Science Models as Value-Added Services for Scholarly Information Systems

The paper introduces scholarly Information Retrieval (IR) as a further dimension that should be considered in the science modeling debate. The IR use case is seen as a validation model of the adequacy of science models in representing and predicting structure and dynamics in science. Particular conceptualizations of scholarly activity and structures in science are used as value-added search services to improve retrieval quality: a co-word model depicting the cognitive structure of a field (used for query expansion), the Bradford law of information concentration, and a model of co-authorship networks (both used for re-ranking search results). An evaluation of the retrieval quality when science model driven services are used turned out that the models proposed actually provide beneficial effects to retrieval quality. From an IR perspective, the models studied are therefore verified as expressive conceptualizations of central phenomena in science. Thus, it could be shown that the IR perspective can significantly contribute to a better understanding of scholarly structures and activities.Comment: 26 pages, to appear in Scientometric

Far-infrared spectroscopic images of M83

We have mapped the nearby face on barred spiral galaxy, M83 in the bright [CII] 158 μm, [OI] 63 and 146 μm, [NII] 122 μm, and [OIII] 88 μm fine-structure lines with the Long Wavelength Spectrometer (LWS) on ISO. The maps are nearly fully sampled, and cover the inner 6.75' x 6' region - essentially the entire optical disk. We also obtained a full LWS grating scan of the nucleus. The lines are detectable over the entire disk, and enhanced at the nucleus, where the [OI] 63 μm and [NII] lines are particularly strong. At the nucleus, the line ratios indicate a strong starburst headed by O9 stars. Surprisingly, the [OI] and [CII] line emission (from photodissociation regions) is not enhanced relative to [NII] (from low density HII regions) on the spiral arms. The line ratios are the same for the spiral arms and interarm regions. We find very strong emission in the [OIII] 88 μm, [OI] 146 μm, and [CII] lines at the intersection of the bar and spiral arm to the SW indicating particularly strong star formation activity there. The [OI] 63 μm/146 μm line ratio is quite small there likely the result of self absorption in the 63 μm line by enveloping clouds. The total luminosity of this emission peak is 1.2 x 109 Lodo

Animating the Carbon Cycle

This a post-print, author-produced version of an article accepted for publication in Ecosystems. Copyright © 2013 Springer Science+Business Media New York. The final publication is available at Springer via http://dx.doi.org/10.1007/s10021-013-9715-7Understanding the biogeochemical processes regulating carbon cycling is central to mitigating atmospheric CO2 emissions. The role of living organisms has been accounted for, but the focus has traditionally been on contributions of plants and microbes. We develop the case that fully “animating” the carbon cycle requires broader consideration of the functional role of animals in mediating biogeochemical processes and quantification of their effects on carbon storage and exchange among terrestrial and aquatic reservoirs and the atmosphere. To encourage more hypothesis-driven experimental research that quantifies animal effects we discuss the mechanisms by which animals may affect carbon exchanges and storage within and among ecosystems and the atmosphere. We illustrate how those mechanisms lead to multiplier effects whose magnitudes may rival those of more traditional carbon storage and exchange rate estimates currently used in the carbon budget. Many animal species are already directly managed. Thus improved quantitative understanding of their influence on carbon budgets may create opportunity for management and policy to identify and implement new options for mitigating CO2 release at regional scales.US National Science FoundationNERCBBSRCNippon Foundatio

Integrated multi-modality image-guided navigation for neurosurgery: open-source software platform using state-of-the-art clinical hardware.

PURPOSE: Image-guided surgery (IGS) is an integral part of modern neuro-oncology surgery. Navigated ultrasound provides the surgeon with reconstructed views of ultrasound data, but no commercial system presently permits its integration with other essential non-imaging-based intraoperative monitoring modalities such as intraoperative neuromonitoring. Such a system would be particularly useful in skull base neurosurgery. METHODS: We established functional and technical requirements of an integrated multi-modality IGS system tailored for skull base surgery with the ability to incorporate: (1) preoperative MRI data and associated 3D volume reconstructions, (2) real-time intraoperative neurophysiological data and (3) live reconstructed 3D ultrasound. We created an open-source software platform to integrate with readily available commercial hardware. We tested the accuracy of the system's ultrasound navigation and reconstruction using a polyvinyl alcohol phantom model and simulated the use of the complete navigation system in a clinical operating room using a patient-specific phantom model. RESULTS: Experimental validation of the system's navigated ultrasound component demonstrated accuracy of [Formula: see text] and a frame rate of 25 frames per second. Clinical simulation confirmed that system assembly was straightforward, could be achieved in a clinically acceptable time of [Formula: see text] and performed with a clinically acceptable level of accuracy. CONCLUSION: We present an integrated open-source research platform for multi-modality IGS. The present prototype system was tailored for neurosurgery and met all minimum design requirements focused on skull base surgery. Future work aims to optimise the system further by addressing the remaining target requirements

Knockout studies reveal an important role of <i>plasmodium</i> lipoic acid protein ligase a1 for asexual blood stage parasite survival

Lipoic acid (LA) is a dithiol-containing cofactor that is essential for the function of a-keto acid dehydrogenase complexes. LA acts as a reversible acyl group acceptor and 'swinging arm' during acyl-coenzyme A formation. The cofactor is post-translationally attached to the acyl-transferase subunits of the multienzyme complexes through the action of octanoyl (lipoyl): &lt;i&gt;N&lt;/i&gt;-octanoyl (lipoyl) transferase (LipB) or lipoic acid protein ligases (LplA). Remarkably, apicomplexan parasites possess LA biosynthesis as well as scavenging pathways and the two pathways are distributed between mitochondrion and a vestigial organelle, the apicoplast. The apicoplast-specific LipB is dispensable for parasite growth due to functional redundancy of the parasite's lipoic acid/octanoic acid ligases/transferases. In this study, we show that &lt;i&gt;LplA1&lt;/i&gt; plays a pivotal role during the development of the erythrocytic stages of the malaria parasite. Gene disruptions in the human malaria parasite &lt;i&gt;P.falciparum&lt;/i&gt; consistently were unsuccessful while in the rodent malaria model parasite &lt;i&gt;P. berghei&lt;/i&gt; the &lt;i&gt;LplA1&lt;/i&gt; gene locus was targeted by knock-in and knockout constructs. However, the &lt;i&gt;LplA1&lt;/i&gt; &lt;sup&gt;(-)&lt;/sup&gt; mutant could not be cloned suggesting a critical role of LplA1 for asexual parasite growth &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. These experimental genetics data suggest that lipoylation during expansion in red blood cells largely occurs through salvage from the host erythrocytes and subsequent ligation of LA to the target proteins of the malaria parasite

P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments

Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes

A Novel Assay to Trace Proliferation History In Vivo Reveals that Enhanced Divisional Kinetics Accompany Loss of Hematopoietic Stem Cell Self-Renewal

BACKGROUND: The maintenance of lifelong blood cell production ultimately rests on rare hematopoietic stem cells (HSCs) that reside in the bone marrow microenvironment. HSCs are traditionally viewed as mitotically quiescent relative to their committed progeny. However, traditional techniques for assessing proliferation activity in vivo, such as measurement of BrdU uptake, are incompatible with preservation of cellular viability. Previous studies of HSC proliferation kinetics in vivo have therefore precluded direct functional evaluation of multi-potency and self-renewal, the hallmark properties of HSCs. METHODOLOGY/PRINCIPAL FINDINGS: We developed a non-invasive labeling technique that allowed us to identify and isolate candidate HSCs and early hematopoietic progenitor cells based on their differential in vivo proliferation kinetics. Such cells were functionally evaluated for their abilities to multi-lineage reconstitute myeloablated hosts. CONCLUSIONS: Although at least a few HSC divisions per se did not influence HSC function, enhanced kinetics of divisional activity in steady state preceded the phenotypic changes that accompanied loss of HSC self-renewal. Therefore, mitotic quiescence of HSCs, relative to their committed progeny, is key to maintain the unique functional and molecular properties of HSCs

Eradication of chronic myeloid leukemia stem cells: a novel mathematical model predicts no therapeutic benefit of adding G-CSF to imatinib

Imatinib mesylate induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML), yet many patients have detectable BCR-ABL transcripts in peripheral blood even after prolonged therapy. Bone marrow studies have shown that this residual disease resides within the stem cell compartment. Quiescence of leukemic stem cells has been suggested as a mechanism conferring insensitivity to imatinib, and exposure to the Granulocyte-Colony Stimulating Factor (G-CSF), together with imatinib, has led to a significant reduction in leukemic stem cells in vitro. In this paper, we design a novel mathematical model of stem cell quiescence to investigate the treatment response to imatinib and G-CSF. We find that the addition of G-CSF to an imatinib treatment protocol leads to observable effects only if the majority of leukemic stem cells are quiescent; otherwise it does not modulate the leukemic cell burden. The latter scenario is in agreement with clinical findings in a pilot study administering imatinib continuously or intermittently, with or without G-CSF (GIMI trial). Furthermore, our model predicts that the addition of G-CSF leads to a higher risk of resistance since it increases the production of cycling leukemic stem cells. Although the pilot study did not include enough patients to draw any conclusion with statistical significance, there were more cases of progression in the experimental arms as compared to continuous imatinib. Our results suggest that the additional use of G-CSF may be detrimental to patients in the clinic