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Tumor necrosis factor α (TNFα) is thought to mediate both protective and detrimental manifestations of the inflammatory response. Recently, thalidomide (α-n–phthalimidoglutarimide) was shown to partially inhibit monocyte TNFα production (by 50–70%) both in vivo and in vitro. More efficient inhibition of TNFα may, however, be necessary to rescue the host from more acute and extensive toxicities of TNFα-mediated inflammation. Three structural analogues of thalidomide were selected for study based on increased activity against TNFα production. The parent drug and the analogs were tested in vitro in human peripheral blood mononuclear cell cultures for their effects on lipopolysaccharide (LPS) induced cytokine protein and mRNA production using ELISAs and Northern blot hybridization. The in vitro effects of the drugs were then confirmed in vivo in a mouse model of LPS induced lethality. The new compounds (two esters and one amide) showed increased inhibition of TNFα production by LPS-stimulated human monocytes, relative to the parent drug thalidomide. The analogs and the parent drug enhanced the production of interleukin 10 (IL-10), but had little effect on IL-6 and IL-1β protein and mRNA production. When tested in vivo, the amide analog protected 80% of LPS-treated mice against death from endotoxin induced shock. Analogs of thalidomide designed to better inhibit TNFα production in vitro have correspondingly greater efficacy in vivo. These finding may have therapeutic implication for the treatment of human diseases characterized by acute and extensive TNFα production such as tuberculous meningitis or toxic shock.

Previously, we identified the genetic variant -241 (-/G) (rs11453459) in the PP2A-Aα gene (PPP2R1A) promoter and demonstrated that this variant influences the DNA-binding affinity of nuclear factor-kappa B (NF-κB). In this study, we further confirmed that the transcriptional activity of PPP2R1A may be regulated by NF-κB through the functional genetic variant -241 (-/G). Moreover, we also demonstrated that the methylation status of CpG islands in the promoter of PPP2R1A influences the activity of this gene promoter. Few studies have examined the role of this -241 (-/G) variant in genetic or epigenetic regulation in hepatocellular carcinoma (HCC). To investigate whether this functional variant in the PPP2R1A promoter is associated with the risk of HCC and confirm the function of the -241 (-/G) variant in the HCC population, we conducted a case-control study involving 251 HCC cases and 252 cancer-free controls from a Han population in southern China. Compared with the -241 (--) homozygote, the heterozygous -241 (-G) genotype (adjusted OR = 0.32, 95% confidence interval (CI) = 0.17-0.58, P

This paper provides an explanation of transfer function about how the agile service development works. The emphasis of individuals' subjective initiate and social team behaviour in current agile service development methods facilitates pouring plenty of developing resources into efforts that predominates the developing process. The essential of agile service development also implies the improvement direction to establish more powerful agile development method to meet rapidly evolving service requirements.

Serine-threonine protein phosphatase 2A (PP2A) is a trimeric holoenzyme that plays an integral role in the regulation of cell growth, differentiation, and apoptosis. The substrate specificity and (sub)cellular localization of the PP2A holoenzymes are highly regulated by interaction with a family of regulatory B subunits (PP2A-Bs). The regulatory subunit PP2A-B/PR55δ (PP2A-Bδ) is involving in the dephosphorylation of PP2A substrates and is crucial for controlling entry into and exit from mitosis. The molecular mechanisms involved in the regulation of expression of PP2A-Bδ gene (PPP2R2D) remain largely unknown. To explore genetic variations in the 5′-flanking region of PPP2R2D gene as well as their frequent haplotypes in the Han Chinese population and determine whether such variations have an impact on transcriptional activity, DNA samples were collected from 70 healthy Chinese donors and sequenced for identifying genetic variants in the 5′-flanking region of PPP2R2D. Four genetic variants were identified in the 1836 bp 5′-flanking region of PPP2R2D. Linkage disequilibrium (LD) patterns and haplotype profiles were constructed for the genetic variants. Using serially truncated human PPP2R2D promoter luciferase constructs, we found that a 601 bp (−540 nt to +61 nt) fragment constitutes the core promoter region. The subcloning of individual 5′-flanking fragment revealed the existence of three haplotypes in the distal promoter of PPP2R2D. The luciferase reporter assay showed that different haplotypes exhibited distinct promoter activities. The EMSA revealed that the −462 G>A variant influences DNA-protein interactions involving the nuclear factor 1 (NF1). In vitro reporter gene assay indicated that cotransfection of NF1/B expression plasmid could positively regulate the activity of PPP2R2D proximal promoter. Introduction of exogenous NF1/B expression plasmid further confirmed that the NF1 involves in the regulation of PPP2R2D gene expression. Our findings suggest that functional genetic variants and their haplotypes in the 5′-flanking region of PPP2R2D are critical for transcriptional regulation of PP2A-Bδ.

Mammalian spermatogenesis is a highly regulated multistage process of sperm generation. It is hard to uncover the real function of a testis specific gene in vitro since the in vitro model is not yet mature. With the development of the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated 9) system, we can now rapidly generate knockout mouse models of testis specific genes to study the process of spermatogenesis in vivo. SYCP3-like X-linked 2 (SLX2) is a germ cell specific component, which contains a Cor1 domain and belongs to the XLR (X-linked, lymphocyte regulated) family. Previous studies suggested that SLX2 might play an important role in mouse spermatogenesis based on its subcellular localization and interacting proteins. However, the function of SLX2 in vivo is still elusive. Here, to investigate the functions of SLX2 in spermatogenesis, we disrupted the Slx2 gene by using the CRISPR/Cas9 system. Since Slx2 is a testis specific X-linked gene, we obtained knockout male mice in the first generation and accelerated the study process. Compared with wild-type mice, Slx2 knockout mice have normal testis and epididymis. Histological observation of testes sections showed that Slx2 knockout affected none of the three main stages of spermatogenesis: mitosis, meiosis and spermiogenesis. In addition, we further confirmed that disruption of Slx2 did not affect the number of spermatogonial stem cells, meiosis progression or XY body formation by immunofluorescence analysis. As spermatogenesis was normal in Slx2 knockout mice, these mice were fertile. Taken together, we showed that Slx2 itself is not an essential gene for mouse spermatogenesis and CRISPR/Cas9 technique could speed up the functional study of testis specific X-linked gene in vivo.

Pseudocubic SrRuO3 (100) epitaxial thin films were successfully fabricated on Si (100) with a SrO buffer layer of 6nm thickness by pulsed laser deposition (PLD). Reflection high-energy electron diffraction (RHEED) revealed that the epitaxial growth of SrO occurred on naturally oxidized Si substrates, followed by the epitaxial growth of SrRuO3. X-ray diffraction (XRD) revealed high crystallinity with a full-width at half maximum (FWHM) of 1.9° in the SrRuO3 (200) rocking curve. XRD study of the in-plane orientation clarified a cube-on-cube epitaxy in which SrRuO3 was rotated by 45° with respect to Si . Deoxidization of SiO2 on Si by Sr is thought to play an important role in realizing the epitaxial growth of SrO.

Currently virtual reality technology has a positive impact on the consumers' behavior of online shopping. The interface design of the three-dimensional dynamic visual sense meets the more people's experience of visual perception from technical point of view. But there is little research on the virtual situation design of electronic shopping. The paper clarifies that virtual reality technology shall be combined with situation design through the animation experiments on the hypothetical shopping situation. If technology is combined with the design, consumers' friendly user experience will be improved. People will get more pleasure from online shopping. And it elaborates the principles and methods of design.

The serine-threonine protein phosphatase 2A (PP2A) is a heterotrimeric enzyme family that plays an essential regulatory role in cell growth, differentiation, and apoptosis. Mutations in the genes encoding PP2A-Aα/β subunits are associated with tumorigenesis and other human diseases. To explore whether genetic variations in the promoter region of the PP2A-Aα gene (PPP2R1A) and their frequent haplotypes in the Han Chinese population have an impact on transcriptional activity, we collected DNA samples from 63 healthy Chinese donors and searched for genetic variations in the 5'-flanking promoter region of PPP2R1A (PPP2R1Ap). Haplotypes were characterized by Haploview analysis and individual subcloning. A set of molecular and functional experiments was performed using reporter genes and electrophoretic mobility shifting assay (EMSA). Seven genetic variations were identified within the promoter locus (2038bp) of PPP2R1A. Linkage disequilibrium (LD) patterns and haplotype profiles were analyzed using the identified genetic variants. Using serially truncated human PPP2R1A promoter luciferase constructs, we found that a 685bp (-448nt to +237nt) fragment around the transcription start site (TSS) was the core promoter region. Individual subcloning revealed the existence of six haplotypes in this proximal promoter region of PPP2R1Ap. Using luciferase reporter assays, we found that different haplotypes bearing different variant alleles exhibit distinct promoter activities. The EMSA revealed that the -241 -/G variant influences DNA-protein interactions involving the transcription factor NF-κB, which may regulate the activity of the PPP2R1A proximal promoter. Our findings suggest that functional genetic variants in the proximal promoter of the PP2A-Aα gene and their haplotypes are critical in the regulation of transcriptional activation.

Cell tracking is a fundamental problem for studying live cell dynamics. A novel approach for low frame rate cell tracking in fluorescent microscopy image is herein proposed. The method is based on sliding band filter detection and Delaunay triangulation sub-graph matching. With this approach we can track a large amount of small cells without their motion model and not relying on cell motion continuity between consecutive images. The effectiveness and robustness of the method were validated by visual inspection and on a ground truth dataset.

Thin ZnO nanobelts with average width of 7.5 nm have been synthesized using vapor phase transport method. It was found that stacking faults directed the growth of the thin nanobelts along the (0110) direction with {2110} top/bottom surfaces and {0001} side surfaces. The {0002} stacking fault with translation of 1/3(0110) extends throughout entire length of the ZnO nanobelts. The growth steps at the {0110} growth fronts resulted from the {0002} stacking fault are believed to direct fast axial growth of the thin ZnO nanobelts. The thin ZnO nanobelts are expected to be promising candidates for highly sensitive chemical and biological sensor applications.

A method of night-time pedestrian detection by fusion of visual and infrared video was proposed. At first, infrared video is denoised by spatio-temporal filtering, then bright regions which corresponding to high temperature regions in infrared video frames are segmented by seeded region growing algorithm, then pedestrian are detected by fusion of region-color and region-shape information, at last, infrared video and visual video are fused to enhance detection result. Results show that combination of CCD and IR camera sensors can help to solve night-time surveillance problem.

We propose a hybrid method of seeded region growing and region hue-area information fusion for object segmentation under patterned background. At first, image is segmented into many small regions according to hue homogeneity by seeded region growing algorithm, then background texture mode is discovered by the regions' hue-area information fusion, finally, the background texture is removed according to the discovered background mode and seeded region growing, the residual region is the object segmentation result. Experimental results show that the method can be used in object segmentation under patterned background.

The paper presents a spatial-color model of object and develops an efficient visual tracking algorithm based on particle filter. This spatial-color model captures richer information than the general color histogram because it incorporates spatial distribution of pixels in addition to color. In order to fast compute the weight of each particle, the Integral Images for computation of histogram, mean and variance are proposed, with which the parameters of spatial-color histograms can be computed by using only simple arithmetic operations and thus the computation load is reduce to linear complexity. Experiments on real image sequences show our method results in more accurate tracking than a standard color particle filter.

Graphene/carbon aerogels (RF) were prepared via a Sol-Gel process in graphene oxide (GO) solution using resorcinol (R) and formaldehyde (F) as carbon precursor. The structure, morphology and pore-size distribution of the samples were characterized by XRD, Raman spectrum, SEM and N2 adsorption desorption method. The results indicate that graphene can act as nucleation and growth sites for carbon aerogels. At low mass loading level of RF, a macroporous structure is formed, and the structure of carbon aerogels originates from sheet-structure of GO precursor. With increasing the mass of RF, RF carbon aerogel results in dispersed and thickened carbon platelets. At high mass loading levels, carbon spheres are obtained. Meanwhile, with increasing the mass of RF, the specific surface area of the aerogel increases firstly and then decreases, reaching the maximum value of 841 m 2 /g when w(GO)/w(RF)=1︰50. Electrochemical measurements show that GO/RF-100 has the highest specific capacitance of 169 F/g in 6 mol/L KOH

In this paper, multiperson decision making is explored based on raw relation sets (Chen, 2002), in which three types of basic order relationships between any two objects are used to define the order relationships among a set of objects. Different order relationships among the same set of objects may be produced by different evaluators (or evaluation criteria) and there is also an order relationship among the evaluators themselves. In this paper, all evaluators are assumed to be of the same importance. This method emphasizes using qualitative (or un-weighted) order relationships but it is also capable of handling weighted order relationships.

The top-N query problem is to find the N results that satisfy the query condition the best but not necessarily completely. It is gaining importance in relational databases and in e-commerce where services and products are sold on the Internet. This paper addresses three important issues related to the top-N query problem in a relational database context. First, we propose a new query language to facilitate the specification of various top-N queries. This language adds new features to existing languages. Second, we make a case that the sum function is a more appropriate distance function for ranking tuples when attributes involved in a top-N query are incomparable. Third, based on the sum distance function, we discuss how to process top-N queries.

Thalidomide, (1), is a known inhibitor of TNF-alpha release in LPS stimulated human PBMC. Herein we describe the TNF-alpha inhibitory activity of amino substituted analogs of thalidomide (1) and its isoindolin-1-one analog, EM-12 (2). The 4-amino substituted analogs were found to be potent inhibitors of TNF-alpha release in LPS stimulated human PBMC.

Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.

The ordered half-wall alumina nanotubes (HWANs) were synthesized in an oxalic acid solution via a two-step aluminium anodic oxidation process. Their optical properties are closely associated with the annealing temperature and time. The emission peak of HWANs appears at about 302 nm, which has probably resulted from the 1B → 1A transition. Compared with the Al2O3 powders, a distinct blue shift in the as-prepared HWANs occurs. A schematic drawing of the possible formation of HWANs is proposed and two possible mechanisms for the blue shift are discussed. It can be concluded that the electron transitions to the excited states at 5.3, 4.5 and 4.4 eV (F+ centres) account for the photoluminescence of HWANs at high annealing temperatures.

A variety of two-dimensional and three-dimensional ZnO nanostructures induced by five types of twinning have been synthesized using a thermal evaporation approach. Self-assembled ZnO nanostructures induced by and twinnings are dominant in the products. ZnO nanostructures self-assembled by , and twinnings constitute a low fraction of the total. The sizes of the self-assembled ZnO nanostructures are determined by the polarity-induced fast [0001] growth of the ZnO nanoneedle building blocks. The configurations and morphologies are determined by twinning type. Twinning is proved to be an effect method to self-assemble ZnO nanoneedle building blocks into two-dimensional and three-dimensional nanostructures with different configurations and morphologies.

Powders of polymer and α‐Fe2O3 nanoparticles were pressed into pellets. The samples were annealed at 250°C in pure hydrogen flow. X-ray diffraction spectra indicate that there is a complete phase transformation from α‐Fe2O3 to Fe3O4. Giant negative magnetoresistance (MR) was observed at room temperature and the MR ratio is over 14% in an applied field of 5.5T. The maximum MR ratio is higher than 22% at 130K. The drastic enhancement of the MR ratio is attributed to the fact that the polymer is an excellent barrier material and, more importantly, prevents the oxidation of the surface of Fe3O4. Our results clearly suggest that there is a high degree of spin polarization at room temperature for half-metallic Fe3O4.

Epitaxial Cr-doped Ti2O3 films show giant negative magnetoresistance up to –365% at 2 K. The resistivity of the doped samples follows the behavior expected of spin (magnetic) polarons at low temperature. Namely, rho= rho0 exp(T0/T)p, where p = 0.5 in zero field. A large applied field quenches the spin polarons and p is reduced to 0.25 expected for lattice polarons. The formation of spin polarons is an indication of strong exchange coupling between the magnetic ions and holes in the system.

Conductive SrRuO3 films were deposited on {001} Si substrates by pulsed-laser deposition using SrO as buffer layers. The microstructure and orientation relationships (ORs) of the constituting layers were investigated by X-ray diffraction, transmission electron microscopy, high-resolution electron microscopy and energy dispersive X-ray spectroscopy. Good epitaxial growth of SrO and SrRuO3 films on the Si substrates was achieved. Multiple domains were formed in the SrRuO3 films. The domain boundaries were nearly perpendicular to the interface between the SrRuO3 films and the SrO buffer layers. Three ORs among Si, SrO and SrRuO3 were observed, indicating a new OR between Si and SrO.