bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of survival in surgical unresectable lung cancer by artificial neural networks including genetic polymorphisms and clinical parameters
Authors: Hsia Te‐Chun , Chiang Hung‐Chih , Chiang David , Hang Liang‐Wen , Tsai Fuu‐Jen , Chen Wen‐Chi
Published: November 2003

Lung cancer, a common malignancy in Taiwan, involves multiple factors, including genetics and environmental factors. The survival time is very short once cancer is diagnosed as being in advanced stage and surgically unresectable. Therefore, a good model of prediction of disease outcome is important for a treatment plan. We investigated the survival time in advanced lung cancer by using computer science from the genetic polymorphism of the p21 and p53 genes in conjunction with patients' general data. We studied 75 advanced and surgical unresectable lung cancer patients. The prediction of survival time was made by comparing real data obtained from follow‐up periods with data generated by an artificial neural network (ANN). The most important input variable was the clinical staging of lung cancer patients. The second and third most important variables were pathological type and responsiveness to treatment, respectively. There were 25 neurons in the input layer, four neurons in the hidden layer‐1, and one neuron in the output layer. The predicted accuracy was 86.2%. The average survival time was 12.44 ± 7.95 months according to real data and 13.16 ± 1.77 months based on the ANN results. ANN provides good prediction results when clinical parameters and genetic polymorphisms are considered in the model. It is possible to use computer science to integrate the genetic polymorphisms and clinical parameters in the prediction of disease outcome. Data mining provides a promising approach to the study of genetic markers for advanced lung cancer. J. Clin. Lab. Anal. 17:229–234, 2003. © 2003 Wiley‐Liss, Inc.
Aerosol chemical composition in Asian continental outflow during the TRACE‐P campaign: Comparison with PEM‐West B
Authors: Dibb Jack E. , Talbot Robert W. , Scheuer Eric M. , Seid Garry , Avery Melody A. , Singh Hanwant B.
Published: November 2003

Aerosol associated soluble ions and the radionuclide tracers 7Be and 210Pb were quantified in 414 filter samples collected in spring 2001 from the DC‐8 during the Transport and Chemical Evolution over the Pacific (TRACE‐P) campaign. Binning the data into near Asia (flights from Hong Kong and Japan) and remote Pacific (all other flights) revealed large enhancements of NO3−, SO4=, C2O4=, NH4+, K+, Mg2+, and Ca2+ near Asia. The boundary layer and lower troposphere were most strongly influenced by continental outflow, and the largest enhancements were seen in Ca2+ (a dust tracer) and NO3− (reflecting uptake of HNO3 onto the dust). Comparing the TRACE P near Asia bin with earlier results from the same region during PEM‐West B (in 1994) shows at least twofold enhancements during TRACE P in most of the ions listed above. Calcium and NO3− were most enhanced in this comparison as well (more than sevenfold higher in the boundary layer and threefold higher in the lower troposphere). Independent estimation of Asian emissions of gaseous precursors of the aerosol‐associated ions suggest only small changes between the two missions, and precipitation fields do not suggest any significant difference in the efficiency of the primary sink, precipitation scavenging. It thus appears that with the possible exception of dust, the enhancements of aerosol‐associated species during TRACE P cannot be explained by stronger sources or weaker sinks. We argue that the enhancements largely reflect the fact that TRACE P focused on characterizing Asian outflow, and thus the DC‐8 was more frequently flown into regions that were influenced by well‐organized flow off the continent.
Regional‐scale chemical transport modeling in support of the analysis of observations obtained during the TRACE‐P experiment
Authors: Carmichael G. R. , Tang Y. , Kurata G. , Uno I. , Streets D. , Woo J.‐H. , Huang H. , Yienger J. , Lefer B. , Shetter R. , Blake D. , Atlas E. , Fried A. , Apel E. , Eisele F. , Cantrell C. , Avery M. , Barrick J. , Sachse G. , Brune W. , Sandholm S. , Kondo Y. , Singh H. , Talbot R. , Bandy A. , Thorton D. , Clarke A. , Heikes B.
Published: November 2003

Data obtained during the TRACE‐P experiment is used to evaluate how well the CFORS/STEM‐2K1 regional‐scale chemical transport model is able to represent the aircraft observations. Thirty‐one calculated trace gas and aerosol parameters are presented and compared to the in situ data. The regional model is shown to accurately predict many of the important features observed. The mean values of all the model parameters in the lowest 1 km are predicted within ±30% of the observed values. The correlation coefficients (R) for the meteorological parameters are found to be higher than those for the trace species. For example, for temperature, R > 0.98. Among the trace species, ethane, propane, and ozone show the highest values (0.8 < R < 0.9), followed by CO, SO2, and NOy. NO and NO2 had the lowest values (R < 0.4). Analyses of pollutant transport into the Yellow Sea by frontal events are presented and illustrate the complex nature of outflow. Biomass burning from SE Asia is transported in the warm conveyor belt at altitudes above ∼2 km and at latitudes below 30N. Outflow of pollution emitted along the east coast of China in the postfrontal regions is typically confined to the lower ∼2 km and results in high concentrations with plume‐like features in the Yellow Sea. During these situations the model underpredicts CO and black carbon (among other species). An analysis of ozone production in this region is also presented. In and around the highly industrialized regions of East Asia, where fossil fuel usage dominates, ozone is NMHC‐limited. South of ∼30–35N, ozone production is NOx‐limited, reflecting the high NMHC/NOx ratios due to the large contributions to the emissions from biomass burning, biogenics sources, and biofuel usage in central China and SE Asia.
The new Athena alpha particle X‐ray spectrometer for the Mars Exploration Rovers
Authors: Rieder R. , Gellert R. , Brückner J. , Klingelhöfer G. , Dreibus G. , Yen A. , Squyres S. W.
Published: November 2003

The new alpha particle X‐ray spectrometer (APXS) is part of the Athena payload of the two Mars Exploration Rovers (MER). The APXS sensor head is attached to the turret of the instrument deployment device (IDD) of the rover. The APXS is a very light‐weight instrument for determining the major and minor elemental composition of Martian soils, rocks, and other geological materials at the MER landing sites. The sensor head has simply to be docked by the IDD on the surface of the selected sample. X‐ray radiation, excited by alpha particles and X rays of the radioactive sources, is recorded by a high‐resolution X‐ray detector. The X‐ray spectra show elements starting from sodium up to yttrium, depending on their concentrations. The backscattered alpha spectra, measured by a ring of detectors, provide additional data on carbon and oxygen. By means of a proper calibration, the elemental concentrations are derived. Together with data from the two other Athena instruments mounted on the IDD, the samples under investigation can be fully characterized. Key APXS objectives are the determination of the chemistry of crustal rocks and soils and the examination of water‐related deposits, sediments, or evaporates. Using the rock abrasion tool attached to the IDD, issues of weathering can be addressed by measuring natural and abraded surfaces of rocks.
Anticipated synchronization: A metaphorical linear view
Authors: Calvo Oscar , Chialvo Dante R. , Eguı́luz Victor M. , Mirasso Claudio , Toral Raúl
Published: November 2003

We study the regime of anticipated synchronization recently described on a number of dynamical systems including chaotic ones. We use simple linear caricatures to show the minimal setups able to reproduce the basic facts described.
Communication with a chaotic traveling wave tube microwave generator
Authors: Dronov Vasily , Hendrey Matthew R. , Antonsen Thomas M. , Ott Edward
Published: November 2003

Traveling wave tubes (TWTs) are vacuum electronic amplifiers (see Beck, Gittins, and Pierce) that are commonly used for communication in the centimeter wavelength range. Increasing demand for high data flow in wireless communication systems (satellite communication systems are a good example) raises needs for making TWT’s more compact and efficient. Motivated by this we suggest a scheme in which a TWT with feedback is operated in a highly nonlinear regime where the device behaves chaotically. The chaos is controlled using small controls. Then, at the receiving end a receiving TWT synchronizes to the chaotic transmitter and amplifies the received signal with nearly no distortion. Results on numerical simulations of the proposed scheme are reported and used to evaluate its effectiveness.
On the long-run average growth rate of chaotic systems
Authors: Huang Weihong
Published: November 2003

For a discrete dynamical process defined by Xt=F(Xt−1,Xt−2,…,Xt−k), where Xt∈R+n, the growth rate for the ith endogenous variable is conventionally defined as git≡(xit+1−xit)/xit. It is shown that, when the trajectories of xit exhibit periodic or aperiodic (chaotic) fluctuations within a bounded range, the long-run average growth rates are always positive, that is, 〈git〉≡limT→∞1/T∑t=1Tgit>0,∀i, so as to induce an illusion of growth. The fact is generic in the sense of being irrespective of the dynamic structure of F. Moreover, the same characteristic exists even if the process is reversed. Economic implications and applications are discussed. It is concluded that the statistical inequalities provide additional measures to check the validity of different discrete models or to test different specifications from empirical time series.
Multimodal synchronization of chaos
Authors: Campos E. , Urı́as J. , Rulkov N. F.
Published: November 2003

An elementary notion of master–slave synchronization that accepts multimodal synchronization is introduced. We prove rigorously that the attractor of a coupled pair in a regime of multimodal synchronization is the graph of a multivalued function. Our framework provides the theoretical basis for some practical tools for detection of multimodal synchrony in experiments. Results are illustrated with the analysis of experiments with coupled electronic oscillators.
Male mate choice and patterns of paternity in the polyandrous, sexually cannibalistic orb-web spider, Nephila plumipes
Authors: Elgar Mark A. , Bruce Mathew J. , Crespigny Fleur E. Champion de , Cutler Anna R. , Cutler Cathryn L. , Gaskett Anne C. , Herberstein Marie E. , Ramamurthy Sharada , Schneider Jutta M.
Published: November 2003

Studies that investigate patterns of paternity in polyandrous species typically employ double-mating trials, in which the paternity share of each male is established by either the sterile male technique or using genetic markers. However, polyandrous females may mate with more than two males and, in some species, triple-mating trials produce different patterns of paternity from double-mating trials. We investigated patterns of paternity share in triple-mating trials of the sexually cannibalistic orb-web spider Nephila plumipes. These experiments reveal little quantitative changes to paternity share when more than two males mate with the female; the third male apparently diluted the fertilisation success of the second male but not of the first male. Sexual cannibalism had little impact on the fertilisation success of the first male, but greatly increased the fertilisation success of the third male. When offered a choice, males did not prefer to mate with virgin over mated females, but males that chose virgin females were significantly heavier than those that chose mated females.
Task variations and attention shifts in young children’s category learning
Authors: Ford Ruth M.
Published: November 2003

Two studies examined the conditions under which 6-year-old children succeeded in discovering prototypical information within ill-defined categories for fictitious animals that had salient individuating properties. Following either incidental or intentional learning of a single category, children attended to both prototypical and instance-specific features when judging the category membership of new examples (Experiment 1). When the same category was contrasted with a similar category in a sorting-with-feedback procedure, children relied on prototypical features in categorisation despite the fact that instance-specific features dominated their recognition-memory judgements (Experiment 2). The results show young children to be capable of shifting their attention to different kinds of category attributes according to the conditions of category formation and the nature of the assessment task.
Directly Assessing the Relationship between Irrelevant Speech and Articulatory Suppression
Authors: Neath Ian , Farley Lisa A. , Surprenant Aimée M.
Published: November 2003

Larsen and Baddeley (2003) examine whether the disruption caused by articulatory suppression on immediate memory tasks is similar to or different from the disruption caused by irrelevant speech. Based on experiments in which they test whether the phonological similarity effect is present or absent, they conclude that articulatory suppression and irrelevant speech are different. We assessed whether articulatory suppression and irrelevant speech are similar or different by correlating the disruption each causes. A significant correlation obtained, indicating a relation between the two. These apparently different conclusions can be readily resolved by adopting the view that articulatory suppression, irrelevant speech, and many other factors vary in the degree to which they are likely to cause subjects to abandon reliance on phonological/acoustic cues in particular tasks.
Disruption of Verbal Stm by Irrelevant Speech, Articulatory Suppression, and Manual Tapping: Do they have a Common Source?
Authors: Larsen Janet D. , Baddeley Alan
Published: November 2003

Under appropriate conditions, immediate serial verbal recall is impaired by irrelevant speech, articulatory suppression, and syncopated tapping. Interpretation of these variables in terms of the phonological loop component of working memory assumes separate phonological storage and articulatory rehearsal processes. In contrast, the Object-Oriented Episodic Record (O-OER) of Jones and the feature theory of Neath interpret these and other phenomena in terms of a unitary multimodal system. Three experiments investigate these disrupting tasks, with each experiment emphasizing one parameter. In each case, recall of phonologically similar and dissimilar letter sequences is compared as a marker of the presence or absence of phonological coding. In Experiment 1, subjects heard or articulated a single item, or tapped a single key at equal intervals. Only articulatory suppression impaired performance; it also abolished the effects of phonological similarity. Experiment 2 was identical, except that items were heard, or generated in a syncopated rhythm. Both suppression and tapping impaired performance to an equivalent extent and obliterated the effect of phonological similarity. Syncopated irrelevant speech caused a modest but significant impairment in performance. Experiment 3 was identical to Experiment 1, except that six tokens were used. Irrelevant speech and tapping had a clear impact on recall, but neither removed the phonological similarity effect. Again articulatory suppression had a major impact on performance and removed the effect of phonological similarity. We conclude that the pattern of results readily fits the phonological loop hypothesis, provided one accepts Saito's proposal that generating syncopated sequences uses common processes with speech production. It is not clear how the results can be explained by either the O-OER or the feature hypothesis.
Reification of phonological storage
Authors: Macken William J. , Jones Dylan M.
Published: November 2003

We question the arguments and data presented by Larsen and Baddeley (this issue 2003) in support of the phonological loop account of verbal short-term memory on a number of grounds. These include the correlation between effect size and the presence of a phonological similarity effect in the data, and the existence elsewhere in the literature of effects of articulatory suppression and interference between verbal and nonverbal information that undermines the phonological loop account. We question the idea that short-term memory phenomena are best conceived of in terms of phonological storage, and we sketch an alternative perspective that does not rely on the notion of a bespoke phonological store, an entity that we argue represents a reification.
The Interplay of Stop Signal Inhibition and Inhibition of Return
Authors: Taylor Tracy L. , Ivanoff Jason
Published: November 2003

Inhibition of return (IOR) refers to slower responding to a stimulus that appears in the same rather than a different location as that of a preceding stimulus. The goal of the present study was to examine the relationship between IOR and stop signal inhibition. Participants were presented with two stimuli (S1 and S2) on each trial. On half of the trials (go trials), participants were required to make a speeded button-press response to report the location of S1; on the other half of trials (stop trials), they were required to cancel the response to S1, as indicated by the appearance of a stop signal at a variable delay (stop signal delay, SSD) after the appearance of S1. Success in cancelling an S1 response varied directly as a function of the SSD: The longer the delay, the more difficult it was for participants to cancel the prepared response. We examined the magnitude of IOR in the S2 reaction times as a function of whether participants made a correct go response to S1, made an erroneous non-cancelled response to S1, or successfully cancelled a response to S1. Our results indicated that the presentation of a stop signal increased the magnitude of IOR, even when the S1 response was not successfully cancelled. However, this was true only when the to-be-cancelled response involved the same effectors as the response used to reveal IOR. These results suggest that there may be a motor component to IOR that is sensitive to the same inhibitory processes that are used to cancel responses in a stop signal paradigm.
The Irrelevant Sound Effect: What Needs Modelling, and a Tentative Model
Authors: Page M. P. A. , Norris D. G.
Published: November 2003

This paper reviews the literature on the irrelevant sound effect and concludes that, contrary to some claims, the data consistently show that irrelevant sound and articulatory suppression are not functionally equivalent. We evaluate the contribution of Larsen and Baddeley (2003 in this issue) and briefly discuss additional data in support of their position. We perform an error analysis on data from their third experiment and simulate detailed aspects of those data using our primacy model of immediate serial recall. Our model is briefly related to a number of findings in the literature on irrelevant sound.
Patterns of co‐morbidity between alcohol use and other substance use in the Australian population
Authors: DEGENHARDT LOUISA , HALL WAYNE
Published: November 2003

The present study describes patterns of co‐morbidity between alcohol use and other substance use problems in the Australian population using data from the 1997 National Survey of Mental Health and Well‐Being. Multiple regression analyses examined whether the observed associations between alcohol and other drug use disorders were explained by other variables, including demographic characteristics and neuroticism. We also assessed whether the presence of co‐morbid substance use disorders affected treatment seeking for a mental health problem. Alcohol use was related strongly to the use of other substances. Those who did not report alcohol use within the past 12 months were less likely to report using tobacco, cannabis, sedatives, stimulants or opiates. Higher rates again were observed among those with alcohol use disorders: half (51%) of those who were alcohol‐dependent were regular tobacco smokers, one‐third had used cannabis (32%); 15% reported other drug use; 15% met criteria for a cannabis use disorder and 7% met criteria for another drug use disorder. These associations were not accounted for by the demographic and other variables considered here. Co‐morbid substance use disorders (sedatives, stimulants or opioids) predicted a high likelihood of seeking treatment for a mental health problem among alcohol‐dependent people.
The relationship of conduct disorder to attempted suicide and drug use history among methadone maintenance patients
Authors: DARKE SHANE , ROSS JOANNE , LYNSKEY MICHAEL
Published: November 2003

In order to examine the effects of a diagnosis of childhood conduct disorder (CD) on history of attempted suicide and drug use, unconfounded by early onset heroin use, 181 methadone maintenance patients who commenced heroin use after the age of 15 were interviewed. CD was diagnosed in 54% of patients. Compared to other patients, CD patients were younger and less educated. The onset of drug use, injecting drug use and heroin use occurred, on average, 2 years earlier than in other patients, and they had broader histories of injecting polydrug use. CD patients were more likely to have attempted suicide and to have been hospitalized after an attempt, and to have attempted suicide while enrolled in their current treatment. The current study indicates that a history of CD increases the risk of attempted suicide over and above the higher risks associated with injecting drug use per se.
The monitoring of drug trends in Australia
Authors: SHAND FIONA , TOPP LIBBY , DARKE SHANE , MAKKAI TONI , GRIFFITHS PAUL
Published: November 2003

Recently, there has been increased recognition of the importance of drug information systems (DIS), highlighting the need for an internationally coordinated approach to data collection and advocating the regular assessment of a range of areas. Accurate information provides policy makers with the evidence to evaluate current strategies and to plan future strategies. An effective drug information system (DIS) must collect comprehensive, detailed and in‐depth data, while also being sensitive to emergent trends and placing these changes into the context of longer‐term trends. An integrated and comprehensive system combines both sensitive (or lead) and slower but more reliable lag indicators. This article reviews conceptual frameworks for DIS and developments in international systems. It then considers the range of DIS in Australia and then describes two integrated monitoring systems with an early warning function: the Illicit Drug Reporting System (IDRS) and the Drug Use Monitoring Australia (DUMA) Programme. Both systems collate sensitive lead indicators, and provide timely information about emerging drug trends in Australia. Together, these two systems are best‐placed to provide effective early warning of new trends in illicit drug markets, and constitute an important component of the overall approach to the monitoring of drug use and associated harms in Australia.
From scrubland to vintage wine: Australia's response to substance‐related problems in the last 40 years*
Authors: RANKIN JAMES G.
Published: November 2003

Over the last 40 years Australia's response to substance‐related problems compared with most western nations has been outstandingly good. Since the 1960s concerns about problems of substance use have expanded from a focus on alcohol to include tobacco and a wide range of other licit as well as illicit psychoactive substances. During this period there have been major advances in our knowledge and understanding of substance‐related problems and effective methods of prevention, intervention and treatment. In parallel has been the development of a large number of non‐government, government and professional organizations concerned with problems of substance use. These groups, individually and collectively, have contributed to the development of policies, plans, resources and programmes to prevent and minimize substance‐related harm. Although significant progress in these endeavours took place between 1960 and 1986, there has been accelerated growth since and largely as a result of the establishment of the National Campaign Against Drug Abuse in 1986 and the ensuing National Drug Strategy and the Illicit Drug Strategy. However, much of this more recent success was possible because of the existence of the organizations, networks and infrastructures established in the earlier period and the Nation's general health, social and educational programmes. These initiatives have been associated with reductions in alcohol and tobacco use and related problems and evidence of reductions in some problem areas associated with illicit drug use. Despite these gains, there have been areas of failure and missed opportunities. Finally, it is critical to ensure that past achievements and opportunities for continued successful initiatives are not undermined by identifiable impediments and risks that could imperil the philosophy, goals, infrastructure and programmes that form the basis for Australia's success to date.
Early unsupervised drinking—reducing the risks. The School Health and Alcohol Harm Reduction Project
Authors: MCBRIDE NYANDA , FARRINGDON FIONA , MIDFORD RICHARD , MEULENERS LYNN , PHILLIPS MIKE
Published: November 2003

The School Health and Alcohol Harm Reduction Project (SHAHRP) aimed to reduce alcohol‐related harm by enhancing students' abilities to identify and deal with high‐risk drinking situations and issues. The SHAHRP study involved a quasi‐experimental research design, incorporating intervention and control groups and measuring change over a 32‐month period. The study occurred in metropolitan, government secondary schools (13–17‐year‐olds) in Perth, Western Australia. The 14 intervention and control schools involved in the SHAHRP study represent approximately 23% of government secondary schools in the Perth metropolitan area. The sample was selected using cluster sampling, with stratification by socio‐economic area, and involved over 2300 intervention and control students from junior secondary schools. The retention rate of the study was 75.9% over 32 months. The intervention incorporated evidence‐based approaches to enhance potential for behaviour change in the target population. The intervention was a classroom‐based programme, with an explicit harm minimization goal, and was conducted in two phases over a 2‐year period. The results were analysed by baseline context of alcohol use to assess the impact of the programme on students with varying experience with alcohol. Knowledge and attitudes were modified simultaneously after the first phase of the intervention in all baseline context of use groups. The programme had little behavioural impact on baseline supervised drinkers; however, baseline non‐drinkers and unsupervised drinkers were less likely to consume alcohol in a risky manner, compared to their corresponding control groups. In line with programme goals, early unsupervised drinkers from the intervention group were also significantly less likely to experience harm associated with their own use of alcohol compared to the corresponding control group. Unsupervised drinkers experienced 18.4% less alcohol‐related harm after participating in both phases of the programme and this difference was maintained (19.4% difference) 17 months after the completion of the programme. This study indicates that a school drug education programme needs to be offered in several phases, that programme components may need to be included to cater for the differing baseline context of use groups, and that early unsupervised drinkers experience less alcohol‐related harm after participating in a harm reduction programme.
Hepatitis C‐related discrimination among heroin users in Sydney: drug user or hepatitis C discrimination?
Authors: DAY CAROLYN , ROSS JOANNE , DOLAN KATE
Published: November 2003

The hepatitis C virus (HCV) is a common infection among injecting drug users. There are currently few available data on the extent (or prevalence) of HCV‐related discrimination. This study examined perceived discrimination among a sample of heroin users and sought to determine whether the discrimination was attributed to their drug user or HCV status. Heroin users were recruited through needle and syringe programmes and methadone clinics in Sydney and were asked about discrimination in the preceding 12 months. Four hundred and one heroin users were recruited, of whom 59% reported being HCV‐positive. Discrimination was reported by 22% of the 237 IDUs who reported being HCV‐positive, with 17% reporting that the discrimination occurred in the preceding 12 months. Sixty‐seven incidents were reported, of which half were perceived to be due to their drug user status, 15% of these incidents were due to HCV status and 25% due to a combination of both. Twenty‐five incidents occurred in a health‐care setting, of which 13 resulted in the service being withheld. HCV is a serious public health concern, and if IDU are to be encouraged into drug treatment it is essential that service providers are perceived to be non‐discriminatory. In managing IDU patients, health care workers need to be cognisant of the impact that their attitude has on treatment outcome.
Different Roles of a Rat Cortical Thymic Epithelial Cell Line In Vitro on Thymocytes and Thymocyte Hybridoma Cells: Phagocytosis, Induction of Apoptosis, Nursing and Growth Promoting Activities
Authors: Vučević Dragana , Čolić Miodrag , Popović Petar , Gašić Sonja
Published: November 2003

In this work, the interaction between a rat cortical thymic epithelial cell (TEC) line (R‐TNC.1) with nursing activity and thymocytes as well as BWRT 8 thymocyte hybridoma (TH) cells has been studied. The R‐TNC.1 cell line significantly bound thymocytes and TH. Binding was stronger during the first 30 min of cell incubation and was followed by a progressive deadhesion. Among adherent thymocytes the proportion of apoptotic cells increased with culture time which was a consequence of higher capacity of the line for binding of apoptotic than viable cells and induction of apoptosis in a subset of adherent thymocytes. Emperiopolesis activity of this thymic nurse cell (TNC) line was manifested by engulfment of thymocytes as well as TH cells. A subset of viable intra‐TNC thymocytes has been triggered to die by apoptosis, whereas other internalized thymocytes have been stimulated to proliferate, as measured by an increase in the percentage of cells in mitosis and higher incorporation of bromodeoxyuridine (BrdU), in comparison to thymocytes cultivated alone. A significant stimulation of proliferation of engulfed TH cells was also observed. The R‐TNC.1 cell line efficiently phagocytosed both apoptotic thymocytes and TH, and the process is followed by intra‐TNC destruction of ingested cells. Cumulatively, these results suggest different role of the R‐TNC.1 clone: phagocytosis of apoptotic cells; induction of apoptotic cell death in a subset of both bound and internalized thymocytes and stimulation of proliferation of a subset of intra‐TNC thymocytes or TH cells.
Processing by proprotein convertases is required for glypican-3 modulation of cell survival, Wnt signaling, and gastrulation movements
Authors: De Cat Bart , Muyldermans Sin-Ya , Coomans Christien , Degeest Gisèle , Vanderschueren Bernadette , Creemers John , Biemar Frédéric , Peers Bernard , David Guido
Published: November 2003

Glypican (GPC)-3 inhibits cell proliferation and regulates cell survival during development. This action is demonstrated by GPC3 loss-of-function mutations in humans and mice. Here, we show that the GPC3 core protein is processed by a furinlike convertase. This processing is essential for GPC3 modulating Wnt signaling and cell survival in vitro and for supporting embryonic cell movements in zebrafish. The processed GPC3 core protein is necessary and sufficient for the cell-specific induction of apoptosis, but in vitro effects on canonical and noncanonical Wnt signaling additionally require substitution of the core protein with heparan sulfate. Wnt 5A physically associates only with processed GPC3, and only a form of GPC3 that can be processed by a convertase is able to rescue epiboly and convergence/extension movements in GPC3 morphant embryos. Our data imply that the Simpson–Golabi–Behmel syndrome may in part result from a loss of GPC3 controls on Wnt signaling, and suggest that this function requires the cooperation of both the protein and the heparan sulfate moieties of the proteoglycan.
Rab27A and its effector MyRIP link secretory granules to F-actin and control their motion towards release sites
Authors: Desnos Claire , Schonn Jean-Sébastien , Huet Sébastien , Tran Viet Samuel , El-Amraoui Aziz , Raposo Graça , Fanget Isabelle , Chapuis Catherine , Ménasché Gaël , de Saint Basile Geneviève , Petit Christine , Cribier Sophie , Henry Jean-Pierre , Darchen François
Published: November 2003

The GTPase Rab27A interacts with myosin-VIIa and myosin-Va via MyRIP or melanophilin and mediates melanosome binding to actin. Here we show that Rab27A and MyRIP are associated with secretory granules (SGs) in adrenal chromaffin cells and PC12 cells. Overexpression of Rab27A, GTPase-deficient Rab27A-Q78L, or MyRIP reduced secretory responses of PC12 cells. Amperometric recordings of single adrenal chromaffin cells revealed that Rab27A-Q78L and MyRIP reduced the sustained component of release. Moreover, these effects on secretion were partly suppressed by the actin-depolymerizing drug latrunculin but strengthened by jasplakinolide, which stabilizes the actin cortex. Finally, MyRIP and Rab27A-Q78L restricted the motion of SGs in the subplasmalemmal region of PC12 cells, as measured by evanescent-wave fluorescence microscopy. In contrast, the Rab27A-binding domain of MyRIP and a MyRIP construct that interacts with myosin-Va but not with actin increased the mobility of SGs. We propose that Rab27A and MyRIP link SGs to F-actin and control their motion toward release sites through the actin cortex.
Morphologically distinct microtubule ends in the mitotic centrosome of Caenorhabditis elegans
Authors: O'Toole Eileen T. , McDonald Kent L. , Mäntler Jana , McIntosh J. Richard , Hyman Anthony A. , Müller-Reichert Thomas
Published: November 2003

During mitosis, the connections of microtubules (MTs) to centrosomes and kinetochores are dynamic. From in vitro studies, it is known that the dynamic behavior of MTs is related to the structure of their ends, but we know little about the structure of MT ends in spindles. Here, we use high-voltage electron tomography to study the centrosome- and kinetochore-associated ends of spindle MTs in embryonic cells of the nematode, Caenorhabditis elegans. Centrosome-associated MT ends are either closed or open. Closed MT ends are more numerous and are uniformly distributed around the centrosome, but open ends are found preferentially on kinetochore-attached MTs. These results have structural implications for models of MT interactions with centrosomes.
Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain
Authors: Bisogno Tiziana , Howell Fiona , Williams Gareth , Minassi Alberto , Cascio Maria Grazia , Ligresti Alessia , Matias Isabel , Schiano-Moriello Aniello , Paul Praveen , Williams Emma-Jane , Gangadharan Uma , Hobbs Carl , Di Marzo Vincenzo , Doherty Patrick
Published: November 2003

Diacylglycerol (DAG) lipase activity is required for axonal growth during development and for retrograde synaptic signaling at mature synapses. This enzyme synthesizes the endocannabinoid 2-arachidonoyl-glycerol (2-AG), and the CB1 cannabinoid receptor is also required for the above responses. We now report on the cloning and enzymatic characterization of the first specific sn-1 DAG lipases. Two closely related genes have been identified and their expression in cells correlated with 2-AG biosynthesis and release. The expression of both enzymes changes from axonal tracts in the embryo to dendritic fields in the adult, and this correlates with the developmental change in requirement for 2-AG synthesis from the pre- to the postsynaptic compartment. This switch provides a possible explanation for a fundamental change in endocannabinoid function during brain development. Identification of these enzymes may offer new therapeutic opportunities for a wide range of disorders.
p120 catenin associates with kinesin and facilitates the transport of cadherin–catenin complexes to intercellular junctions
Authors: Chen Xinyu , Kojima Shin-ichiro , Borisy Gary G. , Green Kathleen J.
Published: November 2003

p120 catenin (p120) is a component of adherens junctions and has been implicated in regulating cadherin-based cell adhesion as well as the activity of Rho small GTPases, but its exact roles in cell–cell adhesion are unclear. Using time-lapse imaging, we show that p120-GFP associates with vesicles and exhibits unidirectional movements along microtubules. Furthermore, p120 forms a complex with kinesin heavy chain through the p120 NH2-terminal head domain. Overexpression of p120, but not an NH2-terminal deletion mutant deficient in kinesin binding, recruits endogenous kinesin to N-cadherin. Disruption of the interaction between N-cadherin and p120, or the interaction between p120 and kinesin, leads to a delayed accumulation of N-cadherin at cell–cell contacts during calcium-initiated junction reassembly. Our analyses identify a novel role of p120 in promoting cell surface trafficking of cadherins via association and recruitment of kinesin.
Ca2+ influx–independent synaptic potentiation mediated by mitochondrial Na+-Ca2+ exchanger and protein kinase C
Authors: Yang Feng , He Xiang-ping , Russell James , Lu Bai
Published: November 2003

Activity-dependent modulation of synaptic transmission is an essential mechanism underlying many brain functions. Here we report an unusual form of synaptic modulation that depends on Na+ influx and mitochondrial Na+-Ca2+ exchanger, but not on Ca2+ influx. In Ca2+-free medium, tetanic stimulation of Xenopus motoneurons induced a striking potentiation of transmitter release at neuromuscular synapses. Inhibition of either Na+ influx or the rise of Ca2+ concentrations ([Ca2+]i) at nerve terminals prevented the tetanus-induced synaptic potentiation (TISP). Blockade of Ca2+ release from mitochondrial Na+-Ca2+ exchanger, but not from ER Ca2+ stores, also inhibited TISP. Tetanic stimulation in Ca2+-free medium elicited an increase in [Ca2+]i, which was prevented by inhibition of Na+ influx or mitochondrial Ca2+ release. Inhibition of PKC blocked the TISP as well as mitochondrial Ca2+ release. These results reveal a novel form of synaptic plasticity and suggest a role of PKC in mitochondrial Ca2+ release during synaptic transmission.
MT1-MMP–dependent, apoptotic remodeling of unmineralized cartilage
Authors: Holmbeck Kenn , Bianco Paolo , Chrysovergis Kali , Yamada Susan , Birkedal-Hansen Henning
Published: November 2003

Skeletal tissues develop either by intramembranous ossification, where bone is formed within a soft connective tissue, or by endochondral ossification. The latter proceeds via cartilage anlagen, which through hypertrophy, mineralization, and partial resorption ultimately provides scaffolding for bone formation. Here, we describe a novel and essential mechanism governing remodeling of unmineralized cartilage anlagen into membranous bone, as well as tendons and ligaments. Membrane-type 1 matrix metalloproteinase (MT1-MMP)–dependent dissolution of unmineralized cartilages, coupled with apoptosis of nonhypertrophic chondrocytes, mediates remodeling of these cartilages into other tissues. The MT1-MMP deficiency disrupts this process and uncouples apoptotic demise of chondrocytes and cartilage degradation, resulting in the persistence of “ghost” cartilages with adverse effects on skeletal integrity. Some cells entrapped in these ghost cartilages escape apoptosis, maintain DNA synthesis, and assume phenotypes normally found in the tissues replacing unmineralized cartilages. The coordinated apoptosis and matrix metalloproteinase-directed cartilage dissolution is akin to metamorphosis and may thus represent its evolutionary legacy in mammals.
Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA
Authors: Kobielak Krzysztof , Pasolli H. Amalia , Alonso Laura , Polak Lisa , Fuchs Elaine
Published: November 2003

Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft. Without BMPRIA activation, GATA-3 is down-regulated and its regulated control of IRS differentiation is compromised. In contrast, Lef1 is up-regulated, but its regulated control of hair differentiation is still blocked, and BMPRIA-null follicles fail to activate Lef1/β-catenin–regulated genes, including keratin genes. Wnt-mediated transcriptional activation can be restored by transfecting BMPRIA-null keratinocytes with a constitutively activated β-catenin. This places the block downstream from Lef1 expression but upstream from β-catenin stabilization. Because mice lacking the BMP inhibitor Noggin fail to express Lef1, our findings support a model, whereby a sequential inhibition and then activation of BMPRIA is necessary to define a band of hair progenitor cells, which possess enough Lef1 and stabilized β-catenin to activate the hair specific keratin genes and generate the hair shaft.
Traffic control
Authors: Peifer Mark , Yap Alpha S.
Published: November 2003

Proteins of the p120 family have been implicated in the regulation of cadherin-based cell adhesion, but their relative importance in this process and their mechanism of action have remained less clear. Three papers in this issue suggest that p120 plays a key role in maintaining normal levels of cadherin in mammalian cells, and that it may do so by regulating cadherin trafficking (Chen et al., 2003; Davis et al., 2003; Xiao et al., 2003).
Human Chest Wall Function while Awake and during Halothane Anesthesia
Authors: Warner David O. , Warner Mark A. , Ritman Erik L.
Published: November 2003

Background

Data concerning chest wall configuration and the activities of the major respiratory muscles that determine this configuration during anesthesia in humans are limited. The aim of this study was to determine the effects of halothane anesthesia on respiratory muscle activity and chest wall shape and motion during spontaneous breathing.

Methods

Six human subjects were studied while awake and during 1 MAC halothane anesthesia. Respiratory muscle activity was measured using fine-wire electromyography electrodes. Chest wall configuration was determined using images of the thorax obtained by three-dimensional fast computed tomography. Tidal changes in gas volume were measured by integrating respiratory gas flow, and the functional residual capacity was measured by a nitrogen dilution technique.

Results

While awake, ribcage expansion was responsible for 25 +/- 4% (mean +/- SE) of the total change in thoracic volume (delta Vth) during inspiration. Phasic inspiratory activity was regularly present in the diaphragm and parasternal intercostal muscles. Halothane anesthesia (1 MAC) abolished activity in the parasternal intercostal muscles and increased phasic expiratory activity in the abdominal muscles and lateral ribcage muscles. However, halothane did not significantly change the ribcage contribution to delta Vth (18 +/- 4%). Intrathoracic blood volume, measured by comparing changes in total thoracic volume and gas volume, increased significantly during inspiration both while awake and while anesthetized (by approximately 20% of delta Vth, P < 0.05). Halothane anesthesia significantly reduced the functional residual capacity (by 258 +/- 78 ml), primarily via an inward motion of the end-expiratory position of the ribcage. Although the diaphragm consistently changed shape, with a cephalad displacement of posterior regions and a caudad displacement of anterior regions, the diaphragm did not consistently contribute to the reduction in the functional residual capacity. Halothane anesthesia consistently increased the curvature of the thoracic spine measured in the saggital plane.

Conclusions

The authors conclude that (1) ribcage expansion is relatively well preserved during halothane anesthesia despite the loss of parasternal intercostal muscle activity; (2) an inward displacement of the ribcage accounts for most of the decrease in functional residual capacity caused by halothane anesthesia, accompanied by changes in diaphragm shape that may be related to motion of its insertions on the thoracoabdominal wall; and (3) changes in intrathoracic blood volume constitute a significant fraction of delta Vth during tidal breathing.
The Dose-Response Relationship of Ondansetron in Preventing Postoperative Emesis in Pediatric Patients Undergoing Ambulatory Surgery
Authors: Watcha Mehernoor F. , Bras Paul J. , Cieslak Gary D. , Pennant John H.
Published: November 2003

Background

Postoperative nausea and vomiting is a distressing anesthetic complication that may delay discharge after ambulatory surgery. Effective prophylaxis for postoperative nausea and vomiting can be achieved in adults with lower doses of ondansetron, a 5-hydroxytryptamine subtype 3 receptor antagonist, compared with chemotherapy-induced emesis. However, the doses of ondansetron used in preventing postoperative nausea and vomiting in children are based on data from chemotherapy-induced emesis. The dose-related efficacy of intravenous ondansetron in the prophylaxis of postoperative emesis in the pediatric outpatient population was determined.

Methods

In a double-blind, randomized placebo-controlled study, 130 patients (mean age 5.7 +/- 3.4 yr) received placebo, 10, 50, or 100 micrograms/kg ondansetron during a standardized anesthetic. Episodes of postoperative vomiting or retching were recorded.

Results

Intravenous ondansetron in a dose of 50 micrograms/kg was more effective than placebo or a dose of 10 micrograms/kg in controlling the incidence and frequency of emesis in the hospital and during the first 24 postoperative hours. Increasing the dose of ondansetron to 100 micrograms/kg intravenously did not significantly reduce the incidence or frequency of emesis compared to 50 micrograms/kg intravenously.

Conclusions

Intravenous ondansetron in a dose of 50 micrograms/kg is as effective as larger doses for the prophylaxis of emesis in children undergoing surgical procedures known to be associated with an increased risk for postoperative nausea and vomiting.