250 research outputs found

    Temperature dependent asymmetry of the nonlocal spin-injection resistance: evidence for spin non-conserving interface scattering

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    We report nonlocal spin injection and detection experiments on mesoscopic Co-Al2O3-Cu spin valves. We have observed a temperature dependent asymmetry in the nonlocal resistance between parallel and antiparallel configurations of the magnetic injector and detector. This strongly supports the existence of a nonequilibrium resistance that depends on the relative orientation of the detector magnetization and the nonequilibrium magnetization in the normal metal providing evidence for increasing interface spin scattering with temperature.Comment: 5 pages, 4 figures, accepted for publication in PRL, minor corrections (affiliation, acknowledgements, typo

    Resolution of diaschisis contributes to early recovery from post-stroke aphasia

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    Diaschisis is a phenomenon observed in stroke that is defined as neuronal dysfunction in regions spared by the infarction but connected to the lesion site. We combined lesion network mapping and task-based functional MRI in 71 patients with post-stroke aphasia to investigate, whether diaschisis and its resolution contribute to early loss and recovery of language functions. Language activation acquired in the acute, subacute and chronic phase was analyzed in compartments with high and low normative resting-state functional connectivity to the lesion site on an individual basis. Regions with high compared to regions with low lesion connectivity showed a steeper increase in language reactivation from the acute to the subacute phase. This finding is compatible with the assumption of resolution of diaschisis. Additionally, language performance in the subacute phase and improvement from the subacute to the chronic phase significantly correlated with the diaschisis effect and its resolution, respectively, suggesting a behavioral relevance of this effect. We therefore assume that undamaged but functionally connected regions become dysfunctional due to missing input from the lesion contributing to the aphasic deficit. Since these regions are structurally intact, dysfunction resolves over time contributing to the rapid early behavioral improvement observed in aphasic stroke patients. Our results demonstrate that diaschisis and its resolution might be a relevant mechanism of early loss and recovery of language function in acute stroke patients

    Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid

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    BACKGROUND: Group 2 innate lymphoid cells (ILC2s) play critical roles in induction and exacerbation of allergic airway inflammation. Thus, clarification of the mechanisms that underlie the regulation of ILC2 activation has received significant attention. Although ILCs are divided into three major subsets that mirror helper effector T-cell subsets, counterpart subsets of regulatory T (Treg) cells have not been well characterized. OBJECTIVE: We sought to determine the factors that induce regulatory ILCs (ILCregs). METHODS: IL-10+ ILCregs induced from ILC2s by retinoic acid (RA) were analyzed using RNA-sequencing and flow cytometry. ILCregs were evaluated in human nasal tissues from healthy individuals and patients with chronic rhinosinusitis with nasal polyp (CRSwNP), and in lung tissues from house dust mite (HDM)- or saline-treated mice. RESULTS: RA induced IL-10 secretion by human ILC2s, but not type-2 cytokines. IL-10+ ILCregs, converted from ILC2s by RA stimulation, expressed a Treg-like signature with the expression of IL-10, CTLA-4 and CD25, with down regulated effector type 2-related markers such as CRTH-2 and ST2, and suppressed activation of CD4+ T cells and ILC2s. ILCregs were rarely detected in human nasal tissue from healthy individuals or lung tissues from saline-treated mice, but were increased in nasal tissues from patients with CRSwNP and in lung tissues from HDM-treated mice. Enzymes for RA synthesis were up-regulated in airway epithelial cells during type-2 inflammation in vivo and by IL-13 in vitro. CONCLUSION: We have identified a unique immune regulatory and anti-inflammatory pathway by which RA converts ILC2s to ILCregs. Interactions between airway epithelial cells and ILC2s play an important roles in the generation of ILCregs

    Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1) is an immunogenic antigen found in EVs released from pre-acetabular glands of invading cercariae.

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    Funder: IBERS, Aberystwyth University PhD studentshipFunder: Higher Education Funding Council for Wales (HEFCW) - Global Challenges Research FundExtracellular Vesicles (EVs) are an integral component of cellular/organismal communication and have been found in the excreted/secreted (ES) products of both protozoan and metazoan parasites. Within the blood fluke schistosomes, EVs have been isolated from egg, schistosomula, and adult lifecycle stages. However, the role(s) that EVs have in shaping aspects of parasite biology and/or manipulating host interactions is poorly defined. Herein, we characterise the most abundant EV-enriched protein in Schistosoma mansoni tissue-migrating schistosomula (Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1)). Comparative sequence analysis demonstrates that lev1 orthologs are found in all published Schistosoma genomes, yet homologs are not found outside of the Schistosomatidae. Lifecycle expression analyses collectively reveal that smlev1 transcription peaks in cercariae, is male biased in adults, and is processed by alternative splicing in intra-mammalian lifecycle stages. Immunohistochemistry of cercariae using a polyclonal anti-recombinant SmLEV1 antiserum localises this protein to the pre-acetabular gland, with some disperse localisation to the surface of the parasite. S. mansoni-infected Ugandan fishermen exhibit a strong IgG1 response against SmLEV1 (dropping significantly after praziquantel treatment), with 11% of the cohort exhibiting an IgE response and minimal levels of detectable antigen-specific IgG4. Furthermore, mice vaccinated with rSmLEV1 show a slightly reduced parasite burden upon challenge infection and significantly reduced granuloma volumes, compared with control animals. Collectively, these results describe SmLEV1 as a Schistosomatidae-specific, EV-enriched immunogen. Further investigations are now necessary to uncover the full extent of SmLEV1's role in shaping schistosome EV function and definitive host relationships

    Extension of Earth-Moon libration point orbits with solar sail propulsion

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    This paper presents families of libration point orbits in the Earth-Moon system that originate from complementing the classical circular restricted three-body problem with a solar sail. Through the use of a differential correction scheme in combination with a continuation on the solar sail induced acceleration, families of Lyapunov, halo, vertical Lyapunov, Earth-centred, and distant retrograde orbits are created. As the solar sail circular restricted three-body problem is non-autonomous, a constraint defined within the differential correction scheme ensures that all orbits are periodic with the Sun’s motion around the Earth-Moon system. The continuation method then starts from a classical libration point orbit with a suitable period and increases the solar sail acceleration magnitude to obtain families of orbits that are parametrised by this acceleration. Furthermore, different solar sail steering laws are considered (both in-plane and out-of-plane, and either fixed in the synodic frame or fixed with respect to the direction of sunlight), adding to the wealth of families of solar sail enabled libration point orbits presented. Finally, the linear stability properties of the generated orbits are investigated to assess the need for active orbital control. It is shown that the solar sail induced acceleration can have a positive effect on the stability of some orbit families, especially those at the L2 point, but that it most often (further) destabilises the orbit. Active control will therefore be needed to ensure long-term survivability of these orbits

    Survey of highly non-Keplerian orbits with low-thrust propulsion

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    Celestial mechanics has traditionally been concerned with orbital motion under the action of a conservative gravitational potential. In particular, the inverse square gravitational force due to the potential of a uniform, spherical mass leads to a family of conic section orbits, as determined by Isaac Newton, who showed that Kepler‟s laws were derivable from his theory of gravitation. While orbital motion under the action of a conservative gravitational potential leads to an array of problems with often complex and interesting solutions, the addition of non-conservative forces offers new avenues of investigation. In particular, non-conservative forces lead to a rich diversity of problems associated with the existence, stability and control of families of highly non-Keplerian orbits generated by a gravitational potential and a non-conservative force. Highly non-Keplerian orbits can potentially have a broad range of practical applications across a number of different disciplines. This review aims to summarize the combined wealth of literature concerned with the dynamics, stability and control of highly non-Keplerian orbits for various low thrust propulsion devices, and to demonstrate some of these potential applications

    Spin effects in single electron tunneling

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    An important consequence of the discovery of giant magnetoresistance in metallic magnetic multilayers is a broad interest in spin dependent effects in electronic transport through magnetic nanostructures. An example of such systems are tunnel junctions -- single-barrier planar junctions or more complex ones. In this review we present and discuss recent theoretical results on electron and spin transport through ferromagnetic mesoscopic junctions including two or more barriers. Such systems are also called ferromagnetic single-electron transistors. We start from the situation when the central part of a device has the form of a magnetic (or nonmagnetic) metallic nanoparticle. Transport characteristics reveal then single-electron charging effects, including the Coulomb staircase, Coulomb blockade, and Coulomb oscillations. Single-electron ferromagnetic transistors based on semiconductor quantum dots and large molecules (especially carbon nanotubes) are also considered. The main emphasis is placed on the spin effects due to spin-dependent tunnelling through the barriers, which gives rise to spin accumulation and tunnel magnetoresistance. Spin effects also occur in the current-voltage characteristics, (differential) conductance, shot noise, and others. Transport characteristics in the two limiting situations of weak and strong coupling are of particular interest. In the former case we distinguish between the sequential tunnelling and cotunneling regimes. In the strong coupling regime we concentrate on the Kondo phenomenon, which in the case of transport through quantum dots or molecules leads to an enhanced conductance and to a pronounced zero-bias Kondo peak in the differential conductance.Comment: topical review (36 figures, 65 pages), to be published in J. Phys.: Condens. Matte

    New Insights into Blastocystis spp.: A Potential Link with Irritable Bowel Syndrome

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    International audienceBlastocystis spp. belong to the phylum Stramenopila, a complex and heterogeneous evolutionary assemblage of heterotrophic and photosynthetic protozoa [1]. Interestingly, this is the only stramenopile living in the lower digestive tract of humans, and it also lives in other mammals, birds, reptiles, amphibians, and insects [1]. Even though isolates were reported to be morphologically indistinguishable, an extensive genetic variation among isolates from both humans and animals has been observed. Thirteen subtypes (ST1-ST13), with the first nine being found in humans, have been identified based on genes coding for the small-subunit ribosomal RNA [2]. Preferential repartition of STs exists among animals that appear to constitute the main reservoir for environmental dissemination and human contamination

    An ultra-deep sequencing strategy to detect sub-clonal TP53 mutations in presentation chronic lymphocytic leukemia cases using multiple polymerases

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    Chronic lymphocytic leukaemia (CLL) is the most common clonal B-cell disorder characterized by clonal diversity, a relapsing and remitting course, and in its aggressive forms remains largely incurable. Current front-line regimes include agents such as fludarabine, which act primarily via the DNA damage response pathway. Key to this is the transcription factor p53. Mutations in the TP53 gene, altering p53 functionality, are associated with genetic instability, and are present in aggressive CLL. Furthermore, the emergence of clonal TP53 mutations in relapsed CLL, refractory to DNA-damaging therapy, suggests that accurate detection of sub-clonal TP53 mutations prior to and during treatment may be indicative of early relapse. In this study, we describe a novel deep sequencing workflow using multiple polymerases to generate sequencing libraries (MuPol-Seq), facilitating accurate detection of TP53 mutations at a frequency as low as 0.3%, in presentation CLL cases tested. As these mutations were mostly clustered within the regions of TP53 encoding DNA-binding domains, essential for DNA contact and structural architecture, they are likely to be of prognostic relevance in disease progression. The workflow described here has the potential to be implemented routinely to identify rare mutations across a range of diseases

    Solid-state NMR applied to photosynthetic light-harvesting complexes

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    This short review describes how solid-state NMR has provided a mechanistic and electronic picture of pigment–protein and pigment–pigment interactions in photosynthetic antenna complexes. NMR results on purple bacterial antenna complexes show how the packing of the protein and the pigments inside the light-harvesting oligomers induces mutual conformational stress. The protein scaffold produces deformation and electrostatic polarization of the BChl macrocycles and leads to a partial electronic charge transfer between the BChls and their coordinating histidines, which can tune the light-harvesting function. In chlorosome antennae assemblies, the NMR template structure reveals how the chromophores can direct their self-assembly into higher macrostructures which, in turn, tune the light-harvesting properties of the individual molecules by controlling their disorder, structural deformation, and electronic polarization without the need for a protein scaffold. These results pave the way for addressing the next challenge, which is to resolve the functional conformational dynamics of the lhc antennae of oxygenic species that allows them to switch between light-emitting and light-energy dissipating states
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