The effect of FASN inhibition on the growth and metabolism of a cisplatin-resistant ovarian carcinoma model.

Overexpression of fatty acid synthase (FASN), a key regulator of the de novo synthesis of fatty acids, has been demonstrated in a variety of cancers and is associated with poor prognosis and increased multidrug resistance. Inhibition of FASN with the anti-obesity drug orlistat has been shown to have significant anti-tumourigenic effects in many cancers, notably breast and prostate. In our study, we investigated whether FASN inhibition using orlistat is an effective adjunctive treatment for ovarian cancers that have become platinum resistant using a cisplatin-resistant ovarian tumour xenograft model in mice. Mice were treated with orlistat or cisplatin or a combination and metabolite analysis and histopathology were performed on the tumours ex vivo. Orlistat decreased tumour fatty acid metabolism by inhibiting FASN, cisplatin reduced fatty acid β-oxidation, and combination treatment delayed tumour growth and induced apoptotic and necrotic cell death in cisplatin-resistant ovarian cancer cells over and above that with either treatment alone. Combination treatment also decreased glutamine metabolism, nucleotide and glutathione biosynthesis and fatty acid β-oxidation. Our data suggest that orlistat chemosensitised platinum-resistant ovarian cancer to treatment with platinum and resulted in enhanced efficacy

Analysis of spatial variability for the development of reduced lead body surface maps

The spatial frequency of measurement points from standard ECG systems lacks accuracy to diagnose local variability in cardiac activity on the torso. Body Surface Mapping (BSM) improves this accuracy, but lacks the simplicity to be implemented in clinic on a regular basis. Reduced-lead BSM system improves applicability, but currently no standardization of lead reduction has been agreed upon. This research investigates the reduction of BSMs based on Lomb-Scargle Spectral Analysis to determine an appropriate electrode positioning through spatial frequency assessment. Based on the measurement of 13 healthy volunteers, a 128 electrode system could be reduced to a 36 electrode system and an 84 electrode system for ventricular and atrial activity measurements, respectively, with up to 10% loss of the full information provided by the original body surface potential map. Further research will investigate the appropriate positions of these electrodes and the effect of lead reduction for various cardiac abnormalities

Emanuele Tesauro nos trópicos: caminhos de uma tradução e crítica teórico-histórica em Organização do Conhecimento

After a series of historical-epistemological studies, focused on the Knowledge Organization (KO), which call attention to the thought of Emanuele Tesauro, a seventeenth-century theoretician, the urgency of bringing to discussion about the importance of translation, as a way of updating, his work. The present reflection tries to understand the Brazilian studies on Tesauro developed centrally in the last years, from the epistemological-historical perspective and the philosophy of the language, leading to the (necessary) interpretative experience of translation of the theoretical. The corpus of the proposal is focused on the introductory paragraph of the Categorical Index, a discourse that places Tesauro at the heart of the historical construction of the KO and, at the same time, at the forefront of the challenges of innovation in the contemporary domain. The Tesaurian Index is present in the third chapter, “Cagioni Instrumentali delle argutezze oratorie simboliche et lapidarie”, of his work Il Cannocchiale Aristotelico, published in 1670, an essential treatise for the modern understanding of metaphor as a possibility of understanding the world through language. One of the ways to enable this theoretical and epistemological deepening is the translation of his work, which can be considered a way of interpretation and updating, since it is a work of the seventeenth century. Starting from the point of view that the translation is an exercise of communication between different languages, epochs, histories, finally, cultures, that is to relate the meaning of a word with other words that do not belong to the same culture, the work was done involving four phases: definition of the scope of translation focusing on the relationship between Tesauro and KO, reaching the Categorical Index; first contact with the work with appropriation of the Introduction and the Categorical Index; translation proper, which corresponds to the creative part of the translation; evaluation of the translation in light of the KO lexicon. The Tesauro’s research practice and its work in KO seems immediately adherent, mainly by the (co) incidence of the name between subject and instrument (documentary language). The Tesauro’s metalinguistic character evokes not only a way of understanding Aristotelian rhetoric, but of establishing a writing practice, as well as, together with the presentation of the method of such a practice, filled with the interweaving of information, concepts, practices. This is, in short, Emanuele's twist: he is using logical (analytic-conceptual) Aristotle, but under a rhetorical (discursive) Aristotle's theory to indicate the dynamics of words in relation to things. With epistemological-historical lenses, focused on the constant instance of recontextualization, via the slow and necessary process of translation, Tesauro's thinking opens up, establishing itself not only as adherent, but as co-founder (among many margins of theoretical construction of the domain) of the OC. From the metaphorical plane, we can see that Emanuele Tesauro enters the heart of the most difficult and instigating dilemmas, current and historical, of the KO itself

Dynamical tunneling in molecules: Quantum routes to energy flow

Dynamical tunneling, introduced in the molecular context, is more than two decades old and refers to phenomena that are classically forbidden but allowed by quantum mechanics. On the other hand the phenomenon of intramolecular vibrational energy redistribution (IVR) has occupied a central place in the field of chemical physics for a much longer period of time. Although the two phenomena seem to be unrelated several studies indicate that dynamical tunneling, in terms of its mechanism and timescales, can have important implications for IVR. Examples include the observation of local mode doublets, clustering of rotational energy levels, and extremely narrow vibrational features in high resolution molecular spectra. Both the phenomena are strongly influenced by the nature of the underlying classical phase space. This work reviews the current state of understanding of dynamical tunneling from the phase space perspective and the consequences for intramolecular vibrational energy flow in polyatomic molecules.Comment: 37 pages and 23 figures (low resolution); Int. Rev. Phys. Chem. (Review to appear in Oct. 2007

Hydrography and water masses in the southeastern Arabian Sea during March-June 2003

This paper describes the hydrographic observations in the southeastern Arabian Sea (SEAS) during two cruises carried out in March-June 2003 as part of the Arabian Sea Monsoon Experiment. The surface hydrography during March-April was dominated by the intrusion of low-salinity waters from the south; during May-June, the low-salinity waters were beginning to be replaced by the high-salinity waters from the north. There was considerable mixing at the bottom of the surface mixed layer, leading to interleaving of low-salinity and high-salinity layers. The flow paths constructed following the spatial patterns of salinity along the sections mimic those inferred from numerical models. Time-series measurements showed the presence of Persian Gulf and Red Sea Waters in the SEAS to be intermittent during both cruises: they appeared and disappeared during both the fortnight-long time series

A platform to guide catheter ablation of persistent atrial fibrillation using dominant frequency mapping

Dominant frequency (DF) mapping has been widely used to study the pathophysiology of atrial fibrillation (AF). In this study, a DF mapping system was developed to guide catheter ablation on electro-physiology (EP) procedures of persistent AF patients. The proposed platform has an automated graphical user interface (GUI) that processes non-contact unipolar electrograms (EGMs) recorded simultaneously by St. Jude Ensite Velocity System and provides 3D representation of the left atrium with DF behaviours and phase analysis

Spatiotemporal behaviour of high dominant frequency during persistent atrial fibrillation

Atrial electrograms (EGMs) with high dominant frequency (DF) are believed to represent atrial substrates with periodic activation responsible for the maintenance of persistent atrial fibrillation (persAF). This study aimed to assess the DF spatiotemporal behavior using high density noncontact mapping in persAF. For 8 patients undergoing left atrial (LA) persAF ablation, 2048 noncontact virtual unipolar EGMs were simultaneously collected and after the removal of ventricular far-field activity, Fourier based spectral analysis was used to identify DF on each EGM. Atrial areas with the highest DF (HDF, DF ± 0.25 Hz) were delimited in each frame for all EGMs, creating HDF `clouds'. Cumulative HDF clouds found at each frame were counted in the 3-D LA representation. To further assess the temporal stability of the cloud, the number of EGMs not hosting any HDF was determined for each window over time. The results show the number of occurrences of HDF clouds in the LA. The temporal behavior was analyzed by counting the number of positions on the 3-D representation of the LA not visited by HDF along time. Our results show HDF in persAF is not temporally stable and spatial distribution throughout the atria suggests the existence of driver regions with very rapid and regular activity maintaining AF. Therefore mapping the cumulative HDF might be an interesting strategy for ablation

Dynamic behavior of rotors during human persistent atrial fibrillation as observed using non-contact mapping

Rotors have been related to atrial fibrillation (AF) maintenance. We analyzed the behavior of rotors in persistent AF (persAF) utilizing a novel non-contact methodology and compared this to real time dominant frequency (DF) analysis. 2048 noncontact virtual unipolar atrial electrograms (VEGMs) were collected simultaneously (EnSite Array, St. Jude Medical) from 10 persAF patients (duration: 34 ± 25 months) undergoing left atrial (LA) ablation. After QRST-removal, FFT was used to identify the global DF of the LA (range 4-10 Hz; 1 s time-window; 50 % overlap; highest DF (HDF) (DF -0.25 Hz); up to 20 s/patient). The organization index (OI) was measured and phase was found via Hilbert-transform. Phase singularities (PSs) were tracked and were categorized according to their lifespan into short (lifespan 100 ms). A total of 4578 PSs were tracked. 5.05 % (IQR: 2.75 ~ 30.25 %) of the tracked PSs were long-lived and were observed in 11 % (IQR: 2.75 ~ 17.5 %) of the windows. The windows with rotors showed significantly higher HDF (mean ± SD, 8.0 ± 0.43 Hz vs 7.71 ± 0.50 Hz, p<; 0.0001) and lower OI (0.76 ± 0.04 vs 0.79 ± 0.03, p<; 0.0001) when compared with the short-lived PSs windows. During persAF, the LA showed distinct behaviors as characterized by rotors. Often, no rotors were observed during sustained AF and, when present, the rotors continually switched between organized and disorganized behaviors. Long-lived rotors correlated with higher atrial rates. Our results suggest that rotors are not the sole perpetuating mechanism in persAF