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A Zr‐based amorphous alloy (thickness = 2 mm) is welded by laser welding. The phase composition and microstructure of the welding joints under different laser powers are analyzed by optical microscopy, X‐ray diffraction, and scanning electron microscopy. Mechanical properties of the welded joints under different laser powers are examined using microhardness and tensile testers. The glass forming ability and thermal stability of the welded joints are investigated using differential scanning calorimetry. With an increase in laser power, the degree of crystallization of welded joints increases, their microhardness is in the range 502.3–546.9 HV0.2, and tensile strength is up to 583 MPa (75% of that of the Zr‐based amorphous alloy). Through the research of the article, it can be found that when the laser power increases, the crystallization degree of the welded joint first increases rapidly and then tends to be stable. The lower laser power should be used as far as possible in the case of penetration. [ABSTRACT FROM AUTHOR]

Histone deacetylase 3 (HDAC3) plays an important role in signal-dependent transcription and is dysregulated in diseases such as cancer. Previous studies have shown that the function of HDAC3 requires an activation step, which is mediated by the interactions of HDAC3 with the deacetylase-activation domain (DAD) of nuclear receptor corepressors and inositol tetra-phosphate (IP4). However, the role of the unique HDAC3 C-terminal region in HDAC3 activation is elusive. Here multiple biochemical, structural, and functional studies show that HDAC3 activation requires a priming step mediated by the C terminus to remodel HDAC3 conformation. We show that multiple C-terminal mutations prevent HDAC3 activation by preventing this C terminus-dependent conformational change. Mechanistically, we demonstrate that the C terminusmediated function in altering HDAC3 conformation is required for proper complex formation of HDAC3 with DAD and IP4 by allowing HDAC3 to undergo IP4-dependent interaction with DAD. Remarkably, we found that this C terminus function is conformation dependent, being necessary for HDAC3 activation prior to but not after the conformational change. Together, our study defines two functional states of free HDAC3, reveals the complete HDAC3 activation pathway, and links the C terminus function to the specific interaction between HDAC3 and DAD. These results also have implications in how signaling pathways may converge on the C terminus to regulate HDAC3 and suggest that the C terminus-mediated conformational change could represent a new target for inhibiting HDAC3 in diseases such as cancer. [ABSTRACT FROM AUTHOR]

Background: This study was designed to investigate the effects of a novel carcinogenetic molecule, p130cas (breast cancer antiestrogen resistance protein 1 or BCAR1) on proliferation and cell growth in lung adenocarcinoma. The study also aimed to identify the possible underlying signal networks of BCAR1. Methods: First, we evaluated proliferation, cell colony formation, apoptosis, and cell cycle after BCAR1 was knocked out (KO) using CRISPR‐Cas9 technology in H1975 and H1299 human lung adenocarcinoma cells. Subsequently, BCAR1 was upregulated in 293T cells and immunoprecipitation‐mass spectrometry (IP‐MS) was used with bioinformatics analysis to screen for potential networks of BCAR1 interacting proteins. Ultimately, we validated the correlated expressions of BCAR1 and a selected hub gene, RNA polymerase II subunit A (POLR2A), in 54 lung adenocarcinoma tissues, as well as in H1975 and H1299 cells. Results: Cell proliferation of H1975 and H1299 was significantly inhibited following BCAR1‐KO. Colony formation of H1975 cells was also significantly decreased following BCAR1‐KO. IP‐MS demonstrated 419 potential proteins that may interact with BCAR1. Among them, 68 genes were significantly positively correlated to BCAR1 expression, as verified by TCGA. Six hub genes were revealed by PPI String. High expression of POLR2A, MAPK3, MOV10, and XAB2 predicted poor prognosis in lung adenocarcinoma, as verified by the K‐M plotter database. POLR2A and MAPK3 are involved in both catalytic activity and transferase activity. POLR2A and BCAR1 were significantly increased in lung cancer tissues as compared with matched normal tissues. High expression of POLR2A was significantly positively correlated to BCAR1 overexpression and predicted poor prognosis in 54 lung cancer cases. POLR2A expression was significantly decreased following BCAR1‐KO in H1975 and H1299 cells. Conclusions: BCAR1 promotes proliferation and cell growth, probably via upregulation of POLR2A and subsequent enhancement of catalytic and transferase activities. However, additional robust studies are required to elucidate the mechanisms involved. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical effect of the application of CT navigation in the treatment of lumbar spondylolisthesis with minimally invasive surgery - transforaminal lumbar interbody fusion (MIS-TLIF). Methods: A retrospective study was conducted on 30 patients with lumbar spondylolisthesis who were continuously treated in linyi central hospital from May 2018 to March 2019.The patients were divided into two groups,15 patients treated with MIS-TLIF with the aid of CT navigation during the operation were included into an observation group. Another 15 patients were treated with open transforaminal lumbar interbody fusion as the control group. The baseline information, including gender, age and course of disease, perioperative period and imaging conditions, and VAS and ODI scores of patients in the two groups were collected and analyzed. Results: Fifteen patients were included into the observation group, including 9 male and 6 female patients with an average age of 52.60 ± 6.31 and a course of disease of 16.33 ± 6.00 months. The other 15 patients were included into the observation group, including seven male and eight female patients with an average age of 52.87 ± 7.38 and a course of disease of 19.13 ± 9.89 months. The difference in the gender, age and course of disease between the two groups had no statistical significance (P > 0.05). However, the difference in the duration of operation and intraoperative blood loss between the two groups had statistical significance (P< 0.05). There were no statistically significant differences in wound complications, neurological complications, preoperative slippage rate, postoperative slippage rate, slippage reduction rate and screw placement accuracy (P > 0.05). VAS scores of the two groups were statistically significant from six months after surgery (P < 0.01). There was no significant difference in ODI between the two groups at any time point (P >0.05). VAS and ODI scores were improved at each time point compared with those before surgery. Conclusion: The minimally invasive transforaminal lumbar fusion performed with the aid of CT navigation during the operation shortens the duration of operation and the amount of bleeding, reduces the back pain, is beneficial to the early postoperative functional exercise, and speeds up the postoperative recovery. [ABSTRACT FROM AUTHOR]

CBFA2/RUNX1 partner transcriptional co-repressor 3 (CBFA2T3, also known as MTG16 or ETO2) is a myeloid translocation gene family protein that functions as a master transcriptional corepressor in hematopoiesis. Recently, it has been shown that CBFA2T3 maintains leukemia stem cell gene expression and promotes relapse in acute myeloid leukemia (AML). However, a role for CBFA2T3 in myeloid differentiation of AML has not been reported. Here, we show that CBFA2T3 represses retinoic acid receptor (RAR) target gene expression and inhibits all-trans-retinoic acid (ATRA)-induced myeloid differentiation of AML cells. ChIP-Seq revealed that CBFA2T3 targets the RARa/RXRa cistrome in U937AMLcells, predominantly at myeloid-specific enhancers associated with terminal differentiation. CRISPR/Cas9-mediated abrogation of CBFA2T3 resulted in spontaneous and ATRA-induced activation of myeloid-specific genes in a manner correlated with myeloid differentiation. Importantly, these effects were reversed by CBFA2T3 re-expression. Mechanistic studies showed that CBFA2T3 inhibits RAR target gene transcription by acting at an early step to regulate histone acetyltransferase recruitment, histone acetylation, and chromatin accessibility at RARa target sites, independently of the downstream, RAR-mediated steps of transcription. Finally, we validated the inhibitory effect of CBFA2T3 on RAR in multiple AML subtypes and patient samples. To our knowledge, this is the first study to show that CBFA2T3 down-regulation is both necessary and sufficient for enhancing ATRA-induced myeloid gene expression and differentiation of AML cells. Our findings suggest that CBFA2T3 can serve as a potential target for enhancing AML responsiveness to ATRA differentiation therapies. [ABSTRACT FROM AUTHOR]

In up to 15% of acute myeloid leukemias (AMLs), a recurring chromosomal translocation, termed t(8;21), generates the AML1-eight-twenty-one (ETO) leukemia fusion protein, which contains the DNA-binding domain of Runt-related transcription factor 1 (RUNX1) and almost all of ETO. RUNX1 and the AML1-ETO fusion protein are coexpressed in t(8;21) AML cells and antagonize each other's gene-regulatory functions. AML1-ETO represses transcription of RUNX1 target genes by competitively displacing RUNX1 and recruiting corepressors such as histone deacetylase 3 (HDAC3). Recent studies have shown that AML1-ETO and RUNX1 co-occupy the binding sites of AML1-ETO-activated genes. How this joined binding allows RUNX1 to antagonize AML1-ETO-mediated transcriptional activation is unclear. Here we show that RUNX1 functions as a bona fide repressor of transcription activated by AML1-ETO. Mechanistically, we show thatRUNX1is a component of the HDAC3 corepressor complex and that HDAC3 preferentially binds to RUNX1 rather than to AML1-ETO in t(8;21) AML cells. Studying the regulation of interleukin-8 (IL8), a newly identified AML1-ETO-activated gene, we demonstrate that RUNX1 and HDAC3 collaboratively repress AML1-ETO- dependent transcription, a finding further supported by results of genome-wide analyses of AML1-ETO-activated genes. These and other results from the genome-wide studies also have important implications for the mechanistic understanding of gene-specific coactivator and corepressor functions across the AML1-ETO/RUNX1 cistrome. [ABSTRACT FROM AUTHOR]

As people pay more attention to health, more and more sports have gradually entered people's vision, and martial arts routines are one of them. However, in the martial art routine, the incidence of knee joint injuries is high. After knee joint injuries, it often affects the athletes' athletic ability and performance, and even endangers the body and health, and shortens the life span of the exercise. The purpose of this article is to observe the microscopic rehabilitation of knee joint patella softening in martial arts athletes. This article analyzes the pathogenesis, diagnosis and treatment of patellar osteomalacia, and proposes knee protection for martial arts routine athletes. The experimental part uses a randomized controlled research method. Patients of martial arts routines were taken as the research object. Forty patients who met the criteria were randomly divided into a test group (20 cases) and a control group (20 cases) according to the order of the visit time and random drawing. The test group was given a combination of microscopy and rehabilitation surgery to treat patella sclerosis, while the control group only used conventional surgery to treat patella sclerosis. The efficacy of the two groups was analyzed, and the total effective rate of the control group was 65%, and the total effective rate of the experimental group was 85%. [ABSTRACT FROM AUTHOR]

Background/Aims: Major burn injury is one of the main severe forms of wound which lead to a mass of clinical debilitation, this study was to identify core biomarkers for the recovery of severe burned injury. Methods: Gene expression profiles (GSE19743) from the Gene Expression Omnibus (GEO) was downloaded, followed by background correction, normalization of raw microarray dataset and identification of differential expression genes (DEGs). Soft clustering of DEGs was used for the screening of gene clusters that with sustained increasing (SIG) and decreasing expression (SDG) profiles along with the recovery process of burned injury. The significantly enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of SIGs and SDGs were obtained through the Database for Annotation, Visualization, and Integrated Discovery (DAVID), based on which the miRNAgene regulation network for SIGs and SDGs were constructed from the miRWalk database. Results: Ten clusters were obtained through soft clustering. The SIGs and SDGs were found to be closely associated with the biological processes of immune system. The miRNA-gene regulation network analysis suggested different roles between SIGs and SDGs in the recovery of severe burned injury. Furthermore, a bunch of important biomarkers were identified, which would be helpful in the treatment of burned patients. Conclusion: Our current findings suggest an interesting molecular link between transcriptional regulation potentially involved in immunosuppressive state after major burn injury, which warrants further exploration for their utilization in the treatment of major burn injury. [ABSTRACT FROM AUTHOR]

Nucleic acid polymers can be evolved to exhibit desired properties, including molecular recognition of a molecular target and catalysis of a specific reaction. These properties can be readily evolved despite the dearth of chemical diversity available to nucleic acid polymers, especially when compared to the rich chemical complexity of proteins. Expansion of nucleic acid chemical diversity has therefore been an important thrust for improving their properties for analytical and biomedical applications. Herein, we briefly describe the current state-of-the-art for the sequence-defined incorporation of modifications throughout an evolvable nucleic acid polymer. This includes contributions from our own lab, which have expanded the chemical diversity of nucleic acid polymers closer to the level observed in proteinogenic polymers. Introduction 2 Polymerase-Catalyzed Synthesis of Modified Nucleic Acid Polymers 3 Ligase-Catalyzed Oligonucleotide Polymerization (LOOPER) 4 LOOPER with Small Modifications 5 LOOPER with Large Modifications 6 Evolution of Aptamers Derived from LOOPER Libraries 7 Outlook. [ABSTRACT FROM AUTHOR]

The Mw 6.1 2014 Ludian, Yunnan, China earthquake triggered numerous coseismic landslides that do not appear to be associated with any previously known seismogenic fault. Traditional models of triggering for seismically generated landslides do not provide a reasonable explanation for the landslide pattern observed here. Here the Newmark method is applied to a grid to calculate the minimum accelerations required for slope failures throughout the affected region. The results demonstrate that for much of the study area, the distribution of failure prone slopes is similar to the actual pattern of coseismic landslides, however there are some areas where the model predicts considerably fewer failures than occurred. We suggest that this is a result of the complex source faults that generated the Ludian earthquake, which produced a half-conjugate rupture on nearly EW- and NNW trending faults at depth. The rupture directed much of its seismic moment southeast of the epicenter, increasing ground shaking and the number of resulting landslides. [ABSTRACT FROM AUTHOR]

Background: Acinetobacter baumannii nosocomial ventriculitis/meningitis, especially those due to drug-resistant strains, has substantially increased over recent years. However, limited therapeutic options exist for the Acinetobacter baumannii ventriculitis/meningitis because of the poor penetration rate of most antibiotics through the blood-brain barrier. Case presentation: A 57-year-old male patient developed ventriculitis from an extensively drug-resistant strain of Acinetobacter baumannii after the decompressive craniectomy for severe traumatic brain injury. The patient was successfully treated with intraventricular and intravenous polymyxin B together with intravenous tigecycline. Conclusions: The case illustrates intraventricular polymyxin B can be a therapeutic option against extensively drug-resistant Acinetobacter baumannii ventriculitis. [ABSTRACT FROM AUTHOR]

Press bending is widely used in Al integral panels for the aerospace industry, which, combined with multi-point dies, is an innovative approach. In the forming process, the fracture on integral panels is a fatal flaw. In this study, it mainly presents a core method on how to predict fracture on stiffeners by a novel method-the multi-point press bending. With the combination of a multi-point press bending experiment and corresponding finite element method (FEM) simulation, a suitable ductile criterion was selected to predict fracture on an aircraft Al stiffener. Using the fracture criterion, the fracture moments and fracture positions on stiffeners were determined in the multi-point press bending process. Due to the rapid reconfigurable characteristic of multi-point die, an optimal deformation path was discussed to reduce the fracture risk on stiffeners. It was identified that the Cockcroft criterion proved to be the most favorable ductile fracture criterion to predict fracture on stiffeners. Moreover, in the multi-point press bending process of the 7B04-T7451 Al stiffener, it is not prone to fracture with the increase of forming steps. Multi-point forming with an equidifferent curvature deformation path reduces the fracture risk of stiffeners much more than that with an equidifferent radius deformation path. [ABSTRACT FROM AUTHOR]

Residual stresses generated during the manufacturing process have direct effects on product life cycle and properties. Thus, it is essential to understand the effects of processing on residual stress distribution. In this paper, a technique for through thickness residual stress measurement was developed and tested experimentally. In this technique, a bent plate slotted in the middle of the concave surface leads to springback of the plate. The residual stress distribution and springback induced by local material removal are theoretically analyzed. This 'slotting method' is more convenient than other relaxation methods because it is determined directly from the data and does not require tedious inversion; additionally, it allows the determination of a springback map through thickness residual stress distribution. Here, the research object was a 30-mm-thick aluminum alloy plate that had remaining thickness residual stress induced by bending, and the slotting processes were carried out with FE simulation and experiment, respectively. The simulation results on the residual stress distribution shows consistence with the analytical results. Furthermore, the slotting processes with different groove depths and locations were also investigated. The measured springback data shows minor deviation from the numerical analysis, which verifies that the technique provides a reasonable assessment of the through thickness residual stress distribution and springback. [ABSTRACT FROM AUTHOR]

Antioxidant activity of glycyrrhetinic acid and its metal-containing complexes was investigated. The antioxidant activity behaviours of glycyrrhetinic acid and its metal-containing complexes (coordinated with Fe3+, Cu2+, Zn2+, and Ca2+) on free radicals (•OH, O2 •–, ROO•, and DPPH) was investigated by graphene modified glassy carbon electrode. The free radical-scavenging capacity of glycyrrhetinic acid and its metalcontaining complexes was calculated, respectively. The scavenging capacity order on the •OH radical was glycyrrhetinic acid-Cu > glycyrrhetinic acid-Zn > glycyrrhetinic acid-Fe > glycyrrhetinic acid-Ca > glycyrrhetinic acid. The scavenging order on the O2 •– radical was glycyrrhetinic acid-Zn > glycyrrhetinic acid-Cu > glycyrrhetinic acid-Ca > glycyrrhetinic acid-Fe > glycyrrhetinic acid. The scavenging order on the DPPH radical was glycyrrhetinic acid-Zn > glycyrrhetinic acid–Ca > glycyrrhetinic acid-Fe > glycyrrhetinic acid-Cu > glycyrrhetinic acid. The scavenging order on the ROO• was glycyrrhetinic acid-Fe > glycyrrhetinic acid > glycyrrhetinic acid-Zn > glycyrrhetinic acid-Cu > glycyrrhetinic acid-Ca. Except for the ROO• radical, the scavenging capacity of glycyrrhetinic acid metal-containing complexes with free radicals was significantly higher than that of glycyrrhetinic acid. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a common chronic autoimmune and incurable disease. The aim of the present study was to investigate the therapeutic effect and mechanism of the total saponins of Rhizoma Dioscorea nipponica (TSRDN) in RA. A collagen induced-arthritis (CIA) rat model was established. CIA rats were randomly divided into three groups and lavaged with an equal volume of solvent (CIA group), TSRDN (25 mg/kg/day, RDN group) and tripterygium (TP; 12 mg/kg/day, TP group) for 21 days, respectively. Normal rats served as a control group. Hematoxylin-eosin (HE) staining was used to observe the histopathological injury of synovial tissues. The level of CD31, which used for marking and counting, micro vessel density (MVD) and the expression levels of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription 3 (STAT3) were detected by immunohistochemical analysis. Additionally, the DNA-binding activity of nuclear factor-κB (NF-κB) was determined using an ELISA kit. HE staining showed obvious synovial hyperplasia, inflammatory cell infiltration, pannus formation, cartilage and bone erosion in the CIA group rats. In addition, compared with control group, the level of MVD, the expression of VEGF and STAT3, and the DNA-binding activity of NF-κB were all increased in CIA group rat synovial tissue (all P<0.01); however, TSRDN or tripterygium were able to inhibit these changes (all P<0.01). It was speculated that TSRDN may prevent angiogenesis by inhibiting the expression of STAT3 and the DNA-binding activity of NF-κB p65, thereby potentially improving CIA. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of Dipsacus asperoides (Xue Duan), a traditional Chinese medicine, on rats with spinal cord injury (SCI). Methods: In this study a total of 40 adult rats were used after inducing SCI where Xue Duan was applied on experimental group and phosphate-buffered saline (PBS) was administered in corresponding control groups. Intraperitoneal administration of both compounds for a period of four weeks (28 days) was carried out at a dose of 10 mg/kg/day. Bright field microscopy was performed on the tissues. Results: Bright Field microscopy of tissue sections showed significant reduction in cavity area that resulted from injury, that is from 0.19 ± 0.05 mm2 to 0.09 ± 0.03 mm2 (p < 0.01) in untreated and treated groups respectively. Similarly western blotting results showed a decrease in the expression of NF-κB p65 and I-κBα (p < 0.01). These two compounds are important in increasing secondary pathophysiology in SCI. The results for MPO activity also revealed significantly reduced infiltration of leukocytes to the injury site (p < 0.01). Conclusion: This study reveals the positive effect of the plant material in reducing inflammation in rats with traumatic SCI. [ABSTRACT FROM AUTHOR]

The full vibrational spectra especially those high-lying vibrational energies in the dissociation region of the electronic state of , the state of , the and states of are obtained using the variational algebraic method (VAM). Then, an analytical potential energy function (APEF) with adjustable parameter for each electronic state is determined by the 4-terms variational algebraic energy consistent method (VAECM(4)) based on the VAM vibrational energies. The full vibrational energies, the vibrational spectroscopic constants, the force constants , and the expansion coefficients of the potential are tabulated. Compared with experimental and other calculated results, accurate APEFs, vibrational energy levels and spectroscopic parameters are obtained with the VAECM(4) for the four electronic states of diatomic ions. The results show that the VAECM(4) method also applies to diatomic ion systems. • We find the analytical potentials of other methods may show the unphysical tiny barriers in the asymptotic and dissociation region. • We modify our variational algebraic energy consistent method (VAECM) to adapt to different diatomic ions. • Modified VAECM(4) can obtain the full vibrational spectra and give accurate analytical potential energy functions for diatomic ions. [ABSTRACT FROM AUTHOR]

Post-stretching elongation is a crucial process parameter in stretch bending process because of its significant influence on the forming effects. In this paper, the displacement loading method was presented to control the movement of the jaw in order to avoid the instability of tensile force in mechanical loading method. Typical aluminum hollow profile used in high-speed trains was selected as the research object. Stretch bending process with five levels of post-stretching elongations was carried out by finite element (FE) simulation. The simulation results reveal that an increment of the post-stretching elongation leads to smaller shape error and springback but larger cross-sectional distortion and spatial twist. The forming defects index, which is based on normalizing and weighting four forming defects, was put forward to evaluate comprehensive forming effects. Furthermore, the backtracking method was used to obtain the optimal post-stretching elongation. Experimental validation was conducted on stretch-wrap bending machine. The experiment part meets the processing requirements, thereby validating the reasonability of the optimization method. Measured results showed consistency with numerical analysis which verifies the feasibility of using FE simulation to guide the experiment. [ABSTRACT FROM AUTHOR]

Katz et al. (2014) carried out a study of controls on the size and geometry of landslides using two-dimensional discrete element numerical simulations. One of their conclusions is that in addition to the peak strength of the slope material, the initial slope angle is another factor that controls the amount of material available for landslides, thus the size, of the resultant landslide. It means that in steeper slopes, more material disintegrates for a given material strength, and consequently the produced landslide is larger. However, in our studies based on limit equilibrium simulations, the sliding mass volume decreases with the increasing slope angle for a given material strength, just contrary to the result of Katz et al. One possible explanation is that when the slope angle in our model increases, the geometry of the potential critical slip surface changes, leading to a decrease of the amount of material available for potential sliding that compensates the increasing gravity effect owing to the enlargement of the slope angle. It suggests that there exist different controls of the slope angle on the landslide size for given material strength. [ABSTRACT FROM AUTHOR]

Unsupervised ranking faces one critical challenge in evaluation applications, that is, no ground truth is available. When PageRank and its variants show a good solution in related objects, they are applicable only for ranking from link-structure data. In this work, we focus on unsupervised ranking from multi-attribute data which is also common in evaluation tasks. To overcome the challenge, we propose five essential meta-rules for the design and assessment of unsupervised ranking approaches: scale and translation invariance, strict monotonicity , compatibility of linearity and nonlinearity, smoothness, and explicitness of parameter size. These meta-rules are regarded as high level knowledge for unsupervised ranking tasks. Inspired by the works in [12] and [35] , we propose a ranking principal curve (RPC) model, which learns a one-dimensional manifold function to perform unsupervised ranking tasks on multi-attribute observations. Furthermore, the RPC is modeled to be a cubic Bézier curve with control points restricted in the interior of a hypercube, complying with all the five meta-rules to infer a reasonable ranking list. With control points as model parameters, one is able to understand the learned manifold and to interpret and visualize the ranking results. Numerical experiments of the presented RPC model are conducted on two open datasets of different ranking applications. In comparison with the state-of-the-art approaches, the new model is able to show more reasonable ranking lists. [ABSTRACT FROM AUTHOR]

We have developed a method for the T4 DNA ligase-catalyzed DNA-templated polymerization of 5'-phosphorylated pentanucleotides containing peptide fragments. The polymerization proceeds sequence-specifically to generate DNA-scaffolded peptides in excellent yields. The method has been shown to tolerate peptides ranging from two to eight amino acids in length with a wide variety of functionality. We validated the capabilities of this system in a mock selection for the enrichment of a His-tagged DNA-scaffolded peptide phenotype from a library, which exhibited a 190-fold enrichment after one round of selection. This strategy demonstrates a promising new approach to allowing the generation and in vitro selection of high-affinity reagents based upon single-stranded DNA scaffolding of peptide fragments. [ABSTRACT FROM AUTHOR]

Although widespread vaccination against canine distemper virus (CDV) has been conducted for many decades, several canine distemper outbreaks in vaccinated animals have been reported frequently. In order to detect and differentiate the wild-type and vaccine strains of the CDV from the vaccinated animals, a novel reverse transcription loop-mediated isothermal amplification (RT-LAMP) method was developed. A set of four primers—two internal and two external—were designed to target the H gene for the specific detection of wild-type CDV variants. The CDV-H RT-LAMP assay rapidly amplified the target gene, within 60 min, using a water bath held at a constant temperature of 65 °C. The assay was 100-fold more sensitive than conventional RT-PCR, with a detection limit of 10 −1 TCID 50 ml −1 . The system showed a preference for wild-type CDV, and exhibited less sensitivity to canine parvovirus, canine adenovirus type 1 and type 2, canine coronavirus, and canine parainfluenza virus. The assay was validated using 102 clinical samples obtained from vaccinated dog farms, and the results were comparable to a multiplex nested RT-PCR assay. The specific CDV-H RT-LAMP assay provides a simple, rapid, and sensitive tool for the detection of canines infected with wild-type CDV from canines vaccinated with attenuated vaccine. [ABSTRACT FROM AUTHOR]

Osteopontin (OPN), a secreted acid glycoprotein with a variety of functions, promotes tumor proliferation, differentiation, invasion and metastasis. The aim of the current study was to investigate whether OPN may serve as a potential therapeutic target for human bladder cancer. RNA interference (RNAi) was performed to downregulate the expression of the OPN gene in T24 human bladder cancer cells. The mRNA and protein expression levels of OPN following RNAi were determined using reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. In addition, the cell cycle progression, apoptosis and proliferation were investigated using by flow cytometric analysis and MTT assay. The cell invasion ability was measured using a Matrigel transwell assay. The mRNA and protein expression levels of OPN were found to be significantly downregulated following RNAi. The proliferation and invasion of T24 cells were significantly inhibited in vitro. In conclusion, RNAi-targeting OPN may inhibit the proliferation, invasion and tumorigenicity of human bladder cancer cells. Therefore, OPN may serve as a potential therapeutic target for human bladder cancer. [ABSTRACT FROM AUTHOR]

Repression of peroxisome proliferator-activated receptor γ (PPARγ)-dependent transcription by the nuclear receptor corepressor (NCoR) is important for homeostatic expression of PPARγ target genes in vivo. The current model states that NCoR-mediated repression requires its direct interaction with PPARγ in the repressive conformation. Previous studies, however, have shown that DNA-bound PPARγ is incompatible with a direct, high-affinity association with NCoR because of the inherent ability of PPARγ to adopt the active conformation. Here we show that NCoR acquires the ability to repress active PPARγ-mediated transcription via G protein pathway suppressor 2 (GPS2), a component of the NCoR corepressor complex. Unlike NCoR, GPS2 can recognize and bind the active state of PPARγ. In GPS2-deficient mouse embryonic fibroblast cells, loss of GPS2 markedly reduces the corepressor function of NCoR for PPARγ, leading to constitutive activation of PPARγ target genes and spontaneous adipogenesis of the cells. GPS2, however, is dispensable for repression mediated by unliganded thyroid hormone receptor α or a PPARγ mutant unable to adopt the active conformation. This study shows that GPS2, although dispensable for the intrinsic repression function of NCoR, can mediate a novel corepressor repression pathway that allows NCoR to directly repress active PPARγ-mediated transcription, which is important for the optimal corepressor function of NCoR for PPARγ. Interestingly, GPS2-dependent repression specifically targets PPARγ but not PPARα or PPARδ. Therefore, GPS2 may serve as a unique target to manipulate PPARγ signaling in diseases. [ABSTRACT FROM AUTHOR]

Abstract: The 2008 Wenchuan earthquake in China triggered approximately 200,000 landslides. This study examined a detailed landslide inventory for the event. Based on Newmark's method, the correlation between critical acceleration and landslide occurrence was analyzed for the Beichuan region in Sichuan Province, where various kinds of geohazards occurred due to the earthquake. The results indicate that critical acceleration is a good and reliable criterion to assess slope stability, and that slope gradient and material component are important factors influencing landslide occurrences. It was found that external forces behave differently in different directions. Critical acceleration in horizontal direction is more important for assessing the stability of steeper slopes. This knowledge will help in the understanding of the mechanism of earthquake-triggered landslides and facilitate the combined use of critical acceleration and landslide distribution maps for determining peak ground acceleration in a region without abundant seismic instrument records. [Copyright &y& Elsevier]

A three-dimensional NbO-type MOF with the formula Cu2(EBTC)(H2O)2.[G] (1) (EBTC4- = 1,1'-ethynebenzene- 3,3',5,5'-tetracarboxylate; G = guest molecules and represent DMF, DMSO and H2O) was synthesized using a solvothermal method. The sufficient cavity space in 1 can be used to encapsulate the heterocyclic compounds benzopyrrole (C8H7N), benzofuran (C8H6O) and benzothiophene (C8H6S). The guest-free framework (2) was obtained by heating methanol-exchanged 1 at 130 °C under vacuum. The clathrates [Cu2(EBTC)(H2O)2.1.6C8H7N]∞ (3), [Cu2(EBTC)(H2O)2.2.5C8H6O]∞ (4) and [Cu2(EBTC)- (H2O)2.2C8H6S]∞ (5) were prepared by soaking 2 in C8H7N, C8H6O and C8H6S at 55 °C for 48 h, respectively. 1-5 showed quite similar PXRD patterns, indicating that they have the same framework structure. The IR and Raman spectra and the variable-temperature magnetic susceptibilities were comparatively studied for 1-5; the results disclosed the existence of weakly intermolecular interactions between the -CuC- in the organic linkers and guest molecules, whereas an almost complete absence of intermolecular interactions between the paddle-wheel-type dinuclear Cu2 units and large guest molecules owing to steric hindrance. This study suggests the possibility of these rather useful MOF materials in the removal of organosulfur or organonitrogen compounds that are widely known contaminants in petroleum and fuels via their rationally designed organic linkers. [ABSTRACT FROM AUTHOR]

Background: Influenza A virus has a wide range of hosts. It has not only infected human, but also been reported interspecies transmission from humans to other animals, such as pigs, poultry, dogs and cats. However, prevalence of A (H1N1) pdm09 influenza virus infections in cats in northeastern China is unknown. Therefore, the prevalence of A (H1N1) pdm09 influenza virus infections was performed among cats in northeastern China in this study. Findings: Of all samples in this study, the overall seroprevalence of pandemic (H1N1) 2009 infection in cats was 21% (240/1140). It also showed a higher prevalence rate of pandemic(H1N1) 2009 infection in pet cats (30.6%) than roaming cats (11%) based on NT. In addition, the results also showed a trend of difference in term of species of cats and it was statistically significant. Conclusions: This is the first survey on the seroprevalence of pandemic (H1N1) 2009 infection among cats in northeastern China. This study has observed a relatively high seroprevalence of pandemic (H1N1) 2009 among different cat populations in northeastern China, similar seroprevalence studies should be conducted elsewhere. [ABSTRACT FROM AUTHOR]

This article is concerned with an optimization problem governed by a Timoshenko beam equation with periodic constraints. Firstly, a detail spectral analysis is conducted for the Timoshenko operator related to the homogeneous system. Then, we derive a closed range property of the state equation. Finally, we present the main results: the optimality conditions and the maximum principle for our problem via the closed range theorem. [ABSTRACT FROM AUTHOR]

Abstract: The microstructure and texture evolutions of a rolled Mg–6Al–3Sn (AT63) alloy were investigated during uniaxial tension along the rolling and transverse directions. Combination of experimental examination and Schmid factor analysis indicates that the texture evolution during the two tensions results mainly from dislocation slip. The texture variations in (0002) and (101̄0) poles are related to basal slip and non-basal slips, respectively. The final textures exhibit the lowest SF values not only for basal slip but also for non-basal slips. Our results will be helpful in the investigation of slip mechanism based on texture examination. [Copyright &y& Elsevier]

In this paper, the synchronization problem of general complex networks is investigated by using adaptive control schemes. Time-delay coupling, derivative coupling, nonlinear coupling etc. exist universally in real-world complex networks. The adaptive synchronization scheme is designed for the complex network with multiple class of coupling terms. A criterion guaranteeing synchronization of such complex networks is established by employing the Lyapunov stability theorem and adaptive control schemes. Finally, an illustrative example with numerical simulation is given to show the feasibility and efficiency of theoretical results. [ABSTRACT FROM AUTHOR]

Abstract: Three highly pathogenic H5N5 avian influenza viruses (HPAI), A/duck/Guangdong/wy11/2008 (WY11), A/duck/Guangdong/wy19/2008 (WY19), and A/duck/Guangdong/wy24/2008 (WY24) were isolated from ducks in southern China in April 2008. Here, we characterized these viruses by performing sequencing and phylogenetic analyses of their viral genes, assessing their virulence in ducks and mice, and performing cross-protection experiments in chickens. Sequence analysis revealed that the HA genes of these H5N5 viruses showed 97.1–97.8% homology to A/wild duck/Hunan/211/2005 (H5N1) influenza virus and that their NA genes showed 96.4–96.8% nucleotide identity to the NA gene of A/duck/Hunan/5613/2003 (H6N5) influenza virus, which belongs to the Eurasian lineage. Genotypic analysis indicated that these H5N5 viruses were multiple reassortants among H5N1, H5N2, H6N2, and H6N5 viruses. The analysis of HA clade showed that these H5N5 viruses are clustering into clade 2.3.4. In animal experiments, these H5N5 viruses caused 50% mortality in ducks and 100% mortality in chickens. In cross-protection experiments, the clade 2.3.2 avian influenza vaccine could provide only 75% protection with chickens against H5N5 virus challenge. Moreover, the H5N5 virus replicated efficiently in the lungs of mice, which suggested that the H5N5 viruses have the potential to infect mammalian hosts. Since ducks have served as reassortant vessels, playing pivotal roles in the generation of new subtypes of influenza viruses, it is important to monitor the emergence of this novel subtype of influenza viruses in waterfowl to understand their ecology and evolution and to control the spread of new viruses. [Copyright &y& Elsevier]

Abstract: Uniaxial compression tests were performed on an extruded Mg–6Al–3Sn (AT63) alloy with a dual basal texture, along the extrusion direction (ED), transverse direction (TD) and normal direction (ND). Unlike the single basal texture commonly seen in rolled Mg alloys, for which either extension or contraction twinning is favored in one compression, the dual basal texture appreciates both extension and contraction twinning. Nevertheless extension and contraction twinning display different activities among the three compressions. The results suggest that extension twinning propagates largely for ED compression while it displays limited propagations for TD and ND compressions, although it nucleates at the onset of plasticity for all the three compressions. In contrast, contraction twinning nucleates early and widely for TD and ND compressions while it is largely suppressed for ED compression. It is the wider propagations of extension twinning and belated contraction twinning that result in a larger drop and a higher peak in the strain hardening curve for ED compression. Our results shed some light on deformation mechanisms of the Mg alloys consisting of multiple texture components. [Copyright &y& Elsevier]

Abstract: Plane strain compressions were conducted on a rolled Mg–6Al–3Sn (AT63) alloy plate along the rolling direction (termed in-plane compression, IPC) and normal direction (termed through-thick compression, TTC), respectively. Deformation behaviors (mechanical response, microstructure evolution and macrotexture development) of each plane strain compression were compared against those of equivalent uniaxial compression (UC), and deformation mechanisms of IPC and TTC were investigated in detail. It has been found that the IPC with transverse constraint exhibits enhanced basal slip and retarded extension twinning with respect to the corresponding UC. However, the IPC with normal constraint transforms the main deformation mechanisms (i.e., extension twinning and basal slip) into prismatic slip and directional pyramidal slip. The TTCs, no matter with rolling or transverse constraint, suppress basal slip dramatically and cause directional contraction twins and directional pyramidal slip. The differences in deformation mechanisms between the plane strain compression and the corresponding UC are explained in relation to Schmid factor and strain directionality. Our results shed light on the deformation mechanisms of Mg alloys during plane strain compressions. [Copyright &y& Elsevier]

Abstract: The preparation of high-yield influenza H5N1 vaccine strains is challenging for researchers and manufacturers. Here, we used reverse genetics to generate a high-yield avian influenza vaccine strain based on a novel avian influenza virus. A high-yield attenuated recombinant H5N3 virus (rH5N3-DL) was prepared from the HA gene of A/Goose/Anhui/08 (H5N1), modified by deletion of the multiple basic amino acids at the cleavage site, the NA gene from A/Duck/Germany/1215/73 (H2N3), and the six internal genes from the high-yield A/Goose/Dalian/3/01 (H9N2) virus. rH5N3-DL grew to high HA titers (1:2048) in eggs, eight times those of the parental H5N1 virus, and four times higher than that of rH5N3-PR8 (six internal genes from the high-yield PR8). Infection tests demonstrated that rH5N3-DL was avirulent in chickens, chicken embryos, and mice. rH5N3-DL-vaccinated chickens were fully protected against the morbidity and mortality of a lethal challenge with homologous A/Goose/Anhui/08, but only 80% of chickens were protected after challenge with heterologous A/Goose/Guangdong/1/96. The N3 neuraminidase marker distinguishes rH5N3-DL-vaccinated from H5N1-infected animals. rH5N3-DL is thus a promising vaccine candidate to combat highly pathogenic avian influenza virus infections. The A/Goose/Dalian/3/01 virus could be a promising candidate as providing internal genes donors with high-yield properties in reverse-genetics system and might be applicable for future avian influenza vaccine development. [Copyright &y& Elsevier]

Aims: Quercetin, a flavonoid present in vegetables, has anti-inflammatory properties and potential inhibitory effects on bone resorption. Up to date, the effect of quercetin on lipopolysaccharide (LPS)-induced osteoclastogenesis has not yet been reported. In the current study, we evaluated the effect of quercetin on LPS-induced osteoclast apoptosis and bone resorption. Methods: RAW264.7 cells were non-treated, treated with LPS alone, or treated with both LPS and quercetin. After treatment, the number of osteoclasts, cell viability, bone resorption and osteoclast apoptosis were measured. The expressions of osteoclast-related genes including tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinase-9 (MMP-9) and cathepsin K (CK) were determined by real-time quantitative polymerase chain reaction (qPCR). Protein levels of receptor activator of nuclear factor-&kgr;B (RANK), tumor necrosis factor receptor-associated factor 6 (TRAF6), cyclooxygenase-2 (COX-2), Bax, Bcl-2 and mitogen-activated protein kinases (MAPKs) were measured using Western blotting assays. The MAPK signaling pathway was blocked by pretreatment with MAPK inhibitors. Results: LPS directly promoted osteoclast differentiation of RAW264.7 cells and upregulated the protein expression of RANK, TRAF6 and COX-2; while quercetin significantly decreased the number of LPS-induced osteoclasts in a dose-dependent manner None of the treatments increased cytotoxicity in RAW264.7 cells. Quercetin inhibited mRNA expressions of osteoclast-related genes and protein levels of RANK, TRAF6 and COX-2 in LPS-induced mature osteoclasts. Quercetin also induced apoptosis and inhibited bone resorptive activity in LPS-induced mature osteoclasts. Furthermore, quercetin promoted the apoptotic signaling pathway including increasing the phosphorylation of p38-MAPK, c-Jun N-terminal kinases/stress-activated protein kinases (JNK/SAPK), and Bax, while inhibited Bcl-2 expression. Conclusions: Quercetin could suppress LPS-induced osteoclast bone resorption through blocking RANK signaling and inhibiting the expression of osteoclast-related genes. Quercetin also promoted LPS-induced osteoclast apoptosis via activation of the MAPK apoptotic signaling pathway. These findings suggest that quercetin could be of potential use as a therapeutic agent to treat bacteria-induced bone resorption. [ABSTRACT FROM AUTHOR]

Edible bird's nests have a variety of biological activities, the main components of which are sialic acids. Sialic acids are a group of nine-carbon N-acetylated derivatives of neuraminic acid containing a keto group at position C2 and play important roles in many biological processes. To verify whether the oral administration of edible bird's nests would change the content and distribution of sialic acid components in vivo, a liquid chromatography–mass spectrometry method for the quantitative analysis of sialic acid levels in serum and tissues was developed. In the negative ion mode, the mobile phases consist of 0.1% formic acid in water (A) and acetonitrile (v/v) (B). Isocratic elution was performed with 60% B for 0−15 min. The chromatographic separation was performed on a Morphling HILIC Amide column (2.1 mm × 150 mm, 5 μm) at a flow rate of 0.5 mL min−1. The results showed that the correlation coefficients of the typical calibration curves were all higher than 0.995, exhibiting good linearity. The levels of free and conjugated forms of N-glycolylneuraminic acid (Neu5Gc), N-acetylneuraminic acid (Neu5Ac), and 2-keto-3-deoxy-D-glycero-D-galactonononic acid (KDN) in the serum and different tissues were simultaneously detected after the oral administration of the edible bird's nests at a daily dose of 300 and 700 mg Kg−1 for seven days in mice. Our study found that the oral administration of edible bird's nests can significantly increase the concentration of total sialic acids (Neu5Gc + Neu5Ac + KDN) in serum and spleen and lungs tissues, which may be related to the anti-inflammatory and immune function of edible bird's nest, but further studies are needed to verify this. Neu5Ac was the dominant sialic acid in brain tissue, and Neu5Gc was the dominant sialic acid in serum and other tissues, including heart, liver, spleen, lungs, and kidney. Moreover, we found that the forms of Neu5Ac and Neu5Gc were mainly conjugated in all groups except liver tissue. In conclusion, the method we established had good linearity and accuracy; it allowed the analytes to be effectively separated from the matrix and endogenous substances in serum or tissues, so it could effectively detect the distribution and concentration of free and conjugated forms of sialic acids in serum and tissues, which was beneficial to the research and exploitation of edible bird's nests and sialic acids. [ABSTRACT FROM AUTHOR]

An important step in transcriptional regulation by corepressors N-CoR and SMRT is the formation of a stable and active histone deacetylase 3 (HDAC3)-containing complex. Although N-CoR and SMRT are thought to bind HDAC3 competitively, multiple studies have shown that they do not interfere with the function of each other.Howthis functional independence is sustained under the competitive interaction is unclear. Here, we show that the coupling of corepressor expression with HDAC3 degradation allows cells to maintain a stable level of uncomplexed HDAC3, thereby preventing mutual interference in the assembly of N-CoR and SMRT complexes. The free uncomplexed HDAC3 is highly unstable. Unexpectedly, the rate of HDAC3 degradation is inversely correlated with the expression level of corepressors. Our results indicate that reducing one corepressor accelerates HDAC3 clearance, thus preventing an increase in complex formation between HDAC3 and the other corepressor. In addition, this study also indicates that the formation of a stable and active HDAC3-corepressor complex is a stepwise process in which the C terminus of HDAC3 plays a critical role at late steps of the assembly process. [ABSTRACT FROM AUTHOR]

In the ventilation design for tunnels above 10km, an axial flow fan of great power needs to be set in ventilation shafts. There are few provisions on the setting modes and less discussion of parallel axial flow fan mode in the Specifications for Design of Ventilation and Lighting of Highway Tunnels. All of these bring a lot of difficulties about the axial fan selection, layout and control design. There is no specialized research on axial flow fan for tunnels and no studies on surge and stall under the interaction of parallel axial flow fan in tunnel in spite of the more and more application of parallel axial flow fan. So, this paper conducts a study on surge and stall under the interaction of parallel axial flow fan in tunnels. Through the study on the operating principle and analysis of parallel axial flow fan, we can know that the noise will increase suddenly, which will in turn result in fan vibration and running instability once the stall occurs. When a fan surges, the air volume and pressure, the motor current will fluctuate sharply, which brings significantly increased vibration and noise. At the same time, the rotary blade and the shell are subject to considerable stress effects and the fan will possibly suffer from great damage. The surge will occur in the unstable zone of axial fan performance curve. The strong pulsation and periodic oscillation of the air flow will increase the noise, which is a serious damage to the fan. So an axial fan should avoid this zone in running. With two axial flow fans of the same power parallel, the mutual influence is not very great. Therefore this research will focus on the efficiency in the case of two fans with a high and a low power parallel. Stall will occur if the outside pressure is greater than the outlet pressure. Once the stall happens, the noise will increase suddenly, which will in turn result in fan vibration and running instability. When two fans parallel, i.e. when the power ratio of the parallel fans is over 5.3, the possibility of the small fan's stall is high, otherwise it is small. With regard to the running efficiency of parallel axial flow fans and the starting safety, it is better to parallel two fans, and the fans with adjustable movable vanes or frequency control or the ordinary nonadjustable fans can be used. [ABSTRACT FROM AUTHOR]

TiAl coating was in situ synthesized successfully on pure Ti substrate by laser-cladding technology using aluminum powder as the precursor. The composition and microstructure of the prepared coating were analyzed by transmission electron microscopy, scanning electron microscopy (SEM), and X-ray diffraction technique. Thermal gravimetric analysis was used to evaluate the high-temperature oxidation resistance of the TiAl coating. The friction and wear behavior was tested through sliding against SiN ball at elevated temperature of 20, 100, 300, and 500°C. The morphologies of the worn surfaces and wear debris were also analyzed by SEM and three-dimensional non-contact surface mapping. The results show that the TiAl coating with high microhardness, high-temperature oxidation resistance, and high temperature wear resistance. The pure Ti substrate is dominated by severe adhesion wear, abrasive wear, fracture, and severe plastic deformation at lower temperature, and severe adhesion wear, abrasive wear, plastic deformation, oxidation, and nitriding wear at higher temperature, whereas the TiAl coating experiences only moderate abrasive and adhesive wear when sliding against the SiN ceramic ball counterpart. In addition, the wear debris of the laser-cladding TiAl coating sliding and SiN friction pairs are much smaller than that of pure Ti substrate and SiN friction pairs at elevated temperature. [ABSTRACT FROM AUTHOR]

It is proposed that human decidua contains a population of stem cells that are responsible for the proliferation ability during the process of embryo implantation and placenta formation and that factors in the crosstalk between the decidua and chorion may mediate decidual stem cell differentiation. This study analysed the phenotype of side population (SP) celts and investigated the ctonogenicity and differentiation ability of SP cells in human decidua of early pregnancy. Serum-free culture-conditioned media of human decidua and chorion were obtained from decidua and chorion explant culture. Decidual SP cells were isolated by fluorescence-activated cell sorting. Different inducing media were added and the functional differentiation of decidual SP cells was examined. Decidual SP cells were negative for the mature decidual cell marker CD13 and prolactin and negative for CD34 and CD45 expression. Decidual SP cells formed clones after culture in colony-forming medium and they could form clones again. Differentiated cells expressing CD13 and prolactin were observed and stroma-tike structures expressing CD13 were obtained. These results indicate that decidual SP cells are enriched for stem cell activity. Oestradiol, progesterone and factors in culture-conditioned media of human decidua and chorion induced their proliferation and differentiation. [ABSTRACT FROM AUTHOR]

Salmonid alphavirus (SAV) is an emerging virus in salmonid aquaculture, with SAV-3 being the only subtype found in Norway. Until now, there has been little focus on the alpha interferon (IFN-α)-induced antiviral responses during virus infection in vivo or in vitro in fish. The possible involvement of IFN-γ in the response to SAV-3 is also not known. In this study, the two IFNs were cloned and expressed as recombinant proteins (recombinant IFN-α [rIFN-α] and rIFN-γ) and used for in vitro studies. SAV-3 infection in a permissive salmon cell line (TO cells) results in IFN-α and IFN-stimulated gene (ISG) mRNA upregulation. Preinfection treatment (4 to 24 h prior to infection) with salmon rIFN-α induces an antiviral state that inhibits the replication of SAV-3 and protects the cells against virus-induced cytopathic effects (CPE). The antiviral state coincides with a strong expression of Mx and ISG15 mRNA and Mx protein expression. When rIFN-α is administered at the time of infection and up to 24 h postinfection, virus replication is not inhibited, and cells are not protected against virus-induced CPE. By 40 h postinfection, the alpha subunit of eukaryotic initiation factor 2 (eIF2α) is phosphorylated concomitant with the expression of the E2 protein as assessed by Western blotting. Postinfection treatment with rIFN-α results in a moderate reduction in E2 expression levels in accordance with a moderate downregulation of cellular protein synthesis, an approximately 65% reduction by 60 h postinfection. rIFN-γ has only a minor inhibitory effect on SAV-3 replication in vitro. SAV-3 is sensitive to the preinfection antiviral state induced by rIFN-α, while postinfection antiviral responses or postinfection treatment with rIFN-α is not able to limit viral replication. [ABSTRACT FROM AUTHOR]

Yu L, Guo W-C, Zhao S-H, Tang J, Chen J-L. Mitotic arrest defective protein 2 expression abnormality and its clinicopathologic significance in human osteosarcoma. APMIS 2010; 118: 222–29. Osteosarcoma is the most common primary malignancy of bone. Overexpression of mitotic arrest defective protein 2 (MAD2) is found in many human neoplasms, but its role in the oncogenesis of osteosarcoma is an untouched topic. The objective of this research was to observe the expression of MAD2 in human osteosarcoma and explore its clinicopathologic significance. MAD2 expression was analyzed in 48 primary osteosarcoma cases (19 osteoblastic osteosarcomas, 17 chondroblastic osteosarcomas and 12 fibroblastic osteosarcomas) using immunohistochemistry. A total of 20 normal bone specimens formed a control group. MAD2 was commonly overexpressed in human osteosarcoma. Immunopositivity was higher in tumors with lower differentiation and higher clinical stage. Increased expression of MAD2 was associated with earlier metastasis and poorer survival. Our findings provide evidence that MAD2 contributes to the pathogenesis and development of human osteosarcoma, Testing may have a clinical role in predicting prognosis, selecting appropriate chemotherapeutic strategies and providing novel strategies for osteosarcoma therapy. [ABSTRACT FROM AUTHOR]

Ant colony optimization (ACO) has widely been applied to solve combinatorial optimization problems in recent years. There are few studies, however, on its convergence time, which reflects how many iteration times ACO algorithms spend in converging to the optimal solution. Based on the absorbing Markov chain model, we analyze the ACO convergence time in this paper. First, we present a general result for the estimation of convergence time to reveal the relationship between convergence time and pheromone rate. This general result is then extended to a two-step analysis of the convergence time, which includes the following: 1) the iteration time that the pheromone rate spends on reaching the objective value and 2) the convergence time that is calculated with the objective pheromone rate in expectation. Furthermore, four brief ACO algorithms are investigated by using the proposed theoretical results as case studies. Finally, the conclusions of the case studies that the pheromone rate and its deviation determine the expected convergence time are numerically verified with the experiment results of four one-ant ACO algorithms and four tenant ACO algorithms. [ABSTRACT FROM AUTHOR]

Cyclic dipeptides are relatively simple compounds that can exhibit a great variety of important biological activities. The fragmentation pathways of protonated cyclic dipeptides have been studied by electrospray ionization multistage mass spectrometry (ESI-MSn). The mass spectra studies of the cyclic dipeptides showed that the cyclic dipeptides with the similar substituents, the side chains of amino acid residues at the diketopiperazine ring, followed the same fragmentation pathway. In the fragmentation spectra of protonated cyclic dipeptides, some characteristic fragment ions were observed and could be used to distinguish the cyclic dipeptides. The hydrogen/deuterium (H/D) exchange experiment and the high-resolution mass spectrometry (Q-TOF) were used to verify and rationalize the proposed fragmentation pathways. These observations may have some potential applications in the structural elucidation and interpretation of the mass spectra of homologous compounds. [ABSTRACT FROM AUTHOR]

E proteins are a family of helix-loop-helix transcription factors that play important roles in cell differentiation and homeostasis. They contain at least two activation domains, AD1 and AD2. ETO family proteins and the leukemogenic AML1-ETO fusion protein are corepressors of E proteins. It is thought that ETO represses E-protein activity by interacting with AD1, which competes away p300/CBP histone acetyltransferases. Here we report that E proteins contain another conserved ETO-interacting region, termed DES, and that differential associations with AD1 and DES allow ETO to repress transcription through both chromatin-dependent and chromatin-independent mechanisms. At the chromatin level, AD1 and AD2 cooperatively recruit p300. ETO interacts with AD1 to abolish p300 recruitment and to allow HDAC-dependent silencing. At the post-chromatin-remodeling level, binding to DES enables ETO to directly inhibit activation of the basal transcription machinery. This novel repression mechanism is conserved in ETO family proteins and in the AML1-ETO fusion protein. In addition, the repression capacity exerted by each mechanism is differentially modulated by cross talk among various ETO domains and the AML1 domain of AML1-ETO. In particular, the oligomerization domain of ETO plays a major role in targeting ETO to the DES region and independently potentiates the TAFH domain-mediated AD1 interaction. The ability to exert repression at different levels not only may allow these corepressors to impose robust inhibition of signal-independent transcription but may also allow a rapid response to signals. In addition, our newly defined domain interactions and their interplays have important implications in effectively targeting both E-protein fusion proteins and AML1-ETO found in cancers. [ABSTRACT FROM AUTHOR]

The c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) signaling pathway mediates stress responses in cells. JNK activity is regulated by a protein kinase cascade consisting of a MAPK kinase (MKK) and a MAPK kinase kinase (MAPKKK). β-Arrestin-2 acts as a scaffold by directly binding to the JNK3 isoform and also by recruiting MKK4 and the MAP-KKK apoptosis-signaling kinase-1 (ASK1). In this study, we demonstrate by co-precipitation that the extended N-terminal region of JNK3 mediates binding to the C terminus of β-arrestin-2 and that the N terminus of JNK3 is required for its activation via β-arrestin-2. We have used site-specific mutagenesis to identify key residues within the N terminus of JNK3 that are essential for binding and demonstrate that this region represents an independent β-arrestin-2 binding motif that can be fused to other MAPKs and permit their recruitment to the scaffold complex. In addition, we demonstrate that JNK3 recruits MKK4 to the β-arrestin-2 scaffold complex by binding to the MAPK docking domain (D-domain) located within the N terminus of MKK4. These findings uncover molecular determinants of β-arrestin-2 scaffold complex assembly and assign a previously unrecognized role for the unique extended N terminus of JNK3. [ABSTRACT FROM AUTHOR]

Abstract: Considering the inputs of a feed-forward neural network as random variables, this paper proposes a definition of partial derivative of a function with respect to a random variable in the probability measure space. The mathematical expectation of the mean square or absolute value of the partial derivative is regarded as a type of measure of the network''s sensitivity, which extends Zurada''s sensitivity definition of networks in Zurada et al, [Perturbation method for deleting redundant inputs of perceptron networks, Neurocomputing 14 (1997) 177–193] from the certain environment to the stochastic environment. Furthermore, for the purpose of network''s redundant feature deletion or feature selection, the new sensitivity measure is applied to the sensitivity analysis of Radial Basis Function Neural Networks (RBFNNs). The feasibility and the effectiveness of the sensitivity approach to redundant feature deletion are illustrated. [Copyright &y& Elsevier]

Abstract: In this paper, we study a boundary feedback system of a class of nonuniform undamped Timoshenko beam with both ends free. We give some sufficient conditions and some necessary conditions for the system to have exponential stability. Our method is based on the operator semigroup technique, the multiplier technique, and the contradiction argument of the frequency domain method. [Copyright &y& Elsevier]

Migration of cardiac fibroblasts is implicated in infarct healing and ventricular remodeling. Activation of matrix metalloproteinases induced by three-dimensional type I collagen, the principal component of the myocardial interstitium, is hypothesized to be essential for this migration. By utilizing primary cultures of cardiac fibroblasts and collagen lattice models, we demonstrated that type I collagen induced MMP-2 activation, and cells undergoing a change from isometric tension to mechanical unloading were associated with increased levels of total and active MMP-2 species. The collagen-induced MMP-2 activation coincided with up-regulated cellular levels of both membrane type 1-matrix metalloproteinase (MT1-MMP) and TIMP-2. A fraction of cellular membrane prepared from cells embedded in the collagen lattice containing active MT1-MMP and TIMP-2 was capable of activating pro-MMP-2, and exogenous TIMP-2 had a biphasic effect on this membrane-mediated MMP-2 activation. Interestingly, the presence of 43-kDa MT1-MMP species in a fraction of intracellular soluble proteins prepared from monolayer cells but not cells embedded in the lattices indicates that MT1-MMP metabolizes differently under the two different culture conditions. Treatment of cells embedded in the lattice with furin inhibitor attenuated pro-MT1-MMP processing and MMP-2 activation and impeded cell migration and invasion. These results suggest that the migration and invasion of cardiac fibroblasts is furin-dependent and that the active species of MT1-MMP and MMP-2 may be involved in both events. [ABSTRACT FROM AUTHOR]