Predicting developmental outcomes from regulatory DNA sequence and transcription 17 factor patterns remains an open challenge in physical biology. Using stripe 2 of the even-skipped 18 gene in Drosophila embryos as a case study, we dissect the regulatory forces underpinning a key 19 step along the developmental decision-making cascade: the generation of cytoplasmic mRNA 20 patterns via the control of transcription in individual cells. Using live imaging and computational 21 approaches, we found that the transcriptional burst frequency is modulated across the stripe to 22 control the mRNA production rate. However, we discovered that bursting alone cannot 23 quantitatively recapitulate the formation of the stripe, and that control of the window of time over 24 which each nucleus transcribes even-skipped plays a critical role in stripe formation. Theoretical 25 modeling revealed that these regulatory strategies-bursting and the time window-obey different 26 kinds of regulatory logic, suggesting that the stripe is shaped by the interplay of two distinct 27 underlying molecular processes. 28 29 35the regulatory logic of the enhancer elements that dictate the behavior of these networks, the 36 precise prediction of how gene expression patterns and developmental outcomes are driven by 37 transcription factor concentrations remains a central challenge in the field (Vincent et al., 2016). 38 Predicting developmental outcomes demands a quantitative understanding of the flow of 39 information along the central dogma: how input transcription factors dictate the output rate of 40 1 of 69 Manuscript submitted to bioRxiv mRNA production, how this rate of mRNA production dictates cytoplasmic patterns of mRNA, 41 and how these mRNA patterns lead to protein patterns that feed back into the gene regulatory 42 network. While the connection between transcription factor concentration and output mRNA 43 production rate has been the subject of active research over the last three decades (Lawrence 44 et al.connection between this output rate and 47 In order to uncover the quantitative contribution of these three regulatory strategies to pattern 62 formation, and to determine whether other regulatory strategies are at play, it is necessary to 63 measure the rate of RNA polymerase loading in individual nuclei, in real time, in a living embryo. 64 2 of 69 Manuscript submitted to bioRxiv However, to date, most studies have relied on fixed-tissue techniques such as mRNA FISH and 65 immunofluorescence in order to obtain snapshots of the cytoplasmic distributions of mRNA and 66 protein as development progresses (Jaeger et al., 2004; Fakhouri et al., 2010; Parker et al., 2011; 67 Estrada et al., 2016; Crocker et al., 2016; Verd et al., 2017; Park et al., 2018). Such techniques 68 are virtually silent regarding the regulation of single-cell gene expression over time, and are thus 69 ill-suited to the study of how spatiotemporal variations in transcriptional dynamics give rise to 70 patterns of cytoplasmic mRNA. 71...

Predicting how interactions between transcription factors and regulatory DNA sequence dictate rates of transcription and, ultimately, drive developmental outcomes remains an open challenge in physical biology. Using stripe 2 of the even-skipped gene in Drosophila embryos as a case study, we dissect the regulatory forces underpinning a key step along the developmental decision-making cascade: the generation of cytoplasmic mRNA patterns via the control of transcription in individual cells. Using live imaging and computational approaches, we found that the transcriptional burst frequency is modulated across the stripe to control the mRNA production rate. However, we discovered that bursting alone cannot quantitatively recapitulate the formation of the stripe and that control of the window of time over which each nucleus transcribes even-skipped plays a critical role in stripe formation. Theoretical modeling revealed that these regulatory strategies (bursting and the time window) respond in different ways to input transcription factor concentrations, suggesting that the stripe is shaped by the interplay of 2 distinct underlying molecular processes.

Strong solutions for a 1D fluid-particle interaction non-newtonian model: The bubbling regime Rheology of concentrated soft and hard-sphere suspensions J. Rheol. 57, 1195 (2013); 10.1122/1.4808054 A computational study of the coalescence between a drop and an interface in Newtonian and viscoelastic fluids Experiments on the acoustic vibrations of elastic nanostructures in fluid media have been used to study the mechanical properties of materials, as well as for mechanical and biological sensing. The medium surrounding the nanostructure is typically modeled as a Newtonian fluid. A recent experiment however suggested that high-frequency longitudinal vibration of bipyramidal nanoparticles could trigger a viscoelastic response in water-glycerol mixtures [Pelton et al., "Viscoelastic flows in simple liquids generated by vibrating nanostructures," Phys. Rev. Lett. 111, 244502 (2013)]. Motivated by these experimental studies, we first revisit a classical continuum mechanics problem of the purely radial vibration of an elastic sphere, also called the breathing mode, in a compressible viscous fluid and then extend our analysis to a viscoelastic medium using the Maxwell fluid model. The effects of fluid compressibility and viscoelasticity are discussed. Although in the case of longitudinal vibration of bipyramidal nanoparticles, the effects of fluid compressibility were shown to be negligible, we demonstrate that it plays a significant role in the breathing mode of an elastic sphere. On the other hand, despite the different vibration modes, the breathing mode of a sphere triggers a viscoelastic response in water-glycerol mixtures similar to that triggered by the longitudinal vibration of bipyramidal nanoparticles. We also comment on the effect of fluid viscoelasticity on the idea of destroying virus particles by acoustic resonance. C 2015 AIP Publishing LLC. [http://dx.