The TASCC of Secretion

Author Manuscript 2012 July 05The oncogene-induced activation of signaling pathways involving the tumor suppressor proteins p53 and retinoblastoma is likely an important mechanism for preventing the proliferation of potential cancer cells (1, 2). This activation causes cells to exit the cell division cycle and enter a senescent state, which is characterized by major changes in chromatin structure that are thought to render senescence irreversible. Despite the absence of proliferation, senescent cells are not as quiescent as first thought, as they signal to their surrounding environment by activating a protein secretion program (3, 4). On page 966 of this issue, Narita et al. (5) show that to enable this secretory state, a senescent cell profoundly reorganizes its endomembrane system

The Handover in Hong Kong: Impact on Business Formation

Although the 1997 handover of Hong Kong from the United Kingdom to China was a major political transformation, its impact on new business formation has not been fully scrutinized. Theory suggests contradictory forces may operate before, during, and after such a transformation: either a decline due to uncertainty or an increase due to opportunities created. To determine which force dominated, we first decomposed the analysis by the size of major affected social groups, then analyzed the expected impact. This led us to predict an aggregate depression of business formation, although this effect likely showed great variation and attenuated over time. Our empirical assessment relied on detailed monthly records of business registrations from 1975 to 2013, using GARCH time series modeling to analyze total registrations as well as the proportions for local and non-local businesses. Controlling for macro socioeconomic conditions, we find the registration rate dropped significantly throughout the post-handover era, implying a dominance of uncertainty. Further, new registrations displayed higher volatility following the 1984 announcement of the handover, reflecting shifting public sentiment in the interim about Hong Kong’s economic prospects. We also find a post-handover preference for forming non-local firms with higher asset mobility; this preference diminishes with time

Antecedents of Ethical Decision Making by physician assistants and nurse practitioners: validation of instruments and their application

The dissertation contains studies into the antecedents of ethical decision-making among Dutch physician assistants and nurse practitioners. In this, use was made of existing and self-developed questionnaires that have been validated

The predictive values of a deliberative and a paternalistic attitude towards two situations of moral conflict:A study among Dutch nurse practitioners and physician assistants

Background In this study, we examined the predictive values of a moral deliberate and paternalistic attitude on the propensity of yielding to pressure. In these hypothesised positive and negative relationships, we further sought to ascertain whether moral disengagement plays a pivotal role when individuals deviate from ethical standards, rules and regulations when yielding to pressure. Aim(s) This study's primary aim was to assess the predictive value of a moral deliberative and paternalistic attitude for yielding to pressure when physician assistants (PAs) and nurse practitioners (NPs) face moral conflicts. Method This validation study was cross-sectional and based on a convenience sample of Dutch PAs and NPs. The MSQ-DELIB and MSQ-PATER scales indicate a moral deliberate or paternalistic attitude. These scales were assumed to have a predictive value towards the degree of yielding to pressure by PAs and NPs. Yielding to pressure was measured by two vignettes in which respondents faced a moral conflict (vignette 1: prescribing unindicated antibiotics and vignette 2: discharging a difficult patient from the hospital). Results Only moral deliberation was a significant predictor of yielding to pressure. That is, we found a positive effect in vignette 1 (in which the pressure came from the patient). In contrast, we found a negative relationship in vignette 2 (in which pressure went from the working environment). Paternalism did not affect yielding to pressure in either vignette. Conclusion This study suggests that PAs and NPs having a moral deliberative attitude makes them receptive to pressure exerted by patients to break moral standards. On the other hand, they are more resilient against doing so when this pressure comes from different sources than the patient. Further research is needed to find more conclusive evidence for this differential effect

The Re-Emergence of Foreign Banks in Shanghai: An Ecological Analysis

Is China, met een van de snelst groeiende economieën ter wereld, inderdaad de markt van de hoge opbrengsten en snelle winsten zoals de media en de communis opinio ons willen doen geloven? Dit boek biedt een wat gematigder perspectief. Het laat zien, door de theorieën en methoden van de organisatie-ecologie te gebruiken, dat de complexiteit van de lokale markt vaak wordt onderschat. Op basis van een gedetailleerde analyse van de (wederom) opkomende populatie van buitenlandse banken in Shanghai, laat het zien dat nu meer en meer buitenlandse banken vestigingen opzetten in Shanghai, de concurrentie tussen deze banken dermate toeneemt dat het de toetrede van nieuwe banken in Shanghai in de weg staat. Buitenlandse banken hebben ook te maken met lange wachttijden voordat zij kunnen beginnen met het aanbieden van financiële diensten en daarnaast wordt hun winstgevendheid beïnvloedt door het toenemende aantal lokale banken. Vanuit een theoretisch perspectief dragen de bevindingen van dit onderzoek bij aan de studie naar her-opkomende organisatievormen, de studie naar de ecologische dynamiek voorafgaand aan de toetrede tot een populatie, en theorieën met betrekking tot concurrentie tussen populaties zoals die van de ‘middelenverdeling’.Is China, with one of the world’s fastest growing economies, indeed the market of high returns and quick profits as the popular press and communis opinio seem to suggest? This book offers a more moderated perspective. It shows, by employing theories and methods from the field of organizational ecology, that the intricacies of the local market might frequently have been underestimated. Based on a detailed analysis of the re-emerging population of foreign banks in Shanghai, it points out that as more and more foreign banks set up operations in Shanghai, competition among them is intensifying to the extent that it is deterring the founding of new foreign banks in Shanghai. Foreign banks furthermore face long waiting times before they can start providing banking services and, in addition, their profitability is affected by the growing number of domestic banks. From a theoretical perspective, the findings in this book add significantly to the study of re-emerging organizational forms, the study of ecological dynamics prior to entry into a population, and theories concerning inter-population competition such as resource partitioning.Jeroen Kuilman was born in Hoogezand-Sappemeer on May 8, 1979. He attended Collegium Marianum in Venlo, from which he received his Atheneum diploma in 1997. After high school, Jeroen went on to study International Business at the University of Maastricht. He worked at Hewlett-Packard in Germany in 2000 and was an exchange student at Keimyung University, South Korea, in 2001. In October 2001, Jeroen received his Master’s degree with a thesis on headquarter-subsidiary relationships within multinational corporations. In November 2001, Jeroen became a Ph.D. student in the Department of Organization and Personnel Management at Erasmus University Rotterdam. He traveled to Shanghai at the end of his second year as a doctoral student, to collect data on the history of the local banking industry during three months of field research. In the spring semester of 2004, Jeroen studied at Stanford University where he was trained in ecological theory and methods of analysis. During his time as a doctoral student, he presented papers at several major international conferences and seminars, such as the Annual Meeting of the Academy of Management and the Organizational Ecology Conference at the University of Durham. Jeroen will be working as a post-doctoral researcher at RSM Erasmus University as of November 1, 2005. His main research interests include organizational ecology, industry evolution, and international business

The cerebral cavernous malformation 3 gene is necessary for senescence induction.

Mutations in cerebral cavernous malformation 3 gene are known to result in development of vascular malformations and have recently been proposed to also give rise to meningiomas. We report in this study that lack of CCM3 unexpectedly impairs the senescence response of cells, and this is related to the inability of CCM3-deficient cells to induce the C/EBPβ transcription factor and implement the senescence-associated secretory phenotype. Induction of C/EBPβ and cytokines is also impaired in the absence of CCM3 in response to cytokines in nonsenescent cells, pointing to it being a primary defect and not secondary to impaired senescence. CCM3-deficient cells also have a defect in autophagy at late passages of culture, and this defect is also not dependent on impaired senescence, as it is evident in immortal cells after nutrient starvation. Further, these two defects may be related, as enforcing autophagy in CCM3-deficient late passage cells increases C/EBPβ cytokine expression. These results broaden our knowledge on the mechanisms by which CCM3 deficiency results in disease and open new avenues of research into both CCM3 and senescence biology

Are Dutch patients willing to be seen by a physician assistant instead of a medical doctor?

Background The employment of physician assistants (PAs) is a strategy to improve access to care. Since the new millennium, a handful of countries have turned to PAs as a means to bridge the growing gap between the supply and demand of medical services. However, little is known about this new workforce entity from the patient’s perspective. The objective of this study was to assess the willingness of Dutch patients to be treated by a PA or a medical doctor (MD) under various time constraints and semi-urgent medical scenarios. Methods A total of 450 Dutch adults were recruited to act as surrogate patients. A convenience sample was drawn from patients in a medical office waiting room in a general hospital awaiting their appointments. Each participant was screened to be naive as to what a PA and a nurse practitioner are and then read a definition of a PA and an MD. One of three medical scenarios was assigned to the participants in a patterned 1-2-3 strategy. Patients were required to make a trade-off decision of being seen after 1 hour by a PA or after 4 hours by a doctor. This forced-choice method continued with the same patient two more times with 30 minutes and 4 hours and another one of 2 hours versus 4 hours for the PA and MD, respectively. Results Surrogate patients chose the PA over the MD 96 % to 98 % of the time (depending on the scenario). No differences emerged when analysed by gender, age, or parenthood status. Conclusion Willingness to be seen by a PA was tested a priori to determine whether surrogate Dutch patients would welcome this new health-care provider. The findings suggest that employing PAs, at least in concept, may be an acceptable strategy for improving access to care with this population

Rapid Identification of a Scalable Catalyst for the Asymmetric Hydrogenation of a Sterically Demanding Aryl Enamide

High throughput screening was used to find a cost-effective and scalable catalyst for the asymmetric hydrogenation of a sterically demanding enamide as an intermediate towards a new potent melanocortin receptor agonist useful in the treatment of obesity. Lessons drawn from the testing of a first library of 96 chiral monodentate phosphoramidites led to the design of a second focused library of 16 chiral ligands, allowing the discovery of a new efficient catalyst. This catalyst was based on rhodium and a bulky monodentate phosphite ligand. The catalyst was scaled up and used in the kilogram production of the desired bulky chiral amide