AVERAGE VALUE OF SUM OF EXPONENTS OF RUNS IN A STRING Especially, a maximal repetition, which cannot be extended neither to left nor to right, is called a run. The ratio of the length of the run to its period, i.e., is called an exponent. The sum of exponents of runs in a string is of interest. The maximal value of the sum is still unknown, and the current upper bound is 2.9n given by Crochemore and Ilie, where n is the length of a string. In this paper we show a closed formula which exactly expresses the average value of it for any n and any alphabet size, and the limit of this value per unit length as n approaches infinity. For binary strings, the limit value is approximately 1.13103. Repetitions in strings are an important element in the analysis and processing of strings. We especially focus on the runs, which are non-extendable repetitions. Kolpakov and Kucherov showed that the maximal number of runs ρ(n) in any strings of length n is at most cn for some constant c [4] . Although they gave no value for c, recently there have been several results lowering the value [1, 3, 9, 11] . The currently known best upper bound is c = 1.048 [2, 3] . It is conjectured that c < 1.. A repetition count of run is called an exponent, and the maximal sum of exponents is also well studied [1, 5, 10] . It is proved that the maximal sum of exponents is linear and the current best upper bound is 2.9n [1] . It is conjectured that the sum of exponents is less than 2n.. Although the exact estimation of the maximal number ρ(n) of runs is still unknown, Puglisi and Simpson [8] presented a formula that gives the number of runs in a string of length n on average as follows:. where σ is the alphabet size and µ(n) is the Möbius function.. In this paper, we consider the average value e(n) of sum of exponents of runs in strings of length n and prove that. Moreover, we show that. where L(n) is the number of Lyndon words of length n. We showed a formula which expresses the average value of sum of exponents of runs in strings exactly, although the upper bound of it is still open. The situation is similar to the numbers of runs, as Puglisi and Simpson showed in [8] . Moreover we gave the limit of the value per unit length as the length of strings approaches infinity. For the alphabet size σ = 2, the value is approximately 1.13103.

O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


Three-Dimensional Lattice Boltzmann Model Results For Complex Fluids Ordering The kinetics of domain growth of fluid mixtures quenched from a disordered to a lamellar phase has been studied in three dimensions. We use a numerical approach based on the lattice Boltzmann method (LBM). A novel implementation for LBM which "fuses" the collision and streaming steps is used in order to reduce memory and bandwidth requirements. We find that extended defects between stacks of lamellae with different orientation dominate the late time dynamics. Hydrodynamics is an essential ingredient in the modelling of complex fluids. Many relevant phenomena in soft matter physics depend on the interplay between the mesoscopic structures in the fluid (interfaces, extended objects like polymers, colloidal particles, etc.) and the local velocity field. For example, it is well known that the presence of the velocity field affects the process of phase separation of fluid mixtures quenched below the critical point. Different power-law regimes for the growth of the average size R(t) of the domains of the separating phases are found for different ranges of viscosity. At high viscosity, when diffusion is the physical mechanism operating in phase segregation, one has R ∼ t 1/3 . At lower viscosities, the coupling between surface tension and the velocity field becomes relevant and, depending on if inertial or viscous terms dominate in the Navier-Stokes equation, one has R ∼ t 2/3 or R ∼ t, respectively. 2 Other examples come from the study of rheological properties.. 1 For instance, in shear banding, two phases, one of them metastable or not existing in equilibrium, coexist in a Couette cell having different velocity profiles.. 3 This phenomenon can be described only if the dynamics of the velocity field is taken into account.. The most appropriate approach for describing a given complex fluid system depends on the time and the length scales under investigations. In the study of the dynamics of mesoscopic structures and phase transitions, a microscopic approach would become prohibitive from the computational point of view and coarse-grained models are often more convenient. In this paper we study the ordering properties of a fluid with lamellar configurations whose dynamics is described by a time dependent convection-diffusion equation coupled to the Navier-Stokes equation. The equilibrium properties of the lamellar phase are described by a free-energy model particularly appropriate for di-block copolymers in the weak segregation limit. 4 We use lattice Boltzmann method (LBM) 5 to solve both the dynamical equations presenting a new implementation for LBM which "fuses" the collision and streaming steps to reduce memory and bandwidth requirements. This is not the only possibility when dealing with the numerical solution of a convection-diffusion equation coupled with the Navier-Stokes equation. Indeed, several approaches have been proposed. Finite difference (FD) schemes have been adopted, in the case of thermal lattice Boltzmann models for a single fluid 6 and for multiphase flows, to solve the temperature equation. 7 FD schemes have been used also to solve the dynamics of passive scalars by LBM for fluid flows. 8 An updated discussion on this specific issue can be found in Ref. 9 . While, in general, FD schemes can reduce the amount of required memory, in LBM boundary conditions are more easily implemented and give better numerical stability. Moreover, LBM has a more detailed microscopic description than a FD scheme because the LBM takes into consideration the velocities of the particles.. 10 This aspect could be useful when dealing with mixtures of two fluids with different viscosity and/or mass.. Unlike the case of simple binary mixtures, the problem of lamellar ordering is not well understood and there are no quantitative results for the three-dimensional case. Lamellar order is typical of systems with competing interactions. 11, 12 Examples are di-block copolymer melts, where chains of type A and B, covalently bonded end-to-end in pairs, segregate at low temperatures in regions separated by a stack of lamellae, 13 ternary mixtures where surfactant form interfaces between oil and water, 14 or smectic liquid crystals.. The ordering of lamellar systems is affected by the presence of defects on large scales. Previous studies showed the relevance of hydrodynamics on this process for two-dimensional systems. 11, 12, 16, 17 In particular it was found that characteristic lengths evolve with a complex time dependence. A pre-asymptotic regime with a growth consistent with a power-law behavior is followed later by slower logarithmic growth. 17 This behavior can be interpreted as due to the dynamics of grain boundary defects between domains of differently oriented lamellae. We show in this paper that extended defects also have a prominent role in the three-dimensional case.. The paper is organized as follows. Next section decribes the model and the Lattice Boltzmann equation we used. In Sec. 3, the implementation of the algorithm is briefly presented. Results for lamellar ordering are described in Sec. 4. We have implemented a 3D version of the lattice Boltzmann method where the collision and streaming steps are fused in a new implementation of the algorithm with the benefits of saving memory and bandwidth requirements. We have applied this LBM to study lamellar ordering. Our results show that at low viscosity, order is reached on large scales but extended defects are found to dominate the late time dynamics. Indeed, no complete order can be observed even at very long times on large systems as a consequence of the difficulty of removing defects in three spatial dimensions.

O O O O O O B I O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


The Effect of Poverty on Child Development and Educational Outcomes Poverty affects a child's development and educational outcomes beginning in the earliest years of life, both directly and indirectly through mediated, moderated, and transactional processes. School readiness, or the child's ability to use and profit from school, has been recognized as playing a unique role in escape from poverty in the United States and increasingly in developing countries. It is a critical element but needs to be supported by many other components of a povertyalleviation strategy, such as improved opportunity structures and empowerment of families. The paper reviews evidence from interventions to improve school readiness of children in poverty, both in the United States and in developing countries, and provides recommendations for future research and action. In 2000, the United Nations Millennium Summit adopted eight Millennium Development Goals to be achieved by 2015. The first two goals, to eradicate ex treme poverty and hunger and to achieve universal primary education are intimately related. Poverty limits the chances of educational attainment, and at the same time, educational attainment is one of the prime mechanisms for escaping poverty. Poverty is a persis tent problem throughout the world and has deleterious impacts on almost all aspects of family life and outcomes for children. This paper examines the mecha nisms through which poverty affects child development and educational outcomes, and interventions that have been effective in improving child development and ed ucational outcomes for families in poverty in both the United States and developing countries.. Specifically, this paper examines: 1) the concepts of poverty and child development; 2) mechanisms through which poverty affects child development and educational outcomes, including family functioning and community processes; 3) programs and policies that have alleviated the negative effects of poverty on children's development and have promoted child de velopment and education; and 4) recommendations for future research, programs, and policies to reduce the negative consequences of poverty and promote univer-sal education. The paper addresses the global effects of poverty and educational outcomes by including findings from both developed and developing countries.

O O O B O B I O B I B O O O O O B I O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O B O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B I O B I O O O O O O O O B I O O O O O O O B O O O O O O B I O O O O O O O O B O B I O O O O B O B I O B I O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O B I O O O O O O O B I


Federate Migration in a Service Oriented HLA RTI The High Level Architecture provides a general framework for distributed simulation, promoting reusability and interoperability of simulation components (federates). Large scale distributed simulation, in which federates run on many heterogenous computing machines may benefit from migrating federates among these machines for loadbalancing and fault-tolerance. However, the HLA framework does not provide formal support for federate migration currently. We have previously developed a Service Oriented HLA RTI (SOHR) framework, which provides HLA RTI functionalities via the cooperation of a set of Grid services. SOHR is developed with migration support features by using a decoupled federate design. In this paper, a basic federate migration protocol is first proposed to illustrate the process of federate migration in SOHR. Then two optimized protocols are further developed to overlap federate migration with federate execution for the purpose of reducing migration overhead. Experiments show that the migration overhead is reduced considerably in the optimized protocols. The High Level Architecture (HLA) provides a general framework for large-scale distributed simulation, supporting reusability and interoperabilty of simulation components. It was developed initially by the U.S. Defense Modeling and Simulation Office (DMSO) [3] , and was adopted as IEEE 1516 standard for distributed simulation in September 2000 [7] . An HLA-based simulation is called a federation, which consists of a number of simulation components called federates. The Runtime Infrastructure (RTI) software is an implementation of the HLA interface specification. All communications between federates in the feder-ation are through the underlying RTI. Traditionally, federates are executed with a vendor-specific RTI software, such as the DMSO RTI [3] . Resource arrangements and security measures must be carried out before the actual execution of a distributed simulation across administrative organizations. To address this inflexibility, a service oriented and Grid-based infrastructure is considered as a potential solution.. Grid computing was proposed by Foster in [5] , for flexible, secure and coordinated sharing of geographically distributed computing and data resources. Among various Grid middleware, Globus Toolkit [6] is the de facto standard for Grid computing. Its latest version GT4 offers a collection of Grid services based on OGSA (Open Grid Services Architecture) [4] . It also implements the Web Services Resource Framework (WSRF) [9] and Web Services Addressing (WSAddressing) [14] standards. The service oriented architecture (SOA) reorganizes software applications into a set of cooperating services. These loosely coupled services are published, discovered, mediated, and consumed dynamically. They work together seamlessly and securely over a network to provide functionalities to end users. The services in the SOA relieve the users from detailed knowledge of service implementation and execution platform. The only concern of the users is how to invoke services through predefined service interfaces.. We have previously proposed a Service Oriented HLA RTI (SOHR) framework [10] . It is composed of a set of predefined Grid services based on GT4. These Grid services can be implemented in different manners and deployed to heterogeneous resources. They are discovered and composed dynamically to provide federates with the functionalities of the HLA RTI.. A large-scale simulation in the SOHR framework usually runs on a distributed environment to access shared resources among different organizations, and to achieve high performance and scalability. In other words, a federation may consist of a group of federates running concurrently on heterogenous computing machines. It is desirable to mi-grate federates among these machines for several reasons. Firstly, resources are required by the federate during its execution. However, the required resources may not be available on the machine where the federate is currently executing. Also, the availability of these resources in a distributed computing environment may change during federate execution. Secondly, the imbalance of workload among computing machines may lead to poor performance. To keep the workload balanced, federates are migrated from heavilyloaded machines to lightly-loaded ones. Thirdly, federate migration can reduce communication overhead. If federates communicate with each other frequently, it is beneficial to migrate logically interrelated federates to geographically close machines. Finally, federate fault-tolerance can also be supported by migrating a federate from a faulty machine to a non-faulty one.. Federate migration in SOHR is especially important, because it is a framework to support the execution of distributed simulation on the Grid. A Grid environment is highly unstable and unpredictable. Resources are dynamically shared among a large number of participants on the Grid. The availability of the shared resources may change due to various reasons (e.g., security considerations or machine restarting). Workload and communication overhead vary wildly among participants. The protocols described in this paper exploit the features in SOHR to support efficient federate migration. A one-phase migration protocol is first proposed to illustrate the federate migration process in SOHR. To achieve higher efficiency, two optimized protocols are then developed.. The rest of the paper is organized as follows. Section 2 introduces some related work in federate migration. Section 3 introduces SOHR briefly, and then describes the federate migration protocols. Experimental results are presented and discussed in section 4. Finally, section 5 concludes the paper and outlines future work. Based on the decoupled federate design in SOHR, a federate can be migrated easily. There is no need to transfer the RTI state in the LRI, as MigFed and ResFed are connected to the same LIS and LRI. Only the state of the federate simulation model needs to be transferred in the migration. Three federate migration protocols are proposed in the paper. The one-phase migration protocol is the basic protocol, which illustrates the federate migration process in SOHR. Two optimized protocols are developed to reduce the migration overhead. The two-phase migration can overlap the transfer of static files with continuous execution of MigFed. In the relay-based migration, the transfer of dynamic files and the restoration of the federate are further overlapped with MigFed execution. These protocols can be applied to other RTI implementations that utilize the decoupled federate design, such as the HLA-Grid introduced in [15] and the framework proposed in [2] .. In the future, we will focus on the issue of federate fault tolerance, with the support of federate migration. The migration and fault tolerance of the LS will also be investigated. Meanwhile we will try to exploit the advantages of GT4 in resource management, secure communication and reliable data transfer. Federate migration means transferring a federate from one computing machine to another during execution. It can be realized at different levels. At the operating system level, a federate can be transparently migrated by moving the federate process to the destination machine. However it is time consuming, especially when the source and destination machines are heterogenous. In order to achieve heterogeneity, process state needs to be saved in a machine-independent representation [8] . At the application level, a federate can be restarted on a different machine much more easily. The amount of saved state can be much less than that at the operating system level. However, the programmer or compiler has the responsibility to generate state saving and restoring code. This paper focuses on application level federate migration, assuming that state saving and restoring functions are provided by migrate-enabled federates. A federate saves and transfers its state, and then it restores its state and resumes execution at the destination machine.. However federate migration is much more difficult than normal application migration. In a traditional RTI implementation (e.g, DMSO RTI), a federate consists of a user-designed simulation model and Local RTI Component (LRC). The simulation model performs local computation, while the LRC handles the distributed computation by communicating via the RTI with LRCs of the other federates. The simulation model and LRC are tightly coupled to form a complete federate. Thus, they need to be migrated together to the destination machine. The RTI state (e.g., information of declaration, ownership, time and data distribution management services) needs to be saved and restored during the migration and other federates in the federation should be informed about the migration. There are mainly two types of migration approaches, which have been proposed by various research projects: Federation-wide Save and Restore and "Freeze free" Migration. For simplicity, this paper uses the abbreviation "MigFed" to denote the migrating federate at the source machine, and "ResFed" to denote the restarting federate at the destination machine.

B I O O O O B B O O O O O O O O O B I O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B I O O O O O O O O B B O O O O B B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O B I O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O B O O O O O O O O O O O O O B O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O B O O O B O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


High-Order Finite Element Methods for Moving Boundary Problems with Prescribed Boundary Evolution We introduce a framework for the design of finite element methods for two-dimensional moving boundary problems with prescribed boundary evolution that have arbitrarily high order of accuracy, both in space and in time. At the core of our approach is the use of a universal mesh: a stationary background mesh containing the domain of interest for all times that adapts to the geometry of the immersed domain by adjusting a small number of mesh elements in the neighborhood of the moving boundary. The resulting method maintains an exact representation of the (prescribed) moving boundary at the discrete level, or an approximation of the appropriate order, yet is immune to large distortions of the mesh under large deformations of the domain. The framework is general, making it possible to achieve any desired order of accuracy in space and time by selecting a preferred and suitable finite-element space on the universal mesh for the problem at hand, and a preferred and suitable time integrator for ordinary differential equations. We illustrate our approach by constructing a particular class of methods, and apply them to a prescribed-boundary variant of the Stefan problem. We present numerical evidence for the order of accuracy of our schemes in one and two dimensions. We have presented a general framework for the design of high-order finite element methods for moving boundary problems with prescribed boundary evolution. A key role in our approach was played by universal meshes, which combine the immunity to large mesh distortions enjoyed by conventional fixed-mesh methods with the geometric fidelity of deformingmesh methods. A given accuracy in space and time may be achieved by choosing an appropriate finite element space on the universal mesh and an appropriate time integrator for ordinary differential equations. The order of accuracy of the resulting scheme is suboptimal by one half an order according to theory, although we observed in our numerical examples that terms of optimal order tend to dominate in practice.. Several aspects of this research motivate further study. First, we have yet to address problems for which the boundary itself is an unknown, rather than prescribed. An extension Here, δ ij denotes the Kronecker delta and a

O O O O O B I O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


Rapid

re-meshing

and

re-solution

of

three-dimensional

boundary

element

problems

for

interactive

stress

analysis

'Rapid

re-meshing

and

re-solution

of

three-dimensional

boundary

element

problems

for

interactive

stress

analysis.',

Engineering

analysis

with

boundary

elements.,

pp.

Further

information

on

publisher's

copyright

statement:

NOTICE:

this

is

the

author's

version

of

a

work

that

was

accepted

for

publication

in

Engineering

Analysis

with

Boundary

Elements.

Changes

resulting

from

the

publishing

process,

such

as

peer

review,

editing,

corrections,

structural

formatting,

and

other

quality

control

mechanisms

may

not

be

reected

in

this

document.

Changes

may

have

been

made

to

this

work

since

it

was

submitted

for

publication.

A

denitive

version

was

subsequently

published

in

Engineering

Analysis

with

Boundary

Elements,

September

policyThe

full-text

may

be

used

and/or

reproduced,

and

given

to

third

parties

in

any

format

or

medium,

without

prior

permission

or

charge,

for

personal

research

or

study,

educational,

or

not-for-prot

purposes

provided

that:•

a

full

bibliographic

reference

is

made

to

the

original

source

a

link

is

made

to

the

metadata

record

in

DRO

the

full-text

is

not

changed

in

any

way

The

full-text

must

not

be

sold

in

any

format

or

medium

without

the

formal

permission

of

the

copyright

holders.Please

consult

the

full

DRO

policy

for

further

details.

Structural

design

of

mechanical

components

is

an

iterative

process

that

involves

multiple

stress

analysis

runs;

this

can

be

time

consuming

and

expensive.

It

is

becoming

increasingly

possible

to

make

significant

improvements

in

the

efficiency

of

this

process

by

increasing

the

level

of

interactivity.

One

approach

is

through

real-time

re-analysis

of

models

with

continuously

updating

geometry.

A

key

part

of

such

a

strategy

is

the

ability

to

accommodate

changes

in

geometry

with

minimal

perturbation

to

an

existing

mesh.

This

work

introduces

a

new

re-meshing

algorithm

that

can

generate

and

update

a

boundary

element

mesh

in

real-time

as

a

series

of

small

changes

are

sequentially

applied

to

the

associated

model.

The

algorithm

is

designed

to

make

minimal

updates

to

the

mesh

between

each

step

whilst

preserving

a

suitable

mesh

quality

that

retains

accuracy

in

the

stress

results.

This

significantly

reduces

the

number

of

terms

that

need

to

be

updated

in

the

system

matrix,

thereby

reducing

the

time

required

to

carry

out

a

re-analysis

of

the

model.

A

range

of

solvers

are

assessed

to

find

the

most

efficient

and

robust

method

of

re-solving

the

system.

The

GMRES

algorithm,

using

complete

approximate

LU

preconditioning,

is

found

to

provide

the

fastest

convergence

rate.

Stress

analysis

of

mechanical

components

has

become

an

essential

part

of

the

validation

of

engineering

designs

but

it

can

be

time

consuming

and

expensive.

It

is

desirable

to

shorten

the

design

cycle,

thus

reducing

development

costs

and

enabling

new

products

to

be

brought

to

market

in

the

shortest

time

possible.

It

is

of

particular

importance

to

obtain

the

most

suitable

design

at

the

conceptual

design

stage

as

the

cost

of

any

change

at

later

stages

grows

rapidly.

For

many

components

this

can

be

done

only

through

rapid

computational

analysis

of

a

wide

range

of

initial

geometries..

For

clarity

it

is

necessary

to

precisely

define

the

terms

realtime

and

rapid

analysis

within

the

context

of

this

work.

We

use

the

definitions

of

Margetts

et

al.

Real-time

refers

to

the

analysis

taking

place

within

the

refresh

rate

of

the

media

on

which

the

model

is

viewed.

This

will

typically

be

within

seconds.

Rapid

incorporates

real-time

but

allows

that

the

analysis

may

be

slightly

slower,

taking

place

in

an

acceptably

short

period

of

time

that

the

user

is

prepared

to

wait.

This

is

of

the

order

of

seconds

and

is

synonymous

with

the

definition

of

interactive

given

in

Real-time

analysis

of

two-dimensional

models

is

now

a

reality

However,

real-time

stress

analysis

of

three-dimensional

objects

presents

numerous

additional

challenges.

Over

the

last

decade,

various

schemes

based

on

the

finite

element

method

(FEM)

that

aim

to

provide

interactivity

have

been

presented

Meier

et

al.

review

a

range

of

deformable

models

that

utilise

both

finite

element

(FE)

and

boundary

element

(BE)

techniques.

In

this

paper

we

address

only

BE

implementations.

The

boundary

element

method

(BEM)

is

a

natural

method

to

use

where

re-meshing

is

involved

as

changes

need

to

be

applied

only

to

elements

on

the

surface

of

the

model.

If

the

volume

were

meshed,

as

in

the

case

of

the

FEM,

then

changes

would

propagate

further

through

the

model

and

many

more

degrees

of

freedom

would

be

affected.

Mackie

presents

a

substructuring

approach

that

attempts

to

ameliorate

these

difficulties.

Wang

et

al.

present

a

BEM

based

scheme

for

interactive

analysis

for

surgical

simulation.

Real-time

updating

is

also

of

interest

to

computer

game

developers

to

provide

realistic

deformable

objects.

For

example,

James

and

Pai

discuss

the

use

of

the

BEM

to

provide

physically

accurate

simulation

of

three-dimensional

objects.

However,

as

the

technique

is

used

purely

for

visual

approximation

of

deformations,

a

much

lower

degree

of

accuracy

is

required

and

a

coarse

mesh

can

be

used

resulting

in

a

very

fast

analysis.

Pre-computed

solutions

are

also

utilised..

Concept

Analyst

a

two-dimensional

BE

stress

analysis

package

that

features

real-time

functionality,

has

already

been

developed.

The

current

work

aims

to

extend

this

interactive,

real-time

stress

analysis

capability

into

the

three-dimensional

domain.

This

involves

the

development

of

innovative

techniques

to

generate,

update

and

analyse

the

mesh.

A

key

part

of

achieving

this

goal

is

the

creation

of

a

re-meshing

algorithm.

A

high

quality

initial

mesh

must

be

created

to

produce

an

accurate

ini-tial

analysis

using

the

minimum

number

of

elements.

The

mesh

should

further

be

capable

of

absorbing

some

of

the

distortion

introduced

as

the

user

updates

the

model.

A

concise

data

structure

is

also

required

to

aid

rapid

re-meshing..

Many

authors

have

proposed

algorithms

for

re-meshing

FE

and

BE

models,

often

in

an

adaptive

scheme.

Adaptive

refinement

schemes,

which

are

extensively

reviewed

for

BEs

by

Kita

and

Kamiya

inform

re-meshing

through

the

errors

in

an

initial

analysis.

Depending

on

the

scheme

selected

different

strategies

may

be

employed.

h-refinement

requires

subdivision

of

an

existing

mesh;

p-refinement

retains

the

existing

mesh

but

alters

the

order

of

the

element;

r-refinement

maintains

the

same

number

of

elements

but

requires

regeneration

of

the

entire

mesh.

These

schemes

may

be

used

in

combination,

but

do

not

usually

allow

for

geometrical

changes.

If

the

geometry

of

a

model

is

changing,

it

is

possible

to

refresh

only

affected

areas

of

the

mesh.

This

has

previously

been

applied

to

fluid

flow

problems

using

the

h-refinement

technique

with

the

FEM

However,

some

of

the

methods

employed

could

easily

be

adapted

for

BE

analysis..

It

is

important

to

minimise

the

number

of

elements

updated

during

re-meshing

(Trevelyan

et

al.

have

shown

this

to

be

the

major

factor

in

reducing

re-analysis

response

time,

as

illustrated

in

Figure

Reducing

the

number

of

updated

elements

gives

rise

to

a

reduction

in

both

the

time

to

re-integrate

and

re-assemble

the

linear

system

of

equations

generated

by

the

BEM

and

the

time

required

to

solve

these

equations

Michler

uses

techniques

based

on

radial

basis

functions

to

locally

distort

a

aircraft

mesh

based

on

geometric

changes.

This

approach

is

designed

for

complex

geometry

undergoing

significant

geometric

perturbation.

A

simpler

and

hence

faster

algorithm

has

been

implemented

for

the

basic

geometries

found

in

the

current

work.

However,

Michler's

approach

would

be

appropriate

should

more

complex

models

be

considered..

A

fast

linear

solver,

for

example

GMRES

can

be

employed

to

accelerate

the

re-analysis.

Such

iterative

methods

have

already

been

applied

to

the

BEM

and

have

produced

positive

results.

However,

they

do

not

achieve

the

speed

necessary

for

real-time

re-analysis.

As

the

majority

of

the

mesh

remains

unchanged

when

the

model

geometry

is

updated,

the

results

of

the

initial

solve

can

be

used

to

provide

both

a

suitable

initial

guess

at

the

solution

and

appropriate

preconditioning

of

the

evolving

system

matrix.

Other

linear

solvers

that

utilise

model

order

reduction

have

been

developed

by

Leu

Amsallem

and

Farhat

Ryckelynck

et

al.

and

Kerfriden

et

al.

During

dynamic

updating

of

stress

contours

on

continuously

changing

geometries,

e.g.

as

a

hole

is

dragged

from

one

location

to

another,

it

is

acceptable

to

relax

requirements

on

the

error

associated

with

each

individual

simulation.

Once

the

model

is

finalised

a

more

refined

mesh

can

be

used

to

generate

a

more

accurate

estimation

of

the

stress

distribution..

The

iterative

solvers

discussed

in

Section

were

originally

developed

for

application

in

the

FEM.

Here

they

have

been

applied

to

the

BEM,

which

typically

produces

small,

dense,

non-symmetric

matrices

in

contrast

to

the

large,

sparse

systems

found

in

the

FEM.

Re-analysis

performance

for

three-dimensional

applications

(Reproduced

from

This

paper

is

organised

as

follows.

In

Section

the

BEM

is

introduced.

Section

describes

the

initial

mesh,

defining

element

and

mesh

quality

measures.

In

Section

the

re-meshing

algorithm

is

outlined,

and

this

is

validated,

based

on

stress

results,

in

Section

In

Section

six

different

re-analysis

algorithms

are

discussed.

These

are

assessed

for

numerical

accuracy

and

speed

in

Section

Progress

has

been

made

towards

real-time

three-dimensional

BEM

analysis.

An

algorithm

has

been

introduced

for

updating

a

boundary

element

mesh

to

accommodate

a

geometric

perturbation

whilst

preserving

the

majority

of

the

mesh.

The

scheme

is

highly

efficient

for

small

perturbations;

methods

to

improve

the

scheme

for

larger

changes

have

also

been

discussed.

Through

careful

control

of

propagation

of

re-meshing

from

updated

geometry,

a

boundary

element

mesh

can

be

updated

in

a

computationally

inexpensive

manner

so

that

the

time

required

to

update

the

boundary

element

system

of

equations

can

be

reduced.

An

illustrative

example

has

shown

that

this

can

be

processed

whilst

maintaining

an

appropriate

quality

of

solution..

Several

linear

solvers

have

been

compared

for

solving

this

boundary

element

system

of

equations,

with

the

complete

approximate

LU

preconditioned

GMRES

method

proving

the

most

robust,

outperforming

other

iterative

and

model

order

reduction

based

techniques.

Using

this

method

the

speed

of

the

re-solve

can

be

improved

by

a

factor

of

when

compared

to

a

full

LU

decomposition.

A

GPU

implementation

of

the

GMRES,

BiCGSTAB

and

TFQMR

solvers

has

shown

little

to

no

speed

up

for

the

size

of

system

assessed

in

this

work.

However,

this

should

not

be

too

readily

dismissed

as

an

option

as

GPU

algorithms

and

hardware

characteristics

are

currently

developing

and

improving

rapidly.

Further

optimisation

work

could

lead

to

improved

performance..

Future

work

will

involve

further

reducing

the

time

required

for

the

computationally

expensive

process

of

re-population

of

the

BEM

system

matrix

terms

and

accelerating

the

solution

further

using

adaptive

cross

approximation

(ACA)

O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


Section level search functionality in Europe PMC Background: As the availability of open access full text research articles increases, so does the need for sophisticated search services that make the most of this new content. Here, we present a new feature available in Europe PMC that allows selected sections of full text articles to be searched, including figures and reference lists. Users can now search particular parts of an article, reducing noise and allowing fine-tuning of searches. Here, we presented a new search feature of Europe PMC that enables users to search articles by section type. This is based on a new rule-based section-tagging step prior to Lucene indexing. The section tagger identifies and categorises article section headers into pre-selected section types. The aim of this functionality is to help users fine-tune fulltext searches more usefully.. In the future, we plan to improve the system (perhaps by exploring machine learning approaches) so that sections that currently do not get categorised can be assigned more frequently. This would improve the tagger's recall performance and allow it to be applied to a wider set of articles. Furthermore, we would also like to explore the further development of the Europe PMC interface to make the use of section-limited searching more discoverable to the Europe PMC users, for example, by providing filters for figure legend searching in the context of the main search, or returning text only from the section targeted, rather than the complete article. Life science research articles are narrative accounts of research findings, usually describing methods, experimental results, and providing scientific context to the new work reported. Most typical research articles are structured into sections (segments), most often represented by a logical sequence, known as IMRAD -"Introduction", "Materials & Methods", "Results" and "Discussion" [1] . However, synonyms of these typical section titles are frequently used in articles, according to different journal styles. Furthermore, other types of sections are common, such as "Case Report" in clinical journals, or additional sections such as "Funding Sources". These sections provide useful context for the human reader's understanding of the findings described.. The availability of full text articles online provides the opportunity to develop deep search over the complete article, not just the abstract. While this extends the content available for searching, it can also unfortunately add significant noise in the results returned. For example, for searches that order results by publication date or citation count, the results at the top of the list can have little bearing on the original search term if that term is found only in the Reference list.. There are a few free-to-use services that provide biomedical literature search services on full-text documents, for example, PubMed Central (http://www.ncbi.nlm.nih. gov/pmc), Google Scholar (http://scholar.google.co.uk/), BioText Search Engine (http://biosearch.berkeley.edu) and Yale Image Finder (YIF) (http://krauthammerlab.med.yale. edu/imagefinder/). However, to the best of our knowledge, neither PubMed Central nor Google Scholar allows users to limit searches to, or exclude, particular sections of articles. BioText allows users to limit searches to figure captions and tables, and YIF only allows users to limit searches to figure captions. At Europe PMC (http://europepmc.org) [2] , we have implemented a comprehensive section-level search feature that is applied to incoming full text articles daily, and have exposed it to users both within the default search on the Europe PMC website, and within the Advanced Search form.

B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O B O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


Prediction of biodegradability from structure: Imidazoles A project for the development of Structure-Activity Relationship for Biodegradation is presented. The aim of the project is to assemble sets of structural rules governing the potential microbial degradability of (classes of) chemicals. These rules will provide tools to take into account the biodegradation aspects of a product-and all precursors in the production process-early in the product development. The modeling concept is to take all experimental biodegradation data available and combine structural trends in the data with mechanistical information from degradation pathways. The rules that are derived should give insight into the possibility of biodegradation for specific classes of chemicals, thereby revealing why a compound is biodegradable or not.For the class of imidazole derivatives such rules are derived, and a model degradation mechanism is proposed in analogy to the urocanate-hydratase mechanism from histidine metabolism. The model is validated using 12 imidazole-compounds, which are all predicted correctly to be poorly biodegradable. It is demonstrated that both data analysis and information on enzymatic reaction mechanisms are necessary to yield valid StructureBiodegradation Relationship. Biodegradability highly determines the persistence of chemicals in our environment. The ability of ambient microorganisms to utilize chemicals as nutrient sources secures the transformation of many man-made chemicals that enter the environment. If and how a chemical is biodegraded in the environment will often determine, for a large part, the overall environmental fate of a chemical. The potential of a chemical to be biodegraded also determines whether production process wastes can be treated in an industrial waste-water treatment plant, or have to be treated with other (often more cost-intensive) chemical waste processing methods. Testing the biodegradability of compounds however, is tedious and time-consuming, and negative results in a specific (standardized) test do not necessarily mean that a compound is not biodegradable. This makes it difficult (time-and cost-intensive) * to take the biodegradability of research candidates for new products into account at a very early stage of product development. Therefore, reliable prediction of the biodegradability in the environment of chemicals, based on their chemical structure, would be very useful in risk assessment and environmental fate analyses of existing chemicals. Even more convenient would these predictions be in the development of new chemicals and production processes, where models can give information about chemicals that have not even been synthesized yet.. A BASF project has therefore been initiated, to gather all available information on biodegradation behavior ofchemicals-test results as well as metabolism information-and to look for trends in the data for specific classes of chemicals. External partners are the Laboratory for Microbial Ecology from the University of Konstanz, and the Laboratory for Toxicology and Ecotoxicology from the University of Trier. It is not the aim of the project to develop general, statistical models with abroad applicability, which give a certain probability that a chemical will be biodegradable or not biodegradable in a specific test, since such models have already been the subject of much research in the past [1] [2] [3] [4] [5] . Such models do not fulfill the specific need for more fundamental understanding of biodegradability [1] [2] [3] , which is required in the selection and proposal of research candidates in the development of new products.. The aim of the project is therefore to develop mechanistically based (substructure) models for classes of chemicals which are thought to biodegrade via acommon degradation pathway or mechanism. As an example of our approach, one of these newly developed models is presented here, for the class of imidazole compounds. Only looking at the proposed degradation mechanism for imidazole derivatives (Figs 2 and 3) , it is not obvious that l-N-substituted imidazoles will be hindered in their degradation via a urocanase-like metabolism. Similarly it is not obvious from the data-analysis that all C-substituents on the imidazole ring that have an electron withdrawing effect through resonance or induction will deactivate the imidazole ring towards NAD+ attack, thus making biodegradation more difficult.. 2-Phenyl-imidazole is poorly biodegradable compound, whereas the imidazole-ring substituent is not considered to be electron-withdrawing. This seems to be contradicting the above formulated rules. Preliminary results of quantum-chemical calculations performed on this set of imidazole (results not shown) indicate that the 2-phenyl-substituent to the imidazole ring is not overall electron-withdrawing, but that this substituent has a very distinguished local electron-withdrawing effect on the 4-and 5-imidazole ring position, exactly those positions which would be prone to a electrophilic attack by urocanase bound NAD+.. Apparently, N-substitution of the imidazole ring can block the urocanase mechanism completely. From the preliminary results of the quantum-chemical calculations, it is concluded that the N-substitution does not decrease the biodegradability of the imidazole ring by making the ring less susceptible to electrophilic attack. Possibly imidazole N-substitution hinders the degradation mechanism by disabling the electronic rearrangements in the imidazole ring in the reaction steps after the nucleophilic attack of the urocanase bound NAD+ (see Fig. 3, steps 3 and 4) .. For the class of imidazoles it is shown that it is necessary to use both data-analysis (statistical and/or manual methods) and interpret information from catabolic mechanisms, to come up with meaningful structural rules for biodegradation, which have general validity and thus predictive value.

O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


An Access Delay Model for IEEE 802.11e EDCA Abstract-We analyze the MAC access delay of the IEEE 802.11e enhanced distributed channel access (EDCA) mechanism under saturation. We develop a detailed analytical model to evaluate the influence of all EDCA differentiation parameters, namely AIFS, CWmin, CWmax, and TXOP limit, as well as the backoff multiplier . Explicit expressions for the mean, standard deviation, and generating function of the access delay distribution are derived. By applying numerical inversion on the generating function, we are able to efficiently compute values of the distribution. Comparison with simulation confirms the accuracy of our analytical model over a wide range of operating conditions. We derive simple asymptotics and approximations for the mean and standard deviation of the access delay, which reveal the salient model parameters for performance under different differentiation mechanisms. We also use the model to numerically study the differentiation performance and find that differentiation, though rejected during the standardization process, is an effective differentiation mechanism that has some advantages over the other mechanisms. A quality-of-service (QoS) extension to the original IEEE 802.11 wireless local area network standard [1] , known as IEEE 802.11e [2] , defines a contention-based medium access control (MAC) scheme called enhanced distributed channel access (EDCA). EDCA provides service differentiation by separating flows into different access classes. The differentiation achieved by EDCA is relatively easy to understand in a qualitative sense; however, quantifying the degree of differentiation provided is difficult due to the distributed, contention-based nature of EDCA. Hence, there is a need for accurate performance models to guide the configuration of parameters. In this paper, we develop a detailed analytical model of the packet access delay in a network of 802.11e EDCA stations operating under saturation. In this context, access delay is the time interval between the instant a packet reaches the head of the transmission queue, and the time when the packet is successfully received at the destination station.. Service differentiation in EDCA is effected through four parameterized access categories (ACs). Packets belonging to different ACs are given different access priorities by appropriate tuning of four AC-specific parameters. The parameters define, respectively, the size of AC-dependent guard periods (arbitrary interframe spacing or AIFS), minimum and maximum contention windows (CWmin and CWmax), and lengths of packet bursts or transmission opportunity limit (TXOP limit). A fifth parameter representing the backoff window multiplier, which we denote by , was studied during the standardization process, but was eventually abandoned due to doubts about effectiveness [3] and replaced with a fixed multiplier of 2. In this paper, we substantially extend a model [4] that we developed previously for access delay in the distributed coordination function (DCF) of the original IEEE 802.11 MAC, to EDCA. Our model 1 can scale to an arbitrary number of ACs and accounts for all four standardized differentiation parameters. We also make our model general enough to cover differentiation, so that we can study the characteristics of this mechanism.. Many recent papers have proposed analytical models for various subsets of EDCA functionality [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] . Xiao [7] models CWmin and CWmax differentiation, the authors of [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , and [16] model CWmin, CWmax, and AIFS differentiation, and Peng et al. [17] develop a simple model for TXOP differentiation only. Compared to previous models, our model is novel for the following reasons: 1) it correctly accounts for all four differentiation parameters in the standard, 2) it yields the standard deviation and distributional values of the access delay, as well as the commonly obtained mean access delay, and 3) it provides accurate estimates of these metrics. Ge at al. [18] attempt to explicitly account for all differentiation parameters in their model, but they actually analyze and simulate a p-persistent version of EDCA, which does not have the same characteristics as EDCA. In [12] , it is stated that a four-parameter model can be built by simply inflating the packet length in their threeparameter model to account for TXOP differentiation. However, as we will show in our model development, an accurate model of TXOP differentiation is a nontrivial extension that requires careful consideration of all possible combinations of transmission and collision durations of the different ACs, together with their probabilities of occurrence.. Our analytical model is fully integrated and can capture joint differentiation by up to four parameters (or five including ). However, for ease of understanding, we present the model as three submodels: a collision probability model that estimates the collision probabilities of the different classes, a delay model that accounts for all events that contribute to the access delay, and a TXOP model that accounts for TXOP differentiation. The collision probability and delay models capture the influence of the CWmin, CWmax, and AIFS mechanisms. By virtue of the way in which the TXOP mechanism operates, it becomes natural to treat it as a modeling extension.. A collision probability model is a vital element of any EDCA analysis. All the aforementioned studies use extensions of Bianchi's 2D Markov chain analysis of DCF [19] to derive the collision probabilities. To incorporate AIFS differentiation, the authors of [8] and [9] resort to 3D Markov chains, while Tsai and Wu [10] use a 4D Markov chain. In contrast, the authors of [14] and [15] develop less complex models based on separate 2D and 1D Markov chains. Our collision probability model is based on that of [14] , but uses an average value analysis in place of the 2D Markov chain. This leads to a more intuitive and simple, yet accurate collision probability model.. Our delay and TXOP models are novel and yield detailed statistics of the access delay. Most prior studies of EDCA analyze only throughput and/or mean delay. Exceptions are [9] , where the delay distribution is calculated based on the transient analysis of a Markov chain; [16] , where the delay distribution is approximated by estimating the probabilities of alternate delay outcomes; and [13] , where points of the distribution are obtained by inverting the generating function of the delay distribution. We present a more direct and accurate method to obtain the distribution. Similar to [13] , we derive the generating function of the access delay distribution and obtain distributional values via numerical transform inversion. However, our generating function is more accurate than that of [13] , as we illustrate through a numerical comparison. Further, we obtain explicit expressions for the mean and standard deviation of the access delay. Our moment expressions are derived via direct probabilistic arguments, in contrast to [13] , where differentiation and limit taking of the generating function is advocated. The direct approach is easier because the generating function in question is complicated, making differentiation tedious. Perhaps as a concession to this complexity, Engelstad and Østerbø [13] go no further than state the standard deviation in terms of derivatives of the generating function. As far as we are aware, ours is the first work to obtain an explicit expression for the standard deviation of the delay (or jitter) in EDCA. The expression enables us to develop analytical insights into the relative importance of parameters and to quantify the jitter performance of the differentiation mechanisms.. We confirm that our analytical results for the mean, standard deviation, and distribution of the access delay are accurate through comparison with ns-2 simulation. Typically, our analytical tail distribution is an excellent match with simulation down to 10 À3 , and often beyond. In addition to developing a model, we exploit the model to advance the understanding of EDCA delay performance. We use the model to derive asymptotics for the mean under the assumptions of unlimited retransmissions and the number of stations tending to infinity, and to derive approximations for both the mean and standard deviation under the assumptions of a finite retransmission limit and a large number of stations. The asymptotics and approximations reveal the salient model parameters for performance under each differentiation mechanism, and provide simpler alternatives to the complete analytical expressions for system analysis and design. Our approximation methodology and results are new. Our asymptotic work is inspired by that of Ramaiyan et al. [20] , who obtained asymptotics for throughput ratios under CWmin, AIFS, and differentiation. There are some parallels between their asymptotic throughput ratios and our asymptotic mean delay ratios (since under infinite retransmissions, the mean access delay has a simple relationship with the throughput). Unlike [20] , we derive asymptotic results for the individual ACs as well as the ratios, and a result for TXOP differentiation.. Finally, we perform a detailed numerical study using the analytical model to quantify the differentiation in the mean and standard deviation afforded by CWmin, AIFS, TXOP limit, and . We find that differentiation, though discarded during the standardization process, is an effective differentiation mechanism that has some advantages over the other mechanisms.. The rest of this paper is organized as follows: In Section 2, we present our analytical model, starting with the collision probability model. Next, we describe our access delay model that accounts for the CWmin, CWmax, AIFS, and mechanisms, and derive expressions for the associated moments and generating function. At the end of this section, we present our TXOP model, and derive the moments and generating function when all five differentiation parameters are included. In Section 3, we present asymptotics and approximations. Validation of the analytical model with ns-2 simulation is carried out in Section 4, and then we use the model to assess the nature of the service separation provided by each differentiation mechanism, and to test the accuracy of the approximations. Finally, we state our conclusions in Section 5. Some details not provided in this paper, such as further explanations of derivations and additional numerical results, can be found in the technical report [21] . In this paper, we have developed an accurate and versatile model for the MAC access delay in an IEEE 802.11e EDCA network under saturation. Using the model, we derive asymptotics and approximations for the mean and standard deviation of the access delay. The resultant expressions yield insights into the relative importance of different model parameters. Further simplification is achieved by forming the mean and standard deviation ratios; in particular, for CWmin differentiation, both the mean and standard deviation ratios can be approximated by the ratio of the minimum contention windows, while for TXOP differentiation, the mean and standard deviation ratios can be approximated by the inverse of the ratio of the burst sizes and its square root, respectively. We also use the model to study the effectiveness of CWmin, AIFS, TXOP, and differentiation. We find that the AIFS mechanism gives protection to higher priority traffic under congestion.. On the other hand, the CWmin and TXOP mechanisms give differentiation that is largely insensitive to the load which leads to fairly predictable behavior. Differentiation based on has the desirable property of preserving priority in the delay dispersion relative to the mean.

O O O O O B I B O O O O O O O O B I O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O B B O B I O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O


Summary of Product Characteristics content extraction for a safe drugs usage The use of medications has a central role in health care provision, yet on occasion, it may injure the person taking them as result of adverse drug events. A correct drug choice must be modulated to acknowledge both patients' status and drug-specific information. However, this information is locked in free-text and, as such, cannot be actively accessed and elaborated by computerized applications. The goal of this work lies in extracting content (active ingredient, interaction effects, etc.) from the Summary of Product Characteristics, focusing mainly on drug-related interactions, following a machine learning based approach. We compare two state of the art classifiers: conditional random fields with support vector machines. To this end, we introduce a corpus of 100 interaction sections, hand annotated with 13 labels that have been derived from a previously developed conceptual model. The results of our empirical analysis demonstrate that the two models perform well. They exhibit similar overall performance, with an overall accuracy of about 91%. Adverse drug events (ADEs) have been defined as injuries resulting from medical intervention related to a drug [1] that endanger patient's safety and account for increased heath care costs. Examples include injuries (e.g., rash, confusion, or loss of function) caused by incorrect dosage as well as allergic reactions occurring in a patient not known to be allergic to a given medication and so forth. Many of these injuries suffered by patients are inevitable but at least a quarter may be secondary to medication errors [2] , as errors in medication-management process are generally called [3] . These damages are not unavoidable and can be prevented. According to one estimate, medication errors occur most frequently at the prescribing and administration stages [2] . The rate of medication errors and preventable ADEs represents a serious cause for concern. The Institute of Medicine (IOM) committee, in its report Preventing Medication Error, estimates that more than 1.5 million ADEs are preventable each year in the US alone [2] . This report outlines the main priorities for research on safe medication use that will address this problem. It proposes electronic prescribing, by computerized provider order entry (CPOE) systems, as one of the most highly effective error prevention strategies.. CPOE systems are computer applications that allow direct, electronic entry of orders for medications, laboratory, radiology, referral, and procedures [4] . Several systematic reviews have shown the benefits of CPOE systems [5] [6] [7] [8] [9] [10] resulting from their ability to detect unsafe and potentially fatal medication orders. Computerization in fact enables the delivery of clinical decision support [11] , alerts to guide ordering, allowing for checks for allergies, drug-drug interactions, clinical conditions. One of the factors, which mainly influences the overall performance of such a system, is the quality and validity of the knowledge base underlying the system. Safe medication use requires that providers and consumers synthesize several types of information, including knowledge of the medication itself, as well as understanding of how it may interact with coexisting illnesses and medications, and how its use might be monitored. This information is constantly changing, and while most of the necessary updated knowledge is available somewhere, it is not always readily accessible, creating a situation in which it is almost impossible for health care providers to have current knowledge of every medication they prescribe.. In this work, we consider the problem of automatic extraction of drug information conveyed in the Summary of Product Characteristics (SPC), focusing on a specific section concerned with drug-related interactions. Our contributions are as follows:. 1. We formulate the problem in a machine learning framework, in which we seek to assign the correct semantic label, such as InteractionEffect or ActiveDrugIngredient, to each word, or segment of sentence, of the text. We employ two state of the art classifiers: linear-chain conditional random fields (CRFs) and structural support vector machines (SVMs). These classifiers discriminate between semantically interesting and uninteresting content through the automatic adaptation of hundreds of engineered text characteristics, taking into account the properties of a document, on both a local (word) and global (sentence) level.. 2. We introduce a corpus of 100 interactions sections in Italian language that have been annotated with 13 distinct semantic labels, with respect to a previously implemented ontology. 3. We apply the CRFs and the SVMs to our data set and evaluate their overall and individual label results. Both the classifiers achieve a micro-averaged F 1 -measure (see Section 4.2) greater than 90%, which is promising for real-world applications.. In a next step, the extracted information will be used to populate the ontology, in order to carry out automated reasoning on data. This reasoning process could help, for example, to determine whether it is possible for a particular drug to have any interaction with a particular active ingredient or diagnostic test, to find the effect of a particular interaction and so on. Moreover, ontology population can compensate for the possible lack of completeness and/ or congruence among different SPCs. Like this, such knowledge model can be made available to specific prescription applications, such as CPOE, for integrating the underlying base of knowledge, thus improving the prescription process. We have shown that is possible to perform the task of information extraction from SPCs using supervised machine learning techniques. Although we have focused on drug interactions, the encouraging results and the adaptability of the approach we adopted means that our system has general significance for the extraction of detailed information about drugs (drug targets, contraindications, side effects, etc.). Several studies have addressed the issue of IE in medication domain. Some approaches concentrated their analysis on the extraction of drug names. Levin et al. [20] implemented a system based on lexicon (RxNorm) and regular expressions (Hints List) to extract and normalize drug names from an anesthesia electronic health record, into a standardized terminology. RxNorm and Hints List concepts were used in the mapping module as references for drug names, and medical abbreviations and jargon, respectively. In another study, Sirohi and Peissig [21] performed a dictionary-based NLP study to determine the effects of using varying lexicon to extract drug names from electronic medical records. These authors have shown how the accuracy of results can be enhanced by refining the drug lexicon.. Other studies focus on extracting more specific drug features, such as drug names and dosage. In one example, Evans et al. [22] reported a method of extracting drug and dosage data from a collection of discharge summaries. They first draw a conceptual model of drug-dosage information and then identified this information using a semantically driven extraction module. This module combines readily available NLP facilities from the Clarit system with newly created resources, including a set of pattern rules and a lexicon. A study by Shah and Martinez [23] derived numerical information about daily dosage from unstructured dosage instructions from a patient records database, using a dictionary to standardize words and phrases. Then, they converted the extracted information into structured fields.. Lately, more studies have been geared toward the extraction of a more complete set of drug characteristics. In particular, Gold et al. [24] built Merki, a parser that can extract drug names and other relevant information from discharge summaries using a lexicon and a set of parsing rules. Evaluation showed that the system identified drug names, but other information such as dose and frequency had lower precisions. Similarly, Xu et al. [25] implemented a NLP system, MedEx, which extracts medication information from clinical notes. Relying on a more detailed medication representation model, they integrated a semantic tagger and Chart parser to capture drug names and signature information from clinical narratives and then to map it onto structured representation.. The Third i2b2 NLP Challenge [26] focused on the extraction of medication information, in particular medication names, dosages, routes of administration, frequencies, durations, and reasons for administration, from discharge summaries. Different approaches have been proposed to address this task: rule-based, machine learning, and hybrid systems. Among others, Doan et al. [27] integrated different existing NLP components that included a sentence boundary detection program, a section identification program (SecTag), the MedEx system for tagging medication fields, and finally a context-free grammar for converting the text into a structured format. Tikk and Solt [28] proposed an approach in three steps: NER, context filtering, and relation extraction. While the last two components are rule-based, for NER, they investigated first a rule-based and second a CRFs-based method, which, with enough large training data, showed considerably better performance. Meystre et al. [29] employed a hybrid system, between machine learning and rule-based, called Textractor.. On the whole, current works focus on clinical text narrative. However, Pereira et al. [30] considered another source of information on medications, namely SPCs, and thus addressed the problem of automatic indexing. The authors developed a method to automatically generate a dictionary for use with a French Multi-Terminology Indexing tool.. Only a few published papers address the issue of extracting drug interactions information from narrative text. Segura-Bedmar et al. [31] employed a kernel-based approach that uses SVMs aiming at detecting drug-drug interactions. A more detailed analysis of such work and a comparison with our own are presented in Section 5. SPCs represent a vast source of information for health professionals on how to use medicines safely and effectively. It forms an intrinsic and integral part of marketing authorization. In order to obtain an authorization to place a medicinal product on the market, a SPC shall be included in the application made to the competent authority. A SPC lays out the agreed position (results of physico-chemical, biological or microbiological tests, toxicological and pharmacological tests, clinical trials, etc.) on the medicinal product as collected during the course of the assessment process. Its content is regulated by Article 11 of Directive 2001/83/EC. Accordingly, SPCs of specialty medicines for human use are organized into 12 sections: name, therapeutic categories, active ingredient, excipients, indications, contraindication/side effects, undesired effects, posology, storage precautions, warnings, interactions, and use in case of pregnancy and nursing.. All this information is locked in free-text, the most convenient and natural way to convey medical knowledge for human communication [12] . This narrative form, however, cannot be actively used by health information systems. Reliable access to this comprehensive information, by Natural Language Processing (NLP) systems, can provide a wide range of coded data [12, 13] . Such data will then be available for new or enriched clinical applications, thus facilitating and improving the prescription process. It is therefore an important aspect for improving quality of care and preventing medication errors.. Among NLP techniques, information extraction (IE) methods have been largely employed in the biomedical domain to extract facts from free-text [14] [15] [16] [17] [18] and to make them available for subsequent tasks such as case finding, summarization, decision support, or statistical analysis.. In this work, we therefore propose to extract drug-related interaction information reported in SPC, following a named entity recognition (NER) approach. NER is an important step in an integral IE task and aims at identifying words or phrases in natural language text belonging to certain classes of interest (i.e., Named Entities), such as diseases or drugs, and labeling them with their appropriate type [19] . In NER, an attempt will be made to associate each token with a label that indicates its appropriate domainspecific category. Approaches to NER span a broad range, from rule-based systems to machine learning. Rule-based systems make decisions on sets of hand-written disambiguation rules that play an important role in discovering a named entity, which specify, for example, that an ambiguous word belongs to a particular named entity rather than to another one if it follows another specific named entity.. On the other hand, a typical application of machine learning works to classify a novel instance x as belonging to a particular class y. In the field of label sequence problems such techniques aim at identifying the most likely sequence of labels for the words in any given sentences. These methods generally resolve tagging ambiguities by using training corpus to compute the probability of a given word having a given tag in a given context. Then, they automatically tune their own parameters to maximize their performance on the training corpus. The machine then generalizes from these samples.. Rule-based NER systems can be very effective but require some manual effort. Machine learning approaches can successfully extract named entities but require large annotated training data. Advantages of machine learning approaches are that they do not require human intuition, they are general and clearly separate the algorithm from the data, so that it is easier to apply them to any domain by simply retraining without reprogramming. As we have already stated, we developed a framework for simultaneously recognizing occurrences of multiple entity classes using linear-chain CRFs and structured SVMs. Both of these two supervised machine learning approaches predict words' labels by using a large number of interdependent descriptive characteristics (features) of the input by assigning real-valued weight to these features.. Presented here is an outline of our framework. We propose an approach in five steps. We began by defining a semantic representation model of drug information conveyed in the SPCs, in order to find out the concept to be extracted. In a second step, a preprocessing pass was required for preparing the dataset for the use by the extraction module. Then, we annotated the text by hand, with respect to the previously developed conceptual model. Subsequently, we defined a set of binary features that express some descriptive characteristics of the data, for instance ''current token is capitalized''. Finally, we processed the data through the two discriminative models (CRFs and SVMs): both the algorithms iterate the tokens in the sentence, and label proper tokens with semantic labels, by learning the correspondence between labels and features. We randomly split the 100 interaction sections into two sets, one for training containing 60 sections and one for testing 40 sections. This amounts to a total of 796 input sentences for training and 457 input sentences for testing. We used cross-validation on the training sets to determine reasonable parameter settings of our models. For the linear SVMs, we found the regularization parameter k = 1 to work well. All SVMs results in this paper have been produced using 10 passes through the entire training set. For the variance of the Gaussian regularizer of the CRFs [42] , we used the value 10.

B I I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I I O O O O O O O O O O O O O O O O O O O B I I O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O