996 resultados para KA model


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Model-View-Controller (MVC) is an architectural pattern used in software development for graphical user interfaces. It was one of the first proposed solutions in the late 1970s to the Smart UI anti-pattern, which refers to the act of writing all domain logic into a user interface. The original MVC pattern has since evolved in multiple directions, with various names and may confuse many. The goal of this thesis is to present the origin of the MVC pattern and how it has changed over time. Software architecture in general and the MVC’s evolution within web applications are not the primary focus. Fundamen- tal designs are abstracted, and then used to examine the more recent versions. Prob- lems with the subject and its terminology are also presented.

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Didanosine (ddI) is a component of highly active antiretroviral therapy drug combinations, used especially in resource-limited settings and in zidovudine-resistant patients. The population pharmacokinetics of ddI was evaluated in 48 healthy volunteers enrolled in two bioequivalence studies. These data, along with a set of co-variates, were the subject of a nonlinear mixed-effect modeling analysis using the NONMEM program. A two-compartment model with first order absorption (ADVAN3 TRANS3) was fitted to the serum ddI concentration data. Final pharmacokinetic parameters, expressed as functions of the co-variates gender and creatinine clearance (CL CR), were: oral clearance (CL = 55.1 + 240 x CL CR + 16.6 L/h for males and CL = 55.1 + 240 x CL CR for females), central volume (V2 = 9.8 L), intercompartmental clearance (Q = 40.9 L/h), peripheral volume (V3 = 62.7 + 22.9 L for males and V3 = 62.7 L for females), absorption rate constant (Ka = 1.51/h), and dissolution time of the tablet (D = 0.43 h). The intraindividual (residual) variability expressed as coefficient of variation was 13.0%, whereas the interindividual variability of CL, Q, V3, Ka, and D was 20.1, 75.8, 20.6, 18.9, and 38.2%, respectively. The relatively high (>30%) interindividual variability for some of these parameters, observed under the controlled experimental settings of bioequivalence trials in healthy volunteers, may result from genetic variability of the processes involved in ddI absorption and disposition.

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Subfossil pollen and plant macrofossil data derived from 14C-dated sediment profiles can provide quantitative information on glacial and interglacial climates. The data allow climate variables related to growing season warmth, winter cold, and plant-available moisture to be reconstructed. Continental-scale reconstructions have been made for the mid-Holocene (MH, around 6 ka) and Last Glacial Maximum (LGM, around 21 ka), allowing comparison with palaeoclimate simulations currently being carried out as part of the fifth Assessment Report (AR5) of the Intergovernmental Panel on Climate Change. The synthesis of the available MH and LGM climate reconstructions and their uncertainties, obtained using modern analogue, regression and model-inversion techniques, is presented for four temperature variables and two moisture variables. Reconstructions of the same variables based on surface-pollen assemblages are shown to be accurate and unbiased. Reconstructed LGM and MH climate anomaly patterns are coherent, consistent between variables, and robust with respect to the choice of technique. They support a conceptual model of the controls of Late Quaternary climate change whereby the first-order effects of orbital variations and greenhouse forcing on the seasonal cycle of temperature are predictably modified by responses of the atmospheric circulation and surface energy balance.

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The response of monsoon circulation in the northern and southern hemisphere to 6 ka orbital forcing has been examined in 17 atmospheric general circulation models and 11 coupled ocean–atmosphere general circulation models. The atmospheric response to increased summer insolation at 6 ka in the northern subtropics strengthens the northern-hemisphere summer monsoons and leads to increased monsoonal precipitation in western North America, northern Africa and China; ocean feedbacks amplify this response and lead to further increase in monsoon precipitation in these three regions. The atmospheric response to reduced summer insolation at 6 ka in the southern subtropics weakens the southern-hemisphere summer monsoons and leads to decreased monsoonal precipitation in northern South America, southern Africa and northern Australia; ocean feedbacks weaken this response so that the decrease in rainfall is smaller than might otherwise be expected. The role of the ocean in monsoonal circulation in other regions is more complex. There is no discernable impact of orbital forcing in the monsoon region of North America in the atmosphere-only simulations but a strong increase in precipitation in the ocean–atmosphere simulations. In contrast, there is a strong atmospheric response to orbital forcing over northern India but ocean feedback reduces the strength of the change in the monsoon although it still remains stronger than today. Although there are differences in magnitude and exact location of regional precipitation changes from model to model, the same basic mechanisms are involved in the oceanic modulation of the response to orbital forcing and this gives rise to a robust ensemble response for each of the monsoon systems. Comparison of simulated and reconstructed changes in regional climate suggest that the coupled ocean–atmosphere simulations produce more realistic changes in the northern-hemisphere monsoons than atmosphere-only simulations, though they underestimate the observed changes in precipitation in all regions. Evaluation of the southern-hemisphere monsoons is limited by lack of quantitative reconstructions, but suggest that model skill in simulating these monsoons is limited.

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Climate models are potentially useful tools for addressing human dispersals and demographic change. The Arabian Peninsula is becoming increasingly significant in the story of human dispersals out of Africa during the Late Pleistocene. Although characterised largely by arid environments today, emerging climate records indicate that the peninsula was wetter many times in the past, suggesting that the region may have been inhabited considerably more than hitherto thought. Explaining the origins and spatial distribution of increased rainfall is challenging because palaeoenvironmental research in the region is in an early developmental stage. We address environmental oscillations by assembling and analysing an ensemble of five global climate models (CCSM3, COSMOS, HadCM3, KCM, and NorESM). We focus on precipitation, as the variable is key for the development of lakes, rivers and savannas. The climate models generated here were compared with published palaeoenvironmental data such as palaeolakes, speleothems and alluvial fan records as a means of validation. All five models showed, to varying degrees, that the Arabia Peninsula was significantly wetter than today during the Last Interglacial (130 ka and 126/125 ka timeslices), and that the main source of increased rainfall was from the North African summer monsoon rather than the Indian Ocean monsoon or from Mediterranean climate patterns. Where available, 104 ka (MIS 5c), 56 ka (early MIS 3) and 21 ka (LGM) timeslices showed rainfall was present but not as extensive as during the Last Interglacial. The results favour the hypothesis that humans potentially moved out of Africa and into Arabia on multiple occasions during pluvial phases of the Late Pleistocene.

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This article proposes a deterministic radio propagation model using dyadic Green's function to predict the value of the electric field. Dyadic is offered as an efficient mathematical tool which has symbolic simplicity and robustness, as well as taking account of the anisotropy of the medium. The proposed model is an important contribution for the UHF band because it considers climatic conditions by changing the constants of the medium. Most models and recommendations that include an approach for climatic conditions, are designed for satellite links, mainly Ku and Ka bands. The results obtained by simulation are compared and validated with data from a Digital Television Station measurement campaigns conducted in the Belém city in Amazon region during two seasons. The proposed model was able to provide satisfactory results by differentiating between the curves for dry and wet soil and these corroborate the measured data, (the RMS errors are between 2-5 dB in the case under study).

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Background: Magnetic hyperthermia is currently a clinical therapy approved in the European Union for treatment of tumor cells, and uses magnetic nanoparticles (MNPs) under time-varying magnetic fields (TVMFs). The same basic principle seems promising against trypanosomatids causing Chagas disease and sleeping sickness, given that the therapeutic drugs available have severe side effects and that there are drug-resistant strains. However, no applications of this strategy against protozoan-induced diseases have been reported so far. In the present study, Crithidia fasciculata, a widely used model for therapeutic strategies against pathogenic trypanosomatids, was targeted with Fe3O4 MNPs in order to provoke cell death remotely using TVMFs. Methods: Iron oxide MNPs with average diameters of approximately 30 nm were synthesized by precipitation of FeSO4 in basic medium. The MNPs were added to C. fasciculata choanomastigotes in the exponential phase and incubated overnight, removing excess MNPs using a DEAE-cellulose resin column. The amount of MNPs uploaded per cell was determined by magnetic measurement. The cells bearing MNPs were submitted to TVMFs using a homemade AC field applicator (f = 249 kHz, H = 13 kA/m), and the temperature variation during the experiments was measured. Scanning electron microscopy was used to assess morphological changes after the TVMF experiments. Cell viability was analyzed using an MTT colorimetric assay and flow cytometry. Results: MNPs were incorporated into the cells, with no noticeable cytotoxicity. When a TVMF was applied to cells bearing MNPs, massive cell death was induced via a nonapoptotic mechanism. No effects were observed by applying TVMF to control cells not loaded with MNPs. No macroscopic rise in temperature was observed in the extracellular medium during the experiments. Conclusion: As a proof of principle, these data indicate that intracellular hyperthermia is a suitable technology to induce death of protozoan parasites bearing MNPs. These findings expand the possibilities for new therapeutic strategies combating parasitic infection.

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Grepafloxacin, a new fluoroquinolone, produced bactericidal activity comparable to that of vancomycin and ceftriaxone in the treatment in rabbits of meningitis caused by a pneumococcal strain highly resistant to penicillin (MIC 4 mg/L) (triangle uplog(10) cfu/mL*h for grepafloxacin, -0.32 +/- 0.15; dose, 15 mg/kg iv; triangle uplog(10) cfu/mL*h for vancomycin, -0.39 +/- 0.18; dose, 2 x 20 mg/kg iv; triangle uplog(10) cfu/mL*h for ceftriaxone, -0.32 +/- 0. 12; dose, 125 mg/kg iv). Higher doses of grepafloxacin (30 mg/kg and 2 x 50 mg/kg) did not improve the killing rates. The combination of grepafloxacin with vancomycin was not significantly superior to monotherapies (P > 0.05). In vitro, grepafloxacin was bactericidal at concentrations above the MIC. Using concentrations around the MIC, addition of vancomycin to grepafloxacin showed synergic activity.

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There is a growing number of proxy-based reconstructions detailing the climatic changes that occurred during the last interglacial period (LIG). This period is of special interest, because large parts of the globe were characterized by a warmer-than-present-day climate, making this period an interesting test bed for climate models in light of projected global warming. However, mainly because synchronizing the different palaeoclimatic records is difficult, there is no consensus on a global picture of LIG temperature changes. Here we present the first model inter-comparison of transient simulations covering the LIG period. By comparing the different simulations, we aim at investigating the common signal in the LIG temperature evolution, investigating the main driving forces behind it and at listing the climate feedbacks which cause the most apparent inter-model differences. The model inter-comparison shows a robust Northern Hemisphere July temperature evolution characterized by a maximum between 130–125 ka BP with temperatures 0.3 to 5.3 K above present day. A Southern Hemisphere July temperature maximum, −1.3 to 2.5 K at around 128 ka BP, is only found when changes in the greenhouse gas concentrations are included. The robustness of simulated January temperatures is large in the Southern Hemisphere and the mid-latitudes of the Northern Hemisphere. For these regions maximum January temperature anomalies of respectively −1 to 1.2 K and −0.8 to 2.1 K are simulated for the period after 121 ka BP. In both hemispheres these temperature maxima are in line with the maximum in local summer insolation. In a number of specific regions, a common temperature evolution is not found amongst the models. We show that this is related to feedbacks within the climate system which largely determine the simulated LIG temperature evolution in these regions. Firstly, in the Arctic region, changes in the summer sea-ice cover control the evolution of LIG winter temperatures. Secondly, for the Atlantic region, the Southern Ocean and the North Pacific, possible changes in the characteristics of the Atlantic meridional overturning circulation are crucial. Thirdly, the presence of remnant continental ice from the preceding glacial has shown to be important when determining the timing of maximum LIG warmth in the Northern Hemisphere. Finally, the results reveal that changes in the monsoon regime exert a strong control on the evolution of LIG temperatures over parts of Africa and India. By listing these inter-model differences, we provide a starting point for future proxy-data studies and the sensitivity experiments needed to constrain the climate simulations and to further enhance our understanding of the temperature evolution of the LIG period.

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Terrestrial records of past climatic conditions, such as lake sediments and speleothems, provide data of great importance for understanding environmental changes. However, unlike marine and ice core records, terrestrial palaeodata are often not available in databases or in a format that is easily accessible to the non-specialist. As a consequence, many excellent terrestrial records are unknown to the broader palaeoclimate community and are not included in compilations, comparisons, or modelling exercises. Here we present a compilation of Western European terrestrial palaeo-records covering, entirely or partially, the 60–8-ka INTIMATE time period. The compilation contains 56 natural archives, including lake records, speleothems, ice cores, and terrestrial proxies in marine records. The compilation is limited to include records of high temporal resolution and/or records that provide climate proxies or quantitative reconstructions of environmental parameters, such as temperature or precipitation, and that are of relevance and interest to a broader community. We briefly review the different types of terrestrial archives, their respective proxies, their interpretation and their application for palaeoclimatic reconstructions. We also discuss the importance of independent chronologies and the issue of record synchronization. The aim of this exercise is to provide the wider palaeo-community with a consistent compilation of high-quality terrestrial records, to facilitate model-data comparisons, and to identify key areas of interest for future investigations. We use the compilation to investigate Western European latitudinal climate gradients during the deglacial period and, despite of poorly constrained chronologies for the older records, we summarize the main results obtained from NW and SW European terrestrial records before the LGM.

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Lake Ohrid (Macedonia, Albania) is thought to be more than 1.2 million years old and host more than 300 endemic species. As a target of the International Continental scientific Drilling Program (ICDP), a successful deep drilling campaign was carried out within the scope of the Scientific Collaboration on Past Speciation Conditions in Lake Ohrid (SCOPSCO) project in 2013. Here, we present lithological, sedimentological, and (bio-)geochemical data from the upper 247.8 m composite depth of the overall 569 m long DEEP site sediment succession from the central part of the lake. According to an age model, which is based on 11 tephra layers (first-order tie points) and on tuning of bio-geochemical proxy data to orbital parameters (second-order tie points), the analyzed sediment sequence covers the last 637 kyr. The DEEP site sediment succession consists of hemipelagic sediments, which are interspersed by several tephra layers and infrequent, thin (< 5 cm) mass wasting deposits. The hemipelagic sediments can be classified into three different lithotypes. Lithotype 1 and 2 deposits comprise calcareous and slightly calcareous silty clay and are predominantly attributed to interglacial periods with high primary productivity in the lake during summer and reduced mixing during winter. The data suggest that high ion and nutrient concentrations in the lake water promoted calcite precipitation and diatom growth in the epilimnion during MIS15, 13, and 5. Following a strong primary productivity, highest interglacial temperatures can be reported for marine isotope stages (MIS) 11 and 5, whereas MIS15, 13, 9, and 7 were comparably cooler. Lithotype 3 deposits consist of clastic, silty clayey material and predominantly represent glacial periods with low primary productivity during summer and longer and intensified mixing during winter. The data imply that the most severe glacial conditions at Lake Ohrid persisted during MIS16, 12, 10, and 6, whereas somewhat warmer temperatures can be inferred for MIS14, 8, 4, and 2. Interglacial-like conditions occurred during parts of MIS14 and 8.