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The quadrilateral reassortant IAV A/(H1N1) pdm09 is the pathogen responsible for the first influenza pandemic of the 21st century. The virus spread rapidly among hosts causing high mortality within human population. Efficient accumulation of virions is known to be important for the rapid transmission of virus. However, the mechanism by which A/(H1N1) pdm09 promotes its rapid replication has not been fully studied. Here, we found the NS1 of A/(H1N1) pdm09 mediated complete macroautophagy/autophagy, and then facilitated self-replication, which may be associated with the more rapid spread of this virus compared with H1N1WSN and H3N8JL89. We found that the promotion of self-replication could be mainly attributed to NS1pdm09 strongly antagonizing the inhibitory effect of LRPPRC on autophagy. The interaction between NS1pdm09 and LRPPRC competitively blocked the interaction of LRPPRC with BECN1/Beclin1, resulting in increased recruitment of BECN1 for PIK3C3 (phosphatidylinositol 3-kinase catalytic subunit type 3) and induction of the initiation of autophagy. In conclusion, we uncover the unique molecular mechanism by which A/(H1N1) pdm09 utilizes autophagy to promote self-replication, and we provide theoretical basics for the analysis of the etiological characteristics of the A/(H1N1) pdm09 pandemic and the development of anti-influenza drugs and vaccines. Abbreviations: 293T: human embryonic kidney 293 cells; 293T_LRPPRC: stable LRPPRC expression 293T cells; 3-MA: 3-methyladenine; A549 cells: human non-small cell lung cancer cells; AA: amino acid; ACTB: actin beta; BECN1: beclin 1; BECN1 KO: BECN1 knockout 293T cells; Cal: calyculin A; Co-IP: co-immunoprecipitation; CQ: chloroquine; DC: dendritic cell; Eug: eugenol; GFP: green fluorescent protein; HA: hemagglutinin; HIV: human immunodeficiency virus; IAVs: Influenza A viruses; IFN: interferon; JL89: A/equine/Jilin/1/1989 (H3N8); LAMP2: lysosomal associated membrane protein 2; LRPPRC: leucine rich pentatriicopeptide repeat containing; LRPPRC KO: LRPPRC knockout 293T cells; M2: matrix 2; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MDCK: Madin-Darby canine kidney cells; MOI: multiplicity of infection; MS: mass spectrometry; NP: nucleoprotein; NS1: non-structural protein 1; NS1JL89: non-structural protein 1 of A/equine/Jilin/1/1989 (H3N8); NS1pdm09: non-structural protein 1 of A/(H1N1) pdm09; NS1SC09: non-structural protein 1 of A/Sichuan/2009 (H1N1); NS1WSN: non-structural protein 1 of A/WSN/1933 (H1N1); PB1: polymerase basic protein 1; PB1-F2: alternate reading frame discovered in PB1 gene segment; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PR8: A/PR/8/34 (H1N1); Rapa: rapamycin; RFP: red fluorescent protein; SC09: A/Sichuan/2009 (H1N1); SQSTM1/p62: sequestosome 1; STK4/MST1: serine/threonine kinase 4; TEM: transmission electron microscopy; TOMM20: translocase of outer mitochondrial membrane 20; WHO: World Health Organization; WSN: A/WSN/1933 (H1N1); WSN-NS1JL89: WSN recombinant strain in which NS1 was replaced with that of JL89; WSN-NS1SC09: WSN recombinant strain in which NS1 was replaced with that of SC09.

BACKGROUND Clinical electronic medical records (EMRs) contain important information on patients’ anatomy, symptoms, examinations, diagnoses, and medications. Large-scale mining of rich medical information from EMRs will provide notable reference value for medical research. With the complexity of Chinese grammar and blurred boundaries of Chinese words, Chinese clinical named entity recognition (CNER) remains a notable challenge. Follow-up tasks such as medical entity structuring, medical entity standardization, medical entity relationship extraction, and medical knowledge graph construction largely depend on medical named entity recognition effects. A promising CNER result would provide reliable support for building domain knowledge graphs, knowledge bases, and knowledge retrieval systems. Furthermore, it would provide research ideas for scientists and medical decision-making references for doctors and even guide patients on disease and health management. Therefore, obtaining excellent CNER results is essential. OBJECTIVE We aimed to propose a Chinese CNER method to learn semantics-enriched representations for comprehensively enhancing machines to understand deep semantic information of EMRs by using multisemantic features, which makes medical information more readable and understandable. METHODS First, we used Robustly Optimized Bidirectional Encoder Representation from Transformers Pretraining Approach Whole Word Masking (RoBERTa-wwm) with dynamic fusion and Chinese character features, including 5-stroke code, Zheng code, phonological code, and stroke code, extracted by 1-dimensional convolutional neural networks (CNNs) to obtain fine-grained semantic features of Chinese characters. Subsequently, we converted Chinese characters into square images to obtain Chinese character image features from another modality by using a 2-dimensional CNN. Finally, we input multisemantic features into Bidirectional Long Short-Term Memory with Conditional Random Fields to achieve Chinese CNER. The effectiveness of our model was compared with that of the baseline and existing research models, and the features involved in the model were ablated and analyzed to verify the model’s effectiveness. RESULTS We collected 1379 Yidu-S4K EMRs containing 23,655 entities in 6 categories and 2007 self-annotated EMRs containing 118,643 entities in 7 categories. The experiments showed that our model outperformed the comparison experiments, with F1-scores of 89.28% and 84.61% on the Yidu-S4K and self-annotated data sets, respectively. The results of the ablation analysis demonstrated that each feature and method we used could improve the entity recognition ability. CONCLUSIONS Our proposed CNER method would mine the richer deep semantic information in EMRs by multisemantic embedding using RoBERTa-wwm and CNNs, enhancing the semantic recognition of characters at different granularity levels and improving the generalization capability of the method by achieving information complementarity among different semantic features, thus making the machine semantically understand EMRs and improving the CNER task accuracy.

The innate immune restriction factor SAMHD1 can inhibit diverse viruses in myeloid cells. Mechanistically, SAMHD1 inhibits lentiviral replication including HIV-1 by depleting the nucleotide pool to interfere with their reverse transcription. Equine infectious anemia virus (EIAV) is an ancient lentivirus that preferentially attacks macrophages. However, the mechanism by which EIAV successfully establishes infection in macrophages with functional SAMHD1 remains unclear. Here, we demonstrate that while equine SAMDH1 can limit EIAV replication in equine macrophages at the reverse transcription stage, the antiviral effect is counteracted by the well-known transcriptional regulator Rev, which downregulates equine SAMHD1 through the lysosomal pathway. Remarkably, Rev hijacks BECN1 (beclin 1) and PIK3C3 to mediate SAMHD1 degradation in a canonical macroautophagy/autophagy-independent pathway. Our study illustrates that equine lentiviral Rev possesses important functions in evading cellular innate immunity in addition to its RNA regulatory function, and may provide new insights into the co-evolutionary arms race between SAMHD1 and lentiviruses. Abbreviations:3-MA: 3-methyladenine; AA: amino acid; ACTB: actin beta; AD: activation domain; ATG: autophagy related; Baf A1: bafilomycin A1; BD: binding domain; BECN1: beclin 1; BH3: BCL2-homology-3 domain; BiFC: bimolecular fluorescence complementation; CCD: coiled-coil domain; class III PtdIns3K: class III phosphatidylinositol 3-kinase; CQ: chloroquine; Co-IP: co-immunoprecipitation; dNTPase: dGTP-stimulated deoxynucleoside triphosphate triphosphohydrolase; ECD: evolutionarily conserved domain; EIAV: equine infectious anemia virus; eMDMs: equine monocyte-derived macrophages; GFP: green fluorescent protein; HD: histidine-aspartic; HIV-1: human immunodeficiency virus-1; hpi: hours post infection; hpt: hours post transfection; KO: knockout; LAMP2: lysosomal associated membrane protein 2; LMB: leptomycin B; PMA: phorbol 12-myristate 13-acetate; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; ND: unknown non-essential domain; NES: nuclear export signal; NLS: localization signal; NS: statistically non-significant; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; RBD: RNA binding domain; RT: reverse transcriptase; siRNAs: small interfering RNAs; SAMHD1: SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1; SIV: simian immunodeficiency virus; VN: C-terminal residues of Venus 174 to 238; VC: N-terminal residues 2 to 173 of Venus

We present an all-dielectric chiral photonic crystal that guides the propagation of electromagnetic waves without backscattering for dual bands. The chiral photonic crystal unit cell is composed of four dielectric cylinders with increasing inner diameter clockwise or anticlockwise, which leads to chirality. It is demonstrated that the proposed chiral photonic crystal can generate dual band gaps in the gigahertz frequency range and has two types of edge states, which is similar to topologically protected edge states. Hence, the interface formed by the proposed 2D chiral photonic crystal can guide the propagation of electromagnetic waves without backscattering, and this complete propagation is immune to defects (position disorder or frequency disorder). To illustrate the applicability of the findings in communication systems, we report a duplexer and a power divider based on the presented all-dielectric chiral photonic crystal.

Broadband topological metamaterials hold the key for designing the next generation of integrated photonic platforms and microwave devices given their protected back-scattering-free and unidirectional edge states, among other exotic properties. However, synthesizing such metamaterial has proven challenging. Here, a broadband bandgap (relative bandwidth of more than 43%) Valley-Hall topological metamaterial with deep subwavelength thickness is proposed. The present topological metamaterial is composed of three layers printed circuit boards whose total thickness is 1.524 mm ≈ λ/100. The topological phase transition is achieved by introducing an asymmetry parameter δr. Three mechanically reconfigurable edge states can be obtained by varying interlayer displacement. Their robust transmission is demonstrated through two kinds of waveguide domain walls with cavities and disorders. Exploiting the proposed topological metamaterial, a six-way power divider is constructed and measured as a proof-of-concept of the potential of the proposed technology for future electromagnetic devices.&nbsp

Anaerobic membrane bioreactor (AnMBR) is considered an efficient technique for kitchen wastewater treatment; however, membrane fouling restricts their applicability. In this study, a novel AnMBR with an Fe anode and Ti membrane cathode (electro-AnMBR) was constructed. The reactor exhibited good performance in pollutant removal and antifouling in kitchen wastewater treatment. Compared with the traditional AnMBR, the electro-AnMBR increased phosphate removal by approximately 55% and reduced transmembrane pressure (TMP) by 50%. Coagulation from the Fe

In recent years, in order to increase the capacity and scalability of intra-datacenter (DC) transmission, the optical frequency comb (OFC) source has been considered promising to replace discrete lasers, aiming to reduce the cost of wavelength division multiplexing (WDM) transmission within DC. In this paper, an OFC based coherent architecture is proposed. An OFC, in the receiver side, is split by a splitter with a uniform power ratio and separately used as local oscillators (LOs) to detect the demultiplexed signals. The signal spectrum is copied onto every tone of the LO-OFC, and a large frequency offset (FO) tolerance is achieved. In addition, the required ADC sampling rate is the same as a system without FO. Extensive simulations are conducted. In the simulated coherent WDM transmission system, a 3-tone-OFC is used to provide 3 carriers, and an 11-tone-OFC is split and used to provide LO-OFCs. For a 64GBd polarization multiplexing 16 quadrature amplitude modulation (PM-16QAM) WDM transmission, the tolerances of FO are up to about ±0.3THz and ±0.374THz for the 1st/3rd signal, and the 2nd signal, respectively, below the pre-forward error correction (FEC) bit error rate (BER) level of 1.25×10−2. Moreover, the maximum tolerance of FO linearly increases with the number of effective tones in LO-OFC. Further, extensive experiments with back-to-back connection are conducted to verify the performance. The tolerance of FO is up to >36 GHz for 36GBd PM-16QAM transmission with a 3-tone-LO-OFC below the BER level of 1.25×10−2. The proposed OFC based coherent architecture is a promising solution for intra-DC interconnections with a large FO.

Background: Pituitary adenoma is one of the most common central nervous system tumors. The diagnosis and treatment of pituitary adenoma remain very difficult. Misdiagnosis and recurrence often occur, and experienced neurosurgeons are in serious shortage. A knowledge graph can help interns quickly understand the medical knowledge related to pituitary tumor. Objective: The aim of this study was to develop a data fusion method suitable for medical data using data of pituitary adenomas integrated from different sources. The overall goal was to construct a knowledge graph for pituitary adenoma (KGPA) to be used for knowledge discovery. Methods: A complete framework suitable for the construction of a medical knowledge graph was developed, which was used to build the KGPA. The schema of the KGPA was manually constructed. Information of pituitary adenoma was automatically extracted from Chinese electronic medical records (CEMRs) and medical websites through a conditional random field model and newly designed web wrappers. An entity fusion method is proposed based on the head-and-tail entity fusion model to fuse the data from heterogeneous sources. Results: Data were extracted from 300 CEMRs of pituitary adenoma and 4 health portals. Entity fusion was carried out using the proposed data fusion model. The F1 scores of the head and tail entity fusions were 97.32% and 98.57%, respectively. Triples from the constructed KGPA were selected for evaluation, demonstrating 95.4% accuracy. Conclusions: This paper introduces an approach to fuse triples extracted from heterogeneous data sources, which can be used to build a knowledge graph. The evaluation results showed that the data in the KGPA are of high quality. The constructed KGPA can help physicians in clinical practice.

BACKGROUND Licensed drugs may cause unexpected adverse reactions in patients, resulting in morbidity, risk of mortality, therapy disruptions, and prolonged hospital stays. Officially approved drug package inserts list the adverse reactions identified from randomized controlled clinical trials with high evidence levels and worldwide postmarketing surveillance. Formal representation of the adverse drug reaction (ADR) enclosed in semistructured package inserts will enable deep recognition of side effects and rational drug use, substantially reduce morbidity, and decrease societal costs. OBJECTIVE This paper aims to present an ontological organization of traceable ADR information extracted from licensed package inserts. In addition, it will provide machine-understandable knowledge for bioinformatics analysis, semantic retrieval, and intelligent clinical applications. METHODS Based on the essential content of package inserts, a generic ADR ontology model is proposed from two dimensions (and nine subdimensions), covering the ADR information and medication instructions. This is followed by a customized natural language processing method programmed with Python to retrieve the relevant information enclosed in package inserts. After the biocuration and identification of retrieved data from the package insert, an ADR ontology is automatically built for further bioinformatic analysis. RESULTS We collected 165 package inserts of quinolone drugs from the National Medical Products Administration and other drug databases in China, and built a specialized ADR ontology containing 2879 classes and 15,711 semantic relations. For each quinolone drug, the reported ADR information and medication instructions have been logically represented and formally organized in an ADR ontology. To demonstrate its usage, the source data were further bioinformatically analyzed. For example, the number of drug-ADR triples and major ADRs associated with each active ingredient were recorded. The 10 ADRs most frequently observed among quinolones were identified and categorized based on the 18 categories defined in the proposal. The occurrence frequency, severity, and ADR mitigation method explicitly stated in package inserts were also analyzed, as well as the top 5 specific populations with contraindications for quinolone drugs. CONCLUSIONS Ontological representation and organization using officially approved information from drug package inserts enables the identification and bioinformatic analysis of adverse reactions caused by a specific drug with regard to predefined ADR ontology classes and semantic relations. The resulting ontology-based ADR knowledge source classifies drug-specific adverse reactions, and supports a better understanding of ADRs and safer prescription of medications.

A subcarrier-pairing entropy loading (SubP-EL) scheme with fairly low complexity is proposed for digital subcarrier-multiplexing (SCM) systems with colored signal-to-noise ratio (SNR) distributions. With the constraint of the target entropy, SubP-EL iteratively optimizes the entropy of subcarriers in pair. After convergence, SubP-EL can approach the optimal performance which is evaluated in simulations and experiments by comparison with the brute-force search method. Meanwhile the complexity of SubP-EL is significantly reduced compared with the brute-force search. In particular, in an 8-subcarrier system with five different SNRs, the complexity of SubP-EL is reduced by approximately a factor of 764, 95 and 13 with the entropy granularities of 0.05 bits/2D-symbol, 0.1 bits/2D-symbol and 0.2 bits/2D-symbol, respectively. The performance of SubP-EL is evaluated in simulations and experiments. In the experiments with 345 km fiber transmissions, the average NGMI gain of SubP-EL over the system without entropy loading is 0.0286 for different optical filtering cases.

BACKGROUND Alzheimer disease (AD) is a common and fatal subtype of dementia that remains a challenge to diagnose and treat. This study aimed to identify potential biomarkers that influence the prognosis of AD. MATERIAL AND METHODS A total of 6 gene expression profiles from the Gene Expression Omnibus (GEO) database were assessed for their potential as AD biomarkers. We identified differentially expressed genes (DEGs) using the prediction analysis for microarray (PAM) algorithm and obtained hub genes through the analysis of the protein-protein interaction (PPI) network and module analysis. RESULTS We identified 6 gene expression profiles from the GEO database and assessed their potential as AD biomarkers. Shared gene sets were extracted and integrated into large expression profile matrices. We identified 2514 DEGs including 68 upregulated- and 2446 downregulated genes through analysis of the limma package. We screened 379 significant DEGs including 68 upregulated and 307 downregulated genes for their ability to distinguish AD from control samples using PAM algorithm. Functional enrichment of the 379 target genes was produced from Database for Annotation, Visualization and Integrated Discovery.(DAVID) and included histone function, beta receptor signaling, cell growth, and angiogenesis. The downregulated genes were significantly enriched in MAPK signaling, synaptic signaling, neuronal apoptosis and AD associated pathways. Upon analysis of the PPI network, 32 hub genes including ENO2, CCT2, CALM2, ACACB, ATP5B, MDH1, and PP2CA were screened. Of these hub genes, NFKBIA and ACACB were upregulated and 29 genes were downregulated in AD patients. CONCLUSIONS We screened 379 significant DEGs as potential biomarkers of AD using PAM and obtained 32 hub genes through PPI network and module analysis. These findings reveal new potential AD biomarkers with prognostic and therapeutic value.

A transmitter (Tx) IQ mismatch compensation and monitoring scheme based on post-equalization is proposed for subcarrier-multiplexing systems. The estimation errors of power and phase mismatch are less than 0.1 dB and 0.3 degree, respectively. © 2020 The Author(s)

Lentiviruses harbour high genetic variability for efficient evasion from host immunity. An attenuated equine infectious anaemia (EIA) vaccine was developed decades ago in China and presented remarkably robust protection against EIA. The vaccine was recently proven to have high genomic diversity, particular in env. However, how and to what extent the high env diversity relates to immune protection remains unclear. In this study, we compared immune protections and responses of three groups of horses stimulated by the high-diversity vaccine EIAV_HD, a single molecular clone of the vaccine EIAV_LD with low env diversity, as well as a constructed vaccine strain EIAV_MD with moderate env diversity. The disparity of virus-host interactions between three env diversity-varied groups (5 horses in each group) was evaluated using clinical manifestation, pathological scores, and env-specific antibody. We found the highest titres of env antibodies (Abs) or neutralizing Abs (nAbs) in the EIAV_HD group, followed by the EIAV_MD group, and the lowest titres in the EIAV_LD group (Penv diversity-related linear relationship was observed in the clinical manifestations and pathological changes. This diversity-dependent disparity in changes between the three groups was more distinct after immunosuppression, suggesting that env diversity plays an important role in protection under low host immunocompetence. In summary, inoculation with vaccines with higher genetic diversity could present broader and more efficient protection. Our findings strongly suggest that an abundance of Env antigens are required for efficient protection against lentiviruses.

A joint power optimization method is proposed for the downlink in point-to-multipoint structure based on digital subcarriers. 2.3 dB power budget gain was achieved experimentally with eight 4 GBaud 16QAM subcarriers with a distance difference of 24 km. © 2020 The Author(s)

Terminology facilitates consistent use and semantic integration of heterogeneous, multimodal data within and across domains. This paper presents TBench (Termilology Workbench) for multilingual terminology editing and development within a distributed environment. TBench is a web-service Java tool consisting of two main functionalities that are knowledge construction (i.e.extended model based on ISO25964, batch reusing and constructing multilingual concept hierarchy and relationships) and collaborative control in order to achieve custom extensions, reuse, multilingual alignment, integration and refactoring.

This work describes the design and building of a Chinese clinical terminology (called CCTS). The terminology is similar to an ontology, and will promote the use of Chinese clinical data, such as indexing, retrieval and exchange. The terminology is a TOPL concept framework, which integrates hierarchical structures of Chinese and interenational reference terminology standards for health. Our framework includes 14 subtrees, 2286 classes and 65 relationships.

Human myxovirus resistance protein 2 (huMxB) has been shown to be a determinant type I interferon (IFN)-induced host factor involved in the inhibition of human immunodeficiency virus type 1 (HIV-1) as well as many other primate lentiviruses. This blocking occurs after the reverse transcription of viral RNA and ahead of integration into the host DNA, which is closely connected to the ability of the protein to bind the viral capsid. To date, Mx2s derived from nonprimate animals have shown no capacity for HIV-1 suppression. In this study, we examined the restrictive effect of equine Mx2 (eqMx2) on both equine infectious anemia virus (EIAV) and HIV-1 and investigated possible mechanisms for its specific function. We demonstrated that IFN-α/β upregulates the expression of eqMx2 in equine monocyte-derived macrophages (eMDMs). The overexpression of eqMx2 significantly suppresses the replication of EIAV, HIV-1, and simian immunodeficiency viruses (SIVs) but not that of murine leukemia virus (MLV). The knockdown of eqMx2 transcription weakens the inhibition of EIAV replication by type I interferon. Interestingly, data from immunofluorescence assays suggest that the subcellular localization of eqMx2 changes following virus infection, from being dispersed in the cytoplasm to being accumulated at the nuclear envelope. Furthermore, eqMx2 blocks the nuclear uptake of the proviral genome by binding to the viral capsid. The N-terminally truncated mutant of eqMx2 lost the ability to bind the viral capsid as well as the restriction effect for lentiviruses. These results improve our understanding of the Mx2 protein in nonprimate animals.IMPORTANCE Previous research has shown that the antiviral ability of Mx2s is confined to primates, particularly humans. EIAV has been shown to be insensitive to restriction by human MxB. Here, we describe the function of equine Mx2. This protein plays an important role in the suppression of EIAV, HIV-1, and SIVs. The antiviral activity of eqMx2 depends on its subcellular location as well as its capsid binding capacity. Our results showed that following viral infection, eqMx2 changes its original cytoplasmic location and accumulates at the nuclear envelope, where it binds to the viral capsid and blocks the nuclear entry of reverse-transcribed proviral DNAs. In contrast, huMxB does not bind to the EIAV capsid and shows no EIAV restriction effect. These studies expand our understanding of the function of the equine Mx2 protein.

We evaluated the impact of early embryonic deletion of huntingtin (htt) from pyramidal neurons on cortical development, cortical neuron survival and motor behavior, using a cre-loxP strategy to inactivate the mouse htt gene (Hdh) in emx1-expressing cell lineages. Western blot confirmed substantial htt reduction in cerebral cortex of these Emx-httKO mice, with residual cortical htt in all likelihood restricted to cortical interneurons of the subpallial lineage and/or vascular endothelial cells. Despite the loss of htt early in development, cortical lamination was normal, as revealed by layer-specific markers. Cortical volume and neuron abundance were, however, significantly less than normal, and cortical neurons showed reduced brain-derived neurotrophic factor (BDNF) expression and reduced activation of BDNF signaling pathways. Nonetheless, cortical volume and neuron abundance did not show progressive age-related decline in Emx-httKO mice out to 24 months. Although striatal neurochemistry was normal, reductions in striatal volume and neuron abundance were seen in Emx-httKO mice, which were again not progressive. Weight maintenance was normal in Emx-httKO mice, but a slight rotarod deficit and persistent hyperactivity were observed throughout the lifespan. Our results show that embryonic deletion of htt from developing pallium does not substantially alter migration of cortical neurons to their correct laminar destinations, but does yield reduced cortical and striatal size and neuron numbers. The Emx-httKO mice were persistently hyperactive, possibly due to defects in corticostriatal development. Importantly, deletion of htt from cortical pyramidal neurons did not yield age-related progressive cortical or striatal pathology.

We have previously reported that mild TBI created by focal left-side cranial blast in mice produces widespread axonal injury, microglial activation, and a variety of functional deficits. We have also shown that these functional deficits are reduced by targeting microglia through their cannabinoid type-2 (CB2) receptors using two-week daily administration of the CB2 inverse agonist SMM-189. CB2 inverse agonists stabilize the G-protein coupled CB2 receptor in an inactive conformation, leading to increased phosphorylation and nuclear translocation of the cAMP response element binding protein (CREB), and thus bias activated microglia from a pro-inflammatory M1 to a pro-healing M2 state. In the present study, we showed that SMM-189 boosts nuclear pCREB levels in microglia in several brain regions by 3 days after TBI, by using pCREB/CD68 double immunofluorescent labeling. Next, to better understand the basis of motor deficits and increased fearfulness after TBI, we used unbiased stereological methods to characterize neuronal loss in cortex, striatum, and basolateral amygdala (BLA) and assessed how neuronal loss was affected by SMM-189 treatment. Our stereological neuron counts revealed a 20% reduction in cortical and 30% reduction in striatal neurons bilaterally at 2-3 months post blast, with SMM-189 yielding about 50% rescue. Loss of BLA neurons was restricted to the blast side, with 33% of Thy1+ fear-suppressing pyramidal neurons and 47% of fear-suppressing parvalbuminergic (PARV) interneurons lost, and Thy1-negative fear-promoting pyramidal neurons not significantly affected. SMM-189 yielded 50-60% rescue of Thy1+ and PARV neuron loss in BLA. Thus, fearfulness after mild TBI may result from the loss of fear-suppressing neuron types in BLA, and SMM-189 may reduce fearfulness by their rescue. Overall, our findings indicate that SMM-189 rescues damaged neurons and thereby alleviates functional deficits resulting from TBI, apparently by selectively modulating microglia to the beneficial M2 state. CB2 inverse agonists thus represent a promising therapeutic approach for mitigating neuroinflammation and neurodegeneration.

Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25-40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50-60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits.

Acoustic emission sensors are the most important part of an acoustic emission detection system, which directly determines the validity and accuracy of the detection result. In order to improve the reliability of acoustic emission test results, the sensor’s sensitivity must be calibrated ahead of time. This chapter investigates the face-to-face secondary calibration method and presents the laser vibrometer primary calibration method for acoustic emission sensor sensitivity. A sensor sensitivity calibration system was built. Calibration experiments have been carried out. Finally, measurement uncertainty was analyzed.

For analyzing response characteristics of ultrasonic transducer under different excitation pulses, response function for ultrasonic transducer must be known. In this paper, the transmission transfer function for an ultrasonic transducer is developed based on a two-port network with KLM model. Transducer response characteristics under different excitation pulses are analyzed and compared by MATLAB simulation. The method to measure the impulse response with a laser interferometer is applied. The experimental results are compared with the theoretical ones. Results showed that the amplitude of ultrasonic transducer impulse response has a relationship with the type of excitation pulses.

Impedance is one of the most important characteristics of ultrasonic transducer. This paper focuses on the measurement method of ultrasonic transducer impedance, studying many methods mentioned in domestic and international standard. The voltage-current method is proposed in this paper. What's more, a measurement system based on this method is constructed. Then lots of experiments are performed to prove this method. The result is compared with that measured by using the impedance analyzer, which proves that the voltage-current method can measure the transducer impedance correctly.

Ultrasonic nondestructive testing with characters of fine resolution and low cost has well been developed and widely applied in modern industrial world. The generation of high voltage pulse to excite the transducer has been a critical challenge in an ultrasonic testing system. In this paper a DC/DC converting circuit with an input of 12V and an output of 300V and -300V independently is introduced, so is a pulse generator with pulse width configured by a FPGA with parameters transmitted through a PCI bus by VC++ program. With different connection of the circuit, a positive unipolar pulse, a negative unipolar pulse, a monocycle bipolar pulse and a 2-cycle bipolar pulse can be generated respectively. Finally some pulse characters which may influence the excitation of the ultrasonic transducer are analyzed, the spectrum signature of each type is presented in the later part of this paper.

Acoustic field characteristic is a key factor of the ultrasonic transducer and many acoustic field measuring methods have been studied. However, nowadays hydrophone method which used to measure the acoustical field characteristic of ultrasonic transducer has been wildly used and accepted. This paper introduces an advanced measuring method to get the acoustic field characteristic of the phased array transducer by means of using hydrophone. A new acoustical field scanning method and a synchronization guarantee technique will be introduced. Some experiments have been performed and some interesting phenomena have been found. Then these phenomena have been analyzed and some conclusions have been infered.