Transforming growth factor-beta (TGF-β), a member of the TGF-β cytokine superfamily, is known to bind to sulfated glycosaminoglycans (GAGs), but the nature of this interaction remains unclear. In a recent study, we found that preterm human milk TGF-β2 is sequestered by chondroitin sulfate (CS) in its proteoglycan form. To understand the molecular basis of the TGF-β2–CS interaction, we utilized the computational combinatorial virtual library screening (CVLS) approach in tandem with molecular dynamics (MD) simulations. All possible CS oligosaccharides were generated in a combinatorial manner to give 24 di- (CS02), 192 tetra- (CS04), and 1536 hexa- (CS06) saccharides. This library of 1752 CS oligosaccharides was first screened against TGF-β2 using the dual filter CVLS algorithm in which the GOLDScore and root-mean-square-difference (RMSD) between the best bound poses were used as surrogate markers for in silico affinity and in silico specificity. CVLS predicted that both the chain length and level of sulfation are critical for the high affinity and high specificity recognition of TGF-β2. Interestingly, CVLS led to identification of two distinct sites of GAG binding on TGF-β2. CVLS also deduced the preferred composition of the high specificity hexasaccharides, which were further assessed in all-atom explicit solvent MD simulations. The MD results confirmed that both sites of binding form stable GAG–protein complexes. More specifically, the highly selective CS chains were found to engage the TGF-β2 monomer with high affinity. Overall, this work present key principles of recognition with regard to the TGF-β2–CS system. In the process, it led to the generation of the in silico library of all possible CS oligosaccharides, which can be used for advanced studies on other protein–CS systems. Finally, the study led to the identification of unique CS sequences that are predicted to selectively recognize TGF-β2 and may out-compete common natural CS biopolymers. 相似文献
Fabrication of FinFETs using bulk CMOS instead of silicon on insulator (SOI) technology is of utmost interest as it reduces the process costs. Using well-calibrated device models and 3-D mixed mode simulations, we show that bulk FinFETs can be optimized with identical performances as that of SOI FinFETs. Optimized bulk FinFETs are compared with the corresponding SOI FinFETs for a range of technology nodes using an extensive simulation and design methodology. Further, we extend the concept of body doping in bulk FinFETs to the case of lightly doped fins unlike the heavily doped fin cases reported earlier. The optimum body doping required for bulk FinFETs, and its multiple advantages are also systematically evaluated. We also show that device parasitics play a crucial role in the optimization of nanoscale bulk FinFETs. 相似文献
The range of strains that can be imaged by any practical elastographic imaging system is inherently limited, and a performance measure is valuable to evaluate these systems from the signal and noise properties of their output images. Such a measure was previously formulated for systems employing cross-correlation based time-delay estimators through the strain filter. While the strain filter predicts the signal-to-noise ratio (SNR(e)) for each tissue strain in the elastogram and provides valuable insights into the nature of image noise, it understated the effects of image resolution (axial resolution, as determined by the cross-correlation window length) on the noise. In this work, the strain filter is modified to study the strain noise at multiple resolutions. The effects of finite window length on signal decorrelation and on the variance of the strain estimator are investigated. Long-duration windows are preferred for improved sensitivity, dynamic range, and SNR(e). However, in this limit the elastogram is degraded due to poor resolution. The results indicate that for nonzero strain, a window length exists at which the variance of strain estimator attains its minima, and consequently the elastographic sensitivity, dynamic range and SNR(e) are strongly affected by the selected window length. Simulation results corroborate the theoretical results, illustrating the presence of a window length where the strain estimation variance is minimized for a given strain value. Multiresolution elastography, where the strain estimate with the highest SNR(e) obtained by processing the pre- and post-compression waveforms at different window lengths is used to generate a composite elastogram and is proposed to improve elastograms. All the objective elastogram parameters (namely: SNR(e), dynamic range, sensitivity and the average elastographic resolution-defined as the cross-correlation window length) are improved with multiresolution elastography when compared to the traditional method of utilizing a single window length to generate the elastogram. Experimental results using a phantom with a hard inclusion illustrates the improvement in elastogram obtained using multiresolution analysis. 相似文献
Approaches that enable innate repair mechanisms hold great potential for tissue repair. Herein, biomaterial-assisted sequestration of small molecules is described to localize pro-regenerative signaling at the injury site. Specifically, a synthetic biomaterial containing boronate molecules is designed to sequester adenosine, a small molecule ubiquitously present in the human body. The biomaterial-assisted sequestration of adenosine leverages the transient surge of extracellular adenosine following injury to prolong local adenosine signaling. It is demonstrated that implantation of the biomaterial patch following injury establishes an in situ stockpile of adenosine, resulting in accelerated healing by promoting both osteoblastogenesis and angiogenesis. The adenosine content within the patch recedes to the physiological level as the tissue regenerates. In addition to sequestering endogenous adenosine, the biomaterial is also able to deliver exogenous adenosine to the site of injury, offering a versatile solution to utilizing adenosine as a potential therapeutic for tissue repair. 相似文献
The concept of network caching is determined to be the potential requirement of named data networks (NDN) for enhancing the capabilities of the traditional IP networking. It is responsible for location independent data accesses and optimal bandwidth utilization in multi-path data dissemination. However, the network caching process in NDN introduces security challenges such as content cache poisoning, malicious injection or flooding of the packets and violation in accessing content packets. In this paper, an Improved Merkle Hash Tree-based one-time signature scheme for capability-enhanced security enforcing architecture (IMHT-OTSS-CSEA) is proposed for provisioning data authenticity in a distributed manner for leveraging the capabilities to inform the access privileges of the packets during the process of data dissemination. It is proposed for permitting the routers to verify the forwarded packets’ authenticity in NDN. It is capable in handling the issues that emerge from unsolicited packets during a flooding-based denial of service attacks by supporting the indispensable verification process in routers that confirms the timeliness of packets. The simulation experiments conducted using the open source CCNs platform and Planetlab confirmed a significant mean reduction in delay of 14.61%, superior to the benchmarked schemes. It is identified to minimize the delay incurred in generating bit vectors by a average margin of 13.06%, excellent to the baseline approaches. It also confirmed a mean increase in the true positive rate of 5.42%, a mean increase in the precision rate of 6.04%, decrease in false positive rate of 6.82% and increase in F-measure of 5.62% compared to the baseline approaches in the context of detecting content cache pollution attack respectively.
Wireless Personal Communications - This paper accentuates the paradigm shift in battlefield-environments. In perspective of a decision-maker to enable shrinking of his decision-cycle, the... 相似文献
The gas permeability coefficient of nano and micro composites of natural rubber, carboxylated styrene butadiene rubber and 70:30 natural rubber/carboxylated styrene butadiene rubber blend membranes has been investigated with special reference to type of filler, gases, filler loading and pressure. The layered silicates such as sodium bentonite and sodium fluorohectorite were the nanofillers used and the conventional micro fillers were clay and silica. Latex nanocomposites were characterized by X-ray diffraction technique. The dispersion of layered silicates in the polymer matrix was analysed using transmission electron microscopy. The fluorohectorite silicate showed excellent dispersion in natural rubber matrix. The effect of free volume on the gas barrier properties was investigated by positron annihilation lifetime spectroscopy. It was observed that due to the platelet like morphology and high aspect ratio of layered silicates, the gas barrier properties of nano filled latex membranes were very high. The crosslink density values and extent of reinforcement were estimated in order to correlate with the gas barrier properties. The oxygen/nitrogen selectivity of these membranes were investigated. The diffusion of gas molecules through the polymer was determined by time-lag method and diffusion selectivity of the membranes was computed. 相似文献