Photobiomodulation（PBM）,also known as low level laser therapy,has recently risen to the attention of the ophthalmology community as a promising new approach to treat a variety of retinal conditions including agerela...Photobiomodulation（PBM）,also known as low level laser therapy,has recently risen to the attention of the ophthalmology community as a promising new approach to treat a variety of retinal conditions including agerelated macular degeneration,retinopathy of prematurity,diabetic retinopathy,Leber’s hereditary optic neuropathy,amblyopia,methanol-induced retinal damage,and possibly others.This review evaluates the existing research pertaining to PBM applications in the retina,with a focus on the mechanisms of action and clinical outcomes.All available literature until April 2015 was reviewed using Pub Med and the following keywords：＂photobiomodulation AND retina＂,＂low level light therapy AND retina＂,＂low level laser therapy AND retina＂,and＂FR/NIR therapy AND retina＂.In addition,the relevant references listed within the papers identified through Pub Med were incorporated.The literature supports the conclusion that the low-cost and noninvasive nature of PBM,coupled with the first promising clinical reports and the numerous preclinical-studies in animal models,make PBM well-poised to become an important player in the treatment of a wide range of retinal disorders.Nevertheless,large-scale clinical trials will be necessary to establish the PBM therapeutic ranges for the various retinal diseases,as well as to gain a deeper understanding of its mechanisms of action.展开更多
Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans.Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input...Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans.Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input is completely absent from birth or very early in life（Kupers and Ptito,2014）.More recent studies explored what happens to the visual pathways in the context of acquired blindness.This is particularly relevant as the majority of diseases that cause vision loss occur in the elderly.展开更多
Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not r...Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury.Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases.In this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes.Next,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and clusters.This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.展开更多
In this work,we present a reconfigurable data glove design to capture different modes of human hand-object interactions,which are critical in training embodied artificial intelligence(AI)agents for fine manipulation t...In this work,we present a reconfigurable data glove design to capture different modes of human hand-object interactions,which are critical in training embodied artificial intelligence(AI)agents for fine manipulation tasks.To achieve various downstream tasks with distinct features,our reconfigurable data glove operates in three modes sharing a unified backbone design that reconstructs hand gestures in real time.In the tactile-sensing mode,the glove system aggregates manipulation force via customized force sensors made from a soft and thin piezoresistive material;this design minimizes interference during complex hand movements.The virtual reality(VR)mode enables real-time interaction in a physically plausible fashion:A caging-based approach is devised to determine stable grasps by detecting collision events.Leveraging a state-of-the-art finite element method,the simulation mode collects data on fine-grained four-dimensionalmanipulation events comprising hand and object motions in three-dimensional space and how the object's physical properties(e.g.,stress and energy)change in accordance with manipulation over time.Notably,the glove system presented here is the first to use high-fidelity simulation to investigate the unobservable physical and causal factors behind manipulation actions.In a series of experiments,we characterize our data glove in terms of individual sensors and the overall system.More specifically,we evaluate the system's three modes by①recording hand gestures and associated forces,②improving manipulation fluency in VR,and③producing realistic simulation effects of various tool uses,respectively.Based on these three modes,our reconfigurable data glove collects and reconstructs fine-grained human grasp data in both physical and virtual environments,thereby opening up new avenues for the learning of manipulation skills for embodied AI agents.展开更多
Recent progress in deep learning is essentially based on a“big data for small tasks”paradigm,under which massive amounts of data are used to train a classifier for a single narrow task.In this paper,we call for a sh...Recent progress in deep learning is essentially based on a“big data for small tasks”paradigm,under which massive amounts of data are used to train a classifier for a single narrow task.In this paper,we call for a shift that flips this paradigm upside down.Specifically,we propose a“small data for big tasks”paradigm,wherein a single artificial intelligence(AI)system is challenged to develop“common sense,”enabling it to solve a wide range of tasks with little training data.We illustrate the potential power of this new paradigm by reviewing models of common sense that synthesize recent breakthroughs in both machine and human vision.We identify functionality,physics,intent,causality,and utility(FPICU)as the five core domains of cognitive AI with humanlike common sense.When taken as a unified concept,FPICU is concerned with the questions of“why”and“how,”beyond the dominant“what”and“where”framework for understanding vision.They are invisible in terms of pixels but nevertheless drive the creation,maintenance,and development of visual scenes.We therefore coin them the“dark matter”of vision.Just as our universe cannot be understood by merely studying observable matter,we argue that vision cannot be understood without studying FPICU.We demonstrate the power of this perspective to develop cognitive AI systems with humanlike common sense by showing how to observe and apply FPICU with little training data to solve a wide range of challenging tasks,including tool use,planning,utility inference,and social learning.In summary,we argue that the next generation of AI must embrace“dark”humanlike common sense for solving novel tasks.展开更多
SRY-related HMG-box(Sox) transcription factors are known to regulate central nervous system development and are involved in several neurological diseases.Post-translational modification of Sox proteins is known to alt...SRY-related HMG-box(Sox) transcription factors are known to regulate central nervous system development and are involved in several neurological diseases.Post-translational modification of Sox proteins is known to alter their functions in the central nervous system.Among the different types of post-translational modification,small ubiquitin-like modifier(SUMO) modification of Sox proteins has been shown to modify their transcriptional activity.Here,we review the mechanisms of three Sox proteins in neuronal development and disease,along with their transcriptional changes under SUMOylation.Across three species,lysine is the conserved residue for SUMOylation.In Drosophila,SUMOylation of Sox N plays a repressive role in transcriptional activity,which impairs central nervous system development.However,de SUMOylation of Sox E and Sox11 plays neuroprotective roles,which promote neural crest precursor formation in Xenopus and retinal ganglion cell differentiation as well as axon regeneration in the rodent.We further discuss a potential translational therapy by SUMO site modification using AAV gene transduction and Clustered regularly interspaced short palindromic repeats-Cas9 technology.Understanding the underlying mechanisms of Sox SUMOylation,especially in the rodent system,may provide a therapeutic strategy to address issues associated with neuronal development and neurodegeneration.展开更多
Intracellular signal transduction controlling neuronal development and survival is conveyed by second messengers that are often differentially regulated over space and time.The highly polarized morphology of neurons i...Intracellular signal transduction controlling neuronal development and survival is conveyed by second messengers that are often differentially regulated over space and time.The highly polarized morphology of neurons is conferred by a network of regulatory signaling pathways that determine axon guidance and dendrite formation.Among these,cyclic adenosine monophosphate(cAMP)is a second messenger that is critical for numerous neuronal functions and known to activate and integrate a variety of downstream pathways.In the central nervous system(CNS),cAMP-dependent signaling is involved in growth cone motility,neuronal metabolism,axon extension in vitro,neuroprotection,and survival in vivo.The complexity of cAMP-dependent neuronal physiology and function raises fundamental questions about the mechanisms determining the specificity by which cAMP can regulate these processes.展开更多
AIM:To evaluate concordance between the clinical assessment of glaucomatous progression of the optic disc photography and progression identified by Heidelberg Retina Tomograph(HRT)in patients with suspected primary ju...AIM:To evaluate concordance between the clinical assessment of glaucomatous progression of the optic disc photography and progression identified by Heidelberg Retina Tomograph(HRT)in patients with suspected primary juvenile open angle glaucoma(JOAG).METHODS:Optic disc photographs and corresponding HRTⅡseries were reviewed.Optic disc changes between first and final photographs were noted as well as progression identified by HRT topographic change analysis(TCA)and rim area regression line(RARL)Agreement between progression indentified by photography and HRT methods was assessed.Progression,determined from optic disc photographs by consensus assessment was used as the reference standard.RESULTS:A total of 31 patients(59 eyes)with suspected JOAG were studied.Agreement for progression/no progression between TCA and photography was obtained in 4 progressing eyes and 38stable eyes(71.19%,k=0.11).Agreement for progression/no progression between RARL and photography was detected in 5 progressing eyes and in 34 stable eyes(66.10%,k=0.15).The number of HRT per patient was statistically higher in the progressing group(P=0.034).CONCLUSION:Agreement for detection of longitudinal changes between photography and HRT analysis was poor.One way to improve the chance of discovery of the progression could be increasing the number of HRT examinations.展开更多
Purpose To compare changes in ocular aberrations in children wearing orthokeratology(ortho-k)lenses with a back optic zone diameter(BOZD)of 6 mm(6-MM group)or 5 mm(5-MM group)and their associations with axial elonga-t...Purpose To compare changes in ocular aberrations in children wearing orthokeratology(ortho-k)lenses with a back optic zone diameter(BOZD)of 6 mm(6-MM group)or 5 mm(5-MM group)and their associations with axial elonga-tion(AE)over two years.Methods Seventy Chinese children,aged 6 to 11 years,with myopia between-4.00 to-0.75 D,were randomly allocated to 5-MM and 6-MM groups.Ocular aberrations were measured,rescaled to a 4-mm pupil,and fitted with a 6th order Zernike expansion.Measurements,including axial length,were taken prior to commencing ortho-k treat-ment and then every 6 months over two years.Results After two years,the 5-MM group displayed a smaller horizontal treatment zone(TZ)diameter(by 1.14±0.11 mm,P<0.001)and less AE(by 0.22±0.07 mm,P=0.002)compared with the 6-MM group.A greater increase in total root mean square(RMS)of higher-order aberrations(HOAs),primary spherical aberration(SA)(C_(4)^(0)),and coma were also observed in the 5-MM group at all follow-up visits.The horizontal TZ diameter was significantly associated with changes in RMS HOAs,SA(RMS,primary and secondary SA),and RMS coma.After controlling for base-line parameters,RMS HOAs,RMS SA,RMS coma,and primary(C_(4)^(0))and secondary(C_(6)^(0))SA were significantly associated With AE.Conclusions Ortho-k lenses with a smaller BOzD created a smaller horizontal TZ diameter and a significant increase in total HOAs,total SA,total coma,and primary SA and a decrease in secondary SA.Of these ocular aberrations,total HOAs,total SA,and primary SA were negatively correlated with AE over two years.展开更多
Background The retinal image quality derived from lower-order(LOA)and higher-order aberrations(HOA)for fixed 3-mm and photopic pupil diameters,in children undergoing combined 0.01%atropine and orthokeratology(AOK)vers...Background The retinal image quality derived from lower-order(LOA)and higher-order aberrations(HOA)for fixed 3-mm and photopic pupil diameters,in children undergoing combined 0.01%atropine and orthokeratology(AOK)versus those receiving orthokeratology alone(OK)over two years was evaluated.Methods The visual Strehl ratio based on the optical transfer function(VSOTF),derived from 2nd-to 4th-order terms(LOA and HOA combined),2nd-order terms(LOA only),and 3rd-to 4th-order terms(HOA only)for fixed 3-mm and natural photopic pupil diameters,was compared between the two treatment groups.The individual Zernike coef-ficients fora fixed 3-mm pupil ize of 2nd to 4th,orders,root mean square(RMS)of LOA(Z_(2)^(0),Z_(2)^(-2),and Z_(2)^(2) combined),HOA(3rd to 4th orders inclusive),and coma(Z_(3)^(-1) and Z_(3)^(1) combined)were also compared between the two groups.Results Right eye data of 33 AOK and 35 OK participants were analysed.Under photopic conditions,significantly lower VSOTF based on HOA only was observed in the AOK group compared with that in the OK group at all post-treatment visits(all P<0.05);however,interactions between HOA and LOA resulted in comparable overall retinal image quality(i.e.,VSOTF based on LOA and HOA combined)between the two groups at all visits(all P>0.05).For a fixed 3-mm pupil size,the VSOTF based on HOA only,LOA only,or HOA and LOA combined,were not different between the two groups(all P>0.05).AOK participants had slower axial elongation(mean±SD,0.17±0.19 mm vs.0.35±0.20 mm,P<0.001),a larger photopic pupil size(4.05±0.61 mm vs.3.43±0.41 mm,P<0.001)than OK partici-pants overtwoyears.Conclusions HOA profile related to an enlarged pupil size may provide visual signal influencing eye growth in the AOK group.展开更多
Primary open-angle glaucoma(POAG)is a prevalent cause of blindness worldwide,resulting in degeneration of retinal ganglion cells and permanent damage to the optic nerve.However,the underlying pathogenetic mechanisms o...Primary open-angle glaucoma(POAG)is a prevalent cause of blindness worldwide,resulting in degeneration of retinal ganglion cells and permanent damage to the optic nerve.However,the underlying pathogenetic mechanisms of POAG are currently indistinct,and there has been no effective nonsurgical treatment regimen.The objective of this study is to identify novel biomarkers and potential therapeutic targets for POAG.The mRNA expression microarray datasets GSE27276 and GSE138125,as well as the single-cell high-throughput RNA sequencing(sc RNA-seq)dataset GSE148371 were utilized to screen POAGrelated differentially expressed genes(DEGs).Functional enrichment analyses,protein-protein interaction(PPI)analysis,and weighted gene co-expression network analysis(WGCNA)of the DEGs were performed.Subsequently,the hub genes were validated at a single-cell level,where trabecular cells were annotated,and the mRNA expression levels of target genes in different cell clusters were analyzed.Immunofluorescence and quantitative real-time PCR(q PCR)were performed for further validation.DEGs analysis identified 43 downregulated and 32 upregulated genes in POAG,which were mainly enriched in immune-related pathways,oxidative stress,and endoplasmic reticulum(ER)stress.PPI networks showed that FN1 and DUSP1 were the central hub nodes,while GPX3 and VAV3 were screened out as hub genes through WGCNA and subsequently validated by q PCR.Finally,FN1,GPX3,and VAV3 were determined to be pivotal core genes via single-cell validation.The relevant biomarkers involved in the pathogenesis of POAG,may serve as potential therapeutic targets.Further studies are necessary to unveil the mechanisms underlying the expression variations of these genes in POAG.展开更多
The progressive degradation in the trabecular meshwork(TM)is related to age-related ocular diseases like primary open-angle glaucoma.However,the molecular basis and biological significance of the aging process in TM h...The progressive degradation in the trabecular meshwork(TM)is related to age-related ocular diseases like primary open-angle glaucoma.However,the molecular basis and biological significance of the aging process in TM have not been fully elucidated.Here,we established a dynamic single-cell transcriptomic landscape of aged macaque TM,wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM aging.Furthermore,we divided TM cells into 13 clusters and performed an in-depth analysis on cluster O,which had the highest aging score and the most significant changes in cell proportions between the two groups.Ultimately,we found that the APOE gene was an important differentially expressed gene in cluster O during the aging process,highlighting the close relationship between cell migration and extracellular matrix regulation,and TM function.Our work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components,thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal range.Our work provides valuable insights for future clinical diagnosis and treatment of glaucoma.展开更多
Quantitative phase imaging(QPI)recovers the exact wavefront of light from intensity measurements.Topographical and optical density maps of translucent microscopic bodies can be extracted from these quantified phase sh...Quantitative phase imaging(QPI)recovers the exact wavefront of light from intensity measurements.Topographical and optical density maps of translucent microscopic bodies can be extracted from these quantified phase shifts.We demonstrate quantitative phase imaging at the tip of a coherent fiber bundle using chromatic aberrations inherent in a silicon nitride hyperboloid metalens.Our method leverages spectral multiplexing to recover phase from multiple defocus planes in a single capture using a color camera.Our 0.5mm aperture metalens shows robust quantitative phase imaging capability with a 28°field of view and 0.2πphase resolution(~0.1λin air)for experiments with an endoscopic fiber bundle.Since the spectral functionality is encoded directly in the imaging lens,the metalens acts both as a focusing element and a spectral filter.The use of a simple computational backend will enable real-time operation.Key limitations in the adoption of phase imaging methods for endoscopy such as multiple acquisition,interferometric alignment or mechanical scanning are completely mitigated in the reported metalens based QPI.展开更多
To the Editor:Acute concomitant esotropia(ACE)is an acquired esotropia with a sudden appearance and no pathologic changes on cerebral imaging.There are various treatments for ACE,including extraocular muscle surgery,b...To the Editor:Acute concomitant esotropia(ACE)is an acquired esotropia with a sudden appearance and no pathologic changes on cerebral imaging.There are various treatments for ACE,including extraocular muscle surgery,botulinum toxin A(BTA)injection,prisms,and divergence training.[1]BTA had been used in the treatment of ACE since it was approved by Food and Drug Administration(FDA,USA)in 1989.[2]Some researchers have confirmed that its effect is stable and has unique advantages in the treatment of ACE.展开更多
Background:Intraocular lens(IOL)calcification is a serious condition that can only be treated by removing the clouded lens.Since explantation bears the risk of complications,it is often deferred until the patient find...Background:Intraocular lens(IOL)calcification is a serious condition that can only be treated by removing the clouded lens.Since explantation bears the risk of complications,it is often deferred until the patient finds the symptoms intolerable.Usually,as the IOL opacifies,visual acuity is minimally affected early on.In this study,we assessed the impact of IOL opacification on optical quality.Methods:We analyzed ten opacified explanted IOLs(Oculentis GmbH).Wavefront aberrations were obtained with a SHSOphthalmic device(Optocraft GmbH),which features a Hartmann-Shack sensor.The root mean square(RMS)of higher-order aberrations(HOAs)was compared.The effect of calcification on image quality was assessed through the Strehl ratio(SR).We detected light scattering with a C-Quant(Oculus GmbH)and expressed it as a straylight parameter.Results:At 2 mm,3mm and 4 mm,the mean RMS(±standard deviation)was 0.033μm(±0.026μm),0.044μm(±0.027),and 0.087μm(±0.049),respectively.The mean SR value was 0.81±0.15 at 3 mm,with four IOLs showing a nearly diffraction-limited performance,but in two explants,opacification precluded reliable measurements.Increased straylight was found in all opacified IOLs with a mean value of 150.2±56.3 deg^(2)/sr at 3 mm.Conclusions:We demonstrated that IOL opacification induces HOAs.However,the RMS remained low,which resulted only in a slight reduction of the SR-derived optical quality.On the other hand,we found a severe straylight elevation in the opacified lenses,which may result in dysphotopsia,such as glare,and subjective complaints,despite good visual acuity.展开更多
Orbital floor fractures affect eye movement,but the underlying mechanism remains unclear.Therefore,the present retrospective study aimed to clinically characterize fractures in different inferior.
Dear Editor： Gao et al. published data in Nature Biotechnology （Nat Biotechnol. 2016 May 2） showing that DNA-guided genome editing using the Natronobacterium gregoryi Argonaute （NgAgo） protein targeted 47 mammali...Dear Editor： Gao et al. published data in Nature Biotechnology （Nat Biotechnol. 2016 May 2） showing that DNA-guided genome editing using the Natronobacterium gregoryi Argonaute （NgAgo） protein targeted 47 mammalian genomic loci with a 100% success rate and an efficiency of 21.3%-41.3% at various targets. This report led us to test NgAgo＇s utility in various cells and organisms such as mouse and zebrafish for gene editing.展开更多
文摘Photobiomodulation（PBM）,also known as low level laser therapy,has recently risen to the attention of the ophthalmology community as a promising new approach to treat a variety of retinal conditions including agerelated macular degeneration,retinopathy of prematurity,diabetic retinopathy,Leber’s hereditary optic neuropathy,amblyopia,methanol-induced retinal damage,and possibly others.This review evaluates the existing research pertaining to PBM applications in the retina,with a focus on the mechanisms of action and clinical outcomes.All available literature until April 2015 was reviewed using Pub Med and the following keywords：＂photobiomodulation AND retina＂,＂low level light therapy AND retina＂,＂low level laser therapy AND retina＂,and＂FR/NIR therapy AND retina＂.In addition,the relevant references listed within the papers identified through Pub Med were incorporated.The literature supports the conclusion that the low-cost and noninvasive nature of PBM,coupled with the first promising clinical reports and the numerous preclinical-studies in animal models,make PBM well-poised to become an important player in the treatment of a wide range of retinal disorders.Nevertheless,large-scale clinical trials will be necessary to establish the PBM therapeutic ranges for the various retinal diseases,as well as to gain a deeper understanding of its mechanisms of action.
基金supported by National Institutes of Health Contracts P30-EY008098 and T32-EY017271-06(BethesdaMD)+14 种基金United States Department of Defense DM090217(ArlingtonVA)Alcon Research Institute Young Investigator Grant(Fort WorthTX)Eye and Ear Foundation(PittsburghPA)Research to Prevent Blindness(New YorkNY)Aging Institute Pilot Seed GrantUniversity of Pittsburgh(PittsburghPA)Postdoctoral Fellowship Program in Ocular Tissue Engineering and Regenerative OphthalmologyLouis J.Fox Center for Vision RestorationUniversity of Pittsburgh and UPMC(PittsburghPA)
文摘Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans.Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input is completely absent from birth or very early in life（Kupers and Ptito,2014）.More recent studies explored what happens to the visual pathways in the context of acquired blindness.This is particularly relevant as the majority of diseases that cause vision loss occur in the elderly.
基金supported by NIH Core Grants P30-EY008098the Eye and Ear Foundation of Pittsburghunrestricted grants from Research to Prevent Blindness,New York,NY,USA(to KCC)。
文摘Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury.Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases.In this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes.Next,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and clusters.This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.
基金the National Key Research and Development Program of China(2021ZD0150200)the Beijing Nova Program.
文摘In this work,we present a reconfigurable data glove design to capture different modes of human hand-object interactions,which are critical in training embodied artificial intelligence(AI)agents for fine manipulation tasks.To achieve various downstream tasks with distinct features,our reconfigurable data glove operates in three modes sharing a unified backbone design that reconstructs hand gestures in real time.In the tactile-sensing mode,the glove system aggregates manipulation force via customized force sensors made from a soft and thin piezoresistive material;this design minimizes interference during complex hand movements.The virtual reality(VR)mode enables real-time interaction in a physically plausible fashion:A caging-based approach is devised to determine stable grasps by detecting collision events.Leveraging a state-of-the-art finite element method,the simulation mode collects data on fine-grained four-dimensionalmanipulation events comprising hand and object motions in three-dimensional space and how the object's physical properties(e.g.,stress and energy)change in accordance with manipulation over time.Notably,the glove system presented here is the first to use high-fidelity simulation to investigate the unobservable physical and causal factors behind manipulation actions.In a series of experiments,we characterize our data glove in terms of individual sensors and the overall system.More specifically,we evaluate the system's three modes by①recording hand gestures and associated forces,②improving manipulation fluency in VR,and③producing realistic simulation effects of various tool uses,respectively.Based on these three modes,our reconfigurable data glove collects and reconstructs fine-grained human grasp data in both physical and virtual environments,thereby opening up new avenues for the learning of manipulation skills for embodied AI agents.
文摘Recent progress in deep learning is essentially based on a“big data for small tasks”paradigm,under which massive amounts of data are used to train a classifier for a single narrow task.In this paper,we call for a shift that flips this paradigm upside down.Specifically,we propose a“small data for big tasks”paradigm,wherein a single artificial intelligence(AI)system is challenged to develop“common sense,”enabling it to solve a wide range of tasks with little training data.We illustrate the potential power of this new paradigm by reviewing models of common sense that synthesize recent breakthroughs in both machine and human vision.We identify functionality,physics,intent,causality,and utility(FPICU)as the five core domains of cognitive AI with humanlike common sense.When taken as a unified concept,FPICU is concerned with the questions of“why”and“how,”beyond the dominant“what”and“where”framework for understanding vision.They are invisible in terms of pixels but nevertheless drive the creation,maintenance,and development of visual scenes.We therefore coin them the“dark matter”of vision.Just as our universe cannot be understood by merely studying observable matter,we argue that vision cannot be understood without studying FPICU.We demonstrate the power of this perspective to develop cognitive AI systems with humanlike common sense by showing how to observe and apply FPICU with little training data to solve a wide range of challenging tasks,including tool use,planning,utility inference,and social learning.In summary,we argue that the next generation of AI must embrace“dark”humanlike common sense for solving novel tasks.
基金supported by NIH CORE Grant P30 EY08098 to the Department of Ophthalmology,University of Pittsburgh,the Eye and Ear Foundation of Pittsburgh (to KCC)。
文摘SRY-related HMG-box(Sox) transcription factors are known to regulate central nervous system development and are involved in several neurological diseases.Post-translational modification of Sox proteins is known to alter their functions in the central nervous system.Among the different types of post-translational modification,small ubiquitin-like modifier(SUMO) modification of Sox proteins has been shown to modify their transcriptional activity.Here,we review the mechanisms of three Sox proteins in neuronal development and disease,along with their transcriptional changes under SUMOylation.Across three species,lysine is the conserved residue for SUMOylation.In Drosophila,SUMOylation of Sox N plays a repressive role in transcriptional activity,which impairs central nervous system development.However,de SUMOylation of Sox E and Sox11 plays neuroprotective roles,which promote neural crest precursor formation in Xenopus and retinal ganglion cell differentiation as well as axon regeneration in the rodent.We further discuss a potential translational therapy by SUMO site modification using AAV gene transduction and Clustered regularly interspaced short palindromic repeats-Cas9 technology.Understanding the underlying mechanisms of Sox SUMOylation,especially in the rodent system,may provide a therapeutic strategy to address issues associated with neuronal development and neurodegeneration.
基金supported in part by National Institutes of Health Grant EY026766(to MSK)
文摘Intracellular signal transduction controlling neuronal development and survival is conveyed by second messengers that are often differentially regulated over space and time.The highly polarized morphology of neurons is conferred by a network of regulatory signaling pathways that determine axon guidance and dendrite formation.Among these,cyclic adenosine monophosphate(cAMP)is a second messenger that is critical for numerous neuronal functions and known to activate and integrate a variety of downstream pathways.In the central nervous system(CNS),cAMP-dependent signaling is involved in growth cone motility,neuronal metabolism,axon extension in vitro,neuroprotection,and survival in vivo.The complexity of cAMP-dependent neuronal physiology and function raises fundamental questions about the mechanisms determining the specificity by which cAMP can regulate these processes.
文摘AIM:To evaluate concordance between the clinical assessment of glaucomatous progression of the optic disc photography and progression identified by Heidelberg Retina Tomograph(HRT)in patients with suspected primary juvenile open angle glaucoma(JOAG).METHODS:Optic disc photographs and corresponding HRTⅡseries were reviewed.Optic disc changes between first and final photographs were noted as well as progression identified by HRT topographic change analysis(TCA)and rim area regression line(RARL)Agreement between progression indentified by photography and HRT methods was assessed.Progression,determined from optic disc photographs by consensus assessment was used as the reference standard.RESULTS:A total of 31 patients(59 eyes)with suspected JOAG were studied.Agreement for progression/no progression between TCA and photography was obtained in 4 progressing eyes and 38stable eyes(71.19%,k=0.11).Agreement for progression/no progression between RARL and photography was detected in 5 progressing eyes and in 34 stable eyes(66.10%,k=0.15).The number of HRT per patient was statistically higher in the progressing group(P=0.034).CONCLUSION:Agreement for detection of longitudinal changes between photography and HRT analysis was poor.One way to improve the chance of discovery of the progression could be increasing the number of HRT examinations.
文摘Purpose To compare changes in ocular aberrations in children wearing orthokeratology(ortho-k)lenses with a back optic zone diameter(BOZD)of 6 mm(6-MM group)or 5 mm(5-MM group)and their associations with axial elonga-tion(AE)over two years.Methods Seventy Chinese children,aged 6 to 11 years,with myopia between-4.00 to-0.75 D,were randomly allocated to 5-MM and 6-MM groups.Ocular aberrations were measured,rescaled to a 4-mm pupil,and fitted with a 6th order Zernike expansion.Measurements,including axial length,were taken prior to commencing ortho-k treat-ment and then every 6 months over two years.Results After two years,the 5-MM group displayed a smaller horizontal treatment zone(TZ)diameter(by 1.14±0.11 mm,P<0.001)and less AE(by 0.22±0.07 mm,P=0.002)compared with the 6-MM group.A greater increase in total root mean square(RMS)of higher-order aberrations(HOAs),primary spherical aberration(SA)(C_(4)^(0)),and coma were also observed in the 5-MM group at all follow-up visits.The horizontal TZ diameter was significantly associated with changes in RMS HOAs,SA(RMS,primary and secondary SA),and RMS coma.After controlling for base-line parameters,RMS HOAs,RMS SA,RMS coma,and primary(C_(4)^(0))and secondary(C_(6)^(0))SA were significantly associated With AE.Conclusions Ortho-k lenses with a smaller BOzD created a smaller horizontal TZ diameter and a significant increase in total HOAs,total SA,total coma,and primary SA and a decrease in secondary SA.Of these ocular aberrations,total HOAs,total SA,and primary SA were negatively correlated with AE over two years.
基金supported by The Hong Kong Polytechnic University Teaching Postgraduate Studentship(TPS)Scheme to QiTansupported by a private donation to the School of Optometry,The Hong Kong Polytechnic University.
文摘Background The retinal image quality derived from lower-order(LOA)and higher-order aberrations(HOA)for fixed 3-mm and photopic pupil diameters,in children undergoing combined 0.01%atropine and orthokeratology(AOK)versus those receiving orthokeratology alone(OK)over two years was evaluated.Methods The visual Strehl ratio based on the optical transfer function(VSOTF),derived from 2nd-to 4th-order terms(LOA and HOA combined),2nd-order terms(LOA only),and 3rd-to 4th-order terms(HOA only)for fixed 3-mm and natural photopic pupil diameters,was compared between the two treatment groups.The individual Zernike coef-ficients fora fixed 3-mm pupil ize of 2nd to 4th,orders,root mean square(RMS)of LOA(Z_(2)^(0),Z_(2)^(-2),and Z_(2)^(2) combined),HOA(3rd to 4th orders inclusive),and coma(Z_(3)^(-1) and Z_(3)^(1) combined)were also compared between the two groups.Results Right eye data of 33 AOK and 35 OK participants were analysed.Under photopic conditions,significantly lower VSOTF based on HOA only was observed in the AOK group compared with that in the OK group at all post-treatment visits(all P<0.05);however,interactions between HOA and LOA resulted in comparable overall retinal image quality(i.e.,VSOTF based on LOA and HOA combined)between the two groups at all visits(all P>0.05).For a fixed 3-mm pupil size,the VSOTF based on HOA only,LOA only,or HOA and LOA combined,were not different between the two groups(all P>0.05).AOK participants had slower axial elongation(mean±SD,0.17±0.19 mm vs.0.35±0.20 mm,P<0.001),a larger photopic pupil size(4.05±0.61 mm vs.3.43±0.41 mm,P<0.001)than OK partici-pants overtwoyears.Conclusions HOA profile related to an enlarged pupil size may provide visual signal influencing eye growth in the AOK group.
基金supported by Beijing Traditional Chinese Medicine Technology Development Fund Project (JJ2018-50)the National Natural Science Foundation of China (81901202)+4 种基金Beijing Natural Science Foundation (7222217)the Capital Health Research and Development of Special (2022-4-40918)Clinical Medicine Plus X-Young Scholars ProjectPeking Universitythe Fundamental Research Funds for the Central Universities (PKU2021LCXQ007)。
文摘Primary open-angle glaucoma(POAG)is a prevalent cause of blindness worldwide,resulting in degeneration of retinal ganglion cells and permanent damage to the optic nerve.However,the underlying pathogenetic mechanisms of POAG are currently indistinct,and there has been no effective nonsurgical treatment regimen.The objective of this study is to identify novel biomarkers and potential therapeutic targets for POAG.The mRNA expression microarray datasets GSE27276 and GSE138125,as well as the single-cell high-throughput RNA sequencing(sc RNA-seq)dataset GSE148371 were utilized to screen POAGrelated differentially expressed genes(DEGs).Functional enrichment analyses,protein-protein interaction(PPI)analysis,and weighted gene co-expression network analysis(WGCNA)of the DEGs were performed.Subsequently,the hub genes were validated at a single-cell level,where trabecular cells were annotated,and the mRNA expression levels of target genes in different cell clusters were analyzed.Immunofluorescence and quantitative real-time PCR(q PCR)were performed for further validation.DEGs analysis identified 43 downregulated and 32 upregulated genes in POAG,which were mainly enriched in immune-related pathways,oxidative stress,and endoplasmic reticulum(ER)stress.PPI networks showed that FN1 and DUSP1 were the central hub nodes,while GPX3 and VAV3 were screened out as hub genes through WGCNA and subsequently validated by q PCR.Finally,FN1,GPX3,and VAV3 were determined to be pivotal core genes via single-cell validation.The relevant biomarkers involved in the pathogenesis of POAG,may serve as potential therapeutic targets.Further studies are necessary to unveil the mechanisms underlying the expression variations of these genes in POAG.
基金supported by Beijing Traditional Chinese Medicine Technology Development Fund Project(J2018-50 to C.L.)the National Natural Science Foundation of China(81901202 to C.Y.)+2 种基金Beijing Natural Science Foundation(7222217 to C.Y.)the Capital Health Research and Development of Special(2022-4-40918 to C.Y.)Clinical Medicine Plus X-Young Scholars Project,Peking University,the Fundamental Research Funds for the Central Universities(PKU2021LCXQ007 to C.Y.).
文摘The progressive degradation in the trabecular meshwork(TM)is related to age-related ocular diseases like primary open-angle glaucoma.However,the molecular basis and biological significance of the aging process in TM have not been fully elucidated.Here,we established a dynamic single-cell transcriptomic landscape of aged macaque TM,wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM aging.Furthermore,we divided TM cells into 13 clusters and performed an in-depth analysis on cluster O,which had the highest aging score and the most significant changes in cell proportions between the two groups.Ultimately,we found that the APOE gene was an important differentially expressed gene in cluster O during the aging process,highlighting the close relationship between cell migration and extracellular matrix regulation,and TM function.Our work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components,thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal range.Our work provides valuable insights for future clinical diagnosis and treatment of glaucoma.
基金supported by NSF-2040527.Part of this work was conducted at the Washington Nano-fabrication Facility/Molecular Analysis Facility,a National Nanotechnology Coordinated Infrastructure(NNCI)site at the University of Washington with partial support from the National Science Foundation via awards NNCI-1542101 and NNCI-2025489。
文摘Quantitative phase imaging(QPI)recovers the exact wavefront of light from intensity measurements.Topographical and optical density maps of translucent microscopic bodies can be extracted from these quantified phase shifts.We demonstrate quantitative phase imaging at the tip of a coherent fiber bundle using chromatic aberrations inherent in a silicon nitride hyperboloid metalens.Our method leverages spectral multiplexing to recover phase from multiple defocus planes in a single capture using a color camera.Our 0.5mm aperture metalens shows robust quantitative phase imaging capability with a 28°field of view and 0.2πphase resolution(~0.1λin air)for experiments with an endoscopic fiber bundle.Since the spectral functionality is encoded directly in the imaging lens,the metalens acts both as a focusing element and a spectral filter.The use of a simple computational backend will enable real-time operation.Key limitations in the adoption of phase imaging methods for endoscopy such as multiple acquisition,interferometric alignment or mechanical scanning are completely mitigated in the reported metalens based QPI.
基金Key Program on Basic Research Project of Universities of Henan(No.22B320016)Scientific Research Fund of National Health Commission-Henan Province Medical Science and Technology Project(No.SB201901013)
文摘To the Editor:Acute concomitant esotropia(ACE)is an acquired esotropia with a sudden appearance and no pathologic changes on cerebral imaging.There are various treatments for ACE,including extraocular muscle surgery,botulinum toxin A(BTA)injection,prisms,and divergence training.[1]BTA had been used in the treatment of ACE since it was approved by Food and Drug Administration(FDA,USA)in 1989.[2]Some researchers have confirmed that its effect is stable and has unique advantages in the treatment of ACE.
基金supported by an unrestricted research grant from the Klaus Tschira FoundationHeidelberg,Germany.T.Yildirim is funded by the Physician-Scientist Program of the Heidelberg University,Faculty of Medicine.
文摘Background:Intraocular lens(IOL)calcification is a serious condition that can only be treated by removing the clouded lens.Since explantation bears the risk of complications,it is often deferred until the patient finds the symptoms intolerable.Usually,as the IOL opacifies,visual acuity is minimally affected early on.In this study,we assessed the impact of IOL opacification on optical quality.Methods:We analyzed ten opacified explanted IOLs(Oculentis GmbH).Wavefront aberrations were obtained with a SHSOphthalmic device(Optocraft GmbH),which features a Hartmann-Shack sensor.The root mean square(RMS)of higher-order aberrations(HOAs)was compared.The effect of calcification on image quality was assessed through the Strehl ratio(SR).We detected light scattering with a C-Quant(Oculus GmbH)and expressed it as a straylight parameter.Results:At 2 mm,3mm and 4 mm,the mean RMS(±standard deviation)was 0.033μm(±0.026μm),0.044μm(±0.027),and 0.087μm(±0.049),respectively.The mean SR value was 0.81±0.15 at 3 mm,with four IOLs showing a nearly diffraction-limited performance,but in two explants,opacification precluded reliable measurements.Increased straylight was found in all opacified IOLs with a mean value of 150.2±56.3 deg^(2)/sr at 3 mm.Conclusions:We demonstrated that IOL opacification induces HOAs.However,the RMS remained low,which resulted only in a slight reduction of the SR-derived optical quality.On the other hand,we found a severe straylight elevation in the opacified lenses,which may result in dysphotopsia,such as glare,and subjective complaints,despite good visual acuity.
基金supported by grants from the Scientific Research Fund of National Health Commission-Henan Province Medical Science and Technology Project(No.SB201901013)Basic and Advance Technology Research Project of Henan Province(No.14230410235)。
文摘Orbital floor fractures affect eye movement,but the underlying mechanism remains unclear.Therefore,the present retrospective study aimed to clinically characterize fractures in different inferior.
文摘Dear Editor： Gao et al. published data in Nature Biotechnology （Nat Biotechnol. 2016 May 2） showing that DNA-guided genome editing using the Natronobacterium gregoryi Argonaute （NgAgo） protein targeted 47 mammalian genomic loci with a 100% success rate and an efficiency of 21.3%-41.3% at various targets. This report led us to test NgAgo＇s utility in various cells and organisms such as mouse and zebrafish for gene editing.
