基于体对角线机床位置误差的激光矢量测量分析

机床空间位置误差的测量和补偿是提高加工精度的重要手段.通过分析机床沿4条体对角线的位移误差与空间位置误差间的矢量关系,提出了利用体对角线多步运动测得的位移误差分离机床运动轴位置误差的矢量分析方法.分析结果表明,新方法不仅可以反映机床的几何精度,而且可以快速分离出3个运动轴的9项位置误差,为实施数控机床的空间位置误差补偿提供了理论基础.

数控机床圆轨迹非接触式激光测量原理及应用

圆轨迹测量对数控机床的精度评价非常重要。提出数控机床的非接触式激光测量方法,阐述该方法的特点及设备结构,推导基本数学模型,介绍基本测量流程并给出应用实例。该方法测量精确,操作方便,尤其在小半径高进给这一其他方法的弱势领域表现优异。

三维空间定位精度的高效测量与补偿及校验

介绍数控机床三维空间定位精度测量、补偿和校验的一种高效、精确的方法。通过激光多普勒干涉仪,运用矢量原理和多步测量的方法,通过四次调整测量就可以获得机床的12项误差元素,根据测量出的误差数据可以生成误差补偿代码并用于误差补偿以提高机床三维空间定位精度,最后通过实例验证该测量方法的准确性及高效率。

数控机床空间定位精度的测量与补偿

本文介绍一种使用美国光动公司的激光多谱勒位移测量仪,对数控机床进行空间误差检测的激光矢量测量新方法。该方法可以方便而快速地检测出机床的空间定位精度,包括3个定位误差、6个直线度误差和3个垂直度误差;同时还可以根据测量的空间定位误差数据生成误差补偿的代码,进而可以对其进行空间定位误差的补偿,大幅度提高了数控机床加工精度。

Connected-Vehicle Data Exchanges and Positioning Computing Based on the Publish-Subscribe Paradigm

Connected vehicles for safety and traffic efficient applications require device-to-device connections supporting one-to-many and many-to-many communication, precise absolute and relative positioning and distributed computing. Currently, the 5.9 GHz Dedicated Short Range Communications (DSRC) and 4G-Long-Term Evolution (LTE) are available for connected vehicle services. But both have limitations in reliability or latency over large scale field operational tests and deployment. This paper proposes the device-to-device (D2D) connectivity framework based on publish-subscribe architecture, with Message Queue Telemetry Transport (MQTT) protocol. With the publish-subscribe communication paradigm, road mobile users can exchange data and information in moderate latency and high reliability manner, having the potential to support many Vehicle to Everything (V2X) applications, including vehicle to vehicle (V2V), vehicle to roadside infrastructure (V2I), and vehicle to bicycle (V2B). The D2D data exchanges also facilitate computing for absolute and relative precise real-time kinematic (RTK) posi-tioning. Vehicular experiments were conducted to evaluate the performance of the proposed publish-subscribe MQTT protocols in term of latency and reliability. The latency of data exchanges is measured by One-trip-time (OTT) and the reliability is measured by the packet loss rate (PLR). Our results show that the latency of GNSS raw data exchanges between vehicles through 4G cellular networks at the rate of 10 Hz and the data rates of 10 kbps are less than 300 ms while the reliability is over 96%. Vehicular positioning experiments have also shown that vehicles can exchange raw GNSS data and complete mov-ing-base RTK positioning with the positioning availability of 98%.

3D与3轴校准之间的区别

防止机床在容积定位中产生误差，对精确地加工外形轮廓和其他的3D表面而言是非常关键的。

Application of magnetotactic bacteria as engineering microrobots:Higher delivery efficiency of antitumor medicine

For a significant duration,enhancing the efficacy of cancer therapy has remained a critical concern.Magnetotactic bacteria(MTB),often likened to micro-robots,hold substantial promise as a drug delivery system.MTB,classified as anaerobic,aquatic,and gram-negative microorganisms,exhibit remarkable motility and precise control over their internal biomineralization processes.This unique ability results in the formation of magnetic nanoparticles arranged along filamentous structures in a catenary fashion,enclosed within a membrane.These bacteria possess distinctive biochemical properties that facilitate their precise positioning within complex environments.By harnessing these biochemical attributes,MTB could potentially offer substantial advantages in the realm of cancer therapy.This article reviews the drug delivery capabilities of MTB in tumor treatment and explores various applications based on their inherent properties.The objective is to provide a comprehensive understanding of MTB-driven drug delivery and stimulate innovative insights in this field.

A soft,high-density neuroelectronic array

Techniques to study brain activities have evolved dramatically,yet tremendous challenges remain in acquiring high-throughput electrophysiological recordings minimally invasively.Here,we develop an integrated neuroelectronic array that is filamentary,highdensity and flexible.Specifically,with a design of single-transistor multiplexing and current sensing,the total 256 neuroelectrodes achieve only a 2.3×0.3mm^(2)area,unprecedentedly on a flexible substrate.A single-transistor multiplexing acquisition circuit further reduces noise from the electrodes,decreases the footprint of each pixel,and potentially increases the device’s lifetime.The filamentary neuroelectronic array also integrates with a rollable contact pad design,allowing the device to be injected through a syringe,enabling potential minimally invasive array delivery.Successful acute auditory experiments in rats validate the ability of the array to record neural signals with high tone decoding accuracy.Together,these results establish soft,high-density neuroelectronic arrays as promising devices for neuroscience research and clinical applications.

Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma

The desmoplastic and complex tumor microenvironment of pancreatic ductal adenocarcinoma(PDAC)has presented tremendous challenges for developing effective therapeutic strategies.Strategies targeting tumor stroma,albeit with great potential,have met with limited success due to the lack of knowledge on the molecular dynamics within the tumor microenvironment(TME).In pursuit of a better understanding of the influence of miRNAs on TME reprogramming and to explore circulating miRNAs as diagnostic and prognostic biomarkers for PDAC,using RNA-seq,miRNA-seq,and single-cell RNA-seq(scRNA-seq),we investigated the dysregulated signaling pathways in PDAC TME modulated by miRNAs from plasma and tumor tissue.Our bulk RNA-seq in PDAC tumor tissue identified 1445 significantly differentially expressed genes with extracellular matrix and structure organization as the top enriched pathways.Our miRNA-seq identified 322 and 49 abnormally expressed miRNAs in PDAC patient plasma and tumor tissue,respectively.We found many of the TME signaling pathways were targeted by those dysregulated miRNAs in PDAC plasma.Combined with scRNA-seq from patient PDAC tumor,our results revealed that these dysregulated miRNAs were closely associated with extracellular matrix(ECM)remodeling,cell-ECM communication,epithelial-mesenchymal transition,as well as immunosuppression orchestrated by different cellular components of TME.The findings of this study could assist the development of miRNA-based stromal targeting biomarkers or therapy for PDAC patients.

HDAC inhibitors improve CRISPR-mediated HDR editing efficiency in iPSCs

Genome-edited human induced pluripotent stem cells(iPSCs)hold great promise for therapeutic applications.However,low editing efficiency has hampered the applications of CRISPR-Cas9 technology in creating knockout and homology-directed repair(HDR)-edited iPSC lines,particularly for silent genes.This is partially due to chromatin compaction,inevitably limiting Cas9 access to the target DNA.Among the six HDAC inhibitors we examined,vorinostat,or suberoylanilide hydroxamic acid(SAHA),led to the highest HDR efficiency at both open and closed loci,with acceptable toxicity.HDAC inhibitors equally increased non-homologous end joining(NHEJ)editing efficiencies(~50%)at both open and closed loci,due to the considerable HDAC inhibitor-mediated increase in Cas9 and sgRNA expression.However,we observed more substantial HDR efficiency improvement at closed loci relative to open chromatin(2.8 vs.1.7-fold change).These studies provide a new strategy for HDRediting of silent genes in iPSCs.

Aminoflavone upregulates putative tumor suppressor miR-125b-2-3p to inhibit luminal A breast cancer stem cell-like properties

Metastatic breast cancer is incurable and often due to breast cancer stem cell(CSC)-mediated self-renewal.We previously determined that the aryl hydrocarbon receptor(AhR)agonist aminoflavone(AF)inhibits the expression of the CSC biomarkerα6-integrin(ITGA6)to disrupt the formation of luminal(hormone receptor-positive)mammospheres(3D breast cancer spheroids).In this study,we performed miRNA-sequencing analysis of luminal A MCF-7 mammospheres treated with AF to gain further insight into the mechanism of AF-mediated anti-cancer and anti-breast CSC activity.AF significantly induced the expression of>70 microRNAs(miRNAs)including miR125b-2–3p,a predicted stemness gene regulator.AF-mediated miR125b-2–3p induction was validated in MCF-7 mammospheres and cells.miR125b-2–3p levels were low in breast cancer tissues irrespective of subtype compared to normal breast tissues.While miR125b-2–3p levels were low in MCF-7 cells,they were much lower in AHR100 cells(MCF-7 cells made unresponsive to AhR agonists).The miR125b-2–3p mimic decreased,while the antagomiR125b-2–3p increased the expression of stemness genes ITGA6 and SOX2 in MCF-7 cells.In MCF-7 mammospheres,the miR125b-2–3p mimic decreased only ITGA6 expression although the antagomiR125b-2–3p increased ITGA6,SOX2 and MYC expression.AntagomiR125b-2–3p reversed AF-mediated suppression of ITGA6.The miR125b-2–3p mimic decreased proliferation,migration,and mammosphere formation while the antagomiR125b-2–3p increased proliferation and mammosphere formation in MCF-7 cells.The miR125b-2–3p mimic also inhibited proliferation,mammosphere formation,and migration in AHR100 cells.AF induced AhR-and miR125b2-3p-dependent anti-proliferation,anti-migration,and mammosphere disruption in MCF-7 cells.Our findings suggest that miR125b-2–3p is a tumor suppressor and AF upregulates miR125b-2–3p to disrupt mammospheres via mechanisms that rely at least partially on AhR in luminal A breast cancer cells.

DNA methylome study of human cerebellar tissues identified genes and pathways possibly involved in essential tremor

Background:Essential tremor(ET)is a neurological syndrome of unknown origin with poorly understood etiology and pathogenesis.It is suggested that the cerebellum and its tracts may be involved in the pathophysiology of ET.DNA methylome interrogation of cerebellar tissue may help shine some light on the understanding of the mechanism of the development of ET.Our study used postmortem human cerebellum tissue samples collected from 12 ET patients and 11 matched non-ET controls for DNA methylome study to identify differentially methylated genes in ET.Results:Using Nugen’s Ovation reduced representation bisulfite sequencing(RRBS),we identified 753 genes encompassing 938 CpG sites with significant differences in DNA methylation between the ET and the control group.Identified genes were further analyzed with Ingenuity Pathway Analysis(IPA)by which we identified certain significant pathways,upstream regulators,diseases and functions,and networks associated with ET.Conclusions:Our study provides evidence that there are significant differences in DNA methylation patterns between the ET and control samples,suggesting that the methylation alteration of certain genes in the cerebellum may be associated with ET pathogenesis.The identified genes allude to the GABAergic hypothesis which supports the notation that ET is a neurodegenerative disease,particularly involving the cerebellum.

Spaceflight decelerates the epigenetic clock orchestrated with a global alteration in DNA methylome and transcriptome in the mouse retina

Astronauts exhibit an assortment of clinical abnormalities in their eyes during long-duration spaceflight.The purpose of this studywas to determinewhether spaceflight induces epigenomic and transcriptomic reprogramming in the retina or alters the epigenetic clock.The mice were flown for 37 days in animal enclosure modules on the International Space Station;ground-based control animals weremaintained under similar housing conditions.Mouse retinas were isolated and both DNA methylome and transcriptome were determined by deep sequencing.We found that a large number of genes were differentially methylated with spaceflight,whereas there were fewer differentially expressed genes at the transcriptome level.Several biological pathways involved in retinal diseases such as macular degeneration were significantly altered.Our results indicated that spaceflight decelerated the retinal epigenetic clock.This study demonstrates that spaceflight impacts the retina at the epigenomic and transcriptomic levels,and such changes could be involved in the etiology of eye-related disorders among astronauts.

Computational molecular docking and virtual screening revealed promising SARS-CoV-2 drugs

The pandemic of novel coronavirus disease 2019(COVID-19)has rampaged the world,with more than 58.4 million confirmed cases and over 1.38 million deaths across the world by 23 November 2020.There is an urgent need to identify effective drugs and vaccines to fight against the virus.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)belongs to the family of coronaviruses consisting of four structural and 16 non-structural proteins(NSP).Three non-structural proteins,main protease(Mpro),papain-like protease(PLpro),and RNAdependent RNA polymerase(RdRp),are believed to have a crucial role in replication of the virus.We applied computational ligand-receptor binding modeling and performed comprehensive virtual screening on FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina,Glide,and rDock.Our computational studies identified six novel ligands as potential inhibitors against SARS-CoV-2,including antiemetics rolapitant and ondansetron for Mpro;labetalol and levomefolic acid for PLpro;and leucal and antifungal natamycin for RdRp.Molecular dynamics simulation confirmed the stability of the ligand-protein complexes.The results of our analysis with some other suggested drugs indicated that chloroquine and hydroxychloroquine had high binding energy(low inhibitory effect)with all three proteins—Mpro,PLpro,and RdRp.In summary,our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 inhibitors that may be considered for further clinical studies.

Inhibitory activity of medicinal mushroom Ganoderma lucidum on colorectal cancer by attenuating inflammation

The medicinal mushroom Ganoderma lucidum(GL,Reishi or Lingzhi)exhibits an inhibitory effect on cancers.However,the underlying mechanism of the antitumor activity of GL is not fully understood.In this study,we characterized the gene networks regulated by a commercial product of GL containing a mixture of spores and fruiting bodies namely“GLSF”,in colorectal carcinoma.We found that in vitro co-administration of GLSF extract at non-toxic concentrations significantly potentiated growth inhibition and apoptosis induced by paclitaxel in CT26 and HCT-15 cells.GLSF inhibited NF-κB promoter activity in HEK-293 cells but did not affect the function of P-glycoprotein in K562/DOX cells.Furthermore,we found that when mice were fed a modified diet containing GLSF for 1 month prior to the CT26 tumor cell inoculation,GLSF alone or combined with Nab-paclitaxel markedly suppressed tumor growth and induced apoptosis.RNA-seq analysis of tumor tissues derived from GLSF-treated mice identified 53 differentially expressed genes compared to normal tissues.Many of the GLSFdown-regulated geneswere involved in NF-κB-regulated inflammation pathways,such as IL-1β,IL-11 and Cox-2.Pathway enrichment analysis suggested that several inflammatory pathways involving leukocytemigration and adhesion were most affected by the treatment.Upstream analysis predicted activation of multiple tumor suppressors such asα-catenin and TP53 and inhibition of critical inflammatory mediators.“Cancer”was the major significantly inhibited biological effect of GLSF treatment.These results demonstrate that GLSF can improve the therapeutic outcome for colorectal cancer through a mechanism involving suppression of NF-κB-regulated inflammation and carcinogenesis.

Vegetarian diets,circulating miRNA expression and healthspan in subjects living in the Blue Zone

A long-term vegetarian diet plays a role in the longevity and maintenance of the healthspan,but the underlying mechanisms for these observations are largely unknown.Particularly,it is not known whether a longterm vegetarian dietary pattern may affect the circulating miRNA expression in such a way as to modulate the healthspan.The Adventist Health Study-2(AHS-2)cohort includes a large number of older adults who primarily follow vegetarian dietary patterns and reside in Loma Linda,California,one of five“Blue Zones”in the world in which a higher proportion of the population enjoys a longer than average lifespan.We performedmiRNA-seq in 96 subjects selected from the AHS-2 cohort with different dietary patterns.We identified several differentially expressed miRNAs between vegetarians and non-vegetarians,which are involved in immune response and cytokine signaling,cell growth and proliferation as well as age-related diseases such as cardiovascular diseases and neurodegenerative diseases.Overall,our study showed that a vegetarian diet modulates aging-associated circulating miRNAs in a sex-dependent manner of differential expression for certain miRNAs,which may be related in a beneficial manner to the healthspan.Further investigation is needed to validate these miRNAs as potential biomarkers for diet-modulated longevity in humans.