Exploiting DNA damage repair defects for effective targeting of acute myeloid leukaemia by PARP inhibitors

Abstract for 24th Biennial Congress of the European Association for Cancer Research, 9–12 July 2016, Manchester, UK. Poster Session: Cancer Genomics, Epigenetics and Genome Instability II: Monday 11 July 201

Time-integrated luminosity recorded by the BABAR detector at the PEP-II e+e- collider

This article is the Preprint version of the final published artcile which can be accessed at the link below.We describe a measurement of the time-integrated luminosity of the data collected by the BABAR experiment at the PEP-II asymmetric-energy e+e- collider at the ϒ(4S), ϒ(3S), and ϒ(2S) resonances and in a continuum region below each resonance. We measure the time-integrated luminosity by counting e+e-→e+e- and (for the ϒ(4S) only) e+e-→μ+μ- candidate events, allowing additional photons in the final state. We use data-corrected simulation to determine the cross-sections and reconstruction efficiencies for these processes, as well as the major backgrounds. Due to the large cross-sections of e+e-→e+e- and e+e-→μ+μ-, the statistical uncertainties of the measurement are substantially smaller than the systematic uncertainties. The dominant systematic uncertainties are due to observed differences between data and simulation, as well as uncertainties on the cross-sections. For data collected on the ϒ(3S) and ϒ(2S) resonances, an additional uncertainty arises due to ϒ→e+e-X background. For data collected off the ϒ resonances, we estimate an additional uncertainty due to time dependent efficiency variations, which can affect the short off-resonance runs. The relative uncertainties on the luminosities of the on-resonance (off-resonance) samples are 0.43% (0.43%) for the ϒ(4S), 0.58% (0.72%) for the ϒ(3S), and 0.68% (0.88%) for the ϒ(2S).This work is supported by the US Department of Energy and National Science Foundation, the Natural Sciences and Engineering Research Council (Canada), the Commissariat à l’Energie Atomique and Institut National de Physique Nucléaire et de Physiquedes Particules (France), the Bundesministerium für Bildung und Forschung and Deutsche Forschungsgemeinschaft (Germany), the Istituto Nazionale di Fisica Nucleare (Italy), the Foundation for Fundamental Research on Matter (The Netherlands), the Research Council of Norway, the Ministry of Education and Science of the Russian Federation, Ministerio de Ciencia e Innovación (Spain), and the Science and Technology Facilities Council (United Kingdom). Individuals have received support from the Marie-Curie IEF program (European Union) and the A.P. Sloan Foundation (USA)

Selected Open Problems in Discrete Geometry and Optimization

A list of questions and problems posed and discussed in September 2011 at the following consecutive events held at the Fields Institute, Toronto: Workshop on Discrete Geometry, Conference on Discrete Geometry and Optimization, and Workshop on Optimization. We hope these questions and problems will contribute to further stimulate the interaction between geometers and optimizers

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study Global Burden of Disease Cancer Collaboration

IMPORTANCE: Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning. OBJECTIVE: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015. EVIDENCE REVIEW: Cancer mortality was estimated using vital registration system data, cancer registry incidence data (transformed to mortality estimates using separately estimated mortality to incidence [MI] ratios), and verbal autopsy data. Cancer incidence was calculated by dividing mortality estimates through the modeled MI ratios. To calculate cancer prevalence, MI ratios were used to model survival. To calculate YLDs, prevalence estimates were multiplied by disability weights. The YLLs were estimated by multiplying age-specific cancer deaths by the reference life expectancy. DALYs were estimated as the sum of YLDs and YLLs. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. Countries were categorized by SDI quintiles to summarize results. FINDINGS: In 2015, there were 17.5 million cancer cases worldwide and 8.7 million deaths. Between 2005 and 2015, cancer cases increased by 33%, with population aging contributing 16%, population growth 13%, and changes in age-specific rates contributing 4%. For men, the most common cancer globally was prostate cancer (1.6 million cases). Tracheal, bronchus, and lung cancer was the leading cause of cancer deaths and DALYs in men (1.2 million deaths and 25.9 million DALYs). For women, the most common cancer was breast cancer (2.4 million cases). Breast cancer was also the leading cause of cancer deaths and DALYs for women (523 000 deaths and 15.1 million DALYs). Overall, cancer caused 208.3 million DALYs worldwide in 2015 for both sexes combined. Between 2005 and 2015, age-standardized incidence rates for all cancers combined increased in 174 of 195 countries or territories. Age-standardized death rates (ASDRs) for all cancers combined decreased within that timeframe in 140 of 195 countries or territories. Countries with an increase in the ASDR due to all cancers were largely located on the African continent. Of all cancers, deaths between 2005 and 2015 decreased significantly for Hodgkin lymphoma (-6.1% [95% uncertainty interval (UI), -10.6% to -1.3%]). The number of deaths also decreased for esophageal cancer, stomach cancer, and chronic myeloid leukemia, although these results were not statistically significant. CONCLUSION AND RELEVANCE: As part of the epidemiological transition, cancer incidence is expected to increase in the future, further straining limited health care resources. Appropriate allocation of resources for cancer prevention, early diagnosis, and curative and palliative care requires detailed knowledge of the local burden of cancer. The GBD 2015 study results demonstrate that progress is possible in the war against cancer. However, the major findings also highlight an unmet need for cancer prevention efforts, including tobacco control, vaccination, and the promotion of physical activity and a healthy diet

Hong Kong's Embattled Democracy: Perspectives from East Asian NIEs

This article examines the origins and development of Hong Kong's embattled democracy. It seeks to explain why, although Hong Kong has already acquired most of the "prerequisites" for democratization, its democracy has been so restricted and contested compared to those in the East Asian newly industrialized economies (NIEs). It also argues that Hong Kong possesses much less favorable structural conditions for democratization than its East Asian neighbors because it has a stronger conservative alliance of state and Big Business on the one hand, and a weaker populist alliance of service professionals and grass-roots population on the other. However, the Tiananmen incident of June 1989 revitalized the Hong Kong democracy project almost overnight, and now that the democrats have been strengthened, they have been able to contest the rules of restricted democracy as imposed by the conservative alliance of Beijing and Big Business

Modern east asia in world-systems analysis

Applying the large-scale, holistic, and long-time-span heuristic devices of world-systems analysis, this article highlights the crucial role played by regional geopolitics in East Asian development. In regard to large-scale analysis, this article studies interstate dynamics in East Asia and shows how the strategic locations of China, Japan, and Korea greatly influenced one another's development. This article shows, through holistic analysis, that geopolitics often intertwines with emerging cultural constructs and changing regional dynamics and, through long-term analysis, that contemporary East Asia must be understood in terms of its pre-World War II geopolitical development. This study contributes to the existing literature by reintroducing the often neglected geopolitical context into reinterpreting the roles of the market, Confucianism, the state, and dependency in the contours of East Asian development

The Taiwan-Mainland economic nexus: Sociopolitical origins, state-society impacts, and future prospects

Most researchers on Taiwan's Mainland investment are economists who tend to focus on the economic dimension of the Taiwan-Mainland nexus. Consequently they are unable to explain both the timing (why it started in 1987), the locale (why in Guangdong and Fujian), the ownership (why the preference for sole ownership), the investors (why small and medium enterprises took the lead), and the speed (why such a rapid rate) of Taiwan's Mainland investment. In this respect the aim of this article is to explore the sociopolitical dimension in order to gain a broader picture of the origins, impacts, and prospects of the Taiwan-Mainland nexus. First, we investigate to what extent the origins of Taiwan's Mainland investment were shaped by other than economic factors. Second, we study how the Taiwan-Mainland economic nexus has had a profound impact on Taiwan's state-society relationship. Finally, we briefly examine the future prospects for extending this nexus to the conception of the "Great Chinese Economic Circle."

Democratization in East Asia in the late 1980s: Taiwan breakthrough, Hong Kong frustration

Political history took an unexpected turn in East Asia in the late 1980s. The booming movement in Hong Kong had gone downhill and suffered defeat, while the authoritarian Taiwan state actively sponsored genuine democratic reforms. What then explains the Taiwan democratic breakthrough and the Hong Kong democratic frustration? This article argues that conventional explanations offered in the modernization, the dependency, and the class literature-such as culture, liberal colonialism, wealth, new middle class, bureaucratic-authoritarian state, crises, and absence of conservative class coalition-are unable to account for the divergent paths of democratic development in Taiwan and Hong Kong. As an alternative, this article presents a model that highlights the importance of conjuncture factors. It is argued that since Taiwan and Hong Kong have shared similar structural conditions, researchers have to bring in conjuncture factors such as the historical event of Chinese unification, the capacity of the political agency to promote democratic reforms, and the strategy of protest in order to explain the Taiwan breakthrough and the Hong Kong frustration. © 1993 Springer