Joint rolling-horizon scheduling of materials processing and lot-sizing with sequence-dependent setups

A lot sizing and scheduling problem from a foundry is considered in which key materials are produced and then transformed into many products on a single machine. A mixed integer programming (MIP) model is developed, taking into account sequence-dependent setup costs and times, and then adapted for rolling horizon use. A relax-and-fix (RF) solution heuristic is proposed and computationally tested against a high-performance MIP solver. Three variants of local search are also developed to improve the RF method and tested. Finally the solutions are compared with those currently practiced at the foundry.

Production lot sizing and scheduling with non-triangular sequence-dependent setup times

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Distamycin A affects the stability of NF-kappaB p50-DNA complexes in a sequence-dependent manner

The effect of two different DNA minor groove binding molecules, Hoechst 33258 and distamycin A, on the binding kinetics of NF-κB p50 to three different specific DNA sequences was studied at various salt concentrations. Distamycin A was shown to significantly increase the dissociation rate constant of p50 from the sequences PRDII (5′-GGGAAATTCC-3′) and Ig-κ B (5′-GGGACTTTCC-3′) but had a negligible effect on the dissociation from the palindromic target-κB binding site (5′-GGGAATTCCC-3′). By comparison, the effect of Hoechst 33258 on binding of p50 to each sequence was found to be minimal. The dissociation rates for the protein–DNA complexes increased at higher potassium chloride concentrations for the PRDII and Ig-κB binding motifs and this effect was magnified by distamycin A. In contrast, p50 bound to the palindromic target-κB site with a much higher intrinsic affinity and exhibited a significantly reduced salt dependence of binding over the ionic strength range studied, retaining a KD of less than 10 pM at 150 mM KCl. Our results demonstrate that the DNA binding kinetics of p50 and their salt dependence is strongly sequence-dependent and, in addition, that the binding of p50 to DNA can be influenced by the addition of minor groove-binding drugs in a sequence-dependent manner.

Sequence-dependent conformation of an A-DNA double helix: The crystal structure of the octamer d(G-G-T-A-T-A-C-C)

The crystal structures of the synthetic self-complementary octamer d(G-G-T-A-T-A-C-C) and its 5-bromouracil-containing analogue have been refined to R values of 20% and 14% at resolutions of 1·8 and 2·25 Å, respectively. The molecules adopt an A-DNA type double-helical conformation, which is minimally affected by crystal forces. A detailed analysis of the structure shows a considerable influence of the nucleotide sequence on the base-pair stacking patterns. In particular, the electrostatic stacking interactions between adjacent guanine and thymine bases produce symmetric bending of the double helix and a major-groove widening. The sugar-phosphate backbone appears to be only slightly affected by the base sequence. The local variations in the base-pair orientation are brought about by correlated adjustments in the backbone torsion angles and the glycosidic orientation. Sequence-dependent conformational variations of the type observed here may contribute to the specificity of certain protein-DNA interactions.

Sequence-dependent molecular conformation of polynucleotides: right and left-handed helices

Based upon a stereochemical guideline, two topologically distinct types of helicalduplexes have been deduced for a polynucleotide duplex with alternating purine pyrimidine sequence (PAPP): (a) right-handed uniform (RU) helix and (b) left-handed zig-zag (LZ) helix. Both structures have trinucleoside diphosphate as the basic unit wherein the purine pyrimidine fragment has a different conformation from the pyrimidine-purine fragment. Thus, RU and LZ helices represent two different classes of sequence-dependent molecular conformations for PAPP. The conformationalf eatures of an RU helix of PAPP in B-form and three LZ-helices for B-, D- and Z-forms are discussed.

NUPARM and NUCGEN: software for analysis and generation of sequence dependent nucleic acid structures

Software packages NUPARM and NUCGEN, are described, which can be used to understand sequence directed structural variations in nucleic acids, by analysis and generation of non-uniform structures. A set of local inter basepair parameters (viz. tilt, roll, twist, shift, slide and rise) have been defined, which use geometry and coordinates of two successive basepairs only and can be used to generate polymeric structures with varying geometries for each of the 16 possible dinucleotide steps. Intra basepair parameters, propeller, buckle, opening and the C6...C8 distance can also be varied, if required, while the sugar phosphate backbone atoms are fixed in some standard conformation ill each of the nucleotides. NUPARM can be used to analyse both DNA and RNA structures, with single as well as double stranded helices. The NUCGEN software generates double helical models with the backbone fixed in B-form DNA, but with appropriate modifications in the input data, it can also generate A-form DNA ar rd RNA duplex structures.

A hypothesis on a specific sequence-dependent conformation of DNA and its relation to the binding of the lac-repressor protein

The structure and properties of the double-helical form of the alternating copolymer poly(dA-dT) are considered. Different lines of evidence are interpreted in terms of a structure in which every second phosphate-diester linkage has a conformation different from that of the normal B form. A rationale for this “alternating-B” structure is given which provides an explanation for the effects of chemical modifications of the T residues on the binding of the poly(dA-dT)· poly(dA-dT) to the lac repressor of Escherichia coli.

Analysis of sequence dependent variations in secondary and tertiary structure of tRNA molecules

The double helical regions of the five tRNA(Phe) and two tRNA(Asp) crystal structures have been analyzed using the local basepair step parameters. The sequence dependent effects in the mini double helices of tRNA are very similar to those observed in the crystal structures of oligonucleotides in the A-form, the purine-pyrimidine and purine-purine steps have small roll angles when compared to the fiber models of A-DNA as well as A-RNA, while the pyrimidine-purine doublet steps have large roll angles. The orientation of the basepairs in the D-stem is unusual and invariant i.e. they are different from the other three stems but are very similar in all the five tRNA(Phe) crystal structures, presumably due to tertiary interaction of the Watson-Crick basepairs with other bases, with all bases being highly conserved. The origin of the differences between the tertiary structures of tRNA(Phe) and tRNA(Asp) from yeast has also been investigated. It is found that even though the angle between the acceptor arm and the D-stem is very similar in the two structures, the angle subtended by the acceptor arm and the anticodon arm is smaller in the tRNA(Phe) structure (by more than 10 degrees). This is due to differences in the orientation of the two mini helices constituting the anticodon arm, which are inclined to each other by approximately 25 degrees in tRNA(Phe) and 16 degrees in tRNA(Asp). In addition, the acceptor arm, the D-stem and the anticodon stem are nearly coplanar in tRNA(Phe), while in tRNA(Asp) the anticodon stem projects out of the plane defined by the acceptor arm and the anticodon stem. These two features together lead to a larger separation between the acceptor and anticodon ends in tRNA(Asp) and indicate that the junction between the D-stem and the anticodon stem is quite variable, with features characteristic of a ball-and-socket type joint and determined for each tRNA molecule by the base sequence at the junction.

Single-machine scheduling with past-sequence-dependent setup times and learning effects: a parametric analysis

In this article, we consider the single-machine scheduling problem with past-sequence-dependent (p-s-d) setup times and a learning effect. The setup times are proportional to the length of jobs that are already scheduled; i.e. p-s-d setup times. The learning effect reduces the actual processing time of a job because the workers are involved in doing the same job or activity repeatedly. Hence, the processing time of a job depends on its position in the sequence. In this study, we consider the total absolute difference in completion times (TADC) as the objective function. This problem is denoted as 1/LE, (Spsd)/TADC in Kuo and Yang (2007) ('Single Machine Scheduling with Past-sequence-dependent Setup Times and Learning Effects', Information Processing Letters, 102, 22-26). There are two parameters a and b denoting constant learning index and normalising index, respectively. A parametric analysis of b on the 1/LE, (Spsd)/TADC problem for a given value of a is applied in this study. In addition, a computational algorithm is also developed to obtain the number of optimal sequences and the range of b in which each of the sequences is optimal, for a given value of a. We derive two bounds b* for the normalising constant b and a* for the learning index a. We also show that, when a < a* or b > b*, the optimal sequence is obtained by arranging the longest job in the first position and the rest of the jobs in short processing time order.

7-Amino actinomycin D bound to single-stranded hairpin DNA enhanced by loop sequence-dependent luminescent Eu3+ and Tb3+ binding

Lanthanide Eu3+ and Tb3+ ions have been widely used in luminescent resonance energy transfer (LRET) for bioassays to study metal binding microenvironments. We report here that Eu3+ or Tb3+ can increase the binding affinity of antitumor antibiotic drug agent, 7-amino actinomycin D (7AACTD), binding to 5'-GT/TG-5' or 5'-GA/AG-5' mismatched stem region of the single-stranded hairpin DNA. Further studies indicate that the effect of Eu3+ or Tb3+ on 7AACTD binding is related to DNA loop sequence. Our results will provide new insights into how metal ions can enhance antitumor agents binding to their targets.

Detecting sequence dependent transcriptional pauses from RNA and protein number time series

Background: Evidence suggests that in prokaryotes sequence-dependent transcriptional pauses a?ect the dynamics of transcription and translation, as well as of small genetic circuits. So far, a few pause-prone sequences have been identi?ed from in vitro measurements of transcription elongation kinetics.

Results: Using a stochastic model of gene expression at the nucleotide and codon levels with realistic parameter values, we investigate three di?erent but related questions and present statistical methods for their analysis. First, we show that information from in vivo RNA and protein temporal numbers is su?cient to discriminate between models with and without a pause site in their coding sequence. Second, we demonstrate that it is possible to separate a large variety of models from each other with pauses of various durations and locations in the template by means of a hierarchical clustering and a random forest classi?er. Third, we introduce an approximate likelihood function that allows to estimate the location of a pause site.

Conclusions: This method can aid in detecting unknown pause-prone sequences from temporal measurements of RNA and protein numbers at a genome-wide scale and thus elucidate possible roles that these sequences play in the dynamics of genetic networks and phenotype.

Sequence-dependent structure/function relationships of catalytic peptide-enabled gold nanoparticles generated under ambient synthetic conditions

Peptide-enabled nanoparticle (NP) synthesis routes can create and/or assemble functional nanomaterials under environmentally friendly conditions, with properties dictated by complex interactions at the biotic/abiotic interface. Manipulation of this interface through sequence modification can provide the capability for material properties to be tailored to create enhanced materials for energy, catalysis, and sensing applications. Fully realizing the potential of these materials requires a comprehensive understanding of sequence-dependent structure/function relationships that is presently lacking. In this work, the atomic-scale structures of a series of peptide-capped Au NPs are determined using a combination of atomic pair distribution function analysis of high-energy X-ray diffraction data and advanced molecular dynamics (MD) simulations. The Au NPs produced with different peptide sequences exhibit varying degrees of catalytic activity for the exemplar reaction 4-nitrophenol reduction. The experimentally derived atomic-scale NP configurations reveal sequence-dependent differences in structural order at the NP surface. Replica exchange with solute-tempering MD simulations are then used to predict the morphology of the peptide overlayer on these Au NPs and identify factors determining the structure/catalytic properties relationship. We show that the amount of exposed Au surface, the underlying surface structural disorder, and the interaction strength of the peptide with the Au surface all influence catalytic performance. A simplified computational prediction of catalytic performance is developed that can potentially serve as a screening tool for future studies. Our approach provides a platform for broadening the analysis of catalytic peptide-enabled metallic NP systems, potentially allowing for the development of rational design rules for property enhancement.