PLCs (Programmable Logic Controllers) are the work horse of industrial control systems. Industrial control systems are usually both mission-critical and safety-critical systems. A single software bug in a control system program could cause hardware equipment damage and human life loss. The PLC programs in control systems must provide bug-free and failure-free behaviors in order to avoid accidents. A PLC program must be completely tested for correctness in functionality, reliability, predictability, and safety before it's released for production systems. At a PLC program development stage, hardware devices in the industrial control system are usually not available for testing the PLC program for safety reasons. The often used solution is to use a simulator to simulate the hardware devices' behaviors. The simulator is usually built as a hardware test stand which consists of toggle switches, lamp indicators, and analog signal generators. The shortcoming of this kind of simulators is they are not automated and require lots of user interactions. As a result, they cannot guarantee the accuracy of behaviors of the hardware devices being simulated. This research presents an automated testing tool which automates the hardware device simulation process by using "virtual" wires. The hardware device simulation is part of a test case which is defined in the presented testing tool and downloaded to the PLC controller. This testing tool requires no user interaction during a test run so it reduces the testing cost and time and it can precisely simulate the behaviors of hardware devices

Growth differentiation factor 11 (GDF11) has been implicated in rejuvenating functions in age-related diseases. The molecular mechanisms connecting GDF11 with these anti-aging phenomena, including reverse age-related cardiac hypertrophy and vascular and neurogenic rejuvenation, remain unclear. In this study, we sought to uncover the molecular functions of GDF11 using bioinformatics and network-driven analyses at the human gene and transcription levels using the gene co-expression network analysis, the protein-protein interaction network analysis, and the transcription factor network analysis. Our findings suggested that GDF11 is involved in a variety of functions, such as apoptosis, DNA repair, telomere maintenance, and interaction with key transcription factors, such as MYC proto-oncogene, specificity protein 1, and ETS proto-oncogene 2. The human skin fibroblast premature senescence model was established by UVB. The treatment with 10 ng/mL GDF11 in this cell model could reduce cell damage, reduce the apoptosis rate and the expression of caspase-3, and increase the length of telomeres. Therefore, our findings shed light on the functions of GDF11 and provide insights into the roles of GDF11 in aging.

Recent advances in genome engineering technologies based on the CRISPR-associated RNA-guided endonuclease Cas9 are enabling the systematic interrogation of mammalian genome function. Analogous to the search function in modern word processors, Cas9 can be guided to specific locations within complex genomes by a short RNA search string. Using this system, DNA sequences within the endogenous genome and their functional outputs are now easily edited or modulated in virtually any organism of choice. Cas9-mediated genetic perturbation is simple and scalable, empowering researchers to elucidate the functional organization of the genome at the systems level and establish causal linkages between genetic variations and biological phenotypes. In this Review, we describe the development and applications of Cas9 for a variety of research or translational applications while highlighting challenges as well as future directions. Derived from a remarkable microbial defense system, Cas9 is driving innovative applications from basic biology to biotechnology and medicine.

Spin-center shift (SCS) is a radical process involving 1,2-radical translocation along with a two-electron ionic movement, such as elimination of an adjacent leaving group. Such a process was initially observed in some important biochemical transformations, and the unique property has also attracted considerable interest in synthetic chemistry. Experimental, kinetic, as well as computational studies have been performed, and a series of useful radical transformations have been developed and applied in organic synthesis based on SCS processes in the last 20 years. This Perspective is an overview of radical transformations involving the SCS mechanism.

Background

PIF/Harbinger is the most recently discovered DNA transposon superfamily and is now known to populate genomes from fungi to plants to animals. Mobilization of superfamily members requires two separate element-encoded proteins (ORF1 and TPase). Members of this superfamily also mobilize Tourist-like miniature inverted repeat transposable elements (MITEs), which are the most abundant transposable elements associated with the genes of plants, especially the cereal grasses. The phylogenetic analysis of many plant genomes indicates that MITEs can amplify rapidly from one or a few elements to hundreds or thousands.The most active DNA transposon identified to date in plants or animals is mPing, a rice Tourist-like MITE that is a deletion derivative of the autonomous Ping element. Ping and the closely related Pong are the only known naturally active PIF/Harbinger elements. Some rice strains accumulate ~40 new mPing insertions per plant per generation. In this study we report the development of a yeast transposition assay as a first step in deciphering the mechanism underlying the amplification of Tourist-MITEs.

Results

The ORF1 and TPase proteins encoded by Ping and Pong have been shown to mobilize mPing in rice and in transgenic Arabidopsis. Initial tests of the native proteins in a yeast assay resulted in very low transposition. Significantly higher activities were obtained by mutation of a putative nuclear export signal (NES) in the TPase that increased the amount of TPase in the nucleus. When introduced into Arabidopsis, the NES mutant protein also catalyzed higher frequencies of mPing excision from the gfp reporter gene. Our yeast assay retains key features of excision and insertion of mPing including precise excision, extended insertion sequence preference, and a requirement for two proteins that can come from either Ping or Pong or both elements.

Conclusions

The yeast transposition assay provides a robust platform for analysis of the mechanism underlying transposition catalyzed by the two proteins of PIF/Harbinger elements. It recapitulates all of the features of excision and reinsertion of mPing as seen in plant systems. Furthermore, a mutation of a putative NES in the TPase increased transposition both in yeast and plants.

Most current research on commonsense question answering (CQA) has focused on proposing different techniques in natural language processing and text information retrieval. However, for human cognition, retrieving and organizing desired answers from text knowledge related to commonsense questions is far less intuitive and comprehensive than it is when using multi-modal knowledge, such as related images and videos. Motivated by this, we propose a framework for trying the acquisition of diverse modal information, and embedding and integrating it into CQA tasks, further improving the performance and user experience. Specifically, this paper proposes the integration of multi-modal knowledge, including images, image description statements, image scene graphs, and knowledge sub-graphs, into a CQA system. It introduces a parallel embedding technique for this multi-modal knowledge and employs an alignment-interaction-fusion mechanism to facilitate the seamless integration of this multi-modal knowledge. Through extensive experiments, the effectiveness and superiority of our proposed method are demonstrated.

Targeted nucleases are powerful tools for mediating genome alteration with high precision. The RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system can be used to facilitate efficient genome engineering in eukaryotic cells by simply specifying a 20-nt targeting sequence within its guide RNA. Here we describe a set of tools for Cas9-mediated genome editing via nonhomologous end joining (NHEJ) or homology-directed repair (HDR) in mammalian cells, as well as generation of modified cell lines for downstream functional studies. To minimize off-target cleavage, we further describe a double-nicking strategy using the Cas9 nickase mutant with paired guide RNAs. This protocol provides experimentally derived guidelines for the selection of target sites, evaluation of cleavage efficiency and analysis of off-target activity. Beginning with target design, gene modifications can be achieved within as little as 1-2 weeks, and modified clonal cell lines can be derived within 2-3 weeks.

Plants synthesize jasmonates (JAs) in response to developmental cues or environmental stresses, in order to coordinate plant growth, development or defense against pathogens and herbivores. Perception of pathogen or herbivore attack promotes synthesis of jasmonoyl-L-isoleucine (JA-Ile), which binds to the COI1-JAZ receptor, triggering the degradation of JAZ repressors and induction of transcriptional reprogramming associated with plant defense. Interestingly, some virulent pathogens have evolved various strategies to manipulate JA signaling to facilitate their exploitation of plant hosts. In this review, we focus on recent advances in understanding the mechanism underlying the enigmatic switch between transcriptional repression and hormone-dependent transcriptional activation of JA signaling. We also discuss various strategies used by pathogens and insects to manipulate JA signaling and how interfering with this could be used as a novel means of disease control.

Reprecipitation synthesis has been demonstrated to be a simple and convenient route to fabricate high quality perovskite quantum dots toward display applications, whereas the limited chemical yields (< 10%) and difficulty of purification limited its further application. In order to overcome this issue, we here report a modified emulsion synthesis by introducing phase transfer strategy, which achieving effective extraction of newly formed perovskite quantum dots into non-polar solvent and avoiding the degradation of perovskite quantum dots to a large extent. Based on this strategy, gram-scale CH₃NH₃PbBr₃ quantum dots were fabricated in 10 mL (~0.02 mol/L) colloidal solution with chemical yields larger than 70%. The as fabricated CH₃NH₃PbBr₃ quantum dots exhibit an emission peak of 453 nm and a full width at half maximum of only 14 nm. Moreover, electroluminescent devices based on blue emitting CH₃NH₃PbBr₃ quantum dots were also explored with a maximum luminance of 32 cd/m², showing potential applications in blue light emitting devices.

The ability to direct functional proteins to specific DNA sequences is a long-sought goal in the study and engineering of biological processes. Transcription activator-like effectors (TALEs) from Xanthomonas sp. are site-specific DNA-binding proteins that can be readily designed to target new sequences. Because TALEs contain a large number of repeat domains, it can be difficult to synthesize new variants. Here we describe a method that overcomes this problem. We leverage codon degeneracy and type IIs restriction enzymes to generate orthogonal ligation linkers between individual repeat monomers, thus allowing full-length, customized, repeat domains to be constructed by hierarchical ligation. We synthesized 17 TALEs that are customized to recognize specific DNA-binding sites, and demonstrate that they can specifically modulate transcription of endogenous genes (SOX2 and KLF4) in human cells.