Simulation studies suggest that pooled on-demand services (also referred to as Demand Responsive Transport, ridesharing, shared ride-hailing or shared ridesourcing services) have the potential to ...bring large benefits to urban areas while inducing limited time losses for their users. However, in reality, the large majority of users request individual rides (and not pooled rides) in existing on-demand services, leading to increases in motorised vehicle miles travelled. In this study, we investigate to what extent fare discounts, additional travel time, and the (un)willingness to share the ride with (different numbers of) other passengers play a role in the decision of individuals to share rides. To this end, we design a stated preference study targeting Dutch urban individuals. In our research, we (1) disentangle the sharing aspect from related time–cost trade-offs (e.g. detours), (2) investigate preference heterogeneity regarding the studied attributes and identify distinct market segments, and (3) simulate scenarios to understand the impact of the obtained parameters in the breakdown between individual and pooled services. We find that less than one third of respondents have strong preferences against sharing their rides. Also, we find that different market segments vary not only in their values of the willingness to share, but also in how they perceive this willingness to share (per-ride or proportional to the in-vehicle time). Further, the scenario analysis demonstrates that the share of individuals who are willing to share rides depends primarily on the time–cost trade-offs, rather than on the disutility stemming from pooling rides per se.
Lipid-based nanocarriers for oral peptide delivery Niu, Zhigao; Conejos-Sánchez, Inmaculada; Griffin, Brendan T. ...
Advanced drug delivery reviews,
11/2016, Letnik:
106, Številka:
Pt B
Journal Article
Recenzirano
This article is aimed to overview the lipid-based nanostructures designed so far for the oral administration of peptides and proteins, and to analyze the influence of their composition and ...physicochemical (particle size, zeta potential) and pharmaceutical (drug loading and release) properties, on their interaction with the gastro-intestinal environment, and the subsequent PK/PD profile of the associated drugs. The ultimate goal has been to highlight and comparatively analyze the key factors that may be determinant of the success of these nanocarriers for oral peptide delivery. The article ends with some prospects on the challenges to be addressed for the intended commercial success of these delivery vehicles.
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Dissolved inorganic carbon (DIC) is one of the most important parameters to be measured in seawaters for climate change studies. Its quantitative assessment requires analytical methodologies with ...overall uncertainties around 0.05% RSD for clear evaluation of temporal trends. Herein, two alternative isotope dilution mass spectrometry (IDMS) methodologies (online and species-specific) using an isotope ratio mass spectrometer (IRMS) and two calculation procedures for each methodology have been compared. As a result, a new method for the determination of DIC in seawaters, based on species-specific IDMS with isotope pattern deconvolution calculation, was developed and validated. A 13C-enriched bicarbonate tracer was added to the sample and, after equilibration and acidification, the isotope abundances at CO2 masses 44, 45, and 46 were measured on an IRMS instrument. Notably, early spiking allows correcting for evaporations and/or adsorptions during sample preparation and storage and could be carried out immediately after sampling. Full uncertainty budgets were calculated taking into account all the factors involved in the determination (initial weights, concentration and isotope abundances of standards, and final IRMS measurements). The average DIC value obtained for CRM seawater agreed very well with the certified value. Propagated precision obtained ranged from 0.035 to 0.050% RSD for individual sample triplicates. Reproducibility, assessed by three independent experiments carried out in different working days, was excellent as well (−0.01% and 0.057%, error and full combined uncertainty, respectively). Additionally, the approach proposed improves on established methods by simplicity, higher throughput (15 min per sample), and lower volume requirements (10 mL).
The present study shows the results of solar photo-Fenton oxidation of paracetamol (PCT) and amoxicillin (AMX). Fe2(SO4)3 was used as the source of iron and EDDS as the iron complexing agent, ...employing different doses of hydrogen peroxide. Two aqueous matrices, a synthetic wastewater and real wastewater from El Ejido WWTP effluent (Almeria) were used. In all cases, the process was operated under conditions of natural sunlight.
Results showed that the degradation of both drugs is favoured when the aqueous matrix presents low concentration of carbonates. Under the conditions studied here, degradation percentages above 90% were obtained in the synthetic wastewater and 80% in the actual effluent. The degradation products were determined using liquid chromatography coupled to high-resolution mass spectrometry with hybrid quadrupole time-of-flight analyser. The intermediates detected throughout the oxidative process for both micro-contaminants were mainly products of hydroxylation reactions.
The toxicity of the samples was determined using the bacterium Vibrio fischeri. In the acute toxicity test, it was observed that the bacteria did not undergo inhibition in any of the cases. However, chronic toxicity studies showed that the higher the Hydraulic Retention Time (HRT) employed in the assays, the higher the bacterial inhibition.
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•Solar photo-Fenton successfully degraded microcontaminants under natural sunlight and circumneutral pH.•90% and 80% degradation percentages were obtained in the synthetic wastewater and actual effluent.•In acute toxicity tests, bacteria did not undergo inhibition in any of the cases.
Rotation Forest: A New Classifier Ensemble Method Rodriguez, J.J.; Kuncheva, L.I.; Alonso, C.J.
IEEE transactions on pattern analysis and machine intelligence,
10/2006, Letnik:
28, Številka:
10
Journal Article
Recenzirano
We propose a method for generating classifier ensembles based on feature extraction. To create the training data for a base classifier, the feature set is randomly split into K subsets (K is a ...parameter of the algorithm) and principal component analysis (PCA) is applied to each subset. All principal components are retained in order to preserve the variability information in the data. Thus, K axis rotations take place to form the new features for a base classifier. The idea of the rotation approach is to encourage simultaneously individual accuracy and diversity within the ensemble. Diversity is promoted through the feature extraction for each base classifier. Decision trees were chosen here because they are sensitive to rotation of the feature axes, hence the name "forest". Accuracy is sought by keeping all principal components and also using the whole data set to train each base classifier. Using WEKA, we examined the rotation forest ensemble on a random selection of 33 benchmark data sets from the UCI repository and compared it with bagging, AdaBoost, and random forest. The results were favorable to rotation forest and prompted an investigation into diversity-accuracy landscape of the ensemble models. Diversity-error diagrams revealed that rotation forest ensembles construct individual classifiers which are more accurate than these in AdaBoost and random forest, and more diverse than these in bagging, sometimes more accurate as well
The altered metabolism of tumors has been considered a target for anticancer therapy. However, the relationship between distinct tumor-initiating lesions and anomalies of tumor metabolism in vivo has ...not been addressed. We report that MYC-induced mouse liver tumors significantly increase both glucose and glutamine catabolism, whereas MET-induced liver tumors use glucose to produce glutamine. Increased glutamine catabolism in MYC-induced liver tumors is associated with decreased levels of glutamine synthetase (Glul) and the switch from Gls2 to Gls1 glutaminase. In contrast to liver tumors, MYC-induced lung tumors display increased expression of both Glul and Gls1 and accumulate glutamine. We also show that inhibition of Gls1 kills cells that overexpress MYC and catabolize glutamine. Our results suggest that the metabolic profiles of tumors are likely to depend on both the genotype and tissue of origin and have implications regarding the design of therapies targeting tumor metabolism.
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► MYC and MET affect glucose and glutamine metabolism differently in the liver ► Tissue context affects the outcome of metabolic reprogramming by MYC ► MYC overexpression sensitizes cells to inhibition of Gls1 glutaminase
Although analysis of metals and metalloids, such as arsenic, is widely spread in many different fields, their analysis in gas and liquefied gas samples is still a challenge. A new GC-ICP-MS set up ...has been developed for their simultaneous total and speciation analysis in gas and liquefied gas samples without the need of a preconcentration step. An arsine in nitrogen standard was used for optimization and evaluation of the system. Good linearity and detection limits in the very low ppt level for both total and speciation analyses were found. Liquefied butane pressurized under nitrogen and doped with arsine and a propylene real sample from a cracker plant were analyzed using both external calibration and standard additions methods. The good match between both quantifying approaches demonstrated almost negligible matrix effects, even for the total analysis. Application of the approach to check repartition of volatile elements or species between gas and liquid phases was performed in the real propylene sample. Finally, its potential applicability for the simultaneous total and speciation analysis of other elements, such as Hg, was also proved.
Challenging environmental conditions, including heat and humidity, cold, and altitude, pose particular risks to the health of Olympic and other high-level athletes. As a further commitment to athlete ...safety, the International Olympic Committee (IOC) Medical Commission convened a panel of experts to review the scientific evidence base, reach consensus, and underscore practical safety guidelines and new research priorities regarding the unique environmental challenges Olympic and other international-level athletes face. For non-aquatic events, external thermal load is dependent on ambient temperature, humidity, wind speed and solar radiation, while clothing and protective gear can measurably increase thermal strain and prompt premature fatigue. In swimmers, body heat loss is the direct result of convection at a rate that is proportional to the effective water velocity around the swimmer and the temperature difference between the skin and the water. Other cold exposure and conditions, such as during Alpine skiing, biathlon and other sliding sports, facilitate body heat transfer to the environment, potentially leading to hypothermia and/or frostbite; although metabolic heat production during these activities usually increases well above the rate of body heat loss, and protective clothing and limited exposure time in certain events reduces these clinical risks as well. Most athletic events are held at altitudes that pose little to no health risks; and training exposures are typically brief and well-tolerated. While these and other environment-related threats to performance and safety can be lessened or averted by implementing a variety of individual and event preventative measures, more research and evidence-based guidelines and recommendations are needed. In the mean time, the IOC Medical Commission and International Sport Federations have implemented new guidelines and taken additional steps to mitigate risk even further.
Abstract Aims To provide 12-month prevalence and disability burden estimates of a broad range of mental and neurological disorders in the European Union (EU) and to compare these findings to previous ...estimates. Referring to our previous 2005 review, improved up-to-date data for the enlarged EU on a broader range of disorders than previously covered are needed for basic, clinical and public health research and policy decisions and to inform about the estimated number of persons affected in the EU. Method Stepwise multi-method approach, consisting of systematic literature reviews, reanalyses of existing data sets, national surveys and expert consultations. Studies and data from all member states of the European Union (EU-27) plus Switzerland, Iceland and Norway were included. Supplementary information about neurological disorders is provided, although methodological constraints prohibited the derivation of overall prevalence estimates for mental and neurological disorders. Disease burden was measured by disability adjusted life years (DALY). Results Prevalence: It is estimated that each year 38.2% of the EU population suffers from a mental disorder. Adjusted for age and comorbidity, this corresponds to 164.8 million persons affected. Compared to 2005 (27.4%) this higher estimate is entirely due to the inclusion of 14 new disorders also covering childhood/adolescence as well as the elderly. The estimated higher number of persons affected (2011: 165 m vs. 2005: 82 m) is due to coverage of childhood and old age populations, new disorders and of new EU membership states. The most frequent disorders are anxiety disorders (14.0%), insomnia (7.0%), major depression (6.9%), somatoform (6.3%), alcohol and drug dependence (> 4%), ADHD (5%) in the young, and dementia (1–30%, depending on age). Except for substance use disorders and mental retardation, there were no substantial cultural or country variations. Although many sources, including national health insurance programs, reveal increases in sick leave, early retirement and treatment rates due to mental disorders, rates in the community have not increased with a few exceptions (i.e. dementia). There were also no consistent indications of improvements with regard to low treatment rates, delayed treatment provision and grossly inadequate treatment. Disability: Disorders of the brain and mental disorders in particular, contribute 26.6% of the total all cause burden, thus a greater proportion as compared to other regions of the world. The rank order of the most disabling diseases differs markedly by gender and age group; overall, the four most disabling single conditions were: depression, dementias, alcohol use disorders and stroke. Conclusion In every year over a third of the total EU population suffers from mental disorders. The true size of “disorders of the brain” including neurological disorders is even considerably larger. Disorders of the brain are the largest contributor to the all cause morbidity burden as measured by DALY in the EU. No indications for increasing overall rates of mental disorders were found nor of improved care and treatment since 2005; less than one third of all cases receive any treatment, suggesting a considerable level of unmet needs. We conclude that the true size and burden of disorders of the brain in the EU was significantly underestimated in the past. Concerted priority action is needed at all levels, including substantially increased funding for basic, clinical and public health research in order to identify better strategies for improved prevention and treatment for disorders of the brain as the core health challenge of the 21st century.
This article describes studies on the regioselective acetal protection of monosaccharide-based diols using chiral phosphoric acids (CPAs) and their immobilized polymeric variants, (
)-Ad-TRIP-PS and ...(
)-SPINOL-PS, as the catalysts. These catalyst-controlled regioselective acetalizations were found to proceed with high regioselectivities (up to >25:1 rr) on various d-glucose-, d-galactose-, d-mannose-, and l-fucose-derived 1,2-diols and could be carried out in a regiodivergent fashion depending on the choice of chiral catalyst. The polymeric catalysts were conveniently recycled and reused multiple times for gram-scale functionalizations with catalytic loadings as low as 0.1 mol %, and their performance was often found to be superior to the performance of their monomeric variants. These regioselective CPA-catalyzed acetalizations were successfully combined with common hydroxyl group functionalizations as single-pot telescoped procedures to produce 32 regioisomerically pure differentially protected mono- and disaccharide derivatives. To further demonstrate the utility of the polymeric catalysts, the same batch of (
)-Ad-TRIP-PS catalyst was recycled and reused to accomplish single-pot gram-scale syntheses of 6 differentially protected d-glucose derivatives. The subsequent exploration of the reaction mechanism using NMR studies of deuterated and nondeuterated substrates revealed that low-temperature acetalizations happen via a
-addition mechanism and that the reaction regioselectivity exhibits strong dependence on the temperature. The computational studies indicate a complex temperature-dependent interplay of two reaction mechanisms, one involving an anomeric phosphate intermediate and another via concerted asynchronous formation of an acetal, that results in
-addition products. The computational models also explain the steric factors responsible for the observed C2 selectivities and are consistent with experimentally observed selectivity trends.
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