The tumor border configuration of colorectal cancer as a histomorphological prognostic indicator.

Histomorphological features of colorectal cancers (CRC) represent valuable prognostic indicators for clinical decision making. The invasive margin is a central feature for prognostication shaped by the complex processes governing tumor-host interaction. Assessment of the tumor border can be performed on standard paraffin sections and shows promise for integration into the diagnostic routine of gastrointestinal pathology. In aggressive CRC, an extensive dissection of host tissue is seen with loss of a clear tumor-host interface. This pattern, termed "infiltrative tumor border configuration" has been consistently associated with poor survival outcome and early disease recurrence of CRC-patients. In addition, infiltrative tumor growth is frequently associated with presence of adverse clinicopathological features and molecular alterations related to aggressive tumor behavior including BRAFV600 mutation. In contrast, a well-demarcated "pushing" tumor border is seen frequently in CRC-cases with low risk for nodal and distant metastasis. A pushing border is a feature frequently associated with mismatch-repair deficiency and can be used to identify patients for molecular testing. Consequently, assessment of the tumor border configuration as an additional prognostic factor is recommended by the AJCC/UICC to aid the TNM-classification. To promote the assessment of the tumor border configuration in standard practice, consensus criteria on the defining features and method of assessment need to be developed further and tested for inter-observer reproducibility. The development of a standardized quantitative scoring system may lay the basis for verification of the prognostic associations of the tumor growth pattern in multivariate analyses and clinical trials. This article provides a comprehensive review of the diagnostic features, clinicopathological associations, and molecular alterations associated with the tumor border configuration in early stage and advanced CRC.

Developmental self-construction and -configuration of functional neocortical neuronal networks.

The prenatal development of neural circuits must provide sufficient configuration to support at least a set of core postnatal behaviors. Although knowledge of various genetic and cellular aspects of development is accumulating rapidly, there is less systematic understanding of how these various processes play together in order to construct such functional networks. Here we make some steps toward such understanding by demonstrating through detailed simulations how a competitive co-operative ('winner-take-all', WTA) network architecture can arise by development from a single precursor cell. This precursor is granted a simplified gene regulatory network that directs cell mitosis, differentiation, migration, neurite outgrowth and synaptogenesis. Once initial axonal connection patterns are established, their synaptic weights undergo homeostatic unsupervised learning that is shaped by wave-like input patterns. We demonstrate how this autonomous genetically directed developmental sequence can give rise to self-calibrated WTA networks, and compare our simulation results with biological data.

Reglucosylation of the Benzoxazinoid DIMBOA with Inversion of Stereochemical Configuration is a Detoxification Strategy in Lepidopteran Herbivores

Benzoxazinoids are chemical defenses against herbivores and are produced by many members of the grass family. These compounds are stored as stable glucosides in plant cells and require the activity of glucosidases to release the corresponding toxic aglucones. In maize leaves, the most abundant benzoxazinoid is (2R)-DIMBOA-Glc, which is converted into the toxic DIMBOA upon herbivory. The ways in which three Spodoptera species metabolize this toxin were investigated. (2S)-DIMBOA-Glc, an epimer of the initial plant compound, was observed in the insect frass, and the associated glucosyltransferase activity was detected in the insect gut tissue. The epimeric glucoside produced by the insect was found to be no longer reactive towards plant glucosidases and thus cannot be converted into a toxin. Stereoselective reglucosylation thus represents a detoxification strategy in Spodoptera species that might help to explain their success as agricultural pests on benzoxazinoid-containing crops.

Tumour border configuration in colorectal cancer: proposal for an alternative scoring system based on the percentage of infiltrating margin.

AIMS Information on tumour border configuration (TBC) in colorectal cancer (CRC) is currently not included in most pathology reports, owing to lack of reproducibility and/or established evaluation systems. The aim of this study was to investigate whether an alternative scoring system based on the percentage of the infiltrating component may represent a reliable method for assessing TBC. METHODS AND RESULTS Two hundred and fifteen CRCs with complete clinicopathological data were evaluated by two independent observers, both 'traditionally' by assigning the tumours into pushing/infiltrating/mixed categories, and alternatively by scoring the percentage of infiltrating margin. With the pushing/infiltrating/mixed pattern method, interobserver agreement (IOA) was moderate (κ = 0.58), whereas with the percentage of infiltrating margins method, IOA was excellent (intraclass correlation coefficient of 0.86). A higher percentage of infiltrating margin correlated with adverse features such as higher grade (P = 0.0025), higher pT (P = 0.0007), pN (P = 0.0001) and pM classification (P = 0.0063), high-grade tumour budding (P < 0.0001), lymphatic invasion (P < 0.0001), vascular invasion (P = 0.0032), and shorter survival (P = 0.0008), and was significantly associated with an increased probability of lymph node metastasis (P < 0.001). CONCLUSIONS Information on TBC gives additional prognostic value to pathology reports on CRC. The novel proposed scoring system, by using the percentage of infiltrating margin, outperforms the 'traditional' way of reporting TBC. Additionally, it is reproducible and simple to apply, and can therefore be easily integrated into daily diagnostic practice.

A prospective, randomized, controlled study using OsseoSpeed™ implants placed in maxillary fresh extraction socket: soft tissues response

PURPOSE The aim of this work was to study the peri-implant soft tissues response, by evaluating both the recession and the papilla indexes, of patients treated with implants with two different configurations. In addition, data were stratified by tooth category, smoking habit and thickness of buccal bone wall. MATERIALS AND METHODS The clinical trial was designed as a prospective, randomized-controlled multicenter study. Adults in need of one or more implants replacing teeth to be removed in the maxilla within the region 15-25 were recruited. Following tooth extraction, the site was randomly allocated to receive either a cylindrical or conical/cylindrical implant. The following parameters were studied: (i) Soft tissue recession (REC) measured by comparing the gingival zenith (GZ) score at baseline (permanent restoration) with that of the yearly follow-up visits over a period of 3 years (V1, V2 and V3). (ii) Interdental Papilla Index (PI): PI measurements were performed at baseline and compared with that of the follow-up visits. In addition, data were stratified by different variables: tooth category: anterior (incisors and canine) and posterior (first and second premolar); smoking habit: patient smoker (habitual or occasional smoker at inclusion) or non-smoker (non-smoker or ex-smoker at inclusion) and thickness of buccal bone wall (TB): TB ≤ 1 mm (thin buccal wall) or TB > 1 mm (thick buccal wall). RESULTS A total of 93 patients were treated with 93 implants. At the surgical re-entry one implant was mobile and then removed; moreover, one patient was lost to follow-up. Ninety-one patients were restored with 91 implant-supported permanent single crowns. After the 3-year follow-up, a mean gain of 0.23 mm of GZ was measured; moreover, 79% and 72% of mesial and distal papillae were classified as >50%/ complete, respectively. From the stratification analysis, not significant differences were found between the mean GZ scores of implants with TB ≤ 1 mm (thin buccal wall) and TB > 1 mm (thick buccal wall), respectively (P < 0.05, Mann-Whitney U-test) at baseline, at V1, V2 and V3 follow-up visits. Also, the other variables did not seem to influence GZ changes over the follow-up period. Moreover, a re-growth of the interproximal mesial and distal papillae was the general trend observed independently from the variables studied. CONCLUSIONS Immediate single implant treatment may be considered a predictable option regarding soft tissue stability over a period of 3 years of follow-up. An overall buccal soft tissue stability was observed during the GZ changes from the baseline to the 3 years of follow-up with a mean GZ reduction of 0.23 mm. A nearly full papillary re-growth can be detectable over a minimum period of 2 years of follow-up for both cylindrical and conical/cylindrical implants. Both the interproximal papilla filling and the midfacial mucosa stability were not influenced by variables such as type of fixture configuration, tooth category, smoke habit, and thickness of buccal bone wall of ≤ 1 mm (thin buccal wall).

Aortic morphometry at endograft position as assessed by 3D image analysis affects risk of type I endoleak formation after TEVAR

PURPOSE The purpose of this study was to identify morphologic factors affecting type I endoleak formation and bird-beak configuration after thoracic endovascular aortic repair (TEVAR). METHODS Computed tomography (CT) data of 57 patients (40 males; median age, 66 years) undergoing TEVAR for thoracic aortic aneurysm (34 TAA, 19 TAAA) or penetrating aortic ulcer (n = 4) between 2001 and 2010 were retrospectively reviewed. In 28 patients, the Gore TAG® stent-graft was used, followed by the Medtronic Valiant® in 16 cases, the Medtronic Talent® in 8, and the Cook Zenith® in 5 cases. Proximal landing zone (PLZ) was in zone 1 in 13, zone 2 in 13, zone 3 in 23, and zone 4 in 8 patients. In 14 patients (25%), the procedure was urgent or emergent. In each case, pre- and postoperative CT angiography was analyzed using a dedicated image processing workstation and complimentary in-house developed software based on a 3D cylindrical intensity model to calculate aortic arch angulation and conicity of the landing zones (LZ). RESULTS Primary type Ia endoleak rate was 12% (7/57) and subsequent re-intervention rate was 86% (6/7). Left subclavian artery (LSA) coverage (p = 0.036) and conicity of the PLZ (5.9 vs. 2.6 mm; p = 0.016) were significantly associated with an increased type Ia endoleak rate. Bird-beak configuration was observed in 16 patients (28%) and was associated with a smaller radius of the aortic arch curvature (42 vs. 65 mm; p = 0.049). Type Ia endoleak was not associated with a bird-beak configuration (p = 0.388). Primary type Ib endoleak rate was 7% (4/57) and subsequent re-intervention rate was 100%. Conicity of the distal LZ was associated with an increased type Ib endoleak rate (8.3 vs. 2.6 mm; p = 0.038). CONCLUSIONS CT-based 3D aortic morphometry helps to identify risk factors of type I endoleak formation and bird-beak configuration during TEVAR. These factors were LSA coverage and conicity within the landing zones for type I endoleak formation and steep aortic angulation for bird-beak configuration.

Highly stereoselective decarboxylation of (+)-1-Bromo-1-chloro-2,2,2-trifluoropropanoic acid gives (+)-1-Bromo-1-chloro-2,2,2-trifluoroethane ((+)-Halothane) with retention of configuration

The absolute configuration of the title acid (2) has been determined to be S by X-ray crystallography. Thus, decarboxylation of 2 produces (S)-(+)-halothane with 99% retention of configuration. This behavior is compared to other stereoselective decarboxylation reactions of ?-haloacids from the literature that also give high degrees of retention of configuration when in the form of their quaternary ammonium salts, which contain one proton. The proton of the ammonium salt is necessary to protonate the anionic intermediate formed from decarboxylation. In the absence of this relatively acidic proton, we had previously found that using triethylene glycol (TEG) as both solvent and proton source for the decarboxylation reaction of acid 2 caused poor stereoselectivity. This was in contrast to 1,2,2,2-tetrafluoro-1-methoxypropionic acid (6), which showed a high degree of retention of configuration in TEG. To rationalize this differing behavior we report DFT studies at PCM-B3LYP/6-31++G** level of theory (the results were additionally confirmed with 6-311++G** and aug-cc-pVDZ basis sets). The energy barrier to inversion of configuration of the anionic reaction intermediate of acid 2 (11) is 10.23 kcal/mol. However, we find that the anionic intermediate from acid 6 (10) would rather undergo ?-elimination instead of inversion of configuration. Thus the planar transition state required for inversion of configuration is never reached, regardless of the rate of proton transfer to the anion.

Development of Efficient Techniques for the Analysis and Design of Antennas in Dual-Reflectarray Configuration

This thesis contributes to the analysis and design of printed reflectarray antennas. The main part of the work is focused on the analysis of dual offset antennas comprising two reflectarray surfaces, one of them acts as sub-reflector and the second one acts as mainreflector. These configurations introduce additional complexity in several aspects respect to conventional dual offset reflectors, however they present a lot of degrees of freedom that can be used to improve the electrical performance of the antenna. The thesis is organized in four parts: the development of an analysis technique for dualreflectarray antennas, a preliminary validation of such methodology using equivalent reflector systems as reference antennas, a more rigorous validation of the software tool by manufacturing and testing a dual-reflectarray antenna demonstrator and the practical design of dual-reflectarray systems for some applications that show the potential of these kind of configurations to scan the beam and to generate contoured beams. In the first part, a general tool has been implemented to analyze high gain antennas which are constructed of two flat reflectarray structures. The classic reflectarray analysis based on MoM under local periodicity assumption is used for both sub and main reflectarrays, taking into account the incident angle on each reflectarray element. The incident field on the main reflectarray is computed taking into account the field radiated by all the elements on the sub-reflectarray.. Two approaches have been developed, one which employs a simple approximation to reduce the computer run time, and the other which does not, but offers in many cases, improved accuracy. The approximation is based on computing the reflected field on each element on the main reflectarray only once for all the fields radiated by the sub-reflectarray elements, assuming that the response will be the same because the only difference is a small variation on the angle of incidence. This approximation is very accurate when the reflectarray elements on the main reflectarray show a relatively small sensitivity to the angle of incidence. An extension of the analysis technique has been implemented to study dual-reflectarray antennas comprising a main reflectarray printed on a parabolic surface, or in general in a curved surface. In many applications of dual-reflectarray configurations, the reflectarray elements are in the near field of the feed-horn. To consider the near field radiated by the horn, the incident field on each reflectarray element is computed using a spherical mode expansion. In this region, the angles of incidence are moderately wide, and they are considered in the analysis of the reflectarray to better calculate the actual incident field on the sub-reflectarray elements. This technique increases the accuracy for the prediction of co- and cross-polar patterns and antenna gain respect to the case of using ideal feed models. In the second part, as a preliminary validation, the proposed analysis method has been used to design a dual-reflectarray antenna that emulates previous dual-reflector antennas in Ku and W-bands including a reflectarray as subreflector. The results for the dualreflectarray antenna compare very well with those of the parabolic reflector and reflectarray subreflector; radiation patterns, antenna gain and efficiency are practically the same when the main parabolic reflector is substituted by a flat reflectarray. The results show that the gain is only reduced by a few tenths of a dB as a result of the ohmic losses in the reflectarray. The phase adjustment on two surfaces provided by the dual-reflectarray configuration can be used to improve the antenna performance in some applications requiring multiple beams, beam scanning or shaped beams. Third, a very challenging dual-reflectarray antenna demonstrator has been designed, manufactured and tested for a more rigorous validation of the analysis technique presented. The proposed antenna configuration has the feed, the sub-reflectarray and the main-reflectarray in the near field one to each other, so that the conventional far field approximations are not suitable for the analysis of such antenna. This geometry is used as benchmarking for the proposed analysis tool in very stringent conditions. Some aspects of the proposed analysis technique that allow improving the accuracy of the analysis are also discussed. These improvements include a novel method to reduce the inherent cross polarization which is introduced mainly from grounded patch arrays. It has been checked that cross polarization in offset reflectarrays can be significantly reduced by properly adjusting the patch dimensions in the reflectarray in order to produce an overall cancellation of the cross-polarization. The dimensions of the patches are adjusted in order not only to provide the required phase-distribution to shape the beam, but also to exploit the crosses by zero of the cross-polarization components. The last part of the thesis deals with direct applications of the technique described. The technique presented is directly applicable to the design of contoured beam antennas for DBS applications, where the requirements of cross-polarisation are very stringent. The beam shaping is achieved by synthesithing the phase distribution on the main reflectarray while the sub-reflectarray emulates an equivalent hyperbolic subreflector. Dual-reflectarray antennas present also the ability to scan the beam over small angles about boresight. Two possible architectures for a Ku-band antenna are also described based on a dual planar reflectarray configuration that provides electronic beam scanning in a limited angular range. In the first architecture, the beam scanning is achieved by introducing a phase-control in the elements of the sub-reflectarray and the mainreflectarray is passive. A second alternative is also studied, in which the beam scanning is produced using 1-bit control on the main reflectarray, while a passive subreflectarray is designed to provide a large focal distance within a compact configuration. The system aims to develop a solution for bi-directional satellite links for emergency communications. In both proposed architectures, the objective is to provide a compact optics and simplicity to be folded and deployed.

Reduction of truncation errors in planar, cylindrical and partial spherical near-field antenna measurements

A method to reduce truncation errors in near-field antenna measurements is presented. The method is based on the Gerchberg-Papoulis iterative algorithm used to extrapolate band-limited functions and it is able to extend the valid region of the calculated far-field pattern up to the whole forward hemisphere. The extension of the valid region is achieved by the iterative application of a transformation between two different domains. After each transformation, a filtering process that is based on known information at each domain is applied. The first domain is the spectral domain in which the plane wave spectrum (PWS) is reliable only within a known region. The second domain is the field distribution over the antenna under test (AUT) plane in which the desired field is assumed to be concentrated on the antenna aperture. The method can be applied to any scanning geometry, but in this paper, only the planar, cylindrical, and partial spherical near-field measurements are considered. Several simulation and measurement examples are presented to verify the effectiveness of the method.

Bubble growth by injection of gas into viscous liquids in cylindrical and conical tubes.

The laminar low Mach number flow of a gas in a tube is analyzed for very small and very large values of the inlet-to-wall temperature ratio. When this ratio tends to zero, pressure forces confine the cold gas to a thin core around the axis of the tube. This core is neatly bounded by an ablation front that consumes it at a finite distance from the tube inlet. When the temperature ratio tends to infinity, the temperature of the gas increases smoothly from the wall to the axis of the tube and the shear stress and heat flux are positive at the wall despite the fact that the viscosity and thermal conductivity of the gas scaled with their inlet values tend to zero at the wall.

An Autonomous Engine for Services Configuration and Deployment.

The runtime management of the infrastructure providing service-based systems is a complex task, up to the point where manual operation struggles to be cost effective. As the functionality is provided by a set of dynamically composed distributed services, in order to achieve a management objective multiple operations have to be applied over the distributed elements of the managed infrastructure. Moreover, the manager must cope with the highly heterogeneous characteristics and management interfaces of the runtime resources. With this in mind, this paper proposes to support the configuration and deployment of services with an automated closed control loop. The automation is enabled by the definition of a generic information model, which captures all the information relevant to the management of the services with the same abstractions, describing the runtime elements, service dependencies, and business objectives. On top of that, a technique based on satisfiability is described which automatically diagnoses the state of the managed environment and obtains the required changes for correcting it (e.g., installation, service binding, update, or configuration). The results from a set of case studies extracted from the banking domain are provided to validate the feasibility of this proposa

Impulsive motions of the floating zone

A set of problems concerning the behaviour of a suddenly disturbed ideal floating zone is considered. Mathematical techniques of asymptotic expansions arc used to solve these problems. It is seen that many already available solutions, most of them concerning liquids enclosed in cavities, will be regarded as starting approximations which are valid except in the proximity of the free surface which laterally bounds the floating zone. In particular, the problem of the linear spin-up of an initially cylindrical floating zone is considered in some detail. The presence of a recircuiating fluid pattern near the free surface is detected. This configuration is attributed to the interplay between Coriolis forces and the azimuthal component of the viscous forces.