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.     

Identification of Novel Fragments Binding to the PDZ1-2 Domain of PSD-95

Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by ¹H,¹⁵N HSQC NMR to bind in the small hydrophobic P⁰ pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors.     

Effect of microstructural features on the corrosion behavior of severely deformed Al–Mg–Si alloy

The aim of this study was to determine the influence of severe plastic deformation processing and the changes in microstructure resulting therefrom on the corrosion resistance of an Al–Mg–Si alloy. The alloy was processed using incremental equal channel angular pressing, which caused a reduction in grain size from 15 to 0.9 µm. The grain refinement was accompanied by an increase in the number of grain boundaries and dislocations, and by changes in grain orientation. However, there was no change in the size and number of intermetallic particles, which presumably resulted in a constant number of galvanic couplings. Electrochemical experiments revealed only slight differences between the samples before and after processing. Higher potential transients/oscillations upon immersion and increased corrosion currents in the vicinity of corrosion potential point to slightly higher reactivity of the most refined material. This indicates that intermetallic particles are the most crucial microstructural elements in terms of corrosion resistance. Their impact exceeds that of grain boundaries, in particular, at the stage of corrosion initiation. The development of corrosion attack is controlled more by the microstructure of the matrix as the grain refinement resulted in a less pronounced corrosion attack in comparison with the coarse-grained sample.     

Dual effect synergistically triggered Ce:(Y,Tb)3(Al,Mn)5O12 transparent ceramics enabling a high color-rendering index and excellent thermal stability for white LEDs

Ce:Y₃Al₅O₁₂ transparent ceramics (TCs) with appropriate emission light proportion and high thermal stability are significant to construct white light emitting diode devices with excellent chromaticity parameters. In this work, strategies of controlling crystal-field splitting around Ce³⁺ ion and doping orange-red emitting ion, were adopted to fabricate Ce:(Y,Tb)₃(Al,Mn)₅O₁₂ TCs via vacuum sintering technique. Notably, 85.4 % of the room-temperature luminescence intensity of the TC was retained at 150 °C, and the color rendering index was as high as 79.8. Furthermore, a 12 nm red shift and a 16.2 % increase of full width at half maximum were achieved owing to the synergistic effects of Tb³⁺ and Mn²⁺ ions. By combining TCs with a 460 nm blue chip, a warm white light with a low correlated color temperature of 4155 K was acquired. Meanwhile, the action mechanism of Tb³⁺ ion and the energy transfer between Ce³⁺ and Mn²⁺ ions were verified in prepared TCs.     

Matrix Manipulation of Directly-Synthesized PbS Quantum Dot Inks Enabled by Coordination Engineering

The direct-synthesis of conductive PbS quantum dot (QD) ink is facile, scalable, and low-cost, boosting the future commercialization of optoelectronics based on colloidal QDs. However, manipulating the QD matrix structures still is a challenge, which limits the corresponding QD solar cell performance. Here, for the first time a coordination-engineering strategy to finely adjust the matrix thickness around the QDs is presented, in which halogen salts are introduced into the reaction to convert the excessive insulating lead iodide into soluble iodoplumbate species. As a result, the obtained QD film exhibits shrunk insulating shells, leading to higher charge carrier transport and superior surface passivation compared to the control devices. A significantly improved power-conversion efficiency from 10.52% to 12.12% can be achieved after the matrix engineering. Therefore, the work shows high significance in promoting the practical application of directly synthesized PbS QD inks in large-area low-cost optoelectronic devices.     

keff uncertainty quantification and analysis due to nuclear data during the full lifetime burnup calculation for a small-sized prismatic high temperature gas-cooled reactor

To benefit from recent advances in modeling and computational algorithms,as well as the availability of new covariance data,sensitivity and uncertainty analyses are needed to quantify the impact of uncertain sources on the design parameters of small prismatic high-temperature gas-cooled reactors(HTGRs).In particular,the contribution of nuclear data to the keff uncertainty is an important part of the uncertainty analysis of small-sized HTGR physical calculations.In this study,a small-sized HTGR designed by China Nuclear Power Engineering Co.,Ltd.was selected for keff uncertainty analysis during full lifetime burnup calculations.Models of the cold zero power(CZP)condition and full lifetime burnup process were constructed using the Reactor Monte Carlo Code RMC for neutron transport calculation,depletion calculation,and sensitivity and uncertainty analysis.For the sensitivity analysis,the Contribution-Linked eigenvalue sensitivity/Uncertainty estimation via Track length importance Characterization(CLUTCH)method was applied to obtain sensitive infor-mation,and the"sandwich"method was used to quantify the keff uncertainty.We also compared the keff uncertainties to other typical reactors.Our results show that 235U is the largest contributor to keff uncertainty for both the CZP and depletion conditions,while the contribution of 239Pu is not very significant because of the design of low discharge burnup.It is worth noting that the radioactive capture reaction of 28Si significantly contributes to the keff uncer-tainty owing to its specific fuel design.However,the keff uncertainty during the full lifetime depletion process was relatively stable,only increasing by 1.12％owing to the low discharge burnup design of small-sized HTGRs.These numerical results are beneficial for neutronics design and core parameters optimization in further uncertainty prop-agation and quantification study for small-sized HTGR.     

Spectroscopic properties and thermally stable orange-red luminescence of Sm:Zr:LiNbO3 and Sm:Hf:LiNbO3 for white LED applications

LiNbO₃ crystals activated by Sm³⁺ and co-doped with Zr⁴⁺ (Sm:Zr:LN) or Hf⁴⁺ (Sm:Hf:LN) were prepared by the Czochralski method. Detailed investigation on spectroscopic properties was conducted on the frame of Judd-Ofelt (J-O) theory. The J-O intensity parameters Ω_i (i = 2, 4, 6), fluorescence branching ratios and radiative lifetime of excited level ⁴G_5/2 were determined. Furthermore, the thermal stability of the strong orange-red emissions obtained under near-UV excitation in both crystals was evaluated. As high as 100% and 97% of integrated intensities at room temperature in Sm:Zr:LN and Sm:Hf:LN respectively were retained at 423 K, demonstrating the suppressed thermal attenuation. The temperature sensing performance based on fluorescence intensity ratio strategy was degraded at higher temperatures with relatively low sensitivities, while the shift of CIE chromaticity coordinates of Sm:Zr:LN and Sm:Hf:LN in the orange-red region was insignificant, demonstrating the color constancy with increasing temperature. With the efficient and thermally stable orange-red luminescence, Sm:Zr:LN and Sm:Hf:LN could serve as promising candidate materials for near-UV excited white light-emitting diodes.     

Recent advances in carbon nanotubes-based microwave absorbing composites

With the blossom of information industry, electromagnetic wave technology shows increasingly potential in many fields. Nevertheless, the trouble caused by electromagnetic waves has also drawn extensive attention. For instance, electromagnetic pollution can threaten information safety in vital fields and the normal function of delicate electronic devices. Consequently, electromagnetic pollution and interference become an urgent issue that needs to be addressed. Carbon nanotubes (CNTs) have become a potential candidate to deal with these problems due to many advantages, such as high dielectric loss, remarkable thermodynamic stability, and low density. With the appearance of climbing demands, however, the carbon nanotubes combining various composites have shown greater prospects than the single CNTs in microwave absorbing materials. In this short review, recent advances in CNTs-based microwave absorbing materials were comprehensively discussed. Typically, we introduced the electromagnetic wave absorption mechanism of CNTs-based microwave absorbing materials and generalized the development of CNTs-based microwave absorbers, including CNTs-based magnetic metal composites, CNTs-based ferrite composites, and CNTs-based polymer composites. Ultimately, the growing trend and bottleneck of CNTs-based composites for microwave absorption were analyzed to provide some available ideas to more scientific workers.     

In Vivo Albumin-Binding of a C-Functionalized Cyclam Platform for 64Cu-PET/CT Imaging in Breast Cancer Model

An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2^Mal, has been synthesized and studied for in vivo ⁶⁴Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1^Mal. The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [⁶⁴Cu]Cu-GluCAB-2^Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [⁶⁴Cu]Cu-GluCAB-2^Mal and previous-generation [⁶⁴Cu]Cu-GluCAB-1^Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [⁶⁴Cu]Cu-GluCAB-2^Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [⁶⁴Cu]Cu-Glu-CAB-2^Mal.