Obinutuzumab-Induced B Cell Depletion Reduces Spinal Cord Pathology in a CD20 Double Transgenic Mouse Model of Multiple Sclerosis

B cell-depleting therapies have recently proven to be clinically highly successful in the treatment of multiple sclerosis (MS). This study aimed to determine the effects of the novel type II anti-human CD20 (huCD20) monoclonal antibody (mAb) obinutuzumab (OBZ) on spinal cord degeneration in a B cell-dependent mouse model of MS. Double transgenic huCD20xHIGR3 (CD20dbtg) mice, which express human CD20, were immunised with the myelin fusion protein MP4 to induce experimental autoimmune encephalomyelitis (EAE). Both light and electron microscopy were used to assess myelination and axonal pathology in mice treated with OBZ during chronic EAE. Furthermore, the effects of the already established murine anti-CD20 antibody 18B12 were assessed in C57BL/6 wild-type (wt) mice. In both models (18B12/wt and OBZ/CD20dbtg) anti-CD20 treatment significantly diminished the extent of spinal cord pathology. While 18B12 treatment mainly reduced the extent of axonal pathology, a significant decrease in demyelination and increase in remyelination were additionally observed in OBZ-treated mice. Hence, the data suggest that OBZ could have neuroprotective effects on the CNS, setting the drug apart from the currently available type I anti-CD20 antibodies

Divergent drivers of the microbial methane sink in temperate forest and grassland soils

Aerated topsoils are important sinks for atmospheric methane (CH4) via oxidation by CH4‐oxidizing bacteria (MOB). However, intensified management of grasslands and forests may reduce the CH4 sink capacity of soils. We investigated the influence of grassland land‐use intensity (150 sites) and forest management type (149 sites) on potential atmospheric CH4 oxidation rates (PMORs) and the abundance and diversity of MOB (with qPCR) in topsoils of three temperate regions in Germany. PMORs measurements in microcosms under defined conditions yielded approximately twice as much CH4 oxidation in forest than in grassland soils. High land‐use intensity of grasslands had a negative effect on PMORs (−40%) in almost all regions and fertilization was the predominant factor of grassland land‐use intensity leading to PMOR reduction by 20%. In contrast, forest management did not affect PMORs in forest soils. Upland soil cluster (USC)‐α was the dominant group of MOBs in the forests. In contrast, USC‐γ was absent in more than half of the forest soils but present in almost all grassland soils. USC‐α abundance had a direct positive effect on PMOR in forest, while in grasslands USC‐α and USC‐γ abundance affected PMOR positively with a more pronounced contribution of USC‐γ than USC‐α. Soil bulk density negatively influenced PMOR in both forests and grasslands. We further found that the response of the PMORs to pH, soil texture, soil water holding capacity and organic carbon and nitrogen content differ between temperate forest and grassland soils. pH had no direct effects on PMOR, but indirect ones via the MOB abundances, showing a negative effect on USC‐α, and a positive on USC‐γ abundance. We conclude that reduction in grassland land‐use intensity and afforestation has the potential to increase the CH4 sink function of soils and that different parameters determine the microbial methane sink in forest and grassland soils.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659ESFMinistry of Education, Science and Culture of Mecklenburg‐Western PomeraniaPeer Reviewe

Intrinsic response time of graphene photodetectors

Graphene-based photodetectors are promising new devices for high-speed optoelectronic applications. However, despite recent efforts, it is not clear what determines the ultimate speed limit of these devices. Here, we present measurements of the intrinsic response time of metal-graphene-metal photodetectors with monolayer graphene using an optical correlation technique with ultrashort laser pulses. We obtain a response time of 2.1 ps that is mainly given by the short lifetime of the photogenerated carriers. This time translates into a bandwidth of ~262 GHz. Moreover, we investigate the dependence of the response time on gate voltage and illumination laser power

Photocurrent measurements of supercollision cooling in graphene

The cooling of hot electrons in graphene is the critical process underlying the operation of exciting new graphene-based optoelectronic and plasmonic devices, but the nature of this cooling is controversial. We extract the hot electron cooling rate near the Fermi level by using graphene as novel photothermal thermometer that measures the electron temperature ($T(t)$) as it cools dynamically. We find the photocurrent generated from graphene $p-n$ junctions is well described by the energy dissipation rate $C dT/dt=-A(T^3-T_l^3)$, where the heat capacity is $C=\alpha T$ and $T_l$ is the base lattice temperature. These results are in disagreement with predictions of electron-phonon emission in a disorder-free graphene system, but in excellent quantitative agreement with recent predictions of a disorder-enhanced supercollision (SC) cooling mechanism. We find that the SC model provides a complete and unified picture of energy loss near the Fermi level over the wide range of electronic (15 to $\sim$3000 K) and lattice (10 to 295 K) temperatures investigated.Comment: 7pages, 5 figure

Photoconductivity of biased graphene

Graphene is a promising candidate for optoelectronic applications such as photodetectors, terahertz imagers, and plasmonic devices. The origin of photoresponse in graphene junctions has been studied extensively and is attributed to either thermoelectric or photovoltaic effects. In addition, hot carrier transport and carrier multiplication are thought to play an important role. Here we report the intrinsic photoresponse in biased but otherwise homogeneous graphene. In this classic photoconductivity experiment, the thermoelectric effects are insignificant. Instead, the photovoltaic and a photo-induced bolometric effect dominate the photoresponse due to hot photocarrier generation and subsequent lattice heating through electron-phonon cooling channels respectively. The measured photocurrent displays polarity reversal as it alternates between these two mechanisms in a backgate voltage sweep. Our analysis yields elevated electron and phonon temperatures, with the former an order higher than the latter, confirming that hot electrons drive the photovoltaic response of homogeneous graphene near the Dirac point

Generation of photovoltage in graphene on a femtosecond time scale through efficient carrier heating

Graphene is a promising material for ultrafast and broadband photodetection. Earlier studies addressed the general operation of graphene-based photo-thermoelectric devices, and the switching speed, which is limited by the charge carrier cooling time, on the order of picoseconds. However, the generation of the photovoltage could occur at a much faster time scale, as it is associated with the carrier heating time. Here, we measure the photovoltage generation time and find it to be faster than 50 femtoseconds. As a proof-of-principle application of this ultrafast photodetector, we use graphene to directly measure, electrically, the pulse duration of a sub-50 femtosecond laser pulse. The observation that carrier heating is ultrafast suggests that energy from absorbed photons can be efficiently transferred to carrier heat. To study this, we examine the spectral response and find a constant spectral responsivity between 500 and 1500 nm. This is consistent with efficient electron heating. These results are promising for ultrafast femtosecond and broadband photodetector applications.Comment: 6 pages, 4 figure

Chalcogenide Glass-on-Graphene Photonics

Two-dimensional (2-D) materials are of tremendous interest to integrated photonics given their singular optical characteristics spanning light emission, modulation, saturable absorption, and nonlinear optics. To harness their optical properties, these atomically thin materials are usually attached onto prefabricated devices via a transfer process. In this paper, we present a new route for 2-D material integration with planar photonics. Central to this approach is the use of chalcogenide glass, a multifunctional material which can be directly deposited and patterned on a wide variety of 2-D materials and can simultaneously function as the light guiding medium, a gate dielectric, and a passivation layer for 2-D materials. Besides claiming improved fabrication yield and throughput compared to the traditional transfer process, our technique also enables unconventional multilayer device geometries optimally designed for enhancing light-matter interactions in the 2-D layers. Capitalizing on this facile integration method, we demonstrate a series of high-performance glass-on-graphene devices including ultra-broadband on-chip polarizers, energy-efficient thermo-optic switches, as well as graphene-based mid-infrared (mid-IR) waveguide-integrated photodetectors and modulators