bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypophosphatemia, Hyperphosphaturia, and Bisphosphonate Treatment Are Associated With Survival Beyond Infancy in Generalized Arterial Calcification of Infancy
Authors: Rutsch Frank , Böyer Petra , Nitschke Yvonne , Ruf Nico , Lorenz-Depierieux Bettina , Wittkampf Tanja , Weissen-Plenz Gabriele , Fischer Rudolf-Josef , Mughal Zulf , Gregory John W. , Davies Justin H. , Loirat Chantal , Strom Tim M. , Schnabel Dirk , Nürnberg Peter , Terkeltaub Robert ,   the GACI Study Group
Published: December 2008

Background—

Generalized arterial calcification of infancy has been reported to be frequently lethal, and the efficiency of any therapy, including bisphosphonates, is unknown. A phosphate-poor diet markedly increases survival of NPP1 null mice, a model of generalized arterial calcification of infancy.

Methods and Results—

We performed a multicenter genetic study and retrospective observational analysis of 55 subjects affected by generalized arterial calcification of infancy to identify prognostic factors. Nineteen (34%) patients survived the critical period of infancy. In all 8 surviving patients tested, hypophosphatemia due to reduced renal tubular phosphate reabsorption developed during childhood. Eleven of 17 (65%) patients treated with bisphosphonates survived. Of 26 patients who survived their first day of life and were not treated with bisphosphonates only 8 (31%) patients survived beyond infancy. Forty different homozygous or compound heterozygous mutations, including 16 novel mutations in
ENPP1
, were found in 41 (75%) of the 55 patients. Twenty-nine (71%) of these 41 patients died in infancy (median, 30 days). Seven of the 14 (50%) patients without
ENPP1
mutations died in infancy (median, 9 days). When present on both alleles, the mutation p.P305T was associated with death in infancy in all 5 cases; otherwise, no clear genotype-phenotype correlation was seen.

Conclusion—

ENPP1
coding region mutations are associated with generalized arterial calcification of infancy in ≈75% of subjects. Except for the p.P305T mutation, which was universally lethal when present on both alleles, the identified
ENPP1
mutations per se have no discernable effect on survival. However, survival seems to be associated with hypophosphatemia linked with hyperphosphaturia and also with bisphosphonate treatment.
Being Related
Authors: Mason Jennifer , Tipper Becky
Published: December 2008

This article builds on sociological accounts of the negotiated, creative character of kinship and on previous studies of children's involvement in family life to ask how children actively create and define kinship and relatedness. Drawing on data from a qualitative study with children aged 7—12 in the north of England, the authors identify five interconnected ways in which children made sense of kinship. They explore how children understood genealogical kinship conventions, creatively deployed or interpreted kin terms, and defined some unrelated others as `like family'. The interplay between children's creative agency and adults' involvement in children's kinship is considered.
`Cry and you cry alone'
Authors: Prochner Larry , Hwang Yeonwook
Published: December 2008

This article explores isolation in early childhood education settings in the context of historical and current theories of punishment. The authors conclude that although isolation was reinterpreted in the 20th century in relation to changing theories of learning, teaching and child development, its earlier meanings have endured.
Special Section: Religion as a Large-Scale Justification System
Authors: Shaffer Leigh S.
Published: December 2008

One important goal in Henriques' (2003) Tree of Knowledge (ToK) System is to develop a theory of the emergence of culture. The Justification Hypothesis (JH), which is offered as the missing joint point connecting the cultural sciences to the other sciences, is hoped to be the key to understanding how the evolution of the human mind led to the emergence of cultures conceived as large-scale justification systems. This essay suggests that the origins of religion are connected to human evolution through the development of a Theory of Mind (ToM) and the looking-glass self (Shaffer, 2005). Since ToM is dependent upon the ability to perceive the intentions behind the actions of others, a capacity known as `mind-reading' (Bering, 2002), the JH suggests that religion will emerge as humans turn their mind-reading capacities toward naturally occurring events and engage in animistic attribution (Shaffer, 1984). Religion produces moral codes to help individuals justify themselves, but also produces theodicies which seek to justify the actions of the gods. Since cultural institutions differentiate themselves from each other by pursuing distinct ideological goals, religion also emerges as a separate cultural institution by pursuing the goal of finding meaning in life experiences.
Entrepreneurship and Economic Development in a Developing Country
Authors: Koster Sierdjan , Rai Shailendra Kumar
Published: December 2008

This article analyses the possible link between entrepreneurship and economic development for the case of India. This link has been studied extensively for developed countries, but less so for developing countries. Using the GEM-model as a reference, we expect declining rates of entrepreneurship, as economic development opens up employment possibilities decreasing the number of necessity entrepreneurship. This pattern, however, is not found in the Indian case. Rather, entrepreneurship appears to be an important driver of recent economic growth. This can be explained by the fact that India is very much a service-based economy that facilitates small-scale firms. Although the level of entrepreneurship is increasing over time, the quality of the small firms remains rather stable; the share of registered firms remains equal over time. Given the importance of high-quality entrepreneurship for economic development, it seems that increasing the quality of entrepreneurship should be the main focus of policy measures.
Representing Village
Authors: Thakur Manish K.
Published: December 2008

Rather than focusing on the impact of development on the village in substantive terms, this article critically explores the discursive implications of rural devel–opment. While taking note of the attendant changes in the wake of state–directed process of planned intervention and social reconstruction, it underscores the manner in which the rural development discourse reconfigures the meanings of village in our social imagination. Irrespective of whether rural development programmes fall short of accomplishing their goals, or succeed in meeting the desired targets, they lead to a certain transformation of the terms in which the village is talked about. The village becomes a marker of social difference in the overall context of development and modernization. It is employed as a term of social classification with connotations of the presence, absence or degrees of development. Yet, rural development is the medium in which village is placed in relation to national development. More often than not, village in contemporary times turns out to be a ‘governmentalized locality’.
Leadership Behaviors around the World
Authors: van Emmerik IJ. Hetty , Euwema Martin C. , Wendt Hein
Published: December 2008

This study examined the associations of gender and cultural clusters with two classical leadership styles: consideration and initiating structure. We used a unique database for this study: 64,000 subordinates evaluating the leadership behaviors of their direct supervisors ( N = 13,595), representing 42 countries. Hypotheses were tested using hierarchical regression analysis for cultural clusters. As hypothesized, culture had a stronger impact on leadership behaviors than gender, particularly on initiating structure. In line with predictions, female managers around the world used more consideration. Yet, unexpectedly, women also used more initiating structure. The results suggest that gender differences in managerial behavior are predominantly present in western societies. Results contradict classic stereotypes regarding male and female managerial behaviors. More theory is needed to understand the interaction between gender and culture in relation with leadership. Outcomes have practical implications for HRM practices in international firms and cross cultural leadership training, which should aim at reducing stereotypical thinking on female and male leadership attributes in different cultures.
The Other Nursing Shortage
Authors: Lotas Lynn , McCahon Cheryl , Kavanagh Joan , Dumpe Michelle , Talty Maureen , Knittel Kathleen , O'Malley Cheryl
Published: December 2008

A regional collaborative of one major hospital system and nine schools of nursing has addressed the critical shortage of nursing faculty in Northeast Ohio. This model of institutional collaboration is preparing expert nurse clinicians from the hospital nursing staff to assume clinical faculty roles in regional schools of nursing while maintaining their primary role as clinical staff. The model included the development of a recruitment campaign, a uniform application process, an online database, faculty orientation programs, and continuing faculty development opportunities. Currently, more than 240 clinical nursing staff have applied for the program. Two faculty orientation sessions were attended by more than 100 prospective faculty. Additionally, the first continuing faculty development workshop was attended by more than 170 current and prospective nursing faculty. Now in its third year of implementation, the project is expanding its scope to include a broader base of regional partners and to address the issue of sustainability.
Yes We Can!
Authors: Villeneuve Michael J.
Published: December 2008

Nurses in the 21st century are being called to rise to new levels of practice, including a more influential leadership at senior levels of policy development. Decades of research, good will, and a revolutionary civil rights movement have not resolved the world's staggering health outcome disparities. Nursing has a solution: Many of the most troubling disparities are amenable to effective intervention by the world's nurses through their clinical and policy work. The author challenges nurses to imagine the impact on global health if the elimination of disparities is the core goal of nursing for the 21st century. Moving from individuals and communities to systems levels, nurses must be versed in a range of system-level vital signs that affect policy development including economics, demographics, and access to care. Setting our sights on the elimination of health disparities offers a rallying point around which nursing can coalesce and set human health on a new and more equitable course.
Building Global Alliances in a World of Health Care Inequities
Authors: Lewis Stephen
Published: December 2008

Nurses are at the heart of any effective response to the ongoing HIV/AIDS pandemic in Africa and internationally. Without nurses, we will be unable to provide treatment for the growing numbers of people with HIV/AIDS and victims of violence, famine, and poverty. As countries such as the United States and Canada face nursing shortages, they are looking elsewhere to find nurses. But poaching nurses from other countries, especially those from countries that are struggling for survival, is reprehensible and immoral. If we put our resources in the appropriate places, we can sustain the professional disciplines in the country where they are trained. We need to take an advocacy stance to demand rational policies that will support sustainable health systems.
Uncertain Precedent
Authors: Corley Pamela C.
Published: December 2008

To what extent do lower court judges follow Supreme Court plurality opinions? By examining treatments of Supreme Court cases from the 1976-1986 terms by the Circuit Courts of Appeals from 1976 to 2005, this article addresses the consequences of the Supreme Court's failure to reach a clear majority decision. I find evidence that lower courts are less likely to follow plurality opinions than majority opinions. These findings have implications regarding the authority of the Supreme Court, compliance, and institutional legitimacy.
Exploring the Wealth Returns to Latino Higher Educational Attainment
Authors: Robles Bárbara J.
Published: December 2008

A significant research gap exists in our knowledge of how educational attainment affects wealth building and intergenerational wealth transfers among Latinos. Wealth includes earnings but is a much wider and more fundamental measure of economic mobility. The education—earnings—wealth relationship is explored by constructing estimates of social gains and losses based on work-life earnings profiles for Latino workers. Findings indicate that public investment in Latino higher education results in social benefits by increasing public revenues and contributing to national prosperity.
Colonialism and Carceral Motherhood
Authors: Brown Marilyn , Bloom Barbara E.
Published: December 2008

This article uses data from Hawai`i as a case study to illustrate overlapping, racialized, and gendered regimes of state power in the contemporary post-welfare, neo-liberal political environment. Native Hawaiian families, as a legacy of colonialism, are especially at risk as targets of this control due to strategies of regulation and control coincident with the rise of neo-liberal politics. In this policy environment, penal and welfare practices attempt to shift the responsibility for structural disadvantage onto individuals in marginalized populations, while extending the state's power to police families among a broader network of kin. This article contributes to the literature on gendered state regulation and neo-liberal governance by illustrating patterns of criminalization and expanding child welfare control in this marginalized population.
The Impact of Occupational Culture on Drinking Behavior of Young Adults in the U.S. Navy
Authors: Ames Genevieve M. , Duke Michael R. , Moore Roland S. , Cunradi Carol B.
Published: December 2008

A mixed method study assessed how work culture and drinking norms affect heavy drinking patterns of young adults during their first 3 years in the U.S. Navy. Multivariate logistic regression analysis of the longitudinal survey data showed that normative beliefs were significantly associated with changes in drinking. Findings from thematic analyses of qualitative interviews and naturalistic observations on bases and aboard ships explained those elements of U.S. Navy culture and work environments that affect normative beliefs about drinking behavior.
BK channels in innate immune functions of neutrophils and macrophages
Authors: Essin Kirill , Gollasch Maik , Rolle Susanne , Weissgerber Patrick , Sausbier Matthias , Bohn Erwin , Autenrieth Ingo B. , Ruth Peter , Luft Friedrich C. , Nauseef William M. , Kettritz Ralph
Published: December 2008

Oxygen-dependent antimicrobial activity of human polymorphonuclear leukocytes (PMNs) relies on the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate oxidants. As the oxidase transfers electrons from NADPH the membrane will depolarize and concomitantly terminate oxidase activity, unless there is charge translocation to compensate. Most experimental data implicate proton channels as the effectors of this charge compensation, although large-conductance Ca2+-activated K+ (BK) channels have been suggested to be essential for normal PMN antimicrobial activity. To test this latter notion, we directly assessed the role of BK channels in phagocyte function, including the NADPH oxidase. PMNs genetically lacking BK channels (BK−/−) had normal intracellular and extracellular NADPH oxidase activity in response to both receptor-independent and phagocytic challenges. Furthermore, NADPH oxidase activity of human PMNs and macrophages was normal after treatment with BK channel inhibitors. Although BK channel inhibitors suppressed endotoxin-mediated tumor necrosis factor-α secretion by bone marrow-derived macrophages (BMDMs), BMDMs of BK−/− and wild-type mice responded identically and exhibited the same ERK, PI3K/Akt, and nuclear factor-κB activation. Based on these data, we conclude that the BK channel is not required for NADPH oxidase activity in PMNs or macrophages or for endotoxin-triggered tumor necrosis factor-α release and signal transduction BMDMs.
Relative contribution of CYP2C9 and VKORC1 genotypes and early INR response to the prediction of warfarin sensitivity during initiation of therapy
Authors: Li Chun , Schwarz Ute I. , Ritchie Marylyn D. , Roden Dan M. , Stein C. Michael , Kurnik Daniel
Published: December 2008

Genetic variants in CYP2C9 and VKORC1 strongly affect steady-state warfarin dose. However, these variants also affect early international normalized ratio (INR) values during warfarin initiation. We examined whether CYP2C9/VKORC1 genotypes provide information about warfarin sensitivity additional to that provided by early INR responses. In 214 patients starting warfarin with INR-guided dose adjustments, we determined whether CYP2C9 and VKORC1 genotypes were associated with early measures of warfarin sensitivity (time to INR ≥ lower limit of therapeutic range; time to INR > 4; and first stable warfarin dose) after adjusting for early (days 4-6) and week 1 (days 7-9) INR values. Early INRs were associated with all outcomes (all P < .001) and were more informative than genotypes. For time to INR more than or equal to the lower limit of therapeutic range, adding either early INRs or genotypes to a baseline model (clinical variables only) increased the goodness-of-fit (R2) from 0.05 to 0.42 and 0.19, respectively (full model, R2 = 0.46). For first stable warfarin dose, adding either early INRs or genotypes to the baseline model increased the R2 from 0.08 to 0.32 and 0.27, respectively (full model, R2 = 0.40). After inclusion of week 1 INRs, CYP2C9 (P = .08) and VKORC1 (P = .30) were not associated with stable warfarin dose. Thus, much of the information provided by CYP2C9 and VKORC1 genotypes during warfarin initiation is captured by the early INR response.
Molecular docking studies of dithionitrobenzoic acid and its related compounds to protein disulfide isomerase: computational screening of inhibitors to HIV-1 entry
Authors: Gowthaman Uthaman , Jayakanthan Mannu , Sundar Durai
Published: December 2008

Background

Entry of HIV-1 into human lymphoid requires activities of viral envelope glycoproteins gp120 and gp41, and two host-cell proteins, the primary receptor CD4 and a chemokine co-receptor. In addition, a third cell-surface protein called protein disulfide isomerase (PDI) is found to play a major role in HIV-1 entry. PDI is capable of mediating thio-disulfide interchange reactions and could enable the reduction of gp120 disulfide bonds, which triggers the major conformational changes in gp120 and gp41 required for virus entry. In this scenario, inhibition of HIV-1 entry can be brought about by introducing agents that can block thiol-disulfide interchange reaction of cell surface PDI. There have been studies with agents that inhibit PDI activity, but the exact mode of binding remains to be elucidated; this might provide insights to develop new drugs to target PDI. This study attempts to perceive the mode of binding of dithionitrobenzoic acid (DTNB), and its structurally related compounds on PDI enzyme.

Results

We performed molecular docking simulation with six different inhibitors (ligand), which includes DTNB, NSC695265, thionitrobenzoic acid, 2-nitro-5-thiocyanobenzoic acid, 2-nitro-5-sulfo-sulfonyl-benzoic acid and NSC517871 into the redox-active site [C37-G38-H39-C40] of the PDI enzyme and the activity was inferred by redox inhibitory models. All ligands showed favorable interactions and most of them seemed to bind to hydrophobic amino acids Ala34, Trp36, Cys37, Cys40, His39, Thr68 and Phe80. The redox inhibitory conformations were energetically and statistically favored and supported the evidence from wet laboratory experiments reported in the literature.

Conclusion

We demonstrated that in silico docking experiment can be effectively carried out to recognize the redox inhibitory models of PDI with inhibitor molecules. Interestingly we found that number of docked clusters with each ligand varies in the range of five to eight and conveys that the binding specificity of each inhibitor varies for PDI. We also identified that Cys37 of the enzyme plays an important role in hydrogen bonding with inhibitors. This residue can be considered to being an active site for anti-HIV drug design. Therefore, by inhibiting PDI, one can, not only prevent the viral entry but also circumvent the problem of viral resistance
Predicted mouse peroxisome-targeted proteins and their actual subcellular locations
Authors: Mizuno Yumi , Kurochkin Igor V , Herberth Marlis , Okazaki Yasushi , Schönbach Christian
Published: December 2008

Background

The import of most intraperoxisomal proteins is mediated by peroxisome targeting signals at their C-termini (PTS1) or N-terminal regions (PTS2). Both signals have been integrated in subcellular location prediction programs. However their present performance, particularly of PTS2-targeting did not seem fitting for large-scale screening of sequences.

Results

We modified an earlier reported PTS1 screening method to identify PTS2-containing mouse candidates using a combination of computational and manual annotation. For rapid confirmation of five new PTS2- and two previously identified PTS1-containing candidates we developed the new cell line CHO-perRed which stably expresses the peroxisomal marker dsRed-PTS1. Using CHO-perRed we confirmed the peroxisomal localization of PTS1-targeted candidate Zadh2. Preliminary characterization of Zadh2 expression suggested non-PPARα mediated activation. Notably, none of the PTS2 candidates located to peroxisomes.

Conclusion

In a few cases the PTS may oscillate from "silent" to "functional" depending on its surface accessibility indicating the potential for context-dependent conditional subcellular sorting. Overall, PTS2-targeting predictions are unlikely to improve without generation and integration of new experimental data from location proteomics, protein structures and quantitative Pex7 PTS2 peptide binding assays.
Filtering of false positive microRNA candidates by a clustering-based approach
Authors: Leung Wing-Sze , Lin Marie CM , Cheung David W , Yiu SM
Published: December 2008

Background

MicroRNAs are small non-coding RNA gene products that play diversified roles from species to species. The explosive growth of microRNA researches in recent years proves the importance of microRNAs in the biological system and it is believed that microRNAs have valuable therapeutic potentials in human diseases. Continual efforts are therefore required to locate and verify the unknown microRNAs in various genomes. As many miRNAs are found to be arranged in clusters, meaning that they are in close proximity with their neighboring miRNAs, we are interested in utilizing the concept of microRNA clustering and applying it in microRNA computational prediction.

Results

We first validate the microRNA clustering phenomenon in the human, mouse and rat genomes. There are 45.45%, 51.86% and 48.67% of the total miRNAs that are clustered in the three genomes, respectively. We then conduct sequence and secondary structure similarity analyses among clustered miRNAs, non-clustered miRNAs, neighboring sequences of clustered miRNAs and random sequences, and find that clustered miRNAs are structurally more similar to one another, and the RNAdistance score can be used to assess the structural similarity between two sequences. We therefore design a clustering-based approach which utilizes this observation to filter false positives from a list of candidates generated by a selected microRNA prediction program, and successfully raise the positive predictive value by a considerable amount ranging from 15.23% to 23.19% in the human, mouse and rat genomes, while keeping a reasonably high sensitivity.

Conclusion

Our clustering-based approach is able to increase the effectiveness of currently available microRNA prediction program by raising the positive predictive value while maintaining a high sensitivity, and hence can serve as a filtering step. We believe that it is worthwhile to carry out further experiments and tests with our approach using data from other genomes and other prediction software tools. Better results may be achieved with fine-tuning of parameters.
Analysis of chromatin boundary activity in Drosophila cells
Authors: Li Mo , Belozerov Vladimir E , Cai Haini N
Published: December 2008

Background

Chromatin boundaries, also known as insulators, regulate gene activity by organizing active and repressive chromatin domains and modulate enhancer-promoter interactions. However, the mechanisms of boundary action are poorly understood, in part due to our limited knowledge about insulator proteins, and a shortage of standard assays by which diverse boundaries could be compared.

Results

We report here the development of an enhancer-blocking assay for studying insulator activity in Drosophila cultured cells. We show that the activities of diverse Drosophila insulators including suHw, SF1, SF1b, Fab7 and Fab8 are supported in these cells. We further show that double stranded RNA (dsRNA)-mediated knockdown of SuHw and dCTCF factors disrupts the enhancer-blocking function of suHw and Fab8, respectively, thereby establishing the effectiveness of using RNA interference in our cell-based assay for probing insulator function.

Conclusion

The novel boundary assay provides a quantitative and efficient method for analyzing insulator mechanism and can be further exploited in genome-wide RNAi screens for insulator components. It provides a useful tool that complements the transgenic and genetic approaches for studying this important class of regulatory elements.
Granulosa cells express three inositol 1,4,5-trisphosphate receptor isoforms: cytoplasmic and nuclear Ca2+ mobilization
Authors: Díaz-Muñoz Mauricio , de la Rosa Santander Patricia , Juárez-Espinosa Anna Berenice , Arellano Rogelio O , Morales-Tlalpan Verónica
Published: December 2008

Background

Granulosa cells play an important endocrine role in folliculogenesis. They mobilize Ca2+ from intracellular stores by a coordinated action between 1,4,5 inositol trisphosphate and ryanodine receptors (IP3R and RyR). The aim of this study was to explore the isoforms of IP3Rs expressed in mouse C57BL/6 NHsd granulosa cells, characterizing their intranuclear localization and the relation with other Ca2+-handling proteins.

Methods

Ovarian tissue and granulosa cells were analyzed by multiphotonic and confocal microscopy to determine the intracellular presence of IP3R types 1, 2 and 3, RyR, thapsigargin-sensitive Ca2+-ATPase, and endomembranes. Cellular fractionation and Western blot assays were also used to further confirm the nuclear occurrence of the three IP3R isoforms. Free nuclear and cytosolic Ca2+ concentrations were measured using Fluo-4 AM by confocal microscopy.

Results

By using antibodies and specific fluorophores, was shown that granulosa cells endomembranes contain three isoforms of IP3R, the RyR, and the thapsigargin-sensitive Ca2+-ATPase (SERCA). Interestingly, all these proteins were also detected in the nuclear envelope and in well-defined intranuclear structures. Microsomal membranes depicted characteristic bands of the 3 types of IP3R, but also variants of lower molecular weight. Analysis of nuclear membranes and nucleoplasmic fraction confirmed the nuclear localization of the IP3R types 1, 2 and 3. We demonstrated ATP-induced Ca2+ transients in the nuclear and cytoplasmic compartments. Remarkably, the inhibitory effect on ATP-induced Ca2+ mobilization of brefeldin A was more accentuated in the cytoplasm than in the nucleus.

Conclusion

These findings provide evidence that granulosa cells, including nuclei, express the Ca2+-handling proteins that allow Ca2+ mobilization. All three IP3R were also detected in ovarian slices, including the nuclei of granulosa cells, suggesting that these cells use the three IP3R in situ to achieve their physiological responses.
Differences in physical activity and sedentary time in relation to weight in 8–9 year old children
Authors: Purslow Lisa R , Hill Claire , Saxton Jenny , Corder Kirsten , Wardle Jane
Published: December 2008

Background

The health benefits of physical activity for children are well established. Although objective measures of physical activity are increasingly used there is still a lack of adequate data on physical activity in children. Sex differences in physical activity have been consistently demonstrated and lower levels of physical activity in obese than non-obese children have been shown. However, differences across the whole weight spectrum have not been examined in detail. The aim of this study was to assess associations between physical activity and sedentary time across the weight spectrum in children, and to determine whether the associations differed by sex.

Methods

Participants in the current study were 176 boys and 169 girls aged 8–9 years old taking part in a longitudinal study of associations between eating behaviours, physical activity and weight gain during childhood. Height, weight and waist circumference were measured, and physical activity data were collected using an Actigraph model GT1M worn for 5 consecutive days. Associations between sex, weight and physical activity were analysed using linear regression models.

Results

Boys had higher total activity (mean difference = 119, p < 0.001) and more minutes of moderate and vigorous physical activity (MVPA) (mean difference = 25, p < 0.001) than girls. A higher percentage of boys (72%) than girls (30%) met current physical activity guidelines of 60 minutes MVPA per day. In boys, weight status significantly predicted total activity (p = 0.001) and MVPA (p = 0.001) but there were no significant associations in girls. There was no significant difference in time spent sedentary between boys and girls, and weight status did not predict sedentary time.

Conclusion

In boys, physical activity was progressively lower across the weight spectrum, but in girls physical activity was consistently low across all weight categories. Intervention is required prior to 8 years old to prevent weight-related declines in physical activity in boys and further research is required to determine at what age, if ever, weight related differences in physical activity are apparent in girls.
Excess circulating angiopoietin-2 is a strong predictor of mortality in critically ill medical patients
Authors: Kümpers Philipp , Lukasz Alexander , David Sascha , Horn Rüdiger , Hafer Carsten , Faulhaber-Walter Robert , Fliser Danilo , Haller Hermann , Kielstein Jan T
Published: December 2008

Introduction

The endothelial specific angiopoietin (Ang)-Tie2 ligand-receptor system has been identified as a non-redundant mediator of endothelial activation in experimental sepsis. Binding of circulating Ang-1 to the Tie2 receptor protects the vasculature from inflammation and leakage, whereas binding of Ang-2 antagonises Tie2 signalling and disrupts endothelial barrier function. Here, we examine whether circulating Ang-1 and/or Ang-2 independently predict mortality in a cohort of critically ill medical patients.

Methods

Circulating vascular endothelial growth factor (VEGF), Ang-1 and Ang-2 were prospectively measured in sera from 29 healthy controls and 43 medical ICU patients by immunoradiometric assay (IRMA) and ELISA, respectively. Survival after 30 days was the primary outcome studied.

Results

Median serum Ang-2 concentrations were increasingly higher across the following groups: healthy controls, patients without sepsis, patients with sepsis and patients with septic shock. In contrast, Ang-1 and VEGF concentrations were significantly lower in all patient groups compared with healthy controls. Ang-2 correlated with partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2), tissue hypoxia, Sequential Organ Failure Assessment (SOFA) and Physiology and Chronic Health Evaluation II (APACHE II) score. Multivariate Cox regression analyses confirmed a strong independent prognostic impact of high Ang-2 as a novel marker of 30-day survival.

Conclusions

A marked imbalance of the Ang-Tie system in favour of Ang-2 is present in critically ill medical patients. Our findings highlight the independent prognostic impact of circulating Ang-2 in critical illness. Ang-2 may be used as a readily available powerful predictor of outcome and may open new perspectives to individualise treatment in the ICU.
Acoustic waves in sand-screened deepwater completions: Comparison of experiments and modeling
Authors: Bakulin Andrey , Alexandrov Dmitry , Sidorov Alexander , Kashtan Boris
Published: December 2008

Real-time completion monitoring with acoustic waves has been proposed recently as a method to monitor permeability changes along completions. Typical deepwater completions contain additional layers of sand screen, gravel sand, and perforated casing, which make them quite different from a fluid-filled open borehole. Monitoring changes in flow properties across the completion is crucial because impairment of permeability in any of these layers could cause reduced well productivity. In contrast to an open-hole model, a sand-screened completion supports two tube waves related to an inner fluid column and a gravel suspension in the annulus. To study effects of screen and sand permeability on tube-wave signatures, we construct simple numerical models of various completion scenarios using poroelastic descriptions of screen and sand. Models generally predict that a fast tube wave does not attenuate at either low or high permeability, but experiences resonant attenuation at intermediate frequencies. In contrast, a slow tube wave attenuates completely above a certain permeability value. Models provide a qualitative and sometimes a semiquantitative description for signatures of the fast tube wave. However, they are unable to explain why the slow tube wave is observed in experiments with high permeabilities of sand and screen. We speculate that a better model of complex sand screens is required to match experimental data.
CDK phosphorylation of the discs large tumour suppressor controls its localisation and stability
Authors: Narayan Nisha , Massimi Paola , Banks Lawrence
Published: December 2008

The Discs Large (Dlg) protein is known to be involved in the regulation of cellular proliferation and polarity in a variety of tissues. The human homologue DLG1 is thought to be a tumour suppressor, through formation of a complex with the APC (adenomatous polyposis coli) protein, causing negative regulation of the cell cycle. An alternative oncogenic role has also been proposed, in which the PI3-kinase pathway is activated under the influence of the adenovirus E4 ORF1 protein. The differing roles seem to be related to differences in the precise pattern of expression. However, the biochemical pathways involved in regulating DLG1 function during different phases of the cell cycle remain unclear. In this study we show that phosphorylation is a major post-translational modification of the protein and it affects both location and function. DLG1 lies at the cellular junctions in G1, is enriched in the cytoplasm in S phase and locates to the mitotic spindle in M phase. We also show that DLG1 is phosphorylated by both CDK1 and CDK2 on Ser158 and Ser442. These phosphorylated sites together affect the nuclear localisation of the protein, and implicate the role of phosphorylation on Ser158 and Ser442 in its putative nuclear functions as a tumour suppressor. In addition, the mutants at these sites demonstrate different half-lives as well as different susceptibilities to ubiquitylation, suggesting a role for these phosphorylation events in controlling DLG1 protein stability. These findings establish phosphorylation events as key regulators of DLG1 localisation and function.
Imaging of evoked dense-core-vesicle exocytosis in hippocampal neurons reveals long latencies and kiss-and-run fusion events
Authors: Xia Xiaofeng , Lessmann Volkmar , Martin Thomas F. J.
Published: December 2008

Evoked neuropeptide secretion in the central nervous system occurs slowly, but the basis for slow release is not fully understood. Whereas exocytosis of single synaptic vesicles in neurons and of dense-core vesicles (DCVs) in endocrine cells have been directly visualized, single DCV exocytic events in neurons of the central nervous system have not been previously studied. We imaged DCV exocytosis in primary cultured hippocampal neurons using fluorescent propeptide cargo and total internal reflectance fluorescence microscopy. The majority of Ca2+-triggered exocytic events occurred from immobile plasma-membrane-proximal DCVs in the cell soma, whereas there were few events in the neurites. Strikingly, DCVs in the cell soma exhibited 50-fold greater release probabilities than those in neurites. Latencies to depolarization-evoked fusion for DCVs were surprisingly long, occurring with an average time constant (τ) of 16 seconds for DCVs in the soma and even longer for DCVs in neurites. All of the single DCV release events exhibited rapid fusion-pore openings and closures, the kinetics of which were highly dependent upon Ca2+ levels. These `kiss-and-run' events were associated with limited cargo secretion. Thus, the slow evoked release of neuropeptides could be attributed to very prolonged latencies from stimulation to fusion and transient fusion-pore openings that might limit cargo secretion.
Moesin is required for HIV-1-induced CD4-CXCR4 interaction, F-actin redistribution, membrane fusion and viral infection in lymphocytes
Authors: Barrero-Villar Marta , Cabrero José Román , Gordón-Alonso Mónica , Barroso-González Jonathan , Álvarez-Losada Susana , Muñoz-Fernández M. Ángeles , Sánchez-Madrid Francisco , Valenzuela-Fernández Agustín
Published: December 2008

The human immunodeficiency virus 1 (HIV-1) envelope regulates the initial attachment of viral particles to target cells through its association with CD4 and either CXCR4 or CCR5. Although F-actin is required for CD4 and CXCR4 redistribution, little is known about the molecular mechanisms underlying this fundamental process in HIV infection. Using CD4+ CXCR4+ permissive human leukemic CEM T cells and primary lymphocytes, we have investigated whether HIV-1 Env might promote viral entry and infection by activating ERM (ezrin-radixin-moesin) proteins to regulate F-actin reorganization and CD4/CXCR4 co-clustering. The interaction of the X4-tropic protein HIV-1 gp120 with CD4 augments ezrin and moesin phosphorylation in human permissive T cells, thereby regulating ezrin-moesin activation. Moreover, the association and clustering of CD4-CXCR4 induced by HIV-1 gp120 requires moesin-mediated anchoring of actin in the plasma membrane. Suppression of moesin expression with dominant-negative N-moesin or specific moesin silencing impedes reorganization of F-actin and HIV-1 entry and infection mediated by the HIV-1 envelope protein complex. Therefore, we propose that activated moesin promotes F-actin redistribution and CD4-CXCR4 clustering and is also required for efficient X4-tropic HIV-1 infection in permissive lymphocytes.
Tribology of the ring—bore conjunction subject to a mixed regime of lubrication
Authors: Mishra P C , Rahnejat H , King P D
Published: December 2008

This paper provides a detailed analysis of the compression ring—bore/liner conjunction. The analysis includes ring—bore conformability and global in-plane deformation of ring fitted in situ. The analysis for fitted ring in an out-of-round bore shows very good agreement with precise measurements, using a coordinate measuring machine. The analysis also includes the lubricated conjunction under a transient regime of lubrication, taking into account combined elastohydrodynamics and asperity interactions. The transient nature of the tribological conjunction has been demonstrated, particularly the prevalent mixed/boundary regime of lubrication at the top and bottom dead centres.

The analysis is applied to a high performance motorbike engine subjected to very high impact loads and engine speeds of the order of 13 000 r/min. Furthermore, the predictions of the model show good conformance to the measurements of friction reported by other research workers.
Development and experimental evaluation of an online estimation system for vehicle mass
Authors: Han K-J , Kim I-K , Jo H Y , Huh K-S
Published: December 2008

As active chassis controllers are becoming increasingly complex and sophisticated, the performance of these controllers is very sensitive to a vehicle's inertial parameters such as the vehicle mass and mass centre height. Also, these parameters vary with the number of passengers and with different load situations. In this paper, in order to determine the vehicle mass during arbitrary vehicle manoeuvring, an online estimation system is proposed considering available driving conditions, which includes two estimation algorithms. One is designed on the basis of the vehicle's longitudinal motion using the recursive least-squares method with the disturbance observer technique. The other is designed on the basis of the vehicle's lateral motion by estimating the lateral velocity. Then, two estimation algorithms are combined to extract the vehicle mass information using the recursive least-squares method. The performance of the proposed estimation system is demonstrated through experimental tests.
A mechatronic approach for effective wheel slip control in railway traction
Authors: Mei T X , Yu J H , Wilson D A
Published: December 2008

This article proposes a radically new approach for the detection of wheel slip/slide and re-adhesion control of AC traction motors in railway applications, which provides an important alternative and advantageous technique in traction/braking control systems to maximize the use of adhesion in poor contact conditions. The proposed concept explores the variations in the wheelset dynamic properties caused by the condition changes at the wheel—rail contact, and detects and controls the slip conditions from the dynamic behaviour of a wheelset, indirectly. All the dynamic motions of rail wheelset, which are closely related to wheel—rail contact mechanics, are included in the study; the influence of contact conditions on the relevant modes is assessed, which is essential in the development of a mechatronic solution based on dynamic interactions. This is different from the more general approaches in many other studies on traction controls where the inclusion of only wheelset rotation and longitudinal motions are considered as sufficient. The development of the slip detection and re-adhesion control schemes is presented and comprehensive simulation results are produced to support the proposed idea.
Bond graph model-based fault detection using residual sinks
Authors: Borutzky W
Published: December 2008

In this paper, residual sinks are used in bond graph model-based quantitative fault detection for the coupling of a model of a faultless process engineering system to a bond graph model of the faulty system. By this way, integral causality can be used as the preferred computational causality in both models. There is no need for numerical differentiation. Furthermore, unknown variables do not need to be eliminated from power continuity equations in order to obtain analytical redundancy relations (ARRs) in symbolic form. Residuals indicating faults are computed numerically as components of a descriptor vector of a differential algebraic equation system derived from the coupled bond graphs. The presented bond graph approach especially aims at models with non-linearities that make it cumbersome or even impossible to derive ARRs from model equations by elimination of unknown variables. For illustration, the approach is applied to a non-controlled as well as to a controlled hydraulic two-tank system. Finally, it is shown that not only the numerical computation of residuals but also the simultaneous numerical computation of their sensitivities with respect to a parameter can be supported by bond graph modelling.
Enhanced diagnosis of faults using the digraph approach applied to a dynamic aircraft fuel system
Authors: Kelly E M , Bartlett L M
Published: December 2008

Malfunctions within commercial aircraft can considerably increase both the financial cost of downtime and the disruption caused to passenger travel. For this reason prompt detection, diagnosis, and rectification of faults is imperative to the successful operation of such a system. In this paper the fault diagnostic problem is tackled based on the application of the digraph procedure. Digraphs model the information flow, and hence fault propagation, through a system. A computational method has been successfully developed to conduct the fault diagnostics process and produce a list of the fault combinations determined. The scope of the method has been demonstrated by consideration of two modes of operation to the application of a commercial aircraft fuel system, namely that of a Boeing 777. In addition the paper highlights the contribution of the development of a reduction method to enhance the likelihood of identifying the possible failure causes in three ways from different viewpoints. The three methods provide the option of determining the component at fault, the most probable failure mode cause, and also evidence for a particular component fault.
Quantification of fault trees containing mutually exclusive events
Authors: Contini S
Published: December 2008

This paper presents a method for analysing fault trees that contain independent sets of mutually exclusive (disjoint) events of different cardinality. Disjoint events can be used to model several issues, e.g. multistate systems with multistate components, different attack alternatives in security-related studies, and components in phased mission systems. Basic events of coherent and non-coherent binary trees can be considered as belonging to sets of cardinality 2. Each event is associated with a binary variable, and a labelling technique is used to distinguish the variables belonging to different sets. The proposed analysis method is based on the approach of binary decision diagrams (BDDs). The application of the rules for the construction of the BDD is driven by the labels associated with disjoint variables. The BDD is then transformed into a ternary decision diagram (TDD). The TDD represents a straightforward data structure for performing the probabilistic analysis. Equations are provided to determine the system unavailability and the probability of critical states. Numerical examples clarify the application of the proposed equations.
Coloured Petri nets and a dynamic reliability problem
Authors: Škňouřilová P , Briš R
Published: December 2008

One of the major problems of the system reliability calculation is an implementation of a dynamic behaviour. One way to show a possible representation of dynamic systems is by using coloured stochastic Petri nets (CSPNs). In this paper this approach is applied to one benchmark on the dynamic reliability taken from the literature. The system consists of a tank containing some liquid where the liquid level is controlled by suitable detectors acting on three hardware components that work independently. The modelled system is consequently used as an input for the calculation of the cumulative distribution functions and other characteristics (e.g. reliability of the system). As the next step, this benchmark will be modified. The first system modification is the maintenance action inclusion. The second one is the enhancement of the system by adding another process variable (the liquid temperature within the tank that is dependent on time). The CSPN approach is used to find a suitable representative scheme of these modifications.