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The pile responses induced by adjacent tunnel excavation have been a hot research topic in geotechnical engineering. Tunnel excavation may exert disturbance to the surrounding soil mass and then influence the adjacent pile foundations. In this paper, the random finite difference analysis considering the spatial variations of soil properties is conducted to explore the effect of tunnel excavation on the adjacent pile response by varying the distance of pile away from the tunnel centerline (D), the pile length (L), the pile diameter (dp), the tunnel depth (h), and the anisotropic ratio between the horizontal and the vertical scales of fluctuation (δx/δy). A set of pile response curves are developed to assess the influence of tunnel excavation on the adjacent passive pile foundations in spatially variable clays and provide guidelines for the tunnel excavation in the complex constructed environment.

In an urbanization process, infrastructure elements such as tunnels and deep excavations are widely used to service the development of cities. Owing to the lengthy geological processes of geomaterials and the limited availability of site-specific test data, soil and rock properties exhibiting spatial variability are frequently encountered in geological and geotechnical engineering. This paper presents a comprehensive review of the application of spatial variability in tunneling and deep excavation over the past 20 years. It is found that the spatial variability is generally modeled as a random field (RF) in finite element software, based on random field theory (RFT). This model has been widely used in the design, stability evaluation, and probabilistic analysis of tunnels and excavations. Previous works have proven that the performance of tunnels and deep excavations can be better captured by considering the spatial variability, as compared with conventional deterministic analysis methods. Nonetheless, current research still faces many factual scientific problems. Therefore, this paper also identifies some research gaps, as well as recommendations for further investigations.

In this paper, deterministic stability analyses for soil slopes reinforced with pile of different locations and lengths were conducted firstly to calculate the factor of safety through limit equilibrium method (LEM). Since the effect of inherent uncertainties as well as the spatial variability of soils cannot be reflected via the deterministic factor of safety, probabilistic stability analyses of slopes reinforced with pile in spatially constant soils and spatially variable soils were successively carried out, respectively. The failure probability was determined by random limit equilibrium method (RLEM) considering the influence of different pile locations, pile length and soil statistical parameters. The optimal locations along slope and length of pile were analyzed based on the reliability analyses results in spatially constant soils and spatially variable soils, which were inconsistent with the results via the traditional deterministic methods, with a lower probability of sliding failure. Finally, method was proposed to determine the minimum samples of simulation iterations for investigating the convergence of failure probability of soil slope reinforced with piles. The results revealed that the multiple potential sliding surfaces introduced by the installations of pile would result in the increased uncertainty of slope failures.

In this paper, we obtain two improved Amati correlations of the Gamma-Ray burst (GRB) data via a powerful statistical tool called copula. After calibrating, with the low-redshift GRB data, the improved Amati correlations based on a fiducial $\Lambda$CDM model with $\Omega_\mathrm{m0}=0.3$ and $H_0=70~\mathrm{km~s^{-1}Mpc^{-1}}$, and extrapolating the results to the high-redshift GRB data, we obtain the Hubble diagram of GRB data points. Applying these GRB data to constrain the $\Lambda$CDM model, we find that the improved Amati correlation from copula can give a result well consistent with $\Omega_\mathrm{m0}=0.3$, while the standard Amati and extended Amati correlations do not. This results suggest that when the improved Amati correlation from copula is used in the low-redshift calibration method, the GRB data can be regarded as a viable cosmological explorer. However, the Bayesian information criterion indicates that the standard Amati correlation remains to be favored mildly since it has the least model parameters. Furthermore, once the simultaneous fitting method rather than the low-redshift calibration one is used, there is no apparent evidence that the improved Amati correlation is better than the standard one. Thus, more works need to be done in the future in order to compare different Amati correlations., Comment: 15 pages, 5 figures, accepted for publication in ApJ

Knowledge of the uniaxial compressive responses of rock mass is crucial for evaluating the stability of rock pillar in underground engineering. The inherent spatial variabilities of rock ma...

The temporal synchronization of BOLD signals within white matter (WM) and between WM and grey matter (GM) exhibited intrinsic architecture and cognitive relevance. However, few studies examined the network property within- and between-tissue in Alzheimer’s disease (AD). The hub regions with high weighted degree (WD) were prone to the neuropathological damage of AD. To systematically investigate the changes of hubs within- and between-tissue functional networks in AD patients, we used the resting-state fMRI data of 30 AD patients and 37 normal older adults (NC) from the ADNI open database, and obtained four types of voxel-based WD metrics and four types of distant-dependent WD metrics (ddWD) based on a series of Euclidean distance ranges with a 20mm increment. We found that AD patients showed decreased within-tissue ddWD in the thalamic nucleus and increased between-tissue ddWD in the occipito-temporal cortex, posterior thalamic radiation, and sagittal stratum, compared to NC. We also found that AD patients showed the increased between-tissue FCs between the posterior thalamic radiation and occipito-temporal cortex, and between the sagittal stratum and the salience and executive networks. The dichotomy of decreased and increased ddWD metrics and their locations were consistent with previous studies on the neurodegnerative and compensatory mechanisms of AD, indicating that despite the disruptions, the brain still strived to compensate for the neural inefficiency by reorganizing functional circuits. Our findings also suggested the short-to-medium ranged ddWD metrics between WM and GM as useful biomarker to detect the compensatory changes of functional networks in AD.

This paper presents a simplified procedure to evaluate the failure probability of crossing tunnels considering the spatial variabilities of rock mass properties. Numerical package FLAC3D (Itasca, 2017) was adopted to carry out extensive parameter studies for crossing tunnels. Subsequently, two limit state functions have been developed via the logarithmic regression to estimate the global factor of safety as well as the induced maximum settlement of the existing tunnel. The developed surrogate models were implemented into the Excel First-Order Reliability Method (FORM) spreadsheet to calculate the ultimate limit state failure and the probability that the threshold maximum settlement value is exceeded. The variance reduction technique is incorporated into the FORM analysis for considering the spatial variabilities of rock mass properties. Based on the reliability results, a sensitivity analysis was carried out to determine the critical design factor in construction of crossing tunnel. The proposed method provides an effective way to evaluate the safety and serviceability of tunnelling perpendicularly beneath an existing tunnel in spatial variable rock mass.

Current transformer (CT) is wildly used in the power system. The resistance of CT to DC bias is important for the operation of power system. According to the J-A theory, the hysteresis loop of closed and air gapped core was simulated, and the magnetic properties of air gapped cores with different gap length were studied. Based on the simulink tools, the magnetization curve of core was simplified. Furthermore the simulation model was built for the error investigation of the CT with air gapped core. The angle difference and ratio difference were calculated for the CT with closed and air gapped cores in condition of DC bias. The addition of air gap has little effect on the maximum magnetic density of core. But it reduced the slope of the linear part of the magnetization curve, and the core cannot be easily saturated. The air gapped core can improve the error of the CT under DC bias.

Background: Traditional medical treatments are not effective for some patients with Tourette syndrome (TS). According to the literature, repetitive transcranial magnetic stimulation (rTMS) may be effective for the treatment of TS; however, different targets show different results.Objective: To assess the efficacy and safety of low-frequency rTMS in patients with TS, with the bilateral parietal cortex as the target.Methods: Thirty patients with TS were divided into two groups: active and sham groups. The active group was subjected to 0.5-Hz rTMS at 90% of resting motor threshold (RMT) with 1,200 stimuli/day/side, whereas the sham group was subjected to 0.5-Hz rTMS at 10% of RMT with 1,200 stimuli/day/side with changes in the coil direction. Both groups were bilaterally stimulated over the parietal cortex (P3 and P4 electrode sites) for 10 consecutive days. The symptoms of tics and premonitory urges were evaluated using the Yale Global Tic Severity Scale (YGTSS), Modified Scoring Method for the Rush Video-based Tic Rating Scale (MRVBTS), and Premonitory Urge for Tics Scale (PUTS) scores at baseline, the end of the 10-day treatment, 1 week after treatment, and 1 month after treatment.Results: At the end of the 10-day treatment, the YGTSS total, YGTSS motor tic, YGTSS phonic tic, MRVBTS, and PUTS scores in the active group significantly improved and improvements were maintained for at least 1 month.Conclusions: Low-frequency bilateral rTMS of the parietal cortex can markedly alleviate motor tics, phonic tics, and premonitory urges in patients with TS.

Objective This study aimed to explore a shorter and safer contralateral C7 transposition pathway for the treatment of central upper limb paralysis. Methods From July 2018 to March 2019, 10 patients with central upper limb paralysis underwent posterior cervical 7 nerve transposition. The age of these patients ranged within 31–58 years old (average: 44 years old). These patients comprised of eight male patients and two female patients. Nine patients had cerebral hemorrhage, and one patient had a cerebral infarction. Furthermore, nine patients presented with spastic paralysis of the upper limbs and one patient presented with nonspastic paralysis. The duration of plegia before the operation ranged from 6 to 60 months (average: 26 months). The surgical procedure included transposition of the contralateral cervical 7 nerve root via a posterior vertebral approach under general anesthesia, and the distal part of the contralateral cervical 7 nerve was anastomosed with the proximal part of the ipsilateral cervical 7 nerve. Results The length of the contralateral cervical 7 nerve was 5.16 ± 0.21 cm, which was directly anastomosed with the ipsilateral cervical 7 nerve. Neither case needed nerve transplantation. Most patients had temporary numbness in their healthy fingers, which all disappeared within three months. Up to now, the follow‐up results are as follows: The spasticity of the affected upper limbs in five patients is lower than that before the operation, the pain and temperature sensation of the affected upper limbs in six patients are better than before the operation. Conclusion The distance of nerve transposition can be shortened by a posterior vertebral approach operation, where the contralateral C7 nerve can be anastomosed directly with the ipsilateral C7 nerve which may be effective for nerve regeneration and functional recovery. However, this conclusion still needs further research and verification., This study aimed to explore a shorter and safer contralateral C7 transposition pathway for the treatment of central upper limb paralysis. The distance of nerve transposition can be shortened by a posterior vertebral approach operation, where the contralateral C7 nerve can be anastomosed directly with the ipsilateral C7 nerve. In this approach, nerve transplantation is not needed and it is conducive to nerve regeneration and functional recovery.

Aim. To investigate the expression of glucose transporter 3 (GLUT3) and hypoxia-inducible factor-1α protein (HIF-1α) in meningiomas and analyze the correlation between GLUT3 and HIF-1α expression with the pathological grade of peritumoral brain edema (PTBE) of meningiomas. Methods. In this cross-sectional study, we analyzed meningioma specimens from 160 patients collected from January 1, 2014, to December 1, 2017, by dividing them into a low-grade (WHO I) or high-grade (WHO II and WHO III) group. Immunohistochemical analyses were used to detect the expression level of GLUT3 and HIF-1α in the tumor specimens. Results. The proportion of GLUT3-positive staining in tumors sized 6 cm was 35.9% (37/103), 63.6% (28/44), and 53.8% (7/13), respectively (P=0.007). The proportion of HIF-1α-positive staining in tumors sized 6 cm was 41.7% (43/103), 68.2% (30/44), and 38.5% (5/13), respectively (P=0.010). The proportion of GLUT3-positive staining in the high-grade group and low-grade group was 70.8% (34/48) and 33.9% (38/112), respectively (P<0.001). The proportion of HIF-1α-positive staining in the high-grade group and low-grade group was 62.5% (30/48) and 42.9% (48/112), respectively (P=0.023). GLUT3-positive expression in meningioma PTBE grades 0, I, II, and III was 20.3% (13/64), 41.2% (14/34), 63.6% (21/33), and 82.8% (24/29), respectively (Bonferroni-corrected, P<0.001, α/6=0.008). HIF-1α-positive expression in meningioma PTBE grades 0, I, II, and III was 34.4% (22/64), 47.1% (16/34), 54.5% (18/33), and 75.9% (22/29), respectively (Bonferroni-corrected, P=0.003, α/6=0.008). Spearman’s correlation analysis revealed a correlation between the expression of GLUT3 and HIF-1α in meningiomas (r=0.463, P<0.001). Multivariate analysis revealed that GLUT3-positive expression, HIF-1α-positive expression, and high pathological grade were associated with the development of PTBE (P<0.05). Conclusions. GLUT3 and HIF-1α expression in meningiomas was closely related to the tumor size, pathological grade, and PTBE. This study is the first to report a unique map-like multifocal GLUT3 staining pattern in meningiomas.

Aim To investigate the expression of glucose transporter 3 (GLUT3) and hypoxia-inducible factor-1α protein (HIF-1α) in meningiomas and analyze the correlation between GLUT3 and HIF-1α expression with the pathological grade of peritumoral brain edema (PTBE) of meningiomas. Methods In this cross-sectional study, we analyzed meningioma specimens from 160 patients collected from January 1, 2014, to December 1, 2017, by dividing them into a low-grade (WHO I) or high-grade (WHO II and WHO III) group. Immunohistochemical analyses were used to detect the expression level of GLUT3 and HIF-1α in the tumor specimens. Results The proportion of GLUT3-positive staining in tumors sized 6 cm was 35.9% (37/103), 63.6% (28/44), and 53.8% (7/13), respectively (P = 0.007). The proportion of HIF-1α-positive staining in tumors sized 6 cm was 41.7% (43/103), 68.2% (30/44), and 38.5% (5/13), respectively (P = 0.010). The proportion of GLUT3-positive staining in the high-grade group and low-grade group was 70.8% (34/48) and 33.9% (38/112), respectively (P < 0.001). The proportion of HIF-1α-positive staining in the high-grade group and low-grade group was 62.5% (30/48) and 42.9% (48/112), respectively (P = 0.023). GLUT3-positive expression in meningioma PTBE grades 0, I, II, and III was 20.3% (13/64), 41.2% (14/34), 63.6% (21/33), and 82.8% (24/29), respectively (Bonferroni-corrected, P < 0.001, α/6 = 0.008). HIF-1α-positive expression in meningioma PTBE grades 0, I, II, and III was 34.4% (22/64), 47.1% (16/34), 54.5% (18/33), and 75.9% (22/29), respectively (Bonferroni-corrected, P = 0.003, α/6 = 0.008). Spearman's correlation analysis revealed a correlation between the expression of GLUT3 and HIF-1α in meningiomas (r = 0.463, P < 0.001). Multivariate analysis revealed that GLUT3-positive expression, HIF-1α-positive expression, and high pathological grade were associated with the development of PTBE (P < 0.05). Conclusions GLUT3 and HIF-1α expression in meningiomas was closely related to the tumor size, pathological grade, and PTBE. This study is the first to report a unique map-like multifocal GLUT3 staining pattern in meningiomas.

Rock slope stability is a key research issue in geotechnical engineering. Weak layer is a distinct feature distinguishing the rock slopes from soil types, and its existence considerably controls the slope stability. Taking in to account the differences in mineral composition, sedimentary conditions, stress history and other geological processes, the physical and mechanical parameters of rock mass generally show certain spatial variability. On the other hand, for slope failures such as landslides, rockfall and debris flows, earthquake is one of the main triggering factors. In this paper, an efficient framework is presented to evaluate the stability of the rock slope with weak layers considering spatial variability of rock mass strength properties under seismic loading. A rock slope model with weak layer is established, followed by modeling of both the spatial variability of cohesion ( c ) as well as friction angle ( ϕ ) of rock material and weak layer characterized by random field method. Random seismic loading is applied via the pseudo-static method. The Latin Hypercube Sampling (LHS) is adopted to calculate the failure probability of rock slope. The results indicate that the spatial variability of weak layer has more influence on the slope stability than that of rock material, and the influence of seismic randomness cannot be neglected. In addition, under different seismic loadings, the spatial variability of weak layers and seismic randomness have different effects on slope failure probability.

Objective The underlying pathology of brain leading to cognitive impairment in Parkinson’s disease (PD) remains poorly understood. The aim of our study was to test the hypothesis that mild cognitive impairment (MCI) in PD may be related to atrophy of special gray matter regions. Methods High-resolution T1-weighted magnetic resonance images of the brains and comprehensive cognitive function tests were acquired in 37 PD patients and 21 healthy controls (HC) from September 2013 to October 2014. Patients were divided into two groups: PD with MCI (PD-MCI, n = 18) and PD with normal cognition (PDNC, n = 19). Gray matter density differences were analyzed using voxel-based morphometry (VBM). VBM and cognitive results, UPDRS scores and Hoehn–Yahr stages were compared between PD-MCI, PDCN and HC group, and correlation analyses were performed between those brain areas and cognition scores, UPDRS scores and disease duration, which showed significant group differences. Results The demographic data and motor severity among three groups were similar. However, comprehensive cognitive function results were more severe in PD-MCI than the other two groups. Compared to the HC group, the PDNC group showed reductions in gray matter density in frontal, temporal, parietal, bilateral insula lobes and many other regions of brain. Besides above changes, the PD-MCI group also revealed gray matter concentration decrease in left hippocampus and thalamus, and these changes still remained when compared with the PDNC group. The HC group did not show any more areas of atrophy in gray matter than others. Gray matter loss in PD represented significant correlations with global cognitive scores, motor severity or disease duration in some of these atrophic regions. Conclusion The initial stages of cognitive function decline in patients with PD is closely associated with gray matter atrophy in left hippocampus and thalamus. These two regions may serve as potential imaging biomarkers for PD-MCI.

Background Anxiety and depression are two frequent comorbidities of Parkinson's disease (PD). However, the underlying neural mechanism is still unclear and the studies on their neural correlates were insufficient. Methods Using voxel-based neuroanatomical and functional connectivity (FC) measures, i.e. grey matter volume, fractional anisotropy, and weighted degree centrality (WD), we examined their correlations with the severity levels of anxious and depressive symptoms in 36 PD patients. Results Positive correlations were shown between anxiety and the WDs in the left amygdala, and between depression and short-ranged WDs in the left parahippocampal gyrus. Using these two regions as the seeds, we found that the severity levels of anxiety and depression were positively correlated with the FCs between the two seeds and the areas in the default mode network (DMN), while negatively correlated with the FCs between the two seeds and the prefrontal and superior temporal cortices. Anxiety was also positively correlated with the FC between the amygdala and the superior parietal lobule. Limitations The severity levels of anxious and depressive symptoms of our participants is relatively mild than some previous studies. The cross-sectional design of this study cannot clarify the etiological relationship between PD and two comorbidities. Conclusions Our results were in line with the key roles of the amygdala and parahippocampal gyrus in anxiety and depression, and reflected the distinct effects of the DMN, prefrontal and superior temporal cortices, and sensory-motor regions on emotional regulation. The identification of these neural substrates might assist clinical monitoring mood disturbances in PD.

The retroviral integrase plays an essential role in the integration of reverse-transcribed retroviral cDNA into the host cell genome, and serves as an important target for anti-viral therapeutics. In this study, we identified the COP9 signalosome subunit 6 (CSN6) as a novel avian leukosis virus (ALV) integrase binding protein. Co-immunoprecipitation and GST pull-down assays showed that CSN6 bound to ALV integrase likely through direct interaction of CSN6 to the catalytic core of the integrase. We further demonstrated CSN6 inhibited integrase activity in vitro; knockdown of CSN6 in DF-1 promoted ALV production. These results indicated that CSN6 may be a negative regulator of ALV replication by binding to and inhibiting integrase. Our findings provided the insight into the integrase-based host defense system and may have implications in the development of integrase-based anti-viral strategies.

The basal ganglia-cortical circuits are important for information process to brain function. However, chronic recording of single-unit activities in the basal ganglia nucleus has not yet been well established. We present a movable bundled microwire array for chronic subthalamic nucleus (STN) single-unit electrocorticogram co-recording. The electrode assembly contains a screw-advanced microdrive and a microwire array. The array consists of a steel guide tube, five recording wires and one referenced wire which form the shape of a guiding hand, and one screw electrode for cortico-recording. The electrode can acquire stable cortex oscillation-driven STN firing units in rats under different behaving conditions for 8 weeks. We achieved satisfying signal-to-noise ratio, portions of cells retaining viability, and spike waveform similarities across the recording sections. Using this method, we investigated neural correlations of the basal ganglia-cortical circuits in different behaving conditions. This method will become a powerful tool for multi-region recording to study normal statements or movement disorders.

Objective The central mechanisms underlying postherpetic neuralgia (PHN) pain remains unknown. The primary purpose of this study was to identify microstructural white matter changes closely related to the PHN pain by means of diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) analysis. Methods DTI data of the brains were obtained from 8 PHN patients and 8 healthy controls (HC) that were matched in age, gender, and educational level. DTI metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were separately compared between the two groups using TBSS analysis to detect subtle microstructural changes. Partial correlation analyses were also conducted to evaluate the association between the altered DTI measures and clinical features. Results Average diffusion indices of white matter skeletons in the whole-brain showed no significant difference between the two groups. However, compared to the HC group, patients with PHN pain revealed reductions in localized FA and AD values in white matter underlying insula, occipital lobe, cerebellum, precentral gyrus, and many other regions, but without distinct change in regional MD and RD levels. In addition, decline of FA and AD values in patients represented significant negative correlations with PHN pain duration when the effect of VAS scores were excluded. Conclusion The current study suggest that there exists altered microstructure integrity of white matter in multiple brain regions in patients with PHN, and these changes increase in size as the duration of the pain increases. These findings might provide a new insight into the mechanism of PHN pain in brain.

The spatial variability is an inherent property of soil materials, which heavily affected the failure probability of slope. In the present study, deterministic analysis with factor of safety and reliability analysis in uniform soil grounds and spatial variable soil conditions are successively carried out to investigate the effect of uncertainties and the spatial variability of soil on the stability of slope reinforced with piles using random limit equilibrium method (RLEM). The optimal location and length of pile are also analysed based on the calculation results of RLEM, which is inconsistent with the results of traditional deterministic method. The obtained results demonstrate the significant effect of the spatial variability on the failure probability of slope reinforced with pile.

a b s t r a c t An indirect enzyme-linked immunosorbent assay (iELISA) that could detect immunoglobulin G antibodies against avian hepatitis E virus (HEV) was developed. This assay employs a truncated C-terminal 268- amino acid recombinant ORF2 protein from an avian HEV genotype 3 strain isolated in China (CaHEV) as the coating antigen. The antigen concentration and serum dilution were optimized using a checkerboard titration. A cut-off value of 0.368 at OD450 nm was determined by testing 120 positive and 200 negative chicken sera for avian HEV antibodies using the two-graph receiver operating characteristic (TG-ROC) analysis. This iELISA has a sensitivity of 96.1% and a specificity of 95.8%. The overall agreement between the iELISA and a corresponding Western blot was 97%. The iELISA was used to evaluate the seroprevalence of avian HEV in poultry farms in the Shandong province. The avian HEV seropositive rate of 35.9% was determined by testing 1871 serum samples that were collected from 10 chicken flocks ranged from 10 to 60 weeks of age. The iELISA that was developed in this study can be used for detection of immunoglobulin G antibodies against avian HEV. © 2012 Published by Elsevier B.V.

Avian leukosis virus subgroup J poses a great threat to the poultry industry in China. To reduce the economic losses, a quick method for detection of ALV-J antigen is required for diagnosis and identification of the congenitally transmitting hens. In this study, we report the production and evaluation of one monoclonal antibody (MAb) suitable for achieving these goals. The gp85 gene of avian leukosis virus subgroup J CAUHM01 China isolates was subcloned into the expression vectors pGEX-6p-1 and pET28a and successfully expressed in E. coli. After immunizing BALB/c mice with recombinant His-Jgp85 protein, splenic cells from immunized mice were fused with SP2/0 myeloma cells to produce hybridomas. We isolated and characterized one ALV-J gp85-specific MAb by determining its titer, affinity and IgG subclass. In addition, we performed epitope mapping and determined the epitope for the MAb 1E3 to be 81-92 aa of ALV-J gp85 protein (LPWDPQELDILG). Bioinformatics analysis and IFA studies revealed that this epitope is conserved among all ALV-J isolates and that this antibody could serve as a useful reagent for ALV-J detection and diagnosis.

Multivariate Granger causality is a well-established approach for inferring information flow in complex systems, and it is being increasingly applied to map brain connectivity. Traditional Granger causality is based on vector autoregressive (AR) or mixed autoregressive moving average (ARMA) model, which are potentially affected by errors in parameter estimation and may be contaminated by zero-lag correlation, notably when modeling neuroimaging data. To overcome this issue, we present here an extended canonical correlation approach to measure multivariate Granger causal interactions among time series. The procedure includes a reduced rank step for calculating canonical correlation analysis (CCA), and extends the definition of causality including instantaneous effects, thus avoiding the potential estimation problems of AR (or ARMA) models. We tested this approach on simulated data and confirmed its practical utility by exploring local network connectivity at different scales in the epileptic brain analyzing scalp and depth-EEG data during an interictal period.

Ten H9N2 influenza virus strains isolated from diseased chickens in different farms in China during 1995 to 1999 were antigenically and genetically characterized. The haemagglutinins of the isolates were not related to those of A/quail/Hong Kong/G1/97 (H9N2) (Qa/HK/G1/97), but were closely related to that of A/chicken/Hong Kong/G9/97 (H9N2) (Ck/HK/G9/97). The neuraminidase of these isolates had a deletion of three amino acid residues at positions 63 to 65 as compared with those of Ck/HK/G9/97, while that of Qa/HK/G1/97 lacked two amino acids at positions 38 and 39. The PB2 genes of the isolates were not related to those of Qa/HK/G1/97 or Ck/HK/G9/97, but showed some relationship to that of A/duck/Hong Kong/Y439/97 (H9N2) (Dk/HK/Y439/97). The PB1 genes of the isolates were not related to those of the three representative strains. The PA, NP, M, and NS genes of the isolates belonged to the same lineage as those of Ck/HK/G9/97, and were distinct from those of Qa/HK/G1/97 and Dk/HK/Y439/97. The present results indicate that H9N2 influenza viruses prevalent in chicken populations in China belong genetically to one lineage and are distinct from Qa/HK/G1/97, presumed to be the donor of the internal protein genes of the highly pathogenic H5N1 influenza virus in Hong Kong in 1997.

BACKGROUND: Glioblastoma is the most common and most lethal form of brain tumor in human. Unfortunately, there is still no effective therapy to this fatal disease and the median survival is generally less than one year from the time of diagnosis. Discovery of ligands that can bind specifically to this type of tumor cells will be of great significance to develop early molecular imaging, targeted delivery and guided surgery methods to battle this type of brain tumor. METHODOLOGY/PRINCIPAL FINDINGS: We discovered two target-specific aptamers named GBM128 and GBM131 against cultured human glioblastoma cell line U118-MG after 30 rounds selection by a method called cell-based Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX). These two aptamers have high affinity and specificity against target glioblastoma cells. They neither recognize normal astraglial cells, nor do they recognize other normal and cancer cell lines tested. Clinical tissues were also tested and the results showed that these two aptamers can bind to different clinical glioma tissues but not normal brain tissues. More importantly, binding affinity and selectivity of these two aptamers were retained in complicated biological environment. CONCLUSION/SIGNIFICANCE: The selected aptamers could be used to identify specific glioblastoma biomarkers. Methods of molecular imaging, targeted drug delivery, ligand guided surgery can be further developed based on these ligands for early detection, targeted therapy, and guided surgery of glioblastoma leading to effective treatment of glioblastoma.

BackgroundCurrent vaccines to avian influenzae virus (AIV), a highly contagious disease of birds, need to be constantly updated due to the high level of variation in the target antigens. Therefore, a vaccine that could induce broad cross protection against AIV is required. The M2 membrane protein is structurally conserved amongst AIV subtypes but tends in induce a poor immune response, whereas C3d has been shown in many species to enhance immunogenicity. In this study, we investigated the potential of M2-avian C3d fusion proteins to provide effective immunity.ResultsWe fused chicken complement C3d to sM2 (M2 protein with the transmembrane region deleted) of AIV and expressed four fusion proteins, GST (Glutathione S-transferase tagged proteins in pGEX expression vector) -C3d-sM2, GST-C3d-L2-sM2, GST-C3d-L1-C3d-sM2 and GST-C3d-L1-C3d-L2-sM2 were used to immunize mice. In addition, Specific pathogen free (SPF) chickens were inoculated with the plasmids pcDNA-sM2, pcDNA-C3d-L1-C3d-L2-sM2, GST-sM2 and GST-C3d-L1-C3d-L2-sM2. The immune response was monitored by an enzyme-linked immunosorbent assay (ELISA) for sM2 antibody, and all the test animals were challenged with A/chicken/Bei Jing/WD9/98 (H9N2) virus. Results revealed that the anti-sM2 antibody in mice and chickens vaccinated with these proteins was higher than the nonfused forms of sM2, the GST-C3d-L1-C3d-L2-sM2 groups have conferred the highest 30% and 20% protection ratio in mice and chickens respectively. In addition, the pcDNA-C3d-L1-C3d-L2-sM2 also enhances the antibody responses to sM2 compared to pcDNA-sM2 in chickens, and acquired 13.3% protection ratio.ConclusionThese results indicated that chicken C3d enhanced the humoral immunity against AIV M2 protein either fused proteins expressed by the prokaryotic system or with the DNA vaccine. Nevertheless, in view of the poor protection ratio for these animals, we speculated that this is not a worthy developing of vaccine in these constructs.

Sepsis remains a major health concern across the world. The effects of stress on host resistance to sepsis are still not very clear. To explore the effects of chronic stress on sepsis’ we examined the impact of restraint stress on the resistance of mice to sepsis. Interestingly, it was found that restraint stress enhanced the antisepsis resistance of mice and the concentrations of the proinflammatory cytokines IL-1, IL-6, IL-12, and TNF-α in the blood of stressed mice were dramatically reduced post Escherichia coli infection or LPS treatment as compared with that of controls (p < 0.05). In addition, the mRNA expressions of glucocorticoid-induced leucine zipper (GILZ) were up-regulated in the spleen and peritoneal macrophages of mice receiving restraint stress or dexamethasone treatment. These results demonstrate that restraint stress enhances the resistance of mice to sepsis, supporting corticotherapy for sepsis and proposing restraint-stressed mouse as an animal model to elucidate mechanisms of stress-associated, antisepsis resistance.

Unlike traditional virus isolation and sequencing approaches, sequence-independent amplification based viral metagenomics technique allows one to discover unexpected or novel viruses efficiently while bypassing culturing step. Here we report the discovery of the first Sicinivirus isolate (designated as strain JSY) of picornaviruses from commercial layer chickens in mainland China by using a viral metagenomics technique. This Sicinivirus isolate, which contains a whole genome of 9,797 nucleotides (nt) excluding the poly(A) tail, possesses one of the largest picornavirus genome so far reported, but only shares 88.83% and 82.78% of amino acid sequence identity to that of ChPV1 100C (KF979332) and Sicinivirus 1 strain UCC001 (NC_023861), respectively. The complete 939 nt 5′UTR of the isolate strain contains at least twelve stem-loop domains (A–L), representing the highest set of loops reported within Sicinivirus genus. The conserved 'barbell-like' structure was also present in the 272 nt 3′UTR of the isolate as that in the 3′ UTR of Sicinivirus 1 strain UCC001. The 8,586 nt large open reading frame encodes a 2,862 amino acids polyprotein precursor. Moreover, Sicinivirus infection might be widely present in commercial chicken farms in Yancheng region of the Jiangsu Province as evidenced by all the tested stool samples from three different farms being positive (17/17) for Sicinivirus detection. This is the first report on identification of Sicinivirus in commercial layer chickens with a severe clinical disease in mainland China, however, further studies are needed to evaluate the pathogenic potential of this picornavirus in chickens.

Staphylococcus sciuri are important human pathogens responsible for endocarditis, peritonitis, septic shock, urinary tract infection, pelvic inflammatory disease and wound infections. However, little information is known regarding the pathogenicity of S. sciuri to animals. From the pericardial fluid of a diseased piglet with exudative epidermitis (EE), we isolated a strain of Staphylococcus in pure culture. Surprisingly, this isolate was a member of S. sciuri rather than S. hyicus as identified by its biochemical traits and also by analysis of 23S ribosomal DNA using Internal Transcribed Spacer PCR. In addition, inoculation of newborn piglets with 1x10(10) CFU of the isolate by oral feeding or intra-muscular injection successfully reproduced EE in piglets, which suggested that the oral intake of the pathogen by the animals is one of the major routes of exposure. These unexpected findings prioritized S. sciuri as important zoonotic agents, which may have ramifications for human medicine.

Avian infectious bronchitis virus (AIBV) is classified as a member of the genus coronavirus in the family coronaviridae. The enveloped virus has a positive-sense, single-stranded RNA genome of approximately 28 kilo-bases, which has a 5′ cap structure and 3′ polyadenylation tract. The complete genome sequence of infectious bronchitis virus (IBV), Beijing isolate, was determined by cloning sequencing and primer walking. The whole genome is 27733 nucleotides in length, has ten open reading frames: 5′ -orf1a-orf1ab-s-3a-3b-e-m-6a-6b-n-3′. Alignments of the genome sequence of IBV Beijing isolate with those of two AIBV strains and one SARS coronavirus were performed respectively. The genome sequence of IBV Beijing isolate compared with that of the IBV strain LX4 (uncompleted, 19440 bp in size) was 91.2% similarity. However, the full-length genome sequence of IBV Beijing isolate was 85.2% identity to that of IBV Strain Beaudette, and was only 50.8% homology to that of SARS coronavirus. The results showed that the genome of IBV has remarkable variation. And IBV Beijing isolate is not closely related to SARS coronavirus. Phylogenetic analyses based on the whole genome sequence, S protein, M protein and N protein, also showed that AIBV Beijing isolate is lone virus in group III and is distant from SARS coronavirus. In conclusion, this study will contribute to the studies of diagnosis and diseases control on IBV in China.