利用有限资源打造独一无二公司

有目的的选择是任何一家企业都必须要面临的决策之一。而最成功的公司都会非常清醒地去选择它们将要提供的产品、服务、客户群和营销渠道。与选择并驾齐驱的、摆在企业面前的另一重大挑战是:如何更好的利用有限资源——时间、金钱和人力资源——进行投资。所以,在销售、营销和服务的数据库中进行有目的的划分以提高有意识的选择将成为公司客户管理活动最有价值的奖品。并非所有的顾客都是平等的,因此,必须将有限的资源投入到那些最有潜在价值顾客身上,也就是将有限的资源直接投入到最能够得到回报的地方。我将这一举措称之为“以顾客需要为…     

Robust evaluation of fixed‐event forecast rationality

In this paper we introduce a new testing procedure for evaluating the rationality of fixed‐event forecasts based on a pseudo‐maximum likelihood estimator. The procedure is designed to be robust to departures in the normality assumption. A model is introduced to show that such departures are likely when forecasters experience a credibility loss when they make large changes to their forecasts. The test is illustrated using monthly fixed‐event forecasts produced by four UK institutions. Use of the robust test leads to the conclusion that certain forecasts are rational while use of the Gaussian‐based test implies that certain forecasts are irrational. The difference in the results is due to the nature of the underlying data. Copyright © 2001 John Wiley & Sons, Ltd.     

Lgr5 marks cycling, yet long-lived, hair follicle stem cells

In mouse hair follicles, a group of quiescent cells in the bulge is believed to have stem cell activity. Lgr5, a marker of intestinal stem cells, is expressed in actively cycling cells in the bulge and secondary germ of telogen hair follicles and in the lower outer root sheath of anagen hair follicles. Here we show that Lgr5(+) cells comprise an actively proliferating and multipotent stem cell population able to give rise to new hair follicles and maintain all cell lineages of the hair follicle over long periods of time. Lgr5(+) progeny repopulate other stem cell compartments in the hair follicle, supporting the existence of a stem or progenitor cell hierarchy. By marking Lgr5(+) cells during trafficking through the lower outer root sheath, we show that these cells retain stem cell properties and contribute to hair follicle growth during the next anagen. Expression analysis suggests involvement of autocrine Hedgehog signaling in maintaining the Lgr5(+) stem cell population.     

The landscape of recombination in African Americans

Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P?value 相似文献   

TULA-2, a novel histidine phosphatase, regulates bone remodeling by modulating osteoclast function

Bone is a dynamic tissue that depends on the intricate relationship between protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTP) for maintaining homeostasis. PTKs and PTPs act like molecular on and off switches and help modulate differentiation and the attachment of osteoclasts to bone matrix regulating bone resorption. The protein T cell ubiquitin ligand-2 (TULA-2), which is abundantly expressed in osteoclasts, is a novel histidine phosphatase. Our results show that of the two family members, only TULA-2 is expressed in osteoclasts and that its expression is sustained throughout the course of osteoclast differentiation, suggesting that TULA-2 may play a role during early as well late stages of osteoclast differentiation. Skeletal analysis of mice that do not express TULA or TULA-2 proteins (DKO mice) revealed that there was a decrease in bone volume due to increased osteoclast numbers and function. Furthermore, in vitro experiments indicated that bone marrow precursor cells from DKO mice have an increased potential to form osteoclasts. At the molecular level, the absence of TULA-2 in osteoclasts results in increased Syk phosphorylation at the Y352 and Y525/526 residues and activation of phospholipase C gamma 2 (PLCγ2) upon engagement of immune-receptor-tyrosine-based-activation-motif (ITAM)—mediated signaling. Furthermore, expression of a phosphatase-dead TULA-2 leads to increased osteoclast function. Taken together, these results suggest that TULA-2 negatively regulates osteoclast differentiation and function.     

Deliberative Inquiry: Integrated Ways of Working in Children Services

In striving for greater integration of children services across a number of government and non government agencies, this paper examines the effect of drawing on deliberative inquiry as the lever for realising greater alignment across agencies. The paper discusses the need for improvement in UK local government children??s services and then offers a review of the dialogue based inquiry approaches. In so doing, the paper highlights the Socratic mode of inquiry, emphasising the dual strategies of penetrative questioning, elenchus, and the process of founding new knowledge through working through confusion, aporia. This paper then reports how a London borough realised sustained change through the adoption of deliberative inquiry. The study achieved successful integration through the penetrating and contextually sensitive dialogue the inquiry participants generated, allowing them to develop the capability for realising effective organisational change. The paper concludes that deliberative inquiry facilitates individuals to speak their concerns in a manner that prompts ??consensually accepted beliefs?? to emerge through paying equal attention to the motivation of the inquiry participants, as well as to the reality of the contextual demands they need to confront.     

An isoform of the vacuolar (H+)-ATPase accessory subunit Ac45

The vacuolar (H⁺)-ATPase (V-ATPase) is the main regulator of intraorganellar pH and in neuroendocrine cells is controlled by its accessory subunit, Ac45. Here, we report the discovery of the first isoform of a V-ATPase accessory subunit, namely an Ac45-like protein, denoted Ac45LP. Phylogenetic analysis revealed a lineage-dependent evolutionary history: Ac45 is absent in birds, and Ac45LP is absent in placental mammals, whereas all other tetrapod species contain both genes. In contrast to Ac45, Ac45LP is not proteolytically cleaved, a prerequisite for proper Ac45 routing. Intriguingly, Xenopus Ac45LP mRNA was expressed in developing neural tissue and in neural crest cells. In adult Xenopus, Ac45 mRNA is widely expressed mostly in neuroendocrine tissues, while Ac45LP mRNA expression was found to be restricted to the kidney and the lung. This novel Ac45LP may provide additional possibilities for V-ATPase regulation during neurodevelopment as well as in kidney and lung cells.