Enhanced Collateral Growth by Double Transplantation of Gene-Nucleofected Fibroblasts in Ischemic Hindlimb of Rats

BACKGROUND: Induction of neovascularization by releasing therapeutic growth factors is a promising application of cell-based gene therapy to treat ischemia-related problems. In the present study, we have developed a new strategy based on nucleofection with alternative solution and cuvette to promote collateral growth and re-establishment of circulation in ischemic limbs using double transplantation of gene nucleofected primary cultures of fibroblasts, which were isolated from rat receiving such therapy. METHODS AND RESULTS: Rat dermal fibroblasts were nucleofected ex vivo to release bFGF or VEGF165 in a hindlimb ischemia model in vivo. After femoral artery ligation, gene-modified cells were injected intramuscularly. One week post injection, local confined plasmid expression and transient distributions of the plasmids in other organs were detected by quantitative PCR. Quantitative micro-CT analyses showed improvements of vascularization in the ischemic zone (No. of collateral vessels via micro CT: 6.8±2.3 vs. 10.1±2.6; p<0.05). Moreover, improved collateral proliferation (BrdU incorporation: 0.48±0.05 vs. 0.57±0.05; p<0.05) and increase in blood perfusion (microspheres ratio: gastrocnemius: 0.41±0.10 vs. 0.50±0.11; p<0.05; soleus ratio: soleus: 0.42±0.08 vs. 0.60±0.08; p<0.01) in the lower hindlimb were also observed. CONCLUSIONS: These results demonstrate the feasibility and effectiveness of double transplantation of gene nucleofected primary fibroblasts in producing growth factors and promoting the formation of collateral circulation in ischemic hindlimb, suggesting that isolation and preparation of gene nucleofected cells from individual accepting gene therapy may be an alternative strategy for treating limb ischemia related diseases

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Challenges of additive manufacturing technologies from an optimisation perspective

Three-dimensional printing offers varied possibilities of design that can be bridged to optimisation tools. In this review paper, a critical opinion on optimal design is delivered to show limits, benefits and ways of improvement in additive manufacturing. This review emphasises on design constrains related to additive manufacturing and differences that may appear between virtual and real design. These differences are explored based on 3D imaging techniques that are intended to show defect related processing. Guidelines of safe use of the term “optimal design” are derived based on 3D structural information

Calculating Co-Seismic Three-Dimensional Displacements from InSAR Observations with the Dislocation Model-Based Displacement Direction Constraint: Application to the 23 July 2020 Mw6.3 Nima Earthquake, China

As one of the most prevailing geodetic tools, the interferometric synthetic aperture radar (InSAR) technique can accurately obtain co-seismic displacements, but is limited to the one-dimensional line-of-sight (LOS) measurement. It is therefore difficult to completely reveal the real three-dimensional (3D) surface displacements with InSAR. By employing azimuth displacement observations from pixel offset tracking (POT) and multiple aperture InSAR (MAI) techniques, 3D displacements of large-magnitude earthquakes can be obtained by integrating the ascending and descending data. However, this method cannot be used to accurately realize the 3D surface displacement measurements of small-magnitude earthquakes due to the low accuracies of the POT/MAI-derived azimuth displacement measurements. In this paper, an alternative method is proposed to calculate co-seismic 3D displacements from ascending and descending InSAR-LOS observations with the dislocation model-based displacement direction constraint. The main contribution lies in the two virtual observation equations that are obtained from the dislocation model-based forward-modeling 3D displacements, which are then combined with the ascending/descending InSAR observations to calculate the 3D displacements. The basis of the two virtual observation equations is that the directions of the 3D displacement vectors are very similar for real and model-based 3D displacements. In addition, the weighted least squares (WLS) method is employed to solve the final 3D displacements, which aims to consider and balance the possible errors in the InSAR observations as well as the dislocation model-based displacement direction constraint. A simulation experiment demonstrates that the proposed method can achieve more accurate 3D displacements compared with the existing methods. The co-seismic 3D displacements of the 2020 Nima earthquake are then accurately obtained by the proposed method. The results show that co-seismic displacements are dominated by the vertical displacement, the magnitude of the horizontal displacement is relatively small, and the overall displacement pattern fits well with the tensile rupture

RansomBlocker: A low-overhead ransomware-proof SSD

© 2019 Association for Computing Machinery.We present a low-overhead ransomware-proof SSD, called RansomBlocker (RBlocker). RBlocker provides 100% full protections against all possible ransomware attacks by delaying every data deletion until no attack is guaranteed. To reduce storage overheads of the delayed deletion, RBlocker employs a time-out based backup policy. Based on the fact that ransomware must store encrypted version of target files, early deletions of obsolete data are allowed if no encrypted write was detected for a short interval. Otherwise, RBlocker keeps the data for an interval long enough to guarantee no attack condition. For an accurate in-line detection of encrypted writes, we leverages entropy- and CNN-based detectors in an integrated fashion. Our experimental results show that RBlocker can defend all types of ransomware attacks with negligible overheads.N

Prog. Chem.

Ionic liquids, which are considered as the sustainable &quot;green product&quot;, are gaining increasing interest due to their physical and chemical characteristics. Although a lot of efforts have been focused on the investigation of their syntheses and applications, structure-property/activity relationships of ionic liquids are poorly known to us. The quantitative structure-property/activity relationships (QSPR/QSAR) research methods and steps are described systematically in this article. The latest researches of quantitative structure-property/activity relationships on the melting points of ionic liquids, the infinite dilution activity coefficients of organic compounds, surface tensions of ionic liquids, conductivities of ionic liquids, solubility of organic solutes in ionic liquids, viscosities of ionic liquids and biological toxicity and degradation of ionic liquids are reviewed. Both advantages and disadvantages of the QSPR/QSAR used in the ionic liquid property prediction are discussed, and the prospective of this research area is proposed.Ionic liquids, which are considered as the sustainable "green product", are gaining increasing interest due to their physical and chemical characteristics. Although a lot of efforts have been focused on the investigation of their syntheses and applications, structure-property/activity relationships of ionic liquids are poorly known to us. The quantitative structure-property/activity relationships (QSPR/QSAR) research methods and steps are described systematically in this article. The latest researches of quantitative structure-property/activity relationships on the melting points of ionic liquids, the infinite dilution activity coefficients of organic compounds, surface tensions of ionic liquids, conductivities of ionic liquids, solubility of organic solutes in ionic liquids, viscosities of ionic liquids and biological toxicity and degradation of ionic liquids are reviewed. Both advantages and disadvantages of the QSPR/QSAR used in the ionic liquid property prediction are discussed, and the prospective of this research area is proposed

Ascertaining the Carbon Hybridization States of Synthetic Polymers with X-ray Induced Auger Electron Spectroscopy

X-ray induced Auger electron spectroscopy was used to evaluate synthetic polymers containing carbons with differing degrees of sp-, sp2-, and sp3-hybridization states as well as heteroatoms. For comparison, a series of related small molecules was also studied. Linear correlations were observed and a universal calibration method for quantifying the average hybridization states of a wide variety of synthetic polymeric materials is offered. © 2018 American Chemical Societ