Protein oxidative modifications:new mass spectrometry approaches to detection in biological samples

In inflammatory diseases, release of oxidants leads to oxidative damage to proteins. The precise nature of oxidative damage to individual proteins depends on the oxidant involved. Chlorination and nitration are markers of modification by the myeloperoxidase-H2O2-Cl- system and nitric oxide-derived oxidants, respectively. Although these modifications can be detected by western blotting, currently no reliable method exists to identify the specific sites damage to individual proteins in complex mixtures such as clinical samples. We are developing novel LCMS2 and precursor ion scanning methods to address this. LC-MS2 allows separation of peptides and detection of mass changes in oxidized residues on fragmentation of the peptides. We have identified indicative fragment ions for chlorotyrosine, nitrotyrosine, hydroxytyrosine and hydroxytryptophan. A nano-LC/MS3 method involving the dissociation of immonium ions to give specific fragments for the oxidized residues has been developed to overcome the problem of false positives from ions isobaric to these immonium ions that exist in unmodified peptides. The approach has proved able to identify precise protein modifications in individual proteins and mixtures of proteins. An alternative methodology involves multiple reaction monitoring for precursors and fragment ions are specific to oxidized and chlorinated proteins, and this has been tested with human serum albumin. Our ultimate aim is to apply this methodology to the detection of oxidative post-translational modifications in clinical samples for disease diagnosis, monitoring the outcomes of therapy, and improved understanding of disease biochemistry.

Enclosing the behavior of a hybrid system up to and beyond a Zeno point

Even simple hybrid systems like the classic bouncing ball can exhibit Zeno behaviors. The existence of this type of behavior has so far forced simulators to either ignore some events or risk looping indefinitely. This in turn forces modelers to either insert ad hoc restrictions to circumvent Zeno behavior or to abandon hybrid modeling. To address this problem, we take a fresh look at event detection and localization. A key insight that emerges from this investigation is that an enclosure for a given time interval can be valid independently of the occurrence of a given event. Such an event can then even occur an unbounded number of times, thus making it possible to handle certain types of Zeno behavior.

Fuzzy knowledge-based approach to treating uncertainty in inventory control

Inventory control in complex manufacturing environments encounters various sources of uncertainity and imprecision. This paper presents one fuzzy knowledge-based approach to solving the problem of order quantity determination, in the presence of uncertain demand, lead time and actual inventory level. Uncertain data are represented by fuzzy numbers, and vaguely defined relations between them are modeled by fuzzy if-then rules. The proposed representation and inference mechanism are verified using a large numbers of examples. The results of three representative cases are summarized. Finally a comparison between the developed fuzzy knowledge-based and traditional, probabilistic approaches is discussed.

Information Supply of Geo-information Systems for the Forecasting Problem of the Avalanche Danger

This article is dedicated to the vital problem of the creation of GIS-systems for the monitoring, prognostication and control of technogenic natural catastrophes. The decrease of risks, the protection of economic objects, averting the human victims, caused by the dynamism of avalanche centers, depends on the effectiveness of the prognostication procedures of avalanche danger used. In the article the structure of a prognostication subsystem information input is developed and the technology for the complex forecast of avalanche-prone situations is proposed.

Application of the Multivariate Prediction Method to Time Series

* This work was financially supported by RFBR-04-01-00858.

Hough Transform Approach to Identification of Flare Stars in Multi-exposure Plate Images

ACM Computing Classification System (1998): I.2.8 , I.2.10, I.5.1, J.2.

The Darboux Problem for a Class of 3-D Weakly Hyperbolic Equations

Недю Попиванов, Цветан Христов - Изследвани са някои тримерни аналози на задачата на Дарбу в равнината. През 1952 М. Протер формулира нови тримерни гранични задачи както за клас слабо хиперболични уравнения, така и за някои хиперболично-елиптични уравнения. За разлика от коректността на двумерната задача на Дарбу, новите задачи са некоректни. За слабо хиперболични уравнения, съдържащи младши членове, ние намираме достатъчни условия както за съществуване и единственост на обобщени решения с изолирана степенна особеност, така и за единственост на квази-регулярни решения на задачата на Протер.

On the k-anonymization of time-varying and multi-layer social graphs

The popularity of online social media platforms provides an unprecedented opportunity to study real-world complex networks of interactions. However, releasing this data to researchers and the public comes at the cost of potentially exposing private and sensitive user information. It has been shown that a naive anonymization of a network by removing the identity of the nodes is not sufficient to preserve users’ privacy. In order to deal with malicious attacks, k -anonymity solutions have been proposed to partially obfuscate topological information that can be used to infer nodes’ identity. In this paper, we study the problem of ensuring k anonymity in time-varying graphs, i.e., graphs with a structure that changes over time, and multi-layer graphs, i.e., graphs with multiple types of links. More specifically, we examine the case in which the attacker has access to the degree of the nodes. The goal is to generate a new graph where, given the degree of a node in each (temporal) layer of the graph, such a node remains indistinguishable from other k-1 nodes in the graph. In order to achieve this, we find the optimal partitioning of the graph nodes such that the cost of anonymizing the degree information within each group is minimum. We show that this reduces to a special case of a Generalized Assignment Problem, and we propose a simple yet effective algorithm to solve it. Finally, we introduce an iterated linear programming approach to enforce the realizability of the anonymized degree sequences. The efficacy of the method is assessed through an extensive set of experiments on synthetic and real-world graphs.

Enclosing the behavior of a hybrid automaton up to and beyond a Zeno point

Even simple hybrid automata like the classic bouncing ball can exhibit Zeno behavior. The existence of this type of behavior has so far forced a large class of simulators to either ignore some events or risk looping indefinitely. This in turn forces modelers to either insert ad-hoc restrictions to circumvent Zeno behavior or to abandon hybrid automata. To address this problem, we take a fresh look at event detection and localization. A key insight that emerges from this investigation is that an enclosure for a given time interval can be valid independent of the occurrence of a given event. Such an event can then even occur an unbounded number of times. This insight makes it possible to handle some types of Zeno behavior. If the post-Zeno state is defined explicitly in the given model of the hybrid automaton, the computed enclosure covers the corresponding trajectory that starts from the Zeno point through a restarted evolution.

An aspect-oriented approach to designing role-based access control services

Access control (AC) limits access to the resources of a system only to authorized entities. Given that information systems today are increasingly interconnected, AC is extremely important. The implementation of an AC service is a complicated task. Yet the requirements to an AC service vary a lot. Accordingly, the design of an AC service should be flexible and extensible in order to save development effort and time. Unfortunately, with conventional object-oriented techniques, when an extension has not been anticipated at the design time, the modification incurred by the extension is often invasive. Invasive changes destroy design modularity, further deteriorate design extensibility, and even worse, they reduce product reliability. ^ A concern is crosscutting if it spans multiple object-oriented classes. It was identified that invasive changes were due to the crosscutting nature of most unplanned extensions. To overcome this problem, an aspect-oriented design approach for AC services was proposed, as aspect-oriented techniques could effectively encapsulate crosscutting concerns. The proposed approach was applied to develop an AC framework that supported role-based access control model. In the framework, the core role-based access control mechanism is given in an object-oriented design, while each extension is captured as an aspect. The resulting framework is well-modularized, flexible, and most importantly, supports noninvasive adaptation. ^ In addition, a process to formalize the aspect-oriented design was described. The purpose is to provide high assurance for AC services. Object-Z was used to specify the static structure and Predicate/Transition net was used to model the dynamic behavior. Object-Z was extended to facilitate specification in an aspect-oriented style. The process of formal modeling helps designers to enhance their understanding of the design, hence to detect problems. Furthermore, the specification can be mathematically verified. This provides confidence that the design is correct. It was illustrated through an example that the model was ready for formal analysis. ^

Abstractions to support dynamic adaptation of communication frameworks for user-centric communication

The convergence of data, audio and video on IP networks is changing the way individuals, groups and organizations communicate. This diversity of communication media presents opportunities for creating synergistic collaborative communications. This form of collaborative communication is however not without its challenges. The increasing number of communication service providers coupled with a combinatorial mix of offered services, varying Quality-of-Service and oscillating pricing of services increases the complexity for the user to manage and maintain ‘always best’ priced or performance services. Consumers have to manually manage and adapt their communication in line with differences in services across devices, networks and media while ensuring that the usage remain consistent with their intended goals. This dissertation proposes a novel user-centric approach to address this problem. The proposed approach aims to reduce the aforementioned complexity to the user by (1) providing high-level abstractions and a policy based methodology for automated selection of the communication services guided by high-level user policies and (2) providing services through the seamless integration of multiple communication service providers and providing an extensible framework to support the integration of multiple communication service providers. The approach was implemented in the Communication Virtual Machine (CVM), a model-driven technology for realizing communication applications. The CVM includes the Network Communication Broker, the layer responsible for providing a network-independent API to the upper layers of CVM. The initial prototype for the NCB supported only a single communication framework which limited the number, quality and types of services available. Experimental evaluation of the approach show the additional overhead of the approach is minimal compared to the individual communication services frameworks. Additionally the automated approach proposed out performed the individual communication services frameworks for cross framework switching.

Strategic positioning of Taiwan in the outsourcing market: Evidence from information technology services and electronic manufacturing outsourcing to China

In outsourcing relationships with China, the Electronic Manufacturing (EM) and Information Technology Services (ITS) industry in Taiwan may possess such advantages as the continuing growth of its production value, complete manufacturing supply chain, low production cost and a large-scale Chinese market, and language and culture similarity compared to outsourcing to other countries. Nevertheless, the Council for Economic Planning and Development of Executive Yuan (CEPD) found that Taiwan's IT services outsourcing to China is subject to certain constraints and might not be as successful as the EM outsourcing (Aggarwal, 2003; CEPD, 2004a; CIER, 2003; Einhorn and Kriplani, 2003; Kumar and Zhu, 2006; Li and Gao, 2003; MIC, 2006). Some studies examined this issue, but failed to (1) provide statistical evidence about lower prevalence rates of IT services outsourcing, and (2) clearly explain the lower prevalence rates of IT services outsourcing by identifying similarities and differences between both types of outsourcing contexts. This research seeks to fill that gap and possibly provide potential strategic guidelines to ITS firms in Taiwan. This study adopts Transaction Cost Economics (TCE) as the theoretical basis. The basic premise is that different types of outsourcing activities may incur differing transaction costs and realize varying degrees of outsourcing success due to differential attributes of the transactions in the outsourcing process. Using primary data gathered from questionnaire surveys of ninety two firms, the results from exploratory analysis and binary logistic regression indicated that (1) when outsourcing to China, Taiwanese firms' ITS outsourcing tends to have higher level of asset specificity, uncertainty and technical skills relative to EM outsourcing, and these features indirectly reduce firms' outsourcing prevalence rates via their direct positive impacts on transaction costs; (2) Taiwanese firms' ITS outsourcing tends to have lower level of transaction structurability relative to EM outsourcing, and this feature indirectly increases firms' outsourcing prevalence rates via its direct negative impacts on transaction costs; (3) frequency does influence firms' transaction costs in ITS outsourcing positively, but does not bring impacts into their outsourcing prevalence rates, (4) relatedness does influence firms' transaction costs positively and prevalence rates negatively in ITS outsourcing, but its impacts on the prevalence rates are not caused by the mediation effects of transaction costs, and (5) firm size of outsourcing provider does not affect firms' transaction costs, but does affect their outsourcing prevalence rates in ITS outsourcing directly and positively. Using primary data gathered from face-to-face interviews of executives from seven firms, the results from inductive analysis indicated that (1) IT services outsourcing has lower prevalence rates than EM outsourcing, and (2) this result is mainly attributed to Taiwan's core competence in manufacturing and management and higher overall transaction costs of IT services outsourcing. Specifically, there is not much difference between both types of outsourcing context in the transaction characteristics of reputation and most aspects of overall comparison. Although there are some differences in the feature of firm size of the outsourcing provider, the difference doesn't cause apparent impacts on firms' overall transaction costs. The medium or above medium difference in the transaction characteristics of asset specificity, uncertainty, frequency, technical skills, transaction structurability, and relatedness has caused higher overall transaction costs for IT services outsourcing. This higher cost might cause lower prevalence rates for ITS outsourcing relative to EM outsourcing. Overall, the interview results are consistent with the statistical analyses and provide support to my expectation that in outsourcing to China, Taiwan's electronic manufacturing firms do have lower prevalence rates of IT services outsourcing relative to EM outsourcing due to higher transaction costs caused by certain attributes. To solve this problem, firms' management should aim at identifying alternative strategies and strive to reduce their overall transaction costs of IT services outsourcing by initiating appropriate strategies which fit their environment and needs.

How does problem based learning fit with cognitive load theory?

This paper reports on an investigation with first year undergraduate Product Design and Management students within a School of Engineering. The students at the time of this investigation had studied fundamental engineering science and mathematics for one semester. The students were given an open ended, ill formed problem which involved designing a simple bridge to cross a river. They were given a talk on problem solving and given a rubric to follow, if they chose to do so. They were not given any formulae or procedures needed in order to resolve the problem. In theory, they possessed the knowledge to ask the right questions in order to make assumptions but, in practice, it turned out they were unable to link their a priori knowledge to resolve this problem. They were able to solve simple beam problems when given closed questions. The results show they were unable to visualise a simple bridge as an augmented beam problem and ask pertinent questions and hence formulate appropriate assumptions in order to offer resolutions.

Least Squares Approach to Inverse Problems in Musculoskeletal Biomechanics

Inverse simulations of musculoskeletal models computes the internal forces such as muscle and joint reaction forces, which are hard to measure, using the more easily measured motion and external forces as input data. Because of the difficulties of measuring muscle forces and joint reactions, simulations are hard to validate. One way of reducing errors for the simulations is to ensure that the mathematical problem is well-posed. This paper presents a study of regularity aspects for an inverse simulation method, often called forward dynamics or dynamical optimization, that takes into account both measurement errors and muscle dynamics. The simulation method is explained in detail. Regularity is examined for a test problem around the optimum using the approximated quadratic problem. The results shows improved rank by including a regularization term in the objective that handles the mechanical over-determinancy. Using the 3-element Hill muscle model the chosen regularization term is the norm of the activation. To make the problem full-rank only the excitation bounds should be included in the constraints. However, this results in small negative values of the activation which indicates that muscles are pushing and not pulling. Despite this unrealistic behavior the error maybe small enough to be accepted for specific applications. These results is a starting point start for achieving better results of inverse musculoskeletal simulations from a numerical point of view.

A Finite Element to Perform 3D Shakedown Analysis for Limited Kinematic Hardening Materials

The use of the Design by Analysis (DBA) route is a modern trend in pressure vessel and piping international codes in mechanical engineering. However, to apply the DBA to structures under variable mechanical and thermal loads, it is necessary to assure that the plastic collapse modes, alternate plasticity and incremental collapse (with instantaneous plastic collapse as a particular case), be precluded. The tool available to achieve this target is the shakedown theory. Unfortunately, the practical numerical applications of the shakedown theory result in very large nonlinear optimization problems with nonlinear constraints. Precise, robust and efficient algorithms and finite elements to solve this problem in finite dimension has been a more recent achievements. However, to solve real problems in an industrial level, it is necessary also to consider more realistic material properties as well as to accomplish 3D analysis. Limited kinematic hardening, is a typical property of the usual steels and it should be considered in realistic applications. In this paper, a new finite element with internal thermodynamical variables to model kinematic hardening materials is developed and tested. This element is a mixed ten nodes tetrahedron and through an appropriate change of variables is possible to embed it in a shakedown analysis software developed by Zouain and co-workers for elastic ideally-plastic materials, and then use it to perform 3D shakedown analysis in cases with limited kinematic hardening materials