From Questions to Effective Answers: On the Utility of Knowledge-Driven Querying Systems for Life Sciences Data

We compare two distinct approaches for querying data in the context of the life sciences. The first approach utilizes conventional databases to store the data and intuitive form-based interfaces to facilitate easy querying of the data. These interfaces could be seen as implementing a set of "pre-canned" queries commonly used by the life science researchers that we study. The second approach is based on semantic Web technologies and is knowledge (model) driven. It utilizes a large OWL ontology and same datasets as before but associated as RDF instances of the ontology concepts. An intuitive interface is provided that allows the formulation of RDF triples-based queries. Both these approaches are being used in parallel by a team of cell biologists in their daily research activities, with the objective of gradually replacing the conventional approach with the knowledge-driven one. This provides us with a valuable opportunity to compare and qualitatively evaluate the two approaches. We describe several benefits of the knowledge-driven approach in comparison to the traditional way of accessing data, and highlight a few limitations as well. We believe that our analysis not only explicitly highlights the specific benefits and limitations of semantic Web technologies in our context but also contributes toward effective ways of translating a question in a researcher's mind into precise computational queries with the intent of obtaining effective answers from the data. While researchers often assume the benefits of semantic Web technologies, we explicitly illustrate these in practice

Design, analysis and test verification of advanced encapsulation systems, phase 2 program results

Optical, electrical isolation, thermal structural, structural deflection, and thermal tests are reported. The utility of the optical, series capacitance, and structural deflection models was verified

Supersymmetry, quark confinement and the harmonic oscillator

We study some quantum systems described by noncanonical commutation relations formally expressed as [q,p]=ihbar(I + chi H), where H is the associated (harmonic oscillator-like) Hamiltonian of the system, and chi is a Hermitian (constant) operator, i.e. [H,chi]=0 . In passing, we also consider a simple (chi=0 canonical) model, in the framework of a relativistic Klein-Gordon-like wave equation.Comment: To be published in Journal of Physics A: Mathematical and Theoretical (2007

A Semantic Problem Solving Environment for Integrative Parasite Research: Identification of Intervention Targets for Trypanosoma cruzi

Effective research in parasite biology requires analyzing experimental lab data in the context of constantly expanding public data resources. Integrating lab data with public resources is particularly difficult for biologists who may not possess significant computational skills to acquire and process heterogeneous data stored at different locations. Therefore, we develop a semantic problem solving environment (SPSE) that allows parasitologists to query their lab data integrated with public resources using ontologies. An ontology specifies a common vocabulary and formal relationships among the terms that describe an organism, and experimental data and processes in this case. SPSE supports capturing and querying provenance information, which is metadata on the experimental processes and data recorded for reproducibility, and includes a visual query-processing tool to formulate complex queries without learning the query language syntax. We demonstrate the significance of SPSE in identifying gene knockout targets for T. cruzi. The overall goal of SPSE is to help researchers discover new or existing knowledge that is implicitly present in the data but not always easily detected. Results demonstrate improved usefulness of SPSE over existing lab systems and approaches, and support for complex query design that is otherwise difficult to achieve without the knowledge of query language syntax

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Radiating Effectiveness of Annular-Finned Space Radiators, Including Mutual Irradiation between Radiator Elements

the authors also provide an approximate quantitative number for the accuracy of the numerical results. Based on the authors' results of Figs. 8 and 9, the fully developed periodic flow is achieved at x/L = 4 and 30 for Re = 200 and 1600 respectively for L/H = 1. Would the authors first quantitatively define the periodic fully developed flow, and then provide the tabular values of x/L as functions of L/H and Re for L/H = 0.2,0.5,1,2 and 5, and the covered range of Re. A research task remains further refining the analytical model to correlate better the performance of interrupted wall surface with the experimental results. Subsequently, the more complex heat exchanger surfaces could be analyzed. In the meanwhile, this paper by Prof. Sparrow and his colleagues serves as a reminder that the flow and heat transfer phenomena in a compact heat exchanger are too complex to analyze. A better quantitative understanding of the flow phenomena is essential for better correlations and improved heat exchanger design. Additional Reference Authors' Closure We are appreciative of the perspectives conveyed by Dr. Shah's Discussion. With regard to the role of vortices and wakes, there are, assuredly, conditions where they will affect both the heat transfer and friction. On the other hand, there are conditions for which no significant effect will be felt. Perspectives on these conditions are conveyed in references [11] and [12]. In connection with the identification of the periodically developed regime in Figs. 8 and 9, there is considerable latitude depending on the selected criterion. Since all portions of a velocity or temperature profile do not develop with equal rapidity, there are various criteria that can be employed. It was for this reason that we did not quote development lengths in the paper. Additional References 11 Kottke, V., Blenke, H., and Schmidt, K. G., "The Influence of Nose Section and Turbulence Intensity on the Flow Around Thick Plates in Parallel Flow," Warme-und Stoffubertragung, Vol. 10,1977, pp. 159-174. 12 Loehrke, R. I., Roadman, R. E., and Read, G. W" ASME Paper The purpose of this discussion is to point out how one of Minning's results can be generalized. In his analysis of the inverted conical frustrum, Minning has chosen to express his results in terms of four variables-the cone half angle fi, the height of the frustrum h, the radial location of the differential element p, and the vertical distance from the differential element to the extended frustrums' vertex s. In my view, this last choice is not the natural one and indeed it obscures the generality of the result expressed by equation It appears that a better choice of variable would be the radius of the frustrum in the plane of the element or ring, which is given by r = -s tan fi. If s is thereby eliminated from equation With respect to this latter point, one may note, as was done for a cylinder by Sparrow, et al. [1] that the shape factor in question can be considered as the sum of two parts-one being a circular segment and, in this case, the other being a tilted triangular plate frustrum. 1 By C. P. Minning, published in the August, 1977 issue of the JOURNAL OP HEAT TRANSFER, Vol. 99, No. 3, The Aerospace Corporation, El Segundo, CA 90245. Since the former is known [2], the latter can be readily obtained and subsequently expressed in variables more suitable for that configuration. This, of course, introduces new possibilities too numerous to mention. Finally, since Minning does not mention any analytical checks of his result, it is pointed out that, when /3 = 0, it reduces to a form equivalent to that for the cylinder [1]. Additional References 1 Sparrow, E. M., Miller, G. B., and Jonsson, V. K., "Radiating Effectiveness of Annular-Finned Space Radiators, Including Mutual Irradiation between Radiator Elements," Journal Aerospace Sciences, Vol. 29, 1962, pp. 1291-1299 2 Sparrow, E. M., "A New and Simpler Formulation for Radiative Angle Factors," ASME JOURNAL OF HEAT TRANSFER, Vol. 85,1963, pp. 81-88. Author's Closure I appreciate Dr. Nelson's pointing out that the applicability of equation An alternate expression that avoids this confusion can be derived by substitution of the relation r = -s tanjtf, as suggested by Dr. Nelson, and the relation a = (7r/2) -fi into equation C^)] [(h cot a + r) -In this expression, a is the angle between the plane of dAi and the sloping side of the conical frustrum. Values of a are always positive and lie in the range 0 < « < TT. For 0 < « < 7r/2, the frustrum opens upward away from the plane of dA\. For 7r/2 < a < w, the frustrum opens downward toward the plane of dAi. The special case, a = it 12

Spliced Leader Trapping Reveals Widespread Alternative Splicing Patterns in the Highly Dynamic Transcriptome of Trypanosoma brucei

Trans-splicing of leader sequences onto the 5′ends of mRNAs is a widespread phenomenon in protozoa, nematodes and some chordates. Using parallel sequencing we have developed a method to simultaneously map 5′splice sites and analyze the corresponding gene expression profile, that we term spliced leader trapping (SLT). The method can be applied to any organism with a sequenced genome and trans-splicing of a conserved leader sequence. We analyzed the expression profiles and splicing patterns of bloodstream and insect forms of the parasite Trypanosoma brucei. We detected the 5′ splice sites of 85% of the annotated protein-coding genes and, contrary to previous reports, found up to 40% of transcripts to be differentially expressed. Furthermore, we discovered more than 2500 alternative splicing events, many of which appear to be stage-regulated. Based on our findings we hypothesize that alternatively spliced transcripts present a new means of regulating gene expression and could potentially contribute to protein diversity in the parasite. The entire dataset can be accessed online at TriTrypDB or through: http://splicer.unibe.ch/

High Throughput Selection of Effective Serodiagnostics for Trypanosoma cruzi infection

The diagnosis of Trypanosoma cruzi infection (the cause of human Chagas disease) is difficult because the symptoms of the infection are often absent or non-specific, and because the parasites themselves are usually below the level of detection in the infected subjects. Therefore, diagnosis generally depends on the measurement of T. cruzi–specific antibodies produced in response to the infection. However, current methods to detect anti–T. cruzi antibodies are relatively poor. In this study, we have conducted a broad screen of >400 T. cruzi proteins to identify those proteins which are best able to detect anti–T. cruzi antibodies. Using a set of proteins selected by this screen, we were able to detect 100% of >100 confirmed positive human cases of T. cruzi infection, as well as suspect cases that were negative using existing tests. This protein panel was also able to detect apparent changes in infection status following drug treatment of individuals with chronic T. cruzi infection. The results of this study should allow for significant improvements in the detection of T. cruzi infection and better screening methods to avoid blood transfusion–related transmission of the infection, and offer a crucial tool for determining the success or failure of drug treatment and other intervention strategies to limit the impact of Chagas disease