The recent advent of deep artificial neural networks has resulted in a dramatic increase in performance for object classification and detection.While pre-trained with everyday objects,we find that a state-of-the-art o...The recent advent of deep artificial neural networks has resulted in a dramatic increase in performance for object classification and detection.While pre-trained with everyday objects,we find that a state-of-the-art object detection architecture can very efficiently be fine-tuned to work on a variety of object detection tasks in a high-power laser laboratory.In this paper,three exemplary applications are presented.We show that the plasma waves in a laser±plasma accelerator can be detected and located on the optical shadowgrams.The plasma wavelength and plasma density are estimated accordingly.Furthermore,we present the detection of all the peaks in an electron energy spectrum of the accelerated electron beam,and the beam charge of each peak is estimated accordingly.Lastly,we demonstrate the detection of optical damage in a high-power laser system.The reliability of the object detector is demonstrated over1000 laser shots in each application.Our study shows that deep object detection networks are suitable to assist online and offline experimental analysis,even with small training sets.We believe that the presented methodology is adaptable yet robust,and we encourage further applications in Hz-level or kHz-level high-power laser facilities regarding the control and diagnostic tools,especially for those involving image data.展开更多
Absorption spectroscopy of fundamental ro-vibrational transitions in the mid-infrared region provides a powerful tool for studying the structure and dynamics of molecules in the gas phase and for sensitive and quantit...Absorption spectroscopy of fundamental ro-vibrational transitions in the mid-infrared region provides a powerful tool for studying the structure and dynamics of molecules in the gas phase and for sensitive and quantitative gas sensing.Laser frequency combs permit novel approaches to perform broadband molecular spectroscopy.Multiplex dual-comb spectroscopy without moving parts can achieve particularly high speed,sensitivity and resolution.However,achieving Doppler-limited resolution in the mid-infrared still requires overcoming instrumental challenges.Here we demonstrate a new approach based on difference-frequency generation of frequency-agile near-infrared frequency combs that are produced using electro-optic modulators.The combs have a remarkably flat intensity distribution,and their positions and line spacings can be freely selected by simply dialing a knob.Using the proposed technique,we record,in the 3-μm region,Doppler-limited absorption spectra with resolved comb lines within milliseconds,and precise molecular line parameters are retrieved.Our technique holds promise for fast and sensitive time-resolved studies of,for example,trace gases.展开更多
Plastids communicate their developmental and physiological status to the nucleus via retrograde signaling,allowing nuclear gene expression to be adjusted appropriately.Signaling during plastid biogenesis and responses...Plastids communicate their developmental and physiological status to the nucleus via retrograde signaling,allowing nuclear gene expression to be adjusted appropriately.Signaling during plastid biogenesis and responses of mature chloroplasts to environmental changes are designated“biogenic”and“operational”controls,respectively.A prominent example of the investigation of biogenic signaling is the screen for gun(genomes uncoupled)mutants.Although the first five gun mutants were identified 30 years ago,the functions of GUN proteins in retrograde signaling remain controversial,and that of GUN1 is hotly disputed.Here,we provide background information and critically discuss recently proposed concepts that address GUN-related signaling and some novel gun mutants.Moreover,considering heme as a candidate in retrograde signaling,we revisit the spatial organization of heme biosynthesis and export from plastids.Although this review focuses on GUN pathways,we also highlight recent progress in the identification and elucidation of chloroplast-derived signals that regulate the acclimation response in green algae and plants.Here,stress-induced accumulation of unfolded/misassembled chloroplast proteins evokes a chloroplast-specific unfolded protein response,which leads to changes in the expression levels of nucleus-encoded chaperones and proteases to restore plastid protein homeostasis.We also address the importance of chloroplast-derived signals for activation of flavonoid biosynthesis leading to production of anthocyanins during stress acclimation through sucrose non-fermenting 1-related protein kinase 1.Finally,a framework for identification and quantification of intercompartmental signaling cascades at the proteomic and metabolomic levels is provided,and we discuss future directions of dissection of organelle-nucleus communication.展开更多
Laser-plasma physics has developed rapidly over the past few decades as lasers have become both more powerful and more widely available.Early experimental and numerical research in this field was dominated by single-s...Laser-plasma physics has developed rapidly over the past few decades as lasers have become both more powerful and more widely available.Early experimental and numerical research in this field was dominated by single-shot experiments with limited parameter exploration.However,recent technological improvements make it possible to gather data for hundreds or thousands of different settings in both experiments and simulations.This has sparked interest in using advanced techniques from mathematics,statistics and computer science to deal with,and benefit from,big data.At the same time,sophisticated modeling techniques also provide new ways for researchers to deal effectively with situation where still only sparse data are available.This paper aims to present an overview of relevant machine learning methods with focus on applicability to laser-plasma physics and its important sub-fields of laser-plasma acceleration and inertial confinement fusion.展开更多
The 18 kDa translocator protein(TSPO)located on the outer mitochondrial membrane regulates several key cellular processes including mitochondrial homeostasis,cholesterol transport,apoptosis,cell proliferation,and main...The 18 kDa translocator protein(TSPO)located on the outer mitochondrial membrane regulates several key cellular processes including mitochondrial homeostasis,cholesterol transport,apoptosis,cell proliferation,and maintenance of mitochondrial health(Rupprecht et al.,2022,2023).TSPO is expressed in both peripheral organs and the central nervous system,with a more pronounced expression in tissues that produce steroids.The main reason why TSPO has garnered so much attention is because it plays a key role in neurosteroidogenesis by transferring cholesterol from the outer to the inner mitochondrial membrane,which is the rate-limiting step in neurosteroid synthesis.A cholesterol-recognizing amino acid consensus domain has been identified in the cytosolic C terminus of the TSPO protein by both in vitro and site-directed mutagenesis experiments(Li et al.,2001).However,the role of TSPO in the process of neurosteroid synthesis has been challenged by several studies,particularly TSPO knockout models,which suggest that TSPO removal does not affect the phenotype or the system’s viability(Tu et al.,2014).However,ligands targeting TSPO have been shown to enhance levels of neurosteroids which suggests that neurosteroidogenesis is one of the major functional roles mediated by the TSPO protein.展开更多
3D super-resolution microscopy with nanometric resolution is a key to fully complement ultrastructural techniques with fluorescence imaging.Here,we achieve 3D super-resolution by combining the 2D localization of pMINF...3D super-resolution microscopy with nanometric resolution is a key to fully complement ultrastructural techniques with fluorescence imaging.Here,we achieve 3D super-resolution by combining the 2D localization of pMINFLUX with the axial information of graphene energy transfer(GET)and the single-molecule switching by DNA-PAINT.We demonstrate≤2 nm localization precision in all 3 dimension with axial precision reaching below 0.3 nm.In 3D DNA-PAINT measurements,structural features,i.e.,individual docking strands at distances of 3 nm,are directly resolved on DNA origami structures.pMINFLUX and GET represent a particular synergetic combination for super-resolution imaging near the surface such as for cell adhesion and membrane complexes as the information of each photon is used for both 2D and axial localization information.Furthermore,we introduce local PAINT(L-PAINT),in which DNA-PAINT imager strands are equipped with an additional binding sequence for local upconcentration improving signal-to-background ratio and imaging speed of local clusters.L-PAINT is demonstrated by imaging a triangular structure with 6 nm side lengths within seconds.展开更多
AIM:To measure the difference of intraoperative central macular thickness(CMT)before,during,and after membrane peeling and investigate the influence of intraoperative macular stretching on postoperative best corrected...AIM:To measure the difference of intraoperative central macular thickness(CMT)before,during,and after membrane peeling and investigate the influence of intraoperative macular stretching on postoperative best corrected visual acuity(BCVA)outcome and postoperative CMT development.METHODS:A total of 59 eyes of 59 patients who underwent vitreoretinal surgery for epiretinal membrane was analyzed.Videos with intraoperative optical coherence tomography(OCT)were recorded.Difference of intraoperative CMT before,during,and after peeling was measured.Pre-and postoperatively obtained BCVA and spectral-domain OCT images were analyzed.RESULTS:Mean age of the patients was 70±8.13y(range 46-86y).Mean baseline BCVA was 0.49±0.27 log MAR(range 0.1-1.3).Three and six months postoperatively the mean BCVA was 0.36±0.25(P=0.01 vs baseline)and 0.38±0.35(P=0.08 vs baseline)log MAR respectively.Mean stretch of the macula during surgery was 29%from baseline(range 2%-159%).Intraoperative findings of macular stretching did not correlate with visual acuity outcome within 6mo after surgery(r=-0.06,P=0.72).However,extent of macular stretching during surgery significantly correlated with less reduction of CMT at the fovea centralis(r=-0.43,P<0.01)and 1 mm nasal and temporal from the fovea(r=-0.37,P=0.02 and r=-0.50,P<0.01 respectively)3mo postoperatively.CONCLUSION:The extent of retinal stretching during membrane peeling may predict the development of postoperative central retinal thickness,though there is no correlation with visual acuity development within the first 6mo postoperatively.展开更多
Laser-plasma accelerated(LPA)proton bunches are now applied for research fields ranging from ultra-high-dose-rate radiobiology to material science.Yet,the capabilities to characterize the spectrally and angularly broa...Laser-plasma accelerated(LPA)proton bunches are now applied for research fields ranging from ultra-high-dose-rate radiobiology to material science.Yet,the capabilities to characterize the spectrally and angularly broad LPA bunches lag behind the rapidly evolving applications.The OCTOPOD translates the angularly resolved spectral characterization of LPA proton bunches into the spatially resolved detection of the volumetric dose distribution deposited in a liquid scintillator.Up to 24 multi-pinhole arrays record projections of the scintillation light distribution and allow for tomographic reconstruction of the volumetric dose deposition pattern,from which proton spectra may be retrieved.Applying the OCTOPOD at a cyclotron,we show the reliable retrieval of various spatial dose deposition patterns and detector sensitivity over a broad dose range.Moreover,the OCTOPOD was installed at an LPA proton source,providing real-time data on proton acceleration performance and attesting the system optimal performance in the harsh laser-plasma environment.展开更多
Two-dimensional(2D)semiconductors possess strongly bound excitons,opening novel opportunities for engineering light-matter interaction at the nanoscale.However,their in-plane confinement leads to large non-radiative e...Two-dimensional(2D)semiconductors possess strongly bound excitons,opening novel opportunities for engineering light-matter interaction at the nanoscale.However,their in-plane confinement leads to large non-radiative exciton–exciton annihilation(EEA)processes,setting a fundamental limit for their photonic applications.In this work,we demonstrate suppression of EEA via enhancement of light-matter interaction in hybrid 2D semiconductor-dielectric nanophotonic platforms,by coupling excitons in WS2 monolayers with optical Mie resonances in dielectric nanoantennas.The hybrid system reaches an intermediate light-matter coupling regime,with photoluminescence enhancement factors up to 102.Probing the exciton ultrafast dynamics reveal suppressed EEA for coupled excitons,even under high exciton densities>10^(12)cm^(−2).We extract EEA coefficients in the order of 10^(−3),compared to 10^(−2)for uncoupled monolayers,as well as a Purcell factor of 4.5.Our results highlight engineering the photonic environment as a route to achieve higher quantum efficiencies,for low-power hybrid devices,and larger exciton densities,towards strongly correlated excitonic phases in 2D semiconductors.展开更多
Presented is a novel way to combine snapshot compressive imaging and lateral shearing interferometry in order to capture the spatio-spectral phase of an ultrashort laser pulse in a single shot.A deep unrolling algorit...Presented is a novel way to combine snapshot compressive imaging and lateral shearing interferometry in order to capture the spatio-spectral phase of an ultrashort laser pulse in a single shot.A deep unrolling algorithm is utilized for snapshot compressive imaging reconstruction due to its parameter efficiency and superior speed relative to other methods,potentially allowing for online reconstruction.The algorithm’s regularization term is represented using a neural network with 3D convolutional layers to exploit the spatio-spectral correlations that exist in laser wavefronts.Compressed sensing is not typically applied to modulated signals,but we demonstrate its success here.Furthermore,we train a neural network to predict the wavefronts from a lateral shearing interferogram in terms of Zernike polynomials,which again increases the speed of our technique without sacrificing fidelity.This method is supported with simulation-based results.While applied to the example of lateral shearing interferometry,the methods presented here are generally applicable to a wide range of signals,including Shack-Hartmann-type sensors.The results may be of interest beyond the context of laser wavefront characterization,including within quantitative phase imaging.展开更多
In a recent Cell publication,Cheong et al.uncover how COVID-19 causes IL-6 induced epigenetic reprogramming of human immune stem cells,which causes lasting alterations in the composition and response characteristics o...In a recent Cell publication,Cheong et al.uncover how COVID-19 causes IL-6 induced epigenetic reprogramming of human immune stem cells,which causes lasting alterations in the composition and response characteristics of circulating immune cells.1 The study provides important insights into the mechanisms by which SARSCoV-2 infections impact the human immune system and is an important hook into unraveling the mechanisms of post-acute sequelae of COVID-19(PASC)commonly referred to as longCOVID.展开更多
Dear Editor,Colorectal cancer(CRC)is the third most deadly can-cer worldwide[1].The mortality of CRC has remained high due to limited treatment options for metastatic CRC(mCRC)[2].Epithelial-mesenchymal transition(EMT...Dear Editor,Colorectal cancer(CRC)is the third most deadly can-cer worldwide[1].The mortality of CRC has remained high due to limited treatment options for metastatic CRC(mCRC)[2].Epithelial-mesenchymal transition(EMT)is an important contributor to mCRC[2].The c-MYC proto-oncogene(MYC)-induced transcription factor AP4(TFAP4/AP4)isadriverofEMT,therebypresumablyfacil-itates mCRC[3,4].The mitogen-activated protein kinase(MAPK)/c-JunN-terminalkinase(JNK)/activatorprotein-1(AP-1)pathway has been implicated in the regulation of EMT and mCRC[5].展开更多
The acoustic pulse emitted from the Bragg peak of a laser-accelerated proton bunch focused into water has recently enabled the reconstruction of the bunch energy distribution.By adding three ultrasonic transducers and...The acoustic pulse emitted from the Bragg peak of a laser-accelerated proton bunch focused into water has recently enabled the reconstruction of the bunch energy distribution.By adding three ultrasonic transducers and implementing a fast data analysis of the filtered raw signals,I-BEAT(Ion-Bunch Energy Acoustic Tracing)3D now provides the mean bunch energy and absolute lateral bunch position in real-time and for individual bunches.Relative changes in energy spread and lateral bunch size can also be monitored.Our experiments at DRACO with proton bunch energies between 10 and 30 MeV reveal sub-MeV and sub-mm resolution.In addition to this 3D bunch information,the signal strength correlates also with the absolute bunch particle number.展开更多
Electrochemical CO2 reduction is a promising strategy for the utilization of CO2 and intermittent excess electricity.Cu is the only single metal catalyst that can electrochemically convert CO2 into multicarbon product...Electrochemical CO2 reduction is a promising strategy for the utilization of CO2 and intermittent excess electricity.Cu is the only single metal catalyst that can electrochemically convert CO2 into multicarbon products.However,Cu exhibits an unfavorable activity and selectivity for the generation of C2 products because of the insufficient amount of CO*provided for the C‐C coupling.Based on the strong CO2 adsorption and ultrafast reaction kinetics of CO*formation on Pd,an intimate CuPd(100)interface was designed to lower the intermediate reaction barriers and improve the efficiency of C2 product formation.Density functional theory(DFT)calculations showed that the CuPd(100)interface enhanced the CO2 adsorption and decreased the CO2*hydrogenation energy barrier,which was beneficial for the C‐C coupling.The potential‐determining step(PDS)barrier of CO2 to C2 products on the CuPd(100)interface was 0.61 eV,which was lower than that on Cu(100)(0.72 eV).Encouraged by the DFT calculation results,the CuPd(100)interface catalyst was prepared by a facile chemical solution method and characterized by transmission electron microscopy.CO2 temperature‐programmed desorption and gas sensor experiments further confirmed the enhancement of the CO2 adsorption and CO2*hydrogenation ability of the CuPd(100)interface catalyst.Specifically,the obtained CuPd(100)interface catalyst exhibited a C2 Faradaic efficiency of 50.3%±1.2%at‒1.4 VRHE in 0.1 M KHCO3,which was 2.1 times higher than that of the Cu catalyst(23.6%±1.5%).This study provides the basis for the rational design of Cu‐based electrocatalysts for the generation of multicarbon products by fine‐tuning the intermediate reaction barriers.展开更多
Characterizing exact energy density distributions for laser-accelerated ion bunches in a medium is challenging due to very high beam intensities and the electro-magnetic pulse emitted in the laser-plasma interaction.I...Characterizing exact energy density distributions for laser-accelerated ion bunches in a medium is challenging due to very high beam intensities and the electro-magnetic pulse emitted in the laser-plasma interaction.Ion-bunch energy acoustic tracing allows for reconstructing the spatial energy density from the ionoacoustic wave generated upon impact in water.We have extended this approach to tracing ionoacoustic modulations of broad energy distributions by introducing thin foils in the water reservoir to shape the acoustic waves at distinct points along the depth-dose curve.Here,we present first simulation studies of this new detector and reconstruction approach,which provides an online read-out of the deposited energy with depth within the centimeter range behind the ion source of state-of-the-art laser-plasma-based accelerators.展开更多
Background:IgG-class autoantibodies to N-Methyl-D-Aspartate(NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis.Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with ...Background:IgG-class autoantibodies to N-Methyl-D-Aspartate(NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis.Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results.We measured NMDA antibodies in a large,well phenotyped sample of Parkinson patients without and with cognitive impairment(n=296)and controls(n=295)free of neuropsychiatric disease.Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment.Methods:NMDA antibodies were analysed in the serum of patients and controls using well established validated assays.We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics.Results:The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients(13%)than in controls(22%)and higher than in previous studies in both groups.NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment,nor with quantitative indicators of disease severity and cognitive impairment.A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients.Conclusion:It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g.to Parkinson disease with dementia,while NMDA IgG antibodies define a separate disease of its own.展开更多
Neurodegenerative diseases are characterized by a progressive dysfunction of the nervous system.Often associated with atrophy of the affected central or peripheral nervous structures,they include diseases such as Park...Neurodegenerative diseases are characterized by a progressive dysfunction of the nervous system.Often associated with atrophy of the affected central or peripheral nervous structures,they include diseases such as Parkinson’s Disease(PD),Alzheimer’s Disease and other dementias,Genetic Brain Disorders,Amyotrophic Lateral Sclerosis(ALS or Lou Gehrig’s Disease),Huntington’s Disease,Prion Diseases,and others.The prevalence of neurodegenerative diseases has increased over the last years.This has had a major impact both on patients and their families and has exponentially increased the medical bill by hundreds of billions of Euros.Therefore,understanding the role of environmental and genetic factors in the pathogenesis of PD is crucial to develop preventive strategies.While some authors believe that PD is mainly genetic and that the aging of the society is the principal cause for this increase,different studies suggest that PD may be due to an increased exposure to environmental toxins.In this article we review epidemiological,sociological and experimental studies to determine which hypothesis is more plausible.Our conclusion is that,at least in idiopathic PD(iPD),the exposure to toxic environmental substances could play an important role in its aetiology.展开更多
The next generation of high-power lasers enables repetition of experiments at orders of magnitude higher frequency than what was possible using the prior generation.Facilities requiring human intervention between lase...The next generation of high-power lasers enables repetition of experiments at orders of magnitude higher frequency than what was possible using the prior generation.Facilities requiring human intervention between laser repetitions need to adapt in order to keep pace with the new laser technology.A distributed networked control system can enable laboratory-wide automation and feedback control loops.These higher-repetition-rate experiments will create enormous quantities of data.A consistent approach to managing data can increase data accessibility,reduce repetitive data-software development and mitigate poorly organized metadata.An opportunity arises to share knowledge of improvements to control and data infrastructure currently being undertaken.We compare platforms and approaches to state-of-the-art control systems and data management at high-power laser facilities,and we illustrate these topics with case studies from our community.展开更多
A photonic connection between turbulence and spin glasses has been recently established both theoretically and experimentally using a random fiber laser as a photonic platform.Besides unveiling this interplay,it links...A photonic connection between turbulence and spin glasses has been recently established both theoretically and experimentally using a random fiber laser as a photonic platform.Besides unveiling this interplay,it links the works of two 2021 Nobel laureates in Physics.展开更多
The Centre for Advanced Laser Applications in Garching,Germany,is home to the ATLAS-3000 multi-petawatt laser,dedicated to research on laser particle acceleration and its applications.A control system based on Tango C...The Centre for Advanced Laser Applications in Garching,Germany,is home to the ATLAS-3000 multi-petawatt laser,dedicated to research on laser particle acceleration and its applications.A control system based on Tango Controls is implemented for both the laser and four experimental areas.The device server approach features high modularity,which,in addition to the hardware control,enables a quick extension of the system and allows for automated data acquisition of the laser parameters and experimental data for each laser shot.In this paper we present an overview of our implementation of the control system,as well as our advances in terms of experimental operation,online supervision and data processing.We also give an outlook on advanced experimental supervision and online data evaluation–where the data can be processed in a pipeline–which is being developed on the basis of this infrastructure.展开更多
基金support by the operating resources of the Centre for Advanced Laser Applications(CALA)support from the Alexander von Humboldt Stiftung+1 种基金support from the BMBF under contract number 05K19WMBsupport from the German Research Agency,DFG Project No.453619281
文摘The recent advent of deep artificial neural networks has resulted in a dramatic increase in performance for object classification and detection.While pre-trained with everyday objects,we find that a state-of-the-art object detection architecture can very efficiently be fine-tuned to work on a variety of object detection tasks in a high-power laser laboratory.In this paper,three exemplary applications are presented.We show that the plasma waves in a laser±plasma accelerator can be detected and located on the optical shadowgrams.The plasma wavelength and plasma density are estimated accordingly.Furthermore,we present the detection of all the peaks in an electron energy spectrum of the accelerated electron beam,and the beam charge of each peak is estimated accordingly.Lastly,we demonstrate the detection of optical damage in a high-power laser system.The reliability of the object detector is demonstrated over1000 laser shots in each application.Our study shows that deep object detection networks are suitable to assist online and offline experimental analysis,even with small training sets.We believe that the presented methodology is adaptable yet robust,and we encourage further applications in Hz-level or kHz-level high-power laser facilities regarding the control and diagnostic tools,especially for those involving image data.
基金European Research Council(Advanced Investigator Grant 267854)Munich Center for Advanced Photonics Max Planck Foundation+1 种基金IXCORE Fondation pour la RecherchePARI PHOTCOM Région Bourgogne,Labex ACTION program(Contract No.ANR-11-LABX-0001-01).
文摘Absorption spectroscopy of fundamental ro-vibrational transitions in the mid-infrared region provides a powerful tool for studying the structure and dynamics of molecules in the gas phase and for sensitive and quantitative gas sensing.Laser frequency combs permit novel approaches to perform broadband molecular spectroscopy.Multiplex dual-comb spectroscopy without moving parts can achieve particularly high speed,sensitivity and resolution.However,achieving Doppler-limited resolution in the mid-infrared still requires overcoming instrumental challenges.Here we demonstrate a new approach based on difference-frequency generation of frequency-agile near-infrared frequency combs that are produced using electro-optic modulators.The combs have a remarkably flat intensity distribution,and their positions and line spacings can be freely selected by simply dialing a knob.Using the proposed technique,we record,in the 3-μm region,Doppler-limited absorption spectra with resolved comb lines within milliseconds,and precise molecular line parameters are retrieved.Our technique holds promise for fast and sensitive time-resolved studies of,for example,trace gases.
基金supported by the Deutsche Forschungsgemeinschaft(TRR175,project C01 to T.K.,project C02 to M.S.,project C04 to B.G.,project C05 to K.K.and D.L.,project C06 to A.S.R.,and project D03 to T.N.).
文摘Plastids communicate their developmental and physiological status to the nucleus via retrograde signaling,allowing nuclear gene expression to be adjusted appropriately.Signaling during plastid biogenesis and responses of mature chloroplasts to environmental changes are designated“biogenic”and“operational”controls,respectively.A prominent example of the investigation of biogenic signaling is the screen for gun(genomes uncoupled)mutants.Although the first five gun mutants were identified 30 years ago,the functions of GUN proteins in retrograde signaling remain controversial,and that of GUN1 is hotly disputed.Here,we provide background information and critically discuss recently proposed concepts that address GUN-related signaling and some novel gun mutants.Moreover,considering heme as a candidate in retrograde signaling,we revisit the spatial organization of heme biosynthesis and export from plastids.Although this review focuses on GUN pathways,we also highlight recent progress in the identification and elucidation of chloroplast-derived signals that regulate the acclimation response in green algae and plants.Here,stress-induced accumulation of unfolded/misassembled chloroplast proteins evokes a chloroplast-specific unfolded protein response,which leads to changes in the expression levels of nucleus-encoded chaperones and proteases to restore plastid protein homeostasis.We also address the importance of chloroplast-derived signals for activation of flavonoid biosynthesis leading to production of anthocyanins during stress acclimation through sucrose non-fermenting 1-related protein kinase 1.Finally,a framework for identification and quantification of intercompartmental signaling cascades at the proteomic and metabolomic levels is provided,and we discuss future directions of dissection of organelle-nucleus communication.
基金The authors acknowledge the use of GPT-3[288](text-davinci-003)in the copy-editing process of this manuscript.
文摘Laser-plasma physics has developed rapidly over the past few decades as lasers have become both more powerful and more widely available.Early experimental and numerical research in this field was dominated by single-shot experiments with limited parameter exploration.However,recent technological improvements make it possible to gather data for hundreds or thousands of different settings in both experiments and simulations.This has sparked interest in using advanced techniques from mathematics,statistics and computer science to deal with,and benefit from,big data.At the same time,sophisticated modeling techniques also provide new ways for researchers to deal effectively with situation where still only sparse data are available.This paper aims to present an overview of relevant machine learning methods with focus on applicability to laser-plasma physics and its important sub-fields of laser-plasma acceleration and inertial confinement fusion.
基金supported by the German Research Foundation(Deutsche Forschungsgemeinschaft)(DFG),project number 422179811 to RR and RA 689/12-1 to GR.
文摘The 18 kDa translocator protein(TSPO)located on the outer mitochondrial membrane regulates several key cellular processes including mitochondrial homeostasis,cholesterol transport,apoptosis,cell proliferation,and maintenance of mitochondrial health(Rupprecht et al.,2022,2023).TSPO is expressed in both peripheral organs and the central nervous system,with a more pronounced expression in tissues that produce steroids.The main reason why TSPO has garnered so much attention is because it plays a key role in neurosteroidogenesis by transferring cholesterol from the outer to the inner mitochondrial membrane,which is the rate-limiting step in neurosteroid synthesis.A cholesterol-recognizing amino acid consensus domain has been identified in the cytosolic C terminus of the TSPO protein by both in vitro and site-directed mutagenesis experiments(Li et al.,2001).However,the role of TSPO in the process of neurosteroid synthesis has been challenged by several studies,particularly TSPO knockout models,which suggest that TSPO removal does not affect the phenotype or the system’s viability(Tu et al.,2014).However,ligands targeting TSPO have been shown to enhance levels of neurosteroids which suggests that neurosteroidogenesis is one of the major functional roles mediated by the TSPO protein.
基金support by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)under Germany's Excellence Strategy-EXC 089/1-390776260,201269156-SFB1032.
文摘3D super-resolution microscopy with nanometric resolution is a key to fully complement ultrastructural techniques with fluorescence imaging.Here,we achieve 3D super-resolution by combining the 2D localization of pMINFLUX with the axial information of graphene energy transfer(GET)and the single-molecule switching by DNA-PAINT.We demonstrate≤2 nm localization precision in all 3 dimension with axial precision reaching below 0.3 nm.In 3D DNA-PAINT measurements,structural features,i.e.,individual docking strands at distances of 3 nm,are directly resolved on DNA origami structures.pMINFLUX and GET represent a particular synergetic combination for super-resolution imaging near the surface such as for cell adhesion and membrane complexes as the information of each photon is used for both 2D and axial localization information.Furthermore,we introduce local PAINT(L-PAINT),in which DNA-PAINT imager strands are equipped with an additional binding sequence for local upconcentration improving signal-to-background ratio and imaging speed of local clusters.L-PAINT is demonstrated by imaging a triangular structure with 6 nm side lengths within seconds.
文摘AIM:To measure the difference of intraoperative central macular thickness(CMT)before,during,and after membrane peeling and investigate the influence of intraoperative macular stretching on postoperative best corrected visual acuity(BCVA)outcome and postoperative CMT development.METHODS:A total of 59 eyes of 59 patients who underwent vitreoretinal surgery for epiretinal membrane was analyzed.Videos with intraoperative optical coherence tomography(OCT)were recorded.Difference of intraoperative CMT before,during,and after peeling was measured.Pre-and postoperatively obtained BCVA and spectral-domain OCT images were analyzed.RESULTS:Mean age of the patients was 70±8.13y(range 46-86y).Mean baseline BCVA was 0.49±0.27 log MAR(range 0.1-1.3).Three and six months postoperatively the mean BCVA was 0.36±0.25(P=0.01 vs baseline)and 0.38±0.35(P=0.08 vs baseline)log MAR respectively.Mean stretch of the macula during surgery was 29%from baseline(range 2%-159%).Intraoperative findings of macular stretching did not correlate with visual acuity outcome within 6mo after surgery(r=-0.06,P=0.72).However,extent of macular stretching during surgery significantly correlated with less reduction of CMT at the fovea centralis(r=-0.43,P<0.01)and 1 mm nasal and temporal from the fovea(r=-0.37,P=0.02 and r=-0.50,P<0.01 respectively)3mo postoperatively.CONCLUSION:The extent of retinal stretching during membrane peeling may predict the development of postoperative central retinal thickness,though there is no correlation with visual acuity development within the first 6mo postoperatively.
基金the DRACO laser team and UPTD team for excellent experiment supportpartially supported by H2020 Laserlab Europe V(PRISES,contract No.871124)+2 种基金by the European Union’s Horizon 2020 Research and Innovation Programme Impulse(grant agreement No.871161)the support of the Weizmann-Helmholtz Laboratory for Laser Matter Interaction(WHELMI)The experimental part of the University Proton Therapy Dresden(UPTD)facility has received funding from the European Union’s Horizon 2020 Research and Innovation Program(grant agreement No.730983(INSPIRE))
文摘Laser-plasma accelerated(LPA)proton bunches are now applied for research fields ranging from ultra-high-dose-rate radiobiology to material science.Yet,the capabilities to characterize the spectrally and angularly broad LPA bunches lag behind the rapidly evolving applications.The OCTOPOD translates the angularly resolved spectral characterization of LPA proton bunches into the spatially resolved detection of the volumetric dose distribution deposited in a liquid scintillator.Up to 24 multi-pinhole arrays record projections of the scintillation light distribution and allow for tomographic reconstruction of the volumetric dose deposition pattern,from which proton spectra may be retrieved.Applying the OCTOPOD at a cyclotron,we show the reliable retrieval of various spatial dose deposition patterns and detector sensitivity over a broad dose range.Moreover,the OCTOPOD was installed at an LPA proton source,providing real-time data on proton acceleration performance and attesting the system optimal performance in the harsh laser-plasma environment.
基金S.A.M.acknowledges the Lee Lucas chair in physics and funding by the EPSRC(EP/WO1707511)the Australian Research Council(Centre of Excellence in Future Low-Energy Electronics Technologies-CE 170100039)+1 种基金L.S.further acknowledges funding support through a Humboldt Research Fellowship from the Alexander von Humboldt FoundationOur studies were partially supported by the Center for NanoScience(CeNS)-Faculty of Physics,Ludwig-Maximilians University Munich.
文摘Two-dimensional(2D)semiconductors possess strongly bound excitons,opening novel opportunities for engineering light-matter interaction at the nanoscale.However,their in-plane confinement leads to large non-radiative exciton–exciton annihilation(EEA)processes,setting a fundamental limit for their photonic applications.In this work,we demonstrate suppression of EEA via enhancement of light-matter interaction in hybrid 2D semiconductor-dielectric nanophotonic platforms,by coupling excitons in WS2 monolayers with optical Mie resonances in dielectric nanoantennas.The hybrid system reaches an intermediate light-matter coupling regime,with photoluminescence enhancement factors up to 102.Probing the exciton ultrafast dynamics reveal suppressed EEA for coupled excitons,even under high exciton densities>10^(12)cm^(−2).We extract EEA coefficients in the order of 10^(−3),compared to 10^(−2)for uncoupled monolayers,as well as a Purcell factor of 4.5.Our results highlight engineering the photonic environment as a route to achieve higher quantum efficiencies,for low-power hybrid devices,and larger exciton densities,towards strongly correlated excitonic phases in 2D semiconductors.
基金supported by the Independent Junior Research Group‘Characterization and control of high-intensity laser pulses for particle acceleration’,DFG Project No.453619281We would also like to acknowledge UKRI-STFC grant ST/V001655/1.
文摘Presented is a novel way to combine snapshot compressive imaging and lateral shearing interferometry in order to capture the spatio-spectral phase of an ultrashort laser pulse in a single shot.A deep unrolling algorithm is utilized for snapshot compressive imaging reconstruction due to its parameter efficiency and superior speed relative to other methods,potentially allowing for online reconstruction.The algorithm’s regularization term is represented using a neural network with 3D convolutional layers to exploit the spatio-spectral correlations that exist in laser wavefronts.Compressed sensing is not typically applied to modulated signals,but we demonstrate its success here.Furthermore,we train a neural network to predict the wavefronts from a lateral shearing interferogram in terms of Zernike polynomials,which again increases the speed of our technique without sacrificing fidelity.This method is supported with simulation-based results.While applied to the example of lateral shearing interferometry,the methods presented here are generally applicable to a wide range of signals,including Shack-Hartmann-type sensors.The results may be of interest beyond the context of laser wavefront characterization,including within quantitative phase imaging.
文摘In a recent Cell publication,Cheong et al.uncover how COVID-19 causes IL-6 induced epigenetic reprogramming of human immune stem cells,which causes lasting alterations in the composition and response characteristics of circulating immune cells.1 The study provides important insights into the mechanisms by which SARSCoV-2 infections impact the human immune system and is an important hook into unraveling the mechanisms of post-acute sequelae of COVID-19(PASC)commonly referred to as longCOVID.
基金This work was supported by German Cancer Aid/Deutsche Krebshilfe grants(70114235 and 70112245)to Heiko Hermeking.
文摘Dear Editor,Colorectal cancer(CRC)is the third most deadly can-cer worldwide[1].The mortality of CRC has remained high due to limited treatment options for metastatic CRC(mCRC)[2].Epithelial-mesenchymal transition(EMT)is an important contributor to mCRC[2].The c-MYC proto-oncogene(MYC)-induced transcription factor AP4(TFAP4/AP4)isadriverofEMT,therebypresumablyfacil-itates mCRC[3,4].The mitogen-activated protein kinase(MAPK)/c-JunN-terminalkinase(JNK)/activatorprotein-1(AP-1)pathway has been implicated in the regulation of EMT and mCRC[5].
基金supported by the German Research Foundation (DFG) within the Research Training Group GRK 2274the Bundesministerium für Bildung und Forschung (BMBF) within project 01IS17048financial support by the BMBF within projects 05P18WMFA1 and 05P21WMFA1
文摘The acoustic pulse emitted from the Bragg peak of a laser-accelerated proton bunch focused into water has recently enabled the reconstruction of the bunch energy distribution.By adding three ultrasonic transducers and implementing a fast data analysis of the filtered raw signals,I-BEAT(Ion-Bunch Energy Acoustic Tracing)3D now provides the mean bunch energy and absolute lateral bunch position in real-time and for individual bunches.Relative changes in energy spread and lateral bunch size can also be monitored.Our experiments at DRACO with proton bunch energies between 10 and 30 MeV reveal sub-MeV and sub-mm resolution.In addition to this 3D bunch information,the signal strength correlates also with the absolute bunch particle number.
文摘Electrochemical CO2 reduction is a promising strategy for the utilization of CO2 and intermittent excess electricity.Cu is the only single metal catalyst that can electrochemically convert CO2 into multicarbon products.However,Cu exhibits an unfavorable activity and selectivity for the generation of C2 products because of the insufficient amount of CO*provided for the C‐C coupling.Based on the strong CO2 adsorption and ultrafast reaction kinetics of CO*formation on Pd,an intimate CuPd(100)interface was designed to lower the intermediate reaction barriers and improve the efficiency of C2 product formation.Density functional theory(DFT)calculations showed that the CuPd(100)interface enhanced the CO2 adsorption and decreased the CO2*hydrogenation energy barrier,which was beneficial for the C‐C coupling.The potential‐determining step(PDS)barrier of CO2 to C2 products on the CuPd(100)interface was 0.61 eV,which was lower than that on Cu(100)(0.72 eV).Encouraged by the DFT calculation results,the CuPd(100)interface catalyst was prepared by a facile chemical solution method and characterized by transmission electron microscopy.CO2 temperature‐programmed desorption and gas sensor experiments further confirmed the enhancement of the CO2 adsorption and CO2*hydrogenation ability of the CuPd(100)interface catalyst.Specifically,the obtained CuPd(100)interface catalyst exhibited a C2 Faradaic efficiency of 50.3%±1.2%at‒1.4 VRHE in 0.1 M KHCO3,which was 2.1 times higher than that of the Cu catalyst(23.6%±1.5%).This study provides the basis for the rational design of Cu‐based electrocatalysts for the generation of multicarbon products by fine‐tuning the intermediate reaction barriers.
基金the support of the BMBFFSP APPA collaboration project 05P18WMFA1 and 05P21WMFA1the German Research Foundation (DFG) - Research Training Group GRK 2274+1 种基金the DFG project 403225886the Konrad Adenauer Stiftung
文摘Characterizing exact energy density distributions for laser-accelerated ion bunches in a medium is challenging due to very high beam intensities and the electro-magnetic pulse emitted in the laser-plasma interaction.Ion-bunch energy acoustic tracing allows for reconstructing the spatial energy density from the ionoacoustic wave generated upon impact in water.We have extended this approach to tracing ionoacoustic modulations of broad energy distributions by introducing thin foils in the water reservoir to shape the acoustic waves at distinct points along the depth-dose curve.Here,we present first simulation studies of this new detector and reconstruction approach,which provides an online read-out of the deposited energy with depth within the centimeter range behind the ion source of state-of-the-art laser-plasma-based accelerators.
基金Intramural funding of the Dept.of Neurology,Kiel University.
文摘Background:IgG-class autoantibodies to N-Methyl-D-Aspartate(NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis.Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results.We measured NMDA antibodies in a large,well phenotyped sample of Parkinson patients without and with cognitive impairment(n=296)and controls(n=295)free of neuropsychiatric disease.Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment.Methods:NMDA antibodies were analysed in the serum of patients and controls using well established validated assays.We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics.Results:The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients(13%)than in controls(22%)and higher than in previous studies in both groups.NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment,nor with quantitative indicators of disease severity and cognitive impairment.A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients.Conclusion:It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g.to Parkinson disease with dementia,while NMDA IgG antibodies define a separate disease of its own.
文摘Neurodegenerative diseases are characterized by a progressive dysfunction of the nervous system.Often associated with atrophy of the affected central or peripheral nervous structures,they include diseases such as Parkinson’s Disease(PD),Alzheimer’s Disease and other dementias,Genetic Brain Disorders,Amyotrophic Lateral Sclerosis(ALS or Lou Gehrig’s Disease),Huntington’s Disease,Prion Diseases,and others.The prevalence of neurodegenerative diseases has increased over the last years.This has had a major impact both on patients and their families and has exponentially increased the medical bill by hundreds of billions of Euros.Therefore,understanding the role of environmental and genetic factors in the pathogenesis of PD is crucial to develop preventive strategies.While some authors believe that PD is mainly genetic and that the aging of the society is the principal cause for this increase,different studies suggest that PD may be due to an increased exposure to environmental toxins.In this article we review epidemiological,sociological and experimental studies to determine which hypothesis is more plausible.Our conclusion is that,at least in idiopathic PD(iPD),the exposure to toxic environmental substances could play an important role in its aetiology.
基金A.J.acknowledges the support from DOE Grant#DESC0016804.
文摘The next generation of high-power lasers enables repetition of experiments at orders of magnitude higher frequency than what was possible using the prior generation.Facilities requiring human intervention between laser repetitions need to adapt in order to keep pace with the new laser technology.A distributed networked control system can enable laboratory-wide automation and feedback control loops.These higher-repetition-rate experiments will create enormous quantities of data.A consistent approach to managing data can increase data accessibility,reduce repetitive data-software development and mitigate poorly organized metadata.An opportunity arises to share knowledge of improvements to control and data infrastructure currently being undertaken.We compare platforms and approaches to state-of-the-art control systems and data management at high-power laser facilities,and we illustrate these topics with case studies from our community.
文摘A photonic connection between turbulence and spin glasses has been recently established both theoretically and experimentally using a random fiber laser as a photonic platform.Besides unveiling this interplay,it links the works of two 2021 Nobel laureates in Physics.
基金Federal Republic of Germany and the Free State of Bavaria for funding the CALA infrastructure(15171 E 0002)and its operation.the Independent Junior Research Group“Characterization and control of high-intensity laser pulses for particle acceleration”,DFG Project No.453619281.+1 种基金N.W.was supported via the IMPULSE project by the European Union Framework Program for Research and Innovation Horizon 2020 under grant agreement No.871161.the Bundesministerium für Bildung und Forschung(BMBF)within project 01IS17048.J.G.acknowledges support from the German Academic scholarship foundation.
文摘The Centre for Advanced Laser Applications in Garching,Germany,is home to the ATLAS-3000 multi-petawatt laser,dedicated to research on laser particle acceleration and its applications.A control system based on Tango Controls is implemented for both the laser and four experimental areas.The device server approach features high modularity,which,in addition to the hardware control,enables a quick extension of the system and allows for automated data acquisition of the laser parameters and experimental data for each laser shot.In this paper we present an overview of our implementation of the control system,as well as our advances in terms of experimental operation,online supervision and data processing.We also give an outlook on advanced experimental supervision and online data evaluation–where the data can be processed in a pipeline–which is being developed on the basis of this infrastructure.
