Evaluation of genetic response of mesenchymal stem cells to nanosecond pulsed electric fields by whole transcriptome sequencing

BACKGROUND Mesenchymal stem cells(MSCs)modulated by various exogenous signals have been applied extensively in regenerative medicine research.Notably,nanosecond pulsed electric fields(nsPEFs),characterized by short duration and high strength,significantly influence cell phenotypes and regulate MSCs differentiation via multiple pathways.Consequently,we used transcriptomics to study changes in messenger RNA(mRNA),long noncoding RNA(lncRNA),microRNA(miRNA),and circular RNA expression during nsPEFs application.AIM To explore gene expression profiles and potential transcriptional regulatory mechanisms in MSCs pretreated with nsPEFs.METHODS The impact of nsPEFs on the MSCs transcriptome was investigated through whole transcriptome sequencing.MSCs were pretreated with 5-pulse nsPEFs(100 ns at 10 kV/cm,1 Hz),followed by total RNA isolation.Each transcript was normalized by fragments per kilobase per million.Fold change and difference significance were applied to screen the differentially expressed genes(DEGs).Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to elucidate gene functions,complemented by quantitative polymerase chain reaction verification.RESULTS In total,263 DEGs were discovered,with 92 upregulated and 171 downregulated.DEGs were predominantly enriched in epithelial cell proliferation,osteoblast differentiation,mesenchymal cell differentiation,nuclear division,and wound healing.Regarding cellular components,DEGs are primarily involved in condensed chromosome,chromosomal region,actin cytoskeleton,and kinetochore.From aspect of molecular functions,DEGs are mainly involved in glycosaminoglycan binding,integrin binding,nuclear steroid receptor activity,cytoskeletal motor activity,and steroid binding.Quantitative real-time polymerase chain reaction confirmed targeted transcript regulation.CONCLUSION Our systematic investigation of the wide-ranging transcriptional pattern modulated by nsPEFs revealed the differential expression of 263 mRNAs,2 miRNAs,and 65 lncRNAs.Our study demonstrates that nsPEFs may affect stem cells through several signaling pathways,which are involved in vesicular transport,calcium ion transport,cytoskeleton,and cell differentiation.

Prevascularized Micro‑/Nano‑Sized Spheroid/Bead Aggregates for Vascular Tissue Engineering

Efficient strategies to promote microvascularization in vascular tissue engineering,a central priority in regenerative medicine,are still scarce;nano-and micro-sized aggregates and spheres or beads harboring primitive microvascular beds are promising methods in vascular tissue engineering.Capillaries are the smallest type and in numerous blood vessels,which are distributed densely in cardiovascular system.To mimic this microvascular network,specific cell components and proangiogenic factors are required.Herein,advanced biofabrication methods in microvascular engineering,including extrusion-based and droplet-based bioprinting,Kenzan,and biogripper approaches,are deliberated with emphasis on the newest works in prevascular nano-and micro-sized aggregates and microspheres/microbeads.

Pores Created by Laser Surface Modification of Poly(vinylalcohol)-Collagen with Glycosaminoglycan Scaffold for Cell Culture in Tissue Engineering

A PVA-GAG-COL composite scaffold is fabricated by polyvinyl alcohol （PVA）, glyeosaminoglycan （GAG） and collagen （COL）. Laser surface modification technology is used to make holes on the surface of the scaffolds. Inside and outside interconnection micro-porous structure is obtained. Bioeompatibility test of the scaffolds shows that PVA-GAG-COL scaffold can promote the adhesion and proliferation of the fibroblast. Also, fibroblast can grow normally on the scaffolds with pore diameter from 115 um to 255 um and pore distance from 500 um to 2000 um. PVA-GAG-COL scaffolds possess excellent cell biocompatibility. The porous structure is suitable for cell culture in tissue engineering.

一种基于非线性参数的心血管健康状况定量评测方法(英文)

目的研究定量评测心血管系统功能状况的方法。方法首先记录运动实验的心电信号,经信号处理得到运动心率变异信号,然后从中提取近似熵,复杂度以及散点图中的长轴、短轴和面积等5个参数,采用判别分析对两组典型人群进行判别分类。结果在判别分析基础上建立一个百分制评分体系,并根据得分区间划分为4个等级。为了验证该评分体系的有效性,对3组健康状况不同的人群进行了打分,包括60位中年高血压患者,50位老年者以及110位年轻的健康者。结论3组人群的健康状况评测结果与实际情况相符合,说明所提出的方法可以对测试者的心血管健康状况进行有效地评测。

A new specialized visual acuity chart for amblyopic children aged 3-5 years old:development and its clinical applications

AIM:To Introduce a new specialized visual acuity chart for amblyopic children aged 3-5 years old and its clinical applications.METHODS:The new visual acuity chart and notations were designed based on Weber-Fechner law.The optotypes were red against a white background and were specially shaped four basic geometric symbols:circle,square,triangle,and cross.A regular geometric progression of the optotype sizes and distribution was employed to arrange in 14 lines.The progression rate of the optotype size between two lines was 1.2589 and the testing distance was 3m.Visual acuity score could be recorded as logMAR notation or decimal notation.Agestratified diagnostic criteria for amblyopia established by consensus statement on diagnosis of amblyopia(2011)among members of the Strabismus and Pediatric Ophthalmology Group,Ophthalmology Society,Chinese Medical Association(SPOGOSCMA)were illustrated in the new visual acuity chart.RESULTS:When assessing visual acuity in children aged 3-5 years old,this new visual acuity chart that consists of four symmetrical shapes(triangle,square,cross,and circle)overcame an inability to recognize the letters of the alphabet and difficulties in designating the direction of black abstract symbols such as the tumbling’E’or Landolt’C’,which the subjects were prone to lose interest in.The visual acuity score may be recorded indifferent notations:decimal acuity and logMAR.These two notations can be easily converted each other in the new eye chart.The measurements of this new chart not only showed a significant correlation and a good consistency with the international standard logarithmic visual acuity chart(r=0.932,P【0.01),but also indicated a high test-retest reliability(89%of retest scores were within 0.1 logMAR units of the initial test score).CONCLUSION:The results of this study support the validity and reliability of distance visual acuity measurements using the new eye chart in children aged3 to 5 years over a wide range of visual acuities,and the new eye chart is great for early detection of amblyopia.It can be applied in various clinical settings.

Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson’s disease?

Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson＇s disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups （PBS injection） demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase （dopaminergic neuronal marker） staining and G protein-activated inward rectifier potassium channel 2 （A9 dopaminergic neuronal marker） were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stern cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.

PGE2 activates EP4 in subchondral bone osteoclasts to regulate osteoarthritis

Prostaglandin E2(PGE2), a major cyclooxygenase-2(COX-2) product, is highly secreted by the osteoblast lineage in the subchondral bone tissue of osteoarthritis(OA) patients. However, NSAIDs, including COX-2 inhibitors, have severe side effects during OA treatment. Therefore, the identification of novel drug targets of PGE2 signaling in OA progression is urgently needed. Osteoclasts play a critical role in subchondral bone homeostasis and OA-related pain. However, the mechanisms by which PGE2 regulates osteoclast function and subsequently subchondral bone homeostasis are largely unknown. Here, we show that PGE2 acts via EP4 receptors on osteoclasts during the progression of OA and OA-related pain. Our data show that while PGE2 mediates migration and osteoclastogenesis via its EP2 and EP4 receptors, tissue-specific knockout of only the EP4 receptor in osteoclasts(EP4 Lys M) reduced disease progression and osteophyte formation in a murine model of OA. Furthermore, OA-related pain was alleviated in the EP4 Lys M mice, with reduced Netrin-1 secretion and CGRP-positive sensory innervation of the subchondral bone. The expression of plateletderived growth factor-BB(PDGF-BB) was also lower in the EP4 Lys Mmice, which resulted in reduced type H blood vessel formation in subchondral bone. Importantly, we identified a novel potent EP4 antagonist, HL-43, which showed in vitro and in vivo effects consistent with those observed in the EP4 Lys Mmice. Finally, we showed that the Gαs/PI3 K/AKT/MAPK signaling pathway is downstream of EP4 activation via PGE2 in osteoclasts. Together, our data demonstrate that PGE2/EP4 signaling in osteoclasts mediates angiogenesis and sensory neuron innervation in subchondral bone, promoting OA progression and pain, and that inhibition of EP4 with HL-43 has therapeutic potential in OA.

COLOR CORRECTION FOR HIGH-DEFINITION ELECTRONIC ENDOSCOPE

The subtle color distinction is the important function of electronic endoscope imaging diagnosis.However,after image acquisition,transmission and display,color distortions of intracorporeal organs or tissues occur inevitably,which are adverse to analyze image features accurately or to diagnose early pathological changes.A real-time color correction algorithm based on fourneighborhood and polynomial regression in YUV color space is proposed.Based on polynomial regression the color correction matrix is calculated in YUV color space according to the dierences between standard values of color checker and measured values of that imaged by the endoscope.As the correction is only executed on U and V components in YUV color space,the defect that the color of corrected images in RGB color space will change along with luminance can be avoided,and then the stability of image color is improved.Owing to four-neighborhood processing,the signal-to-noise ratio of corrected images is enhanced and the processing speed of correction algorithm is accelerated.The average color dierence is reduced from 0.3944 to 0.2850 by application of the proposed algorithm in high-denition electronic endoscope.A total of 17 frames per second can be achieved at the resolution of 1280
800,and the color characteristics of the image after processing match that of human visual system.

Endogenous motion of liver correlates to the severity of portal hypertension

BACKGROUND Degree of portal hypertension(PH)is the most important prognostic factor for the decompensation of liver cirrhosis and death,therefore adequate care for patients with liver cirrhosis requires timely detection and evaluation of the presence of clinically significant PH(CSPH)and severe PH(SPH).As the most accurate method for the assessment of PH is an invasive direct measurement of hepatic venous pressure gradient(HVPG),the search for non-invasive methods to diagnose these conditions is actively ongoing.AIM To evaluate the feasibility of parameters of endogenously induced displacements and strain of liver to assess degree of PH.METHODS Of 36 patients with liver cirrhosis and measured HVPG were included in the casecontrol study.Endogenous motion of the liver was characterized by derived parameters of region average tissue displacement signal(dantero,dretro,dRMS)and results of endogenous tissue strain imaging using specific radiofrequency signal processing algorithm.Average endogenous strainμand standard deviationσof strain were assessed in the regions of interest(ROI)(1 cm×1 cm and 2 cm×2 cm in size)and different frequency subbands of endogenous motion(0-10 Hz and 10-20 Hz).RESULTS Four parameters showed statistically significant(P<0.05)correlation with HVPG measurement.The strongest correlation was obtained for the standard deviation of strain(estimated at 0-10 Hz and 2 cm×2 cm ROI size).Three parameters showed statistically significant differences between patient groups with CSPH,but only dretro showed significant results in SPH analysis.According to ROC analysis area under the curve(AUC)of theσROI[0…10Hz,2 cm×2 cm]parameter reached 0.71(P=0.036)for the diagnosis of CSPH;with a cut-off value of 1.28μm/cm providing 73%sensitivity and 70%specificity.AUC for the diagnosis of CSPH forμROI[0…10Hz,1 cm×1 cm]was 0.78(P=0.0024);with a cut-off value of 3.92μm/cm providing 73%sensitivity and 80%specificity.Dretro parameter had an AUC of 0.86(P=0.0001)for the diagnosis of CSPH and 0.84(P=0.0001)for the diagnosis of SPH.A cut-off value of-132.34μm yielded 100%sensitivity for both conditions,whereas specificity was 80%and 72%for CSPH and SPH respectively.CONCLUSION The parameters of endogenously induced displacements and strain of the liver correlated with HVPG and might be used for non-invasive diagnosis of PH.

Prostate Specific Antigen Promoter-Driven Adenovirus-Mediated Expression of Both ODC and AdoMetDC Antisenses Inhibit Prostate Cancer Growth

Objective：To generate recombinant adenovirus that could simultaneously express ornithine decarboxylase（ODC） and S-adenosylmethionine decarboxylase（AdoMetDC） antisenses specifically in prostate cancer cells,and evaluate its inhibitory effect on prostate cancer in vivo.Methods：Fragments of ODC and AdoMetDC genes were generated by PCR,cloned into the pPGL-PSES,and then recombined with pAdEasy-1 vectors in AdEasy-1 cells.Ad-PSES-ODC-AdoMetDCas virus was produced in HEK293 cells.Following transfection with Ad-PSES-ODC-AdoMetDCas,the levels of ODC or AdoMetDC were determined by RT-PCR and western blot assays.The effect of Ad-PSES-ODC-AdoMetDCas treatment on tumor formation and growth was evaluated in xenograft models of prostate cancers in vivo.Results：The plasmid pAdEasy-PSES-ODC-AdoMetDCas was successfully constructed and the recombinant Ad-PSES-ODC-AdoMetDCas adenovirus was produced.Transfection with Ad-PSES-ODC-AdoMetDCas adenovirus significantly inhibited the expression of ODC and AdoMetDC genes specifically in prostate DU145 cells,but not H1299,HT29 and HepG2 cancer cells,and disrupted the ability of DU145 cells to form solid prostate cancer in vivo.Intratumoral treatment with Ad-PSES-ODC-AdoMetDCas adenovirus significantly inhibited the growth of engrafted prostate tumors in vivo.Conclusion：The recombinant Ad-PSES-ODC-AdoMetDCas adenovirus specifically reduces the expression of both ODC and AdoMetDC genes in prostate cells and may be used for treatment of prostate cancers at the clinic.

Retraction of lumbar disc herniation achieved by noninvasive techniques: A case report

BACKGROUND Lumbar disc herniation(LDH)has emerged as one of the most common causes of low back pain.The routine treatment approach involves chemonucleolysis therapy,discectomy by percutaneous endoscopy,and percutaneous laser disc decompression.Unfortunately,all of these methods carry inherent risk of causing harm to the patient and,as such,there is an unmet but urgent need for an effective and safe noninvasive treatment for LDH.The purpose of this report is to describe a non-invasive method for re-absorption of LDH.CASE SUMMARY A 34-year-old woman was admitted with a complaint of waist pain that she reported as having become acutely aggravated over the past 3 d and accompanied by discomfort in the right lower limb.Her self-reported medical history included persistent postpartum low back pain from 7 years prior.Physical exam showed positivity for neck flexion test(Lindner sign)and supine abdomen test;the straight leg-raising test showed right 60(+)and left 80(-).Findings from standard imaging(magnetic resonance)and collective physical examinations indicated a L5/S1 herniated lumbar disc.Treatment consisted of three-dimensional(balanced regulating)spinal manipulation and acupuncture,upon which the LDH resolved by retraction.CONCLUSION Following L5/S1 herniated lumbar disc diagnosis,three-dimensional(balanced regulating)spinal manipulation combined with acupuncture therapy is an effective treatment.

A near-vision chart for children aged 3-5 years old:new designs and clinical applications

AIM:To introduce a new near-vision chart for children aged 3-5 years old and its clinical applications.METHODS:Thenewnear-visionchartwhichcombined the Bailey-Lovie layout with a newly devised set of symmetry symbols was designed based on WeberFechner law.It consists of 15 rows of symmetry symbols,corresponding to a visual acuity range from 1.3 to 0.1logMAR.The optotypes were red against a white background and were specially shaped four basic geometric symbols:circle,square,triangle,and cross,which matched the preschool children’s cognitive level.A regular geometric progression of the optotype sizes and distribution was employed to arrange in 15 lines.The progression rate of the optotype size between two lines was 1.2589 and two smaller groups of optotypes ranging from 0.7 to-0.1 logMAR were included for repetitive testing.A near visual acuity was recorded in logMAR or decimal,and the testing distance was 25 cm.RESULTS:This new near-vision chart with pediatric acuity test optotypes which consists of 4 different symbols(triangle,square,cross,and circle)met the national and international eye chart design guidelines.When performing the near visual acuity assessment in preschoolers(3-5y old).It overcame an inability to recognize the letters of the alphabet and difficulties in designating the direction of black abstract symbols such as the tumbling’E’or Landolt’C’,which the subjects were prone to lose interest in.Near vision may be recorded in different notations:decimal acuity and logMAR.These two notations can be easily convertedeach other in the new near-vision chart.The measurements of this new chart not only showed a significant correlation and a good consistency with the Chinese national standard logarithmic near-vision chart(r=0.932,P【0.01),but also indicated good test-retest reliability(89%of retest scores were within 0.1 logMAR units of the initial test score)and a high response rate.CONCLUSION:The results of this study support the validity and reliability of near visual acuity measurements using the new near-vision chart in children aged 3-5y over a wide range of visual acuities,and the new eye chart was especially suitable for the detection of amblyopia risk factors and low vision examination in children(3-5y of age).It can be applied in routine clinical practice.

Preparation of Agarose Sulfate and Its Antithrombogenicity

As one of the seaweed polysaccharide, agarose has received much attention because of its biocompatibility. However, its application in biomedical field was limited with its biological inertia. Modification with some functional groups is needed to obtain agarose derivatives with biological activity and expand its applications. Consequently, agarose was sulfated with chlorosulfonic acid-pyridine with formamide as dispersing agent. The orthogonal test result showed that the optimal reaction condition was the reaction time being 4 h, the reaction temperature 65 ℃ and the ratio of chlorosulfonic acid to agarose 1-4（mL/g）. Two kinds of the insoluble agarose sulfate （below 37 ℃） were synthesized with degree of substitution （DS） being 0.17 and 0.43 respectively. Infrared spectroscopy （IR） and tac nuclear magnetic resonance （13C-NMR） spectroscopy results proved that C3_6 in agarose was sulfated. Their hydrophobic property and BSA adsorption capacity rose with increasing DS, while the adsorption of lib was reduced. The anti-clotting properties of agarose sulfate were significantly improved, and agarose sulfate could protect red blood cells from deformation after adsorption of BSA. These findings demonstrate that the cold-water insoluble agarose sulfate has a promise for applications as heoarin-like material in anticoagulation or endothelial re^enera＇Lion scaffold.

Smart control plane for information centric network-internet service provider networks

The information centric network(ICN)has been widely discussed in current researches.The ICN interoperation with a traditional IP network and caching methods are one of the research topics of interest.For economic reasons,the capability of applying the ICN to internet service providers(ISPs)with various traditional IP protocols already implemented,especially IGP,MPLS,VRF,and TE,does not require any change on the IP network infrastructure.The biggest concern of ISPs is related to their customers’contents delivery speed.In this paper,we consider ICN caching locations in ISP by using the concept of locator/ID separation protocol(LISP)for interoperation between a traditional IP address and name-based ICN.To be more specific,we propose a new procedure to determine caching locations in the ICN by using the cuckoo search algorithm(CSA)for finding the best caching locations of information chunks.Moreover,we create the smart control plane(SCP)scheme which is an intelligent controlling,managing,and mapping system.Its function is similar to the software defined network concept.We show how the proposed SCP system works in both synthetic small network and real-world big network.Finally,we show and evaluate the performance of our algorithm comparison with the simple search method using the shortest path first algorithm.

Evaluating nerve guidance conduits for peripheral nerve injuries:a novel normalization method

The peripheral nervous system （PNS） is composed of the nerves and ganglia outside of the brain and spinal cord whose primary function is to connect the central nervous system to the limbs and organs. A peripheral nerve injury （PNI） is damage to the nerves and/or its surrounding tissue. These injuries can affect up to 5% of patients that are hospitalized for trauma （Taylor et al., 2008） and over 50,000 surgical repair procedures are performed annually in the United States alone （Evans, 2001）.

Differences in Heart Stroke Volume between Han and Korean-Chinese Nationalities and Correlative Factors

Objective To compare the differences in stroke volume （SV） and stroke volume index （Sl） between Han and Korean-Chinese and to investigate the correlated risk factors. Methods A total of 1 647 Han and 876 Korean-Chinese aged 10-80 years were investigated. SV, SI, cardiac output, cardiac output index, heart rate （HR）, systemic vascular resistance （SVR）, systemic vascular resistance index （SVRI）, and blood pressure were measured. Results SV/SI values in Korean-Chinese were lower than those in the Han of the same sex and age. Covariance analysis showed that, apart from the effect of sex, age and body mass index （BMI）, the differences in SV and SI between the two cohorts were still significant （P〈O.O01）. Multiple regression analysis revealed that the SV difference between the two ethnicities was affected （in descending order from a strong to weak correlation） by SVR, SVRI, HR, diastolic blood pressure, mean arterial pressure, BMI, and systolic blood pressure, while the SI difference was affected by SVR, SVRI, HR, mean arterial pressure, diastolic and systolic blood pressure, and BMI. Conclusion The Fact that SV and SI in Korean-Chinese are lower than those in Han is related with higher SVR, HR and blood pressure in the Korean-Chinese.

Effects of Plasma Proteins on <i>Staphylococcus epidermidis</i>RP62A Adhesion and Interaction with Platelets on Polyurethane Biomaterial Surfaces

Plasma proteins influence the initial adhesion of bacteria to biomaterials as well as interactions between bacteria and blood platelets on blood-contacting medical devices. In this paper, we study the effects of three human plasma proteins, albumin, fibrinogen (Fg), and fibronectin (Fn), on the adhesion of Staphylococcus epidemidis RP62A to polyurethane biomaterial surfaces, and also address how these three proteins affect bacterial interactions with human platelets on materials. Measurements of bacterial adhesion on polymer surfaces pre-adsorbed with a variety of proteins demonstrate that Fn leads to increased bacterial adhesion, with the order of effectiveness being Fn 》Fg > albumin. Immuno-AFM (atomic force microscopy) was used to assess the Fn adsorption/activity on surfaces and bacterial cell membranes by looking at molecular scale events. A correlation between molecular scale Fn adsorption and macroscale bacterial adhesion was observed, with an increased numbers of Fn-receptor recognition events measured on cell surfaces as compared to Fg-receptor recognition events, suggesting Fn is an important protein in bacterial adhesion. Monoclonal antibodies recognizing either the carboxyl-terminus or amino-terminus of Fn were coupled to AFM probes and used to assess the orientation of Fn adsorbed on a surface, with an increased amount of Fn carboxyl-terminus availability corresponding to higher bacterial adhesion. Interactions between bacteria and platelets were demonstrated with fluorescence and AFM imaging on the polyurethane surfaces, with albumin inhibiting bacteria-platelet interaction and platelet activation, and both Fg and Fn promoting adhesion of bacteria to platelets and apparent platelet activation, resulting in bacteria/platelet aggregation.

Combining Gene-Phenotype Association Matrix with KEGG Pathways to Mine Gene Modules Using Data Set in GAW17

Currently, genome-wide association studies have been proved to be a powerful approach to identify risk loci. However, the molecular regulatory mechanisms of complex diseases are still not clearly understood. It is therefore important to consider the interplay between genetic factors and biological networks in elucidating the mechanisms of complex disease pathogenesis. In this paper, we first conducted a genome-wide association analysis by using the SNP genotype data and phenotype data provided by Genetic Analysis Workshop 17, in order to filter significant SNPs associated with the diseases. Second, we conducted a bioinformatics analysis of gene-phenotype association matrix to identify gene modules (biclusters). Third, we performed a KEGG enrichment test of genes involved in biclusters to find evidence to support their functional consensus. This method can be used for better understanding complex diseases.

Anatomical Modeling of Brain Vasculature in Two-Photon Microscopy by Generalizable Deep Learning

Objective and Impact Statement.Segmentation of blood vessels from two-photon microscopy(2PM)angiograms of brains has important applications in hemodynamic analysis and disease diagnosis.Here,we develop a generalizable deep learning technique for accurate 2PM vascular segmentation of sizable regions in mouse brains acquired from multiple 2PM setups.The technique is computationally efficient,thus ideal for large-scale neurovascular analysis.Introduction.Vascular segmentation from 2PM angiograms is an important first step in hemodynamic modeling of brain vasculature.Existing segmentation methods based on deep learning either lack the ability to generalize to data from different imaging systems or are computationally infeasible for large-scale angiograms.In this work,we overcome both these limitations by a method that is generalizable to various imaging systems and is able to segment large-scale angiograms.Methods.We employ a computationally efficient deep learning framework with a loss function that incorporates a balanced binary-cross-entropy loss and total variation regularization on the network’s output.Its effectiveness is demonstrated on experimentally acquired in vivo angiograms from mouse brains of dimensions up to 808×808×702μm.Results.To demonstrate the superior generalizability of our framework,we train on data from only one 2PM microscope and demonstrate high-quality segmentation on data from a different microscope without any network tuning.Overall,our method demonstrates 10×faster computation in terms of voxels-segmented-per-second and 3×larger depth compared to the state-of-the-art.Conclusion.Our work provides a generalizable and computationally efficient anatomical modeling framework for brain vasculature,which consists of deep learning-based vascular segmentation followed by graphing.It paves the way for future modeling and analysis of hemodynamic response at much greater scales that were inaccessible before.

Short-tim e spectrum discrim ination between transientevoked otoacoustic em ission and stim ulus artifact

Transient Evoked Otoacoustic Emission(TEOAE) has been widely researched and applied in auditory field during these years.Correctly indentifying TEOAE is the basis of study and application.Aiming at the limitations of the traditional TEOAE identification methods,this study put forward a new discrimination criterion between TEOAE and residual stimulus artifact in time frequency domain according to their different features.This method has been demonstrated to improve the correctness of identification,and will help the accurate diagnosis of cochlear function.