CAS9 is a genome mutator by directly disrupting DNA-PK dependent DNA repair pathway.

With its high efficiency for site-specific genome editing and easy manipulation, the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR associated protein 9 (CAS9) system has become the most widely used gene editing technology in biomedical research. In addition, significant progress has been made for the clinical development of CRISPR/CAS9 based gene therapies of human diseases, several of which are entering clinical trials. Here we report that CAS9 protein can function as a genome mutator independent of any exogenous guide RNA (gRNA) in human cells, promoting genomic DNA double-stranded break (DSB) damage and genomic instability. CAS9 interacts with the KU86 subunit of the DNA-dependent protein kinase (DNA-PK) complex and disrupts the interaction between KU86 and its kinase subunit, leading to defective DNA-PK-dependent repair of DNA DSB damage via non-homologous end-joining (NHEJ) pathway. XCAS9 is a CAS9 variant with potentially higher fidelity and broader compatibility, and dCAS9 is a CAS9 variant without nuclease activity. We show that XCAS9 and dCAS9 also interact with KU86 and disrupt DNA DSB repair. Considering the critical roles of DNA-PK in maintaining genomic stability and the pleiotropic impact of DNA DSB damage responses on cellular proliferation and survival, our findings caution the interpretation of data involving CRISPR/CAS9-based gene editing and raise serious safety concerns of CRISPR/CAS9 system in clinical application

A NOVEL EVALUATION APPROACH TO FINDING LIGHTWEIGHT MACHINE LEARNING ALGORITHMS FOR INTRUSION DETECTION IN COMPUTER NETWORK

Building practical and efficient intrusion detection systems in computer network is important in industrial areas today and machine learning technique provides a set of effective algorithms to detect network intrusion. To find out appropriate algorithms for building such kinds of systems, it is necessary to evaluate various types of machine learning algorithms based on specific criteria. In this paper, we propose a novel evaluation formula which incorporates 6 indexes into our comprehensive measurement, including precision, recall, root mean square error, training time, sample complexity and practicability, in order to find algorithms which have high detection rate, low training time, need less training samples and are easy to use like constructing, understanding and analyzing models. Detailed evaluation process is designed to get all necessary assessment indicators and 6 kinds of machine learning algorithms are evaluated. Experimental results illustrate that Logistic Regression shows the best overall performance

The response to dynamical modulation of the optical lattice for fermions in the Hubbard model

Fermionic atoms in a periodic optical lattice provide a realization of the single-band Hubbard model. Using Quantum Monte Carlo simulations along with the Maximum Entropy Method, we evaluate the effect of a time-dependent perturbative modulation of the optical lattice amplitude on atomic correlations, revealed in the fraction of doubly-occupied sites. Our treatment extends previous approaches which neglected the time dependence of the on-site interaction, and shows that this term changes the results in a quantitatively significant way. The effect of modulation depends strongly on the filling-- the response of the double occupation is significantly different in the half-filled Mott insulator from the doped Fermi liquid region.Comment: 4 pages, 4 figure

A Method of Decreasing Time Delay for A Tele-surgery System

Abstract -The haptics-based master-slave system for Minimally Invasive Surgery is a promising way to protect surgeons from long time radiation and to train novice doctors to learn basic wire or catheter handling skills. However, the time delay of transmission of visual video and the time difference between image information and force signals restrict the application of this technology in some extent. In this paper, we proposed a new method to reduce time delay effectively. At the slave side, the tip of the active catheter is tracked in real time to provide information on the location of the catheter in the blood vessel model. And then transmitted the coordinate values to the master site. At the master site, the location of the catheter was reappeared in the navigation chart which is the same structure with the blood vessels at master side according to the coordinate values received from the slave side. Therefore the transmission time of image information is decreased. Experimental results are given to illustrate the accuracy of our method

Quantum-Enhanced Diamond Molecular Tension Microscopy for Quantifying Cellular Forces

The constant interplay and information exchange between cells and their micro-environment are essential to their survival and ability to execute biological functions. To date, a few leading technologies such as traction force microscopy, have been broadly used in measuring cellular forces. However, the considerable limitations, regarding the sensitivity and ambiguities in data interpretation, are hindering our thorough understanding of mechanobiology. Herein, we propose an innovative approach, namely quantum-enhanced diamond molecular tension microscopy (QDMTM), to precisely quantify the integrin-based cell adhesive forces. Specifically, we construct a force sensing platform by conjugating the magnetic nanotags labeled, force-responsive polymer to the surface of diamond membrane containing nitrogen vacancy (NV) centers. Thus, the coupled mechanical information can be quantified through optical readout of spin relaxation of NV centers modulated by those magnetic nanotags. To validate QDMTM, we have carefully performed corresponding measurements both in control and real cell samples. Particularly, we have obtained the quantitative cellular adhesion force mapping by correlating the measurement with established theoretical model. We anticipate that our method can be routinely used in studying important issues like cell-cell or cell-material interactions and mechanotransduction.Comment: 51 pages, 20 figure

Optical studies of structural phase transition in the vanadium-based kagome metal ScV6Sn6

In condensed matter physics, materials with kagome lattice exhibit exotic emergent quantum states, including charge density wave (CDW), superconductivity and magnetism. Very recently, hexagonal kagome metal ScV6Sn6 was found to undergo fascinating first-order structural phase transition at around 92 K and a 3x3x3 CDW modulation. The bulk electronic band properties are enlightened for comprehending the origin of the structural phase transition. Here, we perform a optical spectroscopy study on the monocrystalline compound across the transition temperature. The structural transition gives rise to the abrupt changes of optical spectra without observing gap development behavior. The optical measurements revealed a sudden reconstruction of the band structure after transition. We emphasize that the phase transition is of the first order and distinctly different from the conventional density-wave type condensation. Our results provide insight into the origin of the structural phase transition in the new kagome metal compound.Comment: 7 pages, 4 figure

Pump-induced terahertz conductivity response and peculiar bound state in Mn3Si2Te6

We report the significant enhancement on ultrafast terahertz optical conductivity and the unexpected formation of a polaronic-like state in semiconductor Mn3Si2Te6 at room temperature. With the absorption of pump photons, the low-frequency terahertz photoconductivity spectrum exhibits a significant rise, quickly forming a broad peak and subsequently shifting to higher energy. The short-lived nature of the broad peak, as well as the distribution of optical constants, strongly points towards a transient polaron mechanism. Our study not only provides profound insights into the remarkable photoelectric response of Mn3Si2Te6 but also highlights its significant potential for future photoelectric applications

Strong nonlinear optical response and transient symmetry switching in Type-II Weyl semimetal β\beta-WP2

The topological Weyl semimetals with peculiar band structure exhibit novel nonlinear optical enhancement phenomena even for light at optical wavelengths. While many intriguing nonlinear optical effects were constantly uncovered in type-I semimetals, few experimental works focused on basic nonlinear optical properties in type-II Weyl semimetals. Here we perform a fundamental static and time-resolved second harmonic generation (SHG) on the three dimensional Type-II Weyl semimetal candidate $\beta$-WP$_2$. Although $\beta$-WP$_2$ exhibits extremely high conductivity and an extraordinarily large mean free path, the second harmonic generation is unscreened by conduction electrons, we observed rather strong SHG response compared to non-topological polar metals and archetypal ferroelectric insulators. Additionally, our time-resolved SHG experiment traces ultrafast symmetry switching and reveals that polar metal $\beta$-WP$_2$ tends to form inversion symmetric metastable state after photo-excitation. Intense femtosecond laser pulse could optically drive symmetry switching and tune nonlinear optical response on ultrafast timescales although the interlayer coupling of $\beta$-WP$_2$ is very strong. Our work is illuminating for the polar metal nonlinear optics and potential ultrafast topological optoelectronic applications.Comment: 8 pages, 5 figure

TGF-β1-Mediated Leukocyte Cell-Derived Chemotaxin 2 Is Associated With Liver Fibrosis in Biliary Atresia

ObjectiveBiliary atresia (BA) presents as a severe infantile cholangiopathy disease, characterized by progressive liver fibrosis and the resulting poor prognosis. Leukocyte cell-derived chemotaxin 2 (LECT2) was proposed as the key gene associated with hepatic fibrosis in BA, but the molecular mechanism is unclear. This study aims to investigate the function of LECT2 in BA.MethodsA total of 53 patients were enrolled in this study; 36 patients with BA, and 17 control patients with cholestasis, including congenital biliary dilations, biliary hypoplasia, and inspissated bile syndrome. The role of LECT2 in BA was analyzed using histological and cytological tests. The correlation between LECT2 and infiltrating immune cells was further analyzed by bioinformatics. The analyses were conducted using correlational analyses and ROC curves.ResultsLECT2 was highly expressed in infants with BA and positively related with fibrosis (0.1644 ± 0.0608 vs. 0.0779 ± 0.0053, p < 0.0001; rs = 0.85, p < 0.0001). Serum levels of LECT2 showed high distinguishing features for patients with BA having an AUC of 0.95 (95% CI: 0.90–1.00). CD163 was highly expressed in the aggravation of fibrosis (0.158 ± 0.062 vs. 0.29 ± 0.078, p < 0.0001), and the expression of LECT2 was positively correlated with the accumulation of CD163+ macrophages (r = 0.48, p = 0.003). The bioinformatic analysis also showed that LECT2 was positively correlated with macrophage M2 (r = 0.34, p = 0.03). TGF-β1 and CD163 colocalized to the portal area in the livers of patients with BA. Moreover, TGF-β1 upregulated the expression of LECT2.ConclusionLECT2 is highly expressed in both BA liver tissue and serum, and serum LECT2 is a potential diagnostic biomarker of BA. Meanwhile, TGF-β1 is secreted by macrophages to regulate LECT2 associated with BA liver fibrosis