bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient computation of strict minimal siphons for a class of Petri nets models of automated manufacturing systems
Authors: Wang A.R. , Li Z.W. , Jia J.Y.
Published: February 2010

As a structural object of Petri nets, siphons play a key role in the development of deadlock prevention policies for resource allocation systems. The siphon solution in Petri nets has been extensively investigated in the literature. Since the number of siphons in a net grows quickly and in the worst case grows exponentially with respect to the size of a net, their computation is expensive. This paper aims to find the strict minimal number of siphons in a class of Petri nets, called extended systems of linear simple sequential process with resources, which can model flexible manufacturing systems where there exist no flexible processing routings except for the idle state and each operation state may require more than one sort of resources. First, a relationship between structural properties and strict minimal siphons in the class of Petri net is verified. Second, we define the resource digraph of the class net. Finally, based on the obtained results, a method to find the set of strict minimal siphons is proposed. A running example is used to demonstrate the proposed methods.
Organizational Identification and Serendipitous Value Creation in Post-Acquisition Integration
Authors: Colman Helene Loe , Lunnan Randi
Published: February 2010

This study tells the story of two acquisitions made by a company the authors call Multifirm. Multifirm acquired two targets, Datagon and Teknico. The Datagon employees immediately identified with Multifirm, and the integration process was characterized by few conflicts and satisfied employees. The Teknico employees, on the other hand, failed to identify with Multifirm, and the integration process was fraught with disruptions and conflicts. Contrary to the conventional wisdom of identity threats, Multifirm reported that more value was created from the acquisition of Teknico than from Datagon. In this article, we try to understand why this was the case.
Filling the Parenting Gap? Grandparent Involvement With U.K. Adolescents
Authors: Tan Jo-Pei , Buchanan Ann , Flouri Eirini , Attar-Schwartz Shalhevet , Griggs Julia
Published: February 2010

With people living longer and more mothers working, there is some evidence that grandparents are more involved in rearing the next generation. Although there is research in the United Kingdom on kinship care, there is no national research on the extent of grandparent involvement from the perspective of young people. This, the first national survey of 1,478 adolescents in England and Wales, demonstrates the very considerable amount of informal care given by grandparents to adolescents.The findings showed that factors in the wider ecology of children, their parents, grandparents, and the community influenced grandparent—grandchild involvement. In particular, more regular contact and stronger grandparent/grandchild closeness, greater parental encouragement to visit grandparents, better health in grandparents, and less deprivation in the community were significantly associated with more active grandparent involvement. The article concludes that because grandparents may be filling the parenting gap for hard-working parents, there is a case for greater recognition of their role as family supporters.
An Analysis of Human Motion Detection Systems Use During Elder Exercise Routines
Authors: Alexander Gregory L. , Havens Timothy C. , Rantz Marilyn , Keller James , Casanova Abbott Carmen
Published: February 2010

Human motion analysis provides motion pattern and body pose estimations. This study integrates computer-vision techniques and explores a markerless human motion analysis system. Using human—computer interaction (HCI) methods and goals, researchers use a computer interface to provide feedback about range of motion to users. A total of 35 adults aged 65 and older perform three exercises in a public gym while human motion capture methods are used. Following exercises, participants are shown processed human motion images captured during exercises on a customized interface. Standardized questionnaires are used to elicit responses from users during interactions with the interface. A matrix of HCI goals (effectiveness, efficiency, and user satisfaction) and emerging themes are used to describe interactions. Sixteen users state the interface would be useful, but not necessarily for safety purposes. Users want better image quality, when expectations are matched satisfaction increases, and unclear meaning of motion measures decreases satisfaction.
The Stability of Self-Control Among South Korean Adolescents
Authors: Yun Ilhong , Walsh Anthony
Published: February 2010

Gottfredson and Hirschi’s general theory of crime has been widely tested. Yet one of their key hypotheses—the stability of self-control—has received little attention from researchers, and no known study has examined the applicability of the stability hypothesis in a non-Western context. Given Gottfredson and Hirschi’s claim that their low self-control theory transcends cultural and national boundaries, we tested the hypothesis with a nationally representative sample of South Korean adolescents using 5-year panel data. Consistent with studies conducted in the United States, our results offer partial support for Gottfredson and Hirschi’s stability hypothesis. We also provide comparative interpretations of our findings in the South Korean context.
Youth Attitudes Toward Dating Violence in Thailand
Authors: Pradubmook-Sherer Penchan
Published: February 2010

This study assessed the occurrences and intensity of psychological, physical, and sexual attitudes toward dating violence among Thai youths, and examined possible variables related to the formation of these attitudes.The random sample consisted of 1,296 male and female adolescents from high school, vocational school, and out-of-school groups. Thai youths in general reported attitudes that were supportive of dating violence. The variables more closely related to attitudes toward dating violence were personal variables. Peer influence, partner relationships, and family characteristics were related to higher support for dating violence. Females reported higher endorsement of dating violence than males. The theoretical and practical implications of the results are discussed, and recommendations for policy makers are drawn.
Systematic Screening for Emotional and Behavioral Disorders at the High School Level
Authors: Kalberg Jemma Robertson , Lane Kathleen Lynne , Driscoll Steven , Wehby Joseph
Published: February 2010

The authors examined the utility of a modified version of the Systematic Screening for Behavior Disorders for use at the high school level to address issues of comorbidity. Results suggested that the modified version was able to discriminate among students with varying degrees of risk in terms of academic performance as measured by GPA. In terms of convergent validity, teachers were able to differentiate between the social skills of students rated with typical behaviors and those at risk for externalizing or comorbid behaviors in terms of cooperation, self-control, school adjustment, and empathy skills. Furthermore, teachers were better able to discriminate externalizing behaviors relative to internalizing behaviors. Overall, solely relying on teacher nominations may be sufficient for discriminating between the presence versus absence of risk. However, it may not be sufficient to discriminate among the presence of different types of risk, particularly internalizing behaviors. Limitations and educational implications are discussed.
A high-resolution stalagmite record of the Holocene East Asian monsoon from Mt Shennongjia, central China
Authors: Jinguo Dong  , Yongjin Wang  , Hai Cheng  , Hardt Ben , Edwards R. Lawrence , Xinggong Kong  , Jiangying Wu  , Shitao Chen  , Dianbing Liu  , Xiuyang Jiang  , Kan Zhao
Published: February 2010

High-resolution oxygen isotope (δ18O) profiles of six stalagmites from Sanbao Cave in Hubei province, central China, established with 1413 oxygen isotope data and 65 230Th ages, provide a continuous history of East Asian Summer Monsoon (EASM) intensity for the period from 13—0.2 thousand years before present (ky BP, relative to AD 1950). The δ 18O record includes four distinct stages in the evolution of the EASM: (1) an abrupt transition (~11.5 ky BP) into the Holocene; (2) a period of gradual increase in monsoon intensity (11.5—9.5 ky BP); (3) the maximum humid period (9.5—6.5 ky BP); and (4) a period of gradual decline in monsoon intensity (6.5—0.2 ky BP). Comparison of Sanbao with regional records of comparable resolution reveals that the timing of the beginning and end of the Holocene Optimum (as defined by the minimum in δ18 O) was similar in the Indian and East Asian monsoon systems. This supports the idea that shifts in the monsoon tied to shifts in the mean position of the Inter-Tropical Convergence Zone (ITCZ) may control monsoon intensity throughout the entire low-latitude region of Asia on orbital timescales. This observation also supports the idea that the fluctuations in δ18 O recorded across southern Asia reflect broad changes in the monsoon, as opposed to local meteoric precipitation. The EASM records from Sanbao largely follow orbital-scale insolation changes, yet exhibit similar variability to Greenland ice core δ18O on millennial to centennial scales during the early to middle Holocene ( r = 0.94).
Individual patient advocacy, collective responsibility and activism within professional nursing associations
Authors: Mahlin Margaret
Published: February 2010

The systemic difficulties of health care in the USA have brought to light another issue in nurse—patient advocacy — those who require care yet have inadequate or non-existent access. Patient advocacy has focused on individual nurses who in turn advocate for individual patients, yet, while supporting individual patients is a worthy goal of patient advocacy, systemic problems cannot be adequately addressed in this way. The difficulties nurses face when advocating for patients is well documented in the nursing literature and I argue that, through collective advocacy, professional nursing associations ought to extend the reach of individual nurses in order to address systemic problems in health care institutions and bureaucracies.
Moral distress among nursing and non-nursing students
Authors: Range Lillian M , Rotherham Alicia L
Published: February 2010

Their nursing experience and/or training may lead students preparing for the nursing profession to have less moral distress and more favorable attitudes towards a hastened death compared with those preparing for other fields of study. To ascertain if this was true, 66 undergraduates (54 women, 9 men, 3 not stated) in southeastern USA completed measures of moral distress and attitudes towards hastening death. Unexpectedly, the results from nursing and non-nursing majors were not significantly different. All the present students reported moderate moral distress and strong resistance to any efforts to hasten death but these factors were not significantly correlated. However, in the small sample of nurses in training, the results suggest that hastened death situations may not be a prime reason for moral distress.
Encompassing multiple moral paradigms: A challenge for nursing educators
Authors: Shirin Caldwell Elizabeth , Hongyan Lu  , Harding Thomas
Published: February 2010

Providing ethically competent care requires nurses to reflect not only on nursing ethics, but also on their own ethical traditions. New challenges for nurse educators over the last decade have been the increasing globalization of the nursing workforce and the internationalization of nursing education. In New Zealand, there has been a large increase in numbers of Chinese students, both international and immigrant, already acculturated with ethical and cultural values derived from Chinese Confucian moral traditions. Recently, several incidents involving Chinese nursing students in morally conflicting situations have led to one nursing faculty reflecting upon how moral philosophy is taught to non-European students and the support given to Chinese students in integrating the taught curriculum into real-life clinical practice settings. This article uses a case study involving a Chinese student to reflect on the challenges for both faculty members and students when encountering situations that present ethical dilemmas.
Engaging, Exploring, and Experiencing Multicultural Music in Australian Music Teacher Education: The Changing Landscape of Multicultural Music Education
Authors: Southcott Jane , Joseph Dawn
Published: February 2010

In multicultural Australia, the development of positive intercultural attitudes is essential in the creation of a harmonious society. Music education is a powerful medium to address cultural inclusivity. The 2005 National Review of School Music Education challenges Australian higher education institutions to prepare programs that explore multiculturalism to engender tolerance. This research explored how final year teacher education students at Monash University and Deakin University (Victoria, Australia) engage with music of other cultures and how this affects their understanding of cultural diversity in school music. From 2005 to 2008, teacher education students undertaking music methodologies were invited to participate in semi-structured interviews. The data collected from the interviews were transcribed and analyzed using interpretative phenomenological analysis, and from these data, we developed patterns of meaning that are reported thematically: student teachers’ beliefs, attitudes, and understandings of multiculturalism and the classroom realities of multiculturalism.The findings contribute to how we, as tertiary educators, evaluate our role and programs.
Argument, institutional process, and human rights sanctions in democratic foreign policy
Authors: Walldorf C. William
Published: February 2010

When do humanitarian norms lead great powers, especially democracies, to impose sanctions against strategic partners and allies? I argue that answering more specific questions like this in space and time requires constructivists to focus greater attention on institutional and ideational process. Agents are central to policy change. But the ideational and institutional context in which agents build arguments determines when this change is more or less likely. In this vein, I argue that three factors in liberal states — legislatures, the nature of activist pressure, and strategic ideas — explain when humanitarian norms produce sanctions. I demonstrate the argument through a study of US Cold War relations with South Africa, Turkey, and Greece. Among other contributions, this article demonstrates how attention to process can extend the constructivist agenda into a series of new empirical domains and open avenues for contributions to important policy debates.
Punishing the Poor—a debate
Authors: Mayer Margit
Published: February 2010

While in broad agreement about the growing importance of workfare and punitive tendencies in contemporary politics, this article raises four questions about Wacquant’s model of a neoliberal state. Besides pointing out the fuzzy definition of the target group of punitive regulation, it questions whether penal containment is generalizable as ‘core’ of the neoliberal state. Third, it critiques the selective treatment of contemporary poverty policies (excluding a variety of, for example, activating, neoliberal policies), built on a skewed view of the transition from a supposedly generous ‘nanny state’ to a strict ‘daddy state’. Fourth, it challenges the claim of ‘overall fitness’ of punitive containment of urban marginality and the absence of agency and contradictions from the model.
Applying Social Work Approaches, Harm Reduction, and Practice Wisdom to Better Serve Those with Alcohol and Drug Use Disorders
Authors: Karoll Brad R.
Published: February 2010

• Summary: This article reviews, particularly with reference to USA sources, the empowerment perspective, the strengths perspective, and the harm reduction approach as they relate to clinical application in serving those affected with alcohol or drug use disorders.

• Findings: Social work practitioners have long been educated in applying empowerment processes and the strengths perspective to better serve their clients. However, applying the harm reduction approach, particularly to the population of those with substance use disorders, has only recently been discussed in social work literature.

• Applications : The purpose of this article is to provide social work practitioners with relevant information pertinent to the empowerment perspective, the strengths perspective, and the harm reduction approach as they apply to helping those with substance use disorders. It also proposes various strategies involved in the assessment process, treatment planning, and treatment derived from practice experience that integrates these important social work approaches to possibly better assist this population.
Retraction: Urban African American Girls at Risk: An Exploratory Study of Service Needs and Provision
Authors: Brubaker Sarah Jane , Fox Kristan C.
Published: February 2010

Brubaker, S. J., & Fox, K.C., (2010) Urban African American girls at risk: An exploratory study of service needs and provision. Youth Violence and Juvenile Justice. 8(2), 122-137. Original DOI: 10.1177/1541204009361179. This article has been retracted due to the republishing of this article in the July 2010 issue of Youth Violence and Juvenile Justice, 8(3). The July issue will be a special issue titled Issues in Race and Social Control, dedicated to the author of the article, Kristan C. Fox. Please find the republished article now in Youth Violence and Juvenile Justice 8(3), 250-265, DOI: 10.1177/1541204010376319.
Does Cueing Training Improve Physical Activity in Patients With Parkinson’s Disease?
Authors: Lim Inge , van Wegen Erwin , Jones Diana , Rochester Lynn , Nieuwboer Alice , Willems Anne-Marie , Baker Katherine , Hetherington Vicki , Kwakkel Gert
Published: February 2010

Background. Patients with Parkinson’s disease (PD) are encouraged to stay active to maintain their mobility. Ambulatory activity monitoring (AM) provides an objective way to determine type and amount of gait-related daily activities. Objective . To investigate the effects of a home cueing training program on functional walking activity in PD. Methods. In a single-blind, randomized crossover trial, PD patients allocated to early intervention received cueing training for 3 weeks, whereas the late intervention group received training in the following 3 weeks. Training was applied at home, using a prototype cueing device. AM was applied at baseline, 3, 6, and 12 weeks in the patient’s home, to record body movements. Postures and motions were classified as percentage of total time spent on ( a) static activity, further specified as % sitting and % standing, and ( b) % dynamic activity, further specified as % walking, % walking periods exceeding 5 seconds (W>" xbd="1983" xhg="1960" ybd="1440" yhg="1401"/>5s) and 10 seconds (W>10s). Random coefficient analysis was applied. Results. A total of 153 patients participated in this trial. Significant improvements were found for dynamic activity (β= 4.46; P < .01), static activity (β=-3.34; P < .01), walking (β= 4.23; P < .01), W>5s (β = 2.63; P < .05), and W>10s (β = 2.90; P < .01). All intervention effects declined significantly at 6 weeks follow-up. Conclusion. Cueing training in PD patients’ own home significantly improves the amount of walking as recorded by AM. Treatment effects reduced after the intervention period, pointing to the need for permanent cueing devices and follow-up cueing training.
Transnational Children’s Television
Authors: Lustyik Katalin
Published: February 2010

/ This article examines children’s television in the context of the debate on media globalization by positioning Viacom-owned Nickelodeon, currently beamed into more than 400 million households, as a quintessential type of transnational television that is critical to understanding the contemporary landscape of media industries and cultures worldwide. The author argues that the majority of globally branded children’s television networks, in comparison to other types of transnational television often associated with multidirectional media flow, tend to be merely clones of the original US versions. However, this argument is intended to move beyond traditional references to either cultural or American imperialism. By counterposing two locales, the article uses Nickelodeon’s operations in New Zealand and Australia as a case study to critically examine the corporate practice of localization employed by a US transnational children’s multimedia brand in different media markets.
Trapeziometacarpal joint implants can be evaluated by roentgen stereophotogrammetric analysis
Authors: Hansen T. B. , Larsen K. , Bjergelund L. , Stilling M.
Published: February 2010

Both marker-based roentgen stereophotogrammetric analysis (RSA) and model-based RSA have been helpful evaluation tools in hip and knee arthroplasty. The purpose of this study was to test both model-based and marker-based RSA in the evaluation of total joint prostheses of the trapeziometacarpal joint. In a phantom study, the precision of marker-based RSA was tested with a cemented polyethylene cup and compared with the precision of model-based RSA in an uncemented Elektra screw cup. The precision of model-based RSA of the metacarpal stem was tested using an uncemented Elektra metacarpal stem. In a clinical study 11 patients had double stereo radiographs followed by RSA analysis. The precision of translation in both marker-based and model-based RSA was sufficient for clinical use, but rotation cannot be estimated with sufficient precision.
Tumours of the Hand: a Review On Histology of Bone Malignancies
Authors: Baumhoer D. , Jundt G.
Published: February 2010

Malignant bone tumours of the hands are uncommon. Although almost all lesions that occur in other parts of the skeleton can also affect the hands, their frequency, distribution and clinical characteristics differ. This review focusses on the histology of these tumours and gives an overview of the main differential diagnoses. Close correlation to radiologic and clinical features usually leads to the correct diagnosis.
Apelin induces enlarged and nonleaky blood vessels for functional recovery from ischemia
Authors: Kidoya Hiroyasu , Naito Hisamichi , Takakura Nobuyuki
Published: February 2010

The efficacy of therapeutic angiogenesis for revascularization in ischemia using genes, proteins, and cells has been established. For further improvement, processes allowing enlargement of the luminal cavity to facilitate efficient blood flow need to be facilitated. Recently, we found that expression of APJ and its specific ligand, apelin, is seen in endothelial cells when angiogenesis is taking place during embryogenesis. Apelin-deficient mice are viable but have narrow intersomitic vessels during embryogenesis and narrow blood vessels in the trachea and skin after birth. Apelin induces the formation of larger cords of endothelial cells, mainly mediated by cell-cell aggregation, resulting in the generation of larger blood vessels. Here we report that transgenic overexpression of apelin in keratinocytes induces enlarged but not leaky blood vessels in the dermis. In the hind limb ischemia model, apelin together with vascular endothelial growth factor (VEGF) effectively induced functional vessels larger than with VEGF alone. Endogenous apelin is required for the suppression of VEGF-, histamine-, or inflammation-induced vascular hyperpermeability. Apelin inhibited the down-modulation of vascular endothelial-cadherin by VEGF, resulting in suppression of hyperpermeability. Our results suggest apelin efficacy for therapeutic angiogenesis.
SPRIT: Identifying horizontal gene transfer in rooted phylogenetic trees
Authors: Hill Tobias , Nordström Karl JV , Thollesson Mikael , Säfström Tommy M , Vernersson Andreas KE , Fredriksson Robert , Schiöth Helgi B
Published: February 2010

Background

Phylogenetic trees based on sequences from a set of taxa can be incongruent due to horizontal gene transfer (HGT). By identifying the HGT events, we can reconcile the gene trees and derive a taxon tree that adequately represents the species' evolutionary history. One HGT can be represented by a rooted Subtree Prune and Regraft (RSPR) operation and the number of RSPRs separating two trees corresponds to the minimum number of HGT events. Identifying the minimum number of RSPRs separating two trees is NP-hard, but the problem can be reduced to fixed parameter tractable. A number of heuristic and two exact approaches to identifying the minimum number of RSPRs have been proposed. This is the first implementation delivering an exact solution as well as the intermediate trees connecting the input trees.

Results

We present the SPR Identification Tool (SPRIT), a novel algorithm that solves the fixed parameter tractable minimum RSPR problem and its GPL licensed Java implementation. The algorithm can be used in two ways, exhaustive search that guarantees the minimum RSPR distance and a heuristic approach that guarantees finding a solution, but not necessarily the minimum one. We benchmarked SPRIT against other software in two different settings, small to medium sized trees i.e. five to one hundred taxa and large trees i.e. thousands of taxa. In the small to medium tree size setting with random artificial incongruence, SPRIT's heuristic mode outperforms the other software by always delivering a solution with a low overestimation of the RSPR distance. In the large tree setting SPRIT compares well to the alternatives when benchmarked on finding a minimum solution within a reasonable time. SPRIT presents both the minimum RSPR distance and the intermediate trees.

Conclusions

When used in exhaustive search mode, SPRIT identifies the minimum number of RSPRs needed to reconcile two incongruent rooted trees. SPRIT also performs quick approximations of the minimum RSPR distance, which are comparable to, and often better than, purely heuristic solutions. Put together, SPRIT is an excellent tool for identification of HGT events and pinpointing which taxa have been involved in HGT.
Genome-wide analysis of aberrant methylation in human breast cancer cells using methyl-DNA immunoprecipitation combined with high-throughput sequencing
Authors: Ruike Yoshinao , Imanaka Yukako , Sato Fumiaki , Shimizu Kazuharu , Tsujimoto Gozoh
Published: February 2010

Background

Cancer cells undergo massive alterations to their DNA methylation patterns that result in aberrant gene expression and malignant phenotypes. However, the mechanisms that underlie methylome changes are not well understood nor is the genomic distribution of DNA methylation changes well characterized.

Results

Here, we performed methylated DNA immunoprecipitation combined with high-throughput sequencing (MeDIP-seq) to obtain whole-genome DNA methylation profiles for eight human breast cancer cell (BCC) lines and for normal human mammary epithelial cells (HMEC). The MeDIP-seq analysis generated non-biased DNA methylation maps by covering almost the entire genome with sufficient depth and resolution. The most prominent feature of the BCC lines compared to HMEC was a massively reduced methylation level particularly in CpG-poor regions. While hypomethylation did not appear to be associated with particular genomic features, hypermethylation preferentially occurred at CpG-rich gene-related regions independently of the distance from transcription start sites. We also investigated methylome alterations during epithelial-to-mesenchymal transition (EMT) in MCF7 cells. EMT induction was associated with specific alterations to the methylation patterns of gene-related CpG-rich regions, although overall methylation levels were not significantly altered. Moreover, approximately 40% of the epithelial cell-specific methylation patterns in gene-related regions were altered to those typical of mesenchymal cells, suggesting a cell-type specific regulation of DNA methylation.

Conclusions

This study provides the most comprehensive analysis to date of the methylome of human mammary cell lines and has produced novel insights into the mechanisms of methylome alteration during tumorigenesis and the interdependence between DNA methylome alterations and morphological changes.
Caspase-1 genetic variation is not associated with Alzheimer's disease risk
Authors: Vázquez-Higuera José Luis , Rodríguez-Rodríguez Eloy , Sánchez-Juan Pascual , Mateo Ignacio , Pozueta Ana , Martínez-García Ana , Frank Ana , Valdivieso Fernando , Berciano José , Bullido María J , Combarros Onofre
Published: February 2010

Background

Interleukin (IL)-1β is a potent proinflammatory cytokine markedly overexpressed in the brains of patients with Alzheimer's disease (AD), and also involved in development of atherosclerosis and coronary artery disease. Caspase-1 (CASP1), formerly called IL-1β converting enzyme (ICE), mediates the cleavage of the inactive precursor of IL-1β into the biologically active form. CASP1 genetic variation (G+7/in6A, rs501192) has been associated with susceptibility to myocardial infarction and cardiovascular death risk. We examined the contribution of this gene to the susceptibility for AD.

Methods

We examined genetic variations of CASP1 by genotyping haplotype tagging SNPs (htSNPs) (rs501192, rs556205 and rs530537) in a group of 628 Spanish AD cases and 722 controls.

Results

There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by age, gender or APOE ε4 allele.

Conclusion

Our negative findings in the Spanish population argue against the hypothesis that CASP1 genetic variations are causally related to AD risk.
Angiotensin II type 2 receptor signaling significantly attenuates growth of murine pancreatic carcinoma grafts in syngeneic mice
Authors: Doi Chiyo , Egashira Noboru , Kawabata Atsushi , Maurya Dharmendra Kumar , Ohta Naomi , Uppalapati Deepthi , Ayuzawa Rie , Pickel Lara , Isayama Yuka , Troyer Deryl , Takekoshi Susumu , Tamura Masaaki
Published: February 2010

Background

Pancreatic cancer is one of the most aggressive human malignancies, with a very poor prognosis. To evaluate the effect of angiotensin II (Ang II) type 2 receptor (AT2) expression in the host's body on the growth of pancreatic carcinoma, we have investigated the growth of mouse pancreatic ductal carcinoma grafts in syngeneic wild type and AT2receptor-deficient (AT2-KO) mice.

Methods

The role of AT2receptor-signaling in stromal cells on the growth of murine pancreatic carcinoma cells (PAN02) was studied using variousin vitroandin vivoassays.In vivocell proliferation, apoptosis, and vasculature in tumors were monitored by Ki-67 immunostaining, TUNEL assay, and von Willebrand factor immunostaining, respectively. In the co-culture study, cell proliferation was measured by MTT cell viability assay. All the data were analyzed using t-test and data were treated as significant whenp< 0.05.

Results

Our results show that the growth of subcutaneously transplanted syngeneic xenografts of PAN02 cells, mouse pancreatic ductal carcinoma cells derived from the C57/BL6 strain, was significantly faster in AT2-KO mice compared to control wild type mice. Immunohistochemical analysis of tumor tissue revealed significantly more Ki-67 positive cells in xenografts grown in AT2-KO mice than in wild type mice. The index of apoptosis is slightly higher in wild type mice than in AT2-KO mice as evaluated by TUNEL assay. Tumor vasculature number was significantly higher in AT2-KO mice than in wild type mice.In vitroco-culture studies revealed that the growth of PAN02 cells was significantly decreased when grown with AT2receptor gene transfected wild type and AT2-KO mouse-derived fibroblasts. Faster tumor growth in AT2-KO mice may be associated with higher VEGF production in stromal cells.

Conclusions

These results suggest that Ang II regulates the growth of pancreatic carcinoma cells through modulating functions of host stromal cells; Moreover, Ang II AT2receptor signaling is a negative regulator in the growth of pancreatic carcinoma cells. These findings indicate that the AT2receptor in stromal fibroblasts is a potentially important target for chemotherapy for pancreatic cancer.
Increased expression of collagens, transforming growth factor-β1, and -β3 in gluteal muscle contracture
Authors: Zhao Chen-Guang , He Xi-Jing , Lu Bin , Li Hao-Peng , Kang An-Jing
Published: February 2010

Backgroud

Gluteal muscle contracture (GMC) is a multi-factor human chronic fibrotic disease of the gluteal muscle. Fibrotic tissue is characterized by excessive accumulation of collagen in the muscle's extracellular matrix. Transforming growth factor (TGF)-β1 and -β2 are thought to play an important role in fibrogenesis, while TGF-β3 is believed to have an anti-fibrotic function. We hypothesize that the expression of collagen and TGF-βs would be up-regulated in GMC patients.

Methods

The expression of collagen type I, type III and TGF-βs were studied in 23 fibrotic samples and 23 normal/control samples in GMC patients using immunohistochemistry, reverse transcription and polymerase chain reaction (RT-PCR) and western bolt analysis.

Results

Compared to the unaffected adjacent muscle, increased expression of TGF-β1 and -β3 was associated with deposition of collagen type I and type III in the fibrotic muscle of the GMC patients at the mRNA level. Strong up-regulation of these proteins in fibrotic muscle was confirmed by immunohistochemical staining and western blot analysis. TGF-β2 was not up-regulated in relation to GMC.

Conclusion

This study confirmed our hypothesis that collagen types I, III, TGF-β1 and TGF-β3 were up-regulated in biopsy specimens obtained from patients with GMC. Complex interaction of TGF-β1 with profibrotic function and TGF-β3 with antifibrotic function may increase synthesis of collagens and thereby significantly contribute to the process of gluteal muscle scarring in patients with GMC.
Consumers of natural health products: natural-born pharmacovigilantes?
Authors: Walji Rishma , Boon Heather , Barnes Joanne , Austin Zubin , Welsh Sandy , Baker G Ross
Published: February 2010

Background

Natural health products (NHPs), such as herbal medicines and vitamins, are widely available over-the-counter and are often purchased by consumers without advice from a healthcare provider. This study examined how consumers respond when they believe they have experienced NHP-related adverse drug reactions (ADRs) in order to determine how to improve current safety monitoring strategies.

Methods

Qualitative semi-structured interviews were conducted with twelve consumers who had experienced a self-identified NHP-related ADR. Key emergent themes were identified and coded using content analysis techniques.

Results

Consumers were generally not comfortable enough with their conventional health care providers to discuss their NHP-related ADRs. Consumers reported being more comfortable discussing NHP-related ADRs with personnel from health food stores, friends or family with whom they had developed trusted relationships. No one reported their suspected ADR to Health Canada and most did not know this was possible.

Conclusion

Consumers generally did not report their suspected NHP-related ADRs to healthcare providers or to Health Canada. Passive reporting systems for collecting information on NHP-related ADRs cannot be effective if consumers who experience NHP-related ADRs do not report their experiences. Healthcare providers, health food store personnel, manufacturers and other stakeholders also need to take responsibility for reporting ADRs in order to improve current pharmacovigilance of NHPs.
A Genome-wide screen identifies frequently methylated genes in haematological and epithelial cancers
Authors: Dunwell Thomas , Hesson Luke , Rauch Tibor A , Wang Lihui , Clark Richard E , Dallol Ashraf , Gentle Dean , Catchpoole Daniel , Maher Eamonn R , Pfeifer Gerd P , Latif Farida
Published: February 2010

Background

Genetic as well as epigenetic alterations are a hallmark of both epithelial and haematological malignancies. High throughput screens are required to identify epigenetic markers that can be useful for diagnostic and prognostic purposes across malignancies.

Results

Here we report for the first time the use of the MIRA assay (methylated CpG island recovery assay) in combination with genome-wide CpG island arrays to identify epigenetic molecular markers in childhood acute lymphoblastic leukemia (ALL) on a genome-wide scale. We identified 30 genes demonstrating methylation frequencies of ≥25% in childhood ALL, nine genes showed significantly different methylation frequencies in B vs T-ALL. For majority of the genes expression could be restored in methylated leukemia lines after treatment with 5-azaDC. Forty-four percent of the genes represent targets of the polycomb complex. In chronic myeloid leukemia (CML) two of the genes, (TFAP2A and EBF2), demonstrated increased methylation in blast crisis compared to chronic phase (P < 0.05). Furthermore hypermethylation of an autophagy related gene ATG16L2 was associated with poorer prognosis in terms of molecular response to Imatinib treatment. Lastly we demonstrated that ten of these genes were also frequently methylated in common epithelial cancers.

Conclusion

In summary we have identified a large number of genes showing frequent methylation in childhood ALL, methylation status of two of these genes is associated with advanced disease in CML and methylation status of another gene is associated with prognosis. In addition a subset of these genes may act as epigenetic markers across hematological malignancies as well as common epithelial cancers.
Comparative effects of oleoyl-estrone and a specific β3-adrenergic agonist (CL316, 243) on the expression of genes involved in energy metabolism of rat white adipose tissue
Authors: Ferrer-Lorente Raquel , Cabot Cristina , Fernández-López José-Antonio , Alemany Marià
Published: February 2010

Background

The combination of oleoyl-estrone (OE) and a selective β3-adrenergic agonist (B3A; CL316,243) treatment in rats results in a profound and rapid wasting of body reserves (lipid).

Methods

In the present study we investigated the effect of OE (oral gavage) and/or B3A (subcutaneous constant infusion) administration for 10 days to overweight male rats, compared with controls, on three distinct white adipose tissue (WAT) sites: subcutaneous inguinal, retroperitoneal and epididymal. Tissue weight, DNA (and, from these values cellularity), cAMP content and the expression of several key energy handling metabolism and control genes were analyzed and computed in relation to the whole site mass.

Results

Both OE and B3A significantly decreased WAT mass, with no loss of DNA (cell numbers). OE decreased and B3A increased cAMP. Gene expression patterns were markedly different for OE and B3A. OE tended to decrease expression of most genes studied, with no changes (versus controls) of lipolytic but decrease of lipogenic enzyme genes. The effects of B3A were widely different, with a generalized increase in the expression of most genes, including the adrenergic receptors, and, especially the uncoupling protein UCP1.

Discussion

OE and B3A, elicit widely different responses in WAT gene expression, end producing similar effects, such as shrinking of WAT, loss of fat, maintenance of cell numbers. OE acted essentially on the balance of lipolysis-lipogenesis and the blocking of the uptake of substrates; its decrease of synthesis favouring lipolysis. B3A induced a shotgun increase in the expression of most regulatory systems in the adipocyte, an effect that in the end favoured again the loss of lipid; this barely selective increase probably produces inefficiency, which coupled with the increase in UCP1 expression may help WAT to waste energy through thermogenesis.

Conclusions

There were considerable differences in the responses of the three WAT sites. OE in general lowered gene expression and stealthily induced a substrate imbalance. B3A increasing the expression of most genes enhanced energy waste through inefficiency rather than through specific pathway activation. There was not a synergistic effect between OE and B3A in WAT, but their combined action increased WAT energy waste.
A rapid and robust assay for detection of S-phase cell cycle progression in plant cells and tissues by using ethynyl deoxyuridine
Authors: Kotogány Edit , Dudits Dénes , Horváth Gábor V , Ayaydin Ferhan
Published: February 2010

Background

Progress in plant cell cycle research is highly dependent on reliable methods for detection of cells replicating DNA. Frequency of S-phase cells (cells in DNA synthesis phase) is a basic parameter in studies on the control of cell division cycle and the developmental events of plant cells. Here we extend the microscopy and flow cytometry applications of the recently developed EdU (5-ethynyl-2'-deoxyuridine)-based S-phase assay to various plant species and tissues. We demonstrate that the presented protocols insure the improved preservation of cell and tissue structure and allow significant reduction in assay duration. In comparison with the frequently used detection of bromodeoxyuridine (BrdU) and tritiated-thymidine incorporation, this new methodology offers several advantages as we discuss here.

Results

Applications of EdU-based S-phase assay in microscopy and flow cytometry are presented by using cultured cells of alfalfa, Arabidopsis, grape, maize, rice and tobacco. We present the advantages of EdU assay as compared to BrdU-based replication assay and demonstrate that EdU assay -which does not require plant cell wall digestion or DNA denaturation steps, offers reduced assay duration and better preservation of cellular, nuclear and chromosomal morphologies. We have also shown that fast and efficient EdU assay can also be an efficient tool for dual parameter flow cytometry analysis and for quantitative assessment of replication in thick root samples of rice.

Conclusions

In plant cell cycle studies, EdU-based S-phase detection offers a superior alternative to the existing S-phase assays. EdU method is reliable, versatile, fast, simple and non-radioactive and it can be readily applied to many different plant systems.
Cytokines levels, Severity of acute mucositis and the need of PEG tube installation during chemo-radiation for head and neck cancer - a prospective pilot study
Authors: Meirovitz Amichay , Kuten Michal , Billan Salem , Abdah-Bortnyak Roxolyana , Sharon Anat , Peretz Tamar , Sela Mordechai , Schaffer Moshe , Barak Vivian
Published: February 2010

Background

The purpose of this pilot study was to detect a correlation between serum cytokine levels and severity of mucositis, necessitating installation of a percutaneous endoscopic gastrostomy tube (PEG) in head and neck (H&N) cancer patients receiving combined chemo-radiation therapy.

Patients and Methods

Fifteen patients with H&N epithelial cancer were recruited to this study. All patients received radiotherapy to the H&N region, with doses ranging from 50-70 Gy. Chemotherapy with cisplatin, carboplatin, 5-fluorouracil and taxanes was given to high-risk patients, using standard chemotherapy protocols. Patients were evaluated for mucositis according to WHO common toxicity criteria, and blood samples were drawn for inflammatory (IL-1, IL-6, IL-8, TNF-α) and anti-inflammatory (IL-10) cytokine levels before and during treatment.

Results

A positive correlation was found between IL-6 serum levels and severity of mucositis and dysphagia; specifically, high IL-6 levels at week 2 were correlated with a need for PEG tube installation. A seemingly contradictory correlation was found between low IL-8 serum levels and a need for a PEG tube.

Conclusion

These preliminary results, indicating a correlation between IL-6 and IL-8 serum levels and severity of mucositis and a need for a PEG tube installation, justify a large scale study.
Insulation of a synthetic hydrogen metabolism circuit in bacteria
Authors: Agapakis Christina M , Ducat Daniel C , Boyle Patrick M , Wintermute Edwin H , Way Jeffrey C , Silver Pamela A
Published: February 2010

Background

The engineering of metabolism holds tremendous promise for the production of desirable metabolites, particularly alternative fuels and other highly reduced molecules. Engineering approaches must redirect the transfer of chemical reducing equivalents, preventing these electrons from being lost to general cellular metabolism. This is especially the case for high energy electrons stored in iron-sulfur clusters within proteins, which are readily transferred when two such clusters are brought in close proximity. Iron sulfur proteins therefore require mechanisms to ensure interaction between proper partners, analogous to many signal transduction proteins. While there has been progress in the isolation of engineered metabolic pathways in recent years, the design of insulated electron metabolism circuits in vivo has not been pursued.

Results

Here we show that a synthetic hydrogen-producing electron transfer circuit in Escherichia coli can be insulated from existing cellular metabolism via multiple approaches, in many cases improving the function of the pathway. Our circuit is composed of heterologously expressed [Fe-Fe]-hydrogenase, ferredoxin, and pyruvate-ferredoxin oxidoreductase (PFOR), allowing the production of hydrogen gas to be coupled to the breakdown of glucose. We show that this synthetic pathway can be insulated through the deletion of competing reactions, rational engineering of protein interaction surfaces, direct protein fusion of interacting partners, and co-localization of pathway components on heterologous protein scaffolds.

Conclusions

Through the construction and characterization of a synthetic metabolic circuit in vivo, we demonstrate a novel system that allows for predictable engineering of an insulated electron transfer pathway. The development of this system demonstrates working principles for the optimization of engineered pathways for alternative energy production, as well as for understanding how electron transfer between proteins is controlled.