River flow is mainly controlled by climate, physiography and regulations, but their relative importance over large landmasses is poorly understood. Here we show from computational modelling that ...hydropower regulation is a key driver of flow regime change in snow-dominated regions and is more important than future climate changes. This implies that climate adaptation needs to include regulation schemes. The natural river regime in snowy regions has low flow when snow is stored and a pronounced peak flow when snow is melting. Global warming and hydropower regulation change this temporal pattern similarly, causing less difference in river flow between seasons. We conclude that in snow-fed rivers globally, the future climate change impact on flow regime is minor compared to regulation downstream of large reservoirs, and of similar magnitude over large landmasses. Our study not only highlights the impact of hydropower production but also that river regulation could be turned into a measure for climate adaptation to maintain biodiversity on floodplains under climate change.Global warming and hydropower regulations are major threats to future fresh-water availability and biodiversity. Here, the authors show that their impact on flow regime over a large landmass result in similar changes, but hydropower is more critical locally and may have potential for climate adaptation in floodplains.
Recent progress in nanofabrication and additive manufacturing have facilitated the building of nanometer-scale three-dimensional (3D) structures, that promise to lead to an emergence of new ...functionalities within a number of fields, compared to state-of-the-art two dimensional systems. In magnetism, the move to 3D systems offers the possibility for novel magnetic properties not available in planar systems, as well as enhanced performance, both of which are key for the development of new technological applications. In this review paper we will focus our attention on 3D magnetic systems and how their magnetic configuration can be retrieved using x-ray magnetic nanotomography. We will start with an introduction to magnetic materials, and their relevance to our everyday life, along with the growing impact that they will have in the coming years in, for example, reducing energy consumption. We will then briefly introduce common methods used to study magnetic materials, such as electron holography, neutron and x-ray imaging. In particular, we will focus on x-ray magnetic circular dichroism (XMCD) and how it can be used to image magnetic moment configurations. As a next step we will introduce tomography for 3D imaging, and how it can be adapted to study magnetic materials. Particular attention will be given to explaining the reconstruction algorithms that can be used to retrieve the magnetic moment configuration from the experimental data, as these represent one of the main challenges so far, as well as the different experimental geometries that are available. Recent experimental results will be used as specific examples to guide the reader through each step in order to make sure that the paper will be accessible for those interested in the topic that do not have a specialized background on magnetic imaging. Finally, we will describe the future prospects of such studies, identifying the current challenges facing the field, and how these can be tackled. In particular we will highlight the exciting possibilities offered by the next generation of synchrotron sources which will deliver diffraction limited beams, as well as with the extension of well-established methodologies currently implemented for the study of two-dimensional magnetic materials to achieve higher dimensional investigations.
Strong evidence has been presented linking chronic inflammation to the onset and pathogenesis of cancer. The multifunctional pro‐inflammatory protein macrophage migration inhibitory factor (MIF) ...occupies a central role in the inflammatory pathway and has been implicated in the tumorigenesis, angiogenesis, and metastasis of many cancer phenotypes. This review highlights the current state of the art, which presents MIF, and the second member of the MIF structural superfamily, d‐DT (MIF2), as significant mediators in the inflammatory–cancer axis. Although the mechanism by which MIF asserts its biological activity has yet to be fully understood, it has become clear in recent years that for certain phenotypes of cancer, MIF represents a valid therapeutic target. Current research efforts have focused on small molecule approaches that target MIF's unique tautomerase active site and neutralization of MIF with anti‐MIF antibodies. These approaches have yielded promising results in a number of preclinical murine cancer models and have helped to increase our understanding of MIF biological activity. More recently, MIF's involvement in a number of key protein–protein interactions, such as with CD74 and HSP90, has been highlighted and provides a novel platform for the development of anti‐MIF chemotherapeutic strategies in the future.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The quantum superposition principle allows massive particles to be delocalized over distant positions. Though quantum mechanics has proved adept at describing the microscopic world, quantum ...superposition runs counter to intuitive conceptions of reality and locality when extended to the macroscopic scale, as exemplified by the thought experiment of Schrödinger's cat. Matter-wave interferometers, which split and recombine wave packets in order to observe interference, provide a way to probe the superposition principle on macroscopic scales and explore the transition to classical physics. In such experiments, large wave-packet separation is impeded by the need for long interaction times and large momentum beam splitters, which cause susceptibility to dephasing and decoherence. Here we use light-pulse atom interferometry to realize quantum interference with wave packets separated by up to 54 centimetres on a timescale of 1 second. These results push quantum superposition into a new macroscopic regime, demonstrating that quantum superposition remains possible at the distances and timescales of everyday life. The sub-nanokelvin temperatures of the atoms and a compensation of transverse optical forces enable a large separation while maintaining an interference contrast of 28 per cent. In addition to testing the superposition principle in a new regime, large quantum superposition states are vital to exploring gravity with atom interferometers in greater detail. We anticipate that these states could be used to increase sensitivity in tests of the equivalence principle, measure the gravitational Aharonov-Bohm effect, and eventually detect gravitational waves and phase shifts associated with general relativity.
Full text
Available for:
IJS, KISLJ, NUK, SBMB, SIK, UL, UM, UPUK
Macrophage migration inhibitory factor (MIF) was the original cytokine, described almost 50 years ago and has since been revealed to be an important player in pro-inflammatory diseases. Recent work ...using MIF mouse models has revealed new roles for MIF. In this review, we present an increasing body of evidence implicating the key pro-inflammatory cytokine MIF in specific biological activities related directly to cancer growth or contributing towards a microenvironment favouring cancer progression.
Blood relations: Nanoparticles that enter the bloodstream become coated with proteins. Four apolipoproteins are consistently recovered on model copolymer nanoparticles by using a centrifugation ...procedure (see electropherogram); their interaction with the nanoparticles is stronger than that of other plasma proteins with higher abundance.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Fibrocytes are a distinct population of blood-borne cells that display a unique cell surface phenotype (collagen I+/CD11b+/CD13+/CD34+/CD45RO+/MHC class II+/CD86+) and exhibit potent ...immunostimulatory activities. Circulating fibrocytes rapidly enter sites of tissue injury, suggesting an important role for these cells in wound repair. However, the regulatory processes that govern the differentiation of blood-borne fibrocytes and the mechanisms that underlie the migration of these cells to wound sites are currently not known. We report herein that ex vivo cultured fibrocytes can differentiate from a CD14+-enriched mononuclear cell population and that this process requires contact with T cells. Furthermore, we demonstrate that TGF-beta1 (1-10 ng/ml), an important fibrogenic and growth-regulating cytokine involved in wound healing, increases the differentiation and functional activity of cultured fibrocytes. Because fibrocytes home to sites of tissue injury, we examined the role of chemokine/chemokine receptor interactions in fibrocyte trafficking. We show that secondary lymphoid chemokine, a ligand of the CCR7 chemokine receptor, acts as a potent stimulus for fibrocyte chemotaxis in vitro and for the homing of injected fibrocytes to sites of cutaneous tissue injury in vivo. Finally, we demonstrate that differentiated, cultured fibrocytes express alpha smooth muscle actin and contract collagen gels in vitro, two characteristic features of wound-healing myofibroblasts. These data provide important insight into the control of fibrocyte differentiation and trafficking during tissue repair and significantly expand their potential role during wound healing.
Despite three decades of successful, predominantly phenotype-driven discovery of the genetic causes of monogenic disorders, up to half of children with severe developmental disorders of probable ...genetic origin remain without a genetic diagnosis. Particularly challenging are those disorders rare enough to have eluded recognition as a discrete clinical entity, those with highly variable clinical manifestations, and those that are difficult to distinguish from other, very similar, disorders. Here we demonstrate the power of using an unbiased genotype-driven approach to identify subsets of patients with similar disorders. By studying 1,133 children with severe, undiagnosed developmental disorders, and their parents, using a combination of exome sequencing and array-based detection of chromosomal rearrangements, we discovered 12 novel genes associated with developmental disorders. These newly implicated genes increase by 10% (from 28% to 31%) the proportion of children that could be diagnosed. Clustering of missense mutations in six of these newly implicated genes suggests that normal development is being perturbed by an activating or dominant-negative mechanism. Our findings demonstrate the value of adopting a comprehensive strategy, both genome-wide and nationwide, to elucidate the underlying causes of rare genetic disorders.
Full text
Available for:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Ideally, the results from models operating at different scales should agree in trend direction and magnitude of impacts under climate change. However, this implies that the sensitivity to climate ...variability and climate change is comparable for impact models designed for either scale. In this study, we compare hydrological changes simulated by 9 global and 9 regional hydrological models (HM) for 11 large river basins in all continents under reference and scenario conditions. The foci are on model validation runs, sensitivity of annual discharge to climate variability in the reference period, and sensitivity of the long-term average monthly seasonal dynamics to climate change. One major result is that the global models, mostly not calibrated against observations, often show a considerable bias in mean monthly discharge, whereas regional models show a better reproduction of reference conditions. However, the sensitivity of the two HM ensembles to climate variability is in general similar. The simulated climate change impacts in terms of long-term average monthly dynamics evaluated for HM ensemble medians and spreads show that the medians are to a certain extent comparable in some cases, but have distinct differences in other cases, and the spreads related to global models are mostly notably larger. Summarizing, this implies that global HMs are useful tools when looking at large-scale impacts of climate change and variability. Whenever impacts for a specific river basin or region are of interest, e.g. for complex water management applications, the regional-scale models calibrated and validated against observed discharge should be used.
Abstract The kinematic mechanisms associated with elevated externally applied valgus knee moments during non-contact sidestepping and subsequent anterior cruciate ligament (ACL) injury risk are not ...well understood. To address this issue, the residual reduction algorithm (RRA) in OpenSim was used to create nine subject-specific, full-body (37 degrees of freedom) torque-driven simulations of athletic males performing unplanned sidestep (UnSS) sport tasks. The RRA was used again to produce an optimized kinematic solution with reduced peak valgus knee torques during the weight acceptance phase of stance. Pre-to-post kinematic optimization, mean peak valgus knee moments were significantly reduced by 44.2 Nm ( p =0.045). Nine of a possible 37 upper and lower body kinematic changes in all three planes of motion were consistently used during the RRA to decrease peak valgus knee moments. The generalized kinematic strategy used by all nine simulations to reduce peak valgus knee moments and subsequent ACL injury risk during UnSS was to redirect the whole-body center of mass medially, towards the desired direction of travel.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PDF
