Topology optimization of flexure hinges with a prescribed compliance matrix based on the adaptive spring model and stress constraint

This paper focuses on the configuration design of flexure hinges with a prescribed compliance matrix and preset rotational center position. A new method for the topology optimization of flexure hinges is proposed based on the adaptive spring model and stress constraint. The hinge optimization model is formulated by maximizing the bending displacement with a spring while optimizing the compliance matrix to a prescribed value. To avoid numerical instability, an artificial spring is used as an auxiliary calculation, and a new strategy is developed for adaptively adjusting the spring stiffness according to the prescribed compliance matrix. The maximum stress of flexure hinge is limited by using a normalized P-norm of the effective von Mises stress, and a position constraint of rotational center is proposed to predetermine the position of the rotational center. In addition, to reduce the error of the stress measurement, a simple but effective filtering method is presented to obtain a complete black-and-white design. Numerical examples are used to verify the proposed method. Topology results show that the obtained flexure hinges have the prescribed compliance matrix and preset rotational center position while also meeting the stress requirements.     

Computational Investigation Identified Potential Chemical Scaffolds for Heparanase as Anticancer Therapeutics

Heparanase (Hpse) is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains. Its upregulated expression is implicated in tumor growth, metastasis and angiogenesis, thus making it an attractive target in cancer therapeutics. Currently, a few small molecule inhibitors have been reported to inhibit Hpse, with promising oral administration and pharmacokinetic (PK) properties. In the present study, a ligand-based pharmacophore model was generated from a dataset of well-known active small molecule Hpse inhibitors which were observed to display favorable PK properties. The compounds from the InterBioScreen database of natural (69,034) and synthetic (195,469) molecules were first filtered for their drug-likeness and the pharmacophore model was used to screen the drug-like database. The compounds acquired from screening were subjected to molecular docking with Heparanase, where two molecules used in pharmacophore generation were used as reference. From the docking analysis, 33 compounds displayed higher docking scores than the reference and favorable interactions with the catalytic residues. Complex interactions were further evaluated by molecular dynamics simulations to assess their stability over a period of 50 ns. Furthermore, the binding free energies of the 33 compounds revealed 2 natural and 2 synthetic compounds, with better binding affinities than reference molecules, and were, therefore, deemed as hits. The hit compounds presented from this in silico investigation could act as potent Heparanase inhibitors and further serve as lead scaffolds to develop compounds targeting Heparanase upregulation in cancer.     

Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.     

Effect of α-Lipoic Acid on the Development of Human Skin Equivalents Using a Pumpless Skin-on-a-Chip Model

Owing to the prohibition of cosmetic animal testing, various attempts have recently been made using skin-on-a-chip (SOC) technology as a replacement for animal testing. Previously, we reported the development of a pumpless SOC capable of drug testing with a simple drive using the principle that the medium flows along the channel by gravity when the chip is tilted using a microfluidic channel. In this study, using pumpless SOC, instead of drug testing at the single-cell level, we evaluated the efficacy of α-lipoic acid (ALA), which is known as an anti-aging substance in skin equivalents, for skin tissue and epidermal structure formation. The expression of proteins and changes in genotyping were compared and evaluated. Hematoxylin and eosin staining for histological analysis showed a difference in the activity of fibroblasts in the dermis layer with respect to the presence or absence of ALA. We observed that the epidermis layer became increasingly prominent as the culture period was extended by treatment with 10 μM ALA. The expression of epidermal structural proteins of filaggrin, involucrin, keratin 10, and collagen IV increased because of the effect of ALA. Changes in the epidermis layer were noticeable after the ALA treatment. As a result of aging, damage to the skin-barrier function and structural integrity is reduced, indicating that ALA has an anti-aging effect. We performed a gene analysis of filaggrin, involucrin, keratin 10, integrin, and collagen I genes in ALA-treated human skin equivalents, which indicated an increase in filaggrin gene expression after ALA treatment. These results indicate that pumpless SOC can be used as an in vitro skin model similar to human skin, protein and gene expression can be analyzed, and it can be used for functional drug tests of cosmetic materials in the future. This technology is expected to contribute to the development of skin disease models.     

Understanding the asymmetric perceptions of smartphone security from security feature perspective: A comparative study

Smartphones are being used and relied on by people more than ever before. The open connectivity brings with it great convenience and leads to a variety of risks that cannot be overlooked. Smartphone vendors, security policy designers, and security application providers have put a variety of practical efforts to secure smartphones, and researchers have conducted extensive research on threat sources, security techniques, and user security behaviors. Regrettably, smartphone users do not pay enough attention to mobile security, making many efforts futile. This study identifies this gap between technology affordance and user requirements, and attempts to investigate the asymmetric perceptions toward security features between developers and users, between users and users, as well as between different security features. These asymmetric perceptions include perceptions of quality, perceptions of importance, and perceptions of satisfaction. After scoping the range of smartphone security features, this study conducts an improved Kano-based method and exhaustively analyzes the 245 collected samples using correspondence analysis and importance satisfaction analysis. The 14 security features of the smartphone are divided into four Kano quality types and the perceived quality differences between developers and users are compared. Correspondence analysis is utilized to capture the relationship between the perceived importance of security features across different groups of respondents, and results of importance-satisfaction analysis provide the basis for the developmental path and resource reallocation strategy of security features. This article offers new insights for researchers as well as practitioners of smartphone security.     

Single-Cell Microgels for Diagnostics and Therapeutics

Cell encapsulation within hydrogel droplets is transforming what is feasible in multiple fields of biomedical science such as tissue engineering and regenerative medicine, in vitro modeling, and cell-based therapies. Recent advances have allowed researchers to miniaturize material encapsulation complexes down to single-cell scales, where each complex, termed a single-cell microgel, contains only one cell surrounded by a hydrogel matrix while remaining <100 μm in size. With this achievement, studies requiring single-cell resolution are now possible, similar to those done using liquid droplet encapsulation. Of particular note, applications involving long-term in vitro cultures, modular bioinks, high-throughput screenings, and formation of 3D cellular microenvironments can be tuned independently to suit the needs of individual cells and experimental goals. In this progress report, an overview of established materials and techniques used to fabricate single-cell microgels, as well as insight into potential alternatives is provided. This focused review is concluded by discussing applications that have already benefited from single-cell microgel technologies, as well as prospective applications on the cusp of achieving important new capabilities.     

Environmentally Friendly Graphene Inks for Touch Screen Sensors

Graphene-based materials have attracted significant attention in many technological fields, but scaling up graphene-based technologies still faces substantial challenges. High-throughput top-down methods generally require hazardous, toxic, and high-boiling-point solvents. Here, an efficient and inexpensive strategy is proposed to produce graphene dispersions by liquid-phase exfoliation (LPE) through a combination of shear-mixing (SM) and tip sonication (TS) techniques, yielding highly concentrated graphene inks compatible with spray coating. The quality of graphene flakes (e.g., lateral size and thickness) and their concentration in the dispersions are compared using different spectroscopic and microscopy techniques. Several approaches (individual SM and TS, and their combination) are tested in three solvents (N-methyl-2-pyrrolidone, dimethylformamide, and cyrene). Interestingly, the combination of SM and TS in cyrene yields high-quality graphene dispersions, overcoming the environmental issues linked to the other two solvents. Starting from the cyrene dispersion, a graphene-based ink is prepared to spray-coat flexible electrodes and assemble a touch screen prototype. The electrodes feature a low sheet resistance (290 Ω □⁻¹) and high optical transmittance (78%), which provide the prototype with a high signal-to-noise ratio (14 dB) and multi-touch functionality (up to four simultaneous touches). These results illustrate a potential pathway toward the integration of LPE-graphene in commercial flexible electronics.     

Modeling Sialidosis with Neural Precursor Cells Derived from Patient-Derived Induced Pluripotent Stem Cells

Sialidosis, caused by a genetic deficiency of the lysosomal sialidase gene (NEU1), is a systemic disease involving various tissues and organs, including the nervous system. Understanding the neurological dysfunction and pathology associated with sialidosis remains a challenge, partially due to the lack of a human model system. In this study, we have generated two types of induced pluripotent stem cells (iPSCs) with sialidosis-specific NEU1^G227R and NEU1^V275A/R347Q mutations (sialidosis-iPSCs), and further differentiated them into neural precursor cells (iNPCs). Characterization of NEU1^G227R- and NEU1^V275A/R347Q- mutated iNPCs derived from sialidosis-iPSCs (sialidosis-iNPCs) validated that sialidosis-iNPCs faithfully recapitulate key disease-specific phenotypes, including reduced NEU1 activity and impaired lysosomal and autophagic function. In particular, these cells showed defective differentiation into oligodendrocytes and astrocytes, while their neuronal differentiation was not notably affected. Importantly, we found that the phenotypic defects of sialidosis-iNPCs, such as impaired differentiation capacity, could be effectively rescued by the induction of autophagy with rapamycin. Our results demonstrate the first use of a sialidosis-iNPC model with NEU1^G227R- and NEU1^V275A/R347Q- mutation(s) to study the neurological defects of sialidosis, particularly those related to a defective autophagy–lysosome pathway, and may help accelerate the development of new drugs and therapeutics to combat sialidosis and other LSDs.     

Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.