401 research outputs found

    An Analysis of Phase Transition in NK Landscapes

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    In this paper, we analyze the decision version of the NK landscape model from the perspective of threshold phenomena and phase transitions under two random distributions, the uniform probability model and the fixed ratio model. For the uniform probability model, we prove that the phase transition is easy in the sense that there is a polynomial algorithm that can solve a random instance of the problem with the probability asymptotic to 1 as the problem size tends to infinity. For the fixed ratio model, we establish several upper bounds for the solubility threshold, and prove that random instances with parameters above these upper bounds can be solved polynomially. This, together with our empirical study for random instances generated below and in the phase transition region, suggests that the phase transition of the fixed ratio model is also easy

    Alien Registration- Culberson, Dorothy J. (Presque Isle, Aroostook County)

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    https://digitalmaine.com/alien_docs/33792/thumbnail.jp

    Consistency and Random Constraint Satisfaction Models

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    In this paper, we study the possibility of designing non-trivial random CSP models by exploiting the intrinsic connection between structures and typical-case hardness. We show that constraint consistency, a notion that has been developed to improve the efficiency of CSP algorithms, is in fact the key to the design of random CSP models that have interesting phase transition behavior and guaranteed exponential resolution complexity without putting much restriction on the parameter of constraint tightness or the domain size of the problem. We propose a very flexible framework for constructing problem instances withinteresting behavior and develop a variety of concrete methods to construct specific random CSP models that enforce different levels of constraint consistency. A series of experimental studies with interesting observations are carried out to illustrate the effectiveness of introducing structural elements in random instances, to verify the robustness of our proposal, and to investigate features of some specific models based on our framework that are highly related to the behavior of backtracking search algorithms

    Seawater alkalinity determination by the pH method

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    The coefficient fH used in the seawater alkalinity method of Anderson and Robinson (1946), has been redetermined at 25°C. We have found that fH = 0.741 ±0,005 for salinities between 30‰ and 41‰…

    Random Graph Coloring - a Statistical Physics Approach

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    The problem of vertex coloring in random graphs is studied using methods of statistical physics and probability. Our analytical results are compared to those obtained by exact enumeration and Monte-Carlo simulations. We critically discuss the merits and shortcomings of the various methods, and interpret the results obtained. We present an exact analytical expression for the 2-coloring problem as well as general replica symmetric approximated solutions for the thermodynamics of the graph coloring problem with p colors and K-body edges.Comment: 17 pages, 9 figure

    Ploidy Reductions in Murine Fusion-Derived Hepatocytes

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    We previously showed that fusion between hepatocytes lacking a crucial liver enzyme, fumarylacetoacetate hydrolase (FAH), and wild-type blood cells resulted in hepatocyte reprogramming. FAH expression was restored in hybrid hepatocytes and, upon in vivo expansion, ameliorated the effects of FAH deficiency. Here, we show that fusion-derived polyploid hepatocytes can undergo ploidy reductions to generate daughter cells with one-half chromosomal content. Fusion hybrids are, by definition, at least tetraploid. We demonstrate reduction to diploid chromosome content by multiple methods. First, cytogenetic analysis of fusion-derived hepatocytes reveals a population of diploid cells. Secondly, we demonstrate marker segregation using ß-galactosidase and the Y-chromosome. Approximately 2–5% of fusion-derived FAH-positive nodules were negative for one or more markers, as expected during ploidy reduction. Next, using a reporter system in which ß-galactosidase is expressed exclusively in fusion-derived hepatocytes, we identify a subpopulation of diploid cells expressing ß-galactosidase and FAH. Finally, we track marker segregation specifically in fusion-derived hepatocytes with diploid DNA content. Hemizygous markers were lost by ≥50% of Fah-positive cells. Since fusion-derived hepatocytes are minimally tetraploid, the existence of diploid hepatocytes demonstrates that fusion-derived cells can undergo ploidy reduction. Moreover, the high degree of marker loss in diploid daughter cells suggests that chromosomes/markers are lost in a non-random fashion. Thus, we propose that ploidy reductions lead to the generation of genetically diverse daughter cells with about 50% reduction in nuclear content. The generation of such daughter cells increases liver diversity, which may increase the likelihood of oncogenesis

    Network conduciveness with application to the graph-coloring and independent-set optimization transitions

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    We introduce the notion of a network's conduciveness, a probabilistically interpretable measure of how the network's structure allows it to be conducive to roaming agents, in certain conditions, from one portion of the network to another. We exemplify its use through an application to the two problems in combinatorial optimization that, given an undirected graph, ask that its so-called chromatic and independence numbers be found. Though NP-hard, when solved on sequences of expanding random graphs there appear marked transitions at which optimal solutions can be obtained substantially more easily than right before them. We demonstrate that these phenomena can be understood by resorting to the network that represents the solution space of the problems for each graph and examining its conduciveness between the non-optimal solutions and the optimal ones. At the said transitions, this network becomes strikingly more conducive in the direction of the optimal solutions than it was just before them, while at the same time becoming less conducive in the opposite direction. We believe that, besides becoming useful also in other areas in which network theory has a role to play, network conduciveness may become instrumental in helping clarify further issues related to NP-hardness that remain poorly understood

    Iterative focused screening with biological fingerprints identifies selective Asc-1 inhibitors distinct from traditional high throughput screening

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    N-methyl-d-aspartate receptors (NMDARs) mediate glutamatergic signaling that is critical to cognitive processes in the central nervous system, and NMDAR hypofunction is thought to contribute to cognitive impairment observed in both schizophrenia and Alzheimer’s disease. One approach to enhance the function of NMDAR is to increase the concentration of an NMDAR coagonist, such as glycine or d-serine, in the synaptic cleft. Inhibition of alanine–serine–cysteine transporter-1 (Asc-1), the primary transporter of d-serine, is attractive because the transporter is localized to neurons in brain regions critical to cognitive function, including the hippocampus and cortical layers III and IV, and is colocalized with d-serine and NMDARs. To identify novel Asc-1 inhibitors, two different screening approaches were performed with whole-cell amino acid uptake in heterologous cells stably expressing human Asc-1: (1) a high-throughput screen (HTS) of 3 M compounds measuring 35S l-cysteine uptake into cells attached to scintillation proximity assay beads in a 1536 well format and (2) an iterative focused screen (IFS) of a 45 000 compound diversity set using a 3H d-serine uptake assay with a liquid scintillation plate reader in a 384 well format. Critically important for both screening approaches was the implementation of counter screens to remove nonspecific inhibitors of radioactive amino acid uptake. Furthermore, a 15 000 compound expansion step incorporating both on- and off-target data into chemical and biological fingerprint-based models for selection of additional hits enabled the identification of novel Asc-1-selective chemical matter from the IFS that was not identified in the full-collection HTS

    Recognizing Treelike k-Dissimilarities

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    A k-dissimilarity D on a finite set X, |X| >= k, is a map from the set of size k subsets of X to the real numbers. Such maps naturally arise from edge-weighted trees T with leaf-set X: Given a subset Y of X of size k, D(Y) is defined to be the total length of the smallest subtree of T with leaf-set Y . In case k = 2, it is well-known that 2-dissimilarities arising in this way can be characterized by the so-called "4-point condition". However, in case k > 2 Pachter and Speyer recently posed the following question: Given an arbitrary k-dissimilarity, how do we test whether this map comes from a tree? In this paper, we provide an answer to this question, showing that for k >= 3 a k-dissimilarity on a set X arises from a tree if and only if its restriction to every 2k-element subset of X arises from some tree, and that 2k is the least possible subset size to ensure that this is the case. As a corollary, we show that there exists a polynomial-time algorithm to determine when a k-dissimilarity arises from a tree. We also give a 6-point condition for determining when a 3-dissimilarity arises from a tree, that is similar to the aforementioned 4-point condition.Comment: 18 pages, 4 figure

    Polynomial iterative algorithms for coloring and analyzing random graphs

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    We study the graph coloring problem over random graphs of finite average connectivity cc. Given a number qq of available colors, we find that graphs with low connectivity admit almost always a proper coloring whereas graphs with high connectivity are uncolorable. Depending on qq, we find the precise value of the critical average connectivity cqc_q. Moreover, we show that below cqc_q there exist a clustering phase c∈[cd,cq]c\in [c_d,c_q] in which ground states spontaneously divide into an exponential number of clusters. Furthermore, we extended our considerations to the case of single instances showing consistent results. This lead us to propose a new algorithm able to color in polynomial time random graphs in the hard but colorable region, i.e when c∈[cd,cq]c\in [c_d,c_q].Comment: 23 pages, 10 eps figure
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