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Immunocheckpoint proteins of tumor infiltrating lymphocytes play an important role in tumor prognosis in the course of tumor clinicopathology. PD‐1 (Programmed cell death protein 1) is an important immunosuppressive molecule. By binding to PD‐L1 (programmed cell death‐ligand 1), it blocks TCR and its costimulus signal transduction, inhibits the activation and proliferation of T cells, depletes the function of effector T cells, and enables tumor cells to achieve immune escape. In recent years, immunocheckpoint blocking therapy targeting the PD‐1/PD‐L1 axis has achieved good results in a variety of malignant tumors, pushing tumor immunotherapy to a new milestone, such as anti‐PD‐1 monoclonal antibody Nivolumab, Pembrolizumab, and anti‐PD‐L1 monoclonal antibody Atezolizumab, which are considered as potential antitumor drugs. It was found in clinical use that some patients obtained long‐term efficacy, but most of them developed drug resistance recurrence in the later stage. The high incidence of drug resistance (including primary and acquired drug resistance) still cannot be ignored, which limited its clinical application and became a new problem in this field. Due to tumor heterogeneity, current limited research shows that PD‐1 or PD‐L1 monoclonal antibody drug resistance may be related to the following factors: mutation of tumor antigen and antigen presentation process, multiple immune checkpoint interactions, immune microenvironment changes dynamically, activation of oncogenic pathways, gene mutation and epigenetic changes of key proteins in tumors, tumor competitive metabolism, and accumulation of metabolites, etc, mechanisms of resistance are complex. Therefore, it is the most urgent task to further elucidate the mechanism of immune checkpoint inhibitor resistance, discover multitumor universal biomarkers, and develop new target agents to improve the response rate of immunotherapy in patients. In this study, the mechanism of anti‐PD‐1/PD‐L1 drug resistance in tumors, the potential biomarkers for predicting PD‐1 acquired resistance, and the recent development of combination therapy were reviewed one by one. It is believed that, based on the complex mechanism of drug resistance, it is of no clinical significance to simply search for and regulate drug resistance targets, and it may even produce drug resistance again soon. It is speculated that according to the possible tumor characteristics, three types of treatment methods should be combined to change the tumor microenvironment ecology and eliminate various heterogeneous tumor subsets, so as to reduce tumor drug resistance and improve long‐term clinical efficacy. Based on the analysis of existing studies, ICB resistance involves complex network regulatory mechanisms, and the countermeasures against certain drug resistance mechanisms cannot solve the drawbacks of clinical drug resistance. In terms of treatment, traditional basic treatment, evidence‐based treatment of tumor type, and individual precision therapy should be integrated to comprehensively remove all subsets of cells in heterogeneous tumors.

This book is about the role and potential of using digital technology in designing teaching and learning tasks in the mathematics classroom and explores mathematics task design when digital technology is part of the teaching and learning environment.

The argillaceous fine-silt gas hydrate reservoirs, characterized by high clay content(20–25%) and the median sand grain size(10–15 μm), pose extreme challenges to sand control. Based on analyses of existing sand production laws and plugging mechanisms, the paper focuses on the characteristics of argillaceous fine-silt reservoirs and systematically reviews conventional sand control methods and the small-scale simulation devices. An innovative full-scale experimental evaluation device was developed, enabling simulation of sand control screens performance under different well deviation angles, and the dynamic down-hole conditions, and a corresponding plugging test and evaluation method was established. The experimental investigations via the device revealed the plugging characteristics of sand control screens in the target reservoirs: sand-mudstone interbedding induces clay hydration and swelling, driving fine particles into the screen’s sand retention layer; coupled with the layer’s irregular, heterogeneous pores, this hinders particle expulsion and drastically reduces screen permeability. Further, the study clarified the influence laws and sensitivity of four key factors( clay content, mineral composition, well inclination angle, and production rate) on sand screen performance. The dominant factors were identified as clay content and production rate: screen permeability dropped sharply when clay content reached 55%, and declined fluctuatingly with increasing production rate (40–160 L/min) until stabilizing beyond a critical threshold. The non-dominant factors included mineral composition and well inclination angle: montmorillonite content exceeding 45% exacerbated plugging (synergistically amplified by production rate), while screen permeability decreased moderately from 426 mD (0°, vertical well) to 300 mD (90°, horizontal well), with well inclination angle exerting insignificant sensitivity on plugging. These findings hold critical guidance for sand control in argillaceous fine-silt hydrate reservoirs. It is necessary to maintain a dynamic balance between the effective sand control and optimal productivity release.

\"Task-based language teaching is an approach which differs from traditional approaches by emphasizing the importance of engaging learners' natural abilities for acquiring language incidentally through the performance of tasks that draw learners' attention to form. Drawing on the multiple perspectives and expertise of five leading authorities in the field, this books provides a comprehensive and balanced account of task-based language teaching (TBLT). Split into five sections, the book provides an historical account of the development of TBLT and introduces the key issues facing the area. A number of different theoretical perspectives that have informed TBLT are presented, followed by a discussion on key pedagogic aspects - syllabus design, methodology of a task-based lesson, and task-based assessment. The final sections consider the research that has investigated the effectiveness of TBLT, addresses critiques and suggest directions for future research. Task-based language teaching is now mandated by many educational authorities throughout the world and this book serves as a core source of information for researchers, teachers and students\"-- Provided by publisher.

Practitioners of economic geography recognize innovation as the key factor in sustainable economic development and urging a city to evolve. Urban development evolves from manufacturing-based development to knowledge-based development. Identifying the future benefits of urban development is a research issue. This work analyzes development performance based on quantitative indices of critical knowledge and innovation that enhance economic growth and influence society and competitiveness. The research further identifies the possibility of knowledge dissemination and innovation. This work investigates the key factors encouraging the development of a knowledge-based city for Helsinki, Melbourne, and Hsinchu in terms of economy, society, environment, and management, and observes that the progressive and positive circular stimulation for a city requires not only the cultivation of human capital, but also the construction of social environment and internal relations to form a high-density knowledge network. This work demonstrates that Hsinchu Science Park acts as a highly stimulated and highly interactive knowledge engine by building a dynamic innovation model based on circular stimulation of knowledge feedback to construct an urban environment and series of talent networks. The city, ultimately, reaches a virtuous cycle for innovation and achieves critical factors for the evolution of a knowledge-based city.

Scientific literacy is approached on the premise that language is key to understand the nature of both learning and participation, in scientists{u2019} practices as well as in liberal education for citizenship. Some of the questions that are addressed in the book are: {u2022} What does it take to be able to participate in different arenas in society involving science? {u2022} How does everyday language relate to scientific language? {u2022} How can students{u2019} texts be analyzed to gain insights into their learning? {u2022} How can images be analyzed alongside verbal language? This book offers a thorough introduction to key ideas in M. A. K. Halliday{u2019}s systemic functional grammar through examples and practical analysis. Detailed analysis is offered of science textbooks and curriculum documents, classroom talk, experimental work, and students{u2019} discussions of complex environmental issues. Further, an analytical model guiding the design and analysis of science learning discourses is introduced. The book starts with introducing excerpts from whole-class discussions, group work, experimental reports and textbooks as text-in-context. From this starting point, key aspects of language are carefully explained. The role of grammatical metaphor in the development of science knowledge is an important topic throughout the book. Tools for analyzing multimodal representations, intertextuality and multiple voices are also among the topics covered for understanding and analyzing school science discourses.

Sometimes, it is impossible to conduct tests with the use of the GNSS system, or the obtained results of the measurements made differ significantly from the predicted accuracy. The most common cause of the problems (external factors, faulty results) are interference disturbances from other radio telecommunication systems. The subject of this paper is to conduct research, the essence of which is an in-depth analysis in the field of elimination of LTE interference signals of the GNSS receiver, that is based on the developed effective methods on counteracting the phenomenon of interference signals coming from this system and transmitted on the same frequency. Interference signals are signals transmitted in the GNSS operating band, and unwanted signals may cause incorrect processing of the information provided to the end-user about his position, speed, and current time. This article presents methods of identifying and detecting interference signals, with particular emphasis on methods based on spatial processing of signals transmitted by the LTE system. A comparative analysis of the methods of detecting an unwanted signal was made in terms of their effectiveness and complexity of their implementation. Moreover, the concept of a new comprehensive anti-interference solution was proposed. It includes, among others, information on the various stages of GNSS signal processing in the proposed system, in relation to the algorithms used in traditional GNSS receivers. The final part of the article presents the obtained research results and the resulting significant observations and practical conclusions.

\"The Handbook of Classroom Discourse and Interaction is an authoritative reference work exploring the latest research, methodologies, and theories related to classroom language, teaching, and learning\"-- Provided by publisher.

We introduce a novel class of factor analysis methodologies for the joint analysis of multiple studies. The goal is to separately identify and estimate (1) common factors shared across multiple studies, and (2) study-specific factors. We develop an Expectation Conditional-Maximization algorithm for parameter estimates and we provide a procedure for choosing the numbers of common and specific factors. We present simulations for evaluating the performance of the method and we illustrate it by applying it to gene expression data in ovarian cancer. In both, we clarify the benefits of a joint analysis compared to the standard factor analysis. We have provided a tool to accelerate the pace at which we can combine unsupervised analysis across multiple studies, and understand the cross-study reproducibility of signal in multivariate data. An R package (MSFA), is implemented and is available on GitHub.