A universal method of information retrieval evaluation: the missing link M and the universal IR surface The paper shows that the present evaluation methods in information retrieval (basically recall R and precision P and in some cases fallout F) lack universal comparability in the sense that their values depend on the generality of the IR problem. A solution is given by using all "parts" of the database, including the non-relevant documents and also the notretrieved documents. It turns out that the solution is given by introducing the measure M being the fraction of the not-retrieved documents that are relevant (hence the "miss" measure). We prove that -independent of the IR problem or of the IR action -the quadruple (P,R,F,M) belongs to a universal IR surface, being the same for & l IR-activities.This universality is then exploited by defining a new measure for evaluation in IR allowing for unbiased comparisons of all IR results. We also show that only using 1, 2 or even 3 measures from the set {P,R,F,M} necessary leads to evaluation measures that are nonuniversal and hence not capable of comparing different IR situations. Quantitative evaluation in information retrieval is performed -very classically -by means of the measures precision (P) and recall (R), defined as follows. Let Q denote the database (universe) in which an IR search (based on a given problem) is executed. As usual we suppose that we can determine in a unique, dichotomous way whether a document is relevant for the problem (transformed into a query according to the IR system's rules) or not. Let us denote by re1 the set of relevant documents and by ret the set of retrieved documents. Then we have the following definitions :. where I . I denotes the cardinality of the set, i.e. the number of documents in it. Denote briefly iret=Q\ret and -rel=Q\rel, the set of not-retrieved documents and the set of nonrelevant documents respectively. Sometimes (see below for references) also the following measure is considered, called fallout (F) :. The following formula is easily derived from (I), (2) and (3) and appears e.g. in Salton and Mc Gill (1987) (p. 175) and Van Rijsbergen (1979) ( p. 149) where G denotes the "generality" of the problem : the fraction of relevant documents (describing indeed the degree of generality of the problem).. A simple, but important remark of S. Dominich (see Dominich (2001) ), which is not more than a reformulation of (4), was the starting point for the results of the present paper. It goes as follows : from (4) and (5) it is easy to see that Formula (6) is interpreted in Dominich (2001) , p. 226-227 as the effectiveness surface of IR, corresponding to a given problem or query q. He rightly points out that the shape of this surface is the same for every IR system. Keeping the problem fixed (hence fixed G), different IR techniques (e.g. relevance feedback but this is only an example) can give different values of P, R and F but they are constraint to the surface (6).. The starting observation of this paper is that, as long as we are on the same effectiveness surface, we can perfectly compare, say, two sets of IR results : (PI, R,, F,) and (P,, R,, F,) . In other words, within the limitation of a given G (a given problem) we can compare the above triplets. Rephrased in a "negative" way, comparing two triplets as above is not possible if G varies, e.g. for different problems, since we are on different effectiveness surfaces.. Based on the above observations we can, formally, define the concepts of "surface", "semiuniversal surface" and "universal surface" as follows. The concept of surface (in kdimensional space Itk, here k=4) is well-known and is described by an equation of the form where f is a real valued function on 3-dimensional space JR3 and C is a constant w.r.t. x,y and z. Surface (7) will be called semi-universal for IR if this constant depends on G (as in (5)) or on (its dual interpretation, see e.g. Egghe and Rousseau (1997) ) the fraction of retrieved documents (describing the degree of generality of the retrieval result). This means that, as in (6), any triplet (x,y,z), given G (or G') fixed, belongs to this surface and, hence, any two such triplets can be compared (on this surface). If this constant is independent of G & G', hence if C is a universal constant (independent on the IR problem or IR system) we say that (7) is a universal surface for IR.. In this paper we want to discuss the following question :. : Can one construct a surface such that an^ two IR results (independent of a problem or of the IR system) remain on this surface? In short, can one construct a universal surface for IR?. We firstly note that the measures P, R and F only use the sets ret, rel, ire1 and also in G only re1 is appearing. Hence i r e t , the set of not-retrieved documents is not taken into account. Already for purely principal or formal reasons, this is not acceptable. The dichotomous situation relllrel versus retllret gives rise to a 2x2 contingency table, hence 4 cells from which only 3 are used in the above measures. Using all 4 cells is similar to the approach in Heaps (1978) where, for the determination of the entropy of a retrieval system, one also uses the information (entropy) coming from all 4 cells as mentioned above.. Another (principal) reason why also i r e t should be used (if one also uses irel) is the duality principle in IR as explained in Egghe and Rousseau (1997) , namely the duality between documents and queries, between indexing and search formulation, between re1 and ret. In the vector space model (see e.g. Salton and Mc Gill (1987) ) there is even equality between documents and queries (namely a vector with a certain fixed number of coordinates).. These remarks and the fact that the effectiveness surface (6) has the constant Gl(1-G), which is only referring to the problem (to re1 and not to ret) shows that this theory should be completed. This will be done in the next section, where the "missing" measure M (miss) will be (re-)introduced and where its properties are proved. "Re-introduced" refers to the fact that in LISA as well as in ISA no English language publication defines this measure and that the "origin" of the use of this measure in a Danish, French and two Russian articles (all of them more than 25 years ago) is not traceable. We will find 3 new efficiency surfaces, hence 4 together with (6). All of these surfaces are not completely universal : two of them (as (6)) depend on the problem (on rel) and the other two depend on the IR action (on ret) so that only IR results can be compared if 1 re1 1 is constant (first two surfaces) or if / ret I is fixed (the other two surfaces).. We however deduct from these ("semi-universal") surfaces a totally universal surface, where the four measures P, R, F and M are involved (and nothing else). In other words, an^ two IR results (no matter what re1 or ret is) are on this surface and hence can be compared. We will show that this surface has the equation and we call it the universal IR surface. This finishes the next section.. The third section studies properties of this surface exploiting the universality of it by defining a uniform distance between any search result (P, R, F, M) and the vector (in IR4). representing the perfect search : (1, 1, 0, 0). Properties of this distance are given and the paper closes with some examples and an open problem.

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


Multiple Views Analysis Of Software Designs Designs are expressed in terms of structure, behavior, objects, modules, and functions which, once consolidated, become design blueprints. This paper describes a formal framework for expressing, analyzing, and comparing multiple views of designs. The analysis of multiple designs or views using di erent design notations is proposed as a strategy to enhance design quality by providing a systematic identi cation of design defects and discrepancies. Views are formalized, analyzed independently, and then compared to each other. The type of design discrepancies identi ed are omission of information, incompatible information, and inconsistencies between views. In the process of modeling a system, the software designer generates a set of designs each of which captures what may be deemed pertinent features of the system ( Figure 1 ). This simple approach to generating several perspective-based blueprints or multiple views to provide a multi{angled understanding of a problem has been employed routinely and successfully in other engineering elds. For example, architects and civil engineers develop various plans each representing a view (e.g., dead-load distribution, electrical wiring layout, air conditioning layout, etc.) that emphasizes some particular aspects. Thus, a view can be thought of as a model describing a subset of the relevant attributes of the system.. The focus of this research is to establish a formal framework for expressing, comparing, and analyzing multiple views of designs in order to derive complementary and contradictory information. The views are expressed in two di erent design notations 1]. Speci cally, we consider a functional view captured by a Data Flow Diagram (DFD) notation, and a functional/structural view captured by a Structure Tulane University EECS Department, New Orleans, LA 70118 1 Chart (SC) notation. An essential part of our work was dedicated to the de nition of a formalism in which the views and notations were formalized and analyzed. Second, the development of a systematic and formal approach to provide multiple views analysis support at the design phase was elaborated. While multiple views analysis is a subject of active research, our approach is novel and unique in integrating the following two aspects: (1) its emphasis on design methods; and (2) its use of well-established formal foundations.. The paper is organized as follows. Section 2 is an overview of the state of the art regarding the use, manipulation, integration and analysis of multiple views. In section 2, , a formal representation of graphical designs is described. In section 4, our approach to multiple views analysis is introduced and explained. In section 5, the analysis process is described. In section 6, an example to illustrate our approach is covered. Section 7 concludes the paper. During design formulation, designs are subjected to an evaluation and veri cation process, the goal of which is the detection of design errors. The analysis of di erent designs or \views" using di erent design notations has been proposed to achieve this goal. The formal support for the use of multiple views at the design stage with the purpose to detect design discrepancies was provided by formalizing the notation and the analysis process. Speci cally in this work, a Data Flow Design and a Structure Chart Design capture a speci c view of a system. Each view is formalized, independently analyzed, that is, each formalized view is checked for validity. The multiple view analysis, relying on the abstract interpretation framework, compares two abstract views, and identi es discrepancies between them. The type of design discrepancies identi ed were omission of information, missing information, and inconsistencies between views. E cient use of information captured by multiple views represent a key issue in small scale design improvement process. Alternatively, the support that the proposed framework could provide in large complex systems design development might be considered (i.e. support of multiple \views" in software architecture). The use of Multiple Views in software development is not a new technique. For instance, datagrams and actigrams in SADT de ne a multiple views design 2]. Recently, research in multiple views has focused on making the approach explicit by addressing issues related to notations, analysis, tools integration, and bene ts. Multiple views have been used in requirements elicitation 3], domain modeling, requirements de nition and speci cation 4], program development systems 5], and software design reuse 6].. The viewpoint resolution technique is used to validate requirements 3]. A language is used to express di erent viewpoints, and a set of analogy heuristics is devised to analyze them syntactically. The heuristics help detect missing information and con icting information. Also, a classi cation (hierarchies) among several viewpoints is provided. The analysis process, and the manipulation and representation of knowledge are supported with automated tools 7]. Domain modeling with hierarchies of alternative viewpoints bases its modeling strategy on developming a hierarchy of con icting viewpoints representations 7] . As the elicitation process proceeds, hierarchies among the views are generated. Lower levels of a hierarchy contain con icting and uncertain viewpoints. Viewpoint creation and manipulation is provided by an automated analyzer. The viewpoint framework addresses the problem of multiple perspectives, which includes factors such as the development of composite systems, an environment with many participants, several representation schemes, diverse domain knowledge, and di ering development strategies 4]. The viewpoint framework provides a basis for dealing with the structure, organization and management of di erent perspectives, consistency among perspectives, and concurrent collaboration among participants. The representation and integration of multiple views using a canonical graph representation (semantic program graphs) is proposed in 8]. This is in essence a new intermediate design notation that acts as a common notation to express other notations.

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


Optimizing data intensive GPGPU computations for DNA sequence alignment MUMmerGPU uses highly-parallel commodity graphics processing units (GPU) to accelerate the data-intensive computation of aligning next generation DNA sequence data to a reference sequence for use in diverse applications such as disease genotyping and personal genomics. MUMmerGPU 2.0 features a new stackless depth-first-search print kernel and is 13Â faster than the serial CPU version of the alignment code and nearly 4Â faster in total computation time than MUMmerGPU 1.0. We exhaustively examined 128 GPU data layout configurations to improve register footprint and running time and conclude higher occupancy has greater impact than reduced latency. MUMmerGPU is available open-source at http://www.mummergpu.sourceforge.net. Graphics Processing Units (GPUs) were originally designed for efficient data-parallel graphics computations, such as in scene rasterization or lighting effects. However, as GPUs have become more powerful with dozens or hundreds of stream processors, researchers have begun using them for general-purpose (GPGPU) computations. Early attempts to exploit GPU's high level of parallelism for non-graphical tasks required application developers first re-cast their problem into graphics primitives, and re-interpret graphical results. However, recent toolkits from both nVidia [1] and ATI [2] have enabled developers to write functions called kernels in a restricted variant of C that execute in parallel on the stream processors. High-level toolkits coupled with powerful, low cost hardware have sparked huge interest in developing GPGPU versions of data-parallel applications.. Read mapping is a data-parallel computation essential to genome re-sequencing, a rapidly growing area of research. In this computation, millions of short DNA sequences, called reads, obtained from a donor are individually aligned to a reference genome to find all locations where each read occurs in the reference sequence, with allowance for slight mismatches for biological and technical reasons. Read mapping can be used, for example, to catalog differences in one person's genome relative to the reference human genome, or compare the genomes of model organisms such as Drosophila melanogaster (fruit fly) or Arabidopsis thaliana (thale cress). Researchers use this information for a wide variety of analyses, since even a single nucleotide difference can have a dramatic effect on health and disease. Next-generation DNA sequencing technologies from Illumina, 454 Life Sciences, and Applied Biosystems have recently become extremely popular because they can create billions of bases of sequence data in a single sequencing run at relatively low cost [3] . The DNA of James Watson, a co-discoverer of the molecule's structure, was recently sequenced using technology from 454 Life Sciences in just two months. Biotechnology researchers believe that within the next several years, an individual will be able to have his or her DNA sequenced in only a few days and for as little as $1000 [4] . Despite their popularity, the most widely used sequence alignment programs are unable to handle the extreme workload required by the new technology. The MUMmerGPU system uses the highly parallel graphics cards from nVidia and their CUDA GPGPU toolkit to process next generation sequencing reads in a fraction of the time of other programs [5] .. MUMmerGPU 2.0 uses the same suffix tree based match kernel as described in the original version of MUMmerGPU, but we have added several significant improvements to increase performance and capabilities for the overall application. First, we implemented a new query streaming model in which reads are streamed past overlapping segments of the reference, allowing us to compute alignments to Mammalian-sized reference genomes. Second, we implemented a new GPU-based print-kernel that post-processes the tree coordinates from the match kernel into exact alignment coordinates suitable for printing. This computation had previously been the limiting factor in end-to-end application time for commonly used parameters. The print kernel performs the computation via an iterative depth-first-search on the suffix tree using a constant amount of memory and no stack. This non-traditional implementation is required to meet the severe restrictions on kernel code, but is between 1.5-and 4-fold faster than the previous (CPU-based) version of the routine. Popov et al recently reported a different algorithm for traversing trees in a CUDA kernel [6] which requires additional pointers between the leaf nodes in a kd-tree, but our technique is applicable to any tree without additional pointers. Finally, we optimized performance for both kernels by identifying the best organization of the DNA sequencing reads and suffix tree in GPU memory. We explore and report on 128 variations of the data layout policy, and quantify the tradeoffs involved for kernel complexity, cache use, and data placement. We find that optimizing these choices can greatly accelerate performance, and mistuned choices have an equal but negative effect on performance compared to the naï ve version. Processor occupancy dominated performance for our data-intensive application, but techniques that reduce GPU memory latency without compromising occupancy were also generally beneficial. We describe several techniques to reduce kernel register footprint and thus improve occupancy that are widely applicable to GPGPU programs. Overall, MUMmerGPU 2.0 is nearly 4Â faster in total computation time than the originally published version of the code for the most commonly encountered workloads. MUMmerGPU 2.0 is a significant advance over MUMmerGPU 1.0, featuring improved functionality and higher performance over previous versions of the code. With the new query streaming data model, MUMmerGPU 2.0 can map reads to genomes as large or larger than the human genome. The new GPU-based print kernel post-processes the suffix tree matches into full MEMs, and provides a major performance boost, between 1.5Â and 4Â, over the serial CPU version in MUMmerGPU 1.0. This kernel required a non-traditional stackless implementation of a depth-first-search of the suffix tree. Its tree-walking technique is applicable to essentially any common tree data structure, and thus we expect many data processing tasks could benefit from running on the GPU. In the future, we plan to extend MUMmerGPU with a second post-processing GPU kernel that computes inexact alignments.. Both the match and print kernels benefited from our exhaustive analysis of seven data organization policies. The impact of individual policies is often surprising and counterintuitive, and we encourage other GPGPU developers to carefully measure their applications when making such decisions. Our analysis shows occupancy is the main determining factor of dataintensive kernel performance. We are optimistic that new versions of the CUDA compiler will simplify reaching high occupancy, but currently, it is imperative that developers monitor their register footprint, and reduce it when possible. The next most important factor is proper use of the textures. The texture cache is very small, and haphazard use of textures will quickly overwhelm it. Instead, applications should only use textures for the most important data. Data reordering can be used to improve locality and cache hit rate, but since different workloads may have different access patterns, developers should select a reordering that is appropriate for the most common workload. Reordering also affects thread divergence, and we recommend that developers consider reordering strategies that reduce divergence, even when not using cached memory.. Data-intensive applications are believed to be less well suited than arithmetic-intensive applications. Nevertheless, our highly data-intensive application MUMmerGPU achieves significant speedup over the serial CPU-based application. A large part of this speedup is due to tuning techniques that may be used in any GPGPU application. The enormous volume of sequencing reads produced by next generation sequencing technologies demands new computational methods. Our software enables individual life science researchers to analyze genetic variations using the supercomputer hidden within their desktop computer. Our exhaustive policy analysis shows occupancy is the single most important factor for the performance of data-intensive applications. This is because higher occupancy allows for more threads to be executed concurrently. Higher occupancy has the added benefit that memory latency can be better hidden with more threads. As such we attempted to improve occupancy of all configurations by reducing their register footprint. In several configurations, we successfully reduced register use to reach 66% occupancy by making small adjustments to the kernel code, such as moving variable declarations to the tightest Fig. 9 . (Top) the print kernel's register footprint (y-axis) depends on whether a configuration uses merged arrays for the suffix tree. In some configurations, only 16 registers are used, increasing occupancy to 66% and dramatically reducing running time (bottom). possible scope, and using bit masks instead of named fields within structs. We also used more aggressive techniques such as using goto's to intentionally disable some compiler optimizations with some success. The CUDA compiler NVCC is actively being developed, and as its register allocation and optimization routines improve, it should be easier to achieve higher occupancy. Our analysis finds proper use of the texture cache is also critical. Haphazardly placing data in texture memory in the hopes of reducing latency is dangerous. The texture cache is limited to 8 KB per multiprocessor, so cache competition can easily hurt overall performance. Furthermore, using textures instead of global memory can reduce occupancy and slow execution. Conversely, proper use of cache that places the most important data in textures can greatly improve performance.. Data reordering can also greatly improve performance. Our results show that it universally improved performance when aligning short reads to a large reference, which we expect to be the most common read mapping use case. For this type of workload, data reordering unexpectedly reduced divergence and warp serialization. Normally used to increase locality and reduce latency, data reordering also is a promising avenue for reducing thread divergence. We plan to explore other reordering strategies in future versions of MUMmerGPU. However, reordering should be used with caution and careful measurement. In MUMmerGPU, it was used to improve cache hit rate in two-dimensional textures, but storing the tree in twodimensions turned out to be a universally bad choice, despite the claims that the texture cache is optimized for 2D locality. Similarly, merging the node and children halves into the same array was supposed to improve data locality and thus cache performance, but this improvement was lost in most configurations to increased register footprint and reduced occupancy from the more complicated addressing.. These conclusions reflect properties and design decisions concerning the current nVidia graphics processing line, and may fail to hold in the future as the hardware and CUDA evolve. A policy analysis such as the one presented here can help identify high performance policy configurations, and can help ''future-proof" an application against rapidly evolving hardware. Ideally, MUMmerGPU would be able to self-tune its policies for an individual system, and we are considering such functionality. In the short term, MUMmerGPU's instrumentation and alternate policy implementations remains in the code, so the application can adapt to new nVidia hardware and CUDA versions as they appear.

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


Improved shape for multi-surface blends For many design applications, where multiple primary surface pieces meet, the distribution of curvature is more important than formally achieving exact curvature continuity. For parametric spline surfaces, when constructing a multi-sided surface cap, we demonstrate a strong link between the uniform variation of the re-parameterization between (boundary) data of the joining pieces and a desirable distribution of curvature. We illustrate this interdependence between parameterization quality and surface quality by developing a G 1 bi-quintic surface cap consisting of n pieces that smoothly fills holes in a piecewise bi-cubic tensor-product spline complex. These bi-5 surface caps have arguably better shape than higher-degree, formally curvature continuous alternatives. Mathematically, since a given surface may be arbitrarily re-parameterized, the differential-geometric properties of surfaces do not depend on the choice of parameterization. In practice, in particular in the CAD context of a low-degree spline representations joining multiple primary surfaces via a multi-sided cap, we observe a strong correlation between the layout of parameter lines and the quality of the resulting surface. Varying the metric, as represented by the reparameterization, as uniformly as possible from the regular tensor-product spline setup along the boundary of the cap to its irregular, starlike center, appears to be crucial for good curvature distribution. Here our measure of quality is that the curvatures present in the primary surfaces along the boundaries of the surface cap average out in the cap without introducing unnecessary oscillations in the highlight lines.. The importance of a uniform layout of parameter lines in constructive algorithms can partly be explained by the strategy of setting degrees of freedom. Coefficients not already determined by formal smoothness constraints, are, in the absence of other constraints, set by minimizing functionals that combine the partial derivatives of the surface. The more gently this metric transitions from the standard tensor-product layout (n = 4) at the border to the meeting of n = 4 patches at the center, the better such functionals address the geometric properties of the resulting surface cap.. The contribution of this paper is two-fold. First, we document the interplay of parameterization and shape, and point out the value of reparameterizing all boundary data including the first derivative. Second, we present a surface construction of moderate degree bi-5 with n patches to cap a tensor-product bi-cubic spline complex where n spline patches join. The visual, highlight line and even curvature quality of these caps is comparable and, at times, superior to more complex curvature continuous constructions, see Fig. 1 . Where n = 3 pieces come together, Theorem 1 establishes that symmetric G 1 caps of any degree are automatically curvature continuous at their central irregular point.. This new result is part of a series of practical algorithms by the authors (see e.g. [KP09, KP13, KP14] ) that explore the non-linear problem of surface construction with good shape -towards a better understanding of the mathematical properties that capture and optimize surface shape. Our approach is guided by testing against an obstacle course of hard synthetic input data [KP15] that are designed to expose the shortcomings of the existing methods.. Overview. Section 2 reviews comparable surface constructions. Section 3 formulates the surface blending problem. Section 4 explains the construction in the generic case when n > 4 and Section 5 discusses the decisions that lead to the construction. This section also compares the new construction to the G 2 constructions [LS08, KP13] . Section 6 focuses on the important special case n = 3.. Figure 1: Shape distribution for three methods, Catmull-Clark subdivision [CC78] , the degree bi-7 construction [LS08] and the new degree bi-5 method presented in this paper. The last two methods can fill an n-sided hole in a bi-cubic C 2 tensor-product spline patch complex using n polynomial pieces. Top row: highlight line shading. Bottom row: Gauss-curvature-scaled surface normals. (The Gauss curvature of Catmull-Clark surfaces diverges near the extraordinary point.). 2. Shape and curvature of selected surface constructions. The entertainment industry, led by Pixar, has adopted Catmull-Clark subdivision [CC78] as a main modeling tool. Subdivision is conceptually simple in that it evokes mesh refinement and provides sufficient quality for animation. However, subdivision surfaces have not entered main stream CAD processing both because they only generalize uniform polynomial splines and because the resulting surfaces consist of infinitely many pieces. The quality of Catmull-Clark subdivision surfaces near the limit point is often poor (Fig. 1e) and the dominant limit shape is always a saddle [KPR04] . [Lev06, KP07] improve the curvature distribution but still use infinitely many surface pieces. A number of surface constructions offer formally high smoothness, but at the cost of a non-standard representation. Examples are global manifold constructions [WP97, GHQ06] and constructions using exponentials [YZ04] . Early spline constructions of G 2 surfaces [Pra97, Rei98, Ye97] were not developed with focus on shape and they are of higher degree: the degree of [Pra97, Rei98] is bi-6 if the surface shape is restricted to be quadratic in a neighborhood of irregular points and bi-9 or higher otherwise. [Ye97] yields degree bi-9. The two low-degree G 2 constructions [GZ99, Pet02a] can suffer from visible shape defects where n > 5 patches meet.. To improve shape, functionals of the type. that act on each coordinate of a surface independently, have been advocated as 'fairness' functionals [HKD93, Gre94, Gre96, LGS99, Sar00, WN01]. If the first fundamental form of the resulting surfaces is close to the identity, e.g. if the parameterization is uniform, these functionals can be viewed as penalizing deviation from a surface of low polynomial degree and this may prevent oscillation of the surface and surface normal. Indeed, [LS08] uses an analogue of F 4 to set extraneous degrees of freedom when capping a bi-3 spline complex. The resulting caps of degree bi-7 are generally of high quality but the transition across the boundary of the cap is not as good as it could be, see Fig. 1c , and the case of three patches meeting does not yield satisfactory highlight lines. Although the presented surface construction only guarantees tangent continuity, it carefully leverages the interplay of parameterization and shape to generate caps whose visual, highlight line and even curvature quality is comparable and, at times, superior to more complex curvature continuous constructions. Key construction principles are increased smoothness at the irregular point and immediate reparameterization of all boundary data to better extend shape into the multi-sided cap.. The n-sided caps constructed by the algorithm in this paper are of degree bi-5 in the general case and of only degree bi-4 when n = 3. They consist of only n pieces. The low degree and high flexibility make the new construction easy to use for iso-geometric analysis as demonstrated in [NKP14] .

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


The periodic boundary value problem for semilinear elastic beam equations: The resonance case This paper discusses the existence of generalized solutions to periodic boundary value problems for semilinear elastic beam equations under a resonance condition. The argument presented makes use of the global inverse theorem and Galerkin's method. Let Ω = (0, 2π ) × (0, π ) ⊂ R 2 and H = [L 2 (Ω )] n , with integer n ≥ 1. Now H is a real Hilbert space with inner product u, v = 2π 0 π 0 (u(t, x), v(t, x))dxdt.. (1.1). Note that (·, ·) denotes the Euclidean inner product in R n . The norms induced by ·, · and (·, ·) are denoted by · and | · |, respectively. We consider the system of semilinear elastic beam equations described by the following partial differential equation:. u tt + u x x x x − f (t, x, u) = h(t, x), ∀(t, x) ∈ J, (1.2) with the boundary value conditions, u(t, 0) = u(t, π ) = u x x (t, 0) = u x x (t, π ) = 0, (1.3) where J = [0, 2π ] × [0, π], f : J × R n → R n satisfies the Carathéodory conditions and h : J → R n . We will look for periodic solutions so we will need u(0, x) = u(2π, x), u t (0, x) = u t (2π, x), ∀x ∈ [0, π].. (1.4). Much work has been done on the existence of periodic solutions for the beam equations (1.2)-(1.4); we refer the reader to [1] [2] [3] [4] [5] and the references therein. In [3] , the nonlinear term f (t, x, u) is a power approximately; and in [4] more general nonlinearities are considered. Besides other assumptions, the function f is required to be symmetric in the following sense: there exist constants α, β, M > 0 such that α f (t, x, u) ≤ f (t, x, −u) ≤ β f (t, x, u), for u ≥ M.. (1.5). Therefore, functions with different powers, say g(t, x, u) = |u| p−2 u, u ≥ 0; |u| q−2 u, u < 0; (1.6) where p, q > 2 and p = q, are excluded. In [1, 2] , by using Galerkin's method, and working in finite dimensional spaces and passing to the limit, that case is discussed. In [7, 8] , Galerkin's type arguments are also adopted to study the semilinear wave equation with periodic-Dirichlet boundary conditions. In this paper, motivated by [6, 7, 9, 11] , with the use of a version of the global inverse function theorem and Galerkin's method, we present a result on the existence and uniqueness of generalized solutions to the periodic-Dirichlet problem (GPDS, for short) for the semilinear elastic beam equation under a resonance condition. Our result avoids the above restrictions on f (t, x, u). In fact we allow the nonlinearity f (t, x, u) when (u → ∞) to interact with points of resonance.. Here, by a GPDS for (1.2) we mean a function u ∈ H such that. holds for all ∀v ∈ C 2 (Ω , R n ) and which satisfies the following conditions:. The set σ (L) = {m 4 − l 2 |m ∈ Z , l ∈ N * } is called the set of points of resonance of (1.2)-(1.4), where Z is the set of all integers and N * is the set of all positive integers and zero. The periodic boundary value problem (1.2)-(1.4) is said to be at resonance if the following conditions hold:. There exist two constant symmetric n × n matrices A and B such that. and, if λ 11 ≤ λ 12 ≤ · · · ≤ λ 1n and λ 21 ≤ λ 22 ≤ · · · ≤ λ 2n are the eigenvalues of A and B, λ 1i ≤ λ 2i , for i = 1, . . . , n respectively, then. note that the relation A ≤ B means that B − A is positive semi-definite.. To be more precise, we will prove in this paper that if f is continuously differentiable, f (t, x, u) is symmetric and satisfies. then there exists a unique GPDS to (1.2); here I is an n × n identity matrix, A and B are two real symmetric matrices (and we assume that λ 1i , λ 2i ∈ σ (L) are consecutive, for i = 1, . . . , n, where λ 1i , λ 2i are the eigenvalues of A and B respectively) and α(s), β(s) are two continuous and nonincreasing functions from [0, ∞) to (0, ∞).. and λ 11 ≤ λ 12 ≤ · · · ≤ λ 1n , λ 21 ≤ λ 22 ≤ · · · ≤ λ 2n , λ 1i < λ 2i for each i.

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


A Structured Approach for Designing Collaboration Experiences for Virtual Worlds Abstract An ideal online, three-dimensional (3D) virtual environment would provide a space in which users can move freely, interact intuitively with all kinds of objects, recognize familiar people, and communicate in a natural manner with others -all in a realistic setting that evokes a feeling of really being a part of the virtual world. Additionally, it would allow displaying complex content or data in innovative and useful ways that neglect the limitations imposed by physical reality. Such an environment has the potential to move remote collaboration and learning to another level of quality. But even if such platforms were available today (and they soon will be), without the right kind of choreography, script, or setup, users might still not know how to best benefit from such an infrastructure.. We believe that today's available virtual worlds are already capable of adding significant value to collaborative work and collaborative learning. However, an exploration of collaborative activities in the virtual world Second Life has shown that companies, institutions, and educators mostly do not make use of the distinct features of a 3D environment, although there are promising approaches (Schmeil & Eppler, 2009 ). These distinct opportunities of virtual worlds make them an interesting new medium for collaborative activities, much more than the possibility of simulating the physical world (Irani, Hayes, & Dourish, 2008) . Others agree that in order to maximize the benefits from using virtual worlds the capabilities of the medium have yet to be thoroughly examined (Davis, Murphy, Owens, Khazanchi, & Zigurs, 2009 ).. Moreover, many of the virtual environments that are currently (mid 2011) advertised as offering great productivity boosts for collaborative work emphasize the collaborative editing of text documents, spreadsheets, and presentation slides that are mounted on big virtual walls -a method of working together that may work just as well (or even better) without gathering in a 3D virtual space. Working on two-dimensional (2D) tasks (on interactive walls) in a 3D environment can be understood as a step back in the ongoing paradigm shift in the design of interaction. It also ignores the opportunities of embodied interaction; being embodied as the natural form of human existence lets collaborators interact and communicate naturally using their bodies (Dourish, 2001) . Virtual environments that feature virtual embodiment (or avatars) provide "an interesting ecology of embodied interaction" (Jarmon, 2009) . Fortifying the positive impact of virtual embodiment, research into mirror neurons and body language has shown it is important to people to see their body and the bodies of others (Bray & Konsynski, 2007) .. Consequently, our premise is that embodiment in an immersive and configurable environment allows for new, valuable, and innovative forms of working and learning together. Firstly, our research formally describes the necessary elements for online, visual, and spatial collaboration to improve collaboration in these virtual environments or virtual. Secondly, it develops and identifies novel and existing collaboration patterns that can be described in that formalism. In this paper, we present our framework for avatar-based collaboration in online 3D virtual environments based on semiotics theory. The framework represents a blueprint for how collaborative group interaction patterns in virtual environments can be described or generated. The framework is distinctive with respect to its two ways of use: collaboration patterns can be generated or documented either by starting with a goal, or by starting with the infrastructure of objects and actions available. We also present a study of the first application case of the framework, which showcases 13 collaborative learning patterns. We believe that this framework forms a first important step in the process of formalizing collaboration in virtual environments -a task that is crucial in order to progress the application of 3D virtual environments for serious and productive uses.. The remainder of this paper is structured as follows: In Section 2, we define online virtual environments and present their advantages for collaboration. In Section 3, we present our framework that helps to formalize the design elements and necessary infrastructure of collaboration patterns in online virtual environments. We also describe the development of the framework in detail and the research methodology that we followed. In Section 4, we discuss the case study. We conclude by reviewing our contribution and highlighting directions of future research.

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 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 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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 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 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


Identification of AMP-activated protein kinase targets by a consensus sequence search of the proteome Background: AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine protein kinase that is activated by cellular perturbations associated with ATP depletion or stress. While AMPK modulates the activity of a variety of targets containing a specific phosphorylation consensus sequence, the number of AMPK targets and their influence over cellular processes is currently thought to be limited. Maintenance of cellular health requires the orchestration of multiple metabolic pathways and signaling cascades whose effects sum to maintain cellular homeostasis. AMP-activated protein kinase (AMPK) has emerged as a major regulator of cellular metabolism through activation of signaling cascades that are protective against stress. AMPK is composed of three subunits (α, β, and γ), and its activation occurs via AMP-dependent and -independent mechanisms leading to phosphorylation of the α subunit at Thr172. While elevation of the AMP: ATP ratio promotes AMP binding to the γ subunit, which permits activation by LKB1, Ca 2+ influx elicits activation by CaMKKβ independent of the AMP: ATP ratio [1] [2] [3] . In addition to Thr172 phosphorylation a variety of posttranslational modifications including phosphorylation at sites other than Thr172 as well as myristolation of the β subunit can control AMPK activation [4] .. Once activated, AMPK initiates an array of signaling cascades by phosphorylating proteins with a βϕβXXXS/ TXXXϕ consensus sequence (hydrophobic, φ = M, L, I, F, or V; basic, β = R, K, or H, X = any amino acid, S/T = phosphorylation site) [5, 6] . AMPK targets often contain slight variants of this consensus sequence, because AMPK can phosphorylate sites flanked by amino acid sequences lacking the basic residues in the −4/-6 positions. Additionally, the −5 hydrophobic residue may be shifted to the −4 position [7] . Understanding how AMPK exerts its protective effects via various signaling pathways requires knowledge of all of AMPK targets, which may be more extensive than currently recognized. To explore this possibility, we mapped its phosphorylation consensus sequence to both human and mouse proteomes. Delineation of AMPK networks involved integration of these data into Gaggle software to organize putative targets based on function. Along with knowledge gained from an extensive literature review, networks were constructed and then used to predict pathways linking the putative targets [8] . This approach yielded an extraordinarily large group of putative AMPK targets and suggested several novel pathways. The predicted pathways from this approach have the potential to redefine the role of AMPK as a survival master switch responding to stress imposed on the cell.

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


Performance Evaluation of an Advanced DWDM RoFSO System for Transmitting Multiple RF Signals With the increase of communication demand and the emergence of new services, various innovative wireless technologies have been deployed recently. Free Space Optics (FSO) links combined with Radio over Fiber (RoF) technology can realize a cost-effective heterogeneous wireless access system for both urban and rural areas. In this paper, we introduce a newly developed advanced DWDM Radio-on-FSO (RoFSO) system capable of simultaneously transmitting multiple Radio Frequency (RF) signals carrying various wireless services including W-CDMA, WLAN IEEE802.11g and ISDB-T signals over FSO link. We present an experimental performance evaluation of transmitting RF signals using the RoFSO system over a 1 km link under different deployment environment conditions. This work represents a pioneering attempt, based on a realistic operational scenario, aiming at demonstrating the RoFSO system can be conveniently used as a reliable alternative broadband wireless technology for complementing optical fiber networks in areas where the deployment of optical fiber is not feasible. key words: Radio on Free Space Optics (RoFSO), Radio over Fiber (RoF), W-CDMA, ISDB-T, WLAN Transmission of RF signals by means of optical fiber links, referred to as Radio over Fiber (RoF), has been utilized for many years to facilitate wireless access. In RoF implementation, to distribute the RF signals from central station to remote stations, RF signals are placed on optical carriers and transmitted over high capacity optical fiber cables. The advantages of RoF include distributing RF signals at large bandwidth, immunity to radio frequency interference, low attenuation loss and dynamic resource allocation [1] , [2] . However, RoF is dependent on the availability and cost of the installed optical fiber cables.. Free Space Optics (FSO) is the technology in which modulated optical signal is propagated over free space without using optical fiber medium. The advantages of FSO communications include ease of deployment, license free operation, high transmission security, high bit rates, full duplex transmission and protocol transparency. Depending on deployment scenario and application [3] , [4] . FSO links can conveniently be used to transmit RF signals, referred to as Manuscript received March 9, 2009 . Manuscript revised June 8, 2009 . † The authors are with the Graduate School of Global Information and Telecommunication Studies/Institute (GITS/GITI), Waseda University, Tokyo, 169-0051 Japan.. † † The authors are with the Departement of Electrical, Electronic and Information Engineering, Graduate School of Engineering, Osaka University, Suita-shi, 565-0871 Japan.. a) E-mail: bekkali@fuji.waseda.jp DOI: 10.1587/transfun.E92.A.2697. Radio-on-Free Space Optics (RoFSO), where the physical connection by the means of optical fiber cables is impractical, due to high costs or other considerations, with similar capacity of optical fiber [5] . The performance of RoFSO link can be degraded by many effects, such as fog, rain, atmospheric turbulence and the non-ideal characteristics of optical transmitters and receivers. To achieve high quality RF signals reception over the RoFSO system the link has to be engineered to perform in environments affected by atmospheric turbulence, low visibility, rain, building sway, etc.. Recently researches investigating the transmission of RF signals using FSO links have been reported in [6] , [7] . In [6] , investigation of simultaneous transmission of multiple analog RF signals over a FSO link spanning 3 m using WDM technology is presented. In this setup the used antenna does not utilize any tracking function because of the short distance and real operational environment characteristics are not reflected. Whereas in [7] , transmission of single cellular signal using conventional FSO systems operating at 810 nm and 1550 nm over a 500 m link is investigated. However, in these researches, the authors did not consider the influence of atmosphere which is considered as the limited factor to FSO communication on the performance of transmitted RF signals over FSO links. Apart from the above-mentioned published work, so far the authors are not aware of any significant attempt to measure, characterize and quantify the transmission of RF signals in RoFSO implementations taking into account actual deployment environment characteristics.. In this paper we present results obtained from experimental demonstration of the newly developed advanced DWDM RoFSO system capable of simultaneously transmitting multiple wireless services including W-CDMA, WLAN IEEE802.11g and terrestrial digital broadcasting TV (ISDB-T) signals over a 1 km link. This work represents a more realistic operational scenario with the aim of demonstrating long term system performance under different deployment environment conditions. This paper is organized as follows. In Sect. 2, we describe the design concept and operation characteristics of the DWDM RoFSO system. Sections 3 and 4 present the experimental setup and the transmission results and analysis of W-CDMA, WLAN and ISDB-T signals using the RoFSO link. Finally, Sect. 5 concludes the paper and gives directions for future work. An experimental evaluation on simultaneous transmission of different kinds of wireless service signals using a newly developed advanced DWDM RoFSO system under real operational environment has been presented. Important performance metric parameters for evaluating the quality of W-CDMA, ISDB-T and WLAN IEEE 802.11g/a signals transmission using RoFSO link have been measured and characterized under various atmospheric influences and weather conditions.. From the initial results on the performance evaluation of the RoFSO system we have confirmed that for W-CDMA signal transmission the minimum required received optical power should be −15 dBm without post EDFA and −20 dBm when using post EDFA. In the case of ISDB-T Layer A and Layer B signal transmission the BER measured data showed a CDF of 99% and 72% respectively of the values appearing below the specified error correction limit. Finally for the WLAN 802.11g transmission the CDF of the spectrum mask measurement showed 99% successful pass. These results confirm the technical feasibility and practicality of utilizing the RoFSO system as a universal platform for providing ubiquitous wireless services.. Future work involves investigation on performance analysis of the RoFSO system in the service area, the improvement in the tracking mechanism and performance improvement of the different RoF modules utilized for each RF wireless service. Extensive measurements will be conducted to obtain further experimentally derived models for a better understanding of the system performance. To evaluate the transmission performance of the developed advanced DWDM RoFSO system, we setup up two RoFSO antennas on the rooftop of two buildings in Waseda University campus area in Tokyo city. The two buildings are separated by a distance of 1 km which is within the range of typical application distance for FSO links [4] , [14] . A schematic diagram representing the experimental setup of the RoFSO system is shown in Fig. 2 . Placed at one site are signal generators for producing different kind of wireless service signals which are then multiplexed together and transmitted via the DWDM RoFSO link by the RoFSO antenna placed on the buildings rooftop. At the second site, signal analyzers and other devices for measuring and recording the quality of the received RF and optical signals, weather data (temperature, visibility, rainrate etc) as well as atmospheric conditions like scintillation effects are placed.. In the RoFSO system configuration two interface units are included; an optical interface unit (Optical IF unit) and a RoF interface unit (RF IF unit). The optical interface unit consists of a wavelength multiplex and de-multiplex device, boost and post amplifier and an optical circulator to isolate the transmit and received signals. On the other hand, the RoF interface unit has RoF modules responsible for the electrical to optical signal conversion and vice versa corresponding to each wireless service RF signal under investigation.. The success of all FSO links depends on a optimized link budget. In this experimental investigation the FSO link was designed and engineered to provide enough link margin to compensate for losses. However, The link margin is dependent on the requirement of the FSO link availability, and the kind of wireless services to be transmitted over RoFSO link. The 1Km RoFSO link parameters are given in Table 2 . The link parameters include the optical losses inherent in the RoFSO system devices as well as the light loss during propagation. In order to describe the FSO link losses due to the atmospheric turbulence, rain, low visibility and tracking loss, several models were published in the literature [3] , [4] .. In our experimental setup and inverstigation the test signals under consideration include standard digital signal at 2.5 Gbps, cellular signals (3GPP W-CDMA signal) at 2 GHz, WLAN signal (IEEE 802.11g/a at 2.4 GHz and 5 GHz respectively) as well as digital terrestrial television broadcasting (ISDB-T) signal at the UHF band [470 MHz, 770 MHz]; all transmitted simultaneously using DWDM technology over the RoFSO link. We evaluate the DWDM RoFSO system performance by measuring and analyzing the quality of the RF signals transmitted over it based on the quality metric parameters specified in the standards for transmission of the different kind of wireless services. Figure 3 depicts the received optical signal WDM spectrum showing from left to right: the ISDB-T, W-CDMA, 802.11g and 802.11a signals carrying wavelengths. The WDM wavelengths are separated using the ITU-T Recommendation G.692 100 GHz grid spacing [15] . Except for the 802.11g wavelength, the rest of the WDM signals show ideal characteristics because they are generated using signal generators which produce signals waveforms with almost ideal characteristics. The 802.11g signal is slightly different because it is an actual WLAN 802.11g access point (AP) signal connection via the RoFSO link. The received WDM spectrum depicted in Fig. 3 shows a stable performance. The wavelength assignments for the wireless services signals downlink and uplink are given in Table 3 . Channel 33 which is designated as "free" and is used for evaluating the RoFSO system performance in terms of BER by transmitting a 2.5 Gbps digital signal.

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


Using interspike intervals to quantify noise effects on spike trains in temperature encoding neurons Abstract This paper examines how noise interacts with the non-linear dynamical mechanisms of neuronal stimulus. We study the spike trains generated by a minimal Hodgkin-Huxley type model of a cold receptor neuron. The distributions of interspike intervals(ISIs) of purely deterministic simulations exhibit considerable differences compared to the noisy ones. We quantify the effect of noise using ISI return plots and the ISI-distance recently proposed by Kreuz et al. (J Neurosci Meth, 165:151-161, 2007). It is shown that the spike trains of a cold receptor neuron are more strongly affected by noise for low temperatures than for high temperatures. This trend is also observed in both regimes of cold receptors: tonic firing(which occurs for low and high temperatures) and bursting (which occurs for intermediate temperatures). Nonlinear systems can change their dynamics qualitatively if they are subjected to noise (Horsthemke and Lefever 1984; Freeman 2009) . Classical example for this are neuronal models due to their excitability. The most common models in theoretical neuroscience are the integrate-andfire (IF) model, the Hodgkin-Huxley (HH) model (Hodgkin and Huxley 1952) , these models consist of differential equations that are able to reproduce observed neuronal behavior such as excitability and the presence of refractory periods. When these models are driven by noise, a variety of excitation phenomena including stochastic resonance and coherence resonance has been observed (Lindner et al. 2004) .. Especially, signal encoding in temperature sensitive skin receptors exhibit the qualitative varieties of impulse pattern with contribution of noise. For further examination of the principle encoding properties and the effects of noise, Braun et al used a minimal Hodgkin-Huxley type computer model to simulate temperature dependencies of cold receptors (Braun et al. 1998a, b) . This model shows bifurcations from tonic firing to burst discharges, and transitions from subthreshold oscillations to skipping and regular firing. The corresponding data analysis suggest that addition of noise can considerably extend the dynamical behavior of the system (Braun et al. 2001 (Braun et al. , 2003 .. Many different measures have been introduced to characterize the spike train pattern and effects of noise. Some of them are using post-stimulus time histogram (PSTH) (Mainen and Sejnowski 1995; Berry et al. 1997) to define the events, bursts of high firing rate; other methods quantify the occurrence of given spike patterns and measure their robustness (Eiesinga et al. 2002) ; Also a quantification of the degree of similarity or dissimilarity between two spike trains is introduced (Victor and Purpura 1996; van Rossum 2001; Schreiber et al. 2003; Hunter and Milton 2003; Quian Quiroga et al. 2002) ; or a measure enhance the saliency of neural responses by synchronizing the spikes emitted by neuronal populations (Wolf Singer 2009) . A common property of most measures is the necessity to fix the appropriate time scale for the analysis (for example, the length of the time window or the width of the filter). This choice is difficult for dynamical phenomena for which the time scale either varies strongly with the parameter , or which involve feature on several time scales simultaneously (which is typically the case in spike trains of bursting neurons subject to noise).. Except the traditional methods, in this paper, we use ISIdistance, a new method recently introduced by Kreuz et al. (2007) , to characterize effects of noise in a Hodgkin-Huxley type model of temperature encoding. This is a simple approach that extracts information from the interspike intervals by evaluating the ratio of the instantaneous firing rates, which is complementary to the spike-based approaches. Since no binning is used, it is self-adaptive.. The remainder of the paper is organized as follows: in Sect. 2 we describe a simplified Hodgkin-Huxley type model of cold receptor. Spike train patterns and bifurcation diagrams of deterministic and stochastic simulations at different temperatures are shown, while the return plots of these spike train data are also discussed. The following Sect. 3 contains a short description of the spike detection algorithm and definition of the ISI-distance, then we compare the deterministic and stochastic simulations at different temperatures by measuring the ISI-distance between them. Conclusions are given in Sect. 4. In conclusion, we study the noise effect in the temperature encoding of neuronal spike trains in a cold receptor model. With the addition of noise, this minimal model can generate a variety of impulse patterns and allow continuous transitions from rhythmic bursting to subthreshold oscillations with occasional spikes. Thus, noise can be seen as estimations of the actual dynamics underlying the experimental data. For example, the return plots indicate that longer intervals have a less exact phase-locking than shorter ones and suggest that noise is not only essential for spike-generation but also interferes with the oscillatory activity. This stochastic phenomena means that signal encoding can be different with the change of noise level. The result might also suitable for signal encoding in many other neurons in the peripheral and central nervous system in the mammalian brain. For a better understanding of noise effect, here, we use the ISI-distance to explore how noise affects the pattern variability of the cold receptor. The method and results in this study may be instructive for the study of neural encoding of spike trains under noisy environment. In our future study, we will consider the relationship between the effect of noise on ISI-distance and the dynamics of the firing patterns.

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


Evaluating semantic similarity and relatedness over the semantic grouping of clinical term pairs Introduction: This article explores how measures of semantic similarity and relatedness are impacted by the semantic groups to which the concepts they are measuring belong. Our goal is to determine if there are distinctions between homogeneous comparisons (where both concepts belong to the same group) and heterogeneous ones (where the concepts are in different groups). Our hypothesis is that the similarity measures will be significantly affected since they rely on hierarchical is-a relations, whereas relatedness measures should be less impacted since they utilize a wider range of relations. In addition, we also evaluate the effect of combining different measures of similarity and relatedness. Our hypothesis is that these combined measures will more closely correlate with human judgment, since they better reflect the rich variety of information humans use when assessing similarity and relatedness. Method: We evaluate our method on four reference standards. Three of the reference standards were annotated by human judges for relatedness and one was annotated for similarity. Results: We found significant differences in the correlation of semantic similarity and relatedness measures with human judgment, depending on which semantic groups were involved. We also found that combining a definition based relatedness measure with an information content similarity measure resulted in significant improvements in correlation over individual measures. Availability: The semantic similarity and relatedness package is an open source program available from Semantic similarity and relatedness measures quantify the degree to which two concepts are similar (e.g., liver-organ) or related (e.g., headache-aspirin). Relatedness encompasses many kinds of relations, but generally shows how associated two concepts are with each other. For example, a headache can be treated with aspirin. Similarity is a specific relation that is a subset of relatedness, and is based on the degree to which two concepts are connected through hierarchical is-a relations. For example, organ could be an ancestor of liver in an is-a hierarchy, and would therefore have a high similarity score. Headache and aspirin, on the other hand, are not closely connected by any is-a relations, and so would have a low similarity score. However, since they may be connected by other kinds of relations (e.g., treated by) they could have a very high relatedness score.. The automated discovery of groups of semantically similar or related concepts and terms is critical to improving the retrieval [1] and clustering [2] of biomedical and clinical documents, and the development of biomedical terminologies and ontologies [3] . As such, a number of different similarity measures have been developed for the biomedical domain. These have been evaluated intrinsically via comparisons to various human reference standards [4, 5] , as well as extrinsically depending on how well they contribute to the performance of secondary applications [6, 7] . However, to date there has been little work that considers the type of concept being evaluated. Our objective is to evaluate how measures of similarity and relatedness perform depending on the semantic groups of the concepts involved.. Similarity measures find paths between concepts in an is-a hierarchy. Concept pairs from different semantic groups may well be in different hierarchies and therefore not be connected by is-a relations. In addition, these different hierarchies may have different levels of granularity and coverage. Given these considerations, our hypothesis is that there will be a large degree of change in the correlation of similarity measures with human reference standards when the concepts in a pair are from different semantic groups. Our results support this hypothesis. We found that no single measure performed best over all the different semantic group pairs.. In this work, we also combined measures based on the hypothesis that measures of similarity and relatedness will be complementary, and may result in more robust measures that more closely correlate with human judgments. Our goal is to identify pairs of measures that provide complementary information that will improve our ability to quantify the degree of similarity and relatedness between two terms. Bill et al. [8] showed that a linear combination of the similarity measures proposed by Resnik [9] and Lin [10] increased the accuracy of identifying similar terms. The results, here in this paper, show that combining relatedness and similarity measures improved correlation scores overall. However, these results varied depending on the reference standard used and so no single pair of measures was found to always improve correlation.. This article is organized as follows. Section 2 provides an overview of the Unified Medical Language System (UMLS), which is our main source of data on concepts and their relations. Section 3 reviews the measures of semantic similarity and relatedness used in this study. Section 4 describes resources used beyond the UMLS for formulating some of the measures. The reference standards used in our evaluation are introduced in Section 5, and the details of our experiments on these standards are summarized in Section 6. Our results are presented in Section 7, and the article closes with our conclusions in Section 8. In this paper, we analyzed the correlation of semantic similarity and relatedness measures to human judgments over various semantic groupings of the term pairs. The results show that no one measure performed best over all of the semantic grouping pairs analyzed in this article. The results also indicated that using similarity measures on term pairs across disparate semantic groupings does not result in high correlation because there is little taxonomy information connecting them; relatedness measures are a better choice for these term pairs. In the future, we would like to analyze additional semantic groupings in order to determine if this is the case across all semantic groups.. We also analyzed the results of combining various measures to determine if they are complementary. The results showed that combining relatedness and similarity measures improved the correlation scores; specifically we found that using lesk and the i-jcn measure obtained the highest overall correlation over the datasets; although vector with lch or i-jcn also performed well. In the future, we plan to explore and develop additional measures that incorporate aspects of semantic similarity and relatedness measures into a single measure.. In the future, we also plan to evaluate what constitutes a high correlation and at what level do the measures need to correlate with human judgments to be practically useful. In an intrinsic evaluation, such as this study, it is difficult to pick out a particular correlation level and say 'this is good enough'. Therefore, we plan to conduct an extrinsic evaluation by analyzing the measures with respect to their correlation in a secondary application.

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