157 research outputs found

    Tuning spontaneous emission through waveguide cavity effects in semiconductor nanowires

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    The ability to tailor waveguide cavities and couple them with quantum emitters has developed a realm of nanophotonics encompassing, for example, highly efficient single photon generation or the control of giant photon nonlinearities. Opening new grounds by pushing the interaction of the waveguide cavity and integrated emitters further into the deep subwavelength regime, however, has been complicated by nonradiative losses due to the increasing importance of surface defects when decreasing cavity dimensions. Here, we show efficient suppression of nonradiative recombination for thin waveguide cavities using core-shell semiconductor nanowires. We experimentally reveal the advantages of such nanowires, which host mobile emitters, that is, free excitons, in a one-dimensional (1D) waveguide, highlighting the resulting potential for tunable, active, nanophotonic devices. In our experiment, controlling the nanowire waveguide diameter tunes the luminescence lifetime of excitons in the nanowires across 2 orders of magnitude up to 80 ns. At the smallest wire diameters, we show that this luminescence lifetime can be manipulated by engineering the dielectric environment of the nanowires. Exploiting this unique handle on the spontaneous emission of mobile emitters, we demonstrate an all-dielectric spatial control of the mobile emitters along the axis of the 1D nanowire waveguide

    Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma

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    Tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, combined with the immunomodulatory drug lenalidomide was clinically active with a good tolerability profile in the open-label, single-arm, phase II L-MIND study of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem-cell transplantation. To assess long-term outcomes, we report an updated analysis with ≥35 months' follow-up. Patients were aged >18 years, had received one to three prior systemic therapies (including ≥1 CD20-targeting regimen) and Eastern Cooperative Oncology Group performance status 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during cycles 1-3, then every 2 weeks during cycles 4-12. Lenalidomide (25 mg orally) was administered on days 1-21 of cycles 1-12. After cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was best objective response rate. After ≥35 months' follow-up (data cut-off: October 30, 2020), the objective response rate was 57.5% (n=46/80), including a complete response in 40.0% of patients (n=32/80) and a partial response in 17.5% of patients (n=14/80). The median duration of response was 43.9 months (95% confidence interval [95% CI]: 26.1-not reached), the median overall survival was 33.5 months (95% CI: 18.3-not reached) and the median progression-free survival was 11.6 months (95% CI: 6.3-45.7). There were no unexpected toxicities. Subgroup analyses revealed consistent long-term efficacy results across most subgroups of patients. This extended follow-up of L-MIND confirms the long duration of response, meaningful overall survival, and well-defined safety profile of tafasitamab plus lenalidomide followed by tafasitamab monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation. ClinicalTrials.gov identifier: NCT02399085

    Origin and Manipulation of Stable Vortex Ground States in Permalloy Nanotubes

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    We present a detailed study on the static magnetic properties of individual permalloy nanotubes (NTs) with hexagonal cross-sections. Anisotropic magnetoresistance (AMR) measurements and scanning transmission X-ray microscopy (STXM) are used to investigate their magnetic ground states and its stability. We find that the magnetization in zero applied magnetic field is in a very stable vortex state. Its origin is attributed to a strong growth-induced anisotropy with easy axis perpendicular to the long axis of the tubes. AMR measurements of individual NTs in combination with micromagnetic simulations allow the determination of the magnitude of the growth-induced anisotropy for different types of NT coatings. We show that the strength of the anisotropy can be controlled by introducing a buffer layer underneath the magnetic layer. The magnetic ground states depend on the external magnetic field history and are directly imaged using STXM. Stable vortex domains can be introduced by external magnetic fields and can be erased by radio-frequency magnetic fields applied at the center of the tubes via a strip line antenna

    Signaling of Human Frizzled Receptors to the Mating Pathway in Yeast

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    Frizzled receptors have seven membrane-spanning helices and are considered as atypical G protein-coupled receptors (GPCRs). The mating response of the yeast Saccharomyces cerevisiae is mediated by a GPCR signaling system and this model organism has been used extensively in the past to study mammalian GPCR function. We show here that human Frizzled receptors (Fz1 and Fz2) can be properly targeted to the yeast plasma membrane, and that they stimulate the yeast mating pathway in the absence of added Wnt ligands, as evidenced by cell cycle arrest in G1 and reporter gene expression dependent on the mating pathway-activated FUS1 gene. Introducing intracellular portions of Frizzled receptors into the Ste2p backbone resulted in the generation of constitutively active receptor chimeras that retained mating factor responsiveness. Introducing intracellular portions of Ste2p into the Frizzled receptor backbone was found to strongly enhance mating pathway activation as compared to the native Frizzleds, likely by facilitating interaction with the yeast Gα protein Gpa1p. Furthermore, we show reversibility of the highly penetrant G1-phase arrests exerted by the receptor chimeras by deletion of the mating pathway effector FAR1. Our data demonstrate that Frizzled receptors can functionally replace mating factor receptors in yeast and offer an experimental system to study modulators of Frizzled receptors

    Temporal Accumulation and Decision Processes in the Duration Bisection Task Revealed by Contingent Negative Variation

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    The duration bisection paradigm is a classic task used to examine how humans and other animals perceive time. Typically, participants first learn short and long anchor durations and are subsequently asked to classify probe durations as closer to the short or long anchor duration. However, the specific representations of time and the decision rules applied in this task remain the subject of debate. For example, researchers have questioned whether participants actually use representations of the short and long anchor durations in the decision process rather than merely a response threshold that is derived from those anchor durations. Electroencephalographic (EEG) measures, like the contingent negative variation (CNV), can provide information about the perceptual and cognitive processes that occur between the onset of the timing stimulus and the motor response. The CNV has been implicated as an electrophysiological marker of interval timing processes such as temporal accumulation, representation of the target duration, and the decision that the target duration has been attained. We used the CNV to investigate which durations are involved in the bisection categorization decision. The CNV increased in amplitude up to the value of the short anchor, remained at a constant level until about the geometric mean (GM) of the short and long anchors, and then began to resolve. These results suggest that the short anchor and the GM of the short and long anchors are critical target durations used in the bisection categorization decision process. In addition, larger mean N1P2 amplitude differences were associated with larger amplitude CNVs, which may reflect the participant’s precision in initiating timing on each trial across a test session. Overall, the results demonstrate the value of using scalp-recorded EEG to address basic questions about interval timing

    Growth and yield of mixed versus pure stands of Scots pine (Pinus sylvestris L. ) and European beech (Fagus sylvatica L.) analysed along a productivity gradient through Europe

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    Mixing of complementary tree species may increase stand productivity, mitigate the effects of drought and other risks, and pave the way to forest production systems which may be more resource-use efficient and stable in the face of climate change. However, systematic empirical studies on mixing effects are still missing for many commercially important and widespread species combinations. Here we studied the growth of Scots pine (Pinus sylvestris L.) and European beech (Fagus sylvatica L.) in mixed versus pure stands on 32 triplets located along a productivity gradient through Europe, reaching from Sweden to Bulgaria and from Spain to the Ukraine. Stand inventory and taking increment cores on the mainly 60-80 year-old trees and 0.02-1.55 ha sized, fully stocked plots provided insight how species mixing modifies the structure, dynamics and productivity compared with neighbouring pure stands. In mixture standing volume (+12 %), stand density (+20 %), basal area growth (+12 %), and stand volume growth (+8 %) were higher than the weighted mean of the neighbouring pure stands. Scots pine and European beech contributed rather equally to the overyielding and overdensity. In mixed stands mean diameter (+20 %) and height (+6 %) of Scots pine was ahead, while both diameter and height growth of European beech were behind (−8 %). The overyielding and overdensity were independent of the site index, the stand growth and yield, and climatic variables despite the wide variation in precipitation (520-1175 mm year−1), mean annual temperature (6-10.5 °C), and the drought index by de Martonne (28-61 mm °C−1) on the sites. Therefore, this species combination is potentially useful for increasing productivity across a wide range of site and climatic conditions. Given the significant overyielding of stand basal area growth but the absence of any relationship with site index and climatic variables, we hypothesize that the overyielding and overdensity results from several different types of interactions (light-, water-, and nutrient-related) that are all important in different circumstances. We discuss the relevance of the results for ecological theory and for the ongoing silvicultural transition from pure to mixed stands and their adaptation to climate change.The networking in this study has been sup-ported by COST Action FP1206 EuMIXFOR. All contributors thanktheir national funding institutions to establish, measure, and analysedata from the triplets. The first author also thanks the BayerischenStaatsforsten (BaySF) for supporting the establishment of the plots,the Bavarian State Ministry for Nutrition, Agriculture, and Forestryfor permanent support of the project W 07 ‘‘Long-term experimentalplots for forest growth and yield research’’ (# 7831-22209-2013) andthe German Science Foundation for providing the funds for the pro-jects PR 292/12-1 ‘‘Tree and stand-level growth reactions on droughtin mixed versus pure forests of Norway spruce and European beech’’.Thanks are also due to Ulrich Kern for the graphical artwork, and totwo anonymous reviewers for their constructive criticism

    Action selection and action awareness

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    Human actions are often classified as either internally generated, or externally specified in response to environmental cues. These two modes of action selection have distinct neural bases, but few studies investigated how the mode of action selection affects the subjective experience of action. We measured the experience of action using the subjective compression of the interval between actions and their effects, known as ‘temporal binding’. Participants performed either a left or a right key press, either in response to a specific cue, or as they freely chose. Moreover, the time of each keypress could either be explicitly cued to occur in one of two designated time intervals, or participants freely chose in which interval to act. Each action was followed by a specific tone. Participants judged the time of their actions or the time of the tone. Temporal binding was found for both internally generated and for stimulus-based actions. However, the amount of binding depended on whether or not both the choice and the timing of action were selected in the same way. Stronger binding was observed when both action choice and action timing were internally generated or externally specified, compared to conditions where the two parameters were selected by different routes. Our result suggests that temporal action–effect binding depends on how actions are selected. Binding is strongest when actions result from a single mode of selection

    Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson's Disease

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    The use of dopamine replacement therapies (DRT) in the treatment of Parkinson's disease (PD) can lead to the development of dopamine dysregulation syndrome (DDS) and impulse control disorders (ICD), behavioral disturbances characterized by compulsive DRT self-medication and development of impulsive behaviors. However, the mechanisms behind these disturbances are poorly understood. In animal models of PD, the assessment of the rewarding properties of levodopa (LD), one of the most common drugs used in PD, has produced conflicting results, and its ability to promote increased impulsivity is still understudied. Moreover, it is unclear whether acute and chronic LD therapy differently affects reward and impulsivity. In this study we aimed at assessing, in an animal model of PD with bilateral mesostriatal and mesocorticolimbic degeneration, the behavioral effects of LD therapy regarding reward and impulsivity. Animals with either sham or 6-hydroxydopamine (6-OHDA)-induced bilateral lesions in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) were exposed to acute and chronic LD treatment. We used the conditioned place preference (CPP) paradigm to evaluate the rewarding effects of LD, whereas impulsive behavior was measured with the variable delay-to-signal (VDS) task. Correlation analyses between behavioral measurements of reward or impulsivity and lesion extent in SNc/VTA were performed to pinpoint possible anatomical links of LD-induced behavioral changes. We show that LD, particularly when administered chronically, caused the development of impulsive-like behaviors in 6-OHDA-lesioned animals in the VDS. However, neither acute or chronic LD administration had rewarding effects in 6-OHDA-lesioned animals in the CPP. Our results show that in a bilateral rat model of PD, LD leads to the development of impulsive behaviors, strengthening the association between DRT and DDS/ICD in PD.Portuguese Foundation for Science and Technology: Ciência 2007 Program and IF Development Grant (IF/00111/2013) to AJS, Portuguese Foundation for Science and Technology PhD scholarships attributed to MMC (SFRH/BD/51061/2010), FLC (SFRH/BD/47311/2008) and CS-C (SFRH/BD/51992/2012), and Post-Doctoral Fellowship to HL-A (SFRH/BPD/80118/2011). Neurochemical analysis was funded from ELKE/UOA: 11650. This article has been developed under the scope of the project NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038info:eu-repo/semantics/publishedVersio

    Statistical organelle dissection of Arabidopsis guard cells using image database LIPS

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    To comprehensively grasp cell biological events in plant stomatal movement, we have captured microscopic images of guard cells with various organelles markers. The 28,530 serial optical sections of 930 pairs of Arabidopsis guard cells have been released as a new image database, named Live Images of Plant Stomata (LIPS). We visualized the average organellar distributions in guard cells using probabilistic mapping and image clustering techniques. The results indicated that actin microfilaments and endoplasmic reticulum (ER) are mainly localized to the dorsal side and connection regions of guard cells. Subtractive images of open and closed stomata showed distribution changes in intracellular structures, including the ER, during stomatal movement. Time-lapse imaging showed that similar ER distribution changes occurred during stomatal opening induced by light irradiation or femtosecond laser shots on neighboring epidermal cells, indicating that our image analysis approach has identified a novel ER relocation in stomatal opening
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