Explicit DNase sequence bias modeling enables high-resolution transcription factor footprint detection.

DNaseI footprinting is an established assay for identifying transcription factor (TF)-DNA interactions with single base pair resolution. High-throughput DNase-seq assays have recently been used to detect in vivo DNase footprints across the genome. Multiple computational approaches have been developed to identify DNase-seq footprints as predictors of TF binding. However, recent studies have pointed to a substantial cleavage bias of DNase and its negative impact on predictive performance of footprinting. To assess the potential for using DNase-seq to identify individual binding sites, we performed DNase-seq on deproteinized genomic DNA and determined sequence cleavage bias. This allowed us to build bias corrected and TF-specific footprint models. The predictive performance of these models demonstrated that predicted footprints corresponded to high-confidence TF-DNA interactions. DNase-seq footprints were absent under a fraction of ChIP-seq peaks, which we show to be indicative of weaker binding, indirect TF-DNA interactions or possible ChIP artifacts. The modeling approach was also able to detect variation in the consensus motifs that TFs bind to. Finally, cell type specific footprints were detected within DNase hypersensitive sites that are present in multiple cell types, further supporting that footprints can identify changes in TF binding that are not detectable using other strategies.

Quantitative genetics of CTCF binding reveal local sequence effects and different modes of X-chromosome association.

Associating genetic variation with quantitative measures of gene regulation offers a way to bridge the gap between genotype and complex phenotypes. In order to identify quantitative trait loci (QTLs) that influence the binding of a transcription factor in humans, we measured binding of the multifunctional transcription and chromatin factor CTCF in 51 HapMap cell lines. We identified thousands of QTLs in which genotype differences were associated with differences in CTCF binding strength, hundreds of them confirmed by directly observable allele-specific binding bias. The majority of QTLs were either within 1 kb of the CTCF binding motif, or in linkage disequilibrium with a variant within 1 kb of the motif. On the X chromosome we observed three classes of binding sites: a minority class bound only to the active copy of the X chromosome, the majority class bound to both the active and inactive X, and a small set of female-specific CTCF sites associated with two non-coding RNA genes. In sum, our data reveal extensive genetic effects on CTCF binding, both direct and indirect, and identify a diversity of patterns of CTCF binding on the X chromosome.

The open shop scheduling problem with a given sequence of jobs on one machine

The paper considers the open shop scheduling problem to minimize the make-span, provided that one of the machines has to process the jobs according to a given sequence. We show that in the preemptive case the problem is polynomially solvable for an arbitrary number of machines. If preemption is not allowed, the problem is NP-hard in the strong sense if the number of machines is variable, and is NP-hard in the ordinary sense in the case of two machines. For the latter case we give a heuristic algorithm that runs in linear time and produces a schedule with the makespan that is at most 5/4 times the optimal value. We also show that the two-machine problem in the nonpreemptive case is solvable in pseudopolynomial time by a dynamic programming algorithm, and that the algorithm can be converted into a fully polynomial approximation scheme. © 1998 John Wiley & Sons, Inc. Naval Research Logistics 45: 705–731, 1998

Dynamic analysis of Flip-Chip Self-Alignment

Self-alignment of soldered electronic components such as flip-chips (FC), ball grid arrays (BGA) and optoelectronic devices during solder reflow is important as it ensures good alignment between components and substrates. Two uncoupled analytical models are presented which provide estimates of the dynamic time scales of both the chip and the solder in the self-alignment process. These predicted time scales can be used to decide whether a coupled dynamic analysis is required for the analysis of the chip motion. In this paper, we will show that for flip-chips, the alignment dynamics can be described accurately only when the chip motion is coupled with the solder motion because the two have similar time-scale values. To study this coupled phenomenon, a dynamic modeling method has been developed. The modeling results show that the uncoupled and coupled calculations result in significantly different predictions. The calculations based on the coupled model predict much faster rates of alignment than those predicted using the uncoupled approach.

Optoelectronic packaging interfaces for submicron alignment (OPISA) and the dynamics of laser spot weld formation

The work presented in this paper is part of the OPISA project. This is a collaborative research project between the University of Greenwich and Bookham Technology. This report describes some of the initial work undertaken towards the goal of investigating optoelectronic packaging where alignment issues between optical sources and fibers can arise as part of the fabrication process. The focus of this study is on charting the dynamics of laser spot weld formation. This paper introduces some of the initial simulation work that has been undertaken and presents a model describing a transient heat source applied from a laser pulse to weld a stainless steel sleeve and ferrule and the resulting weld formation

Multiple-locus sequence typing analysis of Bacillus thuringiensis recovered from the phylloplane of clover (Trifolium hybridum) in vegetative form

The chromosomal genotype, as judged by multi locus sequence typing, and the episomal genotype, as judged by plasmid profile and cry gene content, were analyzed for a collection of strains of Bacillus thuringiensis. These had been recovered in vegetative form over a period of several months from the leaves of a small plot of clover (Trifolium hybridum). A clonal population structure was indicated, although greater variation in sequence types (STs) was discovered than in previous collections of B. cereus/B. thuringiensis. Isolates taken at the same time had quite different genotypes, whereas those of identical genotypes were recovered at different times. The profiles of plasmid content and cry genes generally bore no relation to each other nor to the STs. Evidently, although relatively little recombination was occurring in the seven chromosomal genes analyzed, a great deal of conjugal transfer, and perhaps recombination, was occurring involving plasmids. A clinical diarrheal isolate of B. cereus and the commercial biopesticide strain HD-1 of B. thuringiensis, both included as out-groups, were found to have very similar STs. This further emphasizes the role of episomal elements in the characteristics and differentiation of these two species.