Defining Target Volumes for Stereotactic Ablative Radiotherapy of Early-stage Lung Tumours:A Comparison of Three-dimensional F-fluorodeoxyglucose Positron Emission Tomography and Four-dimensional Computed Tomography

Aims: High local control rates are achieved in stage I lung cancer using stereotactic ablative radiotherapy. Target delineation is commonly based on four-dimensional computed tomography (CT) scans. Target volumes defined by positron emission tomography/computed tomography (PET/CT) are compared with those defined by four-dimensional CT and conventional ('three-dimensional') F-fluorodeoxyglucose (F-FDG) PET/CT. Materials and methods: For 16 stage I non-small cell lung cancer tumours, six approaches for deriving PET target volumes were evaluated: manual contouring, standardised uptake value (SUV) absolute threshold of 2.5, 35% of maximum SUV (35%SUV), 41% of SUV (41%SUV) and two different source to background ratio techniques (SBR-1 and SBR-2). PET-derived target volumes were compared with the internal target volume (ITV) from the modified maximum intensity projection (MIP ITV). Volumetric and positional correlation was assessed using the Dice similarity coefficient (DSC). Results: PET-based target volumes did not correspond to four-dimensional CT-based target volumes. The mean DSC relative to MIP ITV were: PET manual = 0.64, SUV2.5 = 0.64, 35%SUV = 0.63, 41%SUV = 0.57. SBR-1 = 0.52, SBR-2 = 0.49. PET-based target volumes were smaller than corresponding MIP ITVs. Conclusions: Conventional three-dimensional F-FDG PET-derived target volumes for lung stereotactic ablative radiotherapy did not correspond well with those derived from four-dimensional CT, including those in routine clinical use (MIP ITV). Caution is required in using three-dimensional PET for motion encompassing target volume delineation. © 2012 The Royal College of Radiologists.

Defining target volumes for stereotactic ablative radiotherapy of early-stage lung tumours: a comparison of three-dimensional 18F-fluorodeoxyglucose positron emission tomography and four-dimensional computed tomography.:PETCT versus 4DCT for SABR in Early Stage NSCLC

AIMS: High local control rates are achieved in stage I lung cancer using
stereotactic ablative radiotherapy. Target delineation is commonly based on
four-dimensional computed tomography (CT) scans. Target volumes defined by
positron emission tomography/computed tomography (PET/CT) are compared with those defined by four-dimensional CT and conventional ('three-dimensional')
(18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT.

MATERIALS AND METHODS: For 16 stage I non-small cell lung cancer tumours, six
approaches for deriving PET target volumes were evaluated: manual contouring,
standardised uptake value (SUV) absolute threshold of 2.5, 35% of maximum SUV
(35%SUV(MAX)), 41% of SUV(MAX) (41%SUV(MAX)) and two different source to
background ratio techniques (SBR-1 and SBR-2). PET-derived target volumes were compared with the internal target volume (ITV) from the modified maximum
intensity projection (MIP(MOD) ITV). Volumetric and positional correlation was
assessed using the Dice similarity coefficient (DSC).

RESULTS: PET-based target volumes did not correspond to four-dimensional CT-based target volumes. The mean DSC relative to MIP(MOD) ITV were: PET manual = 0.64, SUV2.5 = 0.64, 35%SUV(MAX) = 0.63, 41%SUV(MAX) = 0.57. SBR-1 = 0.52, SBR-2 =0.49. PET-based target volumes were smaller than corresponding MIP ITVs.

CONCLUSIONS: Conventional three-dimensional (18)F-FDG PET-derived target volumes for lung stereotactic ablative radiotherapy did not correspond well with those derived from four-dimensional CT, including those in routine clinical use
(MIP(MOD) ITV). Caution is required in using three-dimensional PET for motion
encompassing target volume delineation.

Simultaneously multiply-configurable or superposed molecular logic systems composed of ICT (internal charge transfer) chromophores and fluorophores integrated with one- or two-ion receptors

Integrated "ICT chromophore-receptor" systems show ion-induced shifts in their electronic absorption spectra. The wavelength of observation can be used to reversibly configure the system to any of the four logic operations permissible with a single input (YES, NOT, PASS 1, PASS 0), under conditions of ion input and transmittance output. We demonstrate these with dyes integrated into Tsien's calcium receptor, 1-2. Applying multiple ion inputs to 1-2 also allows us to perform two- or three-input OR or NOR operations. The weak fluorescence output of 1 also shows YES or NOT logic depending on how it is configured by excitation and emission wavelengths. Integrated "receptor(1)-ICT chromophore-receptor(2)" systems 3-5 selectively target two ions into the receptor terminals. The ion-induced transmittance output of 3-5 can also be configured via wavelength to illustrate several logic types including, most importantly, XOR. The opposite effects of the two ions on the energy of the chromophore excited state is responsible for this behaviour. INHIBIT and REVERSE IMPLICATION are two of the other logic types seen here. Integration of XOR logic with a preceding OR operation can be arranged by using three ion inputs. The fluorescence output of these systems can be configured via wavelength to display INHIBIT or NOR logic under two-input conditions. The superposition or multiplicity of logic gate configurations is an unusual consequence of the ability to simultaneously observe multiple wavelengths.

Quantifying the Energy & carbon emissions implications of a 10% electric vehicles target

EU Directive 2009/28/EC on Renewable Energy requires each Member State to ensure 10% of transport energy (excluding aviation and marine transport) comes from renewable sources by 2020 (10% RES-T target). In addition to the anticipated growth in biofuels, this target is expected to be met by the increased electrification of transport coupled with a growing contribution from renewable energy to electricity generation. Energy use in transport accounted for nearly half of Ireland’s total final energy demand and about a third of energy-related carbon dioxide emissions in 2007. Energy use in transport has grown by 6.3% per annum on average in the period 1990 – 2007. This high share and fast growth relative to other countries highlights the challenges Ireland faces in meeting ambitious renewable energy targets. The Irish Government has set a specific target for Electric Vehicles (EV) as part of its strategy to deliver the 10% RES-T target. By 2020, 10% of all vehicles in its transport fleet are to be powered by electricity. This paper quantifies the impacts on energy and carbon dioxide emissions of this 10% EV target by 2020. In order to do this an ‘EV Car Stock’ model was developed to analyse the historical and future make-up of the passenger car portion of the fleet to 2025. Three scenarios for possible take-up in EVs were examined and the associated energy and emissions impacts are quantified. These impacts are then compared to Ireland’s 10% RES-T target and greenhouse gas (GHG) emissions reduction targets for 2020. Two key findings of the study are that the 10% EV target contributes 1.7% to the 10% RES-T target by 2020 and 1.4% to the 20% reduction in Non-ETS emissions by 2020 relative to 2005.

Visual target separation determines the extent of generalisation between opposing visuomotor rotations

Here we investigated the influence of angular separation between visual and motor targets on concurrent adaptation to two opposing visuomotor rotations. We inferred the extent of generalisation between opposing visuomotor rotations at individual target locations based on whether interference (negative transfer) was present. Our main finding was that dual adaptation occurred to opposing visuomotor rotations when each was associated with different visual targets but shared a common motor target. Dual adaptation could have been achieved either within a single sensorimotor map (i.e. with different mappings associated with different ranges of visual input), or by forming two different internal models (the selection of which would be based on contextual information provided by target location). In the present case, the pattern of generalisation was dependent on the relative position of the visual targets associated with each rotation. Visual targets nearest the workspace of the opposing visuomotor rotation exhibited the most interference (i.e. generalisation). When the minimum angular separation between visual targets was increased, the extent of interference was reduced. These results suggest that the separation in the range of sensory inputs is the critical requirement to support dual adaptation within a single sensorimotor mapping.

Fault Diagnosis in Internal Combustion Engines Using Nonlinear Multivariate Statistics

This paper presents a statistical-based fault diagnosis scheme for application to internal combustion engines. The scheme relies on an identified model that describes the relationships between a set of recorded engine variables using principal component analysis (PCA). Since combustion cycles are complex in nature and produce nonlinear relationships between the recorded engine variables, the paper proposes the use of nonlinear PCA (NLPCA). The paper further justifies the use of NLPCA by comparing the model accuracy of the NLPCA model with that of a linear PCA model. A new nonlinear variable reconstruction algorithm and bivariate scatter plots are proposed for fault isolation, following the application of NLPCA. The proposed technique allows the diagnosis of different fault types under steady-state operating conditions. More precisely, nonlinear variable reconstruction can remove the fault signature from the recorded engine data, which allows the identification and isolation of the root cause of abnormal engine behaviour. The paper shows that this can lead to (i) an enhanced identification of potential root causes of abnormal events and (ii) the masking of faulty sensor readings. The effectiveness of the enhanced NLPCA based monitoring scheme is illustrated by its application to a sensor fault and a process fault. The sensor fault relates to a drift in the fuel flow reading, whilst the process fault relates to a partial blockage of the intercooler. These faults are introduced to a Volkswagen TDI 1.9 Litre diesel engine mounted on an experimental engine test bench facility.

Intercepting beats in predesignated target zones

Moving to a rhythm necessitates precise timing between the movement of the chosen limb and the timing imposed by the beats. However, the temporal information specifying the moment when a beat will sound (the moment onto which one must synchronise one's movement) is not continuously provided by the acoustic array. Because of this informational void, the actors need some form of prospective information that will allow them to act sufficiently ahead of time in order to get their hand in the right place at the right time. In this acoustic interception study, where participants were asked to move between two targets in such a way that they arrived and stopped in the target zone at the same time as a beat sounded, we tested a model derived from tau-coupling theory (Lee DN (1998) Ecol Psychol 10:221-250). This model attempts to explain the form of a potential timing guide that specifies the duration of the inter-beat intervals and also describes how this informational guide can be used in the timing and guidance of movements. The results of our first experiment show that, for inter-beat intervals of less than 3 s, a large proportion of the movement (over 70%) can be explained by the proposed model. However, a second experiment, which augments the time between beats so that it surpasses 3 s, shows a marked decline in the percentage of information/movement coupling. A close analysis of the movement kinematics indicates a lack of control and anticipation in the participants' movements. The implications of these findings, in light of other research studies, are discussed.

Synthesis of N3- and 2-NH2-substituted 6,7-diphenylpterins and their use as intermediates for the preparation of oligonucleotide conjugates designed to target photooxidative damage on single-stranded DNA representing the bcr-abl chimeric gene

Two 17-mer oligodeoxynucleotide-5'-linked-(6,7-diphenylpterin) conjugates, 2 and 3, were prepared as photosensitisers for targeting photooxidative damage to a 34-mer DNA oligodeoxynucleotide (ODN) fragment 1 representing the chimeric bcr-abl gene that is implicated in the pathogenesis of chronic myeloid leukaemia (CML). The base sequence in the 17-mer was 3'G G T A G T T A T T C C T T C T T5'. In the first of these ODN conjugates (2) the pterin was attached at its N3 atom, via a -(CH2)3OPO(OH)- linker, to the 5'-OH group of the ODN. Conjugate 2 was prepared from 2-amino-3-(3-hydroxypropyl)-6,7-diphenyl-4(3H)-pteridinone 10, using phosphoramidite methodology. Starting material 10 was prepared from 5-amino-7-methylthiofurazano[3,4-d]pyrimidine 4 via an unusual highly resonance stabilised cation 8, incorporating the rare 2H,6H-pyrimido[6,1-b][1,3]oxazine ring system. In the characterisation of 10 two pteridine phosphazenes, 15 and 29, were obtained, as well as new products containing two uncommon tricyclic ring systems, namely pyrimido[2,1-b]pteridine (20 and 24) and pyrimido[1,2-c]pteridine (27). In the second ODN conjugate the linker was -(CH2)5CONH(CH2)6OPO(OH)- and was attached to the 2-amino group of the pterin. In the preparation of 3, the N-hydroxysuccinimide ester 37 of 2-(5-carboxypentylamino)-6,7-diphenyl-4(3H)-pteridinone was condensed with the hexylamino-modified 17-mer. Excitation of 36 with near UV light in the presence of the single-stranded target 34-mer, 5'T G A C C A T C A A T A A G14 G A A G18 A A G21 C C C T T C A G C G G C C3' 1 caused oxidative damage at guanine bases, leading to alkali-labile sites which were monitored by polyacrylamide gel electrophoresis. Cleavage was observed at all guanine sites with a marked preference for cleavage at G14. In contrast, excitation of ODN-pteridine conjugate 2 in the presence of 1 caused oxidation of the latter predominantly at G18, with a smaller extent of cleavage at G15 and G14 (in the double-stranded portion) and G21. These results contrast with our previous observation of specific cleavage at G21 with ruthenium polypyridyl sensitisers, and suggest that a different mechanism, probably one involving Type 1 photochemical electron transfer, is operative. Much lower yields were found with the ODN-pteridine conjugate 3, perhaps as a consequence of the longer linker between the ODN and the pteridine in this case.

Fgr but not Syk tyrosine kinase is a target for beta2 integrin-induced c-Cbl-mediated ubiquitination in adherent human neutrophils

An early and critical event in beta2 integrin signalling during neutrophil adhesion is activation of Src tyrosine kinases and Syk. In the present study, we report Src kinase-dependent beta2 integrin-induced tyrosine phosphorylation of Cbl occurring in parallel with increased Cbl-associated tyrosine kinase activity. These events concurred with activation of Fgr and, surprisingly, also with dissociation of this Src tyrosine kinase from Cbl. Moreover, the presence of the Src kinase inhibitor PP1 in an in vitro assay had only a limited effect on the Cbl-associated kinase activity. These results suggest that an additional active Src-dependent tyrosine kinase associates with Cbl. The following observations imply that Syk is such a kinase: (i) beta2 integrins activated Syk in a Src-dependent manner, (ii) Syk was associated with Cbl much longer than Fgr was, and (iii) the Syk inhibitor piceatannol (3,4,3´,5´-tetrahydroxy-trans-stilbene) abolished the Cbl-associated kinase activity in an in vitro assay. Effects of the mentioned interactions between these two kinases and Cbl may be related to the finding that Cbl is a ubiquitin E3 ligase. Indeed, we detected beta2 integrin-induced ubiquitination of Fgr that, similar to the phosphorylation of Cbl, was abolished in cells pretreated with PP1. However, the ubiquitination of Fgr did not cause any apparent degradation of the protein. In contrast with Fgr, Syk was not modified by the E3 ligase. Thus Cbl appears to be essential in beta2 integrin signalling, first by serving as a matrix for a subsequent agonist-induced signalling interaction between Fgr and Syk, and then by mediating ubiquitination of Fgr which possibly affects its interaction with Cbl.