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Up to now, survivin has been recommended as a prognostic and diagnostic indicator in glioma patients. However, there are still many controversies. Here, a meta-analysis was conducted to draw a more definitive conclusion on the correlation of survivin with overall survival (OS), age, gender, and WHO grade. Eligible studies were available through careful assessment, and then pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated. Funnel plots were introduced to evaluate the publication bias. Additionally, heterogeneity and sensitivity were also evaluated. In the present meta-analysis, 15 eligible studies with a total of 1,089 patients were incorporated. Survivin expression in gliomas correlated with 2-year OS (n = 8; HR 0.17, 95% CI 0.11-0.26) and 5-year OS (n = 7; HR 0.12, 95% CI 0.07-0.22) in patients. In addition, a fixed-effect model revealed a significant association between survivin and age (male/+; OR 2.10, 95% CI 1.44-3.05) and survivin and WHO grade (I+II/+; OR 0.27, 95% CI 0.19-0.38). No heterogeneity was observed across all studies. According to Begg's and Egger's test and funnel plot, no publication bias was reported. Taken together, our meta-analysis suggests that survivin expression is associated with poor survival, older age, and higher WHO grade and could be suggested as a useful prognostic and diagnostic biomarker, or an effective therapy target.

The plume flow of space thrusters can cause series of harmful effects to spacecraft by impinging on some sensitive surfaces. To prevent the plume impingement effects that a 60N thruster can do to the backflow region, a plume protect cover is intended to be assembled to the thruster. The flow field from the combustion chamber of the thruster to the vacuum environment contains both continuum and rarefied flow regimes, which makes it difficult to model this flow phenomenon by using one single method. The coupled NS/DSMC method is one of the best choices for modeling the continuum-rarefied transitional flows. In present study, a coupled NS/DSMC solver is developed by the authors and is used to estimate the effect of the plume protector assembled to the 60N thruster. The present coupled NS/DSMC solver is constructed with the NS solver NozzleFlow and DSMC solver PWS. Interface location is determined by combining two continuum breakdown parameters. One is the KnGL parameter and the other is the thermal non-equilibrium parameter Ptne. State-based coupling method is adopted to transfer information between the continuum and particles methods. The continuum-rarefied interfaces and gas parameters of the vacuum plume flow field of the thruster are obtained by conducting coupled calculation, which shows that the plume protector can decrease the mass flux density in the back flow region by two orders. The present coupled NS/DSMC method can be a useful tool for the vacuum plume effects analysis.

Notch signaling plays an important role in cell-fate specification in multicellular organisms by regulating cell-cell communication. The Drosophila deltex gene encodes a modulator of the Notch pathway that has been shown to interact physically with the Ankyrin repeats of Notch. We isolated four distinct cDNAs corresponding to mouse homologs of deltex - mouse Deltex1 (MDTX1), mouse Deltex2 (MDTX2), mouse Deltex2DeltaE (MDTX2DeltaE), and mouse Deltex3 (MDTX3). Deduced amino acid sequences of these four cDNAs showed a high degree of similarity to Drosophila Deltex and its human homolog, DTX1 throughout their lengths, even though they possess distinct structural features. MDTX proteins formed homotypic and heterotypic multimers. We found that these genes were expressed in the central, peripheral nervous system and in the thymus, overlapping with those of mouse Notch1. In mammalian tissue culture cells, overexpression of any of the four mouse deltex homologs suppressed the transcriptional activity of E47, a basic helix-loop-helix (bHLH) protein, in a manner similar to suppression by an activated form of human Notch1 or human DTX1. In addition, overexpression of MDTX2 and MDTX2DeltaE in C2C12 cells under differentiation-inducing conditions suppressed the expression of myogenin, one of the myogenic transcriptional factors; this was also similar to a previously reported activity of constitutively activated Notch. Furthermore, misexpression of any of the MDTX genes in Xenopus embryos resulted in an expansion of the region expressing the neural cell adhesion molecule (N-CAM) gene, a marker for the neuroepithelium. Collectively, our results suggest that these mouse deltex homologs are involved in vertebrate Notch signaling and regulation of neurogenesis.

Induced pluripotent stem cells (iPSCs) hold great potential for cell therapy and tissue engineering. Neural crest stem cells (NCSCs) are multipotent that are capable of differentiating into mesenchymal lineages. In this study, we investigated whether iPSC-derived NCSCs (iPSC-NCSCs) have potential for tendon repair. Human iPSC-NCSCs were suspended in fibrin gel and transplanted into a rat patellar tendon window defect. At 4 weeks post-transplantation, macroscopical observation showed that the repair of iPSC-NCSC-treated tendons was superior to that of non-iPSC-NCSC-treated tendons. Histological and mechanical examinations revealed that iPSC-NCSCs treatment significantly enhanced tendon healing as indicated by the improvement in matrix synthesis and mechanical properties. Furthermore, transplanted iPSC-NCSCs produced fetal tendon-related matrix proteins, stem cell recruitment factors, and tenogenic differentiation factors, and accelerated the host endogenous repair process. This study demonstrates a potential strategy of employing iPSC-derived NCSCs for tendon tissue engineering.

We propose a groupwise image registration method using sparse coding and graph theoretic techniques. A sparse coding method is used to estimate image similarity measures among images to registered, yielding asymmetric, groupwise image similarity measures for each image to other images in the group. Based on the asymmetric groupwise image similarity measures among different images, a directed graph is built for learning a manifold of images so that a group center image can be identified and each image can be registered to the center image following a directed shortest path which decomposes a large deformation between two images into a series of small and anatomically meaningful deformations. The groupwise image similarity measures are progressively updated, so does the directed graph, facilitating accurate alignment of a group of images following directed shortest paths derived from the dynamic directed graphs. Compared with state of the art graph based registration methods, our method is more robust and able to achieve better registration accuracy.

A novel method is proposed to match functional connectivity patterns represented by graphs for spatial registration of fMRI data. Different from existing functional connectivity pattern based registration methods that detect corresponding functional units across different subjects by minimizing their difference in functional connectivity strength, our method adopts a graph representation to characterize functional connectivity information among all voxels in fMRI data of each subject, then detects spatial correspondence between subjects using graph matching. To integrate information of both functional connectivity strength and spatial relations, the graph representation of functional connectivity information of fMRI data models each voxel as one graph node and connects each pair of graph nodes with an edge weighted by their functional connectivity strength measure, estimated as correlation coefficient between their functional signals. To make the graph matching computationally feasible, an iterative matching strategy with stochastic resampling is proposed to match graphs of spatially distributed local functional connectivity patterns and subsequently to drive the image registration iteratively. The proposed method has been validated by registering resting state fMRI data of 20 healthy subjects. The validation experiment results have demonstrated that our method can achieve improved inter-subject functional consistency. A comparison experiment result has further indicated that the proposed method can achieve better performance than existing methods.

This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license.-- et al., We report the draft genome of Streptomyces rimosus (ATCC 10970), a soil isolate that produces oxytetracycline, a commercially important and clinically useful antibiotic., We acknowledge financial support from the National Yang-Ming University, Taiwan, for the sequencing project (R.K.), a British Council for Research Projects Network grant (P.A.H. and H.P.), and the British Council/CUC for a Scotland-China Higher Education Research Partnership for PhD Studies (Z.T.).

Tissue-specific stem cells can be coaxed or harvested for tissue regeneration. In this study, we identified and characterized a new type of stem cells from the synovial membrane of knee joint, named neural crest cell-like synovial stem cells (NCCL-SSCs). NCCL-SSCs showed the characteristics of neural crest stem cells: they expressed markers such as Sox10, Sox17 and S100β, were clonable, and could differentiate into neural lineages as well as mesenchymal lineages, although NCCL-SSCs were not derived from neural crest during the development. When treated with transforming growth factor β1 (TGF-β1), NCCL-SSCs differentiated into mesenchymal stem cells (MSCs), lost the expression of Sox17 and the differentiation potential into neural lineages, but retained the potential of differentiating into mesenchymal lineages. To determine the responses of NCCL-SSCs to microfibrous scaffolds for tissue engineering, electrospun composite scaffolds with various porosities were fabricated by co-electrospinning of structural and sacrificial microfibers. The increase in the porosity in microfibrous scaffolds enhanced cell infiltration in vitro and in vivo, but did not affect the morphology and the proliferation of NCCL-SSCs. Interestingly, microfibrous scaffolds with higher porosity increased the expression of chondrogenic and osteogenic genes but suppressed smooth muscle and adipogenic genes. These results suggest that the differentiation of NCCL-SSCs can be controlled by both soluble chemical factors and biophysical factors such as the porosity of the scaffold. Engineering both NCCL-SSCs and scaffolds will have tremendous potential for tissue regeneration.

It is generally accepted that the de-differentiation of smooth muscle cells, from the contractile to the proliferative/synthetic phenotype, has an important role during vascular remodelling and diseases. Here we provide evidence that challenges this theory. We identify a new type of stem cell in the blood vessel wall, named multipotent vascular stem cells. Multipotent vascular stem cells express markers, including Sox17, Sox10 and S100β, are cloneable, have telomerase activity, and can differentiate into neural cells and mesenchymal stem cell-like cells that subsequently differentiate into smooth muscle cells. On the other hand, we perform lineage tracing with smooth muscle myosin heavy chain as a marker and find that multipotent vascular stem cells and proliferative or synthetic smooth muscle cells do not arise from the de-differentiation of mature smooth muscle cells. In response to vascular injuries, multipotent vascular stem cells, instead of smooth muscle cells, become proliferative, and differentiate into smooth muscle cells and chondrogenic cells, thus contributing to vascular remodelling and neointimal hyperplasia. These findings support a new hypothesis that the differentiation of multipotent vascular stem cells, rather than the de-differentiation of smooth muscle cells, contributes to vascular remodelling and diseases.

The aim is to explore the self-regulation mechanism of the rex in Streptomyces rimosus M4018.We cloned the rex of S. rimosus M4018 (Sr-rex) based on its homologoussequence in Streptomyces coelicolor A3(2) and its upstream rex operator (ROP) fragment using PCR and genome walking. An electrophoretic mobility shift assay (EMSA) was applied to analyze the regulation of rex to ROP in vitro.Sr-rex is 846 bp in length and has a 84% identity with the one in S. coelicolor A3(2) in amino acid sequence. It was deposited in Genbank under the accession number GQ849479. The expressed Sr-Rex by E. coli was mainly composed of alpha-helixes and beta-sheets, which was in compliance with the prediction. An Electrophoretic Mobility Shift Assay (EMSA) confirmed the specific binding activity of Sr-Rex with ROP. Meanwhile, we synthesized a 22 bp DNA fragment (ROP1) based on the minimal binding site of ROP. The maximal binding ratio of this fragment to Sr-Rex was 5:1 (molar). NADH negatively affected the binding activity, however, NAD+ had no impact on it.In S. rimosus M4018, the Rex regulated the gene expression of ROP via sensing the intracellular level of NAD (H).

The purpose of the present work is to investigate the coupled CFD/DSMC method using the existing CFD and DSMC codes developed by the authors. The interface between the continuum and particle regions is determined by the gradient-length local Knudsen number. A coupling scheme combining both state-based and flux-based coupling methods is proposed in the current study. Overlapping grids are established between the different grid systems of CFD and DSMC codes. A hypersonic flow over a 2D cylinder has been simulated using the present coupled method. Comparison has been made between the results obtained from both methods, which shows that the coupled CFD/DSMC method can achieve the same precision as the pure DSMC method and obtain higher computational efficiency.

The aromatic polyketide antibiotic oxytetracycline (OTC) is produced by Streptomyces rimosus as an important secondary metabolite. Enhancement of self-resistance is one effective way to improve antibiotic production in Streptomyces spp. In the present study, we aimed to improve the production of OTC by introducing extra copies of the OTC resistance genes, otrA and otrB, into the chromosome of the industrial strain of S. rimosus (SRI). First, otrA and otrB were cloned and ligated with pSET152 to generate the recombinant plasmids pSET152-otrA/otrB, the demethylated pSET152-otrA/otrB by Escherichia coli ET12567(pUZ8002) were then introduced into SRI to yield otrA/ otrB knock-in mutants: SRI-A (otrA) and SRI-B (otrB). Ten selected mutants and the parent SRI strain were cultured in shake flasks. Production of OTC was increased by 67% in one SRI-B mutant compared with the parent strain, suggesting that the enhancement of resistance gene otrB in the antibiotic producer is an effective way to improve OTC biosynthesis. However, introduction of extra copy of otrB could retard growth of mutant cells.

In order to enable microorganisms to manifest their intracellular oxygen levels we constructed a genetic sensor circuitry which converts signals impinging on the cellular redox balance into a reporter gene expression readout. Based on the newly found Streptomyces rimosus redox control system, consisting of Rex modulating Retinopathy of prematurity (ROP)-containing promoters in a NADH-dependent manner, we designed an Escherichia coli sensor transcription control system, which constitutes a Rex transactivator (REDOX) with the ability to bind and activate promoters. When oxygen levels were high and resulted in depleted NADH pools, Rex-specific target promoter (cydP1) driven from the expression of secreted (Green fluorscent protein, GFP) reporter gene was low as a consequence of increased Rex-ROP affinity. Conversely, at hypoxic conditions, it led to high intracellular NADH levels, strongly reduced Rex-ROP interaction and increased GFP expression in E. coli cells. The sensor capacity (oxygen levels) of redox system enabled monitoring of the population's metabolic state in vivo. Our research will not only help to understand the molecular mechanism of the Rex family but also foster progresses in biosensor development.

Induced pluripotent stem cells (iPSCs) hold great promise for cell therapies and tissue engineering. Neural crest stem cells (NCSCs) are multipotent and represent a valuable system to investigate iPSC differentiation and therapeutic potential. Here we derived NCSCs from human iPSCs and embryonic stem cells (ESCs), and investigated the potential of NCSCs for neural tissue engineering. The differentiation of iPSCs and the expansion of derived NCSCs varied in different cell lines, but all NCSC lines were capable of differentiating into mesodermal and ectodermal lineages, including neural cells. Tissue-engineered nerve conduits were fabricated by seeding NCSCs into nanofibrous tubular scaffolds, and used as a bridge for transected sciatic nerves in a rat model. Electrophysiological analysis showed that only NCSC-engrafted nerve conduits resulted in an accelerated regeneration of sciatic nerves at 1 month. Histological analysis demonstrated that NCSC transplantation promoted axonal myelination. Furthermore, NCSCs differentiated into Schwann cells and were integrated into the myelin sheath around axons. No teratoma formation was observed for up to 1 year after NCSC transplantation in vivo. This study demonstrates that iPSC-derived multipotent NCSCs can be directly used for tissue engineering and that the approach that combines stem cells and scaffolds has tremendous potential for regenerative medicine applications.

The aromatic polyketide antibiotic, oxytetracycline (OTC), is produced by Streptomyces rimosus as an important secondary metabolite. High level production of antibiotics in Streptomycetes requires precursors and cofactors which are derived from primary metabolism; therefore it is exigent to engineer the primary metabolism. This has been demonstrated by targeting a key enzyme in the oxidative pentose phosphate pathway (PPP) and nicotinamide adenine dinucleotide phosphate (NADPH) generation, glucose-6-phosphate dehydrogenase (G6PDH), which is encoded by zwf1 and zwf2. Disruption of zwf1 or zwf2 resulted in a higher production of OTC. The disrupted strain had an increased carbon flux through glycolysis and a decreased carbon flux through PPP, as measured by the enzyme activities of G6PDH and phosphoglucose isomerase (PGI), and by the levels of ATP, which establishes G6PDH as a key player in determining carbon flux distribution. The increased production of OTC appeared to be largely due to the generation of more malonyl-CoA, one of the OTC precursors, as observed in the disrupted mutants. We have studied the effect of zwf modification on metabolite levels, gene expression, and secondary metabolite production to gain greater insight into flux distribution and the link between the fluxes in the primary and secondary metabolisms.

This work presents a hybrid method for 2D artery vessel segmentation and diameter measurement in X-Ray angiograms. The proposed method is novel in that tracking-based and model-based approaches are combined. A robust and efficient tracking template, the "annular template", is devised for vessel tracking. It can readily be applied on X-Ray angiograms without any preprocessing. Starting from an initial tracking point given by the user the tracking algorithm iteratively repositions the annular template and thereby detects the vessel boundaries and possible bifurcations. With a user selected end point the tracking process results in a set of points that describes the contour and topology of an artery vessel segment between the initial and end points. A "boundary correction and interpolation" operation refines the extracted points which initialize the Snakes algorithm. Boundary correction adjusts the points to ensure that they lie on the vessel segment of interest. Boundary interpolation adds more points, so that there are sufficiently many points for the Snakes algorithm to generate a smooth and accurate vessel segmentation. After the application of Snakes the resulting points are sequentially connected to represent the vessel contour. Then, the diameters are measured along the extracted vessel contour. The segmentation and measurement results are compared with manually extracted and measured vessel segments. The average Precision, Recall and Jaccard Index of 21 vessel samples are 91.5%, 92.1% and 84.9%, respectively. Compared with ground truth measurements of diameters the average relative error is 8.2%, and the average absolute error is 1.13 pixels.

Human anterior cruciate ligament (ACL) has poor healing ability after injury. The devastating effects of matrix metalloproteinases (MMPs) excess expression are regarded as the main reason. Tissue inhibitor metalloproteinases (TIMPs) may be independent of MMPs inhibition. In this paper, a rat ACL rotating injury apparatus was designed to produce ACL injury. After inducing injury, joint fluids and ACL tissue total proteins were immediately extracted. In addition, ACL tissue was isolated in a culture plate with 1%FBS medium for the ex vivo study. We found MMP-2 in joint fluids increased significantly by 4 folds after ACL injury as a function of time. Ex vivo study showed MMP-2 in the medium and ACL cultured tissue increased significantly respectively to 3 folds and to 6 folds. The joint fluids global MMP increased to 3.5 folds with non-treatment and APMA-treatment in day three. On the gene expression level, the changes in MMP-1 and CD147 have the similar tendency. The ratio of MMP-1/TIMP-1 increased with time after ACL injury. We conclude that MMP-2 increased significantly in the early phase in the joint cavity after ACL injury. The ex vivo study demonstrated the same tendency. Generic MMP Activity Assay (global MMP assay) an dzymography also showed significant increase in MMP activity in joint fluids. These results showed ACL having poor healing ability after injury may not be only due to ACL release of large quantities of MMPs. The important factor may be the alterations in the whole joint cavity's internal environment.

The adult human anterior cruciate ligament (ACL) has poor functional healing response. Transforming growth factor (TGF)-β1 enhances the wound repair by stimulating matrix proteins deposition as well as the proliferation and migration of cells. However, the function of the TGF-β1-induced matrix metalloproteinases' (MMPs) activities in the wound healing process is poorly understood. In this study, exogenous MMP-2 is added to mimic the TGF-β1-induced MMP-2 expression. Role of NF-κB pathway is further examined. Our results show that TGF-β1 induces dramatic elevation of MMP-2 activities and the MMP-2/tissue inhibitors of metalloproteinases ratio. Furthermore, the exogenous MMP-2 significantly promoted in vitro wound healing abilities of ACL fibroblasts that are significantly blocked with the addition of its inhibitors. TGF-β1 also increases the proliferation of ACL fibroblasts whereas MMP-2 alone does not, indicating that MMP-2 activities are not involved in the proliferation. TGF-β1-induced MMP-2 activity is inhibited by Bay11-7082 and Bay11-7085 (NF-κB inhibitors). Our results demonstrate that increased TGF-β1 facilitates the ACL healing process by promoting the fibroblasts migration and proliferation. The migration process is mediated by MMP-2 and NF-κB pathway is involved in TGF-β1-mediated MMP-2 release.

The anterior cruciate ligament, posterior cruciate ligament, cartilage and meniscus in human knee joint have poor healing ability. Accumulation of MMPs in the joint fluids due to knee injury has been considered as the main reason. Our previous experiments showed that synovium may be the major regulator of MMPs in joint cavity after injury. In this paper, we used human synoviocytes harvested from synovium to determine whether mechanical injury and inflammatory factors will induce MMP-2 production in synoviocytes. With zymography, we found that mechanical compression increased the MMP-2 production by 23% under 6% compressions, 61% under 12% compression and 109% under 14% compressions. In addition, TNF-alpha can also elevate the activity of MMP-2 in a dose dependent manner, while IL-1alpha does not. However, mixture of these two factors dramatically increased MMP-2 production by 201%. In addition, mechanical injury had a strong synergistic effect on MMP-2 production with TNF-alpha, IL-1alpha and their mixture, increasing by 207%, 354% and 468% individually. The generic MMP activity assayrevealed that mechanical compression increased the generic activity. APMA treatment increased the generic activity of MMPs induced by compres

The dynamics between inflammatory factors, mechanical stress, and healing factors, in an intra-articular joint, are very complex after injury. Injury to intra-articular tissue [anterior cruciate ligament (ACL), synovium] results in hypoxia, accumulation of various pro-inflammatory factors, cytokines, and metalloproteases. Although the presence of increased amounts of matrix-metalloproteinases (MMP) in the joint fluid after knee injury is considered the key factor for ACL poor healing ability; however, the exact role of collective participants of the joint fluid on MMP-2 activity and production has not been fully studied yet. To investigate the combined effects of mechanical injury, inflammation and hypoxia induced factor-1α (HIF-1α) on induction of MMP-2; we mimicked the microenvironment of joint cavity after ACL injury. The results show that TNF-α and IL-1β elevate the activity of MMP-2 in a dose- and time-dependent manner. In addition, mechanical stretch further enhances the MMP-2 protein levels with TNF-α, IL-1β, and their mixture. CoCl(2) -induced HIF-1α (100 and 500 µM) also increases the levels and activity of MMP-2. Mechanical stretch has a strong additional effect on MMP-2 production with HIF-1α. Our results conclude that mechanical injury, HIF-1α and inflammatory factors collectively induce increased MMP-2 production in ACL fibroblasts, which was inhibited by NF-κB pathway inhibitor (Bay-11-7082).

Human anterior cruciate ligament (ACL) has poor healing ability after injury. Inflammation and accumulation of matrix metalloproteinases (MMPs) in synovial fluids may be involved in the process. Tissue inhibitor metalloproteinases (TIMPs) may be independent of MMPs inhibition. A rat ACL rotating injury apparatus was designed to mimic ACL injury. ACL showed the higher MMP-1/TIMP-1 ratio after injury. Our recently findings demonstrated that MMPs expression and activities elevated significantly in the joint after ACL injury. This maybe one of the important reasons why an injured ACL cannot be repaired.

We present a method for the segmentation of human leg bones and extraction of functional parameters of the femur using MRT images. The novelty consists in the use of dynamic models which will be adapted to the images of individual patients both globally to a whole leg bone and locally to individual parts of a bone. Thresholding and region growing procedures are applied for pre-processing the images. For some parts of bones, for example the femur ball, we use a three dimensional VRML-based (Virtual Reality Modelling Language) femur model as a reference in order to make the segmentation method more robust. Based on the segmentation and the 3D VRML model, we can extract functional (biomechanical) femur parameters which are needed for gait analysis. Automatische Identifizierung von funktionellen kinematischen Knochenmerkmalen durch MRT-Segmentierung fur die Ganganalyse Wir beschreiben eine Methode zur Segmentierung von menschlichen Beinknochen sowie zur Extraktion funktioneller Parameter aus MRT-Bildern, und wenden diese beispielhaft auf den Oberschenkel (Femur) an. Neu ist die Verwendung eines dynamischen Modells, das sowohl den gesamten Beinknochen als auch einzelne Teile des Knochens an die Bilder eines Patienten adaptiert. Zur Vorverarbeitung werden Schwellwertbildung und Region Growing eingesetzt. Fur einige Teile der Knochen, z. B. fur den Femur-Ball, verwenden wir ein 3D VRML-basiertes Modell als Referenz, um die Segmentierung robuster zu machen. Mit der Segmentierung und dem 3D VRML-Modell konnen wir die funktionellen (biomechanischen) Parameter des Femurs fur die Ganganalyse extrahieren.

The anterior cruciate ligament (ACL) of the human knee plays an important role in controlling and stabilizing the knee joint, but has poor healing response, especially in comparison with the medial collateral ligament (MCL), which can heal relatively well. In this study, we detected significant increases in the mRNA levels of multiple matrix metalloproteinases (MMPs) (MMP-1, 2, 7, 9, 11, 14, 17, 21, 23A, 24,25,27 and 28) in ACL fibroblasts after in vitro injury with equi-biaxial stretch chamber. However, only some MMPs (MMP-7, 9,14, 21 and 24) showed increases in injured MCL fibroblasts, and to a much lesser degree than observed in the injured ACL fibroblasts. Zymography revealed 6.3-folds increase of MMP-2 activity in injured ACL but not MCL fibroblasts which parallel with the global MMP activities assay. Bay-11 and curcumin can significantly decrease MMP-2 activities to 13% and 29% in injured ACL fibroblasts respectively, which implies the involvement of p65 subunits of NF-κB and AP-1 pathways. Furthermore, Bay-11 can decrease the global MMP activity released from injured ACL fibroblasts in a dose-dependent manner. In summary, the differential expression and activities of MMPs might help to explain poor healing ability of ACL and p65 subunit of NF-κB might be a potential target to facilitate the ACL repair.

A new scheme, called pre-decorrelating strategy, is proposed for single user detection in the forward direction of centralized DS-CDMA systems. The basic idea is that, instead of the data themselves, the linear combinations of active users' data are transmitted, which can then decorrelate the cross-correlation between users at the receiver. In the flat Rayleigh fading environment, analysis and simulations show that the receiver is much simplified and can well cancel the multiple access interference regardless of the interference powers and without any knowledge of other users' signature waveforms.

This paper introduces a new scheme for single user detection in the forward direction of centralized DS/CDMA systems. The basic idea is that, instead of the data themselves, the linear combinations of active users' data according to the inverse crosscorrelation matrix of their signature waveforms are transmitted. With the proposed scheme, the simple correlator can well cancel the multiple access interference like the decorrelating multiuser detector while the signature waveforms of other users do not need to be known at the receiver. Analysis and simulation results of the performance are presented. >

A new multichannel MAC protocol called hop reservation multiple access (HRMA) for packet-radio networks is introduced, specified and analyzed. HRMA is based on very-slow frequency-hopping spread spectrum (FHSS) and takes advantage of the time slotting necessary for frequency hopping. HRMA allows a pair of communicating nodes to reserve a frequency hop (channel) using a hop reservation and handshake mechanism on every hop to guarantee collision-free data transmission in the presence of hidden terminals. HRMA provides a baseline to offer QoS in ad-hoc networks based on simple half-duplex slow FHSS radios. We analyze the throughput achieved in HRMA for the case of a fully-connected network assuming variable-length packets, and compare it against an ideal multichannel access protocol and the multichannel slotted ALOHA protocol. The numerical results show that HRMA can achieve much higher throughput than multichannel slotted ALOHA in the traffic-load ranges of interest especially when the average packet length is large compared to a slot size, in which case the maximum throughput of HRMA is close to what can be obtained with an ideal protocol.

Because the inductive noise Ldi/dt is induced by the power change and can have disastrous impact on the timing and reliability of the system, high-performance CPU designs are more concerned with the step power reduction instead of the average power reduction. The step power is defined as the power difference between the previous and present clock cycles, and represents the Ldi/dt noise at the microarchitecture level. Two mechanisms at the microarchitecture level are proposed in this paper to reduce the step power of the floating point unit (FPU), as FPU is the potential "hot" spot of Ldi/dt noise. The two mechanisms, ramping up and ramping down FPU based on instruction fetch queue (IFQ) scanning and PC+N instruction diction, can meet any specific step power constraint. We implement and evaluate the two mechanisms using a performance and power simulator based on the SimpleScalar toolset. Experiments using SPEC95 benchmarks show that our method reduces the performance loss by a factor of four when compared to a recent work.

A novel multichannel schedule-based medium access control (MAC) protocol for ad-hoc networks, named collision-avoidance transmission scheduling (CATS) is introduced. CATS allows nodes to contend for and reserve data channels for specific time slots by means of distributed reservation and collision-avoidance handshakes. Contention is limited among nodes within two hops of one another, which provides a very efficient spatial reuse of the bandwidth available. CATS ensures that no collisions occur in successfully reserved data links, even when hidden terminals exist. Reservations in CATS support unicasting, multicasting and broadcasting at link level simultaneously and adapt to dynamic data size. The throughput achieved by CATS is analyzed for unicast traffic and broadcast traffic. Numerical results show that CATS can achieve very high throughput.

The re-creation of the tumor microenvironment including tumor-stromal interactions, cell-cell adhesion and cellular signaling is essential in cancer-related studies. Traditional two-dimensional (2D) cell culture and animal models have been proven to be valid in some areas of explaining cancerous cell behavior and interpreting hypotheses of possible mechanisms. However, a well-defined three-dimensional (3D) in vitro cancer model, which mimics tumor structures found in vivo and allows cell-cell and cell-matrix interactions, has gained strong interest for a wide variety of diagnostic and therapeutic applications. This communication attempts to provide a representative overview of applying 3D in vitro biological model systems for cancer related studies. The review compares and comments on the differences in using 2D models, animal models and 3D in vitro models for cancer research. Recent technologies to construct and develop 3D in vitro cancer models are summarized in aspects of modeling design, fabrication technique and potential application to biology, pathogenesis study and drug testing. With the help of advanced engineering techniques, the development of a novel complex 3D in vitro cancer model system will provide a better opportunity to understand crucial cancer mechanisms and to develop new clinical therapies.

CSL is the primary target of the Notch signaling pathway in mammalian cells. It is a DNA binding protein that generally represses transcription in the absence of Notch signaling and activates transcription upon formation of a ternary complex with NICD, the protease-generated intracellular domain of Notch. Previous mapping experiments identified the central third of CSL as both necessary and sufficient for DNA binding and activation by Notch. Here we show that CSL promotes transcription in 293T cells in the absence of added NICD and that this activity requires both the central domain plus the C-terminal third of the protein. Evidence is presented that argues against a contribution of endogenous NICD and instead supports the possibility that distinct coactivators may directly stimulate the activity of CSL in a cell type-specific manner. This conclusion supports a recent finding that Drosophila CSL (Suppressor of Hairless) can also mediate transcriptional activation in the absence of Notch.

Because the inductive noise Ldi/dt is induced by the power change and can have disastrous impact on the timing and reliability of the system, high-performance CPU designs are more concerned with the step power reduction instead of the average power reduction. The step power is defined as the power difference between the previous and present clock cycles, and represents the Ldi/dt noise at the microarchitecture level. Two mechanisms at the microarchitecture level are proposed in this paper to reduce the step power of the floating point unit (FPU), as FPU is the potential "hot" spot of Ldi/dt noise. The two mechanisms, ramping up and ramping down FPU based on instruction fetch queue (IFQ) scanning and PC+N instruction prediction, can meet any specific step power constraint. We implement and evaluate the two mechanisms using a performance and power simulator based on the SimpleScalar toolset. Experiments using SPEC95 benchmarks show that our method reduces the performance loss by a factor of four when compared to a recent work.

The D. melanogaster germ cell-less (gcl) gene has previously been shown to play a key role in the establishment of the germ cell lineage during fly embryogenesis. To identify other molecules that function with Gcl in this process, we have conducted a yeast two-hybrid screen that utilized Gcl protein as bait. A predominant class of Gcl-interacting clones encodes a species of importin-alpha from Drosophila (karyopherin-alpha3; kap-alpha3), a nuclear-localization sequence binding protein previously shown to act in the transport of proteins from the cytoplasm to the nucleus. The expression of kap-alpha3 is widespread both temporally and spatially throughout the embryo during development, as judged by Northern blotting and whole-mount in situ hybridization to Drosophila embryos, suggesting that it functions at multiple stages of development. Studies of the Gcl/Kap-alpha3 interaction have identified a functional nuclear-localization sequence in Gcl protein which is necessary for an in vivo interaction and for nuclear entry of Gcl, making it likely that one role for Kap-alpha3 is to deliver Gcl protein to the nucleus. The identification of Kap-alpha3 and an in vivo substrate will allow for further characterization of the basis for specificity between importin-alpha molecules and their binding substrates.