The cost, size and availability of electron accelerators are dominated by the achievable accelerating gradient. Conventional high-brightness radio-frequency accelerating structures operate with 30-50 ...MeV m(-1) gradients. Electron accelerators driven with optical or infrared sources have demonstrated accelerating gradients orders of magnitude above that achievable with conventional radio-frequency structures. However, laser-driven wakefield accelerators require intense femtosecond sources and direct laser-driven accelerators suffer from low bunch charge, sub-micron tolerances and sub-femtosecond timing requirements due to the short wavelength of operation. Here we demonstrate linear acceleration of electrons with keV energy gain using optically generated terahertz pulses. Terahertz-driven accelerating structures enable high-gradient electron/proton accelerators with simple accelerating structures, high repetition rates and significant charge per bunch. These ultra-compact terahertz accelerators with extremely short electron bunches hold great potential to have a transformative impact for free electron lasers, linear colliders, ultrafast electron diffraction, X-ray science and medical therapy with X-rays and electron beams.
With the recent advances in ultrabright electron and x-ray sources, it is now possible to extend crystallography to the femtosecond time domain to literally light up atomic motions involved in the ...primary processes governing structural transitions. This review chronicles the development of brighter and brighter electron and x-ray sources that have enabled atomic resolution to structural dynamics for increasingly complex systems. The primary focus is on achieving sufficient brightness using pump-probe protocols to resolve the far-from-equilibrium motions directing chemical processes that in general lead to irreversible changes in samples. Given the central importance of structural transitions to conceptualizing chemistry, this emerging field has the potential to significantly improve our understanding of chemistry and its connection to driving biological processes.
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In this narrative review, we discuss the emerging role of innate immunity in osteoarthritis (OA) joint pain. First, we give a brief description of the pain pathway in the context of OA. Then we ...consider how neuro-immune signaling pathways may promote OA pain. First, activation of neuronal Pattern Recognition Receptors by mediators released in a damaged joint can result in direct excitation of nociceptors, as well as in production of chemokines and cytokines. Secondly, indirect neuro-immune signaling may occur when innate immune cells produce algogenic factors, including chemokines and cytokines, that act on the pain pathway. Neuro-immune crosstalk occurs at different levels of the pathway, starting in the joint but also in the innervating dorsal root ganglia and in the dorsal horn. Synovitis is characterized by recruitment of immune cells, including macrophages, mast cells, and CD4+ lymphocytes, which may contribute to nociceptor sensitization and OA pain through production of algogenic factors that amplify the activation of sensory neurons. We discuss examples where this scenario has been suggested by findings in human OA and in animal models. Overall, increasing evidence suggests that innate immune pathways play an initiating as well as facilitating role in pain, but information on how these pathways operate in OA remains limited. Since these innate pathways are eminently targetable, future studies in this area may provide fruitful leads towards a better management of symptomatic OA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Highlights • Diverse animal models of depression and anxiety have impaired neurogenesis. • Neurogenesis is consistently boosted by antidepressants in animal models when animals are stressed. • ...Ablation of neurogenesis in animal models impairs cognitive functions relevant to depression, but only a minority of studies find that ablation causes depression or anxiety. • Recent human neuroimaging and postmortem studies are consistent with the neurogenic theory, but they are indirect. • A novel drug developed based on the neurogenic theory is promising in animal models.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
The cardiovascular effects of inhaled particle matter (PM) are responsible for a substantial morbidity and mortality attributed to air pollution. Ultrafine particles, like those in diesel ...exhaust emissions, are a major source of nanoparticles in urban environments, and it is these particles that have the capacity to induce the most significant health effects. Research has shown that diesel exhaust exposure can have many detrimental effects on the cardiovascular system both acutely and chronically. This review provides an overview of the cardiovascular effects on PM in air pollution, with an emphasis on ultrafine particles in vehicle exhaust. We consider the biological mechanisms underlying these cardiovascular effects of PM and postulate that cardiovascular dysfunction may be implicated in the effects of PM in other organ systems. The employment of multiple strategies to tackle air pollution, and especially ultrafine particles from vehicles, is likely to be accompanied by improvements in cardiovascular health.
Graphical Abstract
Graphical Abstract
Macroscopic quantum phenomena such as high-temperature superconductivity, colossal magnetoresistance, ferrimagnetism and ferromagnetism arise from a delicate balance of different interactions among ...electrons, phonons and spins on the nanoscale. The study of the interplay among these various degrees of freedom in strongly coupled electron-lattice systems is thus crucial to their understanding and for optimizing their properties. Charge-density-wave (CDW) materials, with their inherent modulation of the electron density and associated periodic lattice distortion, represent ideal model systems for the study of such highly cooperative phenomena. With femtosecond time-resolved techniques, it is possible to observe these interactions directly by abruptly perturbing the electronic distribution while keeping track of energy relaxation pathways and coupling strengths among the different subsystems. Numerous time-resolved experiments have been performed on CDWs, probing the dynamics of the electronic subsystem. However, the dynamics of the periodic lattice distortion have been only indirectly inferred. Here we provide direct atomic-level information on the structural dynamics by using femtosecond electron diffraction to study the quasi two-dimensional CDW system 1T-TaS2. Effectively, we have directly observed the atomic motions that result from the optically induced change in the electronic spatial distribution. The periodic lattice distortion, which has an amplitude of ∼0.1 Å, is suppressed by about 20% on a timescale (∼250 femtoseconds) comparable to half the period of the corresponding collective mode. These highly cooperative, electronically driven atomic motions are accompanied by a rapid electron-phonon energy transfer (∼350 femtoseconds) and are followed by fast recovery of the CDW (∼4 picoseconds). The degree of cooperativity in the observed structural dynamics is remarkable and illustrates the importance of obtaining atomic-level perspectives of the processes directing the physics of strongly correlated systems.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This review documents the development of high-bunch charge electron pulses with sufficient combined spatiotemporal resolution and intensity to literally light up atomic motions. This development ...holds promise in coming to a first-principles understanding of diverse problems, ranging from molecular reaction dynamics and structure-function correlations in biology to cooperativity in strongly correlated electron-lattice systems. It is now possible to directly observe the key modes involved in propagating structural changes and the enormous reduction in dimensionality that occurs in barrier crossing regions, which is central to chemistry and makes reaction mechanisms transferrable concepts. This information will help direct theoretical advances that will undoubtedly lead to generalized principles with respect to scaling relations in structural dynamics that will bridge chemistry to biology. In this quest, the limitations and future directions for further development are discussed to give an overview of the present status of the field.
As next-generation sequencing projects generate massive genome-wide sequence variation data, bioinformatics tools are being developed to provide computational predictions on the functional effects of ...sequence variations and narrow down the search of casual variants for disease phenotypes. Different classes of sequence variations at the nucleotide level are involved in human diseases, including substitutions, insertions, deletions, frameshifts, and non-sense mutations. Frameshifts and non-sense mutations are likely to cause a negative effect on protein function. Existing prediction tools primarily focus on studying the deleterious effects of single amino acid substitutions through examining amino acid conservation at the position of interest among related sequences, an approach that is not directly applicable to insertions or deletions. Here, we introduce a versatile alignment-based score as a new metric to predict the damaging effects of variations not limited to single amino acid substitutions but also in-frame insertions, deletions, and multiple amino acid substitutions. This alignment-based score measures the change in sequence similarity of a query sequence to a protein sequence homolog before and after the introduction of an amino acid variation to the query sequence. Our results showed that the scoring scheme performs well in separating disease-associated variants (n = 21,662) from common polymorphisms (n = 37,022) for UniProt human protein variations, and also in separating deleterious variants (n = 15,179) from neutral variants (n = 17,891) for UniProt non-human protein variations. In our approach, the area under the receiver operating characteristic curve (AUC) for the human and non-human protein variation datasets is ∼0.85. We also observed that the alignment-based score correlates with the deleteriousness of a sequence variation. In summary, we have developed a new algorithm, PROVEAN (Protein Variation Effect Analyzer), which provides a generalized approach to predict the functional effects of protein sequence variations including single or multiple amino acid substitutions, and in-frame insertions and deletions. The PROVEAN tool is available online at http://provean.jcvi.org.
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Available observations suggest that some mountain regions are experiencing seasonal warming rates that are greater than the global land average. There is also evidence from observational and modeling ...studies for an elevation-dependent climate response within some mountain regions. Our understanding of climate change in mountains, however, remains challenging owing to inadequacies in observations and models. In fact, it is still uncertain whether mountainous regions generally are warming at a different rate than the rest of the global land surface, or whether elevation-based sensitivities in warming rates are prevalent within mountains. We review studies of four high mountain regions – the Swiss Alps, the Colorado Rocky Mountains, the Tibetan Plateau/Himalayas, and the Tropical Andes – to examine questions related to the sensitivity of climate change to surface elevation. We explore processes that could lead to enhanced warming within mountain regions and possible mechanisms that can produce altitudinal gradients in warming rates on different time scales. A conclusive understanding of these responses will continue to elude us in the absence of a more comprehensive network of climate monitoring in mountains.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
10.
Valuing Reversible Energy Storage Miller, John R.
Science (American Association for the Advancement of Science),
03/2012, Volume:
335, Issue:
6074
Journal Article
Peer reviewed
A process based on laser-converted graphene is used to fabricate high-value energy storage material.
The development of new materials that provide the capability of high-performance energy storage ...combined with flexibility of fabrication opens up the possibility of a wide range of technological applications. On page 1326 of this issue, El-Kady
et al.
(
1
) describe thin and highly flexible electrochemical capacitors (ECs) that were created by means of a very simple and innovative process. Unlike the usual approaches of making thin graphene electrodes that start with a particulate and use roll-coating, screen printing, or ink-jet printing (
2
), their process involves focusing a low-power laser onto a thin graphene oxide deposit to convert it into graphene. The incorporation of graphene in electrodes created with mechanical processes tends to be in agglomerates that provide little performance advantage over traditional particulate-activated carbon electrodes. El-Kady
et al.
's approach also contrasts with plasma-assisted chemical vapor deposition processes that have been used to grow vertically oriented graphene nanosheet electrodes (
3
). Although graphene structures grown by such methods are well-formed and offer performance advantages over traditional activated carbon materials, they require complicated vacuum process equipment, plus the graphene growth rate is very slow (
4
). The somewhat simple EC electrode fabrication process reported by El-Kady
et al.
therefore appears to circumvent many of the difficulties encountered with traditional processes.
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