Substitution Probabilities Research Articles

Perceived versus actual value of product substitution flexibility: An experimental investigation

Prior literature suggests that in the presence of operational uncertainties such as uncertain demand, firms should deploy operational flexibilities. However, these flexibilities are costly to develop and a correct valuation of these capabilities is necessary to ensure that they are only deployed when the expected benefits exceed the cost. Using a set of behavioral decision-making experiments for inventory of substitutable products, we investigate how decision-makers perform when estimating the value of operational flexibility of product substitution. We found that subjects consistently overestimated the monetary value of product substitution. Furthermore, the overestimation became more acute as demand correlation increased. This behavior is not explained by risk aversion or random errors. Instead, it appears to be driven by fundamental and systematic behavioral biases when estimating the conjunctive probability of substitution. We suggest and validate a decomposition-based approach to mitigate this overestimation.

Authentication codes based on resilient Boolean maps

We introduce three new constructions of systematic authentication codes over finite fields and Galois rings. Our first construction uses resilient functions over finite fields and provides optimal impersonation and substitution probabilities. Our two other constructions are defined over Galois rings: one is based on resilient maps attaining optimal probabilities as well, while the other is based on maps with maximum Fourier transforms. For the special case of characteristic $$p^2$$p2, the maps used on our third construction are bent. Furthermore, we give a generalised construction for the case of characteristic $$p^s$$ps, with $$s \ge 2$$s?2. The second and third codes over Galois rings, restricted to the particular case of Galois fields, are different than the first code introduced in this paper: the corresponding source and tag spaces differ, and the encoding maps classes are pairwise different.

Optimization of Mutation Pressure in Relation to Properties of Protein-Coding Sequences in Bacterial Genomes.

Most mutations are deleterious and require energetically costly repairs. Therefore, it seems that any minimization of mutation rate is beneficial. On the other hand, mutations generate genetic diversity indispensable for evolution and adaptation of organisms to changing environmental conditions. Thus, it is expected that a spontaneous mutational pressure should be an optimal compromise between these two extremes. In order to study the optimization of the pressure, we compared mutational transition probability matrices from bacterial genomes with artificial matrices fulfilling the same general features as the real ones, e.g., the stationary distribution and the speed of convergence to the stationarity. The artificial matrices were optimized on real protein-coding sequences based on Evolutionary Strategies approach to minimize or maximize the probability of non-synonymous substitutions and costs of amino acid replacements depending on their physicochemical properties. The results show that the empirical matrices have a tendency to minimize the effects of mutations rather than maximize their costs on the amino acid level. They were also similar to the optimized artificial matrices in the nucleotide substitution pattern, especially the high transitions/transversions ratio. We observed no substantial differences between the effects of mutational matrices on protein-coding sequences in genomes under study in respect of differently replicated DNA strands, mutational cost types and properties of the referenced artificial matrices. The findings indicate that the empirical mutational matrices are rather adapted to minimize mutational costs in the studied organisms in comparison to other matrices with similar mathematical constraints.

Rational design of antibiotic treatment plans: a treatment strategy for managing evolution and reversing resistance.

The development of reliable methods for restoring susceptibility after antibiotic resistance arises has proven elusive. A greater understanding of the relationship between antibiotic administration and the evolution of resistance is key to overcoming this challenge. Here we present a data-driven mathematical approach for developing antibiotic treatment plans that can reverse the evolution of antibiotic resistance determinants. We have generated adaptive landscapes for 16 genotypes of the TEM β-lactamase that vary from the wild type genotype “TEM-1” through all combinations of four amino acid substitutions. We determined the growth rate of each genotype when treated with each of 15 β-lactam antibiotics. By using growth rates as a measure of fitness, we computed the probability of each amino acid substitution in each β-lactam treatment using two different models named the Correlated Probability Model (CPM) and the Equal Probability Model (EPM). We then performed an exhaustive search through the 15 treatments for substitution paths leading from each of the 16 genotypes back to the wild type TEM-1. We identified optimized treatment paths that returned the highest probabilities of selecting for reversions of amino acid substitutions and returning TEM to the wild type state. For the CPM model, the optimized probabilities ranged between 0.6 and 1.0. For the EPM model, the optimized probabilities ranged between 0.38 and 1.0. For cyclical CPM treatment plans in which the starting and ending genotype was the wild type, the probabilities were between 0.62 and 0.7. Overall this study shows that there is promise for reversing the evolution of resistance through antibiotic treatment plans.

Saccharomyces cerevisiae-based mutational analysis of the bc1 complex Qo site residue 279 to study the trade-off between atovaquone resistance and function.

The bc1 complex is central to mitochondrial bioenergetics and the target of the antimalarial drug atovaquone that binds in the quinol oxidation (Qo) site of the complex. Structural analysis has shown that the Qo site residue Y279 (Y268 in Plasmodium falciparum) is key for atovaquone binding. Consequently, atovaquone resistance can be acquired by mutation of that residue. In addition to the probability of amino acid substitution, the level of atovaquone resistance and the loss of bc1 complex activity that are associated with the novel amino acid would restrict the nature of resistance-driven mutations occurring on atovaquone exposure in native parasite populations. Using the yeast model, we characterized the effect of all the amino acid replacements resulting from a single nucleotide substitution at codon 279: Y279C, Y279D, Y279F, Y279H, Y279N, and Y279S (Y279C, D, F, H, N, and S). Two residue changes that required a double nucleotide substitution, Y279A and W, were added to the series. We found that mutations Y279A, C, and S conferred high atovaquone resistance but decreased the catalytic activity. Y279F had wild-type enzymatic activity and sensitivity to atovaquone, while the other substitutions caused a dramatic respiratory defect. The results obtained with the yeast model were examined in regard to atomic structure and compared to the reported data on the evolution of acquired atovaquone resistance in P. falciparum.

Epigenetic mutagenesis as program of age-related protein dysfunction and aging

DNA methylation plays an important polyfunctional role in ontogenesis of human and mammals. A steep rise in probability of mutational substitution of CpG dinucleotide on TpG dinucleotide in the genome is one of the consequences of DNA methylation. All spectrum (17) of possible DNA and protein mutations caused by CpG-dinucleotide methylation in DNA were characterized, and the three most dangerous mutations (able to result in protein inactivation) were isolated. The computer program that allows one to predict all most probable mutations in the analyzed gene and encoded protein was created. On the example of genes from humans and various mammals, it was demonstrated that the amount of potentially dangerous sites of epigenetic mutagenesis in exons was drastically decreased as a result of genome evolution. But, at the same time, unforced preservation of such sites and their persistence were established, indicating the occurrence of age-related protein dysfunction built into the genome epigenetic program, resulting in apoptosis and aging; this program is based on the set and position of methylated codons in exonic gene regions. It is assumed that the program of epigenetic mutagenesis limits the lifetime of an individual, accelerating the deliverance of the population from long-lived individuals that completed the reproductive period.

Smart vending machine systems: operation and performance

The operation of smart vending machine systems creates decision-making problems under vendor-managed inventory schemes involving product allocation to vending machine storage compartments, replenishment points of products and replenishment thresholds at vending machines, and vehicle routes for inventory replenishments, all of which have critical effects on system profit. This paper considers the operation of smart vending machine systems in which possible product substitutions occur when customers face stock-outs. A simple, intuitive procedure is presented to estimate substitution probabilities, construct an integrated optimisation mathematical model for the operation problem of smart vending machine systems, and develop a two-phase heuristic based on this mathematical model. The results of computational experiments demonstrate the substantial economic benefit of the smart vending machine system over the conventional system. Sensitivity analysis indicates that certain input variables significantly impact the effectiveness of the smart vending machine system. [Received 28 August 2013; Revised 26 December 2013; Accepted 11 March 2014]

The Application of Essential Oils and Silver Nanoparticles for Sterilization of Bermudagrass Explants in in vitro Culture

An important part of plant in vitro techniques is the sterilization of explants and the maintenance of aseptic conditions. Ideally, sterilizing materials should be effective on a vast range of microorganisms at low density. Nowadays, the use of compounds such as essential oils (EOs) and nanoparticles is applicable in microbiology studies. The main objective of this experiment was to study the substitution probability of silver nanoparticles (SNPs), thymol and carvacrol as novel sterilization agents in the tissue culture of Cynodon dactylon. Explants were sterilized with 70% ethanol for 2 min, and then 30% Clorox for 15 min. Sterilization complementary treatments (SNPs, thymol and carvacrol) were applied at different concentrations (100 and 200 mg l-1) with exposure times of 30, 60 and 120 min. According to the results, infection of bermudagrass explants was controlled successfully by SNPs, thymol and carvacrol. Examination of various concentrations in different exposure times showed that 200 mg L-1 SNPs in combination with 100 mg L-1 thymol in 60 min inhibited microbial growth. Thymol and carvacrol were more effective than SNPs in controlling bacteria and fungi contaminations. Finally, these novel agents could be used as an alternative to common chemical treatments for elimination and control of microbial population explants in in vitro conditions.

A Demand Estimation Procedure for Retail Assortment Optimization with Results from Implementations

We consider the problem of choosing, from a set of N potential stock-keeping units (SKUs) in a retail category, K SKUs to be carried at each store to maximize revenue or profit. Assortments can vary by store, subject to a maximum number of different assortments. We view a SKU as a set of attribute levels and also model possible substitutions when a customer's first choice is not in the assortment. We apply maximum likelihood estimation to sales history of the SKUs currently carried by the retailer to estimate the demand for attribute levels and substitution probabilities, and from this, the demand for any potential SKU, including those not currently carried by the retailer. We specify several alternative heuristics for choosing SKUs to be carried in an assortment. We apply this approach to optimize assortments for three real examples: snack cakes, tires, and automotive appearance chemicals. A portion of our recommendations for tires and appearance chemicals were implemented and produced sales increases of 5.8% and 3.6%, respectively, which are significant improvements relative to typical retailer annual comparable store revenue increases. We also forecast sales shares of 1, 11, and 25 new SKUs for the snack cake, tire, and automotive appearance chemical applications, respectively, with mean absolute percentage errors (MAPEs) of 16.2%, 19.1%, and 28.7%, which compares favorably to the 30.7% MAPE for chain sales of two new SKUs reported by Fader and Hardie (1996). This paper was accepted by Yossi Aviv, operations management.

Coding and Detection for Channels With Written-In Errors and Inter-Symbol Interference

Written-in errors (WIEs), which include written-in substitutions, insertions, and deletions, as well as 2-D inter-symbol interference (2-D-ISI), form one of the major challenges for the new emerging bit-patterned media recording technology. Coding and detection scheme with performance/complexity tradeoffs is expected to address such a challenge. In this paper, a new channel model with WIEs and ISI (WIE-ISI) is presented, and the embedded marker code scheme (EMCS) with Bahl-Cocke-Jelinek-Raviv (BCJR) detector is employed to perform channel detection. By investigating the effect of ISI on the WIE-ISI channel considering BCJR detector, a virtual written-in substitution probability is introduced and a new synchronization algorithm with written-in substitution detection (SA-WSD) is developed. The EMCS employing the proposed SA-WSD demonstrates better error correction performance than that of the original SA. Furthermore, the SA-WSD is found to be robust to small estimation errors in the written-in substitution probability.

In silico approach to study adaptive divergence in nucleotide composition of the 16S rRNA gene among bacteria thriving under different temperature regimes.

Bacteria exist in a wide range of habitats ranging from psychrophilic through mesophilic to thermophilic. These different habitats have distinct environmental restriction for their existence. These microorganisms evolve themselves to survive in a specific habitat through the phenotypic and genotypic changes. In the bacterial domain, in silico analysis of 16S rRNA gene sequences using Mega 5.2 software by computing nucleotide composition, and evaluating their significance by statistical analysis using analysis of variance through Statistical Package for the Social Sciences (SPSS) version 16.0, revealed the habitat-specific bias in the occurrence of four types of nucleosides (A, T, C, and G) in the 16S rRNA gene. This hypothesis is also supported by Duncan's multiple range significance test at p=0.05 and also by the clustering of bacterial species of the same habitat group in the neighbor-joining tree of 150 different bacterial species of different psychrophilic, mesophilic, and thermophilic habitats (50 from each). The results on the probability of substitution (transition and transversion) in 16S rRNA gene sequences suggest that there is a habitat-specific selection pressure that possibly happens at the level of replication and repair process that results in a decreasing frequency of occurrence of adenine and thymine in the order psychrophilic>mesophilic>thermophilic species, and in an increasing frequency of occurrence of cytosine and guanine in the order psychrophilic<mesophilic<thermophilic species of bacteria.

Monte Carlo algorithms for Brownian phylogenetic models.

Brownian models have been introduced in phylogenetics for describing variation in substitution rates through time, with applications to molecular dating or to the comparative analysis of variation in substitution patterns among lineages. Thus far, however, the Monte Carlo implementations of these models have relied on crude approximations, in which the Brownian process is sampled only at the internal nodes of the phylogeny or at the midpoints along each branch, and the unknown trajectory between these sampled points is summarized by simple branchwise average substitution rates. A more accurate Monte Carlo approach is introduced, explicitly sampling a fine-grained discretization of the trajectory of the (potentially multivariate) Brownian process along the phylogeny. Generic Monte Carlo resampling algorithms are proposed for updating the Brownian paths along and across branches. Specific computational strategies are developed for efficient integration of the finite-time substitution probabilities across branches induced by the Brownian trajectory. The mixing properties and the computational complexity of the resulting Markov chain Monte Carlo sampler scale reasonably with the discretization level, allowing practical applications with up to a few hundred discretization points along the entire depth of the tree. The method can be generalized to other Markovian stochastic processes, making it possible to implement a wide range of time-dependent substitution models with well-controlled computational precision. The program is freely available at www.phylobayes.org.

Demand Estimation When There are Unobservable Substitutions Amongst Choice Alternatives

Accurate estimates of the future demand and the substitution probabilities between products are important inputs for retail assortment optimization. However, these quantities are difficult to estimate as the estimation involves understanding and modeling of consumer’s choice behavior when a complete choice set is available as well as when the choice set is incomplete (i.e., their response to out-of-stock situations). In this paper, we propose a prospect theory based reference dependent preference structure for consumer choice and use the information available in store scanner sales and inventory data to estimate both the true demand for the products as well as the substitution probabilities between products. We use a combination of theoretical arguments, simulations, and empirical analysis to establish that the proposed reference dependent logit (RDL) model yields robust and efficient estimates. We also compare the performance of RDL against the multinomial logit, two models that use exogenous substitution probabilities, and experts’ opinions regarding what the true substitution probabilities could be.

Rational Design of a New Trypanosoma rangeli Trans-Sialidase for Efficient Sialylation of Glycans

This paper reports rational engineering of Trypanosoma rangeli sialidase to develop an effective enzyme for a potentially important type of reactivity: production of sialylated prebiotic glycans. The Trypanosoma cruzi trans-sialidase and the homologous T. rangeli sialidase has previously been used to investigate the structural requirements for trans-sialidase activity. We observed that the T. cruzi trans-sialidase has a seven-amino-acid motif (197–203) at the border of the substrate binding cleft. The motif differs substantially in chemical properties and substitution probability from the homologous sialidase, and we hypothesised that this motif is important for trans-sialidase activity. The 197–203 motif is strongly positively charged with a marked change in hydrogen bond donor capacity as compared to the sialidase. To investigate the role of this motif, we expressed and characterised a T. rangeli sialidase mutant, Tr13. Conditions for efficient trans-sialylation were determined, and Tr13's acceptor specificity demonstrated promiscuity with respect to the acceptor molecule enabling sialylation of glycans containing terminal galactose and glucose and even monomers of glucose and fucose. Sialic acid is important in association with human milk oligosaccharides, and Tr13 was shown to sialylate a number of established and potential prebiotics. Initial evaluation of prebiotic potential using pure cultures demonstrated, albeit not selectively, growth of Bifidobacteria. Since the 197–203 motif stands out in the native trans-sialidase, is markedly different from the wild-type sialidase compared to previous mutants, and is shown here to confer efficient and broad trans-sialidase activity, we suggest that this motif can serve as a framework for future optimization of trans-sialylation towards prebiotic production.

A New Formulation of Protein Evolutionary Models that Account for Structural Constraints

Despite the importance of a thermodynamically stable structure with a conserved fold for protein function, almost all evolutionary models neglect site-site correlations that arise from physical interactions between neighboring amino acid sites. This is mainly due to the difficulty in formulating a computationally tractable model since rate matrices can no longer be used. Here, we introduce a general framework, based on factor graphs, for constructing probabilistic models of protein evolution with site interdependence. Conveniently, efficient approximate inference algorithms, such as Belief Propagation, can be used to calculate likelihoods for these models. We fit an amino acid substitution model of this type that accounts for both solvent accessibility and site-site correlations. Comparisons of the new model with rate matrix models and alternative structure-dependent models demonstrate that it better fits the sequence data. We also examine evolution within a family of homohexameric enzymes and find that site-site correlations between most contacting subunits contribute to a higher likelihood. In addition, we show that the new substitution model has a similar mathematical form to the one introduced in Rodrigue et al. (Rodrigue N, Lartillot N, Bryant D, Philippe H. 2005. Site interdependence attributed to tertiary structure in amino acid sequence evolution. Gene 347:207-217), although with different parameter interpretations and values. We also perform a statistical analysis of the effects of amino acids at neighboring sites on substitution probabilities and find a significant perturbation of most probabilities, further supporting the significant role of site-site interactions in protein evolution and motivating the development of new evolutionary models similar to the one described here. Finally, we discuss possible extensions and applications of the new substitution model.

ON PERFECT IMITATION RESISTANT CIPHERS OF SUBSTITUTION WITH UNBOUNDED KEY

Constructions of perfect imitation resistant ciphers are investigated in the work. It is well known that Vernam cipher with equiprobable gamma is a perfect cipher but it is not imitation resistant. It is because in Vernam cipher equipotent alphabets for plaintexts and ciphertexts are used. On the basis of A.Yu. Zubov's mathematical model of substitution cipher with unbounded key a model of perfect and imitation resistant cipher is constructed. At that reference cypher of the given model is perfect and reaches lower boundaries for success probability of imitation and substitution of communication.

The Isotopic Anatomies of Molecules and Minerals

Most natural compounds are composed of diverse isotopologues that differ in the number and/or symmetrically unique atomic locations of isotopic substitutions. Little of this isotopic diversity is observed by conventional methods of stable isotope geochemistry, which generally measure concentrations of rare isotopes without constraining differences in isotopic composition between different atomic sites or nonrandom probabilities of multiple isotopic substitutions in the same molecule. Recent advances in analytical instrumentation and methodology have created a set of geochemical tools—geothermometers, biosynthetic signatures, forensic fingerprints—based on these position-specific isotope effects and multiply substituted isotopologues. This progress suggests we are entering a period in which many new geochemical tools of this type will be created. This review describes the principles, background, analytical methods, existing applied tools, and likely future progress of this emerging field.

On hardware-oriented message authentication

The authors consider hardware-oriented message authentication, more specifically universal hash functions. The authors propose a new type of constructions that appear promising. These constructions are based on the framework of universal hash functions, Toeplitz matrices and ɛ-biased sample spaces. Some new theoretical results in this area are derived. The new constructions come at the price of not being able to prove the exact substitution probability. The expected probability is examined both through theoretical methods as well as through simulation.

Retail inventory management with stock-out based dynamic demand substitution

Abstract We consider an inventory management problem of a product category in a retail setting with Poisson arrival processes, stock-out based dynamic demand substitution, and lost sales. The retailer uses a fixed-review period, order-up-to level system to control the inventory levels. We present a computational method to determine the order-up-to levels that maximizes the expected profit with profit margins, inventory holding and substitution costs subject to service-level constraints. Determining expected sales, average inventory levels, and number of substitutions between all products for given demand rates, substitution probabilities, and order-up-to levels is not tractable when there are more than two products. Therefore we present efficient and accurate approximations to approximately compute the same performance measures. The approximate approaches are then used to solve the optimization problem by using a genetic algorithm. In a computational study, we discuss the impact of profit margins, inventory holding and substitution costs, and service level constraints on the order-up-to levels and the expected profits. We show that a retailer can increase its expected profits by incorporating substitution among different products.

녹색물류 환경에서 자판기 공급사슬 운영을 위한 의사결정지원시스템의 개발

Regarding the green environment, it is important to boost the spread of environmentally friendly vending machines and to operate the vehicles for their inventory replenishments while minimizing emissions of greenhouse gases. In general, the vending machine management company lacks capability to operate the supply chain effectively in an integrated way under the dynamic, complex, and stochastic environment. This paper presents a decision support system, termed DSSVM, for the operations of the general and smart vending machine supply chains with stock-out-based, one stage item substitution in a green logistics environment. The DSSVM supports the estimation of item demand and substitution probabilities, determination of operation parameters, supply chain analysis, what-if analysis, and <TEX>$CO_2$</TEX> analysis for which various analytical models are employed.