Combinatorial Scheme Research Articles

Quantitative Control of Organ Shape by Combinatorial Gene Activity

Author SummaryA major challenge in developmental biology is to understand how patterns of gene activity are translated into complex three-dimensional forms, like hearts, wings, or flowers. Addressing this problem has not been easy, partly because of the difficulties in quantifying the effects of genes on shape and also because we lack frameworks that allow hypotheses about underlying mechanisms to be evaluated. Here we address this issue through a combination of experimental and computational approaches, using the Snapdragon flower as a model system. By quantifying the shapes of these flowers in a range of mutants with reduced or increased activity of particular genes, we show how the complex floral shape depends on the way genes act in combination in each petal region. The proposed interactions were tested by incorporating them into a computational model of the growing flower. Quantitative comparisons reveal a good agreement between the shapes generated by the model and those observed experimentally, confirming our underlying hypothesis. The Snapdragon flower, with its tightly fitting upper and lower petals, has evolved as a specialised mechanism for targeting pollinators. Our article shows how the development and evolution of such forms may have arisen by natural tinkering with the local effects of genes on growth.

Molecular remission in advanced acute promyelocytic leukaemia after treatment with the oral synthetic retinoid Tamibarotene

Molecular remission in advanced acute promyelocytic leukaemia after treatment with the oral synthetic retinoid Tamibarotene

High-order expansion of T2×t2 Jahn–Teller potential-energy surfaces in tetrahedral molecules

Methods from Jahn-Teller theory and invariant theory have been combined for the construction of analytic diabatic potential-energy surfaces of triply degenerate states in tetrahedral molecules. The potentials of a threefold degenerate electronic state of T(2) symmetry, subject to the T(2)xt(2) or T(2)x(t(2)+t(2)) Jahn-Teller effect in a three-dimensional or six-dimensional space of nuclear coordinates, respectively, are considered. The permutation symmetry of four identical nuclei is taken into account in the polynomial expansion of the diabatic surfaces. Symmetry adapted polynomials up to high orders are explicitly given and a simple combinatorial scheme was developed to express terms of arbitrary order as products of a small number of polynomials which are invariant under the permutation of identical nuclei. The method is applied to the methane cation in its triply degenerate ground state. The parameters of the analytic surfaces have been fitted to accurate ab initio data calculated at the full-valence CASSCF/MRCI/cc-pVTZ level. A three-sheeted six-dimensional analytic potential-energy surface of the (2)T(2) ground state of CH(4) (+) is reported, which involves terms up to eighth order in the degenerate stretching coordinate, up to 12th order in the degenerate bending coordinate, and up to fourth order in the stretch-bend coupling.

Abstract 676: Induction of apoptosis via control of cell adhesion by peroxisome proliferator activated receptor-gamma agonist in human uterine leiomyoma cells

Abstract Objective : Peroxisome Proliferator-Activated Receptor (PPAR)-gamma ligands constitute important insulin sensitizers that have already been approved for the treatment of human metabolic disorders. It has been previously demonstrated that growth inhibition in human uterine leiomyoma cells mediated by caspase-dependent pathway and death receptor. The present study was designed to further understand the mechanism after uterine leiomyoma and normal myometrial cells were exposed to PPAR gamma agonist, Ciglitizone. Methods : In order to confirm the unknown cellular and biochemical responses to ciglitizone treatment with three uterine leiomyoma and normal myometrial cells, DNA chip analysis were performed. Highly up-regulated genes were confirmed to ascertain effect of PPAR gamma agonist by RT-PCR and Western-blot analysis. To analyze mechanism of invasion and metastasis -associating gene regulation by PPAR-γ ligands, wound healing assay and soft agar assay were performed. Results : DNA chip analysis revealed genes are related with cell adhesion and metastasis genes including plasminogen activating urokinase (PLAU), claudin 1, matrix metallopeptidase 1,2, and 9. Highly down-regulated genes had defense system against cell metastasis in common and was related with adhesion. Treatment with ciglitizone made decrease expression level of above cell adhesion related genes in dose dependent manner by RT-PCR and Western-blot analysis. Furthermore, treatment with ciglitizone in uterine leiomyoma cells decrease the invasion ability of leiomyoma cells and the formation of anchorage-independent colonies in soft agar. Conclusions : These results suggest that PPAR-gamma could be considered as a therapeutic target for diverse disease states in which excessive angiogenesis is implicated, including cancer and uterine leiomyoma. This phenomenon has not been previously reported for PPAR-gamma agonist in uterine leiomyoma. Defining the role of PPARγ in uterine leiomyoma cells will be paramount for a rational design of combinatorial therapy schemes that takes advantage of the potent and well-tolerated PPARγ agonists. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 676.

Blend-In: A Privacy-Enhancing Certificate-Selection Method for Vehicular Communication

This paper presents and analyzes a method for enhancing the privacy of vehicles that use the public-key infrastructure (PKI) to secure communications. In particular, it examines the privacy limitations of a PKI system, where certificates are shared among multiple vehicles using a combinatorial certificate scheme. Such a system was implemented in the U.S. Vehicle Infrastructure Integration (VII) proof-of-concept trial to secure vehicle-to-vehicle (V2V) and vehicle-to-infrastructure (V2I) communication and preserve vehicle privacy. The analysis shows that, in low vehicle densities, there is a high probability that a vehicle may have a locally unique certificate that is not shared by other vehicles. Vehicles using unique certificates may be vulnerable to being tracked or identified. This paper proposes a vehicle-based certificate-selection method for enhancing the privacy of vehicle communications. In our method, a vehicle monitors the certificates in use by neighboring vehicles and identifies those certificates that it also possesses. The vehicle then selects a certificate already in use to secure its own communication. This allows a vehicle to ldquoblend inrdquo to its environment but without substantially increasing an attacker's ability to evade exposure. We provide an analysis of the anonymity and unlinkability properties of the method and demonstrate that it rapidly reduces the number of vehicles using unique certificates to increase privacy.

Single and multi-objective optimal design of water distribution systems: application to the case study of the Hanoi system

This manuscript describes the application of two recent methodologies developed by the authors for single and multi-objective optimal design of water distribution systems. The single-objective model is a hybrid algorithm incorporating decomposition, spanning tree search, and evolutionary computation, while the multi-objective algorithm integrates features form multi-objective genetic algorithms with the Cross Entropy combinatorial optimization scheme. The two models are implemented on the Hanoi water distribution system, one of the more explored systems in the research literature, through base runs and sensitivity analysis. The single-objective model produced the best known least cost solution for split pipe design, while the multi-objective model has shown robustness and well explanatory outcomes. Discussion of the accomplished results and suggestions for future research are provided.

Sensing invasion: Cell surface receptors driving spreading of glioblastoma

Glioblastoma multiforme (GBM) is the most common malignant brain tumour in adults. One main source of its high malignancy is the invasion of isolated tumour cells into the surrounding parenchyma, which makes surgical resection an insufficient therapy in nearly all cases. The invasion is triggered by several cell surface receptors including receptor tyrosine kinases (RTKs), G protein-coupled receptors (GPCRs), TGF-beta receptor, integrins, immunoglobulins, tumour necrosis factor (TNF) family, cytokine receptors, and protein tyrosine phosphatase receptors. The cross-talk between cell-surface receptors and the redundancy of downstream effectors make analysis of invasive signals even more complex. Therapies involving inhibition of single receptors do not give promising outcomes and a thorough knowledge of invasive signals of common and exclusive signalling components is required for design of best combinatory treatment schemes to fight the disease.

A Novel Discriminative Approach Based on Hidden Markov Models and Wavelet Transform to Transformer Protection

In this paper we present a combinatorial scheme based on hidden Markov models (HMM) and wavelet transform (WT) to discriminate between magnetizing inrush currents and internal faults in power transformers. HMMs are powerful tools for transient classification which compute the maximum likelihood probability between training and testing data signals for identification. The WT is employed to extract certain features which reduce the computation burden of HMMs and enhance detection accuracy. The newly extracted feature efficiently discriminates between faults by different trends. The k-means clustering technique is applied to reduce the training procedure time investment. Since the discrimination method is based on the probabilistic characteristics of the signals without application of any deterministic index, more reliable and accurate classification is achieved. This method is independent of the selection thresholds. Based on the proposed algorithm a highspeed relay response (a quarter of a cycle) can be achieved. The suitable performance of this method is demonstrated by simulation of different faults and switching conditions on a power transformer using PSCAD/EMTDC software.

The backcross analysis of complex gametophytic complementary S gene systems in diploid angiosperms

Conventional diallel schemes of pollination between sibs in F1 or I1, families rapidly become unduly difficult to handle in the genetic analysis of complex gametophytic S gene mechanisms. In order to promote research into these mechanisms, their distribution, genetic architecture and mode of team cooperation, a two-step backcross scheme has been elaborated, in which an F1, plant is backcrossed with pollen from its maternal parent. This scheme considers (1) the frequency with which a particular S gene constellation segregates in this F1 plant, and (2) the range of S gene constellations segregating in its maternal parent. Complications in the backcross scheme may arise, which are caused by (1) S genes shared by the two original plants and transmitted to the F1 plant, (2) homozygous S loci occurring in the maternal parent, (3) linkage of S loci, (4) selective fertilization. The complete combinatory scheme, for S gene systems of various degrees of complexity, is presented for overcoming these difficulties in the consideration of the combined set of data in a two-step backcross analysis of complex gametophytic complementary S gene systems in diploid angiosperms.

Combinatorial Systems Evolution: Example of Standard for Multimedia Information

The article addresses the issues of combinatorial evolution of standards in transmission of multimedia information including the following: (a) brief descriptions of basic combinatorial models as multicriteria ranking, knapsack-like problems, clustering, combinatorial synthesis, multistage design, (b) a description of standard series (MPEG) for video information processing and a structural (combinatorial) description of system changes for the standards, (c) a set of system change operations (including multi-attribute description of the operations and binary relations over the operations), (d) combinatorial models for the system changes, and (e) a multistage combinatorial scheme (heuristic) for the analysis of the system changes. Expert experience is used. Numerical examples illustrate the suggested problems, models, and procedures.

A single molecule array for digital targeted molecular analyses

We present a new random array format together with a decoding scheme for targeted multiplex digital molecular analyses. DNA samples are analyzed using multiplex sets of padlock or selector probes that create circular DNA molecules upon target recognition. The circularized DNA molecules are amplified through rolling-circle amplification (RCA) to generate amplified single molecules (ASMs). A random array is generated by immobilizing all ASMs on a microscopy glass slide. The ASMs are identified and counted through serial hybridizations of small sets of tag probes, according to a combinatorial decoding scheme. We show that random array format permits at least 10 iterations of hybridization, imaging and dehybridization, a process required for the combinatorial decoding scheme. We further investigated the quantitative dynamic range and precision of the random array format. Finally, as a demonstration, the decoding scheme was applied for multiplex quantitative analysis of genomic loci in samples having verified copy-number variations. Of 31 analyzed loci, all but one were correctly identified and responded according to the known copy-number variations. The decoding strategy is generic in that the target can be any biomolecule which has been encoded into a DNA circle via a molecular probing reaction.

Relationship between Peripheral Receptor Code and Perceived Odor Quality

The discrimination of thousands of odorants is mediated by several hundred olfactory receptors (ORs). It is generally accepted that the main strategy in encoding odor quality is a combinatorial receptor code scheme, in which odorants are discriminated by different sets of ORs. In the present study, we classified 12 test odorants by their receptor codes and perceived odor qualities to examine whether odorants showing similar receptor codes are also similar in their odor qualities. Similarities of receptor codes between odorants were estimated by the overlapping responses of murine isolated olfactory sensory neurons. In contrast, we conducted a human sensory test to classify the test odorants according to their odor qualities. Despite the difference in species, the groupings of the test odorants were well conserved between receptor code and odor quality. These findings indicate that odorants that are discriminated by murine receptor codes are perceived as different odors by humans and further suggest that similarity of receptor codes correlates with that of odor quality, at least in our test odorants at the concentrations tested.

Crystallization and enzymatic degradation of novel poly(ε-caprolactone-co-propylene succinate) copolymers

A series of novel poly(ε-caprolactone-co-propylene succinate) P(CL-co-PSu) copolymers having low propylene succinate content and high molecular weight were synthesized following a combinatory scheme of ring opening and polycondensation reactions, in an attempt to obtain copolymers of sufficient performance and increased biodegradation rates. Enzymatic hydrolysis of the copolymers was studied in the presence of mixture of Rhizopus delemar and Pseudomonas cepacia lipases. Much higher hydrolysis rates, comparing to neat PCL, were proved by both mass loss measurements and scanning electron microscopy (SEM) observations of the degraded film surfaces. Thermodynamics of cocrystallization and wide-angle X-ray diffraction (WAXD) patterns were investigated to estimate the extent of comonomer cocrystallization. Results of the study showed that comonomer inclusion may hold, though the molar fraction of the comonomer in the PCL crystals is lower than in the bulk. This means that not only the observed decrease of the degree of crystallinity from about 48% for PCL to about 29% for the P(CL-co-PSu) 75/25 favours enzymatic hydrolysis, but also the enrichment of the amorphous phase in the fast degrading propylene succinate units plays its role. The non-isothermal crystallization rates of the copolymers, like the melting points, decreased substantially when the propylene succinate content exceeded 8 mol%. The activation energy of crystallization was calculated using the isoconversional method of Friedman, over the whole range of crystallization temperatures. An increase was found in the activation energy with increasing the comonomer content in the copolymers also proving the reduced symmetry along the copolymer chains due to the presence of comonomer units.

Surface nematic bistability at nanoimprinted topography

The azimuthal nematic bistability was realized by frustration between two azimuthally orthogonal anchoring axes induced by a nanoimprinted groove pattern and mechanical rubbing. The nematic bistability can be explained by the revised Berreman model of groove-induced surface anchoring, recently introduced by Fukuda et al. [Phys. Rev. Lett. 98, 187803 (2007)]. The azimuthal bistability can be tuned in arbitrary direction by changing the groove pitch and rubbing conditions. This simple combinatorial scheme may be considered as a practical candidate for bistable displays with tailored bistable directions required in various liquid crystal device modes.

Synthesis of linoleic acids combinatorially labeled at the vinylic positions as substrates for lipoxygenases

Mammalian lipoxygenases have been implicated in a number of inflammation-related human diseases. Soybean lipoxygenase-1 is the archetypical example of known lipoxygenases. Here we report the synthesis of linoleic acid and (11,11)-d2-linoleic acid which are combinatorially labeled at the vinylic positions (9, 10, 12, and 13). Combinatorial labeling schemes allow for the simultaneous determination of KIEs in enzymatic reactions using NMR. Substrates are, thus, available as probes of detailed mechanism in kinetic isotope effect (KIE) studies of lipoxygenases.

Dynamical decoupling schemes derived from Hamilton cycles

We address the problem of decoupling the interactions in a spin network governed by a pair-interaction Hamiltonian. Combinatorial schemes for decoupling and for manipulating the couplings of Hamiltonians have been developed, which use selective pulses. In this paper, we consider an additional requirement on these pulse sequences: as few different control operations as possible should be used. This requirement is motivated by the fact that to find an optimal implementation of each individual selective pulse will be expensive since it requires to solve a pulse shaping problem. Hence, it is desirable to use as few different selective pulses as possible. As a first result, we show that for d-dimensional systems, where d⩾2, the ability to implement only two control operations is sufficient to turn off the time evolution. Next, we address the case of a bipartite system with local control and show that four different control operations are sufficient. Finally, turning to networks consisting of several d-dimensional nodes, we show that decoupling can be achieved if one is able to control a number of different control operations, which is logarithmic in the number of nodes. We give an explicit family of efficient decoupling schemes with logarithmic number of different pulses based on the classic Hamming codes. We also provide a table of the best known decoupling schemes for small networks of qubits.

A Novel Linear Combinatorial Coding Scheme for Optical CDMA and its Performance

A novel linear combinatorial code (LCC) is first proposed for optical code division multiple access (OCDMA) communication. The LCCs are constructed with some time-domain (one-dimensional) / wavelength-time (two-dimensional) codes with uniform code length in a family of optical orthogonal or pseudo-orthogonal codes. The preference of the proposed LCC is analyzed in comparison with that of optical orthogonal codes. The schemes of encoder and decoder are analyzed. In the proposed scheme, the two important system parameters, namely the probability of error (bit error rate) in terms of multiuser interference and the capacity of codes, are improved notably. Moreover, the bit error rate can be controlled by varying the combinatorial code parameters.

A Sharp Phase Transition Threshold for Elementary Descent Recursive Functions

Harvey Friedman introduced natural independence results for the Peano axioms (PA) via certain schemes of combinatorial well-foundedness. We consider in this article parameterized versions of a specific Friedman-style scheme and classify exactly the threshold for the transition from provability to unprovability in PA. For this purpose we fix a natural Schutte-style bijection between the ordinals below e0 and the positive integers. This coding induces a natural well ordering ≺ on the positive integers. Using bounds on the asymptotic of the resulting global count functions we classify precisely the phase transition for the parameterized hierarchy of elementary descent recursive functions and hence for the combinatorial well-foundedness scheme. Let CWF(g) be the assertion that for all natural numbers K there exists a natural number M which is so large that there does not exist a strictly ≺-descending sequence m0,…,mM of positive integers such that for every i with 0 ≤ i ≤ M we have that mi ≤ K + g(i). For classifying the provable from the unprovable version of CWF(g) (as a problem depending on g) let fα(i):=i|i|Fα-1(i) where | · |k denotes the k-times iterated binary length function and where Fα-1 denotes the functional inverse of the α-th function from the fast growing hierarchy. Then our main result is: PA proves CWF (fα) iff α < ɛ0.

A Systematic and Comprehensive Combinatorial Approach to Simultaneously Improve the Activity, Reaction Specificity, and Thermal Stability of p-Hydroxybenzoate Hydroxylase

We have simultaneously improved the activity, reaction specificity, and thermal stability of p-hydroxybenzoate hydroxylase by means of systematic and comprehensive combinatorial mutagenesis starting from available single mutations. Introduction of random mutations at the positions of four cysteine and eight methionine residues provided 216 single mutants as stably expressed forms in Escherichia coli host cells. Four characteristics, hydroxylase activity toward p-hydroxybenzoate (main activity), protocatechuate-dependent NADPH oxidase activity (sub-activity), ratio of sub-activity to main activity (reaction specificity), and thermal stability, of the purified mutants were determined. To improve the above characteristics for diagnostic use of the enzyme, 11 single mutations (C152V, C211I, C332A, M52V, M52Q, M110L, M110I, M213G, M213L, M276Q, and M349A) were selected for further combinatorial mutagenesis. All possible combinations of the mutations provided 18 variants with double mutations and further combinatorial mutagenesis provided 6 variants with triple mutations and 9 variants with quadruple mutations with the simultaneously improved four properties.

Dynamic combinatorial key management scheme for sensor networks

AbstractSecuring sensor networks has received much attention in the last few years. In a typical field deployment, a sensor network self‐organizes, closely interacts with its physical environment, and works unattended possibly in a hostile environment such as a battlefield. In such environments, sensor networks are subject to node capture as well as a myriad of other attacks. Constrained energy, memory, and computational capabilities of sensor nodes mandate a clever design of security solutions to minimize overhead while maintaining secure communications over the lifespan of the network. In this paper, we propose a Dynamic Combinatorial Key management scheme, DCK, to provide efficient, scalable, and survivable dynamic keying in a clustered sensor network with a large number of sensor nodes. DCK employs the Exclusion‐Basis Systems (EBS) as the underlying framework for key management at both the cluster and the sensor node levels. DCK enhances network security by localizing cluster key management functions, thus, limiting the impact of sensor node capture to the attacked cluster. Within a cluster, DCK decouples key generation, assignment, and distribution, and distributes the key management tasks among cluster nodes. Simulation results show that DCK is efficient in terms of energy consumption and storage. Also, it significantly outperforms other dynamic keying schemes, in particular with regards to energy consumed in key refreshment and re‐keying after node capture. Copyright © 2006 John Wiley &amp; Sons, Ltd.