Molecular imaging of metabolism in cancer metastasis

Cancer progression is characterised by extensive metabolic reprogramming. Renewed enthusiasm in this field has been sparked in part by the realisation that metabolic pathways, oncogenes and tumour suppressors are intimately linked and regulate tumour growth and metastasis through complex reciprocal interactions. The identification of key pathways and enzymes regulating metabolism in cancer cells provides new opportunities for cancer therapy. This has motivated the development of several specific inhibitors targeting metabolic pathways and their therapeutic evaluation in pre-clinical models or in cancer patients. The unravelling of metabolic pathways associated with cancer progression has also highlighted the extensive metabolic heterogeneity that exists between, and within, each cancer type as well as between metastatic sites. The translation of these findings into personalised therapy remains a considerable challenge. To this end, the use of positron emission tomography to non-invasively visualise tumour metabolism is likely to facilitate the implementation of and assessment of new targeted therapies. Here, we briefly review the key metabolic changes associated with cancer progression and discuss recent advances in the field of positron emission tomography for metabolic imaging of cancer and their potential to improve the clinical management of cancer patients

Accelerated convergence of neural network system identification algorithms via principal component analysis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76898/1/AIAA-1998-4440-926.pd

MACE II - A Space Shuttle experiment for investigating adaptive control of flexible spacecraft

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76987/1/AIAA-1998-4319-483.pd

A Survey of Hydroxyl Toward Supernova Remnants: Evidence for Extended 1720 MHz Maser Emission

We present the results of GBT observations of all four ground-state hydroxyl (OH) transitions toward 15 supernova remnants (SNRs) which show OH(1720 MHz) maser emission. This species of maser is well established as an excellent tracer of an ongoing interaction between the SNR and dense molecular material. For the majority of these objects we detect significantly higher flux densities with a single dish than has been reported with interferometric observations. We infer that spatially extended, low level maser emission is a common phenomenon that traces the large-scale interaction in maser-emitting SNRs. Additionally we use a collisional pumping model to fit the physical conditions under which OH is excited behind the SNR shock front. We find the observed OH gas associated with the SNR interaction having columns less than approximately 10^17 per square cm, temperatures of 20 to 125 K, and densities 10^5 per cubic cm.Comment: 24 pages, 23 figures, Accepted to ApJ, March 26, 2008; v2 - added Figure 6, minor clarifications to text in Sections 3 and

Promising pre-clinical validation of targeted radionuclide therapy using a [131I] labelled iodoquinoxaline derivative for an effective melanoma treatment

Targeted internal radionuclide therapy (TRT) would be an effective alternative to current therapies for dissemi- nated melanoma treatment. At our institution, a class of iodobenzamides has been developed as potent melanoma- seeking agents. This review described the preclinical vali- dations of a quinoxaline derivative molecule (ICF01012) as tracer for TRT application. It was selected for its high, specific and long-lasting uptake in tumour with rapid clear- ance from non-target organs providing suitable dosimetry parameters for TRT. Extended in vivo study of metabolic profiles confirmed durable tumoural concentration of the unchanged molecule form. Moreover melanin specificity of ICF01012 was determined by binding assay with syn- thetic melanin and in vivo by SIMS imaging. Then, we showed in vivo that [131I] ICF01012 treatment drastically inhibited growth of B16F0, B16Bl6 and M4Beu tumours whereas [131I] NaI or unlabelled ICF01012 treatment was without significant effect. Histological analysis showed that residual tumour cells exhibit a significant loss of aggres- siveness after treatment. This anti-tumoural effect was associated with a lengthening of the treated-mice survival time and an inhibition of lung dissemination for B16Bl6 model. Results presented here support the concept of TRT using a [131I] labelled iodoquinoxaline derivative for an effective melanoma treatment.<br /

GBT Observations of IC 443: the Nature of OH(1720 MHz) Masers and OH Absorption

We present results of spectral line observations of the ground state transitions of hydroxyl(OH) toward supernova remnant IC 443 carried out with the Green Bank Telescope. At a spatial resolution of 7.2 arcminutes we detect weak, extended OH(1720 MHz) maser emission with OH(1667/5,1612 MHz) absorption along the southern extent of the remnant, where no bright compact maser sources have been observed previously. These newly detected SNR-type masers are coincident with known molecular clumps and a ridge of shocked molecular hydrogen indicative of the SNR shock front interacting with the adjacent molecular cloud. Simultaneous observation of all four ground-state transitions of OH permits us to fit physical conditions of the shocked gas at the interaction site. A simple two-component model for the line profiles yields the physical parameters for detected regions of maser emission including excitation temperature, OH column density and filling factor. Observed line profiles suggest the shock is largely propagating toward the line-of-sight in the region of these newly identified weak masers. The implications of shock geometry and physical parameters in producing extended OH maser emission in SNRs are explored. We also present VLA radio continuum observations at 330 MHz for comparison with OH line observations of the remnant.Comment: 20 pages, 4 figures, 3 tables, submitted to Ap

Ordering phenomena in quasi one-dimensional organic conductors

Low-dimensional organic conductors could establish themselves as model systems for the investigation of the physics in reduced dimensions. In the metallic state of a one-dimensional solid, Fermi-liquid theory breaks down and spin and charge degrees of freedom become separated. But the metallic phase is not stable in one dimension: as the temperature is reduced, the electronic charge and spin tend to arrange themselves in an ordered fashion due to strong correlations. The competition of the different interactions is responsible for which broken-symmetry ground state is eventually realized in a specific compound and which drives the system towards an insulating state. Here we review the various ordering phenomena and how they can be identified by optic and magnetic measurements. While the final results might look very similar in the case of a charge density wave and a charge-ordered metal, for instance, the physical cause is completely different. When density waves form, a gap opens in the density of states at the Fermi energy due to nesting of the one-dimension Fermi surface sheets. When a one-dimensional metal becomes a charge-ordered Mott insulator, on the other hand, the short-range Coulomb repulsion localizes the charge on the lattice sites and even causes certain charge patterns. We try to point out the similarities and conceptional differences of these phenomena and give an example for each of them. Particular emphasis will be put on collective phenomena which are inherently present as soon as ordering breaks the symmetry of the system.Comment: Review article Naturwissenschaften 200

Machine Learning in Automated Text Categorization

The automated categorization (or classification) of texts into predefined categories has witnessed a booming interest in the last ten years, due to the increased availability of documents in digital form and the ensuing need to organize them. In the research community the dominant approach to this problem is based on machine learning techniques: a general inductive process automatically builds a classifier by learning, from a set of preclassified documents, the characteristics of the categories. The advantages of this approach over the knowledge engineering approach (consisting in the manual definition of a classifier by domain experts) are a very good effectiveness, considerable savings in terms of expert manpower, and straightforward portability to different domains. This survey discusses the main approaches to text categorization that fall within the machine learning paradigm. We will discuss in detail issues pertaining to three different problems, namely document representation, classifier construction, and classifier evaluation.Comment: Accepted for publication on ACM Computing Survey

The Relation Between the Surface Brightness and the Diameter for Galactic Supernova Remnants

In this work, we have constructed a relation between the surface brightness ($\Sigma$) and diameter (D) of Galactic C- and S-type supernova remnants (SNRs). In order to calibrate the $\Sigma$-D dependence, we have carefully examined some intrinsic (e.g. explosion energy) and extrinsic (e.g. density of the ambient medium) properties of the remnants and, taking into account also the distance values given in the literature, we have adopted distances for some of the SNRs which have relatively more reliable distance values. These calibrator SNRs are all C- and S-type SNRs, i.e. F-type SNRs (and S-type SNR Cas A which has an exceptionally high surface brightness) are excluded. The Sigma-D relation has 2 slopes with a turning point at D=36.5 pc: $\Sigma$(at 1 GHz)=8.4$^{+19.5}_{-6.3}$$\times10^{-12}$ D$^{{-5.99}^{+0.38}_{-0.33}}$ Wm$^{-2}$Hz$^{-1}$ster$^{-1}$ (for $\Sigma$$\le3.7\times10^{-21}$ Wm$^{-2}$Hz$^{-1}$ster$^{-1}$ and D$\ge$36.5 pc) and $\Sigma$(at 1 GHz)=2.7$^{+2.1}_{-1.4}$$\times$ 10$^{-17}$ D$^{{-2.47}^{+0.20}_{-0.16}}$ Wm$^{-2}$Hz$^{-1}$ster$^{-1}$ (for $\Sigma$$>3.7\times10^{-21}$ Wm$^{-2}$Hz$^{-1}$ster$^{-1}$ and D$<$36.5 pc). We discussed the theoretical basis for the $\Sigma$-D dependence and particularly the reasons for the change in slope of the relation were stated. Added to this, we have shown the dependence between the radio luminosity and the diameter which seems to have a slope close to zero up to about D=36.5 pc. We have also adopted distance and diameter values for all of the observed Galactic SNRs by examining all the available distance values presented in the literature together with the distances found from our $\Sigma$-D relation.Comment: 45 pages, 2 figures, accepted for publication in Astronomical and Astrophysical Transaction

SRAO CO Observation of 11 Supernova Remnants in l = 70 to 190 deg

We present the results of 12CO J = 1-0 line observations of eleven Galactic supernova remnants (SNRs) obtained using the Seoul Radio Astronomy Observatory (SRAO) 6-m radio telescope. The observation was made as a part of the SRAO CO survey of SNRs between l = 70 and 190 deg, which is intended to identify SNRs interacting with molecular clouds. The mapping areas for the individual SNRs are determined to cover their full extent in the radio continuum. We used halfbeam grid spacing (60") for 9 SNRs and full-beam grid spacing (120") for the rest. We detected CO emission towards most of the remnants. In six SNRs, molecular clouds showed a good spatial relation with their radio morphology, although no direct evidence for the interaction was detected. Two SNRs are particularly interesting: G85.4+0.7, where there is a filamentary molecular cloud along the radio shell, and 3C434.1, where a large molecular cloud appears to block the western half of the remnant. We briefly summarize the results obtained for individual SNRs.Comment: Accepted for publication in Astrophysics & Space Science. 12 pages, 12 figures, and 3 table