DFMA-oriented modular and parametric design and secondary splitting of vertical PC components.

The design and production of assembled buildings are difficult to standardise, which limits their extensive application. In this paper, the design for manufacture and assembly (DFMA) concept is applied to the design of vertical precast concrete (PC) components for assembled buildings. Taking vertical PC components as an example, the rapid modelling and whole life-cycle application of DFMA-oriented PC components for assembled buildings are investigated. Firstly, the modular design method is introduced. By combining parametric design and building information modelling (BIM), we propose a modular, parametric design method and process of PC components based on DFMA. Secondly, the design of standard modules after secondary splitting is introduced for a better DFMA-oriented parametric design of PC components. We explored the secondary development process of DFMA and BIM and the module creation process of the parametric standard based on family templates and DFMA. Thirdly, based on the parametric standard module, the application of the optimised whole life cycle of design, manufacture and assembly of PC components is introduced. Finally, the feasibility of this method is verified by practical cases. The design process for PC components is fast, accurate and standardised. The integrated application of BIM is accelerated, and digital collaboration in assembly construction is strengthened. The study results are conducive to establishing a standardised design and production system for PC components, reducing design costs, improving design efficiency and the comprehensive benefits of assembled buildings.

Exploration of a virtual restoration practice route for architectural heritage based on evidence-based design: a case study of the Bagong House.

Architectural heritage is a testament to human and natural development, and the process of human social development can be glimpsed through the study and exploration of heritage. However, in the long history of human social development, architectural heritage is vanishing, and protecting and restoring such heritage is a pressing issue in contemporary society. This study applies the evidence-based theory of medicine to the virtual restoration practice of architectural heritage, which focuses more on scientific data-driven research and decision-making than does traditional restoration. Combined with the practice of evidence-based medicine, the stages of digital conservation of architectural heritage for virtual restoration based on evidence-based design are investigated, forming a comprehensive knowledge system consisting of clear objectives, evidence-based research, evidence assessment, virtual restoration-guided practice, and post feedback. In addition, it is emphasized that the restoration of architectural heritage should be founded on the outcomes obtained through evidence-based practice that have been translated into evidence, in turn creating a rigorous evidence-based system with high-frequency feedback. The final illustration of the procedure is the Bagong House in Wuhan, Hubei Province, China. The examination of this practice line provides a scientific, humanistic, and practicable theoretical framework for the restoration of architectural heritage and fresh ideas for the restoration of other cultural assets, which have significant practical application value.

Observation of Vibrational Dynamics of Orientated Rydberg-Atom-Ion Molecules.

Vibrational dynamics in conventional molecules usually takes place on a timescale of picoseconds or shorter. A striking exception are ultralong-range Rydberg molecules, for which dynamics is dramatically slowed down as a consequence of the huge bond length of up to several micrometers. Here, we report on the direct observation of vibrational dynamics of a recently observed Rydberg-atom-ion molecule. By applying a weak external electric field of a few millivolts per centimeter, we are able to control the orientation of the photoassociated ultralong-range Rydberg molecules and induce vibrational dynamics by quenching the electric field. A high resolution ion microscope allows us to detect the molecule's orientation and its temporal vibrational dynamics in real space. Our study opens the door to the control of molecular dynamics in Rydberg molecules.

Observation of a molecular bond between ions and Rydberg atoms.

Atoms with a highly excited electron, called Rydberg atoms, can form unusual types of molecular bonds1-4. The bonds differ from the well-known ionic and covalent bonds5,6 not only by their binding mechanisms, but also by their bond lengths ranging up to several micrometres. Here we observe a new type of molecular ion based on the interaction between the ionic charge and a flipping-induced dipole of a Rydberg atom with a bond length of several micrometres. We measure the vibrational spectrum and spatially resolve the bond length and the angular alignment of the molecule using a high-resolution ion microscope7. As a consequence of the large bond length, the molecular dynamics is extremely slow. These results pave the way for future studies of spatio-temporal effects in molecular dynamics (for example, beyond Born-Oppenheimer physics).

Beating the classical precision limit with spin-1 Dicke states of more than 10,000 atoms.

Interferometry is a paradigm for most precision measurements. Using N uncorrelated particles, the achievable precision for a two-mode (two-path) interferometer is bounded by the standard quantum limit (SQL), [Formula: see text], due to the discrete (quanta) nature of individual measurements. Despite being a challenging benchmark, the two-mode SQL has been approached in a number of systems, including the Laser Interferometer Gravitational-Wave Observatory and today's best atomic clocks. For multimode interferometry, the SQL becomes [Formula: see text] using M modes. Higher precision can also be achieved using entangled particles such that quantum noises from individual particles cancel out. In this work, we demonstrate an interferometric precision of [Formula: see text] dB beyond the three-mode SQL, using balanced spin-1 (three-mode) Dicke states containing thousands of entangled atoms. The input quantum states are deterministically generated by controlled quantum phase transition and exhibit close to ideal quality. Our work shines light on the pursuit of quantum metrology beyond SQL.

Deterministic entanglement generation from driving through quantum phase transitions.

Many-body entanglement is often created through the system evolution, aided by nonlinear interactions between the constituting particles. These very dynamics, however, can also lead to fluctuations and degradation of the entanglement if the interactions cannot be controlled. Here, we demonstrate near-deterministic generation of an entangled twin-Fock condensate of ~11,000 atoms by driving a arubidium-87 Bose-Einstein condensate undergoing spin mixing through two consecutive quantum phase transitions (QPTs). We directly observe number squeezing of 10.7 ± 0.6 decibels and normalized collective spin length of 0.99 ± 0.01. Together, these observations allow us to infer an entanglement-enhanced phase sensitivity of ~6 decibels beyond the standard quantum limit and an entanglement breadth of ~910 atoms. Our work highlights the power of generating large-scale useful entanglement by taking advantage of the different entanglement landscapes separated by QPTs.

Discovery of pyrazole as C-terminus of selective BACE1 inhibitors.

We recently discovered and reported dual inhibitor 5 of AChE and BACE1 with N-benzylpiperidine ethyl as C-terminus. Compound 5 showed potent inhibitory activities for BACE1, and could reduce endogenous Aß1-40 production in APP transgenic mice. In present work, we rapidly identified substituted triazole as the C-terminus of compound 5 by replacing the benzylpiperidine ethyl group with click chemistry and tested these synthesized compounds by in situ screening assay. As revealed by the crystal structures of BACE1 in complex with our triazole compound 12, we found that Pro70 and Thr72 located in the flap region were the critical components for binding with these inhibitors. With the aid of the crystal structure, a new series of five-membered heterocyclic compounds was prepared in order to explore the structure-activity relationship (SAR) of this class of molecules. From these efforts, pyrazole was discovered as a novel C-terminus of BACE1 inhibitors. After further modification of pyrazole with variable substituents, compound 37 exhibited good potency in enzyme inhibition assay (IC50=0.025 µM) and compound 33 showed moderate inhibition effects on Aß production of APP transfected HEK293 cells. Moreover, these pyrazole derivatives demonstrated good selectivity versus cathepsin D. Our results indicated that the vicinity of Pro70 and Thr72 might be utilized as a subsite, and the discovered pyrazole derivatives might provide useful hints for developing novel BACE1 inhibitors as anti-AD drugs.

Virtual screening and structure-based discovery of indole acylguanidines as potent ß-secretase (BACE1) inhibitors.

Proteolytic cleavage of amyloid precursor protein by ß-secretase (BACE1) is a key step in generating the N-terminal of ß-amyloid (Aß), which further forms into amyloid plaques that are considered as the hallmark of Alzheimer's disease. Inhibitors of BACE1 can reduce the levels of Aß and thus have a therapeutic potential for treating the disease. We report here the identification of a series of small molecules bearing an indole acylguanidine core structure as potent BACE1 inhibitors. The initial weak fragment was discovered by virtual screening, and followed with a hit-to-lead optimization. With the aid of co-crystal structures of two discovered inhibitors (compounds 19 and 25) with BACE1, we explored the SAR around the indole and aryl groups, and obtained several BACE1 inhibitors about 1,000-fold more potent than the initial fragment hit. Accompanying the lead optimization, a previously under-explored sub-site opposite the flap loop was redefined as a potential binding site for later BACE1 inhibitor design.