While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

The purpose of this study is to explore with more rigor and detail the role of social norms in tax compliance. This study draws on Cialdini and Trost’s (The Handbook of Social Psychology: Oxford University Press, Boston, MA, 1998) taxonomy of social norms to investigate with more specificity this potentially decisive (Alm and McKee, Managerial and Decision Economics, 19:259–275, 1998) influence on tax compliance. We test our research hypotheses regarding the direct and indirect influences of social norms using a hypothetical (...) compliance scenario with 174 experienced taxpayers as participants. Factor analysis of the social norm questions successfully identified four distinct social norm constructs, in line with Cialdini and Trost (1998). Results of the path analysis show that individuals’ standards for behavior/ethical beliefs (personal norms) as well as the expectations of close others (subjective norms) directly influence tax compliance decisions, whereas general societal expectations (injunctive norms) and other individuals’ actual behavior (descriptive norms) have an indirect influence. This shows that social norms have important direct as well as indirect influences on tax compliance behavior. We also investigate a number of attitudinal variables that may be related to social norms and taxpayer compliance. The results of this study further clarify the important role that social norms have with regard to taxpayers’ compliance behavior. (shrink)

Circadian rhythms are ∼24‐h biological oscillations that enable organisms to anticipate daily environmental cycles, so that they may designate appropriate day/night functions that align with these changes. The molecular clock in animals and fungi consists of a transcription‐translation feedback loop, the plant clock is comprised of multiple interlocking feedback‐loops, and the cyanobacterial clock is driven by a phosphorylation cycle involving three main proteins. Despite the divergent core clock mechanisms across these systems, all circadian clocks are able to buffer period length (...) against changes in the ambient growth environment, such as temperature and nutrients. This defining capability, termed compensation, is critical to proper timekeeping, yet the underlying mechanism(s) remain elusive. Here we examine the known players in, and the current models for, compensation across five circadian systems. While compensation models across these systems are not yet unified, common themes exist across them, including regulation via temperature‐dependent changes in post‐translational modifications. (shrink)

During the COVID-19 epidemic, personal safety has received increasing attention, leading to behavioral changes. Mobile-wallet makes it easier for people to keep social distance, which helps stop the spread of the COVID-19 virus. Evolving Internet technology has brought about changes in consumer lifestyle. The current situation of COVID-19 has created a business environment to shift from traditional ways and adopt e-commerce solutions worldwide. Grounded in technology acceptance model theory, this study’s objective is two-fold: First, this study intends to examine perceived (...) susceptibility to COVID-19, perceived severity of COVID-19, insecurity and discomfort as the predictors of perceived usefulness and perceived ease of use. Second, the current research intends to test the moderating effect of electronic words-of-mouth on the relationship between attitude and usage intention. Using survey methods, 226 usable responses were collected through a mall intercept survey in Pakistan. Data were analyzed using partial least square. The results revealed that PEOU and PU positively influence attitude toward M-wallet. This study has found that attitude positively influences the usage intention in adopting M-wallet. The results also support the moderating role of eWOM. These findings contribute to the marketing literature in several ways, particularly in Pakistan. This is the first study to use eWOM as a moderating variable in the TAM theory. In addition, this study adds to the current body of knowledge by considering eWOM as a multi-dimensional construct novel in m-wallet literature. (shrink)

We obtain in this paper a representation of the formulae of extensions ofL by generalized quantifiers through functors between categories of first-order structures and partial isomorphisms. The main tool in the proofs is the back-and-forth technique. As a corollary we obtain the Caicedo's version of Fraïssés theorem characterizing elementary equivalence for such languages. We also discuss informally some geometrical interpretations of our results.

DNA double‐strand breaks (DSBs) are extremely hazardous lesions for all DNA‐bearing organisms and the mechanisms of DSB repair are highly conserved. In the eukaryotic mitotic cell cycle, DSBs are often present following DNA replication while, in meiosis, hundreds of DSBs are generated as a prelude to the reshuffling of the maternally and paternally derived genomes. In both cases, the DSBs are repaired by a process called homologous recombinational repair (HRR), which utilises an intact DNA molecule as the repair template. Mitotic (...) and meiotic HRR are managed by ‘checkpoints’ that inhibit cell division until DSB repair is complete. Here we attempt to summarise the substantial recent progress in understanding the checkpoint management of HRR in mitosis (focussing mainly on mammals) and then go on to use this information as a framework for understanding the presumed checkpoint management of HRR in mammalian meiosis. BioEssays 29:974–986, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Buildings are constructed for accommodating living and industrial needs. Floor cleaning robots have been developed to cater to the demand of these buildings. Area coverage and coverage time are crucial performance factors of a floor cleaning robot. Reconfigurable tiling robots have been introduced over fixed shape robots to improve area coverage in floor cleaning applications compared to robots with fixed morphologies. However, area coverage and coverage time of a tiling robot compromised one another. This study proposes a novel concept that (...) considers the ability of a tiling robot to configure both its morphology and size according to the environment. This concept is inspired by the pleomorphism that could be seen in bacteria. In this regard, P-hTetro, a pleomorphic tiling robot that can reconfigure its morphology and size, is considered. A novel coverage strategy for realizing the size reconfiguration is also proposed. According to this strategy, the robot covers obstacle-free areas with its maximum size, while an obstacle cluster is covered after shrinking to an optimum size. The optimum size for reconfiguration is determined by the genetic algorithm based on the arrangement of the environment. The performance and behavior of the proposed P-hTetro have been compared against that of an existing tiling robot which has a fixed size. According to the statistical outcomes, a tiling robot with the ability to reconfigure its size can significantly improve the performance in the aspects of area coverage and coverage time compared to a tiling robot with no ability to reconfigure its size. (shrink)

Background: Discussing treatment risks has become increasingly important in medical communication. Still, despite regulations, physicians must decide how much and what kind of information to present. Objective: To investigate patients’ preference for information about a small risk of a complication of colonoscopy, and whether medical and personal factors contribute to such preference. To propose a disclosure policy related to our results. Design: Vignettes study. Setting: Department of Gastroenterology, Academic Medical Centre, the Netherlands. Patients: 810 consecutive colonoscopy patients. Intervention: A home-sent (...) questionnaire containing three vignettes. Vignettes varied in the indication for colonoscopy, complication severity and level of risk. Patients were invited to indicate their wish to be informed and the importance of such information. In addition, sociodemograhic, illness-related and psychological characteristics were assessed. Main outcome measurements: Wish to be informed and importance of information. Results: Of 810 questionnaires, 68% were returned. Patients generally wished to be informed about low-risk complications, regardless of the indication for colonoscopy or the severity of the complication. The level of risk did matter, though (OR = 2.48, SE = 0.28, p = 0.001). The information was considered less important if done for population screening purposes or diagnosis of colon cancer, if the complication was less severe (bleeding) and if the risk was smaller (0.01% and 0.1%). Patients’ information preference was also related to age, mood and coping style. Limitations: Difficulty of vignettes. Conclusions: Patients generally wish to be informed about all possible risks. However, this might become uninformative. A stepwise approach is suggested. (shrink)

If self-interested behavior conflicts with the collective welfare, rules of cooperation are often installed to prevent egoistic behavior. We hypothesized that installing such rules may instigate personal moral norms of cooperation, but that they fail in doing so when installed by a leader who is self-interested rather than self-sacrificing. Three studies confirmed this and also showed that, consequently, only self-sacrificing leaders were able to install rules that increase cooperation without the need for a perfectly operating monitoring system.

In Chinese scholarship, Xunzi is often regarded as an eclectic Confucian master who accepted some form of utilitarian thoughts (e.g. Fung Yu-lan, Mou Zongsan and Xu Fuguan). This characteristic was also observed by some western scholars such as Benjamin I. Schwartz. In a recent study, I argued that the basic character of Xunzi’s philosophy is utilitarianism in a broad sense based on an examination on his intellectual criticism and political criticism. Xunzi asserts that humans are innately driven by self-interested desires, (...) and he evaluates all intellectual works and political behaviours by their utility. However, he does not limit utility to only basic animal desires such as food and sex. In Xunzi’s view, humans also have innate emotions; hence, these emotions should also be accounted for in their utility. This is similar to John Stuart Mill’s redefinition of Bentham’s concept of utility. Are Xunzi’s and Mill’s concepts of utility exactly the same? This question has yet to be examined. This article is a comparative study between utilitarianism and Xunzi’s philosophy which especially explores the compatibility of these two philosophies. (shrink)

Das Grab des Königs Ninetjer in Saqqara: Architektonische Entwicklung frühzeitlicher Grabanlagen in Ägypten. By Claudia M. Lacher-Raschdorff. Deutsches Archäologisches Institut Kairo, Archäologische Veröffentlichungen, vol. 125. Wiesbaden: Harrassowitz Verlag, 2014. Pp. 295, 44 pls., plans. €247.

In Computer Science stepwise refinement of algebraic specifications is a well-known formal methodology for rigorous program development. This paper illustrates how techniques from Algebraic Logic, in particular that of interpretation, understood as a multifunction that preserves and reflects logical consequence, capture a number of relevant transformations in the context of software design, reuse, and adaptation, difficult to deal with in classical approaches. Examples include data encapsulation and the decomposition of operations into atomic transactions. But if interpretations open such a new (...) research avenue in program refinement, (conceptual) tools are needed to reason about them. In this line, the paper’s main contribution is a study of the correspondence between logical interpretations and morphisms of a particular kind of coalgebras. This opens way to the use of coalgebraic constructions, such as simulation and bisimulation, in the study of interpretations between (abstract) logics. (shrink)

The study presents the broad outlines for a relationalist interpretation of the Indian epistemological doctrine svataḥ prāmāṇya. Due to the inadequacy of the main western interpretations thereof, the paper’s approach can be considered an inference to the best explanation. Its main part is devoted to the typologization of various epistemological doctrines based on the svataḥ prāmāṇya principle in terms of strong and weak disjunctivism. Three paradigm cases of strong disjunctivism and a special variety of weak disjunctivism have thus been identified (...) in Indian epistemology, which allowed to draw a conclusion that strong disjunctivism constituted one of its general paradigms. (shrink)