1,197 research outputs found
Can one predict DNA Transcription Start Sites by studying bubbles?
It has been speculated that bubble formation of several base-pairs due to
thermal fluctuations is indicatory for biological active sites. Recent
evidence, based on experiments and molecular dynamics (MD) simulations using
the Peyrard-Bishop-Dauxois model, seems to point in this direction. However,
sufficiently large bubbles appear only seldom which makes an accurate
calculation difficult even for minimal models. In this letter, we introduce a
new method that is orders of magnitude faster than MD. Using this method we
show that the present evidence is unsubstantiated.Comment: 4 pages, 3 figures, accepted for publication in physical review
letter
SOFTWARE PUBLISHING AND THE ECONOMIC IMPACT OF COPYING
Unauthorized duplication of microcomputer software is apparently commonplace. Recent decisions by major software publishers to drop copy protection may well result in even more unauthorized duplication. This paper addresses the impact of unauthorized software duplication on software publishers\u27 profits. Software clubs of the type suggested by Buchanan (1965) are posited as providing a mechanism whereby software publishers can indirectly appropriate revenue for unauthorized software copies. It is shown that, under certain conditions, software publishers\u27 profits may actually increase when users can make unauthorized copies
Increasing β-catenin/Wnt3A activity levels drive mechanical strain-induced cell cycle progression through mitosis.
Mechanical force and Wnt signaling activate β-catenin-mediated transcription to promote proliferation and tissue expansion. However, it is unknown whether mechanical force and Wnt signaling act independently or synergize to activate β-catenin signaling and cell division. We show that mechanical strain induced Src-dependent phosphorylation of Y654 β-catenin and increased β-catenin-mediated transcription in mammalian MDCK epithelial cells. Under these conditions, cells accumulated in S/G2 (independent of DNA damage) but did not divide. Activating β-catenin through Casein Kinase I inhibition or Wnt3A addition increased β-catenin-mediated transcription and strain-induced accumulation of cells in S/G2. Significantly, only the combination of mechanical strain and Wnt/β-catenin activation triggered cells in S/G2 to divide. These results indicate that strain-induced Src phosphorylation of β-catenin and Wnt-dependent β-catenin stabilization synergize to increase β-catenin-mediated transcription to levels required for mitosis. Thus, local Wnt signaling may fine-tune the effects of global mechanical strain to restrict cell divisions during tissue development and homeostasis
A stitch in time: Efficient computation of genomic DNA melting bubbles
Background: It is of biological interest to make genome-wide predictions of
the locations of DNA melting bubbles using statistical mechanics models.
Computationally, this poses the challenge that a generic search through all
combinations of bubble starts and ends is quadratic.
Results: An efficient algorithm is described, which shows that the time
complexity of the task is O(NlogN) rather than quadratic. The algorithm
exploits that bubble lengths may be limited, but without a prior assumption of
a maximal bubble length. No approximations, such as windowing, have been
introduced to reduce the time complexity. More than just finding the bubbles,
the algorithm produces a stitch profile, which is a probabilistic graphical
model of bubbles and helical regions. The algorithm applies a probability peak
finding method based on a hierarchical analysis of the energy barriers in the
Poland-Scheraga model.
Conclusions: Exact and fast computation of genomic stitch profiles is thus
feasible. Sequences of several megabases have been computed, only limited by
computer memory. Possible applications are the genome-wide comparisons of
bubbles with promotors, TSS, viral integration sites, and other melting-related
regions.Comment: 16 pages, 10 figure
Superhelical Duplex Destabilization and the Recombination Position Effect
The susceptibility to recombination of a plasmid inserted into a chromosome
varies with its genomic position. This recombination position effect is known to
correlate with the average G+C content of the flanking sequences. Here we
propose that this effect could be mediated by changes in the susceptibility to
superhelical duplex destabilization that would occur. We use standard
nonparametric statistical tests, regression analysis and principal component
analysis to identify statistically significant differences in the
destabilization profiles calculated for the plasmid in different contexts, and
correlate the results with their measured recombination rates. We show that the
flanking sequences significantly affect the free energy of denaturation at
specific sites interior to the plasmid. These changes correlate well with
experimentally measured variations of the recombination rates within the
plasmid. This correlation of recombination rate with superhelical
destabilization properties of the inserted plasmid DNA is stronger than that
with average G+C content of the flanking sequences. This model suggests a
possible mechanism by which flanking sequence base composition, which is not
itself a context-dependent attribute, can affect recombination rates at
positions within the plasmid
P5_3 Pigs on the Wing
This article explores the possibility of a pig flying over Battersea Power Station, as shown on the Pink Floyd album ’Animals,’ and the time it would take for the pig’s height to exceed the height of the chimneys. Using the lift force equation, we graphically show the minimum wind velocity required to lift a 70 kg pig 101 m, the height of the Battersea Power Station. We find that for a pig of this mass, a wind velocity of 20.4 ms-1 was required. Furthermore, in order to measure the time for the pig to reach the height of Battersea Power Station, an acceleration of 3.8 ms-2 was calculated; this assumes a severe gale wind velocity of 24 ms-1 as defined by The Met Office. We find that it would take 7.3 s to travel the required height, assuming only vertical movement.
P5_1 ”Everybody knows the Moon is made of cheese...”: Return of the Cheddar
This Letter explores the repercussions of the Moon turning into cheddar, and finds that with the same volume and lighter mass of m = 2.49 × 1022kg, it would escape the Earth’s sphere of influence. We looked at two possible escape trajectories, prograde and retrograde, and found the new orbital distances to be between 0.73AU and 1.00AU, and between 1.00AU and 1.51AU, respectively. Thus potentially carrying the Moon very near to the orbits of Venus or Mars.
P5_2 Spaghettification: Surviving a Black Hole Event Horizon
We found that it is possible to stay conscious falling through the event horizon of aBlack Hole if the mass exceeds 19,000M_sol. This assumes the average person is ofgood health and can stay conscious with a relative force less than 5 g acting upon them
Theoretical Analysis of Competing Conformational Transitions in Superhelical DNA
We develop a statistical mechanical model to analyze the competitive behavior of transitions to multiple alternate conformations in a negatively supercoiled DNA molecule of kilobase length and specified base sequence. Since DNA superhelicity topologically couples together the transition behaviors of all base pairs, a unified model is required to analyze all the transitions to which the DNA sequence is susceptible. Here we present a first model of this type. Our numerical approach generalizes the strategy of previously developed algorithms, which studied superhelical transitions to a single alternate conformation. We apply our multi-state model to study the competition between strand separation and B-Z transitions in superhelical DNA. We show this competition to be highly sensitive to temperature and to the imposed level of supercoiling. Comparison of our results with experimental data shows that, when the energetics appropriate to the experimental conditions are used, the competition between these two transitions is accurately captured by our algorithm. We analyze the superhelical competition between B-Z transitions and denaturation around the c-myc oncogene, where both transitions are known to occur when this gene is transcribing. We apply our model to explore the correlation between stress-induced transitions and transcriptional activity in various organisms. In higher eukaryotes we find a strong enhancement of Z-forming regions immediately 5′ to their transcription start sites (TSS), and a depletion of strand separating sites in a broad region around the TSS. The opposite patterns occur around transcript end locations. We also show that susceptibility to each type of transition is different in eukaryotes and prokaryotes. By analyzing a set of untranscribed pseudogenes we show that the Z-susceptibility just downstream of the TSS is not preserved, suggesting it may be under selection pressure
Improving Behaviour in Schools: Evidence Review
This is the final version. Available from the Education Endowment Foundation via the link in this record"Improving Behaviour in Schools: Guidance Report" is available in ORE at http://hdl.handle.net/10871/37789Education Endowment Foundatio
- …