Multilayered control of myelination:Quick,saltatory conduction of action potentials along nerve fibers requires the electrical insulation of axons by myelinating glia.In the central nervous system,this role is taken u...Multilayered control of myelination:Quick,saltatory conduction of action potentials along nerve fibers requires the electrical insulation of axons by myelinating glia.In the central nervous system,this role is taken up by oligodendrocytes.Oligodendrocytes are marked by the expression of the lineage determinants Sox10 and Olig2 and arise from oligodendrocyte precursor cells(OPCs)during embryonal stages.While the majority of OPCs differentiate into mature oligodendrocytes when nearby axonal segments require myelination,a small subpopulation of OPCs persist as a progenitor pool.Therefore,the timing of myelination and maintenance of the OPC pool both need to be precisely regulated.Different transcription factors either positively or negatively affect oligodendrocyte differentiation and maintenance of the OPC pool as components of a complex gene regulatory network(reviewed in Sock and Wegner,2021).Network activity is additionally influenced by extracellular signaling molecules that bind to receptors on the oligodendroglial cell surface and activate intracellular signaling pathways.How the receptors are linked to the network is poorly understood so far,but pivotal to understanding the overall regulation of central nervous system(CNS)myelination in response to environmental cues.Relevant insights were recently gained for Gpr37(Schmidt et al.,2024),a G-protein coupled receptor(GPCR)with known relevance in differentiating oligodendrocytes(Yang et al,2016).展开更多
The parasitic hydrogen evolution reaction(HER)in the negative half-cell of vanadium redox flow batteries(VRFBs)causes severe efficiency losses.Thus,a deeper understanding of this process and the accompanying bubble fo...The parasitic hydrogen evolution reaction(HER)in the negative half-cell of vanadium redox flow batteries(VRFBs)causes severe efficiency losses.Thus,a deeper understanding of this process and the accompanying bubble formation is crucial.This benchmarking study locally analyzes the bubble distribution in thick,porous electrodes for the first time using deep learning-based image segmentation of synchrotron X-ray micro-tomograms.Each large three-dimensional data set was processed precisely in less than one minute while minimizing human errors and pointing out areas of increased HER activity in VRFBs.The study systematically varies the electrode potential and material,concluding that more negative electrode potentials of-200 m V vs.reversible hydrogen electrode(RHE)and lower cause more substantial bubble formation,resulting in bubble fractions of around 15%–20%in carbon felt electrodes.Contrarily,the bubble fractions stay only around 2%in an electrode combining carbon felt and carbon paper.The detected areas with high HER activity,such as the border subregion with more than 30%bubble fraction in carbon felt electrodes,the cutting edges,and preferential spots in the electrode bulk,are potential-independent and suggest that larger electrodes with a higher bulk-to-border ratio might reduce HER-related performance losses.The described combination of electrochemical measurements,local X-ray microtomography,AI-based segmentation,and 3D morphometric analysis is a powerful and novel approach for local bubble analysis in three-dimensional porous electrodes,providing an essential toolkit for a broad community working on bubble-generating electrochemical systems.展开更多
The development of freestanding and binder-free electrode is an effective approach to perform the inherent capacity of active materials and promote the mechanism study by minimizing the interference from additives.Her...The development of freestanding and binder-free electrode is an effective approach to perform the inherent capacity of active materials and promote the mechanism study by minimizing the interference from additives.Herein,we construct a freestanding cathode composed of MoS_(3)/PPy nanowires(NWs)deposited on porous nickel foam(NF)(MoS_(3)/PPy/NF)through electrochemical methods,which can work efficiently as sulfur-equivalent cathode material for Li-S batteries.The structural stability of the MoS_(3)/PPy/NF cathode is greatly enhanced due to its significant tolerance to the volume expansion of MoS_(3)during the lithiation process,which we ascribe to the flexible 3D framework of PPy NWs,leading to superior cycling performance compared to the bulk-MoS_(3)/NF reference.Eliminating the interference of binder and carbon additives,the evolution of the chemical and electronic structure of Mo and S species during the discharge/charge was studied by X-ray absorption near-edge spectroscopy(XANES).The formation of lithium polysulfides was excluded as the driving cathode reaction mechanism,suggesting the great potential of MoS_(3)as a promising sulfur-equivalent cathode material to evade the shuttle effect for Li-S batteries.The present study successfully demonstrates the importance of structural design of freestanding electrode enhancing the cycling performances and revealing the corresponding mechanisms.展开更多
Glass welding by ultra-short pulsed(USP)lasers is a piece of technology that offers high strength joints with hermetic sealing.The joints are typically formed in glass that is transparent to the laser by exploiting no...Glass welding by ultra-short pulsed(USP)lasers is a piece of technology that offers high strength joints with hermetic sealing.The joints are typically formed in glass that is transparent to the laser by exploiting nonlinear absorption effects that occur under extreme conditions.Though the temperature reached during the process is on the order of a few 1000°C,the heat affected zone(HAZ)is confined to only tens of micrometers.It is this controlled confinement of the HAZ during the joining process that makes this technology so appealing to a multitude of applications because it allows the foregoing of a subsequent tempering step that is typically essential in other glass joining techniques,thus making it possible to effectively join highly heat sensitive components.In this work,we give an overview on the process,development and applications of glass welding by USP lasers.展开更多
Lysosomes are ubiquitous and dynamic organelles with a central role in degradation and recycling of damaged cell components and misfolded proteins,otherwise known as autophagy.Autophagy plays a fundamental role in the...Lysosomes are ubiquitous and dynamic organelles with a central role in degradation and recycling of damaged cell components and misfolded proteins,otherwise known as autophagy.Autophagy plays a fundamental role in the process of correcting cell homeostasis and cellular survival.Unsurprisingly,this process is essential in the central nervous system,as neurons are not able to easily eliminate altered proteins given their post-mitotic state.展开更多
Within this work,we present a system for the measurement of the three-dimensional(3D)trajectories of spatters and entrained particles during laser powder bed fusion(L-PBF)of metals.It is comprised of two ultrahigh-spe...Within this work,we present a system for the measurement of the three-dimensional(3D)trajectories of spatters and entrained particles during laser powder bed fusion(L-PBF)of metals.It is comprised of two ultrahigh-speed cameras and a reconstruction task specific processing reconstruction algorithm.The system enables an automated determination of 3D measures from the trajectories of a large number of tracked particles.Ambiguity evolving from an underdetermined geometrical situation induced by a two-camera setup is resolved within the tracking using a priori knowledge of L-PBF of metals.All processing steps were optimized to run on a graphics processing unit to allow the processing of large amounts of data within an appropriate time frame.The overall approach was validated by a comparison of the measurement results to synthetic images with a known 3D ground truth.展开更多
Lysosomes are the major degradative compartments within eukaryotic cells.Besides their role in the degradation and recycling of intra-and extracellular molecules,they further mediate important biological processes,suc...Lysosomes are the major degradative compartments within eukaryotic cells.Besides their role in the degradation and recycling of intra-and extracellular molecules,they further mediate important biological processes,such as immune signaling and perpetuation of nutrientand energy homeostasis.展开更多
Formation of the node of Ranvier as a highly coordinated event:Saltatory conduction ensures that information in the vertebrate nervous system is rapidly transmitted over large distances and efficiently processed in co...Formation of the node of Ranvier as a highly coordinated event:Saltatory conduction ensures that information in the vertebrate nervous system is rapidly transmitted over large distances and efficiently processed in complex networks.It requires the insulation of axonal segments by myelin and the formation of highly structured nodes of Ranvier that are interspersed at regular intervals between successive myelin sheaths and regenerate the action potential as it propagates along the nerve(Rasband and Peles,2021).展开更多
Sox9–gliogenesis and beyond:Neurons and glial cells are the major neuroectodermal cell types of the vertebrate central nervous system(CNS).Their generation from common progenitor cells takes place mostly during embry...Sox9–gliogenesis and beyond:Neurons and glial cells are the major neuroectodermal cell types of the vertebrate central nervous system(CNS).Their generation from common progenitor cells takes place mostly during embryonic and early postnatal development.After closure of the neural tube,neural epithelial progenitor cells(NEPs)establish the ventricular zone(VZ).By asymmetrical cell division,NEPs first give rise to neuronal precursor cells(NPs)that then differentiate into various types of neurons.Later,NEPs predominantly produce glial precursor cells that become either astroglia or oligodendroglia.展开更多
In this report,we show that hyperspectral high-resolution photoluminescence mapping is a powerful tool for the selection and optimiz1ation of the laser ablation processes used for the patterning interconnections of su...In this report,we show that hyperspectral high-resolution photoluminescence mapping is a powerful tool for the selection and optimiz1ation of the laser ablation processes used for the patterning interconnections of subcells on Cu(Inx,Ga1-x)Se2(CIGS)modules.In this way,we show that in-depth monitoring of material degradation in the vicinity of the ablation region and the identification of the underlying mechanisms can be accomplished.Specifically,by analyzing the standard P1 patterning line ablated before the CIGS deposition,we reveal an anomalous emission-quenching effect that follows the edge of the molybdenum groove underneath.We further rationalize the origins of this effect by comparing the topography of the P1 edge through a scanning electron microscope(SEM)cross-section,where a reduction of the photoemission cannot be explained by a thickness variation.We also investigate the laser-induced damage on P1 patterning lines performed after the deposition of CIGS.We then document,for the first time,the existence of a short-range damaged area,which is independent of the application of an optical aperture on the laser path.Our findings pave the way for a better understanding of P1-induced power losses and introduce new insights into the improvement of current strategies for industry-relevant module interconnection schemes.展开更多
The classical role of adipocytokines is a negative feedback mechanism,providing information about bodily energy reserves to the brain,and thus controlling satiety and food intake (Campfield et al.,1995).Adipose tissue...The classical role of adipocytokines is a negative feedback mechanism,providing information about bodily energy reserves to the brain,and thus controlling satiety and food intake (Campfield et al.,1995).Adipose tissue forms the largest endocrine organ of the body.After the initial description of leptin and its receptor,LEPR/OBR,with its main active isoform OBRb,there was an initial hope for a drugable pathway to counteract the increasing burden of overweight/adiposity,metabolic syndrome,and related disorders (Figure1).展开更多
Bacterial cellulose is a versatile material with applications in many industries. However, the widespread uptake of bacterial cellulose faces challenges including high production costs and lack of scalability. One app...Bacterial cellulose is a versatile material with applications in many industries. However, the widespread uptake of bacterial cellulose faces challenges including high production costs and lack of scalability. One approach to address these obstacles is the use of alternative substrates and media, compared to the Hestrin-Schramm (HS) media. By evaluating and selecting appro- priate media and substrates, the production of bacterial cellulose can be more efficient: enabling sustainable systems and supply chains where less energy and materials are lost, and the output production is increased. The purpose of this paper is to analyze the current landscape of bac- terial cellulose alternative media and substrates (ingredients). Through a systematic review of 198 papers, this review identifies 299 alternative substrates from 12 industries and 101 bacte- rial cellulose-producing strains, which were systematically compared. This review also finds that there are methodological gaps in this field such as data variability, papers mislabelling the HS media or not using a comparison media, and a lack of strain names. This alternative substrate analysis for bacterial cellulose production demonstrates that overall, for some applications al- ternative substrates can be taken into consideration that are not only cheaper, but also produce higher yields than HS media.展开更多
The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in 2019 prompted scientific,medical,and biotech communities to investigate infection-and vaccine-induced immune responses in the context of t...The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in 2019 prompted scientific,medical,and biotech communities to investigate infection-and vaccine-induced immune responses in the context of this pathogen.B-cell and antibody responses are at the center of these investigations,as neutralizing antibodies(nAbs)are an important correlate of protection(COP)from infection and the primary target of SARS-CoV-2 vaccine modalities.In addition to absolute levels,nAb longevity,neutralization breadth,immunoglobulin isotype and subtype composition,and presence at mucosal sites have become important topics for scientists and health policy makers.The recent pandemic was and still is a unique setting in which to study de novo and memory B-cell(MBC)and antibody responses in the dynamic interplay of infection-and vaccine-induced immunity.It also provided an opportunity to explore new vaccine platforms,such as mRNA or adenoviral vector vaccines,in unprecedented cohort sizes.Combined with the technological advances of recent years,this situation has provided detailed mechanistic insights into the development of B-cell and antibody responses but also revealed some unexpected findings.In this review,we summarize the key findings of the last 2.5 years regarding infection-and vaccine-induced B-cell immunity,which we believe are of significant value not only in the context of SARS-CoV-2 but also for future vaccination approaches in endemic and pandemic settings.展开更多
The emerging photovoltaic(PV)technologies,such as organic and perovskite PVs,have the characteristics of complex compositions and processing,resulting in a large multidimensional parameter space for the development an...The emerging photovoltaic(PV)technologies,such as organic and perovskite PVs,have the characteristics of complex compositions and processing,resulting in a large multidimensional parameter space for the development and optimization of the technologies.Traditional manual methods are time-consuming and laborintensive in screening and optimizing material properties.Materials genome engineering(MGE)advances an innovative approach that combines efficient experimentation,big database and artificial intelligence(AI)algorithms to accelerate materials research and development.High-throughput(HT)research platforms perform multidimensional experimental tasks rapidly,providing a large amount of reliable and consistent data for the creation of materials databases.Therefore,the development of novel experimental methods combining HT and AI can accelerate materials design and application,which is beneficial for establishing material-processing-property relationships and overcoming bottlenecks in the development of emerging PV technologies.This review introduces the key technologies involved in MGE and overviews the accelerating role of MGE in the field of organic and perovskite PVs.展开更多
Plants require a number of essential elements in different proportions for ensuring their growth and development.The elemental concentrations in leaves reflect the functions and adaptations of plants under specific en...Plants require a number of essential elements in different proportions for ensuring their growth and development.The elemental concentrations in leaves reflect the functions and adaptations of plants under specific environmental conditions.However,less is known about how the spectrum of leaf elements associated with resource acquisition,photosynthesis and growth regulates forest biomass along broad elevational gradients.We examined the influence of leaf element distribution and diversity on forest biomass by analyzing ten elements(C,N,P,K,Ca,Mg,Zn,Fe,Cu,and Mn)in tree communities situated every 100 meters along an extensive elevation gradient,ranging from the tropical forest(80 meters above sea level)to the alpine treeline(4200 meters above sea level)in the Kangchenjunga Landscape in eastern Nepal Himalayas.We calculated communityweighted averages(reflecting dominant traits governing biomass,i.e.,mass-ratio effect)and functional divergence(reflecting increased trait variety,i.e.,complementarity effect)for leaf elements in a total of 1,859 trees representing 116 species.An increasing mass-ratio effect and decreasing complementarity in leaf elements enhance forest biomass accumulation.A combination of elements together with elevation explains biomass(52.2%of the variance)better than individual elemental trait diversity(0.05%to 21%of the variance).Elevation modulates trait diversity among plant species in biomass accumulation.Complementarity promotes biomass at lower elevations,but reduces biomass at higher elevations,demonstrating an interaction between elevation and complementarity.The interaction between elevation and mass-ratio effect produces heterogeneous effects on biomass along the elevation gradient.Our research indicates that biomass accumulation can be disproportionately affected by elevation due to interactions among trait diversities across vegetation zones.While higher trait variation enhances the adaptation of species to environmental changes,it reduces biomass accumulation,especially at higher elevations.展开更多
In a recent study published in Nature,Garcia et al.use a sophisticated approach to identify fitness-enhancing mutations for T cells that was inspired by cancer evolution.1 The identified CARD11-PIK3R3 gene fusion enha...In a recent study published in Nature,Garcia et al.use a sophisticated approach to identify fitness-enhancing mutations for T cells that was inspired by cancer evolution.1 The identified CARD11-PIK3R3 gene fusion enhanced tumor rejection and persistence of engineered T cells in multiple tumor models and might have the potential to improve efficacy of adoptive T-cell therapies in cancer patients.展开更多
Excessive release of neutrophil extracellular traps(NETs)is associated with disease severity and contributes to tissue injury,followed by severe organ damage.Pharmacological or genetic inhibition of NET release reduce...Excessive release of neutrophil extracellular traps(NETs)is associated with disease severity and contributes to tissue injury,followed by severe organ damage.Pharmacological or genetic inhibition of NET release reduces pathology in multiple inflammatory disease models,indicating that NETs are potential therapeutic targets.Here,we demonstrate using a preclinical basket approach that our therapeutic anti-citrullinated protein antibody(tACPA)has broad therapeutic potential.Treatment with tACPA prevents disease symptoms in various mouse models with plausible NET-mediated pathology,including inflammatory arthritis(IA),pulmonary fibrosis,inflammatory bowel disease and sepsis.We show that citrulline residues in the N-termini of histones 2A and 4 are specific targets for therapeutic intervention,whereas antibodies against other N-terminal post-translational histone modifications have no therapeutic effects.Because citrullinated histones are generated during NET release,we investigated the ability of tACPA to inhibit NET formation.tACPA suppressed NET release from human neutrophils triggered with physiologically relevant human disease-related stimuli.Moreover,tACPA diminished NET release and potentially initiated NET uptake by macrophages in vivo,which was associated with reduced tissue damage in the joints of a chronic arthritis mouse model of IA.To our knowledge,we are the first to describe an antibody with NET-inhibiting properties and thereby propose tACPA as a drug candidate for NET-mediated inflammatory diseases,as it eliminates the noxious triggers that lead to continued inflammation and tissue damage in a multidimensional manner.展开更多
Artificial intelligence is an advanced method to identify novel anticancer targets and discover novel drugs from biology networks because the networks can effectively preserve and quantify the interaction between comp...Artificial intelligence is an advanced method to identify novel anticancer targets and discover novel drugs from biology networks because the networks can effectively preserve and quantify the interaction between components of cell systems underlying human diseases such as cancer.Here,we review and discuss how to employ artificial intelligence approaches to identify novel anticancer targets and discover drugs.First,we describe the scope of artificial intelligence biology analysis for novel anticancer target investigations.Second,we review and discuss the basic principles and theory of commonly used network-based and machine learning-based artificial intelligence algorithms.Finally,we showcase the applications of artificial intelligence approaches in cancer target identification and drug discovery.Taken together,the artificial intelligence models have provided us with a quantitative framework to study the relationship between network characteristics and cancer,thereby leading to the identification of potential anticancer targets and the discovery of novel drug candidates.展开更多
Unburnt hydrocarbon flames produce soot,which is the second biggest contributor to global warming and harmful to human health.The state-of-the-art high-speed imaging techniques,developed to study non-repeatable turbul...Unburnt hydrocarbon flames produce soot,which is the second biggest contributor to global warming and harmful to human health.The state-of-the-art high-speed imaging techniques,developed to study non-repeatable turbulent flames,are limited to million-frames-per-second imaging rates,falling short in capturing the dynamics of critical species.Unfortunately,these techniques do not provide a complete picture of flame-laser interactions,important for understanding soot formation.Furthermore,thermal effects induced by multiple consecutive pulses modify the optical properties of soot nanoparticles,thus making single-pulse imaging essential.Here,we report single-shot laser-sheet compressed ultrafast photography(LS-CUP)for billion-frames-per-second planar imaging of flame-laser dynamics.We observed laser-induced incandescence,elastic light scattering,and fluorescence of soot precursors-polycyclic aromatic hydrocarbons(PAHs)in real-time using a single nanosecond laser pulse.The spatiotemporal maps of the PAHs emission,soot temperature,primary nanoparticle size,soot aggregate size,and the number of monomers,present strong experimental evidence in support of the theory and modeling of soot inception and growth mechanism in flames.LS-CUP represents a generic and indispensable tool that combines a portfolio of ultrafast combustion diagnostic techniques,covering the entire lifecycle of soot nanoparticles,for probing extremely short-lived(picoseconds to nanoseconds)species in the spatiotemporal domain in non-repeatable turbulent environments.Finally,LS-CUP’s unparalleled capability of ultrafast wide-field temperature imaging in real-time is envisioned to unravel mysteries in modern physics such as hot plasma, sonoluminescence, and nuclear fusion.展开更多
基金supported by grants from the Deutsche Forschungsgemeinschaft to MW。
文摘Multilayered control of myelination:Quick,saltatory conduction of action potentials along nerve fibers requires the electrical insulation of axons by myelinating glia.In the central nervous system,this role is taken up by oligodendrocytes.Oligodendrocytes are marked by the expression of the lineage determinants Sox10 and Olig2 and arise from oligodendrocyte precursor cells(OPCs)during embryonal stages.While the majority of OPCs differentiate into mature oligodendrocytes when nearby axonal segments require myelination,a small subpopulation of OPCs persist as a progenitor pool.Therefore,the timing of myelination and maintenance of the OPC pool both need to be precisely regulated.Different transcription factors either positively or negatively affect oligodendrocyte differentiation and maintenance of the OPC pool as components of a complex gene regulatory network(reviewed in Sock and Wegner,2021).Network activity is additionally influenced by extracellular signaling molecules that bind to receptors on the oligodendroglial cell surface and activate intracellular signaling pathways.How the receptors are linked to the network is poorly understood so far,but pivotal to understanding the overall regulation of central nervous system(CNS)myelination in response to environmental cues.Relevant insights were recently gained for Gpr37(Schmidt et al.,2024),a G-protein coupled receptor(GPCR)with known relevance in differentiating oligodendrocytes(Yang et al,2016).
基金financial support through a KekuléPh.D.fellowship by the Fonds der Chemischen Industrie(FCI)support from the China Scholarship Council(No.202106950013)。
文摘The parasitic hydrogen evolution reaction(HER)in the negative half-cell of vanadium redox flow batteries(VRFBs)causes severe efficiency losses.Thus,a deeper understanding of this process and the accompanying bubble formation is crucial.This benchmarking study locally analyzes the bubble distribution in thick,porous electrodes for the first time using deep learning-based image segmentation of synchrotron X-ray micro-tomograms.Each large three-dimensional data set was processed precisely in less than one minute while minimizing human errors and pointing out areas of increased HER activity in VRFBs.The study systematically varies the electrode potential and material,concluding that more negative electrode potentials of-200 m V vs.reversible hydrogen electrode(RHE)and lower cause more substantial bubble formation,resulting in bubble fractions of around 15%–20%in carbon felt electrodes.Contrarily,the bubble fractions stay only around 2%in an electrode combining carbon felt and carbon paper.The detected areas with high HER activity,such as the border subregion with more than 30%bubble fraction in carbon felt electrodes,the cutting edges,and preferential spots in the electrode bulk,are potential-independent and suggest that larger electrodes with a higher bulk-to-border ratio might reduce HER-related performance losses.The described combination of electrochemical measurements,local X-ray microtomography,AI-based segmentation,and 3D morphometric analysis is a powerful and novel approach for local bubble analysis in three-dimensional porous electrodes,providing an essential toolkit for a broad community working on bubble-generating electrochemical systems.
基金supported by the National Science Foundation for Young Scientists of China(21704040)the financial support of the Helmholtz AssociationOpen Access funding enabled and organized by Projekt DEAL
文摘The development of freestanding and binder-free electrode is an effective approach to perform the inherent capacity of active materials and promote the mechanism study by minimizing the interference from additives.Herein,we construct a freestanding cathode composed of MoS_(3)/PPy nanowires(NWs)deposited on porous nickel foam(NF)(MoS_(3)/PPy/NF)through electrochemical methods,which can work efficiently as sulfur-equivalent cathode material for Li-S batteries.The structural stability of the MoS_(3)/PPy/NF cathode is greatly enhanced due to its significant tolerance to the volume expansion of MoS_(3)during the lithiation process,which we ascribe to the flexible 3D framework of PPy NWs,leading to superior cycling performance compared to the bulk-MoS_(3)/NF reference.Eliminating the interference of binder and carbon additives,the evolution of the chemical and electronic structure of Mo and S species during the discharge/charge was studied by X-ray absorption near-edge spectroscopy(XANES).The formation of lithium polysulfides was excluded as the driving cathode reaction mechanism,suggesting the great potential of MoS_(3)as a promising sulfur-equivalent cathode material to evade the shuttle effect for Li-S batteries.The present study successfully demonstrates the importance of structural design of freestanding electrode enhancing the cycling performances and revealing the corresponding mechanisms.
基金The authors gratefully acknowledge support by the Graduate School in Advanced Optical Technologies(SAOT)of the Friedrich–Alexander-University of Erlangen–Nürnberg,and the Bayerisches Laserzentrum GmbH.
文摘Glass welding by ultra-short pulsed(USP)lasers is a piece of technology that offers high strength joints with hermetic sealing.The joints are typically formed in glass that is transparent to the laser by exploiting nonlinear absorption effects that occur under extreme conditions.Though the temperature reached during the process is on the order of a few 1000°C,the heat affected zone(HAZ)is confined to only tens of micrometers.It is this controlled confinement of the HAZ during the joining process that makes this technology so appealing to a multitude of applications because it allows the foregoing of a subsequent tempering step that is typically essential in other glass joining techniques,thus making it possible to effectively join highly heat sensitive components.In this work,we give an overview on the process,development and applications of glass welding by USP lasers.
基金supported by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)(No.125440785–SFB877,project B11)by the Interdisciplinary Center for Clinical Research(IZKF)at the University Hospital of the University of Erlangen-Nuremberg(Jochen-Kalden funding program N8)(both to FZ)。
文摘Lysosomes are ubiquitous and dynamic organelles with a central role in degradation and recycling of damaged cell components and misfolded proteins,otherwise known as autophagy.Autophagy plays a fundamental role in the process of correcting cell homeostasis and cellular survival.Unsurprisingly,this process is essential in the central nervous system,as neurons are not able to easily eliminate altered proteins given their post-mitotic state.
基金The authors gratefully acknowledge funding by the Erlangen Graduate School in Advanced Optical Technologies(SAOT)and by the German Research Foundation(DFG)in the framework of a German excellence initiative.We also thankfully acknowledge the GPU seeding grant for researchers by Nvidia Corp.
文摘Within this work,we present a system for the measurement of the three-dimensional(3D)trajectories of spatters and entrained particles during laser powder bed fusion(L-PBF)of metals.It is comprised of two ultrahigh-speed cameras and a reconstruction task specific processing reconstruction algorithm.The system enables an automated determination of 3D measures from the trajectories of a large number of tracked particles.Ambiguity evolving from an underdetermined geometrical situation induced by a two-camera setup is resolved within the tracking using a priori knowledge of L-PBF of metals.All processing steps were optimized to run on a graphics processing unit to allow the processing of large amounts of data within an appropriate time frame.The overall approach was validated by a comparison of the measurement results to synthetic images with a known 3D ground truth.
基金supported by the Interdisciplinary Center for Clinical Research(IZKF)at the University Hospital of the University of Erlangen-Nuremberg(JochenKalden funding programme N8)。
文摘Lysosomes are the major degradative compartments within eukaryotic cells.Besides their role in the degradation and recycling of intra-and extracellular molecules,they further mediate important biological processes,such as immune signaling and perpetuation of nutrientand energy homeostasis.
基金supported by grants from the Deutsche Forschungsgemeinschaft (DFG) to MW
文摘Formation of the node of Ranvier as a highly coordinated event:Saltatory conduction ensures that information in the vertebrate nervous system is rapidly transmitted over large distances and efficiently processed in complex networks.It requires the insulation of axonal segments by myelin and the formation of highly structured nodes of Ranvier that are interspersed at regular intervals between successive myelin sheaths and regenerate the action potential as it propagates along the nerve(Rasband and Peles,2021).
基金This work was supported by grants from the Deutsche Forschungsgemeinschaft,No.We1326/14 and We1326/15 to MW.
文摘Sox9–gliogenesis and beyond:Neurons and glial cells are the major neuroectodermal cell types of the vertebrate central nervous system(CNS).Their generation from common progenitor cells takes place mostly during embryonic and early postnatal development.After closure of the neural tube,neural epithelial progenitor cells(NEPs)establish the ventricular zone(VZ).By asymmetrical cell division,NEPs first give rise to neuronal precursor cells(NPs)that then differentiate into various types of neurons.Later,NEPs predominantly produce glial precursor cells that become either astroglia or oligodendroglia.
基金the DFG research training group GRK 1896 at Erlangen University and from the Joint Project Helmholtz-Institute Erlangen-Nürnberg(HI-ERN)for Renewable Energy Production under Project DBF01253,respectivelyfinancial support through the“Aufbruch Bayern”initiative of the state of Bavaria(EnCN and Solar Factory of the Future)and the“Solar Factory of the Future”with the Energy Campus Nürnberg(EnCN).
文摘In this report,we show that hyperspectral high-resolution photoluminescence mapping is a powerful tool for the selection and optimiz1ation of the laser ablation processes used for the patterning interconnections of subcells on Cu(Inx,Ga1-x)Se2(CIGS)modules.In this way,we show that in-depth monitoring of material degradation in the vicinity of the ablation region and the identification of the underlying mechanisms can be accomplished.Specifically,by analyzing the standard P1 patterning line ablated before the CIGS deposition,we reveal an anomalous emission-quenching effect that follows the edge of the molybdenum groove underneath.We further rationalize the origins of this effect by comparing the topography of the P1 edge through a scanning electron microscope(SEM)cross-section,where a reduction of the photoemission cannot be explained by a thickness variation.We also investigate the laser-induced damage on P1 patterning lines performed after the deposition of CIGS.We then document,for the first time,the existence of a short-range damaged area,which is independent of the application of an optical aperture on the laser path.Our findings pave the way for a better understanding of P1-induced power losses and introduce new insights into the improvement of current strategies for industry-relevant module interconnection schemes.
基金MR is a fellow of the Clinician Scientist Programme (IZKF,University Hospital Erlangen)Deutsche Forschungsgem einschaft (German Research Foundation+1 种基金270949263/GRK21 62)BMBF funded TreatHSP consortium (01GM1905B)。
文摘The classical role of adipocytokines is a negative feedback mechanism,providing information about bodily energy reserves to the brain,and thus controlling satiety and food intake (Campfield et al.,1995).Adipose tissue forms the largest endocrine organ of the body.After the initial description of leptin and its receptor,LEPR/OBR,with its main active isoform OBRb,there was an initial hope for a drugable pathway to counteract the increasing burden of overweight/adiposity,metabolic syndrome,and related disorders (Figure1).
文摘Bacterial cellulose is a versatile material with applications in many industries. However, the widespread uptake of bacterial cellulose faces challenges including high production costs and lack of scalability. One approach to address these obstacles is the use of alternative substrates and media, compared to the Hestrin-Schramm (HS) media. By evaluating and selecting appro- priate media and substrates, the production of bacterial cellulose can be more efficient: enabling sustainable systems and supply chains where less energy and materials are lost, and the output production is increased. The purpose of this paper is to analyze the current landscape of bac- terial cellulose alternative media and substrates (ingredients). Through a systematic review of 198 papers, this review identifies 299 alternative substrates from 12 industries and 101 bacte- rial cellulose-producing strains, which were systematically compared. This review also finds that there are methodological gaps in this field such as data variability, papers mislabelling the HS media or not using a comparison media, and a lack of strain names. This alternative substrate analysis for bacterial cellulose production demonstrates that overall, for some applications al- ternative substrates can be taken into consideration that are not only cheaper, but also produce higher yields than HS media.
基金Deutsche Forschungsgemeinschaft(German Research Foundation)-Projektnummer 215346292[Winkler]Bavarian consortium for research on the pandemic disease COVID-19(FOR-COVID)[Tenbusch].
文摘The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in 2019 prompted scientific,medical,and biotech communities to investigate infection-and vaccine-induced immune responses in the context of this pathogen.B-cell and antibody responses are at the center of these investigations,as neutralizing antibodies(nAbs)are an important correlate of protection(COP)from infection and the primary target of SARS-CoV-2 vaccine modalities.In addition to absolute levels,nAb longevity,neutralization breadth,immunoglobulin isotype and subtype composition,and presence at mucosal sites have become important topics for scientists and health policy makers.The recent pandemic was and still is a unique setting in which to study de novo and memory B-cell(MBC)and antibody responses in the dynamic interplay of infection-and vaccine-induced immunity.It also provided an opportunity to explore new vaccine platforms,such as mRNA or adenoviral vector vaccines,in unprecedented cohort sizes.Combined with the technological advances of recent years,this situation has provided detailed mechanistic insights into the development of B-cell and antibody responses but also revealed some unexpected findings.In this review,we summarize the key findings of the last 2.5 years regarding infection-and vaccine-induced B-cell immunity,which we believe are of significant value not only in the context of SARS-CoV-2 but also for future vaccination approaches in endemic and pandemic settings.
基金the financial support from the National Natural Science Foundation of China(52394273 and 52373179).
文摘The emerging photovoltaic(PV)technologies,such as organic and perovskite PVs,have the characteristics of complex compositions and processing,resulting in a large multidimensional parameter space for the development and optimization of the technologies.Traditional manual methods are time-consuming and laborintensive in screening and optimizing material properties.Materials genome engineering(MGE)advances an innovative approach that combines efficient experimentation,big database and artificial intelligence(AI)algorithms to accelerate materials research and development.High-throughput(HT)research platforms perform multidimensional experimental tasks rapidly,providing a large amount of reliable and consistent data for the creation of materials databases.Therefore,the development of novel experimental methods combining HT and AI can accelerate materials design and application,which is beneficial for establishing material-processing-property relationships and overcoming bottlenecks in the development of emerging PV technologies.This review introduces the key technologies involved in MGE and overviews the accelerating role of MGE in the field of organic and perovskite PVs.
基金supported by the National Natural Science Foundation of China(Grant No.42030508)the Second Tibetan Plateau Scientific Expedition and Research Program(Grant No.2019QZKK0301)+3 种基金supported by CAS-TWAS President’s Fellowship Program for International Ph.D.studentssupported by Spanish Government(Grant Nos.PID2019-110521GB-I00 and TED2021-132627B-I00)the Catalan Government(Grant No.SGR 2017-1005)and the Fundación“Ramón Areces”(Grant No.CIVP20A6621)supported by the Spanish Government(Grant No.RTI2018-096884-B-C31)。
文摘Plants require a number of essential elements in different proportions for ensuring their growth and development.The elemental concentrations in leaves reflect the functions and adaptations of plants under specific environmental conditions.However,less is known about how the spectrum of leaf elements associated with resource acquisition,photosynthesis and growth regulates forest biomass along broad elevational gradients.We examined the influence of leaf element distribution and diversity on forest biomass by analyzing ten elements(C,N,P,K,Ca,Mg,Zn,Fe,Cu,and Mn)in tree communities situated every 100 meters along an extensive elevation gradient,ranging from the tropical forest(80 meters above sea level)to the alpine treeline(4200 meters above sea level)in the Kangchenjunga Landscape in eastern Nepal Himalayas.We calculated communityweighted averages(reflecting dominant traits governing biomass,i.e.,mass-ratio effect)and functional divergence(reflecting increased trait variety,i.e.,complementarity effect)for leaf elements in a total of 1,859 trees representing 116 species.An increasing mass-ratio effect and decreasing complementarity in leaf elements enhance forest biomass accumulation.A combination of elements together with elevation explains biomass(52.2%of the variance)better than individual elemental trait diversity(0.05%to 21%of the variance).Elevation modulates trait diversity among plant species in biomass accumulation.Complementarity promotes biomass at lower elevations,but reduces biomass at higher elevations,demonstrating an interaction between elevation and complementarity.The interaction between elevation and mass-ratio effect produces heterogeneous effects on biomass along the elevation gradient.Our research indicates that biomass accumulation can be disproportionately affected by elevation due to interactions among trait diversities across vegetation zones.While higher trait variation enhances the adaptation of species to environmental changes,it reduces biomass accumulation,especially at higher elevations.
基金K.S.is supported by grants from the German Federal Ministry of Education and Research(BMBF,project-IDs 01KI2013 and 031L0290B)the Else Kröner-Fresenius-Stiftung(project-ID 2020_EKEA.127)+4 种基金the German Research Foundation(DFG)through the research training group RTG 2504(project-ID 401821119)the Interdisciplinary Center for Clinical Research of the University Hospital of Erlangen(project-ID A98)the European Union(Yellow4FLAVI consortium,project-ID 101137459)J.R.is supported by grants from the German Research Foundation(DFG)(project-ID 210592381-SFB 1054,project-ID 395357507-SFB 1371,project-ID 369799452-TRR 237,project-ID 452881907-TRR 338,project-ID 435874434-RTG 2668,RU 695/12-1)The Leukemia&Lymphoma Society,and the European Research Council(ERC)under the European Union’s Horizon 2020 research and innovation programme(grant agreement No 834154).
文摘In a recent study published in Nature,Garcia et al.use a sophisticated approach to identify fitness-enhancing mutations for T cells that was inspired by cancer evolution.1 The identified CARD11-PIK3R3 gene fusion enhanced tumor rejection and persistence of engineered T cells in multiple tumor models and might have the potential to improve efficacy of adoptive T-cell therapies in cancer patients.
基金Feasibility grants from the Dutch government(MTVLA15144 and NITLS14050).
文摘Excessive release of neutrophil extracellular traps(NETs)is associated with disease severity and contributes to tissue injury,followed by severe organ damage.Pharmacological or genetic inhibition of NET release reduces pathology in multiple inflammatory disease models,indicating that NETs are potential therapeutic targets.Here,we demonstrate using a preclinical basket approach that our therapeutic anti-citrullinated protein antibody(tACPA)has broad therapeutic potential.Treatment with tACPA prevents disease symptoms in various mouse models with plausible NET-mediated pathology,including inflammatory arthritis(IA),pulmonary fibrosis,inflammatory bowel disease and sepsis.We show that citrulline residues in the N-termini of histones 2A and 4 are specific targets for therapeutic intervention,whereas antibodies against other N-terminal post-translational histone modifications have no therapeutic effects.Because citrullinated histones are generated during NET release,we investigated the ability of tACPA to inhibit NET formation.tACPA suppressed NET release from human neutrophils triggered with physiologically relevant human disease-related stimuli.Moreover,tACPA diminished NET release and potentially initiated NET uptake by macrophages in vivo,which was associated with reduced tissue damage in the joints of a chronic arthritis mouse model of IA.To our knowledge,we are the first to describe an antibody with NET-inhibiting properties and thereby propose tACPA as a drug candidate for NET-mediated inflammatory diseases,as it eliminates the noxious triggers that lead to continued inflammation and tissue damage in a multidimensional manner.
文摘Artificial intelligence is an advanced method to identify novel anticancer targets and discover novel drugs from biology networks because the networks can effectively preserve and quantify the interaction between components of cell systems underlying human diseases such as cancer.Here,we review and discuss how to employ artificial intelligence approaches to identify novel anticancer targets and discover drugs.First,we describe the scope of artificial intelligence biology analysis for novel anticancer target investigations.Second,we review and discuss the basic principles and theory of commonly used network-based and machine learning-based artificial intelligence algorithms.Finally,we showcase the applications of artificial intelligence approaches in cancer target identification and drug discovery.Taken together,the artificial intelligence models have provided us with a quantitative framework to study the relationship between network characteristics and cancer,thereby leading to the identification of potential anticancer targets and the discovery of novel drug candidates.
基金The authors thank Dr.Geng Ku for experimental assistance.Y.N.M.gratefully acknowledges the Swedish Research Council for the financial support of grant#IPD2018-06783.
文摘Unburnt hydrocarbon flames produce soot,which is the second biggest contributor to global warming and harmful to human health.The state-of-the-art high-speed imaging techniques,developed to study non-repeatable turbulent flames,are limited to million-frames-per-second imaging rates,falling short in capturing the dynamics of critical species.Unfortunately,these techniques do not provide a complete picture of flame-laser interactions,important for understanding soot formation.Furthermore,thermal effects induced by multiple consecutive pulses modify the optical properties of soot nanoparticles,thus making single-pulse imaging essential.Here,we report single-shot laser-sheet compressed ultrafast photography(LS-CUP)for billion-frames-per-second planar imaging of flame-laser dynamics.We observed laser-induced incandescence,elastic light scattering,and fluorescence of soot precursors-polycyclic aromatic hydrocarbons(PAHs)in real-time using a single nanosecond laser pulse.The spatiotemporal maps of the PAHs emission,soot temperature,primary nanoparticle size,soot aggregate size,and the number of monomers,present strong experimental evidence in support of the theory and modeling of soot inception and growth mechanism in flames.LS-CUP represents a generic and indispensable tool that combines a portfolio of ultrafast combustion diagnostic techniques,covering the entire lifecycle of soot nanoparticles,for probing extremely short-lived(picoseconds to nanoseconds)species in the spatiotemporal domain in non-repeatable turbulent environments.Finally,LS-CUP’s unparalleled capability of ultrafast wide-field temperature imaging in real-time is envisioned to unravel mysteries in modern physics such as hot plasma, sonoluminescence, and nuclear fusion.