bluuebunny/crossref_metadata_2025 huggingface dataset:
A research-based approach to improving student understanding of the vector nature of kinematical concepts
Authors: Shaffer Peter S. , McDermott Lillian C.
Published: September 2005

In this paper we describe a long-term, large-scale investigation of the ability of university students to treat velocity and acceleration as vectors in one and two dimensions. Some serious conceptual and reasoning difficulties identified among introductory students also were common among pre-college teachers and physics graduate students. Insights gained from this research guided the development of instructional materials that help improve student learning at the introductory level and beyond. The results have strong implications for the teaching of undergraduate physics, the professional development of teachers, and the preparation of teaching assistants.
The occupation of a box as a toy model for the seismic cycle of a fault
Authors: González Álvaro , Gómez Javier B. , Pacheco Amalio F.
Published: September 2005

We illustrate how a simple statistical model can describe the quasiperiodic occurrence of large earthquakes. The model idealizes the loading of elastic energy in a seismic fault by the stochastic filling of a box. The emptying of the box after it is full is analogous to the generation of a large earthquake in which the fault relaxes after having been loaded to its failure threshold. The duration of the filling process is analogous to the seismic cycle, the time interval between two successive large earthquakes in a particular fault. The simplicity of the model enables us to derive the statistical distribution of its seismic cycle. We use this distribution to fit the series of earthquakes with magnitude around six that occurred at the Parkfield segment of the San Andreas fault in California. Using this fit, we estimate the probability of the next large earthquake at Parkfield and devise a simple forecasting strategy.
Relation between policies and work related assault: Minnesota Nurses’ Study
Authors: Nachreiner N M , Gerberich S G , McGovern P M , Church T R , Hansen H E , Geisser M S , Ryan A D
Published: September 2005

Aims:To assess the relation between violence prevention policies and work related assault.

Methods:From Phase 1 of the Minnesota Nurses’ Study, a population based survey of 6300 Minnesota nurses (response 79%), 13.2% reported experiencing work related physical assault in the past year. In Phase 2, a case-control study, 1900 nurses (response 75%) were questioned about exposures relevant to violence, including eight work related violence prevention policy items. A comprehensive causal model served as a basis for survey design, analyses, and interpretation. Sensitivity analyses were conducted for potential exposure misclassification and the presence of an unmeasured confounder.

Results:Results of multiple regression analyses, controlling for appropriate factors, indicated that the odds of physical assault decreased for having a zero tolerance policy (OR = 0.5, 95% CI 0.4 to 0.8) and having policies regarding types of prohibited violent behaviours (OR = 0.5, 95% CI 0.3 to 0.9). Analyses adjusted for non-response and non-selection resulted in wider confidence intervals, but no substantial change in effect estimates.

Conclusions:It appears that some work related violence policies may be protective for the population of Minnesota nurses.
The lagged effect of cold temperature and wind chill on cardiorespiratory mortality in Scotland
Authors: Carder M , McNamee R , Beverland I , Elton R , Cohen G R , Boyd J , Agius R M
Published: September 2005

Aims:To investigate the lagged effects of cold temperature on cardiorespiratory mortality and to determine whether “wind chill” is a better predictor of these effects than “dry bulb” temperature.

Methods:Generalised linear Poisson regression models were used to investigate the relation between mortality and “dry bulb” and “wind chill” temperatures in the three largest Scottish cities (Glasgow, Edinburgh, and Aberdeen) between January 1981 and December 2001. Effects of temperature on mortality (lags up to one month) were quantified. Analyses were conducted for the whole year and by season (cool and warm seasons).

Main results:Temperature was a significant predictor of mortality with the strongest association observed between temperature and respiratory mortality. There was a non-linear association between mortality and temperature. Mortality increased as temperatures fell throughout the range, but the rate of increase was steeper at temperatures below 11°C. The association between temperature and mortality persisted at lag periods beyond two weeks but the effect size generally decreased with increasing lag. For temperatures below 11°C, a 1°C drop in the daytime mean temperature on any one day was associated with an increase in mortality of 2.9% (95% CI 2.5 to 3.4), 3.4% (95% CI 2.6 to 4.1), 4.8% (95% CI 3.5 to 6.2) and 1.7% (95% CI 1.0 to 2.4) over the following month for all cause, cardiovascular, respiratory, and “other” cause mortality respectively. The effect of temperature on mortality was not observed to be significantly modified by season. There was little indication that “wind chill” temperature was a better predictor of mortality than “dry bulb” temperature.

Conclusions:Exposure to cold temperature is an important public health problem in Scotland, particularly for those dying from respiratory disease.
The precision of longitudinal lung function measurements: monitoring and interpretation
Authors: Hnizdo E , Yu L , Freyder L , Attfield M , Lefante J , Glindmeyer H W
Published: September 2005

Background:The efficacy of decision making based on longitudinal spirometric measurements depends critically on the precision of the available data, which is determined by the magnitude of the within-person variation.

Aims:Firstly, to describe and investigate two statistical methods—a pairwise estimate of within-person standard deviationspand the reliability coefficientG—for use in the monitoring of precision of longitudinal measurements of forced expiratory volume in one second (FEV1). Secondly, to investigate the effect of longitudinal data precision on the detectable excess rate of decline in FEV1.

Methods:The authors “monitored” retrospectively on a yearly basis the magnitude of the within-person variationspand the coefficientGin 11 workplace based spirometric monitoring programmes conducted from 1987 to 2001 on 12 729 workers in various industrial plants.

Results:The plant-specific mean values s̄p(range 122–166 ml) and Ḡ (range 0.88–0.95), averaged over all years of follow up, correlated well with the plant-specific within-person standard deviationsr(range 130–177 ml) estimated from all longitudinal data. The correlations were 0.90 for s̄pand 0.68 for Ḡ. The average precision of the longitudinal FEV1 measurements affected the duration of follow up needed to identify a “true” excess rate of decline in FEV1 in an individual.

Conclusions:The results show that monitoring of longitudinal spirometry data precision (1) allows that data precision can be improved or maintained at levels that allow individuals with a rapid decline to be identified at an earlier age; and (2) attaches a measure of precision to the data on which decision making is based.
The additional risk of malignant mesothelioma in former workers and residents of Wittenoom with benign pleural disease or asbestosis
Authors: Reid A , de Klerk N , Ambrosini G , Olsen N , Pang S C , Musk A W
Published: September 2005

Aims:To examine the hypothesis that people with benign pleural disease or asbestosis have an increased risk of malignant mesothelioma beyond that attributable to their degree of asbestos exposure.

Methods:Former workers and residents of the crocidolite mining and milling town of Wittenoom are participating in a cancer prevention programme (n = 1988). The first plain chest radiograph taken at the time of recruitment into the cancer prevention programme was read for evidence of benign pleural disease and asbestosis, using the UICC classification. Crocidolite exposure of former workers was derived from employment records and records of dust measurements performed during the operation of the asbestos mine and mill between 1943 and 1966. Based on fibre counts, exposure for former residents was determined using duration of residence and period of residence (before and after a new mill was commissioned in 1957) and interpolation from periodic hygienic measures undertaken from personal monitors between 1966 and 1992. Cox proportional hazards modelling was used to relate benign pleural disease, asbestosis, asbestos exposure, and mesothelioma.

Results:Between 1990 and 2002, there were 76 cases of mesothelioma (56 of the pleura and 20 of the peritoneum). Cases had more radiographic evidence of (all) benign pleural disease, pleural thickening, blunt/obliterated costophrenic angle, and asbestosis than non-cases. Adjusting for time since first exposure (log years), cumulative exposure (log f/ml-years), and age at the start of the programme, pleural thickening (OR = 3.1, 95% CI 1.2 to 7.6) and asbestosis (OR = 3.3, 95% CI 1.3 to 8.6) were associated with an increased risk of peritoneal mesothelioma. There was no increased risk for pleural mesothelioma.

Conclusion:The presence of benign pleural disease, in particular pleural thickening, and asbestosis appears to increase the risk of mesothelioma of the peritoneum, but not of the pleura beyond that attributable to indices of asbestos exposure in this cohort of subjects exposed to crocidolite.
A search strategy for occupational health intervention studies
Authors: Verbeek J , Salmi J , Pasternack I , Jauhiainen M , Laamanen I , Schaafsma F , Hulshof C , van Dijk F
Published: September 2005

Background:As a result of low numbers and diversity in study type, occupational health intervention studies are not easy to locate in electronic literature databases.

Aim:To develop a search strategy that facilitates finding occupational health intervention studies in Medline, both for researchers and practitioners.

Methods:A gold standard of articles was created by going through two whole volumes of 19 biomedical journals, both occupational health specialty and non-occupational health journals. Criteria for occupational health intervention studies were: evaluating an intervention with an occupational health outcome and a study design with a control group. Each journal was searched independently by two of the authors. Search terms were developed by asking specialists and counting word frequencies in gold standard articles.

Results:Out of 11 022 articles published we found 149 occupational health intervention studies. The most sensitive single terms were work*[tw] (sensitivity 71%, specificity 88%) and effect*[tw] (sensitivity 75%, specificity 63%). The most sensitive string was (effect*[tw] OR control*[tw] OR evaluation*[tw] OR program*[tw]) AND (work*[tw] OR occupation*[tw] OR prevention*[tw] OR protect*[tw]) (sensitivity 89%, specificity 78%). The most specific single terms were “occupational health”[tw] (sensitivity 22%, specificity 98%) and effectiveness[tw] (sensitivity 22%, specificity 98%). The most specific string was (program[tw] OR “prevention and control”[sh]) AND (occupational[tw] OR worker*[tw]) (sensitivity 47%, specificity 98%).

Conclusion:No single search terms are available that can locate occupational health intervention studies sufficiently. The authors’ search strings have acceptable sensitivity and specificity to be used by researchers and practitioners respectively. Redefinition and elaboration of keywords in Medline could greatly facilitate the location of occupational health intervention studies.
WHEN TECHNO-INNOVATIVE RELATIONSHIPS BREAK UP WHAT HAPPENS TO THE NETWORK?
Authors: VAALAND TERJE I. , PURCHASE SHARON , OLARU DOINA
Published: September 2005

The aim of the paper is to explore how relationship ending between business partners contributes to changes in the structure of a technology based network. By studying how network structure is affected by the break-up of dyadic actor bonds, we seek to understand the stability of network positions. The study is empirically based on an organized industrial network, which focuses on market and technological innovation within the Norwegian oil and gas industry. We simulated relationship ending between companies and observed that the "disengaging" parties move towards the periphery of the network. This in turn reduces the stability and sustainability of the whole network. The findings have relevance for how companies manage their relationships, and how organized networks with the purpose of technology innovation are managed.
MANAGING INFORMATION IN NEW PRODUCT DEVELOPMENT: A LITERATURE REVIEW
Authors: FRISHAMMAR JOHAN
Published: September 2005

The new product development (NPD) process is frequently described as a sequence of information processing activities, but "information in NPD" occupies a broader conceptual space than the reduction of uncertainty. This article reviews the area of "information in NPD" by examining the literature on environmental scanning, market orientation, gatekeepers, cross-functional integration, and information use. It is argued that we can understand the process of managing information in terms of three steps: Acquiring, sharing and using. A tentative framework for this area is proposed, and managerial implications resulting from this literature review and tentative frame are outlined and presented.
A NOVEL MECHANISM BASED ON ARTIFICIAL LOGICAL SPIDER WEB FOR REROUTING IN MPLS NETWORKS
Authors: YANG XINYU , SHI YI
Published: September 2005

Multiprotocol label switching (MPLS) is a hybrid solution that combines the advantages of easy forwarding with the ability of guaranteeing quality-of-service (QoS). To deliver reliable service, MPLS requires traffic protection and recovery. Rerouting is one such recovery mechanism. In this paper, we propose a novel rerouting model called DDRAAS that is inspired by the spider and its web in nature. We try to establish an artificial logical spider web in the MPLS network to reorganise it into a structure that is more regular and simple. Based on this, we give the definition of the reroute area. Artificial spiders are then used to explore recovery paths dynamically in the reroute area. DDRAAS can be used to calculate the recovery paths in advance in order to protect the work path, while the improved DDRAAS can be a fast rerouting algorithm to calculate and establish recovery paths when faults occur.

We have simulated our mechanism using the MPLS network simulator (MNS) and the performance metrics were compared to those of other proposals. The simulation results show that our mechanism is better in reducing packet loss, disorder and has faster rerouting speed. These improvements help to minimise the effects of link failure and/or congestion.
NOVEL LOW-COMPLEXITY ANT COLONY BASED MULTIUSER DETECTOR FOR DIRECT SEQUENCE CODE DIVISION MULTIPLE ACCESS
Authors: HIJAZI SAMER L. , NATARAJAN BALASUBRAMANIAM
Published: September 2005

In this paper, we present a novel multiuser detection (MUD) technique based on ant colony optimisation (ACO), for synchronous direct sequence code division multiple access systems. ACO algorithms are based on the cooperative foraging strategy of real ants. While an optimal MUD design using an exhaustive search method is prohibitively complex, we show that the ACO-based MUD converges to the optimal bit-error-rate performance in relatively few iterations providing 95% savings in computational complexity. This reduction in complexity is retained even when considering users with unequal received powers.
A MULTIPLE-OBJECTIVES EVOLUTIONARY PERSPECTIVE TO INTERDOMAIN TRAFFIC ENGINEERING
Authors: UHLIG STEVE
Published: September 2005

We present an application of multiple-objectives evolutionary optimisation to the problem of engineering the distribution of the interdomain traffic in the internet. We show that this practical problem requires such a heuristic due to the potentially conflicting nature of traffic-engineering objectives. Furthermore, having to work on the parameter's space (BGP routing) of the real problem makes such techniques as evolutionary optimisation very easy to use. We show the successful application of our algorithm to two practically relevant problems in interdomain traffic engineering.
METAHEURISTIC APPROACHES TO TRAFFIC GROOMING IN WDM OPTICAL NETWORKS
Authors: XU YONG , SALCEDO-SANZ SANCHO , YAO XIN
Published: September 2005

The widespread deployment of WDM optical networks posts lots of new challenges for network designers. Traffic grooming is one of the most common problems. Efficient grooming of traffic can effectively reduce the overall cost of the network. But unfortunately, traffic grooming problems have been shown to be NP-hard. Therefore, new heuristics must be devised to tackle them. Among these approaches, metaheuristics are among the most promising ones. In this paper, we present a thorough and comprehensive survey on various metaheuristic approaches to the grooming of traffic in both static and dynamic patterns in WDM optical networks. Some future challenges and research directions are also discussed in this paper.
AN EXCESS OF DESCRIPTION: Ethnography, Race, and Visual Technologies
Authors: Poole Deborah
Published: September 2005

This essay provides an overview of recent anthropological work on the relationship between racial thought and the visual technologies of photography and film. I argue that anthropologists have moved away from a concern with representation per se in favor of the more complex discursive and political landscapes opened up by the concepts of media and the archive. My review of this work focuses on the affective register of suspicion that has surrounded both visual methods and the idea of race in anthropology. Whereas this suspicion has led some to dismiss visual technologies as inherently racializing or objectifying, I argue that it is possible to reclaim suspicion as a productive site for rethinking the particular forms of presence, uncertainty, and contingency that characterize both ethnographic and visual accounts of the world. I begin by discussing recent work on the photographic archive, early fieldwork photography, and the subsequent move in the 1960s and 1970s from still photography to film and video within the emergent subfield of visual anthropology. Finally, I consider how more recent work on the problem of race in favor of descriptive accounts of mediascapes.
MAPPING INDIGENOUS LANDS
Authors: Chapin Mac , Lamb Zachary , Threlkeld Bill
Published: September 2005

The mapping of indigenous lands to secure tenure, manage natural resources, and strengthen cultures is a recent phenomenon, having begun in Canada and Alaska in the 1960s and in other regions during the last decade and a half. A variety of methodologies have made their appearance, ranging from highly participatory approaches involving village sketch maps to more technical efforts with geographic information systems (GIS) and remote sensing. In general, indigenous mapping has shown itself to be a powerful tool and it has spread rapidly throughout the world. The distribution of mapping projects is uneven, as opportunities are scarce in many parts of the world. This review covers the genesis and evolution of indigenous mapping, the different methodologies and their objectives, the development of indigenous atlases and guidebooks for mapping indigenous lands, and the often uneasy mix of participatory community approaches with technology. This last topic is at the center of considerable discussion as spatial technologies are becoming more available and are increasingly used in rural areas. The growth of GIS laboratories among tribes in the United States and Canada, who frequently have both financial and technical support, is in sharp contrast to groups in the South—primarily Africa, Asia, and Latin America—where resources are in short supply and permanent GIS facilities are rare.
INDIGENOUS MOVEMENTS IN LATIN AMERICA, 1992–2004: Controversies, Ironies, New Directions
Authors: Jackson Jean E. , Warren Kay B.
Published: September 2005

This review examines literature on indigenous movements in Latin America from 1992 to 2004. It addresses ethnic identity and ethnic activism, in particular the reindianization processes occurring in indigenous communities throughout the region. We explore the impact that states and indigenous mobilizing efforts have had on each other, as well as the role of transnational nongovernmental organizations and para-statal organizations, neoliberalism more broadly, and armed conflict. Shifts in ethnoracial, political, and cultural indigenous discourses are examined, special attention being paid to new deployments of rhetorics concerned with political imaginaries, customary law, culture, and identity. Self-representational strategies will be numerous and dynamic, identities themselves multiple, fluid, and abundantly positional. The challenges these dynamics present for anthropological field research and ethnographic writing are discussed, as is the dialogue between scholars, indigenous and not, and activists, indigenous and not. Conclusions suggest potentially fruitful research directions for the future.
INDIGENOUS MOVEMENTS IN AUSTRALIA
Authors: Merlan Francesca
Published: September 2005

The metaphor of “movement” has been applied in limited measure to indigenous action in Australia, and more to recent events (∼1960s and afterwards) than to earlier ones. This review characterizes movement in social-semiotic terms that allow consideration of such a notion over a longer time span and range of social circumstances than is usual in Australianist literature. Examination of a limited number of relatively well-documented cases from differing times and places reveals differences in the grounds of action and kinds of objectification that movements appear to have involved and also a continuing shift toward shared indigenous-nonindigenous understandings and forms of activism in the face of persisting social differentiation. The arguably limited impact of indigenous movements needs to be considered in the light of systematic constraints on them.
Model Selection in Phylogenetics
Authors: Sullivan Jack , Joyce Paul
Published: September 2005

▪ Abstract  Investigation into model selection has a long history in the statistical literature. As model-based approaches begin dominating systematic biology, increased attention has focused on how models should be selected for distance-based, likelihood, and Bayesian phylogenetics. Here, we review issues that render model-based approaches necessary, briefly review nucleotide-based models that attempt to capture relevant features of evolutionary processes, and review methods that have been applied to model selection in phylogenetics: likelihood-ratio tests, AIC, BIC, and performance-based approaches.
Weanling, but not adult, rabbit colon absorbs bile acids: flux is linked to expression of putative bile acid transporters
Authors: Weihrauch Dirk , Kanchanapoo Jainuch , Ao Mei , Prasad Roli , Piyachaturawat Pawinee , Rao Mrinalini C.
Published: September 2005

Intestinal handling of bile acids is age dependent; adult, but not newborn, ileum absorbs bile acids, and adult, but not weanling or newborn, distal colon secretes Cl−in response to bile acids. Bile acid transport involving the apical Na+-dependent bile acid transporter (Asbt) and lipid-binding protein (LBP) is well characterized in the ileum, but little is known about colonic bile acid transport. We investigated colonic bile acid transport and the nature of the underlying transporters and receptors. Colon from adult, weanling, and newborn rabbits was screened by semiquantitative RT-PCR for Asbt, its truncated variant t-Asbt, LBP, multidrug resistance-associated protein 3, organic solute transporter-α, and farnesoid X receptor. Asbt and LBP showed maximal expression in weanling and significantly less expression in adult and newborn rabbits. The ileum, but not the colon, expressed t-Asbt. Asbt, LBP, and farnesoid X receptor mRNA expression in weanling colon parallel the profile in adult ileum, a tissue designed for high bile acid absorption. To examine their functional role, transepithelial [3H]taurocholate transport was measured in weanling and adult colon and ileum. Under short-circuit conditions, weanling colon and ileum and adult ileum showed net bile acid absorption: 1.23 ± 0.62, 5.53 ± 1.20, and 11.41 ± 3.45 nmol·cm−2·h−1, respectively. However, adult colon secreted bile acids (−1.39 ± 0.47 nmol·cm−2·h−1). We demonstrate for the first time that weanling, but not adult, distal colon shows net bile acid absorption. Thus increased expression of Asbt and LBP in weanling colon, which is associated with parallel increases in taurocholate absorption, has relevance in enterohepatic conservation of bile acids when ileal bile acid recycling is not fully developed.
Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β2-microgloblin knockout mice
Authors: Enoh Victor T. , Lin Cheng Y. , Varma Tushar K. , Sherwood Edward R.
Published: September 2005

Our previous studies showed that β2-microglobulin knockout mice treated with anti-asialoGM1 (β2MKO/αAsGM1 mice) are resistant to injury caused by cecal ligation and puncture (CLP). However, CLP-induced injury is complex. Potential mechanisms of injury include systemic infection, cecal ischemia, and translocation of bacterial toxins such as endotoxin and superantigens. Currently, it is unclear which of these mechanisms of injury contributes to mortality in wild-type mice and whether β2MKO/αAsGM1 mice are resistant to any particular mechanisms of injury. In the present study, we hypothesized that systemic infection is the major cause of injury after CLP in wild-type mice and that β2MKO/αAsGM1 mice are resistant to infection-induced injury. To test this hypothesis, wild-type and β2MKO/αAsGM1 mice were treated with the broad-spectrum antibiotic imipenem immediately after CLP to decrease the impact of systemic infection in our model. Treatment of wild-type and β2MKO/αAsGM1 mice with imipenem decreased bacterial counts by at least two orders of magnitude. However, all wild-type mice, whether treated with saline or imipenem, died by 42 h after CLP and had significant hypothermia, metabolic acidosis, and high plasma concentrations of the cytokines interleukin-6, macrophage inflammatory protein-2, and keratinocyte-derived chemokine. β2MKO/αAsGM1 mice showed 40% long-term survival, which was increased to 90% by imipenem treatment. β2MKO/αAsGM1 mice had less hypothermia, decreased metabolic acidosis, and lower cytokine concentrations at 18 h after CLP compared with wild-type mice. These results suggest that infection is not the major cause of mortality for wild-type mice in our model of CLP. Other mechanisms of injury such as cecal ischemia or translocation of microbial toxins may be more important. β2MKO/αAsGM1 mice appear resistant to these early, non-infection-related causes of CLP-induced injury but showed delayed mortality associated with bacterial dissemination, which was ablated by treatment with imipenem.
Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats
Authors: Meyer Leith C. R. , Fuller Andrea , Mitchell Duncan
Published: September 2005

Neurophysiological studies have shown that serotonergic ligands that bind to 5-HT1A, 5-HT7, and 5-HT4serotonin receptors in brain stem have beneficial effects on respiratory neurons during opioid-induced respiratory depression. The effect of these ligands on respiratory function and pulmonary performance has not been studied. We therefore examined the effects of 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT), an agonist of 5-HT1Aand 5-HT7receptors, and zacopride, an agonist of 5-HT4receptors, to establish whether these ligands would reverse opioid-induced respiratory depression and hypoxia without affecting the immobilizing properties of the opioid drug etorphine. When etorphine was used to sedate and immobilize goats, it significantly decreased respiratory rate ( P = 0.013), percent hemoglobin oxygen saturation ( P < 0.0001), and arterial oxygen partial pressure [PaO2; F(10,70)= 5.67, P < 0.05] and increased arterial carbon dioxide partial pressure [ F(10,70)= 3.87, P < 0.05] and alveolar-arterial oxygen partial pressure gradient [A-a gradients; F(10,70)= 8.23, P < 0.0001]. Zacopride and 8-OH-DPAT, coadministered with etorphine, both attenuated the effects of etorphine; respiration rates did not decrease, and percent hemoglobin oxygen saturation and PaO2remained elevated. Zacopride decreased the hypercapnia, indicating an improvement in ventilation, whereas 8-OH-DPAT did not affect the hypercapnia and, therefore, did not improve ventilation. The main beneficial effect of 8-OH-DPAT was on the pulmonary circulation; it improved oxygen diffusion, indicated by the normal A-a gradients, presumably by improving ventilation perfusion ratios. Neither zacopride nor 8-OH-DPAT reversed etorphine-induced catatonic immobilization. We conclude that serotonergic drugs that act on 5-HT1A, 5-HT7, and 5-HT4receptors reverse opioid-induced respiratory depression and hypoxia without reversing catatonic immobilization.
Partial renal ischemia elicits heterogeneous control of renal sympathetic nerve activity to ischemic and nonischemic regions of the kidney
Authors: Shimizu Kiyoshi , Matsukawa Kanji , Murata Jun , Tsuchimochi Hirotsugu , Ninomiya Ishio
Published: September 2005

We tested the hypothesis that renal sympathetic nerve activity (RSNA) to the ischemic and nonischemic regions responded differently during partial ischemia of the kidney in pentobarbital-anesthetized cats. The renal artery divides into two branches at the front of the renal hilus: one branch perfuses predominantly the dorsal half of the kidney, and the other perfuses its ventral half. We identified the innervated area of a renal nerve bundle by supramaximal electrical stimulation and subsequently determined the changes in RSNA in response to occlusion of either renal arterial branch for 3 min. RSNA to the nonischemic region of the kidney gradually decreased by 23 ± 4% during partial renal ischemia, whereas RSNA to the ischemic region of the same kidney showed no significant change. Crushing either all renal nerve bundles or only the renal nerve bundles terminated to the ischemic region abolished the decrease in RSNA to the nonischemic region. Furthermore, intra-arterial administration of a prostaglandin synthesis inhibitor (meclofenamate, 4 mg/kg) abolished the decrease in RSNA to the nonischemic region of the kidney. Following spinal transection at the level of T7, the inhibitory response in RSNA to the nonischemic region disappeared, whereas the RSNA to the ischemic region was markedly augmented by 47 ± 17%. Thus it is likely that renal chemoreceptors activated during renal partial ischemia elicit heterogeneous control of renal sympathetic outflows to the ischemic and nonischemic regions of the same kidney, which may be determined by a net output between the supraspinal inhibitory and spinal excitatory reflexes.
Apolipoprotein A-IV interacts synergistically with melanocortins to reduce food intake
Authors: Gotoh Koro , Liu Min , Benoit Stephen C. , Clegg Deborah J. , Davidson W. Sean , D'Alessio David , Seeley Randy J. , Tso Patrick , Woods Stephen C.
Published: September 2005

Apolipoprotein (apo) A-IV is an anorexigenic gastrointestinal peptide that is also synthesized in the hypothalamus. The goal of these experiments was to determine whether apo A-IV interacts with the central melanocortin (MC) system in the control of feeding. The third ventricular (i3vt) administration of a subthreshold dose of apo A-IV (0.5 μg) potentiated i3vt MC-induced (metallothionein-II, 0.03 nmol) suppression of 30-min feeding in Long-Evans rats. A subthreshold dose of the MC antagonist (SHU9119, 0.1 nmol, i3vt) completely attenuated the anorectic effect of i3vt apo A-IV (1.5 μg). The i3vt apo A-IV significantly elevated the expression of c-Fos in neurons of the paraventricular nucleus of the hypothalamus, but not in the arcuate nucleus or median eminence. In addition, c-Fos expression was not colocalized with proopiomelanocortin-positive neurons. These data support a synergistic interaction between apo A-IV and melanocortins that reduces food intake by acting downstream of the arcuate.
Elevated blood pressure and cardiac hypertrophy after ablation of thegly96/IEX-1gene
Authors: Sommer Stacy L. , Berndt Theresa J. , Frank Elena , Patel Jeetendra B. , Redfield Margaret M. , Dong Xiangyang , Griffin Matthew D. , Grande Joseph P. , van Deursen Jan M. A. , Sieck Gary C. , Romero Juan C. , Kumar Rajiv
Published: September 2005

gly96/IEX 1 is a growth- and apoptosis-regulating, immediate early gene that is widely expressed in epithelial and vascular tissues. In vascular tissues, expression of the gene is induced by mechanical stretch, and overexpression of the gene prevents injury-induced vascular smooth muscle hypertrophy and neointimal hyperplasia. We now show that deletion of the gly96/ IEX-1 gene in mice is associated with development of elevated blood pressure, cardiac hypertrophy, and diminished fractional shortening of the left ventricle. Systolic blood pressure in conscious male gly96/IEX-1−/−mice is 20–25 mmHg higher than in gly96/IEX-1+/+mice. Serum and/or urine concentrations of sodium, potassium, creatinine, angiotensin II, corticosterone, aldosterone, epinephrine, norepinephrine, prostaglandin E2, thromboxane B2, prostaglandin-6-keto-1α, nitrites and nitrates, cAMP, and cGMP are normal in gly96/IEX-1−/−mice. Alterations in dietary sodium intake do not alter blood pressure in gly96/IEX-1−/−mice. Aortic mRNAs for endothelial nitric oxide synthase, guanylate cyclase-α, and cGMP kinase-1 are increased in gly96/IEX-1−/−mice. Treatment with Nω-nitro-l-arginine methyl ester or l-arginine does not alter blood pressure in gly96/IEX-1−/−mice. Gly96/IEX-1−/−mice respond to infused sodium nitroprusside with decrements in blood pressure similar to those seen in wild-type littermate mice. In contrast to gly96/IEX-1 transgenic mice that have abnormalities in immune function, gly96/IEX-1−/−mice have normal lymphoid tissue architecture and a normal complement of T and B cells in lymphoid tissues. Ablation of the gly96/IEX-1 gene results in hypertension and cardiac hypertrophy, suggesting a novel role for this gene in cardiovascular physiology.
Salt and Blood Pressure: Time to Challenge
Authors: Altun Bulent , Arici Mustafa
Published: September 2005

Hypertension is a worldwide epidemic and its control is costly, but still inadequate. The mechanisms underlying the development of primary hypertension remain elusive. Several observations point to the kidney as a primary actor and sodium as the main culprit for development of hypertension. Over the last few decades, experimental, observational and clinical data have continuously indicated that excess salt intake is positively associated with elevated blood pressure and that blood pressure can be significantly reduced with substantial reductions in dietary sodium. This review highlights the pathophysiological mechanisms linking sodium to elevated blood pressure, synthesizes available evidence for the effect of reducing salt intake in controlling blood pressure. It specifically analyzes 6 recent meta-analyses and dietary approaches to stop hypertension.
Mode of Collection Does Not Influence Haematopoietic Content of Umbilical Cord Blood Units from Caesarean Deliveries
Authors: Solves Pilar , Fillol Manuel , López Mara , Perales Alfredo , Bonilla-Musoles Fernando , Mirabet Vicente , Soler M. Angeles , Roig Roberto J.
Published: September 2005

Background: Collection strategy is the first step for collecting good quality cord blood units. There are two main different techniques for collecting cord blood from the umbilical vein: in the delivery room while the placenta is still in the utero by midwifes and obstetricians, or in an adjacent room after placental delivery by cord blood bank trained personal. Our aim was to evaluate the benefits and disadvantages between the two different cord blood collection strategies in caesarean deliveries. Methods: We retrospectively analysed data of cord blood units collected from caesarean deliveries for a 3-year period. Caesarean section was performed with a low uterine transversal incision in all patients according to common obstetrical practice. Cord blood collection was performed before or after placental delivery. Results: Obstetrical and umbilical cord blood data was obtained from 253 caesarean deliveries. No statistically significant difference was observed for obstetrical variables or cord blood variables except for Hct and platelets. Conclusions: We conclude both methods produce comparable TNC, CD34 and CFU counts of cord blood units collected from caesarean sections. Before placental delivery collection avoids the financial investment that generates the presence of cord blood banking personal in the maternity ward.
12/15-Lipoxygenase Regulates Intercellular Adhesion Molecule-1 Expression and Monocyte Adhesion to Endothelium Through Activation of RhoA and Nuclear Factor-κB
Authors: Bolick David T. , Orr A. Wayne , Whetzel Angela , Srinivasan Suseela , Hatley Melissa E. , Schwartz Martin A. , Hedrick Catherine C.
Published: September 2005

Background—12/15-lipoxygenase (12/15-LO) activity leads to the production of the proinflammatory eicosanoids 12-S-hydroxyeicosatetraenoic acid (12SHETE) and 13-S-hydroxyoctadecadienoic acid. We have previously shown a 3.5-fold increase in endothelial intercellular adhesion molecule (ICAM)-1 expression in mice overexpressing the 12/15-LO gene. We examined whether 12/15-LO activity regulated endothelial ICAM-1 expression.

Methods and Results—Freshly isolated aortic endothelial cells (EC) from 12/15-LO transgenic mice had significantly greater nuclear factor-κB (NF-κB) activation and ICAM mRNA expression compared with C57BL/6J control. 12/15-LO transgenic EC showed elevated RhoA activity, and inhibition of RhoA using either C3 toxin or the Rho-kinase inhibitor Y-27632 blocked NF-κB activation, ICAM-1 induction, and monocyte adhesion. Furthermore, we show that 12SHETE activates protein kinase Cα, which forms a complex with active RhoA and is required for NF-κB–dependent ICAM expression in response to 12SHETE.

Conclusions—The 12/15-LO pathway stimulates ICAM-1 expression through the RhoA/protein kinase Cα-dependent activation of NF-κB. These findings identify a major signaling pathway in EC through which 12/15-LO contributes to vascular inflammation and atherosclerosis.
Dietary and Genetic Probes of Atherogenic Dyslipidemia
Authors: Krauss Ronald M.
Published: September 2005

A goal of dietary management of cardiovascular disease risk in patients with obesity and metabolic syndrome is improvement in the atherogenic dyslipidemia comprising elevated triglyceride, reduced high-density lipoprotein (HDL) cholesterol, and increased numbers of small, dense low-density lipoprotein (LDL) particles. Individuals with a genetically influenced trait characterized by a high proportion of small, dense LDL (phenotype B) respond to a low-fat, high-carbohydrate diet with greater reduction of LDL cholesterol, apoprotein B, and mid-sized LDL2 particles than unaffected subjects (phenotype A). In contrast, in phenotype A subjects there is a reciprocal shift from large LDL1 to small LDL3 such that a high proportion convert to phenotype B. There is evidence for heritable effects on these diet-induced subclass changes and for the involvement of specific genes. For example, a haplotype of the
APOA5
gene associated with increased plasma triglyceride and small, dense LDL predicts greater diet-induced reduction of LDL2, a haplotype-specific effect that is strongly correlated with both increased VLDL precursors and LDL4 products. Understanding of such diet-genotype interactions may help to elucidate mechanisms that are responsible for phenotype B and for its differential dietary responsiveness. This information may also ultimately help in identifying those individuals who are most likely to achieve cardiovascular risk benefit from specific dietary interventions.
Heme Is a Carbon Monoxide Receptor for Large-Conductance Ca
2+
-Activated K
+
Channels
Authors: Jaggar Jonathan H. , Li Anlong , Parfenova Helena , Liu Jianxi , Umstot Edward S. , Dopico Alejandro M. , Leffler Charles W.
Published: September 2005

Carbon monoxide (CO) is an endogenous paracrine and autocrine gaseous messenger that regulates physiological functions in a wide variety of tissues. CO induces vasodilation by activating arterial smooth muscle large-conductance Ca
2+
-activated potassium (BK
Ca
) channels. However, the mechanism by which CO activates BK
Ca
channels remains unclear. Here, we tested the hypothesis that CO activates BK
Ca
channels by binding to channel-bound heme, a BK
Ca
channel inhibitor, and altering the interaction between heme and the conserved heme-binding domain (HBD) of the channel α subunit C terminus. Data obtained using thin-layer chromatography, spectrophotometry, mass spectrometry (MS), and MS-MS indicate that CO modifies the binding of reduced heme to the α subunit HBD. In contrast, CO does not alter the interaction between the HBD and oxidized heme (hemin), to which CO cannot bind. Consistent with these findings, electrophysiological measurements of native and cloned (cbv) cerebral artery smooth muscle BK
Ca
channels show that CO reverses BK
Ca
channel inhibition by heme but not by hemin. Site-directed mutagenesis of the cbv HBD from CKACH to CKASR abolished both heme-induced channel inhibition and CO-induced activation. Furthermore, on binding CO, heme switches from being a channel inhibitor to an activator. These findings indicate that reduced heme is a functional CO receptor for BK
Ca
channels, introduce a unique mechanism by which CO regulates the activity of a target protein, and reveal a novel process by which a gaseous messenger regulates ion channel activity.
Noonan Syndrome Mutation Q79R in Shp2 Increases Proliferation of Valve Primordia Mesenchymal Cells via Extracellular Signal–Regulated Kinase 1/2 Signaling
Authors: Krenz Maike , Yutzey Katherine E. , Robbins Jeffrey
Published: September 2005

The molecular pathways regulating valve development are only partially understood. Recent studies indicate that dysregulation of mitogen-activated protein kinase (MAPK) signaling might play a major role in the pathogenesis of congenital valvular malformations, and, in this study, we explored the role of extracellular signal–regulated kinase (ERK) 1/2 activation in valve primordia expressing the Noonan syndrome mutation Q79R-Shp2. Noonan syndrome is an autosomal dominant disease characterized by dysmorphic features and cardiac abnormalities, with frequent pulmonic stenosis. The Q79R mutation of
PTPN11
previously identified in Noonan syndrome families results in a gain-of-function of the encoded protein tyrosine phosphatase Shp2. We compared the effects of wild-type Shp2 and Q79R-Shp2 on endocardial cushion development. Atrioventricular and outflow tract endocardial cushions were excised from chick embryos, infected with wild-type Shp2 or Q79R-Shp2 adenovirus and embedded in a gel matrix. Q79R-Shp2, but not wild-type-Shp2, expression resulted in increased outgrowth of cells into the gel. The dependence of the Q79R-Shp2 effect on ERK1/2 and p38 MAPK signaling was then determined. The MAPK/ERK kinase (MEK)-1 inhibitor U0126, but not the p38-MAPK pathway inhibitor SB203580, abolished the effect of Q79R-Shp2 on cushion outgrowth. Coinfection with Q79R-Shp2 and dominant negative MEK-1 prevented enhanced endocardial cushion outgrowth, whereas expression of constitutively active MEK-1 mimicked the effect of Q79R-Shp2. Furthermore, dissociated cushion cells displayed increased 5-bromodeoxyuridine incorporation when infected with Q79R-Shp2 but not with wild-type Shp2. This promitotic effect was eliminated by U0126. Our results demonstrate that ERK1/2 activation is both necessary and sufficient to mediate the hyperproliferative effect of a gain-of-function mutation of Shp2 on mesenchymal cells in valve primordia.
Cardioprotective Role of the Mitochondrial ATP-Binding Cassette Protein 1
Authors: Ardehali Hossein , O’Rourke Brian , Marbán Eduardo
Published: September 2005

The mechanism by which mitochondria exert protection against oxidant stress is not clear. We recently showed that a purified mitochondrial fraction containing 5 coimmunoprecipitating proteins (succinate dehydrogenase, adenine nucleotide translocator, ATP synthase, inorganic phosphate carrier, and mitochondrial ATP-binding cassette protein 1 or mABC1) displayed mitochondrial ATP-sensitive K
+
-channel activity. mABC1, a member of the ABC family of proteins, is the only protein in this complex whose function is not known. A yeast homologue of mABC1 protein, Mdl1p, was recently identified to have a novel role for induction of cellular resistance to oxidant stress. Based on these observations, we hypothesized that mABC1 plays a key role in protection of myocardial cells against oxidant stress. We studied the function of mABC1 by modulating the levels of this protein in neonatal rat cardiomyocytes using various molecular techniques, followed by assessment of cell viability and measurement of mitochondrial membrane potential. RNA interference resulted in reduced mABC1 mRNA and protein levels and was associated with significantly attenuated loss of tetramethylrhodamine ethyl ester fluorescence under basal conditions and an increase in trypan blue stained cells. In contrast, adenovirally mediated expression of mABC1 resulted in protection against oxidant stress loss of mitochondrial membrane potential. These results support the notion that mABC1 protein plays a major role in cellular protection against oxidant stress, identifying mABC1 as a novel target for cardioprotective therapeutics.
Protective Effect of α-Lipoic Acid in Lipopolysaccharide-Induced Endothelial Fractalkine Expression
Authors: Sung Mi Jeong , Kim Won , Ahn So Young , Cho Chung-Hyun , Koh Gou Young , Moon Sang-Ok , Kim Duk Hoon , Lee Sik , Kang Kyung Pyo , Jang Kyu Yun , Park Sung Kwang
Published: September 2005

Fractalkine is a unique chemokine that functions as a chemoattractant as well as an adhesion molecule on endothelial cells activated by proinflammatory cytokines. Alpha-lipoic acid (LA), a naturally occurring dithiol compound, is an essential cofactor for mitochondrial bioenergetic enzymes. LA improves glycemic control, reduces diabetic polyneuropathies, and mitigates toxicity associated with heavy metal poisoning. The effects of LA on processes associated with sepsis, however, are unknown. We evaluated the antiinflammatory effect of LA on fractalkine expression in a lipopolysaccharide-induced endotoxemia model. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) significantly induced fractalkine mRNA and protein expression in endothelial cells. LA strongly suppressed TNF-α– or IL-1β–induced fractalkine expression in endothelial cells by suppressing the activities of nuclear factor-κB and specificity protein-1. LA also decreased TNF-α– or IL-1β–stimulated monocyte adhesion to human umbilical vein endothelial cells. As shown by immunohistochemistry, fractalkine protein expression was markedly increased by treatment with lipopolysaccharide in arterial endothelial cells, endocardium, and endothelium of intestinal villi. LA suppressed lipopolysaccharide-induced fractalkine protein expression and infiltration of endothelin 1-positive cells into the heart and intestine in vivo. LA protected against lipopolysaccharide-induced myocardial dysfunction and improved survival in lipopolysaccharide-induced endotoxemia. These results suggest that LA could be an effective agent to reduce fractalkine-mediated inflammatory processes in endotoxemia.