bluuebunny/crossref_metadata_2025 huggingface dataset:
A Spectral Element Version of CAM2
Authors: Wang Houjun , Tribbia Joseph J. , Baer Ferdinand , Fournier Aimé , Taylor Mark A.
Published: November 2007

The authors describe a recent development and some applications of a spectral element dynamical core. The improvements and development include the following: (i) the code was converted from FORTRAN 77 to FORTRAN 90; (ii) the dynamical core was extended to the generalized terrain-following, or hybrid η, vertical coordinates; (iii) a fourth-order Runge–Kutta (RK4) method for time integration was implemented; (iv) moisture effects were added in the dynamical system and a semi-Lagrangian method for moisture transport was implemented; and (v) the improved dynamical core was coupled with the Community Atmosphere Model version 2 (CAM2) physical parameterizations and Community Land Model version 2 (CLM2) in such a way that it can be used as an alternative dynamical core in CAM2. This spectral element version of CAM2 is denoted as CAM-SEM. A mass fixer as used in the Eulerian version of CAM2 (CAM-EUL) is also implemented in CAM-SEM. Results from multiyear simulations with CAM-SEM (coupled with CLM2) with climatology SST are also presented and compared with simulations from CAM-EUL. Close resemblances are shown in simulations from CAM-SEM and CAM-EUL. The authors found that contrary to what is suggested by some other studies, the high-order Lagrangian interpolation (with a limiter) using the spectral element basis functions may not be suitable for moisture and other strongly varying fields such as cloud and precipitation.
Combination of Mesoscale and Synoptic Mechanisms for Triggering an Isolated Thunderstorm: Observational Case Study of CSIP IOP 1
Authors: Morcrette Cyril , Lean Humphrey , Browning Keith , Nicol John , Roberts Nigel , Clark Peter , Russell Andrew , Blyth Alan
Published: November 2007

An isolated thunderstorm formed in the southern United Kingdom on 15 June 2005 and moved through the area where a large number of observational instruments were deployed as part of the Convective Storm Initiation Project. Earlier, a convergence line had formed downstream of Devon in the southwest of the United Kingdom in a southwesterly airflow, along which a series of light showers had formed. The depth of these showers was limited by a capping inversion, or lid, at around 2.5 km. The deep thunderstorm convection developed from one of these showers when the convection broke through the lid and ascended up to the next inversion, associated with a tropopause fold at around 6 km. A series of clear-air reflectivity RHIs are used to map the height of the capping inversion and its lifting resulting from the ascent along the convergence line. The origins of the lid are tracked back to some descent from the midtroposphere along dry adiabats. The strength of the lid was weaker along a northwest-to-southeast-oriented region located behind an overrunning upper cold front. The transition from shallow to deep convection occurred where this region with a weaker lid intersected the region with a raised lid, oriented southwest to northeast, downstream of Devon. A very high resolution forecast model that is being developed by the Met Office predicted the isolated thunderstorm successfully. This success depended on the accurate representation of the following two scales: the synoptic-scale and the surface-forced mesoscale convergence line. The interaction between these scales localized the convection sufficiently in space and time for the initiation and subsequent development to be highly predictable despite the relatively poor representation in the model of processes at the cloud scale.
Explicit Numerical Diffusion in the WRF Model
Authors: Knievel Jason C. , Bryan George H. , Hacker Joshua P.
Published: November 2007

Diffusion that is implicit in the odd-ordered advection schemes in early versions of the Advanced Research core of the Weather Research and Forecasting (WRF) model is sometimes insufficient to remove noise from kinematical fields. The problem is worst when grid-relative wind speeds are low and when stratification is nearly neutral or unstable, such as in weakly forced daytime boundary layers, where noise can grow until it competes with the physical phenomena being simulated. One solution to this problem is an explicit, sixth-order numerical diffusion scheme that preserves the WRF model’s high effective resolution and uses a flux limiter to ensure monotonicity. The scheme, and how it was added to the WRF model, are explained. The scheme is then demonstrated in an idealized framework and in simulations of salt breezes and lake breezes in northwestern Utah.
Organizational Change Recipients' Beliefs Scale
Authors: Armenakis Achilles A. , Bernerth Jeremy B. , Pitts Jennifer P. , Walker H. Jack
Published: November 2007

Based on research conducted by organizational scientists dating to the 1940s, the authors identified five important precursors that determine the degree of buy-in by organizational change recipients. The authors assembled these independent precursors into a framework labeled organizational change recipients' beliefs and developed a psychometrically sound self-report questionnaire that can be used to gauge progress of organizational change efforts. The authors describe a series of four studies used to develop a 24-item assessment tool that can be administered at any stage of the change process. The information obtained can serve as (a) a barometer of the degree of buy-in among change recipients, (b) an assessment of deficiencies in specific beliefs that can adversely impact the success of an organizational change, and (c) a basis for planning and executing actions to enhance buy-in among organizational change recipients.
Social and Temporal Influences on Interpretations of Organizational Identity and Acquisition Integration
Authors: Chreim Samia
Published: November 2007

Using a narrative approach, this study analyzes interpretations of organizational identity that emerged among members of autonomous groups brought together as a result of a double acquisition. Comparative analysis of a first set of interviews indicates divergent narratives emerged in two divisions established after the acquisition. Members' meaning construction related to organizational identity focused on such alternative themes as identity enhancement or threat, identity stability or ambiguity, and identity continuity or discontinuity. Differences in interpretations were influenced by the (a) social context that included such elements as encounters with other groups, integration and segregation tactics employed, and level of communication and control from higher level management and (b) temporal context evoked by members as they juxtaposed the past, present, and future identity. Interviews conducted 1 year later indicated changes in the contextual elements and a convergence in the groups' narratives. Implications for the management of acquisitions are presented.
Planning, Organizing, and Conducting a 2-Week Study Abroad Trip for Undergraduate Students: Guidelines for First-Time Faculty
Authors: Koernig Stephen K.
Published: November 2007

This article provides specific recommendations to help faculty members organize, plan, and conduct a short-term overseas study tour. Specifically, strategies are presented to help with managing student anxiety in the pretrip sessions, acclimating the students to their new environment in the early part of the trip, balancing academic content with cultural activities, selecting types of learning activities, and facilitating a student exchange with a local university. A secondary goal of this article is to discuss common on-the-ground problems that the faculty leader may face in the host country. Strategies are presented to help the faculty leader respond to these problems (or prevent them from occurring in the first place).
Developing Graduate Marketing Programs for Economies in Transition
Authors: Chadraba Petr G. , O'Keefe Robert D.
Published: November 2007

This article summarizes some of the authors' experiences in introducing marketing concepts to students involved in the transition from planned to market economies. It addresses critical issues involved in the translation of these concepts within languages that often have no words that are synonymous with these terms. The authors discuss methods for establishing open classroom discussion in countries where pedagogy depended almost solely on lectures and assessment depended almost entirely on memorization rather than the application of terms, definitions, and concepts. The article discusses methods for choosing business cases for discussion and analysis that are relevant to the students' level of experience. The authors show how to use the cases over the period of individual courses and within comprehensive degree programs. Finally, the article discusses the importance of marketing strategy and the concept of choice to the success of economic transition.
The Wretched Refuse of a Teeming Shore? A Critical Examination of the Quality of Undergraduate Marketing Students
Authors: Aggarwal Praveen , Vaidyanathan Rajiv , Rochford Linda
Published: November 2007

What is the quality of students attracted to the marketing major relative to other business majors? Although some anecdotal evidence suggests that undergraduate marketing students are less quantitatively oriented, there has been no comprehensive assessment of the overall quality of marketing students relative to other business students. Using a variety of secondary data analyses from nationwide samples, the authors assess the quality of students choosing marketing as a major. The results paint a grim picture for the marketing discipline. Marketing majors are among the poorest performing students relative to other business majors both coming in to and leaving college. Results from a broad-based sample suggest that marketing educators need to start a dialogue on exactly what set of knowledge and skills core to the discipline are being o fered students and their employers. The authors o fer some solutions and point to areas for additional research.
Creating and Executing an Applied Interdisciplinary Campaign for Domestic Violence Prevention
Authors: Keller Sarah N. , Otjen A. J.
Published: November 2007

This article describes an interdisciplinary, experiential learning project that combined marketing and communications courses at a state university. Two professors from different colleges partnered with a domestic violence center to enable students to create a community-based social marketing campaign. Student assessments indicated success in achieving educational objectives and practical knowledge. The resulting multimedia campaign was well received throughout the state and illustrates opportunities for developing interdisciplinary knowledge and teaching in business and communication studies.
Perceptions and Reality: Creativity in the Marketing Classroom
Authors: McCorkle Denny E. , Payan Janice M. , Reardon James , Kling Nathan D.
Published: November 2007

According to both the popular press and academia, creativity is an important skill for business practice and marketing education. This article addresses “What is creativity?” and “Can creativity be taught or nurtured?” and provides an analysis of both student perceptions about creativity and their levels of creativity. The results indicate that both business and marketing students perceived creativity as important to their career. Marketing students placed greater importance on creativity than other business students and found creativity to be as important to their careers as other important skills (e.g., writing, oral presentation, teamwork, etc.). It was also found that the marketing and other business students believed that creativity is a skill that can be learned. Although marketing students have a better appreciation of the importance of creativity than other business students, they do not appear to be more creative than other business students or nonbusiness students.
Cognitive-Behavioral Profiles of Neurodegenerative Dementias: Beyond Alzheimer's Disease
Authors: Levy James A. , Chelune Gordon J.
Published: November 2007

The neurocognitive and behavioral profiles of vascular dementia and vascular cognitive impairment, dementia with Lewy bodies and Parkinson's disease with dementia, and dementia syndromes associated with frontotemporal lobar degenerations are compared and contrasted with Alzheimer's dementia (AD). Vascular dementia/vascular cognitive impairment is characterized by better verbal memory performance, worse quantitative executive functioning, and prominent depressed mood. Dementia with Lewy bodies and Parkinson's disease with dementia are equally contrasted with AD by defective processing of visual information, better performance on executively supported verbal learning tasks, greater attentional variability, poorer qualitative executive functioning, and the presence of mood-congruent visual hallucinations. The frontal variant of frontotemporal lobar degeneration (frontotemporal dementia) differs from AD by better multimodal retention on learning tasks, different patterns of generative word fluency, defective qualitative executive functioning, and by markedly impairment of comportment. For temporal variants of frontotemporal lobar degenerations, progressive aphasia and semantic dementia, worse language performance relative to AD is typically characteristic. ( J Geriatr Psychiatry Neurol 2007;20:227-238)
Preventing Depression: Culturally Relevant Group Work With Black Women
Authors: Jones Lani V.
Published: November 2007

Recent estimates indicate that 10% to 25% of women in the United States report clinically significant depressive symptoms and that Black women are less likely to obtain care for depression and to receive appropriate treatment when they do seek care. Current mental and social health services necessitate a search for strength-based treatment models that affirm the psychosocial and cultural reality of Black women at risk of depression. The emergent psychosocial competence practice model in mental health represents an innovative paradigm with potential relevance and applicability to preventing depression among Black women. This study evaluates the effectiveness of a culturally relevant group intervention with low-income Black women aimed at reducing depression symptoms and enhancing psychosocial competence, including stress reduction, locus of control, and active coping. Directions for the development of future culturally relevant practice interventions with this population are discussed.
disability activism and the struggle for change
Authors: Barnes Colin
Published: November 2007

This article provides a critical evaluation of recent developments in government policy for disabled people in Britain. A brief outline of the re-definition of disability as social oppression by disabled activists and their organizations is provided. This is followed by a brief outline of its impact on recent government policy which aims to improve the life chances of people with designated `impairments and long term health conditions'. It is argued that although much has been achieved over recent years there is still a long way to go if the language of inclusion is to become more than empty rhetoric. Further, that while disability activism has had an important influence on disability policy in the UK, this very success threatens to undermine its continuity and future.
sexual harassment and abuse of adolescent schoolgirls in South India
Authors: Leach Fiona , Sitaram Shashikala
Published: November 2007

This article reports on a small exploratory study of adolescent girls' experiences of sexual harassment and abuse while attending secondary school in Karnataka State, South India. In South Asia, public discussion of sexual matters, especially relating to children, is largely taboo, and the study uncovers a hidden aspect of schooling, which presents a further barrier to increasing girls' educational participation in India. Data from open-ended interviews and a participatory workshop in two schools revealed that girls were vulnerable to sexual harassment both within the school grounds (mostly by male pupils) and while travelling to and from school (by older boys and adult men), especially on public transport. For some girls, sexual harassment reduced their desire to continue their schooling, for others it increased their fear of being withdrawn if parents came to hear of any incident. Given the reluctance in patriarchal societies to address the abuse and exploitation of women and girls, the authors suggest that further research into this issue is urgently needed.
SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma
Authors: Chen Linfeng , Monti Stefano , Juszczynski Przemyslaw , Daley John , Chen Wen , Witzig Thomas E. , Habermann Thomas M. , Kutok Jeffery L. , Shipp Margaret A.
Published: November 2007

The role of B-cell receptor (BCR)–mediated survival signals in diffuse large B-cell lymphoma (DLBCL) remains undefined. Ligand-induced BCR signaling induces receptor oligomerization, Igα/β immunoreceptor tyrosine-based activation motif (ITAM) phosphorylation, and activation of the spleen tyrosine kinase (SYK), which initiates downstream events and amplifies the initial BCR signal. BCRs also transmit low-level tonic survival signals in the absence of receptor engagement. Herein, we assess the role of SYK-dependent tonic BCR survival signals in DLBCL cell lines and primary tumors and evaluate the efficacy of an ATP-competitive inhibitor of SYK, R406, in vitro. R406 induced apoptosis of the majority of examined DLBCL cell lines. In R406-sensitive DLBCL cell lines, R406 specifically inhibited both tonic- and ligand-induced BCR signaling (autophosphorylation of SYK525/526 and SYK-dependent phosphorylation of the B-cell linker protein [BLNK]). The majority of examined primary DLBCLs also exhibited tonic- and ligand-induced BCR signaling; in these primary tumors, BCR signaling was also inhibited by R406. Of note, BCR-dependent and R406-sensitive DLBCL cell lines were independently identified as “BCR-type” tumors by transcriptional profiling. Therefore, SYK-dependent tonic BCR signaling is an important and potentially targetable survival pathway in some, but not all, DLBCLs. In addition, R406-sensitive DLBCLs can be identified by their transcriptional profiles.
Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study
Authors: Coiffier Bertrand , Lepretre Stéphane , Pedersen Lars Møller , Gadeberg Ole , Fredriksen Henrik , van Oers Marinus H. J. , Wooldridge James , Kloczko Janusz , Holowiecki Jerzy , Hellmann Andrzej , Walewski Jan , Flensburg Mimi , Petersen Jørgen , Robak Tadeusz
Published: November 2007

Safety and efficacy of the fully human anti-CD20 monoclonal antibody, ofatumumab, was analyzed in a multicenter dose-escalating study including 33 patients with relapsed or refractory chronic lymphocytic leukemia. Three cohorts of 3 (A), 3 (B), and 27 (C) patients received 4, once weekly, infusions of ofatumumab at the following doses: (A) one 100 mg and three 500 mg; (B) one 300 mg and three 1000 mg; (C) one 500 mg and three 2000 mg. Sixty-seven percent of the patients were Binet stage B, and the median number of previous treatments was 3. The maximum tolerated dose was not reached. The majority of related adverse events occurred at first infusion, and the number of adverse events decreased at each subsequent infusion. Seventeen (51%) of 33 patients experienced infections, 88% of them of grade 1-2. One event of interstitial pneumonia was fatal; all other cases resolved within one month. The response rate of cohort C was 50% (13/26), one patient having a nodular partial remission and 12 patients partial remission. In conclusion, ofatumumab was found to be well tolerated in patients with chronic lymphocytic leukemia (CLL) in doses up to 2000 mg. Preliminary data on safety and objective response are encouraging and support further studies on the role of ofatumumab in CLL patients. This trial was registered at www.clinicaltrials.gov as no. NCT00093314.
Predicting combinatorial binding of transcription factors to regulatory elements in the human genome by association rule mining
Authors: Morgan Xochitl C , Ni Shulin , Miranker Daniel P , Iyer Vishwanath R
Published: November 2007

Background

Cis-acting transcriptional regulatory elements in mammalian genomes typically contain specific combinations of binding sites for various transcription factors. Although some cis-regulatory elements have been well studied, the combinations of transcription factors that regulate normal expression levels for the vast majority of the 20,000 genes in the human genome are unknown. We hypothesized that it should be possible to discover transcription factor combinations that regulate gene expression in concert by identifying over-represented combinations of sequence motifs that occur together in the genome. In order to detect combinations of transcription factor binding motifs, we developed a data mining approach based on the use of association rules, which are typically used in market basket analysis. We scored each segment of the genome for the presence or absence of each of 83 transcription factor binding motifs, then used association rule mining algorithms to mine this dataset, thus identifying frequently occurring pairs of distinct motifs within a segment.

Results

Support for most pairs of transcription factor binding motifs was highly correlated across different chromosomes although pair significance varied. Known true positive motif pairs showed higher association rule support, confidence, and significance than background. Our subsets of high-confidence, high-significance mined pairs of transcription factors showed enrichment for co-citation in PubMed abstracts relative to all pairs, and the predicted associations were often readily verifiable in the literature.

Conclusion

Functional elements in the genome where transcription factors bind to regulate expression in a combinatorial manner are more likely to be predicted by identifying statistically and biologically significant combinations of transcription factor binding motifs than by simply scanning the genome for the occurrence of binding sites for a single transcription factor.
Characterization, developmental expression and evolutionary features of the huntingtin gene in the amphioxus Branchiostoma floridae
Authors: Candiani Simona , Pestarino Mario , Cattaneo Elena , Tartari Marzia
Published: November 2007

Background

Huntington's disease is an inherited neurodegenerative disorder that is caused by the expansion of an N-terminal polyQ stretch in the huntingtin protein. In order to investigate the hypothesis that huntingtin was already involved in development of the nervous system in the last common ancestor of chordates, we isolated and characterised the huntingtin homologue from the amphioxus Branchiostoma floridae. In the present paper the amphioxus general term must be referred to Branchiostoma floridae.

Results

In this report, we show that the exon-intron organization of the amphioxus huntingtin gene is highly conserved with that of other vertebrates species. The AmphiHtt protein has two glutamine residues in the position of the typical vertebrate polyQ tract. Sequence conservation is greater along the entire length of the protein than in a previously identified Ciona huntingtin. The first three N-terminal HEAT repeats are highly conserved in vertebrates and amphioxus, although exon rearrangement has occurred in this region. AmphiHtt expression is detectable by in situ hybridization starting from the early neurula stage, where it is found in cells of the neural plate. At later stages, it is retained in the neural compartment but also it appears in limited and well-defined groups of non-neural cells. At subsequent larval stages, AmphiHtt expression is detected in the neural tube, with the strongest signal being present in the most anterior part.

Conclusion

The cloning of amphioxus huntingtin allows to infer that the polyQ in huntingtin was already present 540 million years ago and provides a further element for the study of huntingtin function and its evolution along the deuterostome branch.
Developing health science students into integrated health professionals: a practical tool for learning
Authors: Olckers Lorna , Gibbs Trevor J , Duncan Madeleine
Published: November 2007

Background

An integrated sense of professionalism enables health professionals to draw on relevant knowledge in context and to apply a set of professional responsibilities and ethical principles in the midst of changing work environments [1, 2]. Inculcating professionalism is therefore a critical goal of health professional education. Two multi-professional courses for first year Health Science students at the University of Cape Town, South Africa aim to lay the foundation for becoming an integrated health professional [3]. In these courses a diagram depicting the domains of the integrated health professional is used to focus the content of small group experiential exercises towards an appreciation of professionalism. The diagram serves as an organising framework for conceptualising an emerging professional identity and for directing learning towards the domains of 'self as professional' [4, 5].

Objective

This paper describes how a diagrammatic representation of the core elements of an integrated health professional is used as a template for framing course content and for organising student learning. Based on the assumption that all health care professionals should be knowledgeable, empathic and reflective, the diagram provides students and educators with a visual tool for investigating the subjective and objective dimensions of professionalism. The use of the diagram as an integrating point of reference for individual and small group learning is described and substantiated with relevant literature.

Conclusion

The authors have applied the diagram with positive impact for the past six years with students and educators reporting that "it just makes sense". The article includes plans for formal evaluation. Evaluation to date is based on preliminary, informal feedback on the value of the diagram as a tool for capturing the domains of professionalism at an early stage in the undergraduate education of health professional students.
Dental practice satisfaction with preferred provider organizations
Authors: Aseltine Robert H , Reisine Susan , Schilling Elizabeth A , Kennedy James
Published: November 2007

Background

Despite their increasing share of the dental insurance market, little is known about dental practices' satisfaction with preferred provider organizations (PPOs). This analysis examined practice satisfaction with dental PPOs and the extent to which satisfaction was a function of communications from the plan, claims handling and compensation.

Methods

Data were collected through telephone surveys with dental practices affiliated with MetLife between January 2002 and December 2004. Each respondent was asked a series of questions related to their satisfaction with a systematically selected PPO with which they were affiliated. Six different PPO plans had sufficient observations to allow for comparative analysis (total n = 4582). Multiple imputation procedures were used to adjust for item non-response.

Results

While the average level of overall satisfaction with the target plan fell between "very satisfied" and "satisfied," regression models revealed substantial differences in overall satisfaction across the 6 PPOs (p < .05). Statistically significant differences between plans in overall satisfaction were largely explained by differences in the perceived adequacy of compensation. However, differences in overall satisfaction involving two of the PPOs were also driven by satisfaction with claims handling.

Conclusion

Results demonstrate the importance of compensation to dental practice satisfaction with PPOs. However, these results also highlight the critical role of service-related factors in differentiating plans and suggest that there are important non-monetary dimensions of PPO performance that can be used to recruit and retain practices.
Efficacy and safety of artesunate plus amodiaquine in routine use for the treatment of uncomplicated malaria in Casamance, southern Sénégal
Authors: Brasseur Philippe , Agnamey Patrice , Gaye Oumar , Vaillant Michel , Taylor Walter RJ , Olliaro Piero L
Published: November 2007

Background

There are no data on the long term use of an artemisinin combination treatment in moderate or high transmission areas of Africa.

Methods and findings

Artesunate plus amodiaquine (AS+AQ) was used to treat slide-proven Plasmodium falciparum-infected patients of all ages in the Oussouye district, Casamance, Senegal, over a period of six years (2000 to 2005). Efficacy, by Kaplan Meier survival analysis (n = 966), and safety (adverse event rates, n = 752) were determined over 28 days. A weight-based dosing regimen was used for the loose tablets during 2000–2003 (n = 731) and a commercially available co-blister was used during 2004–2005 (n = 235).

Annual crude (non PCR corrected) rates remained stable over the study period [range 88.5–96.7%; overall 94.6 (95% CI 92.9–95.9)]. Nine co-blister treated patients (0.9%) withdrew because of drug-related adverse events; seven had gastrointestinal complaints of whom two were hospitalized for vomiting. By Day 28, the mean total bilirubin (n = 72), AST (n = 94) and ALT (n = 95) values decreased. Three patients had Day 28 AST/ALT values > 40 < 200 IU/L. Changes in white cell counts were unremarkable (n = 87).

Conclusion

AS+AQ in combination was highly efficacious and well-tolerated in this area and justifies the decision to use it as first line treatment. Long-term monitoring of safety and efficacy should continue.
Left hemispheric dominance during auditory processing in a noisy environment
Authors: Okamoto Hidehiko , Stracke Henning , Ross Bernhard , Kakigi Ryusuke , Pantev Christo
Published: November 2007

Background

In daily life, we are exposed to different sound inputs simultaneously. During neural encoding in the auditory pathway, neural activities elicited by these different sounds interact with each other. In the present study, we investigated neural interactions elicited by masker and amplitude-modulated test stimulus in primary and non-primary human auditory cortex during ipsi-lateral and contra-lateral masking by means of magnetoencephalography (MEG).

Results

We observed significant decrements of auditory evoked responses and a significant inter-hemispheric difference for the N1m response during both ipsi- and contra-lateral masking.

Conclusion

The decrements of auditory evoked neural activities during simultaneous masking can be explained by neural interactions evoked by masker and test stimulus in peripheral and central auditory systems. The inter-hemispheric differences of N1m decrements during ipsi- and contra-lateral masking reflect a basic hemispheric specialization contributing to the processing of complex auditory stimuli such as speech signals in noisy environments.
Kisspeptin and GPR54 immunoreactivity in a cohort of 518 patients defines favourable prognosis and clear cell subtype in ovarian carcinoma
Authors: Prentice Leah M , Klausen Christian , Kalloger Steve , Köbel Martin , McKinney Steven , Santos Jennifer L , Kenney Challayne , Mehl Erika , Gilks C Blake , Leung Peter , Swenerton Ken , Huntsman David G , Aparicio Samuel AJ
Published: November 2007

Background

Kisspeptins and their G-protein coupled receptor, GPR54 are required for GnRH release and have been associated with anti-metastatic tumour cell behaviour in model systems. The latter might suggest that their overexpression would be associated with a better prognosis in cancer. However, kisspeptin/GPR54 interactions (autocrine, paracrine, and/or endocrine) could also impact tumour behaviour in a negative manner. Here, for the first time, we associate the immunoreactivity of the kisspeptin/GPR54 ligand-receptor pair with favourable prognosis in a large cohort of ovarian carcinomas.

Methods

Immunohistochemical analysis for kisspeptin and GPR54 was performed on a tissue microarray (TMA) consisting of 518 early stage ovarian carcinomas, all with linked clinical outcome data. The TMA was scored using a staining intensity scale of 0 (negative), +1 (mild-moderate), and +2 (strong). Strong staining cases were considered either kisspeptin or GPR54 positive and designated as 1, while all other cases were considered negative and designated 0. All statistical analysis was conducted using two-sided tests and a p value equal to or less than 0.05 was considered significant.

Results

Kisspeptin and GPR54 immunoreactive cases show a favourable prognosis in univariable disease specific survival (p = 0.0023, p = 0.0092), as well as in overall survival (p = 0.0006, p = 0.0002). Furthermore, kisspeptin is an independent marker for favourable prognosis as determined by multivariable disease specific (p = 0.0046) and overall survival analysis (p = 0.0170), while GPR54 is an independent marker for overall survival only (p = 0.0303). Both kisspeptin positive and GPR54 positive cases are strongly associated with the ovarian carcinoma clear cell subtype (p < 0.0001, p < 0.0001), and GPR54 is significantly associated with favourable prognosis in overall survival within the clear cell subtype (p = 0.0102).

Conclusion

Kisspeptin and GPR54 immunoreactivity are significantly associated with favourable prognosis in both disease specific and overall survival, as well as being significantly associated with the clear cell ovarian carcinoma subtype, thereby creating the first independent prognostic biomarkers specific for ovarian clear cell carcinomas.
Noise-induced switches in network systems of the genetic toggle switch
Authors: Wang Junwei , Zhang Jiajun , Yuan Zhanjiang , Zhou Tianshou
Published: November 2007

Background

Bistability, the capacity to achieve two distinct stable steady states in response to a set of external stimuli, arises within biological systems ranging from theλphage switch in bacteria to cellular signal transduction pathways in mammalian cells. On the other hand, more and more experimental evidence in the form of bimodal population distribution has indicated that noise plays a very important role in the switching of bistable systems. However, the physiological mechanism underling noise-induced switching behaviors remains to be fully understood.

Results

In this paper, we investigate the effect of noises on switching in single and coupled genetic toggle switch systems inEscherichia coli. In the case of the single toggle switch, we show that the multiplicative noises resulting from stochastic fluctuations in degradation rates can induce switching. In the case of the toggle switches interfaced by a quorum-sensing signaling pathway, we find that stochastic fluctuations in degradation rates inside cells, i.e., intracellular noises, can induce synchronized switching, whereas the extracellular noise additive to the common medium can not only entrain all the individual systems to switch in a synchronous manner but also enhance this ordering behavior efficiently, leading a robust collective rhythm in this interacting system.

Conclusion

These insights on the effect of noises would be beneficial to understanding the basic mechanism of how living systems optimally facilitate to function under various fluctuated environments.
Trk signaling regulates neural precursor cell proliferation and differentiation during cortical development
Authors: Bartkowska Katarzyna , Paquin Annie , Gauthier Andrée S. , Kaplan David R. , Miller Freda D.
Published: November 2007

Increasing evidence indicates that development of embryonic central nervous system precursors is tightly regulated by extrinsic cues located in the local environment. Here, we asked whether neurotrophin-mediated signaling through Trk tyrosine kinase receptors is important for embryonic cortical precursor cell development. These studies demonstrate that inhibition of TrkB (Ntrk2)and/or TrkC (Ntrk3) signaling using dominant-negative Trk receptors, or genetic knockdown of TrkB using shRNA, caused a decrease in embryonic precursor cell proliferation both in culture and in vivo. Inhibition of TrkB/C also caused a delay in the generation of neurons, but not astrocytes, and ultimately perturbed the postnatal localization of cortical neurons in vivo. Conversely, overexpression of BDNF in cortical precursors in vivo promoted proliferation and enhanced neurogenesis. Together, these results indicate that neurotrophin-mediated Trk signaling plays an essential, cell-autonomous role in regulating the proliferation and differentiation of embryonic cortical precursors and thus controls cortical development at earlier stages than previously thought.
colliertranscription in a singleDrosophilamuscle lineage: the combinatorial control of muscle identity
Authors: Dubois Laurence , Enriquez Jonathan , Daburon Virginie , Crozet Fabien , Lebreton Gaelle , Crozatier Michèle , Vincent Alain
Published: November 2007

Specification of muscle identity in Drosophila is a multistep process: early positional information defines competence groups termed promuscular clusters, from which muscle progenitors are selected, followed by asymmetric division of progenitors into muscle founder cells (FCs). Each FC seeds the formation of an individual muscle with morphological and functional properties that have been proposed to reflect the combination of transcription factors expressed by its founder. However, it is still unclear how early patterning and muscle-specific differentiation are linked. We addressed this question, using Collier (Col; also known as Knot) expression as both a determinant and read-out of DA3 muscle identity. Characterization of the col upstream region driving DA3 muscle specific expression revealed the existence of three separate phases of cis-regulation, correlating with conserved binding sites for different mesodermal transcription factors. Examination of col transcription in col and nautilus (nau) loss-of-function and gain-of-function conditions showed that both factors are required for col activation in the `naïve' myoblasts that fuse with the DA3 FC, thereby ensuring that all DA3 myofibre nuclei express the same identity programme. Together, these results indicate that separate sets of cis-regulatory elements control the expression of identity factors in muscle progenitors and myofibre nuclei and directly support the concept of combinatorial control of muscle identity.
A neuropeptide hormone cascade controls the precise onset of post-eclosion cuticular tanning inDrosophila melanogaster
Authors: Davis Monica M. , O'Keefe Sandra L. , Primrose David A. , Hodgetts Ross B.
Published: November 2007

A neuropeptide hormone-signalling pathway controls events surrounding eclosion in Drosophila melanogaster. Ecdysis-triggering hormone,eclosion hormone and crustacean cardioactive peptide (CCAP) together control pre-eclosion and eclosion events, whereas bursicon, through its receptor rickets (RK), controls post-eclosion development. Cuticular tanning is a convenient visible marker of the temporally precise post-eclosion developmental progression, and we investigated how it is controlled by the ecdysis neuropeptide cascade. Together, two enzymes, tyrosine hydroxylase (TH,encoded by ple) and dopa decarboxylase (DDC, encoded by Ddc), produce the dopamine that is required for tanning. Levels of both the ple and Ddc transcripts begin to accumulate before eclosion, coincident with the onset of pigmentation of the pharate adult bristles and epidermis. Since DDC activity is high before the post-eclosion onset of tanning, a different factor must be regulated to switch on tanning. Transcriptional control of ple does not regulate the onset of tanning because ple transcript levels remain unchanged from 24 hours before to 12 hours after eclosion. TH protein present before eclosion is degraded,and no TH activity can be detected at eclosion. However, TH protein rapidly accumulates within an hour of eclosion and we provide evidence that CCAP controls this process. Furthermore, we show that TH is transiently activated during tanning by phosphorylation at Ser32, as a result of bursicon signalling. We conclude that the ecdysis hormone cascade acts as a regulatory switch to control the precise onset of tanning by both translational and activational control of TH.
Specification of hypothalamic neurons by dual regulation of the homeodomain protein Orthopedia
Authors: Blechman Janna , Borodovsky Nataliya , Eisenberg Mark , Nabel-Rosen Helit , Grimm Jan , Levkowitz Gil
Published: November 2007

In the developing hypothalamus, a variety of neurons are generated adjacent to each other in a highly coordinated, but poorly understood process. A critical question that remains unanswered is how coordinated development of multiple neuronal types is achieved in this relatively narrow anatomical region. We focus on dopaminergic (DA) and oxytocinergic (OT) neurons as a paradigm for development of two prominent hypothalamic cell types. We report that the development of DA and OT-like neurons in the zebrafish is orchestrated by two novel pathways that regulate the expression of the homeodomain-containing protein Orthopedia (Otp), a key determinant of hypothalamic neural differentiation. Genetic analysis showed that the G-protein-coupled receptor PAC1 and the zinc finger-containing transcription factor Fezl act upstream to Otp. In vivo and in vitro experiments demonstrated that Fezl and PAC1 regulate Otp at the transcriptional and the post-transcriptional levels, respectively. Our data reveal a new genetic network controlling the specification of hypothalamic neurons in vertebrates,and places Otp as a critical determinant underlying Fezl- and PAC1-mediated differentiation.
Dynamin 2 mediates fluid-phase micropinocytosis in epithelial cells
Authors: Cao Hong , Chen Jing , Awoniyi Muyiwa , Henley John R. , McNiven Mark A.
Published: November 2007

It is well-known that dynamin 2 (Dyn2) participates in clathrin- and caveolae-mediated endocytosis; however, the role of Dyn2 in coat-independent endocytic processes remains controversial. Here we demonstrate a role for specific spliced variants of Dyn2 in the micropinocytosis of fluid in epithelial cells, independent of coat-mediated endocytic pathways. A general inhibition of Dyn2 was first performed using either microinjection of anti-dynamin antibodies or Dyn2-siRNA treatment. Both of these methods resulted in reduced uptake of transferrin, a marker for clathrin-mediated endocytosis, and, under unstimulated conditions, reduced the uptake of the fluid-phase markers dextran and horseradish peroxidase (HRP). By contrast, cells treated similarly but stimulated with serum or EGF internalized substantial amounts of dextran or HRP, indicating that Dyn2 is not required for stimulated fluid uptake via macropinocytosis. We next tested whether a specific spliced variant might selectively affect fluid-phase endocytosis. Mutation of specific Dyn2 spliced variants resulted in a differential attenuation of transferrin and dextran internalization. Furthermore, the reduction in fluid uptake in Dyn2-siRNA-treated cells was only rescued upon re-expression of select spliced variants. These findings suggest that Dyn2 function is required for the coat-independent internalization of fluid through endocytic pathways distinct from macropinocytosis and, in addition, implicate different Dyn2 spliced variants in specific endocytic functions.
The processing of double-strand breaks and binding of single-strand-binding proteins RPA and Rad51 modulate the formation of ATR-kinase foci in yeast
Authors: Dubrana Karine , van Attikum Haico , Hediger Florence , Gasser Susan M.
Published: November 2007

Double-strand breaks (DSB) in yeast lead to the formation of repair foci and induce a checkpoint response that requires both the ATR-related kinase Mec1 and its target, Rad53. By combining high-resolution confocal microscopy and chromatin-immunoprecipitation assays, we analysed the genetic requirements for and the kinetics of Mec1 recruitment to an irreparable HO-endonuclease-induced DSB. Coincident with the formation of a 3′ overhang, the Mec1-Ddc2 (Lcd1) complex is recruited into a single focus that colocalises with the DSB site and precipitates with single-strand DNA (ssDNA). The absence of Rad24 impaired cut-site resection, Mec1 recruitment and focus formation, whereas, in the absence of yKu70, both ssDNA accumulation and Mec1 recruitment was accelerated. By contrast, mutation of the N-terminus of the large RPA subunit blocked Mec1 focus formation without affecting DSB processing, arguing for a direct involvement of RPA in Mec1-Ddc2 recruitment. Conversely, loss of Rad51 enhanced Mec1 focus formation independently of ssDNA formation, suggesting that Rad51 might compete for the interaction of RPA with Mec1-Ddc2. In all cases, Mec1 focus formation correlated with checkpoint activation. These observations led to a model that links end-processing and competition between different ssDNA-binding factors with Mec1-Ddc2 focus formation and checkpoint activation.
On the theoretical basis of vibro-frictional actuation in microsystems
Authors: Chatterjee S , Saha A
Published: November 2007

The present article discusses the theoretical basis of generating stepping motion in microsystems. The fundamental principle is to generate asymmetry in friction force in forward and backward motions of a rigid slider by modulating the normal and tangential force. Three architecturally different mechanisms, namely directly driven embedded oscillator, slider on vibrating surface, and slider with embedded oscillator on vibrating surface models, are considered. Simple mathematical models and analytical methods for studying the dynamic characteristics of the systems are developed. Different types of systems are analysed using a unified approach. Dynamic simulation of MATLAB SIMULINK models confirms analytical results.
Aerodynamical Research and Hydraulic Practice
Authors: Fage A.
Published: November 2007

All progressive countries possess aerodynamical laboratories in which scientific researches into the problems of flight are undertaken. Such researches have made, and are capable of making, some contribution to the progress of hydraulic practice. Many of these researches have been carried out with the aid of small-scale models, and the basic principles on which such experiments rest are first considered. It is shown that dimensional analysis indicates the form in which relations between the various parameters which govern fluid flow can best be stated, and suggests the manner in which the governing conditions must be represented on the model to obtain results of the greatest practical value.

The similarity between flows of air and water under corresponding conditions is illustrated. Boundary layer flow is dealt with in some detail, and its influence on resistance and flow phenomena indicated. It is shown that turbulence in a boundary layer may have a beneficial effect on resistance. Methods of controlling flow by the use of guide vanes, slots, boundary jets, fairings, and other devices are described. Attention is directed to those features of wind tunnel design which favour steadiness of flow. The beneficial influence of a large contraction on steadiness is discussed.

Brief reference is made to theoretical and experimental researches undertaken to obtain an insight into the mechanism of fully developed turbulence. The latest resistance formula for a smooth flat plate is given, together with resistance curves for pipes having a specific form of surface roughness. Some modern developments of the theory of a perfect fluid, and applications to problems of a real fluid, are briefly outlined. A method of designing axial-flow reaction turbines and pumps on lines suggested by aerofoil theory is given.