Application of ITC-Based Characterization of Thermodynamic and Kinetic Association of Ligands With Proteins in Drug Design

A comprehensive characterization of the thermodynamic and kinetic profiling of ligands binding to a given target protein is crucial for the hit selection as well as the hit-to-lead-to-drug evolution. Isothermal titration calorimetry (ITC), widely known as an invaluable tool to measure the thermodynamic data, has recently found its way to determine the binding kinetics too. The extensive application of ITC in measurement of both thermodynamic and kinetic data manifests unique roles of ITC in drug discovery and development. This mini-review concentrates on elaborating how to gain the thermodynamic and kinetic data using ITC, highlighting the importance of these data in lead discovery and optimization, and intends to provide an overview of the technical and conceptual advances that offer unprecedented access to protein–ligand recognition by ITC measurement

The low-rank decomposition of correlation-enhanced superpixels for video segmentation

Low-rank decomposition (LRD) is an effective scheme to explore the affinity among superpixels in the image and video segmentation. However, the superpixel feature collected based on colour, shape, and texture may be rough, incompatible, and even conflicting if multiple features extracted in various manners are vectored and stacked straight together. It poses poor correlation, inconsistence on intra-category superpixels, and similarities on inter-category superpixels. This paper proposes a correlation-enhanced superpixel for video segmentation in the framework of LRD. Our algorithm mainly consists of two steps, feature analysis to establish the initial affinity among superpixels, followed by construction of a correlation-enhanced superpixel. This work is very helpful to perform LRD effectively and find the affinity accurately and quickly. Experiments conducted on datasets validate the proposed method. Comparisons with the state-of-the-art algorithms show higher speed and more precise in video segmentation

An investigation of the conductivity of peptide nanostructured hydrogels via molecular self-assembly

Nanoscale, conductive wires fabricated from organic molecules have attracted considerable attention in recent years due to their anticipated applications in the next generation of optical and electronic devices. Such highly ordered 1D nanostructures could be made from a number of routes. One route of particular interest is to self-assemble the wires from biomolecules due to the wide range of assembly methods that can be adapted from nature. For example, biomolecules with aromatic motifs can be self-assembled so that good π-π stacking is achieved in the resultant nanostructure. An additional advantage of using biomolecules is that it enables the interface of the electronic materials with biological systems, which is important for many applications, including nerve cell communication and artificial photosynthesis. In this study, nanowires were prepared by the molecular self-assembly of oligopeptides that were coupled to aromatic components. In order to achieve charge transport though the nanowires, it was imperative that the aromatic components were arranged so that there was π-π stacking with very few structural defects. Therefore, enzymes were used to control the formation of the hydogelators which subsequently self-assembled to produce nanowire networks. Two main systems were studied in this thesis.In the first system, hydrogelators were produced from aromatic peptide amphiphiles via the enzymatic hydrolysis of the methyl ester of fluorenylmethoxycarbonyl (Fmoc)-di/tripeptides. These hydrogelators formed nanostructures due to π-π stacking between the Fmoc groups and H-bonding between the peptides. The nanostructures in turn produced macroscale gel networks. The nanostructures were analyzed by wide angle X-ray diffraction and fluorescence spectroscopy. A combination of Fourier transform infra-red (FTIR), Transmission Electron Microscopy (TEM), Cryo-TEM, and Atomic Force Microscopy (AFM) was used to characterize the networks. The charge transport properties of the dried networks were studied using impedance spectroscopy. Fmoc-L₃ was found to assemble into nanotubes whose walls consisted of 3 self-assembled layers and possessed inner and outer diameters of ~ 9 nm and ~ 18 nm, respectively. The Fmoc-L₃ networks were structurally stabile and were electronically conductive under a vacuum. The sheet resistance of the peptide networks increased with relative humidity due to the increasing ionic conductivity. The resistance of the networks was 0.1 MΩ/sq in air and 500 MΩ/sq in vacuum (pressure: 1.03 mbar) at room temperature. The networks had a band gap of between 1 to 4 eV as measured by UV-Vis spectroscopy and the temperature-impedance studies. Possible routes for aligning the Fmoc-L3 networks were studied in an attempt to improve their conductivity in one direction. In particular, the peptides were assembled under an electric field (0 to 3.75 kV/cm). Random networks were produced at low field strengths, whereas a degree of alignment was obtained at a field strength of 3.75 kV/cm. The conductivity of the aligned networks in the direction of alignment was a factor of three times higher than that of the random networks.The second system studied was Fmoc-dipeptide-OMe hydrogels produced by the enzymatic condensation of an Fmoc-amino acid and an amino acid ester. Preliminary results found that Fmoc-SF-OMe assembled into nanosheets, nanoribbons and spherulites, depending on the temperature at which self-assembly occurred. The Fmoc-XY-OMe films possessed an extremely high resistance (1012 Ω).EThOS - Electronic Theses Online ServiceRein UlijnGBUnited Kingdo

Differential miRNA expression in Rehmannia glutinosa plants subjected to continuous cropping

<p>Abstract</p> <p>Background</p> <p>The productivity of the medicinally significant perennial herb <it>Rehmannia glutinosa </it>is severely affected after the first year of cropping. While there is some information available describing the physiological and environmental causes of this yield decline, there is as yet no data regarding the changes in gene expression which occur when the species is continuously cropped.</p> <p>Results</p> <p>Using a massively parallel (Solexa) DNA sequencing platform, it was possible to identify and quantify the abundance of a large number of <it>R. glutinosa </it>miRNAs. We contrasted the miRNA content of first year crop plants with that of second year crop ones, and were able to show that of 89 conserved (belonging to 25 families) and six novel miRNAs (six families), 29 of the former and three of the latter were differentially expressed. The three novel miRNAs were predicted to target seven genes, and the 29 conserved ones 308 genes. The potential targets of 32 of these differentially expressed miRNAs involved in the main transcription regulation, plant development and signal transduction. A functional analysis of the differentially expressed miRNAs suggested that several of the proposed targets could be directly or indirectly responsible for the development of the tuberous root.</p> <p>Conclusion</p> <p>We have compared differential miRNAs expression in the first year crop (FP) <it>R. glutinosa </it>plants and second year crop (SP) ones. The outcome identifies some potential leads for understanding the molecular basis of the processes underlying the difficulty of maintaining the productivity of continuously cropped <it>R. glutinosa</it>.</p

HULL SHAPE OPTIMIZATION OF SMALL UNDERWATER VEHICLE BASED ON KRIGING-BASED RESPONSE SURFACE METHOD AND MULTI-OBJECTIVE OPTIMIZATION ALGORITHM

Small underwater vehicles have unique advantages in ocean exploration. The resistance and volume of a vehicle are key factors affecting its operation time underwater. This paper aims to develop an effective method to obtain the optimal hull shape of a small underwater vehicle using Kriging-based response surface method (RSM) and multi-objective optimization algorithm. Firstly, the hydrodynamic performance of a small underwater vehicle is numerically investigated using computational fluid dynamics (CFD) method and the value range of related design variables is determined. The mesh convergence is verified to ensure the accuracy of the calculation results. Then, by means of the Latin hypercube sampling (LHS) design of simulation, the Kriging-based RSM model is developed according to the relation between each design variable of the vehicle and the output parameters applied to the vehicle. Based on the Kriging-based RSM model, the optimal hull shape of the vehicle is determined by using Screening and MOGA. As results, the vehicle resistance reduces and volume increases obviously

A Blockchain Traceable Scheme with Oversight Function

Many blockchain researches focus on the privacy protection. However, criminals can leverage strong privacy protection of the blockchain to do illegal crimes (such as ransomware) without being punished. These crimes have caused huge losses to society and users. Implementing identity tracing is an important step in dealing with issues arising from privacy protection. In this paper, we propose a blockchain traceable scheme with oversight function (BTSOF). The design of BTSOF builds on SkyEye (Tianjun Ma et al., Cryptology ePrint Archive 2020). In BTSOF, the regulator must obtain the consent of the committee to enable tracing. Moreover, we construct a non-interactive verifiable multi-secret sharing scheme (VMSS scheme) and leverage the VMSS scheme to design a distributed multi-key generation (DMKG) protocol for the Cramer-Shoup public key encryption scheme. The DMKG protocol is used in the design of BTSOF. We provide the security definition and security proof of the VMSS scheme and DMKG protocol

A Genetic Transformation Method for Cadmium Hyperaccumulator Sedum plumbizincicola and Non-hyperaccumulating Ecotype of Sedum alfredii

The present study demonstrates the development of an Agrobacterium-mediated genetic transformation method for species of the Sedum genus, which includes the Cd/Zn hyperaccumulator Sedum plumbizincicola and the non-hyperaccumulating ecotype of S. alfredii. Multiple shoots were induced from stem nodes of two Sedum plants using Murashige and Skoog (MS) medium containing 0.1 mg/L cytokinin 6-benzyladenine (6-BA) and 1.0 mg/L auxin 1-naphthaleneacetic acid (NAA). The shoot primordia were used as direct targets for Agrobacterium infection. Selection on hygromycin was highly effective in generating Agrobacterium-transformed explants. This callus-free procedure allowed us to obtain transgenic plantlets after rooting hygromycin-resistant shoots on phytohormone-free MS medium containing the antibiotic. The presence and expression of the reporter genes gusA and GFP in transgenic plants were confirmed by a real-time polymerase chain reaction, histochemical GUS assays, and confocal microscopy. This reliable method for genetic transformation of Sedum plants will help us to understand gene functions and the molecular mechanisms underlying Cd hypertolerance and hyperaccumulation in these species

SkyEye: A Traceable Scheme for Blockchain

Many studies focus on the blockchain privacy protection. Unfortunately, the privacy protection brings some issues (e.g., money-laundering problem). Tracing users\u27 identities is a critical step in addressing these issues. When each user\u27s identity in the blockchain data is determined, the regulator can do some regulatory operations (such as Big Data analysis) to decide who should be punished or who should own the lost data. In this paper, we propose SkyEye, a traceable scheme for blockchain, that can be applied to a class of blockchain application. SkyEye enables the regulator to trace users\u27 identities. Moreover, we demonstrate the security of SkyEye under specific cryptographic assumptions. Finally, we implement two prototypes of SkyEye, and evaluate the running time and related data storage requirements by performing the aforementioned prototypes