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

Simultaneous Interpreting : Characteristic of Autonomic Provision of Extreme Cognitive Loads

Simultaneous interpreting is one of the most comprehensive and energy-consuming types of cognitive activity. To work successfully, a simultaneous interpreter must have a specific functional state. The aim of our study was to find out the basic mechanisms of this functional state, the effect of the simultaneous interpreting on cognitive function changes, and the main factors influencing the degree of the regulatory systems strain. Materials and Methods. 33 individuals participated in the study: 22 linguists specially trained in simultaneous translation composed the experimental group and 11 language-qualified people having no skills of simultaneous translation represented the control group. In compliance with the study design, the measurements were performed under the conditions similar to the real work of simultaneous interpreters: the participants working in succession performed professional tasks: shadowing in the native and foreign languages (German and English), simultaneous interpretation of the reports from the native language to the foreign, and vice versa. The interpreters were psychologically tested using ApWay.ru Web platform before and after the performance on the professional tasks: computer campimetry, test for a simple sensorimotor activity, Stroop test, and test for emotional disadaptation level. Cardiointervalogram was telemetrically recorded during the entire experiment. Results. Some specific aspects of autonomic provision of simultaneous interpreting have been unraveled. A significantly greater tension of the autonomic regulation is manifested by the simultaneous interpreters compared to the control group. It was most prominent when translation was done from the foreign language. The total level of stress during the performance on the linguistic tasks appeared to be higher in the control group. In the simultaneous interpreters, in contrast to the control group, there was registered a high activity level of the sympathetic and parasympathetic systems and a marked integration of the cardiac rhythm regulation circuits over the entire period of performing the linguistic tasks. The psychological tests have demonstrated a significantly more confident cognitive control relative to the control group. Thus, a specific functional system has been formed in the simultaneous interpreters providing a successful interaction of various information images (or codes) and consolidation of autonomic and cognitive resources during the performance on professional tasks. Lack of the necessary skills and, consequently, of the task-oriented functional system in the participants of the control group resulted in the enhancement of the non-specific (less effective) stress response.Peer 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

The Active Assembly of the Virgo Cluster: Indications for Recent Group Infall From Early-type Dwarf Galaxies

Virgo is a dynamically young galaxy cluster with substructure in its spatial and kinematic distribution. Here we simultaneously study the phase-space distribution and the main characteristics of Virgo's galaxies, particularly its most abundant galaxy population-the early-type dwarfs-to understand their environmental transformation histories. Aside from known correlations with morphological types-like the larger average clustercentric distance of late-type galaxies-we find an intriguing behavior of early types with magnitudes -17 >= Mr >= -18. They show a large velocity spread and an asymmetric phase-space distribution, similar to the late-type galaxies and different from the early types just 1 mag brighter/fainter. Furthermore, we find a close phase-space aggregation of early-type dwarfs at large clustercentric distance and high relative velocity. Nearly all of them show signatures of disk components, and their colors imply stellar ages that are younger than the population average. They are not located closely together but spread azimuthally around the cluster center. We show that this is expected from simulations of an infalling galaxy group that slowly gets dispersed after its first pericentric passage. We thus conclude that these galaxies are recent arrivals and that the peculiar phase-space distribution of early-type dwarfs is evidence for the ongoing growth of this galaxy population. Studying galaxies based on their phase-space correlations is a unique way to compare the properties of recent and older cluster members and to understand which environment most influenced their present-day characteristics

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