Standard cancer therapies sometimes fail to deliver chemotherapeutic drugs to tumor cells in a safe and effective manner.
Nanotechnology takes the lead in providing new therapeutic options for cancer ...due to major potential for selective targeting and controlled drug release. Antibodies and antibody fragments are attracting much attention as a source of targeting ligands to bind specific receptors that are overexpressed on cancer cells.
Therefore, researchers are devoting time and effort to develop targeting strategies based on nanoparticles functionalized with antibodies, which hold great promise to enhance therapeutic efficacy and circumvent severe side effects.
Several methods have been described to immobilize antibodies on the surface of nanoparticles. However, selecting the most appropriate for each application is challenging but also imperative to preserve antigen binding ability and yield stable antibody-conjugated nanoparticles.
From this perspective, we aim to provide considerable knowledge on the most widely used methods of functionalization that can be helpful for decision-making and design of conjugation protocols as well. This review summarizes adsorption, covalent conjugation (carbodiimide, maleimide and “click” chemistries) and biotin-avidin interaction, while discussing the advantages, limitations and relevant therapeutic approaches currently under investigation.
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•Tumor targeting is promising to address some drawbacks of conventional chemotherapy.•Antibody-conjugated nanoparticles favor a safe and effective drug delivery to tumor.•Immobilization of antibodies should be well-oriented and keep biological activity.•Functionalization of nanoparticles includes covalent and non-covalent methods.•The ideal conjugation method allows a site-specific reaction and a stable coupling.
Context. The seismic data provided by the space-borne missions CoRoT and Kepler enabled us to probe the internal rotation of thousands of evolved low-mass stars. Subsequently, several studies showed ...that current stellar evolution codes are unable to reproduce the low core rotation rates observed in these stars. These results indicate that an additional angular momentum transport process is necessary to counteract the spin up due to the core contraction during the post-main sequence evolution. For several candidates, the transport induced by internal gravity waves (IGW) could play a non-negligible role. Aims. We aim to investigate the effect of IGW generated by penetrative convection on the internal rotation of low-mass stars from the subgiant branch to the beginning of the red giant branch. Methods. A semi-analytical excitation model was used to estimate the angular momentum wave flux. The characteristic timescale associated with the angular momentum transport by IGW was computed and compared to the contraction timescale throughout the radiative region of stellar models at different evolutionary stages. Results. We show that IGW can efficiently counteract the contraction-driven spin up of the core of subgiant stars if the amplitude of the radial-differential rotation (between the center of the star and the top of the radiative zone) is higher than a threshold value. This threshold depends on the evolutionary stage and is comparable to the differential rotation rates inferred for a sample of subgiant stars observed by the satellite Kepler. Such an agreement can therefore be interpreted as the consequence of a regulation mechanism driven by IGW. This result is obtained under the assumption of a smooth rotation profile in the radiative region and holds true even if a wide range of values is considered for the parameters of the generation model. In contrast, on the red giant branch, we find that IGW remain insufficient, on their own, to explain the observations because of an excessive radiative damping. Conclusions. IGW generated by penetrative convection are able to efficiently extract angular momentum from the core of stars on the subgiant branch and accordingly have to be taken into account. Moreover, agreements with the observations reinforce the idea that their effect is essential to regulate the amplitude of the radial-differential rotation in subgiant stars. On the red giant branch, another transport mechanism must likely be invoked.
Context. The space mission Kepler provides us with long and uninterrupted photometric time series of red giants. We are now able to probe the rotational behaviour in their deep interiors using the ...observations of mixed modes. Aims. We aim to measure the rotational splittings in red giants and to derive scaling relations for rotation related to seismic and fundamental stellar parameters. Methods. We have developed a dedicated method for automated measurements of the rotational splittings in a large number of red giants. Ensemble asteroseismology, namely the examination of a large number of red giants at different stages of their evolution, allows us to derive global information on stellar evolution. Results. We have measured rotational splittings in a sample of about 300 red giants. We have also shown that these splittings are dominated by the core rotation. Under the assumption that a linear analysis can provide the rotational splitting, we observe a small increase of the core rotation of stars ascending the red giant branch. Alternatively, an important slow down is observed for red-clump stars compared to the red giant branch. We also show that, at fixed stellar radius, the specific angular momentum increases with increasing stellar mass. Conclusions. Ensemble asteroseismology indicates what has been indirectly suspected for a while: our interpretation of the observed rotational splittings leads to the conclusion that the mean core rotation significantly slows down during the red giant phase. The slow-down occurs in the last stages of the red giant branch. This spinning down explains, for instance, the long rotation periods measured in white dwarfs.
Context. Rotational splittings are currently measured for several main sequence stars and a large number of red giants with the space mission Kepler. This will provide stringent constraints on ...rotation profiles. Aims. Our aim is to obtain seismic constraints on the internal transport and surface loss of the angular momentum of oscillating solar-like stars. To this end, we study the evolution of rotational splittings from the pre-main sequence to the red-giant branch for stochastically excited oscillation modes. Methods. We modified the evolutionary code CESAM2K to take rotationally induced transport in radiative zones into account. Linear rotational splittings were computed for a sequence of 1.3 M sub(middot in circle) models. Rotation profiles were derived from our evolutionary models and eigenfunctions from linear adiabatic oscillation calculations. Results. We find that transport by meridional circulation and shear turbulence yields far too high a core rotation rate for red-giant models compared with recent seismic observations. We discuss several uncertainties in the physical description of stars that could have an impact on the rotation profiles. For instance, we find that the Goldreich-Schubert-Fricke instability does not extract enough angular momentum from the core to account for the discrepancy. In contrast, an increase of the horizontal turbulent viscosity by 2 orders of magnitude is able to significantly decrease the central rotation rate on the red-giant branch. Conclusions. Our results indicate that it is possible that the prescription for the horizontal turbulent viscosity largely underestimates its actual value or else a mechanism not included in current stellar models of low mass stars is needed to slow down the rotation in the radiative core of red-giant stars.
Helioseismology and asteroseismology of red giant stars have shown that distribution of angular momentum in stellar interiors, and the evolution of this distribution with time remains an open issue ...in stellar physics. Owing to the unprecedented quality and long baseline of Kepler photometry, we are able to seismically infer internal rotation rates in γ Doradus stars, which provide the main-sequence counterpart to the red-giants puzzle. Here, we confront these internal rotation rates to stellar evolution models which account for rotationally induced transport of angular momentum, in order to test angular momentum transport mechanisms. On the one hand, we used a stellar model-independent method developed by our team in order to obtain accurate, seismically inferred, buoyancy radii and near-core rotation for 37 γ Doradus stars observed by Kepler. We show that the stellar buoyancy radius can be used as a reliable evolution indicator for field stars on the main sequence. On the other hand, we computed rotating evolutionary models of intermediate-mass stars including internal transport of angular momentum in radiative zones, following the formalism developed in the series of papers started by Zahn (1992, A&A, 265, 115), with the CESTAM code. This code calculates the rotational history of stars from the birth line to the tip of the RGB. The initial angular momentum content has to be set initially, which is done here by fitting rotation periods in young stellar clusters. We show a clear disagreement between the near-core rotation rates measured in the sample and the rotation rates obtained from the evolutionary models including rotationally induced transport of angular momentum following Zahn’s prescriptions. These results show a disagreement similar to that of the Sun and red giant stars in the considered mass range. This suggests the existence of missing mechanisms responsible for the braking of the core before and along the main sequence. The efficiency of the missing mechanisms is investigated. The transport of angular momentum as formalized by Zahn and Maeder cannot explain the measurements of near-core rotation in main-sequence intermediate-mass stars we have at hand.
The use of adhesive bonding in diverse industries such as the automotive and aerospace sectors has grown considerably. In structural construction, adhesive joints provide a unique combination of low ...structural weight, high strength and stiffness, combined with a relatively simple and easily automated manufacturing method, characteristics that are ideal for the development of modern and highly efficient vehicles. In these applications, ensuring that the failure mode of a bonded joint is cohesive rather than adhesive is important since this failure mode is more controlled and easier to model and to predict. This work presents a numerical technique that enables the precise prediction of the bonded joint's behavior regarding not only its failure mode, but also the joint's strength, when inorganic fillers are added to the adhesive. To that end, hollow glass particles were introduced into an epoxy adhesive in different amounts, and a numerical study was carried out to simulate their influence on single lap joint specimens. The numerical results were compared against experimental ones, not only in terms of joint strength, but also their failure pattern. The neat adhesive, which showed 9% and 20% variations in terms of failure load and displacement, respectively. However, looking at the doped configurations, these presented smaller variations of about 2% and 10% for each respective variable. In all cases, by adding glass beads, crack initiation tended to change from adhesive to cohesive but with lower strength and ductility, correctly modeling the general experimental behavior as intended.
Summary
The purpose of this systematic review and meta‐analysis was to estimate the prevalence of personal weight control attempts (weight loss and/or maintenance) worldwide and to identify ...correlates, personal strategies used and the underlying motives. We included epidemiological/observational studies of adults (≥18 years) reporting prevalence of weight control attempts in the past‐year. Seventy‐two studies (n = 1,184,942) met eligibility criteria. Results from high quality studies showed that 42% of adults from general populations and 44% of adults from ethnic‐minority populations reported trying to lose weight, and 23% of adults from general populations reported trying to maintain weight annually. In general population studies, higher prevalence of weight loss attempts was observed in the decade of 2000–2009 (48.2%), in Europe/Central Asia (61.3%) and in overweight/obese individuals and in women (p < 0.01). Of the 37 strategies (grouped in 10 domains of the Oxford Food and Activity Behaviours Taxonomy) and 12 motives reported for trying to control weight, exercising and dieting (within the energy compensation and restraint domains, respectively) and wellbeing and long‐term health were the most prevalent. To our knowledge, this is the first systematic review to investigate weight control attempts worldwide. Key strategies and motives were identified which have implications for future public health initiatives on weight control.
Exercise is one of the most effective strategies to maintain a healthy body and mind, with particular beneficial effects of exercise on promoting brain plasticity, increasing cognition and reducing ...the risk of cognitive decline and dementia in later life. Moreover, the beneficial effects resulting from increased physical activity occur at different levels of cellular organization, mitochondria being preferential target organelles. The relevance of this review article relies on the need to integrate the current knowledge of proposed mechanisms, focus mitochondria, to explain the protective effects of exercise that might underlie neuroplasticity and seeks to synthesize these data in the context of exploring exercise as a feasible intervention to delay cognitive impairment associated with neurodegenerative conditions, particularly Alzheimer disease.
Understanding how super-massive black holes form and grow in the early Universe has become a major challenge
since it was discovered that luminous quasars existed only 700 million years after the Big ...Bang
. Simulations indicate an evolutionary sequence of dust-reddened quasars emerging from heavily dust-obscured starbursts that then transition to unobscured luminous quasars by expelling gas and dust
. Although the last phase has been identified out to a redshift of 7.6 (ref.
), a transitioning quasar has not been found at similar redshifts owing to their faintness at optical and near-infrared wavelengths. Here we report observations of an ultraviolet compact object, GNz7q, associated with a dust-enshrouded starburst at a redshift of 7.1899 ± 0.0005. The host galaxy is more luminous in dust emission than any other known object at this epoch, forming 1,600 solar masses of stars per year within a central radius of 480 parsec. A red point source in the far-ultraviolet is identified in deep, high-resolution imaging and slitless spectroscopy. GNz7q is extremely faint in X-rays, which indicates the emergence of a uniquely ultraviolet compact star-forming region or a Compton-thick super-Eddington black-hole accretion disk at the dusty starburst core. In the latter case, the observed properties are consistent with predictions from cosmological simulations
and suggest that GNz7q is an antecedent to unobscured luminous quasars at later epochs.