Understanding History Book 3 Pdf Download
Ozie Harker
Cottingham went on to point out that we might be able to speed up this process by building shared knowledge of common misconceptions pupils might have. We can then go straight to checking whether pupils have these particular misconceptions, or not. In other words, we can check for understanding (of particular ideas or concepts) rather than what understanding (in a broader sense).
understanding history book 3 pdf download
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Firstly, I must make clear that none of the above means I think that checking for understanding is redundant. It is important. Crucial. There is vital knowledge / understanding that we need to ensure that all pupils have. And we need to rigorously check for this.
What are some of the historical metadata that keeps history evolving? While the constants remain, previous histories relied on accounts of those with Eurocentric perspectives. Newer disciplines such as psychology, the social sciences, and economics have added more inclusive perspectives on events including social and ethnic histories whcih add more depth to our understanding of history. The 1970s saw the start of new branches of history including the addition of womens', African, and Jewish studies programs to U.S universities. One example of these studies' contribution to history is Alex Haley's genealogical research of his family detailed in his book Roots. The book has become a classic because it incorporates the perspective of the people who were enslaved to more intimately illustrate slavery's crushing brutality. The book influenced more people to produce their own geneaology-driven narratives and add their own stories into history.
With history evolving, through new methods, narratives, and influences, what sense do we make of the attempts to tell the truth to others as it is seen through a prism of thoughts and biases? Historians have "nailied jelly to the wall" with varying degrees of success by using the tools that have been created over thousands of years and it is up to the reader, the explorer of the past, to bring to the present what has made us what we are today.
Nirenberg is a historian of Christians, Jews and Muslims in medieval Europe and the Mediterranean. His work explores the history of ideas, particularly medieval ideas about communication, exchange and social relations, as well as ideas of race and racism.
An international team of researchers has found new archaeological and genetic evidence which transforms our understanding of the history of cats in Europe. Domestic cats introduced from the Near East and wildcats native to Europe did not mix until the 1960s, despite being exposed to each other for 2,000 years, according to two research papers published today in Current Biology.
The nature of the Scottish wildcat and its relation to feral domestic cats has long been a mystery. Modern molecular methods and mathematical modelling have helped to provide an understanding of what the Scottish wildcat truly is
The success of cancer immunotherapy, such as ACT and ICI therapies, has demonstrated that immune cells, particularly T cells, can be harnessed to eliminate tumor cells. Despite the sustained clinical efficacy, however, only a fraction of cancer patients benefit from them.93 As a major component of the TME, immune infiltrates have been proven to contribute to tumor progression and immunotherapy responses.94 Therefore, a better understanding of both innate and adaptive immune cells in the TME is essential for deciphering the mechanisms of immunotherapies, defining predictive biomarkers, and identifying novel therapeutic targets.
Single-cell protein analysis is a pivotal approach to understanding the phenotypic heterogeneity of TILs. Mass cytometry, or cytometry by time-of-flight (CyTOF), utilizing metal-isotope-labeled antibodies in combination with finely tuned mass spectrometry-based detection, enables simultaneous quantification of more than 40 proteins from millions of individual cells at low cost.175 By contrast, scRNA-seq, including plate-based and droplet-based strategies27 (Fig. 2a), can quantify thousands of transcripts simultaneously; thus, it is able to reveal rare cell populations, uncover complex regulatory mechanisms, and track the developmental trajectories of distinct cell lineages. Recently, these two approaches have been applied to assess the tumor ecosystems of various cancer types (Fig. 2), as both proteomes and transcriptomes could provide important insights into the functional features of the immune infiltrates in the TME.
Colorectal cancer (CRC) is compelling for immuno-oncologists because tumor-infiltrating immune cells were found to be better predictors for CRC patient survival than histopathological methods.95 In addition, ICIs are effective in CRC patients with microsatellite instability (MSI) but not in microsatellite stable patients,185 the molecular underpinnings of which remain elusive. Li et al. performed transcriptome profiling of CRC tumor ecosystems using scRNA-seq.186 This study provided limited biological insights, especially for immune cell functions in CRC, due to its focus on clustering algorithm development. Notably, Zhang et al. performed comprehensive analyses of T cells in CRC with integrated single T-cell analysis by the RNA sequencing and TCR tracking (STARTRAC) framework.174 They delineated the dynamic relationships of diverse T-cell subsets with distinct functions and clonalities. In addition, they revealed one Th1-like subset preferentially enriched in MSI patients, suggesting the underlying cellular mechanisms for their favorable responses to ICIs. These findings deepen our understanding of T-cell features in CRC tumors and accelerate the dissection of mechanisms of ICI treatment.
While the above baseline profiling of treatment-naive tumors provides the intrinsic properties of TILs in diverse cancer types, treatment- or intervention-based studies can offer better opportunities for understanding the molecular underpinnings of immunotherapies and for developing novel approaches to predict clinical efficacies. Jerby-Arnon et al. investigated malignant cell states in human melanoma tumors before and after ICI treatments with scRNA-seq.199 They discovered that malignant cells could express a resistance program associated with T-cell exclusion and immune evasion, and the inhibition of such a program in combination with immunotherapy could reduce tumor growth. Such findings suggest a new strategy to overcome ICI resistance. Compared with molecular changes in cancer cells, however, more attention has been paid to the phenotypic and functional dynamics of TILs upon ICI treatments. By profiling single immune cells from melanoma patients treated with ICI,200 Sade-Feldman et al. found that two unique states of CD8 T cells expressing TCF7 protein or dysfunctional signatures could predict the success or failure of checkpoint immunotherapies, underlining the clinical significance of heterogeneous T-cell subtypes in the TME. Similarly, Yost et al. performed paired single-cell RNA and TCR sequencing on T cells from patients with basal or squamous cell carcinoma (BCC or SCC) treated with an anti-PD-1 inhibitor and revealed clonal replacement of tumor-specific T cells following PD-1 blockade.201 Specifically, they found that ICI treatment induced the clonal expansion of T cells, while the expanded clones did not derive from pre-existing TILs but instead consisted of novel clonotypes. Such observations underscored the significance of systemic immune responses and the necessity of recruiting peripheral T cells for effective ICI treatment.
Cancer immunotherapy, despite its long history, has blossomed into fruition only in recent years with the advances of multiple forms of treatment, including cancer vaccines, ACT and ICIs. A systematic review of the landmark studies in the progress of cancer immunotherapy could facilitate a better understanding of the basic principles, advantages and limitations of various types of immunotherapies, and thus will help promote the development of novel strategies to circumvent their drawbacks and achieve optimal clinical efficacy.
Despite impressive advances in immunotherapies, obstacles, and challenges, including limited response rates, the inability to predict clinical efficacy, and potential side effects such as autoimmune reactions or cytokine release syndromes, remain and hinder the further application of immunotherapies in clinics.213 Tumor-infiltrating immune cells, in particular T cells, serve as the cellular underpinnings of cancer immunotherapies, and a better understanding of immune cells in the TME is essential for deciphering mechanisms of immunotherapies, defining predictive biomarkers, and identifying novel therapeutic targets. Although the heterogeneous cell populations in the TME stand out as the key barrier to delineate the tumor ecosystems, the advances in single-cell technologies, in particular scRNA-seq and CyTOF, have fostered the explosion of single immune cell characterizations. T cells have been the focus of such analyses, and significant biological insights have been obtained about the engagement of T-cell phenotypic and functional diversity in cancer immunotherapies. A systematic overview of the characteristics of TILs in different cancers would shed light on the distinctive mechanisms of immune responses; thus, a more comprehensive pan-cancer analysis of TILs is warranted to elucidate the differences in responses among different cancer types.
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