Disorder in DNA-Linked Gold Nanoparticle Assemblies

We report experimental observations on the effect of disorder on the phase behavior of DNA-linked nanoparticle assemblies. Variation in DNA linker lengths results in different melting temperatures of the DNA-linked nanoparticle assemblies. We observed an unusual trend of a non-monotonic ``zigzag'' pattern in the melting temperature as a function of DNAlinker length. Linker DNA resulting in unequal DNA duplex lengths introduces disorder and lowers the melting temperature of the nanoparticle system. Comparison with free DNA thermodynamics shows that such an anomalous zigzag pattern does not exist for free DNA duplex melting, which suggests that the disorder introduced by unequal DNA duplex lengths results in this unusual collective behavior of DNA-linked nanoparticle assemblies.Comment: 4 pages, 4 figures, Phys.Rev.Lett. (2005), to appea

Efficient Seeds Computation Revisited

The notion of the cover is a generalization of a period of a string, and there are linear time algorithms for finding the shortest cover. The seed is a more complicated generalization of periodicity, it is a cover of a superstring of a given string, and the shortest seed problem is of much higher algorithmic difficulty. The problem is not well understood, no linear time algorithm is known. In the paper we give linear time algorithms for some of its versions --- computing shortest left-seed array, longest left-seed array and checking for seeds of a given length. The algorithm for the last problem is used to compute the seed array of a string (i.e., the shortest seeds for all the prefixes of the string) in $O(n^2)$ time. We describe also a simpler alternative algorithm computing efficiently the shortest seeds. As a by-product we obtain an $O(n\log{(n/m)})$ time algorithm checking if the shortest seed has length at least $m$ and finding the corresponding seed. We also correct some important details missing in the previously known shortest-seed algorithm (Iliopoulos et al., 1996).Comment: 14 pages, accepted to CPM 201

Sequence context and crosslinking mechanism affect the efficiency of in vivo capture of a protein–protein interaction

Protein–protein interactions (PPIs) are essential for implementing cellular processes and thus methods for the discovery and study of PPIs are highly desirable. An emerging method for capturing PPIs in their native cellular environment is in vivo covalent chemical capture, a method that uses nonsense suppression to site specifically incorporate photoactivable unnatural amino acids (UAAs) in living cells. However, in one study we found that this method did not capture a PPI for which there was abundant functional evidence, a complex formed between the transcriptional activator Gal4 and its repressor protein Gal80. Here we describe the factors that influence the success of covalent chemical capture and show that the innate reactivity of the two UAAs utilized, ( p‐ benzoylphenylalanine (pBpa) and p ‐azidophenylalanine (pAzpa)), plays a profound role in the capture of Gal80 by Gal4. Based upon these data, guidelines are outlined for the successful use of in vivo photo‐crosslinking to capture novel PPIs and to characterize the interfaces. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 391–397, 2014.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102672/1/bip22395.pd

Pattern Matching in Multiple Streams

We investigate the problem of deterministic pattern matching in multiple streams. In this model, one symbol arrives at a time and is associated with one of s streaming texts. The task at each time step is to report if there is a new match between a fixed pattern of length m and a newly updated stream. As is usual in the streaming context, the goal is to use as little space as possible while still reporting matches quickly. We give almost matching upper and lower space bounds for three distinct pattern matching problems. For exact matching we show that the problem can be solved in constant time per arriving symbol and O(m+s) words of space. For the k-mismatch and k-difference problems we give O(k) time solutions that require O(m+ks) words of space. In all three cases we also give space lower bounds which show our methods are optimal up to a single logarithmic factor. Finally we set out a number of open problems related to this new model for pattern matching.Comment: 13 pages, 1 figur

Unzipping Kinetics of Double-Stranded DNA in a Nanopore

We studied the unzipping kinetics of single molecules of double-stranded DNA by pulling one of their two strands through a narrow protein pore. PCR analysis yielded the first direct proof of DNA unzipping in such a system. The time to unzip each molecule was inferred from the ionic current signature of DNA traversal. The distribution of times to unzip under various experimental conditions fit a simple kinetic model. Using this model, we estimated the enthalpy barriers to unzipping and the effective charge of a nucleotide in the pore, which was considerably smaller than previously assumed.Comment: 10 pages, 5 figures, Accepted: Physics Review Letter

A nonlinear dynamic model of DNA with a sequence-dependent stacking term

No simple model exists that accurately describes the melting behavior and breathing dynamics of double-stranded DNA as a function of nucleotide sequence. This is especially true for homogenous and periodic DNA sequences, which exhibit large deviations in melting temperature from predictions made by additive thermodynamic contributions. Currently, no method exists for analysis of the DNA breathing dynamics of repeats and of highly G/C- or A/T-rich regions, even though such sequences are widespread in vertebrate genomes. Here, we extend the nonlinear Peyrard–Bishop–Dauxois (PBD) model of DNA to include a sequence-dependent stacking term, resulting in a model that can accurately describe the melting behavior of homogenous and periodic sequences. We collect melting data for several DNA oligos, and apply Monte Carlo simulations to establish force constants for the 10 dinucleotide steps (CG, CA, GC, AT, AG, AA, AC, TA, GG, TC). The experiments and numerical simulations confirm that the GG/CC dinucleotide stacking is remarkably unstable, compared with the stacking in GC/CG and CG/GC dinucleotide steps. The extended PBD model will facilitate thermodynamic and dynamic simulations of important genomic regions such as CpG islands and disease-related repeats

Technical assistance, neo-colonialism or mutual trade? The experience of an Anglo/Ukrainian/Russian social work practice learning project

Since the collapse of the Soviet Union there has been a steady stream of Western consultants ready to work in Eastern Europe and Russia and share professional and academic expertise and experience. Social work, unknown as a discrete discipline or profession in the Soviet Union, has been a growth area with funding from a variety of sources to help promote East-West partnerships.Social work theory and practice emphasises critical appraisal of policy and embraces issues of power, discrimination and oppression. Social work educators should therefore be especially alert to the complex ethical questions which these kinds of collaborations raise, and adept at finding practical solutions or workable compromises. This article explores these ethical and political issues with reference to a project to develop social work practice learning in a Russian oblast' (region). The project was an ambitious partnership of British, Ukrainian and Russian educators, involving numerous Russian social work and related agencies, and four Russian universities and colleges in one oblast'. The authors use a series of vignettes to help the reader achieve insights into these East-West transactions. The article concludes with a discussion of different interpretations of these dealings, using three prisms: technical assistance, neo-colonialism and mutual trade

Single Molecule Statistics and the Polynucleotide Unzipping Transition

We present an extensive theoretical investigation of the mechanical unzipping of double-stranded DNA under the influence of an applied force. In the limit of long polymers, there is a thermodynamic unzipping transition at a critical force value of order 10 pN, with different critical behavior for homopolymers and for random heteropolymers. We extend results on the disorder-averaged behavior of DNA's with random sequences to the more experimentally accessible problem of unzipping a single DNA molecule. As the applied force approaches the critical value, the double-stranded DNA unravels in a series of discrete, sequence-dependent steps that allow it to reach successively deeper energy minima. Plots of extension versus force thus take the striking form of a series of plateaus separated by sharp jumps. Similar qualitative features should reappear in micromanipulation experiments on proteins and on folded RNA molecules. Despite their unusual form, the extension versus force curves for single molecules still reveal remnants of the disorder-averaged critical behavior. Above the transition, the dynamics of the unzipping fork is related to that of a particle diffusing in a random force field; anomalous, disorder-dominated behavior is expected until the applied force exceeds the critical value for unzipping by roughly 5 pN.Comment: 40 pages, 18 figure