Myc‐driven tumorigenesis involves a non‐transcriptional role for Myc in over‐activating replicative Cdc45‐MCM‐GINS (CMG) helicases. Excessive stimulation of CMG helicases by Myc mismanages CMG function by diminishing the number of reserve CMGs necessary for fidelity of DNA replication and recovery from replicative stresses. One potential outcome of these events is the creation of DNA damage that alters genomic structure/function, thereby acting as a driver for tumorigenesis and tumor heterogeneity. Intriguingly, another potential outcome of this Myc‐induced CMG helicase over‐activation is the creation (...) of a vulnerability in cancer whereby tumor cells specifically lack enough unused reserve CMG helicases to recover from fork‐stalling drugs commonly used in chemotherapy. This review provides molecular and clinical support for this provocative hypothesis that excessive activation of CMG helicases by Myc may not only drive tumorigenesis, but also confer an exploitable “reserve CMG helicase vulnerability” that supports developing innovative CMG‐focused therapeutic approaches for cancer management. (shrink)

Over the past decade or so, a new interdisciplinary field has emerged in the ground between, on the one hand, computer science – and artificial intelligence in particular – and, on the other, the area of philosophy concentrating on the language and structure of argument. There are now hundreds of researchers worldwide who would consider themselves a part of this nascent community. Various terms have been proposed for the area, including "Computational Dialectics," "Argumentation Technology," and "Argument-based Computing," but the term (...) that has stuck is simply Argument & Computation. It encompasses several specific strands of research, such as: . the use of theories of argument, and dialectic in particular, in the design and implementation of protocols for multi-agent action and communication; . the application of theories of argument and rhetoric in natural language processing and affective computing; . the use of argument-based structures for autonomous reasoning in artificial intelligence, and in particular, for defeasible reasoning; . computer-supported collaborative argumentation – the implementation of software tools for enabling online argument in domains such as education and e-government. These strands come together to form the core of a research field that covers parts of artificial intelligence (AI), philosophy, linguistics, and cognitive science, but, increasingly, is building an identity of its own. (shrink)

We construct the set of the title, answering a question of Cholak, Jockusch, and Slaman [1], and discuss its connections with the study of the proof-theoretic strength and effective content of versions of Ramsey's Theorem. In particular, our result implies that every ω-model of RCA 0 + SRT 2 2 must contain a nonlow set.

This article compares the information processing and dynamical systems perspectives on problem solving. Key theoretical constructs of the information-processing perspective include “searching” a “p...

On 30 June 1994 the Social Democratic Party of Japan (SDPJ, formerly the Japan Socialist Party) joined its historic enemy, the Liberal Democratic Party (LDP), to form a coalition government in a Japanese equivalent of Italy's . Competition between the conservative LDP and the progressive socialists had defined the Japanese party system since 1955. In this paper we analyze voter reactions to this and other confusing events surrounding the end of the LDP's 38-year dominance. We find, first, that the Japanese (...) electorate was able to make sense of these events. The political space reflected in public opinion mapped the political space reflected in the mass media remarkably well. Secondly, our findings support the idea that attitudes toward political parties are endogenous to the political process: strategic moves by political actors alter the political space within which they maneuver. Coalitions of strange bedfellows force voters to revise their perceptions of political space and reevaluate their attitudes toward the actors involved. Strange bedfellows seemed less strange, friendlier after they had been seen in bed together. (shrink)

This case recounts the story of Rajat Gupta, a Goldman Sachs board member and seniorpartner emeritus of McKinsey & Co., who was accused by the government of giving critical nonpublicfinancial information to Raj Rajaratnam, Galleon Group founder, during the financial crisisof 2008. The information passed along to Rajaratnam was about a pending $5 billion investment byWarren Buffett’s Berkshire Hathaway in Goldman Sachs at a time when its stock had been faltering.The government alleged that based on this information, Rajaratnam purchased a (...) large number ofshares in the company and then sold them when the deal became public and Goldman’s stock rose.Rajaratnam purportedly made $18 million on these trades. (shrink)

This case recounts the story of Rajat Gupta, a Goldman Sachs board member and seniorpartner emeritus of McKinsey & Co., who was accused by the government of giving critical nonpublicfinancial information to Raj Rajaratnam, Galleon Group founder, during the financial crisisof 2008. The information passed along to Rajaratnam was about a pending $5 billion investment byWarren Buffett’s Berkshire Hathaway in Goldman Sachs at a time when its stock had been faltering.The government alleged that based on this information, Rajaratnam purchased a (...) large number ofshares in the company and then sold them when the deal became public and Goldman’s stock rose.Rajaratnam purportedly made $18 million on these trades. (shrink)

Using the 2005 and 2006 AsiaBarometer surveys I analyze religiosity and secularization in Asia. I find that, in South Asia, identification with a particular religion is the norm and most people pray every day but, in East Asia, religious identification and religious practice are both much less common. Even in secular East Asia, however, the demand for religious services is high and belief in a spiritual world is common. I conclude that secularization does not necessarily produce uniformly secular societies. Turning (...) to the causes and consequences of religiosity, I find surprisingly few significant relationships, results that echo similar analyses in Western Europe. I then discuss the implications of these non-findings. (shrink)

Background:Choice to live and die at home is supported by palliative care policy; however, health resources and access disparity impact on this choice in rural Australia. Rural end-of-life home care is provided by district nurses, but little is known about their role in advocacy for choice in care.Objectives:The study was conducted to review the scope of the empirical literature available to answer the research question: What circumstances influence district nurse advocacy for rural client choice to live and die at home?, (...) and identify gaps in the knowledge.Method:Interpretive scoping methodology was used to search online databases, identify suitable studies and select, chart, analyse and describe the findings.Results:34 international studies revealed themes of ‘the nursing relationship’, ‘environment’, ‘communication’, ‘support’ and ‘the holistic client centred district nursing role.Discussion:Under-resourcing, medicalisation and emotional relational burden could affect advocacy in rural areas.Conclusion:It is not known how district nurses overcome these circumstances to advocate for choice in end-of-life care. Research designed to increase understanding of how rural district nurses advocate successfully for client goals will enable improvements to be made in the quality of end-of-life care offered. (shrink)

In the 1993 general election the Liberal Democratic Party lost power for the first time since it was founded in 1955. The coalition government that followed enacted the most far-reaching political reforms Japan has experienced since the American Occupation. The country has now experienced two elections since these reforms so we can begin to analyze trends and dynamics. It is now possible to make a preliminary evaluation of the effects of these reforms. I evaluate the reforms under three headings: (1) (...) reducing the cost of elections and levels of corruption; (2) replacing candidate-centered with party-centered campaigns; and (3) moving toward a two-party system which would produce alternation in power between the parties of the government and the parties of the opposition. In conclude that, with some notable exceptions, the reforms are working well, about as well as should have been expected. (shrink)

One year ago I entitled my review of Japanese elections . Candidates running against the establishment were defeating candidates who had until recently appeared unbeatable. Most notably, outsider candidates were defeating ainori (supported by all major parties) candidates in gubernatorial elections. A prime example of an outsider candidate defeating the establishment was Prime Minister Koizumi, who defeated the LDP establishment to win the leadership of the LDP. Koizumi's election and subsequent popularity appears to have dampened the trend. Most notably, a (...) well-qualified challenger failed to unseat the incumbent in the Shizuoka gubernatorial election. Once Koizumi's popularity faded, however, the trend in favour of outsiders reappeared. Given an attractive alternative, establishment candidates continue to find themselves in trouble. The clearest recent example comes from the Yokohama mayoral election. (shrink)

This article analyzes narrative illustrations in genetic counseling textbooks as a way of understanding professional habitus--the dispositions that motivate professional behavior. In particular, this analysis shows that there are significant differences in how the textbooks' expository and narrative portions represent Down syndrome, genetic counseling practice, and patient behaviors. While the narrative portions of the text position the genetic counseling profession as working in service to the values of genetic medicine, the expository portions represent genetic counselors as neutral parties. Ultimately, this (...) article argues that this ambiguity is harmful to the production of a professional habitus that is consistent with espoused professional values concerning respect for persons with disabilities and the promotion of psychosocial counseling. (shrink)

The most important election held in 2001 was that to the House of Councillors. Here, however, I will report on several surprising gubernatorial elections and the shocking LDP party presidential election. Each of these elections sent a similar message from the voters: . Powerful political machines using tried and true campaign techniques were repeatedly defeated by novices whose primary attraction was that they were not part of the political establishment.

The results of the 2000 general election can be interpreted in two contradictory ways. On the one hand, the coalition won a comfortable majority with 271 seats to the combined opposition total of 188. On the other hand, the coalition lost 64 seats while the opposition parties gained 35. Though either side could thus claim victory, it was clear from the expressions on the faces of the party leaders that the coalition had lost the election and the opposition had won. (...) This result means, first, that the LDP's strategy of allying itself with Koumei, a religious party based on a particular Buddhist sect, has been called into question by both coalition partners and, second, that the Democratic Party of Japan (DPJ) has been confirmed as the primary alternative to the LDP. (shrink)

The M + 1 Rule, that at equilibrium there should be only one more candidate running than seats available, extended Duverger's Law to the cases of more than one seat per district. Both the M + 1 rule and Duverger's Law have been confirmed repeatedly, albeit always with qualification. Yet we have reached no consensus on the mechanism that produces these two empirical regularities. In this paper I use a simple simulation to test the hypothesis that the mechanism is that (...) candidates retire after some fixed number of consecutive losses. I test the results of the simulation against several different empirical results and find a reasonably good fit. I also add a mechanism for increasing the number of candidates. These results suggest that the M + 1 rule and Duverger's law may be the result not of rational calculation but of some simple set of decision rules. The analysis also illustrates the usefulness of a simulation approach to hypothesis testing. (shrink)

This article introduces a new scale to measure executive servant leadership, situating the need for this scale within the context of ethical leadership and its impacts on followers, organizations and the greater society. The literature on servant leadership is reviewed and servant leadership is compared to other concepts that share dimensions of ethical leadership (e.g., transformational, authentic, and spiritual leadership). Next, the Executive Servant Leadership Scale (ESLS) is introduced, and its contributions and limitations discussed. We conclude with an agenda for (...) future research, describing ways the measure can be used to test hypotheses about organizational moral climate, ethical organizational culture, corporate responsibility, and institutional theory. (shrink)

Coastal ecosystems are increasingly dominated by humans. Consequently, the human dimensions of sustainability science have become an integral part of emerging coastal governance and management practices. But if we are to avoid the harsh lessons of land management, coastal decision makers must recognize that humans are one of the more coastally dependent species in the biosphere. Management responses must therefore confront both the temporal urgency and the very real compromises and sacrifices that will be necessary to achieve a sustainable coastal (...) ecosystem, one that is economically feasible, socially just, and ecologically sound. (shrink)

Clinical trials for acute conditions such as myocardial infarction and stroke pose challenges related to informed consent due to time limitations, stress, and severe illness. Consent processes shou...

Background Informed consent is a requirement for all research. It is not, however, clear how much information is sufficient to make an informed decision about participation in research. Information on an online questionnaire about childhood development was provided through an unfolding electronic participant sheet in three levels of information. Methods 552 participants, who completed the web-based survey, accessed and spent time reading the participant information sheet (PIS) between July 2008 and November 2009. The information behaviour of the participants was investigated. (...) The first level contained less information than might be found on a standard PIS, the second level corresponded to a standard PIS, and the third contained more information than on a standard PIS. The actual time spent on reading the information provided in three incremental levels and the participants' evaluation of the information were calculated. Results 77% of the participants chose to access the first level of information, whereas 12% accessed the first two levels, 6% accessed all three levels of information and 23% participated without accessing information. The most accessed levels of information were those that corresponded to the average reading times. Conclusion The brief information provided in the first level was sufficient for participants to make informed decisions, while a sizeable minority of the participants chose not to access any information at all. This study adds to the debate about how much information is required to make a decision about participation in research and the results may help inform the future development of information sheets by providing data on participants' actual needs when deciding about questionnaire surveys. (shrink)

The lateralized ERP N2pc component has been shown to be an effective marker of attentional object selection when elicited in a visual search task, specifically reflecting the selection of a target item among distractors. Moreover, when targets are known in advance, the visual search process is guided by representations of target features held in working memory at the time of search, thus guiding attention to objects with target-matching features. Previous studies have shown that manipulating working memory availability via concurrent tasks (...) or within task manipulations influences visual search performance and the N2pc. Other studies have indicated that visual vs. spatial working memory manipulations have differential contributions to visual search. To investigate this the current study assesses participants' visual and spatial working memory ability independent of the visual search task to determine whether such individual differences in working memory affect task performance and the N2pc. Participants completed a visual search task to elicit the N2pc and separate visual working memory and spatial working memory assessments. Greater SPWM, but not VWM, ability is correlated with and predicts higher visual search accuracy and greater N2pc amplitudes. Neither VWM nor SPWM was related to N2pc latency. These results provide additional support to prior behavioral and neural visual search findings that spatial WM availability, whether as an ability of the participant's processing system or based on task demands, plays an important role in efficient visual search. (shrink)