1,144 research outputs found
Decoding Single Molecule Time Traces with Dynamic Disorder
Single molecule time trajectories of biomolecules provide glimpses into
complex folding landscapes that are difficult to visualize using conventional
ensemble measurements. Recent experiments and theoretical analyses have
highlighted dynamic disorder in certain classes of biomolecules, whose dynamic
pattern of conformational transitions is affected by slower transition dynamics
of internal state hidden in a low dimensional projection. A systematic means to
analyze such data is, however, currently not well developed. Here we report a
new algorithm - Variational Bayes-double chain Markov model (VB-DCMM) - to
analyze single molecule time trajectories that display dynamic disorder. The
proposed analysis employing VB-DCMM allows us to detect the presence of dynamic
disorder, if any, in each trajectory, identify the number of internal states,
and estimate transition rates between the internal states as well as the rates
of conformational transition within each internal state. Applying VB-DCMM
algorithm to single molecule FRET data of H-DNA in 100 mM-Na solution,
followed by data clustering, we show that at least 6 kinetic paths linking 4
distinct internal states are required to correctly interpret the duplex-triplex
transitions of H-DNA
The Role of Evaluability Bias and the Fairness Effect in the Escalation of Commitment to Troubled Software Product Development Projects
New software product development entails considerable risks. One significant risk is that decision makers can become overly committed to troubled software product development projects (i.e., escalation of commitment). While prior research has identified factors that promote escalation in information technology projects, there has been little attempt to leverage the context of software product development, which can include evaluating attributes of a software product under development and weighing a personal financial reward tied to a successful product launch. In this study, we conducted two experiments to investigate how evaluability bias concerning software attributes and the fairness effect that arises from the relative amount of a personal financial reward influence the escalation of commitment to troubled software product development projects. Our findings suggest that the escalation of commitment to troubled software product development projects is influenced by both evaluability bias, which affects the perceived attractiveness of a software product under development, and the fairness effect, which influences the perceived attractiveness of a personal financial reward tied to a successful product launch. This study contributes to both the information systems literature and the escalation literature by providing novel theoretical explanations as to why escalation occurs in the context of new software product developmen
On instantons as Kaluza-Klein modes of M5-branes
Instantons and W-bosons in 5d maximally supersymmetric Yang-Mills theory arise from a circle compactification of the 6d (2,0) theory as Kaluza-Klein modes and winding self-dual strings, respectively. We study an index which counts BPS instantons with electric charges in Coulomb and symmetric phases. We first prove the existence of unique threshold bound state of (noncommutative) U(1) instantons for any instanton number, and also show that charged instantons in the Coulomb phase correctly give the degeneracy of SU(2) self-dual strings. By studying SU(N) self-dual strings in the Coulomb phase, we find novel momentum-carrying degrees on the worldsheet. The total number of these degrees equals the anomaly coefficient of SU(N) (2,0) theory. We finally show that our index can be used to study the symmetric phase of this theory, and provide an interpretation as the superconformal index of the sigma model on instanton moduli space.1156sciescopu
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Competition between B-Z and B-L transitions in a single DNA molecule: Computational studies
Under negative torsion, DNA adopts left-handed helical forms, such as Z-DNA and L-DNA. Using the random copolymer model developed for a wormlike chain, we represent a single DNA molecule with structural heterogeneity as a helical chain consisting of monomers which can be characterized by different helical senses and pitches. By Monte Carlo simulation, where we take into account bending and twist fluctuations explicitly, we study sequence dependence of B-Z transitions under torsional stress and tension focusing on the interaction with B-L transitions. We consider core sequences, (GC)(n) repeats or (TG)(n) repeats, which can interconvert between the right-handed B form and the left-handed Z form, imbedded in a random sequence, which can convert to left-handed L form with different (tension dependent) helical pitch. We show that Z-DNA formation from the (GC)(n) sequence is always supported by unwinding torsional stress but Z-DNA formation from the (TG)(n) sequence, which are more costly to convert but numerous, can be strongly influenced by the quenched disorder in the surrounding random sequence.National Research Foundation NRF-2012 R1A1A3013044 NRF-2014R1A1A2055681NRF-2012R1A1A2021736IBS-R023-D1NRF-2015R1A2A2A01005916Chemistr
SNP@Ethnos: a database of ethnically variant single-nucleotide polymorphisms
Inherited genetic variation plays a critical but largely uncharacterized role in human differentiation. The completion of the International HapMap Project makes it possible to identify loci that may cause human differentiation. We have devised an approach to find such ethnically variant single-nucleotide polymorphisms (ESNPs) from the genotype profile of the populations included in the International HapMap database. We selected ESNPs using the nearest shrunken centroid method (NSCM), and performed multiple tests for genetic heterogeneity and frequency spectrum on genes having ESNPs. The function and disease association of the selected SNPs were also annotated. This resulted in the identification of 100 736 SNPs that appeared uniquely in each ethnic group. Of these SNPs, 1009 were within disease-associated genes, and 85 were predicted as damaging using the Sorting Intolerant From Tolerant system. This study resulted in the creation of the SNP@Ethnos database, which is designed to make this type of detailed genetic variation approach available to a wider range of researchers. SNP@Ethnos is a public database of ESNPs with annotation information that currently contains 100 736 ESNPs from 10 138 genes, and can be accessed at and or directly at
Inhibition of poly(ADP-ribose)polymerase binding to DNA by thymidine dimer
AbstractThe ability of poly(ADP-ribose)polymerase to bind damaged DNA was assessed by electrophoretic mobility shift assay. DNA binding domain of poly(ADP-ribose)polymerase (PARPDBD) binds to synthetic deoxyribonucleotide duplex 10-mer. However, the synthetic deoxyribonucleotide duplex containing cys-syn thymidine dimer which produces the unwinding of DNA helix structure lost its affinity to PARPDBD. It was shown that the binding of PARPDBD to the synthetic deoxyribonucleotide duplex was not affected by O6-Me-dG which causes only minor distortion of DNA helix structure. This study suggests that the stabilized DNA helix structure is important for poly(ADP-ribose)polymerase binding to DNA breaks, which are known to stimulate catalytic activity of poly(ADP-ribose)polymerase
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