400 research outputs found

    Q-Strategy: A Bidding Strategy for Market-Based Allocation of Grid Services

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    The application of autonomous agents by the provisioning and usage of computational services is an attractive research field. Various methods and technologies in the area of artificial intelligence, statistics and economics are playing together to achieve i) autonomic service provisioning and usage of Grid services, to invent ii) competitive bidding strategies for widely used market mechanisms and to iii) incentivize consumers and providers to use such market-based systems. The contributions of the paper are threefold. First, we present a bidding agent framework for implementing artificial bidding agents, supporting consumers and providers in technical and economic preference elicitation as well as automated bid generation by the requesting and provisioning of Grid services. Secondly, we introduce a novel consumer-side bidding strategy, which enables a goal-oriented and strategic behavior by the generation and submission of consumer service requests and selection of provider offers. Thirdly, we evaluate and compare the Q-strategy, implemented within the presented framework, against the Truth-Telling bidding strategy in three mechanisms – a centralized CDA, a decentralized on-line machine scheduling and a FIFO-scheduling mechanisms

    Multiplex staining depicts the immune infiltrate in colitis-induced colon cancer model

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    Assessment of the host immune response pattern is of increasing importance as highly prognostic and diagnostic, in immune-related diseases and in some types of cancer. Chronic inflammation is a major hallmark in colon cancer formation, but, despite the extent of local inflammatory infiltrate has been demonstrated to be extremely informative, its evaluation is not routinely assessed due to the complexity and limitations of classical immunohistochemistry (IHC). In the last years, technological advance helped in bypassing technical limits, setting up multiplex IHC (mIHC) based on tyramide signal amplification (TSA) method and designing software suited to aid pathologists in cell scoring analysis. Several studies verified the efficacy of this method, but they were restricted to the analysis of human samples. In the era of translational medicine the use of animal models to depict human pathologies, in a more complete and complex approach, is really crucial. Nevertheless, the optimization and validation of this method to species other than human is still poor. We took advantage of Multispectral Imaging System to identify the immunoprofile of Dextran Sulphate Sodium (DSS)-treated mouse colon. We optimized a protocol to sequentially stain formalin fixed paraffin embedded murine colon samples for CD3, CD8a, CD4, and CD4R5B0 antigens. With this approach we obtained a detailed lymphocyte profile, while preserving the morphological tissue context, generally lost with techniques like gene expression profiling or flow cytometry. This study, comparing the results obtained by mIHC with immunophenotyping performed with cytofluorimetric and standard IHC methods validates the potentiality and the applicability of this innovative approach

    Business and Information Technology Alignment Measurement -- a recent Literature Review

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    Since technology has been involved in the business context, Business and Information Technology Alignment (BITA) has been one of the main concerns of IT and Business executives and directors due to its importance to overall company performance, especially today in the age of digital transformation. Several models and frameworks have been developed for BITA implementation and for measuring their level of success, each one with a different approach to this desired state. The BITA measurement is one of the main decision-making tools in the strategic domain of companies. In general, the classical-internal alignment is the most measured domain and the external environment evolution alignment is the least measured. This literature review aims to characterize and analyze current research on BITA measurement with a comprehensive view of the works published over the last 15 years to identify potential gaps and future areas of research in the field.Comment: 12 pages, Preprint version, BIS 2018 International Workshops, Berlin, Germany, July 18 to 20, 2018, Revised Paper

    Simultaneous identification and quantitative determination in urine of the more significant metabolites of synthetic cannabinoids JWH-018, JWH-073, JWH-122 and JWH-250 using authentic references and deuterated isotopologues as internal standards

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    Introduction Synthetic cannabinoids (SC) are substances displaying a high affinity for cannabinoid receptor CB1 and represent the psychoactive agents in herbal mixtures called \u201cSpice\u201d or \u201cK2\u201d which are sold as an incense or smoking material mainly through the Internet. Because of its great abusive potential, several SC are banned in many countries, but despite this, the widespread use of herbal smoking mixtures containing SC may be partially explained by the fact that post-ingestion urines are known to produce negative results in standard toxicological screening methods for cannabis. As a consequence, an increasing number of analytical methods have been developed in forensic and doping control laboratories to enable the detection of illegal intake of these psychoactive substances in human fluids originating from psychiatric patients, emergency units or assessment of fitness to drive. Due to rapid metabolic transformation, the native SC are not usually detectable in urine samples and then the analytical methods must be based on the identification and quantization of their metabolites. Aims The aim of our study is to set-up, using synthesized reference standards, a LC-MS/MS method for routine screening procedures to assess the assumption of JWH-018, JWH-073, JWH 122 and JWH-250, the SC included in Table 1 of narcotic and psychotropic substances banned in Italy. The method gives the simultaneous identification of the three more significant metabolites of each cannabinoid and adequate sensitivity, precision and accuracy are assured by the use of deuterated internal standards. Methods For each of the four cannabinoids were synthesized the three more significant metabolites, the \u3c9- and (\u3c9-1)-hydroxyl and the \u3c9-carboxyl derivatives (\u3c9 position represent the terminal carbon of the N-alkyl side chain) while as internal standards were synthesized the (\u3c9-1)-hydroxyl metabolites trideuterated on the terminal methyl of the side chain. Urine samples were subjected to deconjugation using 30% hydrochloric acid at 90-95\ub0C for 60 min, followed by a solvent extraction procedure with n-hexane-ethyl acetate (9/1 v/v). The LC-MS/MS analysis was performed in positive mode on an API 4000 Triple Quadrupole Mass Spectrometer (AB Sciex) equipped with a 1,8\ub5m Acquity C-18 HSS T3 100 x 2 mm HPLC column (Waters) with isocratic elution (55 % of 10 mM HCOONH4 in water containing 0.1% HCOOH and 45 % of acetonitrile) at 45 \ub0C and at flow rate of 0.4 mL/min. Two transitions in \u2018multiple reaction monitoring\u2019 mode and the retention time have permitted the unambiguous identification of each metabolite which, through the presence of a suitable internal standard, was quantified. Result and discussion All the synthesized compounds were fully characterized with regard to the structure and purity, by 1H,13C NMR and GC-MS (after esterification with CH2N2 for the \u3c9-carboxylic metabolites). For sample treatment, the recovery of the metabolites was evaluated at different pH (1, 3, 5, 9 and 10). The validation of the method was performed testing linearity (0.5-100 ng/mL), reproducibility and accuracy (ranged between -15% and + 15%) at three levels. The method developed was applied to the analysis of urine samples from individuals who have taken SC. This LC-MS/MS method can be used for routine screening of urine specimens from subjects suspected of using \u201cherbal incense\u201d or \u201cSpice\u201d products spiked with the synthetic cannabinoids JWH-018, JWH-073, JWH 122 or JWH-250

    LC-MS/MS method development for quantification of doxorubicin and its metabolite 13-hydroxy doxorubicin in mice biological matrices : Application to a pharmaco-delivery study

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    This study describes the development of simple, rapid and sensitive liquid chromatography tandem mass spectrometry method for the simultaneous analysis of doxorubicin and its major metabolite, doxorubicinol, in mouse plasma, urine and tissues. The calibration curves were linear over the range 5-250ng/mL for doxorubicin and 1.25-25ng/mL for doxorubicinol in plasma and tumor, over the range 25-500ng/mL for doxorubicin and 1.25-25ng/mL for doxorubicinol in liver and kidney, and over the range 25-1000ng/mL for doxorubicin and doxorubicinol in urine. The study was validated, using quality control samples prepared in all different matrices, for accuracy, precision, linearity, selectivity, lower limit of quantification and recovery in accordance with the US Food & Drug Administration guidelines. The method was successfully applied in determining the pharmaco-distribution of doxorubicin and doxorubicinol after intravenously administration in tumor-bearing mice of drug, free or nano-formulated in ferritin nanoparticles or in liposomes. Obtained results demonstrate an effective different distribution and doxorubicin protection against metabolism linked to nano-formulation. This method, thanks to its validation in plasma and urine, could be a powerful tool for pharmaceutical research and therapeutic drug monitoring, which is a clinical approach currently used in the optimization of oncologic treatments

    Large potential for crop production adaptation depends on available future varieties

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    Climate change affects global agricultural production and threatens food security. Faster phenological development of crops due to climate warming is one of the main drivers for potential future yield reductions. To counter the effect of faster maturity, adapted varieties would require more heat units to regain the previous growing period length. In this study, we investigate the effects of variety adaptation on global caloric production under four different future climate change scenarios for maize, rice, soybean, and wheat. Thereby, we empirically identify areas that could require new varieties and areas where variety adaptation could be achieved by shifting existing varieties into new regions. The study uses an ensemble of seven global gridded crop models and five CMIP6 climate models. We found that 39% (SSP5-8.5) of global cropland could require new crop varieties to avoid yield loss from climate change by the end of the century. At low levels of warming (SSP1-2.6), 85% of currently cultivated land can draw from existing varieties to shift within an agro-ecological zone for adaptation. The assumptions on available varieties for adaptation have major impacts on the effectiveness of variety adaptation, which could more than half in SSP5-8.5. The results highlight that region-specific breeding efforts are required to allow for a successful adaptation to climate change

    Mitigation of NH3 emissions due to cattle slurry fertilisation.

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    Agriculture is known as the major source of atmospheric ammonia (NH3). The strategies to reduce the emissions of this gas have become an important focus in many countries to prevent environmental issues and to reduce the loss of nutrients and energy from cropping systems. Appropriate slurry application techniques are fundamental strategies to reduce nitrogen losses. This study presents an evaluation of the best agronomical practices for reducing NH3 emissions from cattle slurry spreading on arable lands. Two different application techniques with two incorporation procedures were assessed in four different field trials in the Po Valley. The NH3 concentration measurements were performed using passive samplers, while a dispersion model has been used for estimating NH3 fluxes at field scale. The best abatement strategy from slurry application has proved to be the direct injection into the soil, with a reduction of about 95% with respect to the surface spreading, while a contextual incorporation was able to reduce the emission of more than 85%

    Long-term CD4+ T-cell count evolution after switching from regimens including HIV nucleoside reverse transcriptase inhibitors (NRTI) plus protease inhibitors to regimens containing NRTI plus non-NRTI or only NRTI

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    BACKGROUND: Data regarding CD4+ recovery after switching from protease inhibitor (PI)-based regimens to regimens not containing PI are scarce. METHODS: Subjects with virological success on first-PI-regimens who switched to NNRTI therapy (NNRTI group) or to nucleoside reverse transcriptase (NRTI)-only (NRTI group) were studied. The effect of the switch on the ongoing CD4+ trend was assessed by two-phase linear regression (TPLR), allowing us to evaluate whether a change in the CD4+ trend (hinge) occurred and the time of its occurrence. Furthermore, we described the evolution of the frequencies in CD4-count classes across four relevant time-points (baseline, before and immediately after the switch, and last visit). Finally, we explored whether the CD4+ counts evolved differently in patients who switched to NNRTI or NRTI-only regimens by considering: the overall CD4+ trends, the time to CD4+ 65 500/mm3 after the switch, and the area-under-the-curve (AUC) of the CD4+ after the switch. RESULTS: Eight hundred and ninety-six patients, followed for a median of 2,121 days, were included. At TPLR, hinges occurred in 581/844 (68.9%), but in only 40/581 (6.9%) within a time interval (180 days) compatible with a possible relationship to the switch; furthermore, in 19/40 cases, CD4+ counts appeared to decrease after the hinges. In comparison with the NNRTI group, the NRTI group showed CD4+ count greater at baseline (P = 0.0234) and before the switch (P 64 0.0001), superior CD4+ T-cell increases after HAART was started, lower probability of not achieving CD4+ 65 500/mm3 (P = 0.0024), and, finally, no significant differences in the CD4+ T-cell AUC after the switch after adjusting for possible confounders (propensity score and pre-switch AUC). Persistence at CD4+ < 200/mm3 was observed in 34/435 (7.5%) patients, and a decrease below this level was found in only 10/259 (3.9%) with baseline CD4+ 65 350/mm3. CONCLUSIONS: Switching from first-line PI to NNRTI- or NRTI-based regimens did not seem to impair CD4+ trend over long-term follow-up. Although the greater CD4+ increases in patients who switched to the NRTI-only regimen was due to higher CD4+ counts before the switch, several statistical analyses consistently showed that switching to this regimen did not damage the ongoing immune-reconstitution. Lastly, the observation that CD4+ T-cell counts remained low or decreased in the long term despite virological success merits further investigation
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