Conditioned facilitation of brain reward function after repeated cocaine administration.

Cocaine lowers brain reward thresholds, reflecting increased brain reward function. The authors investigated whether, similar to acute cocaine administration, cocaine-predictive conditioned stimuli would lower intracranial self-stimulation (ICSS) thresholds. Rats received a saline injection for 5 days, a cocaine injection (10 mg/kg) for 20 consecutive days, then saline for 5 additional days. Thresholds were measured immediately before and 10 min after each injection. The initial 5 saline injections had no effect on thresholds, whereas cocaine significantly lowered thresholds for 20 days. There was no tolerance or sensitization to this effect of cocaine over days. During the last 5 days when cocaine administration was substituted with saline, rats demonstrated a conditioned lowering of thresholds during the 2nd daily ICSS session. These data demonstrate that cocaine-predictive conditioned stimuli induce a conditioned facilitation of brain reward function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Applying model-driven engineering to the development of Rich Internet Applications for Business Intelligence

Business Intelligence (BI) applications have been gradually ported to the Web in search of a global platform for the consumption and publication of data and services. On the Internet, apart from techniques for data/knowledge management, BI Web applications need interfaces with a high level of interoperability (similar to the traditional desktop interfaces) for the visualisation of data/knowledge. In some cases, this has been provided by Rich Internet Applications (RIA). The development of these BI RIAs is a process traditionally performed manually and, given the complexity of the final application, it is a process which might be prone to errors. The application of model-driven engineering techniques can reduce the cost of development and maintenance (in terms of time and resources) of these applications, as they demonstrated by other types of Web applications. In the light of these issues, the paper introduces the S^m4RIA-B methodology, i.e., a model-driven methodology for the development of RIA as BI Web applications. In order to overcome the limitations of RIA regarding knowledge management from the Web, this paper also presents a new RIA platform for BI, called RI@BI, which extends the functionalities of traditional RIAs by means of Semantic Web technologies and B2B techniques. Finally, we evaluate the whole approach on a case study—the development of a social network site for an enterprise project manager.     

Hierarchical Reliable Multicast: Performance Analysis and Optimal Placement of Proxies

This paper studies the use of multicast together with proxy nodes for reliably disseminating data from a single source to a large number of receivers. In order to achieve reliability, data must be retransmitted in case of loss either by the source or by special network nodes, called proxies. Each proxy is responsible for reliably delivering the data to a subgroup it is assigned. The multicast tree is partitioned into subgroups that form a hierarchy rooted at the source, hence the term hierarchical reliable multicast. The performance of this approach strongly depends on the topology and the loss characteristics of the underlying tree and the location of proxies. In the first part of the paper, we study the processing and bandwidth performance of such a reliable multicast dissemination given the tree and the placement of proxies. In the second part of the paper, we develop dynamic programming algorithms that give a placement of a fixed number of proxies on an arbitrary tree that minimizes the bandwidth used for reliable transfer. The first algorithm provides an optimal solution to the multicast proxies location problem in polynomial time, in the number of nodes and proxies. The second is an approximation algorithm that gives a solution with cost within a chosen precision from the optimal, in an improved running time. An optimal and an approximate solution are also provided for the proxies location problem if unicast is used for transmissions. Applications of this dynamic programming approach to related problems are discussed.     

Quattor: Tools and Techniques for the Configuration,Installation and Management of Large-Scale Grid Computing Fabrics

This paper describes the quattor tool suite, a new system for the installation, configuration, and management of operating systems and application software for computing fabrics. At present Unix derivatives such as Linux and Solaris are supported. Quattor is a powerful, portable and modular open source solution that has been shown to scale to thousands of computing nodes and offers a significant reduction in management costs for large computing fabrics. The quattor tool suite includes innovations compared to existing solutions which make it very useful for computing fabrics integrated into grid environments. Evaluations of the tool suite in current large scale computing environments are presented.     

Clinically Applicable Assessment of Tisagenlecleucel CAR T Cell Treatment by Digital Droplet PCR for Copy Number Variant Assessment

Chimeric antigen receptor (CAR) T cell therapy is an innovative immunotherapy for treating cancers in both children and adults with proven utility in numerous clinical trials. Significantly, some CAR T cell therapies have now been approved by relevant national regulatory bodies across numerous countries for clinical therapeutic use outside of clinical trials. One such recently licensed product is tisagenlecleucel, a CAR T therapy approved for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) using autologous T cells from the patient. The genetically engineered T cells target a protein called CD19, common to B cells, through a CAR incorporating a 4-1BB costimulatory domain to improve response. Since tisagenlecleucel is now a standard of care treatment for B-ALL, it is clinically essential to be able to accurately monitor these CAR T cells in patients. Assessment of the copy number variant (CNV) of the CAR T cell products allows this within a clinically acceptable timeframe for optimal patient benefit. However, no standardized method with high reproducibility and efficiency has been described within a routine clinical laboratory setting. Here, we demonstrated a novel digital droplet PCR (ddPCR)-based methodology for the study of CNV (ddPCR-CNV) in 4-1BB CD19-specific CAR T cells with universal applicability across clinical diagnostic laboratories.     

Development of a model for the simultaneous analysis of wheel and rail wear in railway systems

The prediction of wheel and rail wear is a fundamental issue in the railway field, both in terms of vehicle stability and in terms of economic costs (planning of maintenance interventions). In particular the need of an accurate wear model arises from the interest of Trenitalia S.p.A. and Rete Ferroviara Italiana in designing new wheel and rail profiles and new bogie architectures optimized from the wear viewpoint with the aim of improving the wear and stability behavior of the standard ORE S1002 wheel profile matched with the UIC60 rail profile canted at 1/20 rad (which represents the wheel–rail combination adopted by the Italian railway line). In this work the authors present a wear model specifically developed for the evaluation of the wheel and rail profile evolution, the layout of which is made up of two mutually interactive but separate units: a vehicle model for the dynamical analysis and a model for the wear evaluation. Subsequently the new model has been compared with the wear evaluation procedure implemented in Simpack, a widely tested and validated multibody software for the analysis of the railway vehicle dynamics; the comparison aims both to evaluate the model performance (in terms of accuracy and efficiency) and to further validate the wear model (just tested, as regards the wheel wear prediction, in previous works related to the critical Aosta–Pre Saint Didier line). The comparison has been carried out considering a benchmark train composed by a locomotive (E.464) and a passenger vehicle (Vivalto) provided by Trenitalia while the simulations have been performed on a mean Italian railway line (obtained by means of a statistical analysis of the data relative to the whole Italian railway network provided by Rete Ferroviaria Italiana (RFI)).     

Migration of bisphenol A from polycarbonate baby bottles under real use conditions

Migration of the potential endocrine disrupter, bisphenol A (BPA), from 31 polycarbonate (PC) baby bottles into aqueous food simulants was studied under real repetitive use, using a sensitive and fully validated liquid chromatographic method with fluorescence detection. Confirmation of the presence of BPA was performed by liquid chromatography–mass spectrometry (LC–MS). The effects of cleaning in a dishwasher or with a brush, sterilization with boiling water and the temperature of migration were examined. It was shown that temperature was the crucial factor for the migration of BPA from the plastic bottles to water. All samples released BPA in the concentration range 2.4–14.3 µg kg^?1 when filled with boiled water and left at ambient temperature for 45 min. The decrease of BPA release in the sterilization water and in the food simulant over 12 cycles of use indicated that the hypothesis of polymer degradation in water is dubious. Estimated infantile dietary exposure, regarding the use of PC baby bottles, ranged between 0.2 and 2.2 µg kg^?1 bw day^?1, which is below the Tolerable Daily Intake of 50 µg kg^?1 bw recently established by EFSA.     

Genomic Analysis Made It Possible to Identify Gene-Driver Alterations Covering the Time Window between Diagnosis of Neuroblastoma 4S and the Progression to Stage 4

Neuroblastoma (NB) is a tumor of the developing sympathetic nervous system. Despite recent advances in understanding the complexity of NB, the mechanisms that determine its regression or progression are still largely unknown. Stage 4S NB is characterized by a favorable course of disease and often by spontaneous regression, while progression to true stage 4 is a very rare event. Here, we focused on genomic analysis of an NB case that progressed from stage 4S to stage 4 with a very poor outcome. Array-comparative genomic hybridization (a-CGH) on tumor-tissue DNA, and whole-exome sequencing (WES) on exosomes DNA derived from plasma collected at the onset and at the tumor progression, pointed out relevant genetic changes that can explain this clinical worsening. The combination of a-CGH and WES data allowed for the identification iof somatic copy number aberrations and single-nucleotide variants in genes known to be responsible for aggressive NB. KLRB1, MAPK3 and FANCA genes, which were lost at the time of progression, were studied for their possible role in this event by analyzing in silico the impact of their expression on the outcome of 786 NB patients.     

Interannual vineyard crop variability in the Castilla–La Mancha region during the period 1991–1996 with Landsat Thematic Mapper images

The vineyard crop is considered an indicator of vegetation cover processes in the Castilla–La Mancha region, as the crop has undergone far-reaching changes in the last ten years: abandonment, removal of vineyards and replacement with other crops such as cereal. The so-called ‘Change detection’ is a process that allows identification of differences in the state of the vineyard by observing it at different times. Essentially, it involves the ability to quantify temporal effects using multi-temporal datasets.

The aim of this study is to analyse the vineyard variability during the period 1991–1996 using different Landsat-5 Thematic Mapper (TM) images belonging to an identified period that highlights differences in the vegetation phenology changes. The images were firstly georeferenced and radiometrically normalized for the change detection purpose. The study area is located in central Spain and involves five councils belonging to the Castilla–La Mancha region: Mota del Cuervo, Las Mesas, Tomelloso, Socuellamos and Villarrobledo, with a surface area of 174?040?ha. This area is especially cultivated by the vineyard crop. Moreover, the study area was classified with the images acquired in 1991, using the multi-temporal masking techniques for the vineyard inventory.

The changes experimented by the vineyard have been grouped in three categories: cereal (CE), abandoned vineyard (AB) and bare soil (BS). Therefore, two methods of Normalized Difference Vegetation Index (NDVI) image difference and NDVI Change Vector Analysis (CVA) were used to map these categories of change. The results indicate that 28.4% of vineyard area undergoes changes during the period 1991–1996. The results have been checked with the ground data and all information is highly conformed.     

Multisensor comparison of NDVI for a semi‐arid environment in Spain

The joint use of multiresolution sensors from different satellites offers many opportunities to describe vegetation and its dynamics. This paper introduces the concept of a virtual constellation (defined as an ensemble of all Earth Observation satellites in orbit that satisfy common requirements) for agricultural applications and contributes to providing the necessary inter‐sensor calibration methodology for spectral reflectances and NDVI. For this purpose, we performed an observational study, comparing reflectances and the Normalized Difference Vegetation Index (NDVI), from near‐synchronous image pairs of Landsat 7 Enhanced Thematic Mapper Plus (ETM+), as the reference sensor and Landsat 5 Thematic Mapper (TM), IRS 1C/D LISS‐III (LISS), Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER), QuickBird, and NOAA Advanced Very High‐resolution Radiometer (AVHRR). Linear relationships were found for the intercalibration of reflectances and NDVI from one sensor to another, for all sensors, provided that some spatial aggregation was performed. The main source of data dispersion in our linear cross‐sensor translation equations is the geolocation uncertainty inherent in the process of geometric correction. Consequently, spatial aggregation always needs to be performed if (different or the same) sensors are to be used to derive time‐series of biogeophysical parameters over heterogeneous areas. The homogenous zone approach developed here is recommended as an excellent tool for deriving robust new cross‐sensor relationships, provided that the selected homogeneous crops cover the full NDVI range. The linear cross‐sensor relationships derived from one image pair were shown to be valid for the whole season and for all areas with similar vegetation and climate.