Double-stranded break can be repaired by single-stranded oligonucleotides via the ATM/ATR pathway in mammalian cells

Single-stranded oligonucleotide (SSO)-mediated gene modification is a newly developed tool for site-specific gene repair in mammalian cells; however, the corrected cells always show G2/M arrest and cannot divide to form colonies. This phenomenon and the unclear mechanism seriously challenge the future application of this technique. In this study, we developed an efficient SSO-mediated DNA repair system based on double-stranded break (DSB) induction. We generated a mutant EGFP gene with insertions of 24 bp to 1.6 kb in length as a reporter integrated in mammalian cell lines. SSOs were successfully used to delete the insertion fragments upon DSB induction at a site near the insertion. We demonstrated that this process is dependent on the ATM/ATR pathway. Importantly, repaired cell clones were viable. Effects of deletion length, SSO length, strand bias, and SSO modification on gene repair frequency were also investigated. © 2008 Mary Ann Liebert, Inc.published_or_final_versio

Privacy-Preserving Outsourcing of Large-Scale Nonlinear Programming to the Cloud

The increasing massive data generated by various sources has given birth to big data analytics. Solving large-scale nonlinear programming problems (NLPs) is one important big data analytics task that has applications in many domains such as transport and logistics. However, NLPs are usually too computationally expensive for resource-constrained users. Fortunately, cloud computing provides an alternative and economical service for resource-constrained users to outsource their computation tasks to the cloud. However, one major concern with outsourcing NLPs is the leakage of user's private information contained in NLP formulations and results. Although much work has been done on privacy-preserving outsourcing of computation tasks, little attention has been paid to NLPs. In this paper, we for the first time investigate secure outsourcing of general large-scale NLPs with nonlinear constraints. A secure and efficient transformation scheme at the user side is proposed to protect user's private information; at the cloud side, generalized reduced gradient method is applied to effectively solve the transformed large-scale NLPs. The proposed protocol is implemented on a cloud computing testbed. Experimental evaluations demonstrate that significant time can be saved for users and the proposed mechanism has the potential for practical use.Comment: Ang Li and Wei Du equally contributed to this work. This work was done when Wei Du was at the University of Arkansas. 2018 EAI International Conference on Security and Privacy in Communication Networks (SecureComm

Tunneling magnetoresistance in Fe3Si/MgO/Fe3Si(001) magnetic tunnel junctions

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Cell death caused by single-stranded oligodeoxynucleotide-mediated targeted genomic sequence modification

Targeted gene repair directed by single-stranded oligodeoxynucleotides (ssODNs) offers a promising tool for biotechnology and gene therapy. However, the methodology is currently limited by its low frequency of repair events, variability, and low viability of "corrected" cells. In this study, we showed that during ssODN-mediated gene repair reaction, a significant population of corrected cells failed to divide, and were much more prone to undergo apoptosis, as marked by processing of caspases and PARP-1. In addition, we found that apoptotic cell death triggered by ssODN-mediated gene repair was largely independent of the ATM/ATR kinase. Furthermore, we examined the potential involvement of the mismatch repair (MMR) proteins in this "correction reaction-induced" cell death. Result showed that while defective MMR greatly enhanced the efficiency of gene correction, compromising the MMR system did not yield any viable corrected clone, indicating that the MMR machinery, although plays a critical role in determining ssODN-directed repair, was not involved in the observed cellular genotoxic responses. © 2009. Mary Ann Liebert, Inc.published_or_final_versio

Longevity of the Permian Emeishan mantle plume (SW China): 1 Ma, 8 Ma or 18 Ma?

After the formation of the ∼ 260 Ma Emeishan large igneous province, there were two volumetrically minor magmatic pulses at ∼ 252 Ma and ∼ 242 Ma, respectively. Alkaline mafic dykes intruding both 260 Ma and 252 Ma felsic plutons in the Panxi region, southwestern China, have compositions similar to the Emeishan flood basalts. One dyke is dated using the SHRIMP zircon U-Pb technique at 242 ± 2 Ma, ∼ 18 Ma younger than the start of Emeishan magmatism. The dykes have enriched light rare earth element patterns (La/YbN = 4.4-18.8) and trace element patterns similar to the Emeishan flood basalts and average ocean-island basalts. Some trace element ratios of the dykes (Zr/Nb = 3.8-8.2, La/Nb = 0.4-1.7, Ba/La = 7.5-25.6) are somewhat similar to EM1 source material, however, there are differences. Their εNd values (εNd = +2.6 and +2.7) and ISr( ISr = 0.704542 and 0.704554) ratios are indicative of a mantle source. Thus Emeishan magmatism may have lasted for almost 20 Ma after the initial eruption. However, geological evidence precludes the possibility that the post-260 Ma magmatic events were directly related to Emeishan magmatism, which began at and ended shortly after 260 Ma. The 252 Ma plutons and 242 Ma dykes represent volumetrically minor melting of the fossil Emeishan plume-head beneath the Yangtze crust. The 252 Ma magmatic event was likely caused by post-flood basalt extension of the Yangtze crust, whereas the 242 Ma event was caused by decompressional melting associated with the collision between the South China and North China blocks during the Middle Triassic. © 2008 Cambridge University Press.published_or_final_versio

Ellagic acid, a phenolic compound, exerts anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer

Anti-angiogenesis targeting VEGFR-2 has been considered as an important strategy for cancer therapy. Ellagic acid is a naturally existing polyphenol widely found in fruits and vegetables. It was reported that ellagic acid interfered with some angiogenesis-dependent pathologies. Yet the mechanisms involved were not fully understood. Thus, we analyzed its anti-angiogenesis effects and mechanisms on human breast cancer utilizing in-vitro and in-vivo methodologies. The in-silico analysis was also carried out to further analyze the structure-based interaction between ellagic acid and VEGFR-2. We found that ellagic acid significantly inhibited a series of VEGF-induced angiogenesis processes including proliferation, migration, and tube formation of endothelial cells. Besides, it directly inhibited VEGFR-2 tyrosine kinase activity and its downstream signaling pathways including MAPK and PI3K/Akt in endothelial cells. Ellagic acid also obviously inhibited neo-vessel formation in chick chorioallantoic membrane and sprouts formation of chicken aorta. Breast cancer xenografts study also revealed that ellagic acid significantly inhibited MDA-MB-231 cancer growth and P-VEGFR2 expression. Molecular docking simulation indicated that ellagic acid could form hydrogen bonds and aromatic interactions within the ATP-binding region of the VEGFR-2 kinase unit. Taken together, ellagic acid could exert anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer. © 2012 The Author(s).published_or_final_versio

Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats

Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses

Total coloring of 1-toroidal graphs of maximum degree at least 11 and no adjacent triangles

A {\em total coloring} of a graph $G$ is an assignment of colors to the vertices and the edges of $G$ such that every pair of adjacent/incident elements receive distinct colors. The {\em total chromatic number} of a graph $G$, denoted by \chiup''(G), is the minimum number of colors in a total coloring of $G$. The well-known Total Coloring Conjecture (TCC) says that every graph with maximum degree $\Delta$ admits a total coloring with at most $\Delta + 2$ colors. A graph is {\em $1$-toroidal} if it can be drawn in torus such that every edge crosses at most one other edge. In this paper, we investigate the total coloring of $1$-toroidal graphs, and prove that the TCC holds for the $1$-toroidal graphs with maximum degree at least~$11$ and some restrictions on the triangles. Consequently, if $G$ is a $1$-toroidal graph with maximum degree $\Delta$ at least~$11$ and without adjacent triangles, then $G$ admits a total coloring with at most $\Delta + 2$ colors.Comment: 10 page

Transmit Power Minimization for MIMO Systems of Exponential Average BER with Fixed Outage Probability

This document is the Accepted Manuscript version of the following article: Dian-Wu Yue, and Yichuang Sun, ‘Transmit Power Minimization for MIMO Systems of Exponential Average BER with Fixed Outage Probability’, Wireless Personal Communications, Vol. 90 (4): 1951-1970, first available online on 20 June 2016. Under embargo. Embargo end date: 20 June 2017. The final publication is available at Springer via https://link.springer.com/article/10.1007%2Fs11277-016-3432-4This paper is concerned with a wireless multiple-antenna system operating in multiple-input multiple-output (MIMO) fading channels with channel state information being known at both transmitter and receiver. By spatiotemporal subchannel selection and power control, it aims to minimize the average transmit power (ATP) of the MIMO system while achieving an exponential type of average bit error rate (BER) for each data stream. Under the constraints on each subchannel that individual outage probability and average BER are given, based on a traditional upper bound and a dynamic upper bound of Q function, two closed-form ATP expressions are derived, respectively, which can result in two different power allocation schemes. Numerical results are provided to validate the theoretical analysis, and show that the power allocation scheme with the dynamic upper bound can achieve more power savings than the one with the traditional upper bound.Peer reviewe