Superparamagnetic iron oxide nanoparticles for magnetic hyperthermia: recent advancements, molecular effects, and future directions in the omics era

Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted attention in the biomedical field thanks to their ability to prompt hyperthermia in response to an alternated magnetic field. Hyperthermia is well known for inducing cell death, in particular in tumour cells, which seem to have a higher sensitivity to temperature increases. For this reason, hyperthermia has been recommended as a therapeutic tool against cancer. Despite the potentialities of this approach, little is still known about the effects provoked by magnetic hyperthermia at the molecular level, and about the particular cell death mechanisms that are activated. Nevertheless, in-depth knowledge of this aspect would allow improvement of therapeutic outcomes and favour clinical translation. Moreover, in the last few decades, a lot of effort has been put into finding an effective delivery strategy that could improve SPION biodistribution and localisation at the action site. The aim of this review is to provide a general outline of magnetic hyperthermia, focusing on iron oxide nanoparticles and their interactions with magnetic fields, as well as on new strategies to efficiently deliver them to the target site, and on recent in vitro and in vivo studies proposing possible cell death pathways activated by the treatment. We will also cover their current clinical status, and discuss the contributions of omics in understanding molecular interactions between iron oxide nanoparticles and the biological environment

A parametric integer programming algorithm for bilevel mixed integer programs

We consider discrete bilevel optimization problems where the follower solves an integer program with a fixed number of variables. Using recent results in parametric integer programming, we present polynomial time algorithms for pure and mixed integer bilevel problems. For the mixed integer case where the leader's variables are continuous, our algorithm also detects whether the infimum cost fails to be attained, a difficulty that has been identified but not directly addressed in the literature. In this case it yields a ``better than fully polynomial time'' approximation scheme with running time polynomial in the logarithm of the relative precision. For the pure integer case where the leader's variables are integer, and hence optimal solutions are guaranteed to exist, we present two algorithms which run in polynomial time when the total number of variables is fixed.Comment: 11 page

Functional brain activity constrained by structural connectivity reveals cohort-specific features for serum neurofilament light chain

Background: Neuro-axonal brain damage releases neurofilament light chain (NfL) proteins, which enter the blood. Serum NfL has recently emerged as a promising biomarker for grading axonal damage, monitoring treatment responses, and prognosis in neurological diseases. Importantly, serum NfL levels also increase with aging, and the interpretation of serum NfL levels in neurological diseases is incomplete due to lack of a reliable model for age-related variation in serum NfL levels in healthy subjects. Methods: Graph signal processing (GSP) provides analytical tools, such as graph Fourier transform (GFT), to produce measures from functional dynamics of brain activity constrained by white matter anatomy. Here, we leveraged a set of features using GFT that quantified the coupling between blood oxygen level dependent signals and structural connectome to investigate their associations with serum NfL levels collected from healthy subjects and former athletes with history of concussions. Results: Here we show that GSP feature from isthmus cingulate in the right hemisphere (r-iCg) is strongly linked with serum NfL in healthy controls. In contrast, GSP features from temporal lobe and lingual areas in the left hemisphere and posterior cingulate in the right hemisphere are the most associated with serum NfL in former athletes. Additional analysis reveals that the GSP feature from r-iCg is associated with behavioral and structural measures that predict aggressive behavior in healthy controls and former athletes. Conclusions: Our results suggest that GSP-derived brain features may be included in models of baseline variance when evaluating NfL as a biomarker of neurological diseases and studying their impact on personality traits

Recent evolution of an ice‐cored moraine at the Gentianes Pass, Valais Alps, Switzerland

International audienceLateral moraines located in permafrost environments often preserve large amounts of both glacier and periglacial ice. To understand how ice‐cored moraines located in high alpine environments evolve in a context of both glacier retreat and permafrost degradation, we performed 11 terrestrial laser‐scanning measurement campaigns between 2007 and 2014 on a highly anthropogenic overprinted moraine prone to instability. Resulting comparison of the subsequent 3D models allowed to qualitatively and quantitatively analyze the morphological evolution of the moraine. The comparisons indicate a very high geomorphic activity of the moraine including large areas affected by downslope movements of blocks and 10 landslides with a volume between 24 ± 1 and 1,138 ± 47 m3. Data also indicated a very strong ice melt with a loss of ice thickness locally reaching 17.7 m at the foot of the moraine. These results, compared with resistivity and thermal measurements of the ground, suggest the combined role of ice loss at the foot of the moraine and the permafrost activity/warming in triggering these processes

Differences in biological traits composition of benthic assemblages between unimpacted habitats

There is an implicit requirement under contemporary policy drivers to understand the characteristics of benthic communities under anthropogenically-unimpacted scenarios. We used a trait-based approach on a large dataset from across the European shelf to determine how functional characteristics of unimpacted benthic assemblages vary between different sedimentary habitats. Assemblages in deep, muddy environments unaffected by anthropogenic disturbance show increased proportions of downward conveyors and surface deposit-feeders, while burrowing, diffusive mixing, scavenging and predation traits assume greater numerical proportions in shallower habitats. Deep, coarser sediments are numerically more dominated by sessile, upward conveyors and suspension feeders. In contrast, unimpacted assemblages of coarse sediments in shallower regions are proportionally dominated by the diffusive mixers, burrowers, scavengers and predators. Finally, assemblages of gravelly sediments exhibit a relatively greater numerical dominance of non-bioturbators and asexual reproducers. These findings may be used to form the basis of ranking habitats along a functional sensitivity gradient

Public health insurance and entry into self-employment

We estimate the impact of a differential treatment of paid employees versus self-employed workers in a public health insurance system on the entry rate into entrepreneurship. In Germany, the public health insurance system is mandatory for most paid employees, but not for the selfemployed, who usually buy private health insurance. Private health insurance contributions are relatively low for the young and healthy, and until 2013 also for males, but less attractive at the other ends of these dimensions and if membership in the public health insurance allows other family members to be covered by contribution-free family insurance. Therefore, the health insurance system can create incentives or disincentives to starting up a business depending on the family’s situation and health. We estimate a discrete time hazard rate model of entrepreneurial entry based on representative household panel data for Germany, which include personal health information, and we account for non- random sample selection. We estimate that an increase in the health insurance cost differential between self-employed workers and paid employees by 100 euro per month decreases the annual probability of entry into selfemployment by 0.38 percentage points, i.e. about a third of the average annual entry rate. The results show that the phenomenon of entrepreneurship lock, which an emerging literature describes for the system of employer provided health insurance in the USA, can also occur in a public health insurance system. Therefore, entrepreneurial activity should be taken into account when discussing potential health care reforms, not only in the USA and in Germany

Structural and Optical Properties of Diluted Magnetic Ga1−xMnxAs–AlAs Quantum Wells Grown on High-Index GaAs Planes

We report on the structural and optical properties of Ga₁₋ᵪ Mn ᵪ As-AlAs quantum wells (QWs) with χ=0.1% grown by molecular beam epitaxy (MBE) on semi-insulating GaAs substrates with orientations (100), (110), (311)B and (411)B. Atomic force microscopy (AFM), X-ray diffraction (XRD) and photoluminescence (PL) techniques were used to investigate these QWs. AFM results have evidenced the formation of Mn-induced islands, which are randomly distributed on the surface. These islands tend to segregate for samples grown on (110) and (411)B planes, while no clear segregation was observed for samples grown on (100) and (311)B orientations. Results show that the PL line width increases with Mn segregation. XRD measurements were used to determine 2θ,d and cell parameters

The effect of strain and spatial Bi distribution on the band alignment of GaAsBi single quantum well structure

The band line-up and band offset calculations of GaAs0.978Bi0.022/GaAs single quantum well with spatial changes of Bi composition were reported. The spatial Bi profile and a certain amount of the Bi composition in the barrier layer were determined by HR-XRD measurements. Virtual Crystal Approximation and Valence Band Anti-Crossing models were used including strain effects to obtain conduction and valence band edge shifts with Bi incorporation. Photoluminescence (PL) measurements were performed at a low temperature of 8 K as a function of excitation intensity. The PL spectra have shown asymmetric line shapes, which were fitted with different Gaussian functions. Comparing experimental PL results with calculated band edge energies, it was found that optical transition is a type I under low intensity excitation while the optical transition is switched from type I to type II due to the spatial changes in Bi concentrations. The band offsets?Ec/?Ev were also determined