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Inheritance of a BRCA2pathogenic variant conveys a substantial life-time risk of breast cancer. Identification of the cell(s)-of-origin of BRCA2-mutant breast cancer and targetable perturbations that contribute to transformation remains an unmet need for these individuals who frequently undergo prophylactic mastectomy. Using preneoplastic specimens from age-matched, premenopausal females, here we show broad dysregulation across the luminal compartment in BRCA2mut/+tissue, including expansion of aberrant ERBB3loluminal progenitor and mature cells, and the presence of atypical oestrogen receptor (ER)-positive lesions. Transcriptional profiling and functional assays revealed perturbed proteostasis and translation in ERBB3loprogenitors in BRCA2mut/+breast tissue, independent of ageing. Similar molecular perturbations marked tumours bearing BRCA2-truncating mutations. ERBB3loprogenitors could generate both ER+and ER−cells, potentially serving as cells-of-origin for ER-positive or triple-negative cancers. Short-term treatment with an mTORC1 inhibitor substantially curtailed tumorigenesis in a preclinical model of BRCA2-deficient breast cancer, thus uncovering a potential prevention strategy for BRCA2mutation carriers.

Lithium (Li) metal is widely recognized as a promising anode material for next-generation Li secondary batteries, owing to its exceptionally high theoretical specific capacity of 3860 mAh g−1and the lowest reduction potential (−3.04 V vs. standard hydrogen electrode). However, the instability of the native solid electrolyte interphase (SEI) leads to dendrite growth, which poses significant safety risks and contributes to battery degradation. To address this issue, numerous strategies have been proposed to construct artificial SEI with good physical and chemical properties. This paper provides a comprehensive overview of advancements in constructing artificial SEI from the perspective of precursor materials (i.e., inorganic and organic inducers) and construction methods (i.e., in situ and ex situ). It focuses on the compositional and nanostructural changes of SEI engineered by different strategies and explores their resulting functional differences. Based on the summary of various strategies, prospective research directions for the development of artificial SEI are finally envisioned.

For the purpose of investigating the contact erosion characteristics in breaking process of SF6breaker, an erosion experiment was conducted on the tested SF6 circuit breaker. As a result, the relationship between the dynamic resistance and contact travel in various levels of degradation was acquired. The SF6contact state parameters were obtained from the experimental results. Considering the parameters change, the follow-up conclusions can be sum up: (1) The contact travel’s minimum value is deduced to be 14.2 mm; (2) The numerical value of contact resistance has an acceptable range, which is 50∼150μΩfor main contact and 200∼400μΩfor arcing contact, respectively. (3) The measured value of arcing contact attenuate length is 0.318 mm, which remains unchanged in each erosion test. Taking all the mentioned above into consideration, we research on the contact material erosion process during the opening operation and the effect on the circuit breaker property. In the meantime, the theoretical calculation formula of length decrement in arcing contact is deduced. Based on the formula, the calculated value is 0.268 mm for each trial, which is close to the measured value of 0.318 mm. At last, the prediction methods for the SF6circuit breaker’s electrical life is summarized.

Similar to the onshore wind power integrated through AC transmission, the offshore wind power integrated through the modular multilevel converter (MMC) based HVDC also lays remarkable impacts on the stability of the power system. According to grid codes, offshore wind power should be capable of adjusting its active power fast. This paper proposes a fast regulation method at the onshore point of common coupling for offshore wind power by utilizing the energy stored in the distributed capacitors in the MMC. By carefully designing the curve of capacitor energy, the active power can vary expectedly. Meanwhile, no disturbance is placed on the DC-side active power or DC voltage. The effectiveness of the proposed method is verified by electromagnetic simulation.

The small-signal stability problem of power electronic converters has always been a critical concern for safe operation. This paper conducts a comprehensive analysis of the small-signal stability for the hybrid modular multilevel converter (MMC), which is promising in the application of future over-head-line high-voltage-direct-current transmission. The impacts of the strong and weak AC system connection are comparatively researched through eigenvalue-based analysis. The newly emerging factors that hamper the stability are identified for the weak AC system integration. The work in this paper provides valuable guidance for robust control parameter configuration of the hybrid MMC.

Objective:The objective of this review was to synthesise the literature and evaluate the incidence, prevalence and severity of medical device-related pressure ulcers (MDRPU) in adult intensive care patients.Method:Electronic databases and additional grey literature were searched for publications between 2000 and 2017. Outcome measures included cumulative incidence or incidence rate, point prevalence or period prevalence as a primary outcome and the severity and location of the pressure ulcer (PU) as secondary outcome measures. Included studies were assessed for risk of bias using a nine-item checklist for prevalence studies. The heterogeneity was evaluated using 12statistic.Results:We included 13 studies in this review. Prevalence was reported more frequently than incidence. Pooled data demonstrated a high variation in the incidence and prevalence rates ranging from 0.9% to 41.2% in incidence and 1.4% to 121% in prevalence. Heterogeneity was high. Mucosal pressure injuries were the most common stage reported in the incidence studies whereas category II followed by category I were most commonly reported in the prevalence studies. In the incidence studies, the most common location was the ear and in the prevalence studies it was the nose.Conclusion:While MDRPU are common in intensive care patients, it is an understudied area. Inconsistency in the staging of MDRPU, along with variations in data collection methods, study design and reporting affect the reported incidence and prevalence rates. Standardisation of data reporting and collection method is essential for pooling of future studies.

This paper proposed a novel type of DC-DC converter, termed as un-interrupted DC Autotransformer (un-interrupted DC AUTO), which has the capability to ride through DC fault on either side of the converter without blocking any devices. Besides that, the adequately designed converter retains the advantages of DC AUTO technology, namely reduced investment cost and transmission loss. To begin with, the topology and basic attributes of the un-interrupted DC AUTO are illustrated. Then the design goals and the corresponding design procedures are analyzed. Furthermore, an effective control system is proposed to enable the converter steady operation during both normal and faulted conditions. Finally, a 1000 MW ±320 kV/±640 kV test system is built on PSCAD/EMTDC platform to verify the technical feasibility of the proposed converter and the effectiveness of the control strategy.

The numerical simulation of rapid increasing choke pressure method for complete sour gas kick circulations is achieved, by using a transient, multiphase flow model, which has been verified with full-scale kick experimental date. The results indicate that the bottomhole pressure change rules can be classified into four cases based on the behaviour of the key parameter, which is choke pressure increment (ΔPc). Each case follows the identical four phases. Perfect well control procedure can be achieved by accurately adjusting ΔPc. A new method is proposed that could determine more precisely whether the formation flow ultimately stops by comparing the values between two points from bottomhole pressure or from standpipe pressure. The appropriate ΔPc interval can be also ascertained by combining with safe mud density window. The rapid increasing choke pressure method could effectively inhibits the dissolved H2S from releasing and greatly reduce the gas expansion and resulting pressure fluctuation near the wellhead, thus it is quite suitable for sour gas development with low-high H2S content. [Received: May 20, 2014; Accepted: December 13, 2014]