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Dysregulated cellular proliferation represents a hallmark feature across all cancers. Aberrant activation of the cyclin-dependent kinase 4 and 6 (CDK4/6) pathway, independent of mitogenic signaling, engenders uncontrolled breast cancer cell proliferation. Consequently, the advent of CDK4/6 inhibition has constituted a pivotal milestone in the realm of targeted breast cancer therapy. The combination of CDK4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) has emerged as the foremost therapeutic modality for patients afflicted with hormone receptor-positive (HR + )/HER2-negative (HER2-) advanced breast cancer. At present, the Food and Drug Administration (FDA) has sanctioned various CDK4/6i for employment as the primary treatment regimen in HR + /HER2- breast cancer. This therapeutic approach has demonstrated a substantial extension of progression-free survival (PFS), often amounting to several months, when administered alongside endocrine therapy. Within this comprehensive review, we systematically evaluate the utilization strategies of CDK4/6i across various subpopulations of breast cancer and explore potential therapeutic avenues following disease progression during application of CDK4/6i therapy.

Dynamic precision measurement of gravity field is of great significance to the fields of geological surveying, resource exploration, and autonomous navigation now. Current dynamic gravity measurements remain relative, thereby facing the drawbacks of accuracy calibration and measurement value drift of instruments. The operation of the absolute gravimeters in dynamic measurement could solve these problems, whereas during the measurement of absolute gravity in a dynamic environment, the interference and coupling of the dynamic environment is an important issue to research urgently. In this article, we report the new progress on our homemade marine survey system of absolute gravity, and the experimental improvements are introduced compared with the previous system. Furthermore, the experiments of marine gravity surveys campaign are carried out in the Yellow Sea of China. The crossover tracks and repeated survey lines are designed in order to evaluate the performance. The internal coincidence precision of our marine survey system is estimated to be 1.22 mGal, and the results are also in good agreement with the reference data measured by the relative gravimeter, and an external coincidence accuracy of 1.62 mGal is obtained. Finally, the methods of data processing are given in great detail, and the surveyed results are compared with satellite gravity data and the data from the shipborne relative gravimeter. Our results may be helpful for the development of marine absolute gravimeters and the actual shipborne surveys of absolute gravity.

In this article, a novel hybrid method of combining refined composite multiscale permutation ${q}$ -complexity entropy (RCMPQE) and random forest (RF) is developed to locate disconnection faults in a power distribution system. As a feature extraction method, RCMPQE is used to analyze the negative-sequence current to obtain fault features, and then they are input into RF to build a fault location model. The effectiveness of the proposed method is corroborated by referencing a three-feeder distribution network. The results demonstrate that compared with multiscale permutation entropy (MPE), refined composite MPE (RCMPE), and generalized MPE (GMPE), the RCMPQE has stronger feature extraction ability and can abstract more prominent fault information from negative-sequence current signals. The proposed method for locating faults significantly outperforms other commonly employed machine learning models, and it is immune to various levels of noise. Furthermore, the proposed method can perform well with a high fault location accuracy in a new system.

AbstractSome individuals, e.g., those holding multiple directorships, are insiders at multiple firms. When they execute an insider trade at one firm, they may reveal information about the value of all—both the traded insider position and not-traded insider position(s)—the securities held in their “insider portfolio.” We find that insider “not-sold” stocks outperform “not-bought” stocks. Implementable trading strategies that buy not-sold stocks following the disclosure of a sale earn alphas up to 4.8% per year after trading costs. The results suggest that even insider sales that are motivated by liquidity and diversification needs can provide value-relevant information about insider holdings.

•Perceived control carries affective, motivational and protective attributes.•Its affective attribute recruits the ventral striatum.•Its motivational attribute is subserved by dopaminergic transmission.•Its protective attribute is associated with the ventromedial prefrontal cortex.•Perceived control is a transdiagnostic feature across psychopathologies.

Cold atomic gravimeters are attracting more and more attention and activity in the area of gravity measurement and comparison, and the corresponding methods for measurement and traceability need to be explored. Based on two self-developed cold atomic gravimeters, research on the comparison and traceability methods of absolute gravity measurement was carried out. The entire gravity measurement traceability process is divided into two stages: the preliminary traceability in the laboratory and the formal traceability in the absolute gravity reference station. Through comparison of two atomic gravimeters (ZAG-E and ZAG-B) in the laboratory, the degree of equivalence D_D and the normalized deviation E_n of ZAG-E are obtained, which are −2.7±7.6µGal (k=2) and −0.3599, respectively. Relative to the absolute gravity reference at the National Institute of Metrology (NIM) in China, D_D and E_n of ZAG-E are 0.5±12.0µGal (k=2) and 0.0417, respectively. |E_n|≤1 in the two traceability stages, so the results of two traceability stages are acceptable, which indicates the consistency of the comparisons is good. Finally, the absolute gravity measurement value of ZAG-E is traced to the SI units, ensuring its accuracy. A gravity traceability method for atomic gravimeters is given and is very beneficial for the applications of atomic gravimeters in metrology and other fields.

Cue reactivity, a core characteristic of substance use disorders, commonly recruits brain regions that are key nodes in neurocognitive networks, including the default mode network (DMN) and salience network (SN). Whether resting-state temporal dynamic properties of these networks relate to subsequent cue reactivity and cue-induced craving is unknown.

Nicotine enhances the reinforcement of non-drug rewards by increasing nucleus accumbens (NAcc) reactivity to anticipatory cues. This anticipatory effect is selective as no clear evidence has emerged showing that nicotine acutely changes reward receipt reactivity. However, repeated rewarding experiences shift peak brain reactivity from hedonic reward outcome to the motivational anticipatory cue yielding more habitual cue-induced behavior. Given nicotine’s influence on NAcc reactivity and connectivity, it is plausible that nicotine acutely induces this shift and alters NAcc functional connectivity during reward processing. To evaluate this currently untested hypothesis, a randomized crossover design was used in which healthy non-smokers were administered placebo and nicotine (2-mg lozenge). Brain activation to monetary reward anticipation and outcome was evaluated with functional magnetic resonance imaging. Relative to placebo, nicotine induced more NAcc reactivity to reward anticipation. Greater NAcc activation during anticipation was significantly associated with lower NAcc activation to outcome. During outcome, nicotine reduced NAcc functional connectivity with cortical regions including the anterior cingulate cortex, orbitofrontal cortex, and insula. These regions showed the same negative relationship between reward anticipation and outcome as noted in the NAcc. The current findings significantly improve our understanding of how nicotine changes corticostriatal circuit function and communication during distinct phases of reward processing and critically show that these alterations happen acutely following a single dose. The implications of this work explain nicotinic modulation of general reward function, which offer insights into the initial drive to smoke and the subsequent difficulty in cessation.

This paper discusses the field stabilization control of the M5 unit under wind disturbances. The first part is a literature survey of the spectral content of the wind disturbance. Next, a simplified model of a tip/tilt mirror control system is used to analyze the conditions for control-structure interaction. The influence of the asymptotic decay rate of the wind tilt disturbance on the magnitude and spectral content of the control torques is pointed out. A full telescope model is developed to justify a decoupled tip/tilt control design and to analyze the response of the primary mirror M1 to the disturbance generated by the control torques of the M5 unit.

This paper presents a unimorph deformable mirror intended to be used as secondary corrector in space telescopes. The deformable mirror consists of a single-crystal silicon wafer (76.2 mm diameter, 500 μm thickness) covered with an optical coating on the front side and an array of 25 independent piezoelectric transducer (PZT) actuators acting in d_31 mode on the back side. The mirror is mounted on an isostatic support with three position linear actuators controlling the rigid-body motion. The first part of the paper presents the experimental results obtained with the manufactured prototype. The mirror was tested in terms of root mean square (RMS) wavefront error, open-loop long-term stability, voltage budget for active control, rigid-body actuation, reflectivity, and dynamic response. The prototype is fully compliant with the requirements set by the European Space Agency (ESA). The second part of the paper, purely based on numerical simulations, presents a robust way to face thermal distortion, inherent to unimorph architecture.

The tunability of an organic room-temperature phosphorescent (RTP) system is important but rarely reported. In this work, we report a series of host/guest ultralong organic room-temperature phosphorescent materials with lifetime- and color-tuning properties. By doping a nonroom-temperature phosphorescence guest emitter, 1, 8-naphthalimide (NI), into a series of solid host matrices with higher triplet energy levels, the lifetime (0.20–0.81 s) and color (yellow–green) of tunable RTP materials are realized. Phosphorescence quantum yields are up to 19.96%. As the excitation wavelength is switched from 365 to 254 nm, the phosphorescent color changes significantly and the phosphorescent lifetime increases by a factor of almost 2. Notably, the unique dual emission (fluorescence and phosphorescence) of the doped material 4BrBa-NI resulted in a different orange emission. The host/guest doping materials are prepared through cocrystallization or grinding, allowing for efficient energy transfer from the guest to the host. The results indicate that strong intermolecular interactions and the intersystem crossing (ISC) ability of the guest play a significant role. In addition, the security protection and anticounterfeit encryption applications for RTP materials are realized through various methods, such as handwritten pens, screen printing, and dynamic recognition of QR codes, which significantly improve the commercial viability of the RTP materials.