Two-level Word Class Categorization Model in Analytic Languages and Its Implications for POS Tagging in Modern Chinese Corpora

The study of word classes has a history of over 4000 years, and the word class problem in over 1000 analytic languages like Modern Chinese can be seen as the Goldbach Conjecture in linguistics. This paper first outlines the existing problems in the POS tagging of Modern Chinese corpora with a case study of 自信. Then it introduces the Two-level Word Class Categorization Model in analytic languages, which is based on the perspectives of language as a complex adaptive system and the nature of major parts of speech as propositional speech act functions. Finally, the implications of Two-level Word Class Categorization Model for POS tagging in Modern Chinese corpora are explored.

Visualizing Epigenetics: Current Advances and Advantages in HDAC PET Imaging Techniques

Abnormal gene regulation as a consequence of flawed epigenetic mechanisms may be central to the initiation and persistence of many human diseases. However, the association of epigenetic dysfunction with disease and the development of therapeutic agents for treatment are slow. Developing new methodologies used to visualize chromatin-modifying enzymes and their function in the human brain would be valuable for the diagnosis of brain disorders and drug discovery. We provide an overview of current invasive and noninvasive techniques for measuring expression and functions of chromatin-modifying enzymes in the brain, emphasizing tools applicable to histone deacetylase (HDAC) enzymes as a leading example. The majority of current techniques are invasive and difficult to translate to what is happening within a human brain in vivo. However, recent progress in molecular imaging provides new, noninvasive ways to visualize epigenetics in the human brain. Neuroimaging tool development presents a unique set of challenges in order to identify and validate CNS radiotracers for HDACs and other histone-modifying enzymes. We summarize advances in the effort to image HDACs and HDAC inhibitory effects in the brain using positron emission tomography (PET) and highlight generalizable techniques that can be adapted to investigate other specific components of epigenetic machinery. Translational tools like neuroimaging by PET and magnetic resonance imaging provide the best way to link our current understanding of epigenetic changes with in vivo function in normal and diseased brains. These tools will be a critical addition to ex vivo methods to evaluate – and intervene – in CNS dysfunction.Chemistry and Chemical Biolog

Functional biomimetic design of 3D printed polyether-ether-ketone flexible chest wall reconstruction implants for restoration of the respiration

The lack of deformability of rigid chest wall reconstruction (CWR) implants presents a challenge in reducing postoperative respiratory function in patients with large chest wall defects. Flexible poly-ether-ether-ketone (PEEK) CWR implants, consisting of rib components with elliptical cross-section and costal cartilage components featuring wavy structures, were developed with adjustable design parameters that allow quantitative restoration of respiratory function. During the design process, the equivalent elastic moduli of the rib and costal cartilage components were parametrically adjusted in a validated finite element (FE) model of the chest wall to maximise chest wall deformation during respiration, while considering mechanical safety as the boundary condition. The optimal equivalent elastic moduli were then translated into design parameters for the rib and costal cartilage components, based on a database relating the equivalent elastic modulus to the design parameters of the components with elliptical cross-section and wavy structures. The flexible PEEK CWR implant increased the difference in chest circumference during respiration by 12.2% compared to rigid PEEK implant in a clinical case-based study. This study presents a strategy to address the reduced respiratory function in 3D printed CWR implants, providing a pathway for quantitative restoration of respiratory function through parameterised optimisation

The Promotion of Mechanical Properties by Bone Ingrowth in Additive-Manufactured Titanium Scaffolds

Although the initial mechanical properties of additive-manufactured (AM) metal scaffolds have been thoroughly studied and have become a cornerstone in the design of porous orthopaedic implants, the potential promotion of the mechanical properties of the scaffolds by bone ingrowth has barely been studied. In this study, the promotion of bone ingrowth on the mechanical properties of AM titanium alloy scaffolds was investigated through in vivo experiments and numerical simulation. On one hand, the osseointegration characteristics of scaffolds with architectures of body-centred cubic (BCC) and diamond were compared through animal experiments in which the mechanical properties of both scaffolds were not enhanced by the four-week implantation. On the other hand, the influences of the type and morphology of bone tissue in the BCC scaffolds on its mechanical properties were investigated by the finite element model of osseointegrated scaffolds, which was calibrated by the results of biomechanical testing. Significant promotion of the mechanical properties of AM metal scaffolds was only found when cortical bone filled the pores in the scaffolds. This paper provides a numerical prediction method to investigate the effect of bone ingrowth on the mechanical properties of AM porous implants, which might be valuable for the design of porous implants

Fused Deposition Modeling PEEK Implants for Personalized Surgical Application: From Clinical Need to Biofabrication

Three-dimensional printing (3DP) technology is suitable for manufacturing personalized orthopedic implants for reconstruction surgery. Compared with traditional titanium, polyether-ether-ketone (PEEK) is the ideal material for 3DP orthopedic implants due to its various advantages, including thermoplasticity, thermal stability, high chemical stability, and radiolucency suitable elastic modulus. However, it is challenging to develop a well-designed method and manufacturing technique to meet the clinical needs because it requires elaborate details and interplays with clinical work. Furthermore, establishing surgical standards for new implants requires many clinical cases and an accumulation of surgical experience. Thus, there are few case reports on using 3DP PEEK implants in clinical practice. Herein, we formed a team with a lot of engineers, scientists, and doctors and conducted a series of studies on the 3DP PEEK implants for chest wall reconstruction. First, the thoracic surgeons sort out the specific types of chest wall defects. Then, the engineers designed the shape of the implant and performed finite element analysis for every implant. To meet the clinical needs and mechanical requirements of implants, we developed a new fused deposition modeling technology to make personalized PEEK implants. Overall, the thoracic surgeons have used 114 personalized 3DP PEEK implants to reconstruct the chest wall defect and further established the surgical standards of the implants as part of the Chinese clinical guidelines. The surface modification technique and composite process are developed to overcome the new clinical problems of implant-related complications after surgery. Finally, the major challenges and possible solutions to translating 3DP PEEK implants into a mature and prevalent clinical product are discussed in the paper

Dynamic Changes in Subgraph Preference Profiles of Crucial Transcription Factors

Transcription factors with a large number of target genes—transcription hub(s), or THub(s)—are usually crucial components of the regulatory system of a cell, and the different patterns through which they transfer the transcriptional signal to downstream cascades are of great interest. By profiling normalized abundances (A(N)) of basic regulatory patterns of individual THubs in the yeast Saccharomyces cerevisiae transcriptional regulation network under five different cellular states and environmental conditions, we have investigated their preferences for different basic regulatory patterns. Subgraph-normalized abundances downstream of individual THubs often differ significantly from that of the network as a whole, and conversely, certain over-represented subgraphs are not preferred by any THub. The THub preferences changed substantially when the cellular or environmental conditions changed. This switching of regulatory pattern preferences suggests that a change in conditions does not only elicit a change in response by the regulatory network, but also a change in the mechanisms by which the response is mediated. The THub subgraph preference profile thus provides a novel tool for description of the structure and organization between the large-scale exponents and local regulatory patterns

The Ginger-shaped Asteroid 4179 Toutatis: New Observations from a Successful Flyby of Chang'e-2

On 13 December 2012, Chang'e-2 conducted a successful flyby of the near-Earth asteroid 4179 Toutatis at a closest distance of 770 $\pm$ 120 meters from the asteroid's surface. The highest-resolution image, with a resolution of better than 3 meters, reveals new discoveries on the asteroid, e.g., a giant basin at the big end, a sharply perpendicular silhouette near the neck region, and direct evidence of boulders and regolith, which suggests that Toutatis may bear a rubble-pile structure. Toutatis' maximum physical length and width are (4.75 $\times$ 1.95 km) $\pm$10$\%$, respectively, and the direction of the +$z$ axis is estimated to be (250$\pm$5$^\circ$, 63$\pm$5$^\circ$) with respect to the J2000 ecliptic coordinate system. The bifurcated configuration is indicative of a contact binary origin for Toutatis, which is composed of two lobes (head and body). Chang'e-2 observations have significantly improved our understanding of the characteristics, formation, and evolution of asteroids in general.Comment: 21 pages, 3 figures, 1 tabl

Mutations in CLCN6 as a Novel Genetic Cause of Neuronal Ceroid Lipofuscinosis in Patients and a Murine Model

Objective The aim of this study was to explore the pathogenesis of CLCN6-related disease and to assess whether its Cl−/H+-exchange activity is crucial for the biological role of ClC-6. Methods We performed whole-exome sequencing on a girl with development delay, intractable epilepsy, behavioral abnormities, retinal dysfunction, progressive brain atrophy, suggestive of neuronal ceroid lipofuscinoses (NCLs). We generated and analyzed the first knock-in mouse model of a patient variant (p.E200A) and compared it with a Clcn6−/− mouse model. Additional functional tests were performed with heterologous expression of mutant ClC-6. Results We identified a de novo heterozygous p.E200A variant in the proband. Expression of disease-causing ClC-6E200A or ClC-6Y553C mutants blocked autophagic flux and activated transcription factors EB (TFEB) and E3 (TFE3), leading to autophagic vesicle and cholesterol accumulation. Such alterations were absent with a transport-deficient ClC-6E267A mutant. Clcn6E200A/+ mice developed severe neurodegeneration with typical features of NCLs. Mutant ClC-6E200A, but not loss of ClC-6 in Clcn6−/− mice, increased lysosomal biogenesis by suppressing mTORC1-TFEB signaling, blocked autophagic flux through impairing lysosomal function, and increased apoptosis. Carbohydrate and lipid deposits accumulated in Clcn6E200A/+ brain, while only lipid storage was found in Clcn6−/− brain. Lysosome dysfunction, autophagy defects, and gliosis were early pathogenic events preceding neuron loss. Interpretation CLCN6 is a novel genetic cause of NCLs, highlighting the importance of considering CLCN6 mutations in the diagnostic workup for molecularly undefined forms of NCLs. Uncoupling of Cl− transport from H+ countertransport in the E200A mutant has a dominant effect on the autophagic/lysosomal pathway. ANN NEUROL 2024;96:608–62

Stress Shielding and Bone Resorption of Press-Fit Polyether–Ether–Ketone (PEEK) Hip Prosthesis: A Sawbone Model Study

Stress shielding secondary to bone resorption is one of the main causes of aseptic loosening, which limits the lifespan of the hip prostheses and increases the rates of revision surgery. This study proposes a low stiffness polyether–ether–ketone (PEEK) hip prostheses, produced by fused deposition modelling to minimize the stress difference after the hip replacement. The stress shielding effect and the potential bone resorption of the PEEK implant was investigated through both experimental tests and FE simulation. A generic Ti6Al4V implant was incorporated in this study to allow fair comparison as control group. Attributed to the low stiffness, the proposed PEEK implant showed a more natural stress distribution, less stress shielding (by 104%), and loss in bone mass (by 72%) compared with the Ti6Al4V implant. The stiffness of the Ti6Al4V and the PEEK implant were measured through compression tests to be 2.76 kN/mm and 0.276 kN/mm. The factor of safety for the PEEK implant in both static and dynamic loading scenarios were obtained through simulation. Most of the regions in the PEEK implant were tested to be safe (FoS larger than 1) in terms of representing daily activities (2300 N), while the medial neck and distal restriction point of the implant attracts large von Mises stress 82 MPa and 76 MPa, respectively, and, thus, may possibly fail during intensive activities by yield and fatigue. Overall, considering the reduction in stress shielding and bone resorption in cortical bone, PEEK could be a promising material for the patient–specific femoral implants

NPInter: the noncoding RNAs and protein related biomacromolecules interaction database

The noncoding RNAs and protein related biomacromolecules interaction database (NPInter; or ) is a database that documents experimentally determined functional interactions between noncoding RNAs (ncRNAs) and protein related biomacromolecules (PRMs) (proteins, mRNAs or genomic DNAs). NPInter intends to provide the scientific community with a comprehensive and integrated tool for efficient browsing and extraction of information on interactions between ncRNAs and PRMs. Beyond cataloguing details of these interactions, the NPInter will be useful for understanding ncRNA function, as it adds a very important functional element, ncRNAs, to the biomolecule interaction network and sets up a bridge between the coding and the noncoding kingdoms