis for developing its medicinal value.


2021 ◽  
Author(s):  
Yash Lokare

A quantitative description of the violation of the second law of thermodynamics in relatively small classical systems and over short time scales comes from the fluctuation-dissipation theorem. It has been well established both theoretically and experimentally, the validity of the fluctuation theorem to small scale systems that are disturbed from their initial equilibrium states. Some experimental studies in the past have also explored the validity of the fluctuation theorem to nonequilibrium steady states at long time scales in the asymptotic limit. To this end, a theoretical and/or purely numerical model of the integral fluctuation theorem has been presented. An approximate general expression for the dissipation function has been derived for accelerated colloidal systems trapped/confined in power-law traps. Thereafter, a colloidal particle trapped in a harmonic potential (generated by an accelerating one-dimensional optical trap) and undergoing Brownian motion has been considered for the numerical study. A toy model of a quartic potential trap in addition to the harmonic trap has also been considered for the numerical study. The results presented herein show that the integral fluctuation theorem applies not only to equilibrium steady state distributions but also to nonequilibrium steady state distributions of colloidal systems in accelerated frames of reference over long time scales.


2016 ◽  
Author(s):  
Jens M. Turowski ◽  
Rebecca Hodge

Abstract. The cover effect in fluvial bedrock erosion is a major control on bedrock channel morphology and long-term channel dynamics. Here, we suggest a probabilistic framework for the description of the cover effect that can be applied to field, laboratory and modelling data and thus allows the comparison of results from different sources. The framework describes the formation of sediment cover as a function of the probability of sediment being deposited on already alleviated areas of the bed. We define benchmark cases and suggest physical interpretations of deviations from these benchmarks. Furthermore, we develop a reach-scale model for sediment transfer in a bedrock channel and use it to clarify the relations between the sediment mass residing on the bed, the exposed bedrock fraction and the transport stage. We derive system time scales and investigate cover response to cyclic perturbations. The model predicts that bedrock channels achieve grade in steady state by adjusting bed cover. Thus, bedrock channels have at least two characteristic time scales of response. Over short time scales, the degree of bed cover is adjusted such that they can just transport the supplied sediment load, while over long time scales, channel morphology evolves such that the bedrock incision rate matches the tectonic uplift or base level lowering rate.


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