Bruker (China)

The gene therapy achieved by AAV-mediated otoferlin-overexpression is an effective therapeutic strategy for congenital deafness. However, achieving its physiological and endogenous patterns of expression remains challenging. Here, we generate the homologous mutation Otof c.1315 C > T (p.R439*), equivalent to OTOF c.1273 C > T (p.R425*) found in humans with profound deafness, to create a nonsense mutation-induced deaf mouse model. We then deliver the ‘RESTART v3’ system, which is a CRISPR-free RNA base editor for nonsense mutation suppression, into the cochlea of the mice. We achieve physiological otoferlin expression, and the edited premature termination codon is reverse-mutated to the original amino acid. We observe significant hearing restoration and enhancement of the behavioral auditory startle reflex. Thus, our study presents a successful RNA editing strategy to significantly restore hereditary deafness in mice carrying the specific Otof nonsense mutation, which holds great promise for future clinical translation.

The shield cutterhead experiences eccentric loads when excavating through composite strata, leading to potential deviation of the cutterhead. This study examines the static response, modal characteristics, and vibration response of a shield cutterhead in composite strata, utilizing Hertz contact theory. The cutterhead-rock interaction is equivalently modeled as mechanical spring constraints, with contact stiffness derived from elastic contact theory for disc cutter-rock contact. The static and dynamic responses of the cutterhead under maximum thrust and rock-breaking load are analyzed using finite element simulations. Results show that moderately weathered limestone induces larger displacements compared to hard rock. Modal analysis reveals that the natural frequencies increase with rock modulus, with composite strata exhibiting intermediate values compared to the soft and hard rock. Vibration responses under rock-breaking load demonstrate rotational symmetry in uniform strata but asymmetry in composite strata, where the displacement of the upper half exceeds the lower half due to stiffness contrast. This work provides a theoretical framework for optimizing cutterhead design and tunneling parameters in heterogeneous strata.

Despite the symmetric, achiral atomic lattices typically found in binary semiconductor nanocrystals, we show that during their early formation stages, especially in the magic-size cluster (MSC) regime, chirality can be present in these metastable, transient species, which are capable of further self-assembling into high-level chiral superstructures. Through a cation exchange process operating at room temperature, a structurally symmetrical copper sulfide cluster has been successfully converted into a pair of enantiomeric cadmium sulfide MSCs, formulated as Cd28S17I22(PEt3)12 (abbreviated as (+)/(-)-[Cd28S17]). The atomic structures of these two MSCs were established by single-crystal X-ray crystallography. It is revealed that the [Cd28S17] MSCs feature an antisupertetrahedron configuration which has never been observed in reported CdS structures. Remarkably, rather than crystallizing into a racemic mixture, (+)/(-)-[Cd28S17] MSCs naturally crystallize out in an enantiomerically biased manner, sufficiently rendering distinctly opposite chiroptical responses. This behavior reflects genuine circular dichroism activity, which can be directly attributed to the chiral atomic structure of this well-known quantum photonic nanomaterial.

We describe a quantitative statistical and geometric analysis of classical and non-classical modes of twinning in the calcite produced by biomineralization in the shell of the rotaliid foraminifer species Amphistegina lessonii. Foraminifera are responsible for about a quarter of the marine production of CaCO3 and thus play a major role in the natural CO2 sequestration into marine carbonate sediments. The shell calcite of rotaliid foraminifera is nano-twinned and thus quite distinct from inorganic calcite and from biogenic calcite produced by other groups of organisms. Previous work showed that foraminiferal calcite contains a high spatial density of twin walls of the classical 60°|<001> = m.{001} twin, but there was another peak in the range between 75° and 80° in the misorientation statistics of electron backscatter diffraction (EBSD) maps of the same specimen. We checked the significance of all maxima in misorientation by in-depth statistical analysis, thus confirmed the 60°|<001> penetration twinning and found that the 75°–80° maxima are related to new, non-classical, but systematically reoccurring oriented associations of calcite crystals with orientation relationships 78.2°|<991> and 76.6°|<6 −6 1>. If the nano-twinning provides an evolutionary advantage, it may increase the strength and toughness of the feeble mineralized chamber walls of the organisms.

In recent years, the protection of intangible cultural heritage in our country's ethnic minority areas has achieved remarkable results. However, the Manchu people, a valuable cultural heritage of our country, face many challenges in digital protection and dissemination. This article discusses the need for digital protection for Manchu and explores the feasibility and strategies for implementing digital protection. The article proposes innovative ways to protect and develop the Manchu people. First, the article points out key issues in digitizing Manchu documents and highlights the challenges faced in digital preservation. Second, the paper summarises the procedures and methods of digitizing Manchu documents to improve the efficiency and quality of digital preservation. Secondly, the paper analyses the construction of the Manchu corpus and describes the application of natural language processing (NLP) techniques. Furthermore, the paper discusses the construction of a digital platform to support the preservation and dissemination of Manchu documents. Finally, the paper explores future trends in the digital preservation of the Manchu language, highlighting its importance in safeguarding and promoting national cultural identity. This work has also contributed to disseminating Manchu culture to the rest of the world.

A highly strained macrocycle comprisingfour [4]helicene panels,[4]cyclo[4]helicenylene ([4]CH, 1), was synthesized througha one-pot macrocyclization and chemically reduced by alkali metals(Na and K), revealing a four-electron reduction process. The resultingdi-, tri-, and tetraanions of compound 1 were isolatedand crystallographically characterized by X-ray diffraction. Owingto the four axially chiral bi[4]helicenyl fragments, a reversiblestereo transformation of 1 between the (S,R,S,R)- and (S,S,R,R)-configurations was disclosed upon the two-electron uptake, whichwas rationally understood by theoretical calculations. The (S,S,R,R)-configuration of 12– was furtherstabilized in triply reduced and tetra-reduced states, where structuraldeformation led by charges and metal complexation was observed. Thisstudy proposed an approach to alter the configuration of cycloarylenesin addition to thermal treatment.

Advanced packaging challenges standard metrology means, notably optical profilers, by shrinking dimensions and spacings between interconnect (RDL, Bump, via). New needs such as die flatness and roughness also raise up due to the critical requirement of robust stacking into complex 3D assembly. Challenges translate into demand for both higher lateral and vertical resolution. In this talk, we will introduce optical profiler based on White Light Interferometry principle (WLI) which has inherent advantages combining lateral resolution below micron level as well as providing sub-nanometer vertical resolution at all magnifications. We will explain how this technology can not only provide solution for current Re-Distribution Layer (RDL), bump and Under Bump Metallization (UBM) but also scope through new development with future roadmap. Talk will further develop topics into two main directions. The first one consists on studying or monitoring the low roughness of die and supporting sacrificial wafer in case of Chip-on-Wafer-on-Substrate (CoWos). Roughness indeed plays key role in adequate adhesion between die and wafer on top of possible impact from surface contamination. Curvature of die can also trigger issues during anchoring process for which control of overall die shape is beneficial. In both cases, WLI optical profiler fulfills stringent metrology via sub-nanometer vertical resolution along large field of view. Throughput and 10’s picometer (pm) repeatability are then compatible with inline control through integration of wafer handler. The second direction will focus on panel level integration with measurement on next generation RDL. We will illustrate how large optical platform can scope with 600mm by 600 mm panel and provide metrology for Critical Dimensions on RDL. Notably, we will present evidences of metrology capability for 1µm and 0.8µm RDL technology by using newly developed super-resolution algorithm. This algorithm allows 2x enhancement regarding lateral resolution making possible measurement of high dense RDL or bump array. Finally, we will present data regarding high aspect ratio Through Silicon Via (TSV) with regular objective up to 1:20. WLI technology uniquely provides technical advantages such as combination of parallel light injection, ability to scope with weak signals and nanometer repeatability. Conclusion will open possible expansion of technology to measure with high throughput PhotoResist (PR) layer thickness as well as thin insulative oxide layer.