In vivo consequences of deleting EGF repeats 8–12 including the ligand binding domain of mouse Notch1

<p>Abstract</p> <p>Background</p> <p>Notch signaling is highly conserved in the metazoa and is critical for many cell fate decisions. Notch activation occurs following ligand binding to Notch extracellular domain. <it>In vitro </it>binding assays have identified epidermal growth factor (EGF) repeats 11 and 12 as the ligand binding domain of Drosophila Notch. Here we show that an internal deletion in mouse Notch1 of EGF repeats 8–12, including the putative ligand binding domain (lbd), is an inactivating mutation <it>in vivo</it>. We also show that maternal and zygotic <it>Notch1</it>^{<it>lbd</it>/<it>lbd </it>}mutant embryos develop through gastrulation to mid-gestation.</p> <p>Results</p> <p><it>Notch1</it>^{<it>lbd</it>/<it>lbd </it>}embryos died at mid-gestation with a phenotype indistinguishable from <it>Notch1 </it>null mutants. In embryonic stem (ES) cells, Notch1^lbdwas expressed on the cell surface at levels equivalent to wild type Notch1, but Delta1 binding was reduced to the same level as in <it>Notch1 </it>null cells. In an ES cell co-culture assay, Notch signaling induced by Jagged1 or Delta1 was reduced to a similar level in <it>Notch1</it>^{<it>lbd</it><it/>}and <it>Notch1 </it>null cells. However, the <it>Notch1</it>^{<it>lbd</it>/<it>lbd </it>}allele was expressed similarly to wild type Notch1 in <it>Notch1</it>^{<it>lbd</it>/<it>lbd </it>}ES cells and embryos at E8.75, indicating that Notch1 signaling is not essential for the <it>Notch1 </it>gene to be expressed. In addition, maternal and zygotic <it>Notch1 </it>mutant blastocysts developed through gastrulation.</p> <p>Conclusion</p> <p>Mouse Notch1 lacking the ligand binding domain is expressed at the cell surface but does not signal in response to the canonical Notch ligands Delta1 and Jagged1. Homozygous <it>Notch1</it>^{<it>lbd</it>/<it>lbd </it>}mutant embryos die at ~E10 similar to <it>Notch1 </it>null embryos. While Notch1 is expressed in oocytes and blastocysts, Notch1 signaling via canonical ligands is dispensable during oogenesis, blastogenesis, implantation and gastrulation.</p

Intelligent Computing: The Latest Advances, Challenges and Future

Computing is a critical driving force in the development of human civilization. In recent years, we have witnessed the emergence of intelligent computing, a new computing paradigm that is reshaping traditional computing and promoting digital revolution in the era of big data, artificial intelligence and internet-of-things with new computing theories, architectures, methods, systems, and applications. Intelligent computing has greatly broadened the scope of computing, extending it from traditional computing on data to increasingly diverse computing paradigms such as perceptual intelligence, cognitive intelligence, autonomous intelligence, and human-computer fusion intelligence. Intelligence and computing have undergone paths of different evolution and development for a long time but have become increasingly intertwined in recent years: intelligent computing is not only intelligence-oriented but also intelligence-driven. Such cross-fertilization has prompted the emergence and rapid advancement of intelligent computing. Intelligent computing is still in its infancy and an abundance of innovations in the theories, systems, and applications of intelligent computing are expected to occur soon. We present the first comprehensive survey of literature on intelligent computing, covering its theory fundamentals, the technological fusion of intelligence and computing, important applications, challenges, and future perspectives. We believe that this survey is highly timely and will provide a comprehensive reference and cast valuable insights into intelligent computing for academic and industrial researchers and practitioners

Intelligent computing : the latest advances, challenges and future

Computing is a critical driving force in the development of human civilization. In recent years, we have witnessed the emergence of intelligent computing, a new computing paradigm that is reshaping traditional computing and promoting digital revolution in the era of big data, artificial intelligence and internet-of-things with new computing theories, architectures, methods, systems, and applications. Intelligent computing has greatly broadened the scope of computing, extending it from traditional computing on data to increasingly diverse computing paradigms such as perceptual intelligence, cognitive intelligence, autonomous intelligence, and human computer fusion intelligence. Intelligence and computing have undergone paths of different evolution and development for a long time but have become increasingly intertwined in recent years: intelligent computing is not only intelligence-oriented but also intelligence-driven. Such cross-fertilization has prompted the emergence and rapid advancement of intelligent computing

Diffusion through a polycrystalline thin film

Analytical solutions to Fick's second law of diffusion have been simultaneously derived without the restrictions of parabolic profiles along the x-axis in grain boundaries and expressed in a series for both grain interior and grain boundary diffusing through a polycrystalline thin film. The analysis takes segregation of diffusion species at grain boundaries into account. The analytic solutions lead to the concentration profiles in the grain interior and in the grain boundary, to the average-integrated amount of diffusion species at the exit surface, and to the time lag, which can be technologically used for depth profile studies and kinetic accumulation measurements

Performance analysis of different pixel-wise processing methods for depth imaging with single photon detection data

We establish a long-range single photon counting three-dimensional (3D) imaging system based on cage optical structure. Five different pixel-wise processing methods for time-of-flight (TOF) photon counting data are compared with data collected by our 3D imaging system for ranges 40-700 m and a suitable representation model for photon counting data is proposed for pixel-wise processing. Experimental results show that these methods exploit the instrumental response function (IRF), yielding a high-quality 3D image. When the signal photon counts are greater than 13 per pixel, the resulting mean absolute error (MAE) values of the IRF-based methods are better than results from the non-IRF-based methods. Regarding IRF-based methods, the union of subspace (UOS) model-based approach and cross correlation are more suitable than the Markov chain Monte Carlo (MCMC) method in the condition of a small number of return signal photons. These results offer valuable information to promote the implementation of photon counting 3D imaging in real applications

Advancements in developing biomaterials for 3D printing photosensitive resins containing quaternary ammonium molecules for enhanced oral healthcare

In this study, we investigated the development of biomaterials tailored for UV-cured 3D printing technology in oral healthcare. Traditionally, 3D-printed oral healthcare products have exhibited imperfections in antimicrobial and anti-pollution properties, limiting their utility. To address this challenge, we synthesised antimicrobial agents incorporating quaternary ammonium groups through a combination of isophorone diisocyanate (IPDI), hydroxyethyl methacrylate (HEMA), and choline chloride. These agents were then blended with diluents, resins, and photoinitiators to create raw materials suitable for UV-curing 3D printing photosensitive resins. Subsequently, the resins were subjected to digital light processing (DLP) 3D printing for curing. The resulting 3D-printed material underwent rigorous mechanical and antimicrobial testing. Our findings demonstrate that the 3D printed compounds, cured through this process, exhibited exceptional hardness, tensile properties, antimicrobial characteristics, and long-lasting antimicrobial durability. These developments promise widespread adoption and application within the oral healthcare field

A novel water-soluble hydrophobically associating polyacrylamide based on oleic imidazoline and sulfonate for enhanced oil recovery

3-(2-(2-Heptadec-8-enyl-4,5-dihydro-imidazol-1-yl)ethylcarbamoyl)acrylic acid (NIMA), 3-(diallyl-amino)-2-hydroxypropyl sulfonate (NDS), acrylamide (AM) and acrylic acid (AA) were successfully utilized to prepare novel acrylamide-based copolymers (named AM/AA/NIMA and AM/AA/NDS/NIMA) which were functionalized by a combination of imidazoline derivative and/or sulfonate via redox free-radical polymerization. The two copolymers were characterized by infrared (IR) spectroscopy, 1H nuclear magnetic resonance (1H NMR), viscosimetry, pyrene fluorescence probe, thermogravimetry (TG) and differential thermogravimetry (DTG). As expected, the polymers exhibited excellent thickening property, shear stability (viscosity retention rate 5.02% and 7.65% at 1000 s-1) and salt-tolerance (10:000 mg L-1 NaCl: viscosity retention rate up to 17.1% and 10.2%) in comparison with similar concentration partially hydrolyzed polyacrylamide (HPAM). The temperature resistance of the AM/AA/NDS/NIMA solution was also remarkably improved and the viscosity retention rate reached 54.8% under 110 &deg;C. According to the core flooding tests, oil recovery could be enhanced by up to 15.46% by 2000 mg L-1 of the AM/AA/NDS/NIMA brine solution at 80 &deg;C