scholarly journals Tuning transcriptional regulation through signaling: A predictive theory of allosteric induction

2017 ◽  
Author(s):  
Manuel Razo-Mejia ◽  
Stephanie L. Barnes ◽  
Nathan M. Belliveau ◽  
Griffin Chure ◽  
Tal Einav ◽  
...  

AbstractAllosteric regulation is found across all domains of life, yet we still lack simple, predictive theories that directly link the experimentally tunable parameters of a system to its input-output response. To that end, we present a general theory of allosteric transcriptional regulation using the Monod-Wyman-Changeux model. We rigorously test this model using the ubiquitous simple repression motif in bacteria by first predicting the behavior of strains that span a large range of repressor copy numbers and DNA binding strengths and then constructing and measuring their response. Our model not only accurately captures the induction profiles of these strains but also enables us to derive analytic expressions for key properties such as the dynamic range and [EC50]. Finally, we derive an expression for the free energy of allosteric repressors which enables us to collapse our experimental data onto a single master curve that captures the diverse phenomenology of the induction profiles.


1988 ◽  
Vol 129 ◽  
pp. 27-28
Author(s):  
S. C. Unwin ◽  
R. J. Davis

We present a new high dynamic range map of the quasar 3C 273, made from observations with a VLBI network of 12 telescopes. This new map at 18 cm wavelength has one of the highest dynamic ranges yet achieved with VLBI, and it shows the ‘jet’ extending to at least 180 milliarcsec, or 330 pc from the nucleus of the quasar. Strong limits can be placed on the brightness of any ‘counter-jet’ on kiloparsec-scales, as no emission is visible on the opposite side of the ‘core’. Combining with other VLBI, VLA and MERLIN maps shows that the jet is visible and continuous over a very large range of scales, from 1 pc to 40 kpc.



2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qingqiao Xie ◽  
Yuandi Zhuang ◽  
Gaojun Ye ◽  
Tiankuo Wang ◽  
Yi Cao ◽  
...  

AbstractMany soft tissues are compression-stiffening and extension-softening in response to axial strains, but common hydrogels are either inert (for ideal chains) or tissue-opposite (for semiflexible polymers). Herein, we report a class of astral hydrogels that are structurally distinct from tissues but mechanically tissue-like. Specifically, hierarchical self-assembly of amphiphilic gemini molecules produces radial asters with a common core and divergently growing, semiflexible ribbons; adjacent asters moderately interpenetrate each other via interlacement of their peripheral ribbons to form a gel network. Resembling tissues, the astral gels stiffen in compression and soften in extension with all the experimental data across different gel compositions collapsing onto a single master curve. We put forward a minimal model to reproduce the master curve quantitatively, underlying the determinant role of aster-aster interpenetration. Compression significantly expands the interpenetration region, during which the number of effective crosslinks is increased and the network strengthened, while extension does the opposite. Looking forward, we expect this unique mechanism of interpenetration to provide a fresh perspective for designing and constructing mechanically tissue-like materials.



Fractal colloid aggregates are studied with both static and dynamic light scattering. The dynamic light scattering data are scaled onto a single master curve, whose shape is sensitive to the structure of the aggregates and their mass distribution. By using the structure factor determined from computer-simulated aggregates, and including the effects of rotational diffusion, we predict the shape of the master curve for different cluster distributions. Excellent agreement is found between our predictions and the data for the two limiting régimes, diffusion-limited and reaction-limited colloid aggregation. Furthermore, using data from several completely different colloids, we find that the shapes of the master curves are identical for each régime. In addition, the cluster fractal dimensions and the aggregation kinetics are identical in each régime. This provides convincing experimental evidence of the universality of these two régimes of colloid aggregation.



2019 ◽  
Vol 7 (10) ◽  
pp. 454
Author(s):  
Markus Dieser ◽  
Heidi J. Smith ◽  
Thiruvarangan Ramaraj ◽  
Christine M. Foreman

As many bacteria detected in Antarctic environments are neither true psychrophiles nor endemic species, their proliferation in spite of environmental extremes gives rise to genome adaptations. Janthinobacterium sp. CG23_2 is a bacterial isolate from the Cotton Glacier stream, Antarctica. To understand how Janthinobacterium sp. CG23_2 has adapted to its environment, we investigated its genomic traits in comparison to genomes of 35 published Janthinobacterium species. While we hypothesized that genome shrinkage and specialization to narrow ecological niches would be energetically favorable for dwelling in an ephemeral Antarctic stream, the genome of Janthinobacterium sp. CG23_2 was on average 1.7 ± 0.6 Mb larger and predicted 1411 ± 499 more coding sequences compared to the other Janthinobacterium spp. Putatively identified horizontal gene transfer events contributed 0.92 Mb to the genome size expansion of Janthinobacterium sp. CG23_2. Genes with high copy numbers in the species-specific accessory genome of Janthinobacterium sp. CG23_2 were associated with environmental sensing, locomotion, response and transcriptional regulation, stress response, and mobile elements—functional categories which also showed molecular adaptation to cold. Our data suggest that genome plasticity and the abundant complementary genes for sensing and responding to the extracellular environment supported the adaptation of Janthinobacterium sp. CG23_2 to this extreme environment.



Cell Systems ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 456-469.e10 ◽  
Author(s):  
Manuel Razo-Mejia ◽  
Stephanie L. Barnes ◽  
Nathan M. Belliveau ◽  
Griffin Chure ◽  
Tal Einav ◽  
...  


2009 ◽  
Vol 19 (3-4) ◽  
pp. 335-376 ◽  
Author(s):  
ROBERT ATKEY

AbstractMoggi's Computational Monads and Poweret al.'s equivalent notion of Freyd category have captured a large range of computational effects present in programming languages. Examples include non-termination, non-determinism, exceptions, continuations, side effects and input/output. We present generalisations of both computational monads and Freyd categories, which we callparameterisedmonads andparameterisedFreyd categories, that also capture computational effects with parameters. Examples of such are composable continuations, side effects where the type of the state varies and input/output where the range of inputs and outputs varies. By considering structured parameterisation also, we extend the range of effects to cover separated side effects and multiple independent streams of I/O. We also present two typed λ-calculi that soundly and completely model our categorical definitions – with and without symmetric monoidal parameterisation – and act as prototypical languages with parameterised effects.



Author(s):  
Julio Villalba ◽  
Javier Hormigo

AbstractThis article proposes a family of high-radix floating-point representation to efficiently deal with floating-point addition in FPGA devices with no native floating-point support. Since variable shifter implementation (required in any FP adder) has a very high cost in FPGA, high-radix formats considerably reduce the number of possible shifts, decreasing the execution time and area highly. Although the high-radix format produces also a significant penalty in the implementation of multipliers, the experimental results show that the adder improvement overweights the multiplication penalty for most of the practical and common cases (digital filters, matrix multiplications, etc.). We also provide the designer with guidelines on selecting a suitable radix as a function of the ratio between the number of additions and multiplications of the targeted algorithm. For applications with similar numbers of additions and multiplications, the high-radix version may be up to 26% faster and even having a wider dynamic range and using higher number of significant bits. Furthermore, thanks to the proposed efficient converters between the standard IEEE-754 format and our internal high-radix format, the cost of the input/output conversions in FPGA accelerators is negligible.



2005 ◽  
Author(s):  
H. Aryafar ◽  
H. P. Kavehpour

During the coalescence of a drop with a planar interface, a hole is generated in a microscopic film that separates the drop from the interface. An experimental study has been performed to investigate the time dependent behavior of the radius of the hole generated during coalescence. The study consisted of placing drops of various sizes and physical properties on a planar interface. The coalescence process was recorded from underneath the interface with the aid of a high speed digital camera and a prism. The experiment captured two separate processes, film rupture and the closing of the hole. During the film rupture, the hole radius demonstrated a power law time dependence. Dimensional analysis showed the percentage of time the hole used to reach its maximum radius was approximately constant for all drops. Moreover, all dimensionless drop rupture radii and times fit onto a single master curve and were independent of their physical properties during the opening. However during the closing of the hole, the dimensionless time and radii did not fit a master curve analogous to the hole rupture. The closing of the hole is an entirely different event from the opening and is governed by different parameters.



2019 ◽  
Vol 48 (1) ◽  
pp. 121-163 ◽  
Author(s):  
Rob Phillips ◽  
Nathan M. Belliveau ◽  
Griffin Chure ◽  
Hernan G. Garcia ◽  
Manuel Razo-Mejia ◽  
...  

It is tempting to believe that we now own the genome. The ability to read and rewrite it at will has ushered in a stunning period in the history of science. Nonetheless, there is an Achilles’ heel exposed by all of the genomic data that has accrued: We still do not know how to interpret them. Many genes are subject to sophisticated programs of transcriptional regulation, mediated by DNA sequences that harbor binding sites for transcription factors, which can up- or down-regulate gene expression depending upon environmental conditions. This gives rise to an input–output function describing how the level of expression depends upon the parameters of the regulated gene—for instance, on the number and type of binding sites in its regulatory sequence. In recent years, the ability to make precision measurements of expression, coupled with the ability to make increasingly sophisticated theoretical predictions, has enabled an explicit dialogue between theory and experiment that holds the promise of covering this genomic Achilles’ heel. The goal is to reach a predictive understanding of transcriptional regulation that makes it possible to calculate gene expression levels from DNA regulatory sequence. This review focuses on the canonical simple repression motif to ask how well the models that have been used to characterize it actually work. We consider a hierarchy of increasingly sophisticated experiments in which the minimal parameter set learned at one level is applied to make quantitative predictions at the next. We show that these careful quantitative dissections provide a template for a predictive understanding of the many more complex regulatory arrangements found across all domains of life.



Author(s):  
N A Fleck ◽  
K L Johnson ◽  
M E Mear ◽  
L C Zhang

A theory of cold rolling of thin gauge strip is presented which, within the idealizations of homogeneous deformation and a constant coefficient of Coulomb friction, rigorously models the elastic deformation of the rolls and the frictional traction at the interface. In contrast with classical theories (3) it is shown that, for gauges less than a critical value, plastic reduction takes place in two zones, at entry and exit, which are separated by a neutral zone in which the rolls are compressed fiat and there is no slip between the rolls and the strip. Roll load and torque are governed by five independent non-dimensional parameters which express the influence of gauge, reduction, friction and front and back tensions. Values of load and torque have been computed (for zero front and back tensions) for a wide range of thickness, reduction and friction and have been found to collapse approximately on to a single master curve.



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