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Frequency noise is a key limitation factor for frequency sensitive ultra-high precision measurement. An excellent methodology for its calibration is the error signal extracting from a cavity length locking process via Pound–Drever–Hall (PDH) technique, and also can be applied as a noise discriminator for active feedback control. However, the stabilized laser frequency noise performance was poor to meet the applications for ultra-high precision measurement, and no literature has analyzed the cause in detail. In this Letter, we found that various of noise floors in the in-loop sensing and modulation depth in the PDH error signal should be responsible for the poor noise performance. Meanwhile, differing from the theoretical prediction (1.08), the modulation depth in frequency noise feedback controlling should be optimized by simultaneously considering the detector's gain and saturation power, cavity impedance matching, and control loop gain. In our case, it was fixed to be 0.17. The experimental results confirm our theoretical analysis well. Finally, the stabilized laser frequency noises are reduced to 10 − 1 Hz / Hz for out-of-loop and 3 × 10 − 2 Hz / Hz for in-loop. The results demonstrate an efficient settlement solution for active frequency noise feedback control. • Optimizing modulation depth for frequency noise suppression is modelled. • Difference in frequency noise between in-loop and out-of-loop is demonstrated. • In-loop noise is observed on-line with the performance of out-of-loop. • Under optimal parameters, a minimum out-of-loop noise of 10 − 1 Hz / Hz so far is demonstrated. [ABSTRACT FROM AUTHOR]

The emerging phase change materials (PCMs) have attracted much attention due to their unique properties and applications. However, the optical properties of PCM at high pressures have not been well explored. In this work, the microstructure and optical properties of GeTe and Sn-substituted GeTe at high pressures up to 30 GPa have been systematically investigated. We find that the substitution of small amounts of Sn for Ge combined with the introduction of high pressure can induce an optical contrast of 117% in crystalline GeTe, which is even higher than the highest optical contrast reported so far (90%) caused by amorphous GeTe to crystalline GeTe. The pressure-induced contrast does not originate from any phase transition as previously, but from the combined effect of Peierls distortion elimination and Ge vacancy formation, which leads to an increase in carrier concentration. The relationship between pressure/atomic composition, Peierls distortion/vacancy formation, and optical contrast can be well explained by a combination of experiments and theoretical calculations. Therefore, this study reveals the effect of high pressure on the optical properties of PCMs and provides new ideas for the design of high-optical-contrast PCMs. [ABSTRACT FROM AUTHOR]

[Display omitted] Endocrine treatment, particularly tamoxifen, has shown significant improvement in the prognosis of patients with estrogen receptor-positive (ER-positive) breast cancer. However, the clinical utility of this treatment is often hindered by the development of endocrine resistance. Therefore, a comprehensive understanding of the underlying mechanisms driving ER-positive breast cancer carcinogenesis and endocrine resistance is crucial to overcome this clinical challenge. In this study, we investigated the expression of MICAL-L2 in ER-positive breast cancer and its impact on patient prognosis. We observed a significant upregulation of MICAL-L2 expression in ER-positive breast cancer, which correlated with a poorer prognosis in these patients. Furthermore, we found that estrogen-ERβ signaling promoted the expression of MICAL-L2. Functionally, our study demonstrated that MICAL-L2 not only played an oncogenic role in ER-positive breast cancer tumorigenesis but also influenced the sensitivity of ER-positive breast cancer cells to tamoxifen. Mechanistically, as an estrogen-responsive gene, MICAL-L2 facilitated the activation of the AKT/mTOR signaling pathway in ER-positive breast cancer cells. Collectively, our findings suggest that MICAL-L2 could serve as a potential prognostic marker for ER-positive breast cancer and represent a promising molecular target for improving endocrine treatment and developing therapeutic approaches for this subtype of breast cancer. [ABSTRACT FROM AUTHOR]

Exploring new therapeutic diseases for existing drugs plays an essential role in reducing drug development costs. However, existing methods for predicting drug–disease association (DDA) lack fusion to multi-neighborhood information, which limits their ability to generalize and forces them to rely on prior knowledge. To this end, we propose a novel DDA model called the Neighborhood Contrastive Learning Heterogeneous Networks (NCH-DDA). NCH-DDA uses both single-neighborhood and multi-neighborhood feature extraction modules to extract important features of drugs and diseases in parallel from multiple potential spaces, such as heterogeneous networks and similarity networks. NCH-DDA fuses single-neighborhood and multi-neighborhood features using contrastive learning to enhance information interaction in different neighborhood spaces, ultimately obtaining universal domain features of drugs and diseases. NCH-DDA uses a combination of predictive loss and triplet loss to reduce dependence on prior knowledge. In different partition schemes of multiple datasets, NCH-DDA achieved the best performance in predicting DDA, outperforming several current state-of-the-art methods. Moreover, NCH-DDA demonstrated better performance in experiments on data sparsity and drug repositioning for Alzheimer's disease, indicating its greater potential in DDA prediction with sparse omics data and drug repositioning applications. • Neighborhood contrastive model for heterogeneous representation and DDA prediction. • MNFEM and SNFEM capture the important features in multiple potential spaces. • Contrast learning aggregated generic neighborhood features of drugs and diseases. • Presented a mixing optimization strategy to reduce the dependence on prior knowledge. • Four of the top five drugs recommended for AD by NCH-DDA were proved to be effective. [ABSTRACT FROM AUTHOR]

With the development of quantum computing and other fields, dilution refrigerators are required to have greater cooling capacity. More cooling power means larger 3He flow rate and the corresponding gas circulation system. In dry dilution refrigerators, 3He needs to be pressurized by compressor for the high inlet pressure. This paper introduces a dry dilution refrigerator driven by a designed high-power two-stage linear compressor, and the reliability of the compressor is verified by experiments. 3He can be pressurized to a pressure above 200 kPa at a flow rate of nearly 1 mmol/s and be condensed successfully in the condensatiion process. The refrigerator, precooled by a pulse tube cryocooler, can obtain a minimum temperature of 19 mK and a cooling capacity of 250 μW at about 100 mK at the total flow rate of about 0.45 mmol/s. The maximum power of 3He compressor can reach 300 W and the maximum compression ratio is over 10, which can be used as the 3He driver of high-power dilution refrigerators or closed-cycle space dilution refrigerators. [ABSTRACT FROM AUTHOR]

Microglia, as the intrinsic immune cells in the brain, are activated following ischemic stroke. Activated microglia participate in the pathological processes after stroke through polarization, autophagy, phagocytosis, pyroptosis, ferroptosis, apoptosis, and necrosis, thereby influencing the injury and repair following stroke. It has been established that polarized M1 and M2 microglia exhibit pro-inflammatory and anti-inflammatory effects, respectively. Autophagy and phagocytosis in microglia following ischemia are dynamic processes, where moderate levels promote cell survival, while excessive responses may exacerbate neurofunctional deficits following stroke. Additionally, pyroptosis and ferroptosis in microglia after ischemic stroke contribute to the release of harmful cytokines, further aggravating the damage to brain tissue due to ischemia. This article discusses the different functional states of microglia in ischemic stroke research, highlighting current research trends and gaps, and provides insights and guidance for further study of ischemic stroke. • Microglia is important in the repair of ischemic stroke. • Microglial polarization is a double-edged sword in ischemic stroke. • Microglial proper autophagy and phagocytosis contribute to functional recovery after ischemic stroke, while excessive activation may worsen the damage. • Microglial pyroptosis, ferroptosis, apoptosis and necrosis in ischemic stroke is in the preliminary stage. [ABSTRACT FROM AUTHOR]