Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing

Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on electrooculogram.The potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes Ca2+-activated Cl−channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and photoreceptor.In this study,the complete clinical characteristics of two Chinese ARB families were summarized.Methods:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family members.Results:Two novel mutations,c.202T>C(chr11:61722628,p.Y68H)and c.867+97G>A,in the BEST1 gene were identified in the two Chinese ARB families.The novel missense mutation BEST1 c.202T>C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1.Another novel variant,BEST1 c.867+97G>A(chr11:61725867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators.Conclusion:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes.The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.

China’s Change through Future Leaders’Eyes

Together for a Shared Future Compiled by Global Young Leaders Dialogue Price:RMB 118 Paperback,250 pages Published by Foreign Languages Press Together for a Shared Future is co-authored by 35 young people from 26 countries who participated in the project China Tour of the Global Young Leaders Dialogue(GYLD),an institutional platform for idea-sharing among young people from different countries.

How Group Leaders Build Stable Community Buying Groups:A Perspective Based on the Differential Mode of Association

Since 2016,community group buying has grown significantly in China,largely driven by its efficient logistics,supply chains,low prices,and convenience.This model has been further popularized during the COVID-19 pandemic due to its effectiveness in meeting daily needs while minimizing human-to-human contact.A key component of this business model is the“group leaders”-influential individuals within a community responsible for managing group buying activities,which include order collection,supplier liaison,and goods distribution.Their primary task is to form and sustain a reliable community group buying consortium,a task that demands excellent organizational and interpersonal skills.This paper examines this phenomenon using the lens of the differential mode of association,a theoretical model explaining interpersonal relationships in traditional Chinese society.The research indicates that group leaders,through regular interaction with consumers,are able to alter their social network position,increase their influence,understand consumer needs,provide satisfying services,and enhance trust,thereby transforming consumers into loyal group buying participants.This transformation not only brings stability to group buying activities but also reinforces the community influence of group leaders,thus fostering the growth of community group buying.

The Critical Role of Middle Leaders in Schools:Cultivating a Culture of Trust and Supporting Educational Reform

This research delves into the often-underappreciated role of middle leaders in educational organizations,highlighting their significance as the linchpins between senior leadership and classroom teachers.Utilizing qualitative research methods,the study investigates the multifaceted responsibilities,challenges,and contributions of middle leaders in schools.Findings indicate that middle leaders foster a culture of trust within the institution by providing mentorship and guidance to new teachers.They undertake substantial tasks,such as team coordination,grade direction,and student supervision,in addition to their teaching duties.Despite their pivotal role,middle leaders often face mounting pressures and heavy workloads.This research underscores the need to recognize and support middle leaders in educational settings,acknowledging their vital role in fostering cohesion and facilitating the implementation of educational reforms.

振动信号小波leaders多重分形特征提取及性能分析

机械振动信号一般具有非线性、非平稳特性,多重分形特征是表示振动信号几何结构特征的一种重要手段。传统的多重分形特征计算方法计算量大,限制了多重分形特征的应用。小波leaders多重分形分析方法具有坚实的数学基础,且计算简便。针对齿轮正常状态和点蚀故障状态,提出基于小波leaders的多重分形振动信号特征提取及表示方法,提出基于bootstrap技术的最优块长求解算法,并建立振动信号小波leaders多重分形特征的统计性能分析方法。研究结果表明,小波leaders多重分形特征能够很好反映振动信号的几何结构特征,基于块bootstrap方法能有效分析多重分形特征统计性能,为机械设备状态监控和故障诊断提供了一种有效的选择。

Optimizing the Leadership Styles and Establishing a New Teacher-Student Relationship

There're mainly two kinds of behaviors-Task Behaviors(TBs) and Relationship Behaviors(RBs) among the school leadership styles. TBs contribute to achieving the goals, while RBs help to promote the interpersonal relationships. However, different perceptions of social values and morals will have a great influence on establishing the good leader-teacher relationship and the teacher-student relationship, which is also no exception for the leadership styles. Thus, optimizing the leadership styles will enhance the leader-teacher relationship, and also benefit the teacher-student relationship.

Collective coordination of multi-agent systems guided by multiple leaders

A neighbour-based coordination scheme is proposed for a multi-agent system with multiple leaders. Under assumptions of the connectivity of the interconnection topology and a simple first-order dynamics model for each mobile agent, the results show that all the agents will flock to the polytope region formed by the leaders.

Comparing Three of the Leadership Theories: Leader-Member Exchange Theory,transformational Leadership and Team Leadership

Leadership is a complex process.It is one of the most researched areas around the world.It has gained importance in every walk of life from politics to business and from education to social organizations.According to the study of"Leadership in Adult Education Venues",here has a much more clear recognition of leadership:leadership is a process whereby an individual influences a group of individuals to achieve a common goal.There are many approaches of leadership throughout the study of this class,the three theories of leadership I choose to describe in this paper are:Leader-Member Exchange(LMX)Theory,Transformational Leadership,and Team Leadership.

Propagation of positive, negative, and recoil leaders in upward lightning flashes

Leader propagation is a fundamental issue in lightning physics. The propagation characteristics of positive leaders and negative leaders are summarized and compared based on data from high-speed camera and electromagnetic field in rocket-triggered lightning and tower-initiated lightning discharges; available channel base current data recorded in rocket-triggered lightning are also used. The negative leaders propagate in a stepped fashion accompanied by many branches. The stems ahead of the negative leader tip determine the manner and direction of the leader propagation, and even the branching and winding of the lightning channel. The impulsive current, electromagnetic field, and related optical images suggest that the positive leader may develop in a step-like fashion at its initial stage of triggered lightning. However, the stepping processes of the positive leader are obviously different from those of the negative leader. Tower-initiated lightning revealed that the most conspicuous characteristics of the stepwise positive leader involve the intermittent brush-like corona zone in front of the leader tip and the luminosity enhancement of the channel behind the tip. In rockettriggered lightning flashes, the charge transferred during an individual step for the negative leader was nearly an order greater than for the positive counterpart. The successive streamers ahead of the leader tip are essential for both negative and positive leader propagation, and the stems could be formed from one or more streamers in the previous negative streamer zone with the main leader channel dim. High-resolution observation of tower lightning also revealed a new type of bidirectional recoil leader, with polarity contrary to the traditional one, traversing in negative channels associated with tower-initiated and rocket-triggered lightning.

Recent progress in third-generation low alloy steels developed under M^3 microstructure control

During the past thirty years, two generations of low alloy steels(ferrite/pearlite followed by bainite/martensite) have been developed and widely used in structural applications. The third-generation of low alloy steels is expected to achieve high strength and improved ductility and toughness, while satisfying the new demands for weight reduction, greenness, and safety. This paper reviews recent progress in the development of third-generation low alloy steels with an M^3 microstructure, namely, microstructures with multi-phase, meta-stable austenite, and multi-scale precipitates. The review summarizes the alloy designs and processing routes of microstructure control, and the mechanical properties of the alloys.The stabilization of retained austenite in low alloy steels is especially emphasized. Multi-scale nano-precipitates, including carbides of microalloying elements and Cu-rich precipitates obtained in third-generation low alloy steels, are then introduced. The structure–property relationships of third-generation alloys are also discussed. Finally, the promises and challenges to future applications are explored.

Innovation and development of the third-generation hybrid rice technology

The breeding and large-scale application of hybrid rice contribute significantly to the food supply worldwide.Currently,hybrid seed production uses cytoplasmic male sterile(CMS)lines or photoperiod/thermo-sensitive genic male sterile(PTGMS)lines as female parent.Despite huge successes,both systems have intrinsic problems.CMS systems are mainly restricted by the narrow restorer resources that make it difficult to breed superior hybrids,while PTGMS systems are limited by conditional sterility of the male sterile lines that makes the propagation of both PTGMS seeds and hybrid seeds vulnerable to unpredictable climate changes.Recessive nuclear male sterile(NMS)lines insensitive to environmental conditions are widely distributed and are ideal for hybrid rice breeding and production,but the lack of effective ways to propagate the pure NMS lines in a large scale renders it impossible to use them for hybrid rice production.The development of"the third-generation hybrid rice technology"enables efficient propagation of the pure NMS lines in commercial scale.This paper discusses the establishment of"the thirdgeneration hybrid rice technology"and further innovations.This new technology breaks the limitations of CMS and PTGMS systems and will bring a big leap forward in hybrid rice production.

Evaluation of the effects of a leader-training program on public health nurse leadership for staff in Japan

This paper is a report of a study of the effects of a leader-training program, focusing on how public health nurse (PHN) leaders manage staff. In Japan, a system of training after graduation or training after acquisition of the PHN license has not been established. At present, PHN leaders are unable to devote as much time as they previously could to in-service education, and this has made it difficult to establish a suitable full-fledged in-service education system. Therefore, it is paramount for PHN leaders to acquire the necessary competence to train staff efficiently and, ultimately, play a more prominent role in the in-service education of novice PHNs. The effecttiveness of this program was evaluated before and after conducting the program over a 1-year period. A total of 145 leaders working for local government agencies in Japan participated in the program, and data from 87 participants were analyzed. Before the training program, Plan-Do-Check-Act cycle activities were less frequent than after the program. Intervention using a leader-training program that combines group and on-the-job training is effective for PHN leaders.

Determining Leaders and Communities on Networks Using Neighborhood Similarity

Networks are used to represent interactions in a wide variety of fields, like biology, sociology, chemistry, and more. They have a great deal of salient information contained in their structures, which have a variety of applications. One of the important topics of network analysis is finding influential nodes. These nodes are of two kinds —leader nodes and bridge nodes. In this study, we propose an algorithm to find strong leaders in a network based on a revision of neighborhood similarity. This leadership detection is combined with a neighborhood intersection clustering algorithm to produce high quality communities for various networks. We also delve into the structure of a new network, the Houghton College Twitter network, and examine the discovered leaders and their respective followers in more depth than which is frequently attempted for a network of its size. The results of the observations on this and other networks demonstrate that the community partitions found by this algorithm are very similar to those of ground truth communities.

Coordination of Multi-leaders and Multi-followers in Supply Chain of Value-Added Telecom Services

In order to study supply chain of the telecom value-added service,a multi-leaders and multi-followers Stackelberg game model with multiple telecom operators and multiple service providers whose income is composed of information fee division and advertisement was constructed.Then a demonstration was simulated,and the results were compared with the situation of service providers' income only from information fee division.The simulated and compared results indicate that,the enterprises in the supply chain have the nature of pursuing the maximum profits in capital markets;meanwhile,first-mover advantages and some enterprise can get more profits with the information asymmetry.

Opinion Leaders and Lead Users in Marketing and Management Accounting and Impact on Small Business Performance

This paper empirically investigates into the business performance benefit that lead users or opinion leaders among small business owners draw from their higher involvement in management accounting or marketing topics. This work also contributes to a better identification of network members’ roles solely through their ties between each other. Indeed, lead users and opinion leaders can be differentiated by a higher degree centrality in comparison to their peers. However, being an opinion leader or a lead user does not yield a measurable business benefit to the small businesses studied in this sample.

Applications of sediment sudden deposition model based on the third-generation numerical model for shallow water wave

The existing numerical models for nearshore waves are briefly introduced, and the third-generation numerical model for shallow water wave, which makes use of the most advanced productions of wave research and has been adapted well to be used in the environment of seacoast, lake and estuary area, is particularly discussed. The applied model realizes the significant wave height distribution at different wind directions. To integrate the model into the coastal area sediment, sudden deposition mechanism, the distribution of average silt content and the change of sediment sudden deposition thickness over time in the nearshore area are simulated. The academic productions can give some theoretical guidance to the applications of sediment sudden deposition mechanism for stormy waves in the coastal area. And the advancing directions of sediment sudden deposition model are prospected.

基于改进Leaders算子的审计潜在疑点发现

数据库查询方法审计疑点发现依赖于审计人员先验知识,当经验不足且审计数据量巨大时,难以发挥大数据优势并从海量数据中发现疑点。为解决这一问题,提出基于改进Leaders算子迭代聚类的审计大数据潜在疑点发现方法。该方法在无先验知识的情形下,通过Leaders算法自动完成审计大数据的初始聚类,在此基础上通过随机抽样融合方法对初始聚类结果优化,最后通过多次迭代聚类的方法,对实例数较少或可疑程度易被掩盖的小簇进一步聚类,实现审计大数据的精确聚类,并将实例较少且行为明显异常的数据聚类识别为潜在疑点,配合审计人员审计经验快速精确定位审计疑点。实验结果验证了算法的有效性,表明算法有助于从海量数据中自主发现审计疑点,缩小疑点筛查范围,提高审计效率。

Xi Meets European Leaders on Advancing Ties, Global Governance

Chinese President Xi Jinping, French President Emmanuel Macron, German Chancellor Angela Merkel and European Commission President Jean- Claude Juncker met in Paris on March 26 and agreed to strengthen China-European Union (EU) relations and global governance cooperation.