The two Taiwan Strait crises took place during a particularly tense period of the Cold War. Although each incident was relatively brief, their consequences loom large. Based on analyses of newly ...available documents from Beijing, Taipei, and Washington, Pang Yang Huei challenges conventional wisdom that claims Sino-US misperceptions of each other’s strategic concerns were critical in the 1950s. He underscores the fact that Washington, Taipei, and Beijing were actually aware of one another’s strategic intentions during the crises. He also demonstrates conclusively that both “crises" can be understood as a transformation from tacit communication to tacit accommodation. An important contribution of this study is a better understanding of the role of ritual, symbols, and gestures in international relations. While it is true that these two crises resulted in a stalemate, the fact that all parties were able to cultivate talks and negotiations brought relations, especially between the US and China, to a new and more stable level. Simply averting the threat of war was a major achievement. Strait Rituals is an important micro-history of a significant moment during the Cold War and a rich interpretation of the theoretical use of multiple points of view in writing history. It sets a new standard for understanding China’s place in the world.
Identification of the factors critical to the tumor-initiating cell (TIC) state may open new avenues in cancer therapy. Here we show that the metabolic enzyme glycine decarboxylase (GLDC) is critical ...for TICs in non-small cell lung cancer (NSCLC). TICs from primary NSCLC tumors express high levels of the oncogenic stem cell factor LIN28B and GLDC, which are both required for TIC growth and tumorigenesis. Overexpression of GLDC and other glycine/serine enzymes, but not catalytically inactive GLDC, promotes cellular transformation and tumorigenesis. We found that GLDC induces dramatic changes in glycolysis and glycine/serine metabolism, leading to changes in pyrimidine metabolism to regulate cancer cell proliferation. In the clinic, aberrant activation of GLDC correlates with poorer survival in lung cancer patients, and aberrant GLDC expression is observed in multiple cancer types. This link between glycine metabolism and tumorigenesis may provide novel targets for advancing anticancer therapy.
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► Non-small cell lung cancer (NSCLC) tumor-initiating cells express high levels of glycine decarboxylase (GLDC) ► GLDC is an oncogene that promotes cellular transformation ► GLDC activity regulates pyrimidine metabolism in cancer cells ► GLDC expression predicts mortality in NSCLC patients
An enzyme involved in glycine metabolism acts as an oncogene to drive cancer stem cell proliferation and tumorigenesis in non-small cell lung cancer. Aberrant expression of this enzyme occurs in many cancers and correlates with mortality in lung cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The tumour-initiating cell (TIC) model accounts for phenotypic and functional heterogeneity among tumour cells. MicroRNAs (miRNAs) are regulatory molecules frequently aberrantly expressed in cancers, ...and may contribute towards tumour heterogeneity and TIC behaviour. More recent efforts have focused on miRNAs as diagnostic or therapeutic targets. Here, we identified the TIC-specific miRNAs, miR-1246 and miR-1290, as crucial drivers for tumour initiation and cancer progression in human non-small cell lung cancer. The loss of either miRNA impacted the tumour-initiating potential of TICs and their ability to metastasize. Longitudinal analyses of serum miR-1246 and miR-1290 levels across time correlate their circulating levels to the clinical response of lung cancer patients who were receiving ongoing anti-neoplastic therapies. Functionally, direct inhibition of either miRNA with locked nucleic acid administered systemically, can arrest the growth of established patient-derived xenograft tumours, thus indicating that these miRNAs are clinically useful as biomarkers for tracking disease progression and as therapeutic targets.
The 'Nixon Doctrine,' announced on 25 July 1969, which emphasised the singularity of US interest over all others, was a reflection of US war weariness and the President Richard Nixon's political ...constraints. The net effect was the unilateral withdrawal of troops in phases and Vietnamisation returning combat responsibilities to the South Vietnamese. Indeed, negotiations and diplomacy fell short of expectations, failing to force the North Vietnamese to abandon their objectives. However, Vietnamisation, the third leg of Nixon's strategy, became the most visible of Nixon's failures. Such was the debacle that Nixon was sorely tempted to simply walk away concluding, 'Vietnamization has been completed and South Vietnam President Nguyen Van Thieu then can do what he likes.'
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
This article seeks to provide a textured and nuanced conception of the first Asian-African Conference (18-24 April 1955) by structuring four simultaneous, "mosaic" perspectives (for India, China, ...Indonesia and the Philippines) of that multifaceted event. By eschewing hegemonic "Cold War" and "triumphalist" interpretations, one purposefully avoids a rehash of the roles of the USA and the Soviet Union. Their role, in this study, is peripheral. This article highlights the complexity of the conference by a series of analytical snap shots, multiple focuses, recollections and memories, which emphasise the frequently neglected Babel-like environment of the Bandung Conference. The resulting analysis provides capsules of self-contained experiences rather than one unifying story. Ultimately, the highly contentious and disparate viewpoints that the participants brought to the conference underscored the difficulties that Cold War superpowers experienced in creating political-military blocs friendly to their cause. Third World countries, by the nature of their decolonization process and their political expediencies, succeeded in preventing both the superpowers from creating monolithic blocs.
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BFBNIB, DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and ...immune) heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.
Using a prospective cohort for Hepatocellular Carcinoma (the PLANET study), this work revealed a dynamic landscape of phenotypic intra-tumor heterogeneity, providing several novel approaches for patient treatment and prognosis prediction.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In the aftermath of the Korean War, the People's Republic of China was effectively an international pariah. Accounts of this period in Chinese textbooks emphasize how the Chinese turned this around, ...either during the Geneva Conference or the Bandung Conference, through deft planning and enterprise. Yet few pay any attention to how such manipulation of world opinion became increasingly difficult for Beijing after that initial success. One outcome of China's public relations campaign meant friendly Afro-Asia leaders voiced their opinions, in alarming numbers, to their Chinese counterparts regarding issues such as Asian security, mainland China's economic development, and the Taiwan problem. Indeed, recently declassified Chinese Foreign Affairs archive documents demonstrate that China tried to marshal such non-Soviet bloc opinions to its advantage during the first Taiwan Strait crisis (1955). Chinese efforts were successful in that there was no lack of volunteers to air dissent with American foreign policy. But these new allies also wished to mediate between the United States and the Republic of China, on the one side, and mainland China on the other. Moreover, such efforts were often at variance with China's domestic and strategic outlook in the region. China thus had to embark upon an active ‘management’ of disparate world opinions, which was an entirely new endeavour. Although China tried to provide a sanitized ‘script’ for its new friends, most had their own ideas. By the time of the second Taiwan Strait crisis (1958), the volume of third party interference had grown. Overwhelmed by such international attention, China responded by openly rejecting unwelcome mediation efforts and demanded outright condemnation of the United States. Thus, ironically, with its growing prominence on the international stage, China found itself unbearably weighted down by the burden of world opinion, a position previously occupied by the United States.
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BFBNIB, CEKLJ, INZLJ, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK, ZRSKP
Immune evasion is key to cancer initiation and later at metastasis, but its dynamics at intermediate stages, where potential therapeutic interventions could be applied, is undefined. Here we show, ...using multi-dimensional analyses of resected tumours, their adjacent non-tumour tissues and peripheral blood, that extensive immune remodelling takes place in patients with stage I to III hepatocellular carcinoma (HCC). We demonstrate the depletion of anti-tumoural immune subsets and accumulation of immunosuppressive or exhausted subsets along with reduced tumour infiltration of CD8 T cells peaking at stage II tumours. Corresponding transcriptomic modification occur in the genes related to antigen presentation, immune responses, and chemotaxis. The progressive immune evasion is validated in a murine model of HCC. Our results show evidence of ongoing tumour-immune co-evolution during HCC progression and offer insights into potential interventions to reverse, prevent or limit the progression of the disease.
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