A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.     

Analysis of Temperature Effect in Quadruple Gate Nano-scale FinFET

Silicon - Quadruple gate FinFET is a promising candidate among other multi-gate MOS devices due to it’s better scalability and higher short channel effect suppression capability in advanced...     

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.     

Fire safe,sustainable loose furnishing

The aim of this exploratory study has been to investigate the fire properties and environmental aspects of different upholstery material combinations, mainly for domestic applications. An analysis of the sustainability and circularity of selected textiles, along with lifecycle assessment, is used to qualitatively evaluate materials from an environmental perspective. The cone calorimeter was the primary tool used to screen 20 different material combinations from a fire performance perspective. It was found that textile covers of conventional fibres such as wool, cotton and polyester, can be improved by blending them with fire resistant speciality fibres. A new three‐dimensional web structure has been examined as an alternative padding material, showing preliminary promising fire properties with regard to ignition time, heat release rates and smoke production.     

Progressive NO2 Sensors with Rapid Alarm and Persistent Memory-Type Responses for Wide-Range Sensing Using Antimony Triselenide Nanoflakes

Antimony triselenide (Sb₂Se₃) nanoflake-based nitrogen dioxide (NO₂) sensors exhibit a progressive bifunctional gas-sensing performance, with a rapid alarm for hazardous highly concentrated gases, and an advanced memory-type function for low-concentration (<1 ppm) monitoring repeated under potentially fatal exposure. Rectangular and cuboid shaped Sb₂Se₃ nanoflakes, comprising van der Waals planes with large surface areas and covalent bond planes with small areas, can rapidly detect a wide range of NO₂ gas concentrations from 0.1 to 100 ppm. These Sb₂Se₃ nanoflakes are found to be suitable for physisorption-based gas sensing owing to their anisotropic quasi-2D crystal structure with extremely enlarged van der Waals planes, where they are humidity-insensitive and consequently exhibit an extremely stable baseline current. The Sb₂Se₃ nanoflake sensor exhibits a room-temperature/low-voltage operation, which is noticeable owing to its low energy consumption and rapid response even under a NO₂ gas flow of only 1 ppm. As a result, the Sb₂Se₃ nanoflake sensor is suitable for the development of a rapid alarm system. Furthermore, the persistent gas-sensing conductivity of the sensor with a slow decaying current can enable the development of a progressive memory-type sensor that retains the previous signal under irregular gas injection at low concentrations.     

Flow field simulation and pressure drop modeling by a porous medium in PEM fuel cells

For proton-exchange membrane fuel cells, the distribution of reactant flow in the stack is critical to the fuel cell's efficiency. The uneven distribution of reactant flow in the stack may cause poor current density, low performance, and material degradation. To understand and accurately predict the flow field in the proton-exchange membrane fuel cell system, the present study aims to develop a simple correlation to analyze the pressure drop in fuel cell stacks. The flow channel in each cell of a stack is treated as a porous medium, and a power-law model is used to approximate the porous medium momentum source term. For the stacks with fewer cell numbers, namely, 1, 5, and 10 cells, the parameters in the power law are established based on the experimental data. Then, a correlation is developed to simulate the flow and predict the pressure drop in the stack with higher cell numbers (ie, 20 and 40 cells). The simulations show that the pressure drop in each cell of a stack is almost invariable, and the average pressure drop decreases with increasing the number of cells. The flow uniformity in the stacks with different cell numbers is evaluated using the dimensionless pressure drop and the pressure drop ratios. It suggests that the lower the cell number, the more uniform the pressure drop. The developed model is conducive to efficiently designing the flow channel for a fuel cell stack with large cell numbers.     

Fabrication of high-efficiency Yb:Y2O3 laser ceramics without photodarkening

High-efficiency Yb:Y₂O₃ laser ceramics were fabricated using the vacuum-sintering plus hot isostatic pressing (HIP) without sintering additives. High-purity well-dispersed nanocrystalline Yb:Y₂O₃ powder was synthesized using a modified co-precipitation method in-house. The green bodies were first vacuum sintered at a temperature as low as 1430°C and then HIPed at 1450°C. Finally, the samples were air annealed at 800°C for 10 h. Although no sintering aids were used, full density of the samples with excellent optical homogeneity and an inline transmission of 80% at 400 nm could be obtained. Moreover, photodarkening phenomenon was not detected in the ceramics. Preliminary laser experiment with the fabricated ceramics in a two-mirror cavity has demonstrated 32 W continuous-wave (CW) output at ∼1077 nm with an optical-to-optical conversion efficiency of 58.2%. To the best of our knowledge, this is so far the highest CW output power and optical-to-optical conversion efficiency achieved with the Yb³⁺-doped sesquioxide ceramics in a simple two-mirror cavity.     

Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.