Mechanisms of resistance in a human cell line exposed to sequential topoisomerase poisoning

Camptothecins are a new class of anticancer drugs that target DNA topoisomerase I; current efforts are directed toward elucidating optimal combinations of these drugs with other antineoplastic agents. A rationale for the use of sequential therapy involving the combination of camptothecins with topoisomerase II-targeting drugs, such as etoposide, has arisen from observations of increased topoisomerase II protein levels in cell lines resistant to camptothecin. In an effort to understand potential mechanisms of resistance to this strategy, we developed a U-937 cell subline, denoted RERC, that is capable of surviving exposure to sequential topoisomerase poisoning. The RERC cells are 200-fold resistant to camptothecin, 8-fold resistant to etoposide, and 10-fold hypersensitive to cisplatin compared to the parental U-937 cells. Biochemical analyses indicate that the resistant phenotype involves alterations in both topoisomerase I and topoisomerase IIalpha. Topoisomerase I catalytic activity in the resistant cells is similar to that of the parental line but is resistant to camptothecin. Moreover, the resistant cells express a single mRNA species of topoisomerase I that codes for a mutation in codon 533. In addition, topoisomerase IIalpha protein levels are decreased 10-fold in the resistant line, coincident with a two-fold decrease in the expression of topoisomerase IIalpha mRNA. Collectively, these results indicate that resistance to sequential topoisomerase poisoning may involve a reduction in total cellular topoisomerase activity.     

Retrospective adaptive prefetching for interactive Web GIS applications

A major task of a Web GIS (Geographic Information Systems) system is to transfer map data to client applications over the Internet, which may be too costly. To improve this inefficient process, various solutions are available. Caching the responses of the requests on the client side is the most commonly implemented solution. However, this method may not be adequate by itself. Besides caching the responses, predicting the next possible requests from a client and updating the cache with responses for those requests together provide a remarkable performance improvement. This procedure is called “prefetching” and makes caching mechanisms more effective and efficient. This paper proposes an efficient prefetching algorithm called Retrospective Adaptive Prefetch (RAP), which is constructed over a heuristic method that considers the former actions of a given user. The algorithm reduces the user-perceived response time and improves user navigation efficiency. Additionally, it adjusts the cache size automatically, based on the memory size of the client’s machine. RAP is compared with four other prefetching algorithms. The experiments show that RAP provides better performance enhancements than the other methods.     

HamleDT: Harmonized multi-language dependency treebank

We present HamleDT—a HArmonized Multi-LanguagE Dependency Treebank. HamleDT is a compilation of existing dependency treebanks (or dependency conversions of other treebanks), transformed so that they all conform to the same annotation style. In the present article, we provide a thorough investigation and discussion of a number of phenomena that are comparable across languages, though their annotation in treebanks often differs. We claim that transformation procedures can be designed to automatically identify most such phenomena and convert them to a unified annotation style. This unification is beneficial both to comparative corpus linguistics and to machine learning of syntactic parsing.     

One-Way Functions Using Algorithmic and Classical Information Theories

We prove several results relating injective one-way functions, time-bounded conditional Kolmogorov complexity, and time-bounded conditional entropy. First we establish a connection between injective, strong and weak one-way functions and the expected value of the polynomial time-bounded Kolmogorov complexity, denoted here by?E(K ^t (x|f(x))). These results are in both directions. More precisely, conditions on?E(K ^t (x|f(x))) that imply that?f is a weak one-way function, and properties of?E(K ^t (x|f(x))) that are implied by the fact that?f is a strong one-way function. In particular, we prove a separation result: based on the concept of time-bounded Kolmogorov complexity, we find an interval in which every function?f is a necessarily weak but not a strong one-way function. Then we propose an individual approach to injective one-way functions based on Kolmogorov complexity, defining Kolmogorov one-way functions and prove some relationships between the new proposal and the classical definition of one-way functions, showing that a Kolmogorov one-way function is also a deterministic one-way function. A relationship between Kolmogorov one-way functions and the conjecture of polynomial time symmetry of information is also proved. Finally, we relate?E(K ^t (x|f(x))) and two forms of time-bounded entropy, the unpredictable entropy?H ^unp, in which ??one-wayness?? of a function can be easily expressed, and the Yao⁺ entropy, a measure based on compression/decompression schema in which only the decompressor is restricted to be time-bounded.     

A general topology-based framework for adaptive insertion of cohesive elements in finite element meshes

Large-scale simulation of separation phenomena in solids such as fracture, branching, and fragmentation requires a scalable data structure representation of the evolving model. Modeling of such phenomena can be successfully accomplished by means of cohesive models of fracture, which are versatile and effective tools for computational analysis. A common approach to insert cohesive elements in finite element meshes consists of adding discrete special interfaces (cohesive elements) between bulk elements. The insertion of cohesive elements along bulk element interfaces for fragmentation simulation imposes changes in the topology of the mesh. This paper presents a unified topology-based framework for supporting adaptive fragmentation simulations, being able to handle two- and three-dimensional models, with finite elements of any order. We represent the finite element model using a compact and “complete” topological data structure, which is capable of retrieving all adjacency relationships needed for the simulation. Moreover, we introduce a new topology-based algorithm that systematically classifies fractured facets (i.e., facets along which fracture has occurred). The algorithm follows a set of procedures that consistently perform all the topological changes needed to update the model. The proposed topology-based framework is general and ensures that the model representation remains always valid during fragmentation, even when very complex crack patterns are involved. The framework correctness and efficiency are illustrated by arbitrary insertion of cohesive elements in various finite element meshes of self-similar geometries, including both two- and three-dimensional models. These computational tests clearly show linear scaling in time, which is a key feature of the present data-structure representation. The effectiveness of the proposed approach is also demonstrated by dynamic fracture analysis through finite element simulations of actual engineering problems.

A Multiagent Platform for Ubiquitous Service Provision

The Virtual Home Environment is very important in contemporary mobile telecommunications infrastructure as it caters for the ubiquitous provision of services irrespective of network, location and user device. The universality of systems like Universal Mobile Telecommunications System and wi-fi increases the need for the rapid introduction of efficient VHE schemes. In this paper, we study the adoption of Mobile Agents for handling the VHE functionality. Mobile agents are nicely harmonized with the broader idea of VHE as they allow the autonomous execution of tasks by components that roam from node to node and network to network. We present the detailed modeling of a VHE provisioning architecture and investigate its suitability for different use cases and technical options (e.g., end user devices). The adoption of mobile agents for the ubiquitous provision of telecommunication services is quite promising in terms of efficiency. Through a series of experiments we quantify the performance benefits stemming from the adoption of mobile agents in contrast to conventional service provisioning schemes.     

Parsing human skeletons in an operating room

Multiple human pose estimation is an important yet challenging problem. In an operating room (OR) environment, the 3D body poses of surgeons and medical staff can provide important clues for surgical workflow analysis. For that purpose, we propose an algorithm for localizing and recovering body poses of multiple human in an OR environment under a multi-camera setup. Our model builds on 3D Pictorial Structures and 2D body part localization across all camera views, using convolutional neural networks (ConvNets). To evaluate our algorithm, we introduce a dataset captured in a real OR environment. Our dataset is unique, challenging and publicly available with annotated ground truths. Our proposed algorithm yields to promising pose estimation results on this dataset.     

How to trust a few among many

The presence of numerous and disparate information sources available to support decision-making calls for efficient methods of harnessing their potential. Information sources may be unreliable, and misleading reports can affect decisions. Existing trust and reputation mechanisms typically rely on reports from as many sources as possible to mitigate the influence of misleading reports on decisions. In the real world, however, it is often the case that querying information sources can be costly in terms of energy, bandwidth, delay overheads, and other constraints. We present a model of source selection and fusion in resource-constrained environments, where there is uncertainty regarding the trustworthiness of sources. We exploit diversity among sources to stratify them into homogeneous subgroups to both minimise redundant sampling and mitigate the effect of certain biases. Through controlled experiments, we demonstrate that a diversity-based approach is robust to biases introduced due to dependencies among source reports, performs significantly better than existing approaches when sampling budget is limited and equally as good with an unlimited budget.     

Encoding Cryptographic Primitives in a Calculus with Polyadic Synchronisation

We thoroughly study the behavioural theory of epi, a ??-calculus extended with polyadic synchronisation. We show that the natural contextual equivalence, barbed congruence, coincides with early bisimilarity, which is thus its co-inductive characterisation. Moreover, we relate early bisimilarity with the other usual notions, ground, late and open, obtaining a lattice of equivalence relations that clarifies the relationship among the ??standard?? bisimilarities. Furthermore, we apply the theory developed to obtain an expressiveness result: epi extended with key encryption primitives may be fully abstractly encoded in the original epi calculus. The proposed encoding is sound and complete with respect to barbed congruence; hence, cryptographic epi (crypto-epi) gets behavioural theory for free, which contrasts with other process languages with cryptographic constructs that usually require a big effort to develop such theory. Therefore, it is possible to use crypto-epi to analyse and to verify properties of security protocols using equational reasoning. To illustrate this claim, we prove compliance with symmetric and asymmetric cryptographic system laws, and the correctness of a protocol of secure message exchange.