CDKN2A is not the principal target of deletions on the short arm of chromosome 9 in neuroendocrine (Merkel cell) carcinoma of the skin

The majority of small-cell lung cancers (SCLCs) express p16 but not pRb, Given our previous study showing loss of pRb in Merkel cell carcinoma (MCC)/neuroendocrine carcinoma of the skin and the clinicopathological similarities between SCLC acid MCC, we wished to determine if this was also the case in MCC, Twenty-nine MCC specimens from 23 patients were examined for deletions at 10 loci on 9p and I on 9p. No loss of heterozygosity (LO H) was peen in 9 patients including 2 for which tumour and cell line DNAs were examined. Four patients had LOH for all informative loci on 9p, Ten tumours showed more limited regions of loss on 9p, and from these 2 common regions of deletion were determined, Half of all informative cases had LOH at D95168, the most telomeric marker examined, and 3 specimens showed loss of only D9S168, A second region (InFNA-D9S126) showed L0H in 10(44%) cases, and case MCC26 showed LOH for only D9S126, implicating genes centromeric of the CDKN2A locus. No mutations in the coding regions of p16 were seen in 7 cell lines tested, and reactivity to anti-p16 antibody was seen in all Il tumour specimens examined and in 6 of 7 cell lines from 6 patients. Furthermore, all cell lines examined reacted with anti-p 14' antibody, These results suggest that neither transcript of the CDKN2A locus is the target of deletions on 9p in MCC and imply the existence of tumour-suppressor genes mapping both centromeric and telomeric of this locus. (C) 2001 Wiley-Liss, Inc.

G2 phase cell cycle arrest in human skin following UV irradiation

The contribution of the short wavelength ultraviolet (UV) component of sunlight to the aetiology of skin cancer has been widely acknowledged, although its direct contribution to tumour initiation or progression is still poorly understood. The loss of normal cell cycle controls, particularly checkpoint controls, are a common feature of cancer. UV radiation causes both GI and G2 phase checkpoint arrest in vitro cultured cells. In this study we have investigated the cell cycle responses to suberythemal doses of UV on skin. We have utilized short-term whole organ skin cultures, and multi parameter immunohistochemical and biochemical analysis to demonstrate that basal and suprabasal layer melanocytes and keratinocytes undergo a G2 phase cell cycle arrest for up to 48 h following irradiation. The arrest is associated with increased p16 expression but no apparent p53 involvement. This type of organ culture provides a very useful model system, combining the ease of in vitro manipulation with the ability to perform detailed molecular analysis in a normal tissue environment.

Localization of neurotransmitters and calcium binding proteins to neurons of salamander and mudpuppy retinas

We wished to identify the different types of retinal neurons on the basis of their content of neuroactive substances in both larval tiger salamander and mudpuppy retinas, favored species for electrophysiological investigation. Sections and wholemounts of retinas were labeled by immunocytochemical methods to demonstrate three calcium binding protein species and the common neurotransmitters, glycine, GABA and acetylcholine. Double immunostained sections and single labeled wholemount retinas were examined by confocal microscopy. Immunostaining patterns appeared to be the same in salamander and mudpuppy. Double and single cones, horizontal cells, some amacrine cells and ganglion cells were strongly calbindin-immunoreactive (IR). Calbindin-IR horizontal cells colocalized GABA. Many bipolar cells, horizontal cells, some amacrine cells and ganglion cells were strongly calretinin-IR. One type of horizontal cell and an infrequently occurring amacrine cell were parvalbumin-IR. Acetylcholine as visualized by ChAT-immunoreactivity was seen in a mirror-symmetric pair of amacrine cells that colocalized GABA and glycine. Glycine and GABA colocalized with calretinin, calbindin and occasionally with parvalbumin in amacrine cells. (C) 2001 Elsevier Science Ltd. All rights reserved.

Differences between older volunteers and nonvolunteers - Attitudinal, normative, and control beliefs

It has been suggested that older people are a rich potential source of volunteers, as prior literature has highlighted the benefits and rewards of volunteering in later life. This article examines differences between volunteers and nonvolunteers in a random sample of older people resident in Brisbane, Australia. Using the theory of planned behavior as a framework, the article focuses on the beliefs that distinguish those who volunteer from those who do not. Findings from the study allowed for an assessment of both the costs and benefits associated with volunteering; beliefs about the support of others, including the broader community, to volunteer; and beliefs about the barriers that might prevent volunteering. The implications of these finding's to a country with an aging population are discussed.

The impact of an expert's gender on jurors' decisions

This study uses a simulated civil trial to examine the effect of a male expert's testimony in a male-dominated industry as compared to a female expert's testimony in a traditionally female-dominated industry. ... As noted by Cooper et al., research on persuasion has reliably demonstrated that, under conditions of message complexity, people rely on heuristic cues rather than the content of the message when judging its validity. ... Similarly, Swenson, Nash, and Roos determined that a female expert witness in a child custody dispute was perceived as possessing greater expertise than a male expert, although this difference was only marginally significant. Findings from an unpublished dissertation, which investigated the influence of expert gender in a case involving child sexual abuse, also found some support, in terms of whether or not jurors reached a verdict in a specified period of time or remained hung, for the hypothesis that a female expert would be more influential than her male counterpart. ... Within each of these trial domains (construction, women's clothing), the second experimental variable was manipulated by varying the gender of the plaintiff's expert witness, with half of the participants receiving testimony from a female expert (Dr. Elizabeth Pinder) and half of the participants receiving testimony from a male expert (Dr. Michael Pinder).

Status, legitimacy and ingroup bias in the context of an organizational merger

Adopting an intergroup perspective, the research was designed to examine predictors of employee responses to an organizational merger. Data were collected from 120 employees of a newly merged scientific organization. As predicted from social identity theory, the most negative responses to the merger were apparent among the employees of the low status premerger organization. There was also evidence of ingroup bias among both groups of employees involved in the merger—as expected, the bias was most marked on the status-irrelevant dimensions for the employees of the lower status organization, but most marked on the status-relevant dimensions for the employees of the high status organization. Also, in support of social identity theory, the perceived legitimacy of the basis for the status differentiation between the groups was associated with more positive responses to the merger among employees of the low status premerger organization, but with poorer responses among employees of the high status premerger organization. There was consistent evidence that the status by legitimacy interaction was mediated through the extent to which employees of the newly merged organization perceived a common ingroup identity

Employee adjustment to an organizational merger: An intergroup perspective

Adopting an intergroup perspective, the research was designed to examine predictors of employee responses to an organizational merger Data were collected from 465 fleet staff employed in a newly merged airline company. As predicted from social identity theory, the negative effects of the merger were most marked for employees of the low-status premerger organization. Also, as predicted, the perception of permeable intergroup boundaries in the new organization was associated positively with identification with the new organization and both job-related and person-related outcomes among employees of the low-status premerger organization but negatively with person-related outcomes among employees of the high-status premerger organization. As predicted, there was some evidence that the main and interactive effects involving status, perceived permeability, and intergroup contact on employee adjustment were mediated through strength of identification with the new organization.

Incremental parsing in language-based editors: user needs and how to meet them

Incremental parsing has long been recognized as a technique of great utility in the construction of language-based editors, and correspondingly, the area currently enjoys a mature theory. Unfortunately, many practical considerations have been largely overlooked in previously published algorithms. Many user requirements for an editing system necessarily impact on the design of its incremental parser, but most approaches focus only on one: response time. This paper details an incremental parser based on LR parsing techniques and designed for use in a modeless syntax recognition editor. The nature of this editor places significant demands on the structure and quality of the document representation it uses, and hence, on the parser. The strategy presented here is novel in that both the parser and the representation it constructs are tolerant of the inevitable and frequent syntax errors that arise during editing. This is achieved by a method that differs from conventional error repair techniques, and that is more appropriate for use in an interactive context. Furthermore, the parser aims to minimize disturbance to this representation, not only to ensure other system components can operate incrementally, but also to avoid unfortunate consequences for certain user-oriented services. The algorithm is augmented with a limited form of predictive tree-building, and a technique is presented for the determination of valid symbols for menu-based insertion. Copyright (C) 2001 John Wiley & Sons, Ltd.

Time-dependent master equation simulation of complex elementary reactions in combustion: Application to the reaction of (CH2)-C-1 with C2H2 from 300-2000 K

Computational simulations of the title reaction are presented, covering a temperature range from 300 to 2000 K. At lower temperatures we find that initial formation of the cyclopropene complex by addition of methylene to acetylene is irreversible, as is the stabilisation process via collisional energy transfer. Product branching between propargyl and the stable isomers is predicted at 300 K as a function of pressure for the first time. At intermediate temperatures (1200 K), complex temporal evolution involving multiple steady states begins to emerge. At high temperatures (2000 K) the timescale for subsequent unimolecular decay of thermalized intermediates begins to impinge on the timescale for reaction of methylene, such that the rate of formation of propargyl product does not admit a simple analysis in terms of a single time-independent rate constant until the methylene supply becomes depleted. Likewise, at the elevated temperatures the thermalized intermediates cannot be regarded as irreversible product channels. Our solution algorithm involves spectral propagation of a symmetrised version of the discretized master equation matrix, and is implemented in a high precision environment which makes hitherto unachievable low-temperature modelling a reality.

Time evolution in the unimolecular master equation at low temperatures: full spectral solution with scalable iterative methods and high precision

A new method is presented to determine an accurate eigendecomposition of difficult low temperature unimolecular master equation problems. Based on a generalisation of the Nesbet method, the new method is capable of achieving complete spectral resolution of the master equation matrix with relative accuracy in the eigenvectors. The method is applied to a test case of the decomposition of ethane at 300 K from a microcanonical initial population with energy transfer modelled by both Ergodic Collision Theory and the exponential-down model. The fact that quadruple precision (16-byte) arithmetic is required irrespective of the eigensolution method used is demonstrated. (C) 2001 Elsevier Science B.V. All rights reserved.