Multidrug resistance (MDR) in cancer is one of the main limitations for chemotherapy success. Numerous mechanisms are behind the MDR phenomenon wherein the overexpression of the ATP-binding cassette ...(ABC) transporter proteins P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance protein 1 (MRP1) is highlighted as a prime factor. Natural product-derived compounds are being addressed as promising ABC transporter modulators to tackle MDR. Flavonoids and terpenoids have been extensively explored in this field as mono or dual modulators of these efflux pumps. Nitrogen-bearing moieties on these scaffolds were proved to influence the modulation of ABC transporters efflux function. This review highlights the potential of semisynthetic nitrogen-containing flavonoid and terpenoid derivatives as candidates for the design of effective MDR reversers. A brief introduction concerning the major role of efflux pumps in multidrug resistance, the potential of natural product-derived compounds in MDR reversal, namely natural flavonoid and terpenoids, and the effect of the introduction of nitrogen-containing groups are provided. The main modifications that have been performed during last few years to generate flavonoid and terpenoid derivatives, bearing nitrogen moieties, such as aliphatic, aromatic and heterocycle amine, amide, and related functional groups, as well as their P-gp, MRP1 and BCRP inhibitory activities are reviewed and discussed.
•Real-time visual observations of the hydraulic fracturing processes in a natural crystalline rock.•The vertical load does not affect the coalescence at high bridging angles, but affects for ...low.•Long-lasting and short-lasting white patching i.e. process zone, were observed.•Visible cracking was mostly tensile, with minor shear segments along grain boundaries.
Hydraulic fracturing is a method routinely used in oil and gas extraction and in engineered geothermal systems. While applied frequently, there are many aspects of hydraulic fracturing that are not well understood, such as the effect of the vertical load and fracture geometry in the physical processes responsible for the development of hydraulically-created fractures.
This paper presents an experimental study, in which prismatic granite specimens subjected to two different vertical loads (0 and 5 MPa) were hydraulically-fractured by applying a hydraulic pressure inside single and double pre-existing flaws. The fracturing processes were observed using High-Speed Video and High-Resolution cameras. In addition, the fracturing observed in the hydraulic fracturing tests was also compared to uniaxial compression tests performed on similar granite specimens with pre-fabricated flaws but no hydraulic pressure (“dry” tests).
It was observed that cracking initiation was usually preceded by white patches, i.e. a process zone consisting of micro-cracks. There are two types of white patching, namely, “long-lasting”, which last for several seconds before transforming into a physical crack and “short-lasting”, which only exist for fractions of a millisecond, before transforming into a visible crack. The latter seems to be specific to hydraulic fracture tests since it was not observed in tests without hydraulic fracturing. While cracking was mostly tensile, there was also minor shearing along grain boundaries between segments of tensile cracks.
Most importantly, a combined effect of loading conditions and existing flaw geometries on the fracturing processes was observed. At low bridging angles, there is a distinct difference of the coalescence pattern depending on the loading condition: direct coalescence when no vertical load was applied and no coalescence when a vertical load of 5 MPa was applied. At higher bridging angles, there is no effect of the loading conditions. This is consistent with the water pressure at failure (WPmax): for higher bridging angles, WPmax is the same regardless of the loading conditions, while for lower bridging angles WPmax is larger when a vertical load of 5 MPa is applied.
•Acoustic emissions begin to occur at approximately 80% of peak pressure.•55–60% of the radiation pattern could be explained by a double couple mechanism.•Hypocenter locations agree with visually ...observed white patching and crack patterns.•Detected instances of microcrack coalescence with acoustic emissions.•Acoustic emissions could be used to non-uniquely predict crack initiation.
Hydraulic fracturing is routinely used, but the fracturing processes that occur when rocks are hydraulically-fractured are not entirely understood and require further investigation. This study presents the acquisition, analysis and interpretation of acoustic emissions data from a series of laboratory hydraulic fracturing experiments on granite. Specimens with different orientations of two pre-cut flaws were tested under both 0 MPa and 5 MPa of vertical uniaxial stress to understand the effect of the external stress conditions. Acoustic emissions data are related to corresponding visual observations made using high-resolution and high-speed imaging. We find that in general, (1) the AE begin to occur at approximately 80% of peak pressure, (2) the focal mechanisms suggest that 55–60% of the radiation pattern could be explained by a double couple mechanism and is well-explained by simulation results, (3) hypocenter locations tended to agree well with visually observed white patching (process zone) and crack patterns, (4) spatio-temporal analysis revealed points in time at which microcrack coalescence were detected by AE, (5) that the AE could be used to make a non-unique prediction of crack initiation, and lastly (6) that exponential AE energy accumulation in the last 5–10 s prior to crack initiation can be modelled by time-to-failure methods.
Metabolic syndrome (MetS) is a complex condition comprising a 'clustering' of components representing cardiometabolic risk factors for heart disease and diabetes; its prevalence rate is high and ...consequences serious. Evidence suggests that light exposure patterns and misalignment of circadian rhythms might contribute to MetS etiology by impacting energy metabolism and glucose regulation. We hypothesised that individuals with MetS would show disrupted circadian and sleep parameters alongside differences in light exposure profiles. We investigated this using data from a cohort study in Brazil. Data from 103 individuals from the Baependi Heart Cohort Study aged between 50 and 70 were analysed. Motor activity and light exposure were measured using wrist-worn actigraphy devices. Cardiometabolic data were used to calculate the number of MetS components present in each participant, and participants grouped as MetS/non-MetS according to standard guidelines. Between-group comparisons were made for the actigraphy measures; additionally, correlation analyses were conducted. Motor activity and circadian profiles showed no differences between groups. However, the MetS group presented lower light exposure during the day and higher light exposure at night. Correlation analyses, including all participants, showed that greater daytime light exposure and greater light exposure difference between day and night were associated with reduced MetS risk (a lower number of MetS components). Also, the light exposure difference between day and night correlated with body mass index across all participants. The observed results suggest a direct association between light exposure and MetS which appears to not be attributable to disruptions in circadian activity rhythm nor to sleep parameters. This link between light exposure patterns and MetS risk could inform possible prevention strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to identify differences in time-motion, modified training impulse, body load and movement behaviour between defenders, midfielders and forwards, during an 11-a-side ...simulated football game. Twenty elite youth male footballers from the same squad participated in this study (age: 18.1 ± 0.7 years old, body mass: 70.5 ± 4.3 kg, height: 1.8 ± 0.3 m and playing experience: 9.4 ± 1.3 years). All data were collected using GPS units (SPI-Pro, GPSports, Canberra, Australia). The movement behaviour was measured with kinematic data, used to calculate position-specific centroids (defenders, midfielders and forwards), and processed with non-linear statistical procedures (approximate entropy normalised and relative phase). There were significant effects and interactions in all variables across the players' positions. The results showed that displacements of all players (defenders, midfielders and forwards) were nearer and more coordinated with their own position-specific centroids than with the other centroids. However, this coupling effect was stronger in midfield players and weaker in forwards. All players' dynamical positioning showed more irregularity when related to the forwards' centroid, as a consequence of their need to be less predictable when playing. The time-motion and physiological variables showed lower activity in forward players. Adding together, the results may contribute to a better understanding of players' specific performances and football complexity.
Large scale analysis and statistics of socio-technical systems that just a few short years ago would have required the use of consistent economic and human resources can nowadays be conveniently ...performed by mining the enormous amount of digital data produced by human activities. Although a characterization of several aspects of our societies is emerging from the data revolution, a number of questions concerning the reliability and the biases inherent to the big data "proxies" of social life are still open. Here, we survey worldwide linguistic indicators and trends through the analysis of a large-scale dataset of microblogging posts. We show that available data allow for the study of language geography at scales ranging from country-level aggregation to specific city neighborhoods. The high resolution and coverage of the data allows us to investigate different indicators such as the linguistic homogeneity of different countries, the touristic seasonal patterns within countries and the geographical distribution of different languages in multilingual regions. This work highlights the potential of geolocalized studies of open data sources to improve current analysis and develop indicators for major social phenomena in specific communities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Os sentidos do anacronismo Gonçalves, Bruno
História da Historiografia,
04/2022, Letnik:
15, Številka:
38
Journal Article
Recenzirano
Odprti dostop
O objetivo deste balanço é sintetizar o que foi escrito nas últimas décadas sobre o conceito de anacronismo em diferentes campos do conhecimento. O panorama oferecido revela que o anacronismo ...compreende vários significados (dentre eles: atribuição conceitual, ferramenta heurística, tabu profissional e índice de consciência histórica) e que existem estratégias para lidar com ele (criação de tipologias e critérios de admissão, reafirmação do tabu, crítica radical, entre outras). Além disso, o conceito desempenha papel de grande importância nas disputas intelectuais, cuja reflexão oferece uma ocasião privilegiada para o exercício de poder sobre a historiografia. Conclui-se que o anacronismo é um conceito polissêmico, duradouro e polêmico, e que seu valor normativo parece comprometer o estudo de sua história.
Covering: up to December 2011
This review highlights the potential of natural and semisynthetic ursane-type triterpenoids as candidates for the design of multi-target bioactive compounds, with focus ...on their anticancer effects. A brief illustration of the biosynthesis, sources, and general biological effects of the main classes of naturally occurring pentacyclic triterpenoids (PTs) are provided.
Triterpenoids represent a vast group of compounds, including ursane-type ursolic acid, asiatic acid, corosolic acid, pomolic acid, β-boswellic acid, acetyl β-boswellic acid, 11-keto-β-boswellic acid, and acetyl-11-keto-β-boswellic acid. This review summarizes the anticancer effects of these compounds and their semisynthetic derivatives.
Among the realistic ingredients to be considered in the computational modeling of infectious diseases, human mobility represents a crucial challenge both on the theoretical side and in view of the ...limited availability of empirical data. To study the interplay between short-scale commuting flows and long-range airline traffic in shaping the spatiotemporal pattern of a global epidemic we (i) analyze mobility data from 29 countries around the world and find a gravity model able to provide a global description of commuting patterns up to 300 kms and (ii) integrate in a worldwide-structured metapopulation epidemic model a timescale-separation technique for evaluating the force of infection due to multiscale mobility processes in the disease dynamics. Commuting flows are found, on average, to be one order of magnitude larger than airline flows. However, their introduction into the worldwide model shows that the large-scale pattern of the simulated epidemic exhibits only small variations with respect to the baseline case where only airline traffic is considered. The presence of short-range mobility increases, however, the synchronization of subpopulations in close proximity and affects the epidemic behavior at the periphery of the airline transportation infrastructure. The present approach outlines the possibility for the definition of layered computational approaches where different modeling assumptions and granularities can be used consistently in a unifying multiscale framework.
No prior studies have evaluated the efficacy and safety of zolpidem and zopiclone to treat insomnia of demented patients. This randomized, triple-blind, placebo-controlled clinical trial used these ...drugs to treat patients with probable, late onset Alzheimer's dementia (AD) (DSM V and NINCDS-ADRDA criteria) exhibiting insomnia (DSM V criteria and nocturnal NPI scores ≥ 2). Actigraphic records were performed for 7 days at baseline and for 14 days during the treatment period in 62 patients aged 80.5 years in average and randomized at a 1:1:1 ratio for administration of zolpidem 10 mg/day, zopiclone 7.5 mg/day or placebo. Primary endpoint was the main nocturnal sleep duration (MNSD), whereas secondary outcomes were the proportion of the night time slept, awake time after sleep onset (WASO), nocturnal awakenings, total daytime sleep time and daytime naps. Cognitive and functional domains were tested before and after drug/placebo use. Three participants under zopiclone use had intervention interrupted due to intense daytime sedation and worsened agitation with wandering. Zopiclone produced an 81 min increase in MNSD (95% confidence interval (CI): -0.8, 163.2), a 26 min reduction in WASO (95% CI: -56.2, 4.8) and a 2-episode decrease in awakening per night (95% CI: -4.0, 0.4) in average compared to placebo. Zolpidem yielded no significant difference in MNSD despite a significant 22 min reduction in WASO (95% CI: -52.5, 8.3) and a reduction of 1 awakening each night (95% CI: -3.4, 1.2) in relation to placebo. There was a 1-point reduction in mean performance in the symbols search test among zolpidem users (95% CI: -4.1, 1.5) and an almost eight-point reduction in average scores in the digit-symbol coding test among zopiclone users (95% CI: -21.7, 6.2). In summary, short-term use of zolpidem or zopiclone by older insomniacs with AD appears to be clinically helpful, even though safety and tolerance remain issues to be personalized in healthcare settings and further investigated in subsequent trials. This trial was registered in ClinicalTrials.gov Identifier: NCT03075241.
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