bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature increase prevails over acidification in gene expression modulation of amastigote differentiation in Leishmania infantum
Authors: Alcolea Pedro J , Alonso Ana , Gómez Manuel J , Sánchez-Gorostiaga Alicia , Moreno-Paz Mercedes , González-Pastor Eduardo , Toraño Alfredo , Parro Víctor , Larraga Vicente
Published: January 2010

Background

The extracellular promastigote and the intracellular amastigote stages alternate in the digenetic life cycle of the trypanosomatid parasiteLeishmania. Amastigotes develop inside parasitophorous vacuoles of mammalian phagocytes, where they tolerate extreme environmental conditions. Temperature increase and pH decrease are crucial factors in the multifactorial differentiation process of promastigotes to amastigotes. Although expression profiling approaches for axenic, cell culture- and lesion-derived amastigotes have already been reported, the specific influence of temperature increase and acidification of the environment on developmental regulation of genes has not been previously studied. For the first time, we have used customL. infantumgenomic DNA microarrays to compare the isolated and the combined effects of both factors on the transcriptome.

Results

Immunofluorescence analysis of promastigote-specific glycoprotein gp46 and expression modulation analysis of the amastigote-specific A2 gene have revealed that concomitant exposure to temperature increase and acidification leads to amastigote-like forms. The temperature-induced gene expression profile in the absence of pH variation resembles the profile obtained under combined exposure to both factors unlike that obtained for exposure to acidification alone. In fact, the subsequent fold change-based global iterative hierarchical clustering analysis supports these findings.

Conclusions

The specific influence of temperature and pH on the differential regulation of genes described in this study and the evidence provided by clustering analysis is consistent with the predominant role of temperature increase over extracellular pH decrease in the amastigote differentiation process, which provides new insights intoLeishmaniaphysiology.
Acute stress alters transcript expression pattern and reduces processing of proBDNF to mature BDNF in Dicentrarchus labrax
Authors: Tognoli Chiara , Rossi Federica , Di Cola Francesco , Baj Gabriele , Tongiorgi Enrico , Terova Genciana , Saroglia Marco , Bernardini Giovanni , Gornati Rosalba
Published: January 2010

Background

Stress involves alterations of brain functioning that may precipitate to mood disorders. The neurotrophin Brain Derived Neurotrophic Factor (BDNF) has recently been involved in stress-induced adaptation. BDNF is a key regulator of neuronal plasticity and adaptive processes. Regulation of BDNF is complex and may reflect not only stress-specific mechanisms but also hormonal and emotional responses. For this reason we used, as an animal model of stress, a fish whose brain organization is very similar to that of higher vertebrates, but is generally considered free of emotional reactions.

Results

We provide a comprehensive characterization of BDNF gene in the Dicentrarchus labrax and its transcriptional, translational and post-translational regulation following acute stress. While total BDNF mRNA levels are unchanged, BDNF transcripts 1c and 1d resulted down regulated after acute stress. Acute stress induces also a significant increase in proBDNF levels and reduction in mature BDNF suggesting altered regulation of proBDNF proteolytic processing. Notably, we provide here the first evidence that fishes possess a simplified proteolytic regulation of BDNF since the pro28Kda form, generated by the SKI-1 protease in mammals, is absent in fishes because the cleavage site has first emerged in reptilians. Finally, we show that the proBDNF/totBDNF ratio is a highly predictive novel quantitative biomarker to detect stress in fishes with sensitivity = 100%, specificity = 87%, and Negative Predictive Value = 100%.

Conclusion

The high predictivity of proBDNF/totBDNF ratio for stress in lower vertebrates indicates that processing of BDNF is a central mechanism in adaptation to stress and predicts that a similar regulation of pro/mature BDNF has likely been conserved throughout evolution of vertebrates from fish to man.
Breast cancer cell lines carry cell line-specific genomic alterations that are distinct from aberrations in breast cancer tissues: Comparison of the CGH profiles between cancer cell lines and primary cancer tissues
Authors: Tsuji Katumi , Kawauchi Shigeto , Saito Soichiro , Furuya Tomoko , Ikemoto Kenzo , Nakao Motonao , Yamamoto Shigeru , Oka Masaaki , Hirano Takashi , Sasaki Kohsuke
Published: January 2010

Background

Cell lines are commonly used in various kinds of biomedical research in the world. However, it remains uncertain whether genomic alterations existing in primary tumor tissues are represented in cell lines and whether cell lines carry cell line-specific genomic alterations. This study was performed to answer these questions.

Methods

Array-based comparative genomic hybridization (CGH) was employed with 4030 bacterial artificial chromosomes (BACs) that cover the genome at 1.0 megabase resolution to analyze DNA copy number aberrations (DCNAs) in 35 primary breast tumors and 24 breast cancer cell lines. DCNAs were compared between these two groups. A tissue microdissection technique was applied to primary tumor tissues to reduce the contamination of samples by normal tissue components.

Results

The average number of BAC clones with DCNAs was 1832 (45.3% of spotted clones) and 971 (24.9%) for cell lines and primary tumor tissues, respectively. Gains of 1q and 8q and losses of 8p, 11q, 16q and 17p were detected in >50% of primary cancer tissues. These aberrations were also frequently detected in cell lines. In addition to these alterations, the cell lines showed recurrent genomic alterations including gains of 5p14-15, 20q11 and 20q13 and losses of 4p13-p16, 18q12, 18q21, Xq21.1 and Xq26-q28 that were barely detected in tumor tissue specimens. These are considered to be cell line-specific DCNAs. The frequency of the HER2 amplification was high in both cell lines and tumor tissues, but it was statistically different between cell lines and primary tumors (P = 0.012); 41.3 ± 29.9% for the cell lines and 15.9 ± 18.6% for the tissue specimens.

Conclusions

Established cell lines carry cell lines-specific DCNAs together with recurrent aberrations detected in primary tumor tissues. It must therefore be emphasized that cell lines do not always represent the genotypes of parental tumor tissues.
Road traffic crash circumstances and consequences among young unlicensed drivers: A Swedish cohort study on socioeconomic disparities
Authors: Hanna Christina L , Hasselberg Marie , Laflamme Lucie , Möller Jette
Published: January 2010

Background

Young car drivers run a higher risk of road traffic crash and injury not only because of their lack of experience but also because of their young age and their greater propensity for adopting unsafe driving practices. Also, low family socioeconomic position increases the risk of crash and of severe crash in particular. Whether this holds true for young unlicensed drivers as well is not known. Increasing attention is being drawn to the prevalence and practice of unlicensed driving among young people as an important contributor to road traffic fatalities.

Methods

This is a population-based cohort study linking Swedish national register data for a cohort of 1 616 621 individuals born between 1977 and 1991. Crash circumstances for first-time road traffic crash (RTC) were compared considering licensed and unlicensed drivers. The socioeconomic distribution of injury was assessed considering household socioeconomic position, social welfare benefits, and level of urbanicity of the living area. The main outcome measure is relative risk of RTC.

Results

RTCs involving unlicensed drivers were over-represented among male drivers, suspected impaired drivers, severe injuries, crashes occurring in higher speed limit areas, and in fair road conditions. Unlicensed drivers from families in a lower socioeconomic position showed increased relative risks for RTC in the range of 1.75 to 3.25. Those living in rural areas had an increased relative risk for a severe RTC of 3.29 (95% CI 2.47 - 4.39) compared to those living in metropolitan areas.

Conclusions

At the time of the crash, young unlicensed drivers display more risky driving practices than their licensed counterparts. Just as licensed drivers, unlicensed young people from low socioeconomic positions are over-represented in the most severe injury crashes. Whether the mechanisms lying behind those similarities compare between these groups remains to be determined.
Current use of smokeless tobacco among adolescents in the Republic of Congo
Authors: Rudatsikira Emmanuel , Muula Adamson S , Siziya Seter
Published: January 2010

Background

Tobacco use is a leading cause of global morbidity and mortality. Much of the epidemiologic research on tobacco focuses on smoking, especially cigarette smoking, but little attention on smokeless tobacco (SLT).

Methods

Using data from the Republic of Congo Global Youth Tobacco Survey (GYTS) of 2006, we estimated the prevalence of SLT use among in-school adolescents. We also assessed the association between SLT use and cigarette smoking as well as the traditional factors which are associated with cigarette smoking among adolescents (e.g. age, sex, parental or peer smoking). Unadjusted odds ratios (OR) and adjusted odds ratios (AOR) together with their 95% confidence intervals (CI) were used to measure magnitudes of associations.

Results

Of the 3,034 respondents, 18.0% (18.0% males and 18.1% females) reported having used smokeless tobacco (chewing tobacco, sniff or dip) in the last 30 days. In multivariate analysis, no significant associations were observed between age and sex on one hand and current smokeless tobacco use on the other. Cigarette smokers were more than six times likely to report current use of smokeless tobacco (AOR = 6.65; 95% CI [4.84, 9.14]). Having parents or friends smokers was positively associated with using smokeless tobacco (AOR = 1.98; 95% CI [1.51, 2.59] for parents who smoked cigarettes, AOR = 1.82; 95% CI [1.41, 2.69] for some friends who smoked cigarettes, and AOR = 2.02; 95% CI [1.49, 2.47] for most or all friends who smoked cigarettes). Respondents who reported have seen tobacco advertisement on TV, billboards and in newspapers/magazines were 1.95 times more likely to report current use of smokeless tobacco (AOR = 1.95; 95% CI [1.34, 3.08]). Perception that smoking was harmful to health was negatively associated with current use of smokeless tobacco (AOR = 0.60; 95% CI [0.46, 0.78]).

Conclusions

Prevention programs aimed to reduce teen [cigarette] smoking must also be designed to reduce other forms of tobacco use. The teenagers environment at home, at school and at leisure must also be factored in order to prevent their uptake or maintenance of tobacco use.
A randomised controlled trial of total hip arthroplasty versus resurfacing arthroplasty in the treatment of young patients with arthritis of the hip joint
Authors: Achten Juul , Parsons Nick R , Edlin Richard P , Griffin Damian R , Costa Matthew L
Published: January 2010

Background

Hip replacement (arthroplasty) surgery is a highly successful treatment for patients with severe symptomatic arthritis of the hip joint. For older patients, several designs of Total Hip Arthroplasty have shown excellent results in terms of both function and value for money. However, in younger more active patients, there is approximately a 50% failure rate at 25 years for traditional implants. Hip resurfacing is a relatively new arthroplasty technique. In a recent review of the literature on resurfacing arthroplasty it was concluded that the short-term functional results appear promising but some potential early disadvantages were identified, including the risk of femoral neck fracture and collapse of the head of the femur.The aim of the current study is to assess whether there is a difference in functional hip scores at one year post-operation between Total Hip Arthroplasty and Resurfacing Arthroplasty. Secondary aims include assessment of complication rates for both procedures as well cost effectiveness.

Methods/design

All patients medically fit for surgery and deemed suitable for a resurfacing arthroplasty are eligible to take part in this study. A randomisation sequence will be produced and administered independently. After consenting, all patients will be clinically reviewed and hip function, quality of life and physical activity level will be assessed through questionnaires. The allocated surgery will then be performed with the preferred technique of the surgeon. Six weeks post-operation hip function will be assessed and complications recorded. Three, six and 12 months post-operation hip function, quality of life and physical activity level will be assessed. Additional information about patients' out-of-pocket expenses will also be collected.

Trial registration

Current Controlled Trials ISRCTN33354155

UKCLRN portfolio ID 4093
Job requirements compared to medical school education: differences between graduates from problem-based learning and conventional curricula
Authors: Schlett Christopher L , Doll Hinnerk , Dahmen Janosch , Polacsek Ole , Federkeil Gero , Fischer Martin R , Bamberg Fabian , Butzlaff Martin
Published: January 2010

Background

Problem-based Learning (PBL) has been suggested as a key educational method of knowledge acquisition to improve medical education. We sought to evaluate the differences in medical school education between graduates from PBL-based and conventional curricula and to what extent these curricula fit job requirements.

Methods

Graduates from all German medical schools who graduated between 1996 and 2002 were eligible for this study. Graduates self-assessed nine competencies as required at their day-to-day work and as taught in medical school on a 6-point Likert scale. Results were compared between graduates from a PBL-based curriculum (University Witten/Herdecke) and conventional curricula.

Results

Three schools were excluded because of low response rates. Baseline demographics between graduates of the PBL-based curriculum (n = 101, 49% female) and the conventional curricula (n = 4720, 49% female) were similar. No major differences were observed regarding job requirements with priorities for "Independent learning/working" and "Practical medical skills". All competencies were rated to be better taught in PBL-based curriculum compared to the conventional curricula (all p < 0.001), except for "Medical knowledge" and "Research competence". Comparing competencies required at work and taught in medical school, PBL was associated with benefits in "Interdisciplinary thinking" (Δ + 0.88), "Independent learning/working" (Δ + 0.57), "Psycho-social competence" (Δ + 0.56), "Teamwork" (Δ + 0.39) and "Problem-solving skills" (Δ + 0.36), whereas "Research competence" (Δ - 1.23) and "Business competence" (Δ - 1.44) in the PBL-based curriculum needed improvement.

Conclusion

Among medical graduates in Germany, PBL demonstrated benefits with regard to competencies which were highly required in the job of physicians. Research and business competence deserve closer attention in future curricular development.
Cell aggregation induces phosphorylation of PECAM-1 and Pyk2 and promotes tumor cell anchorage-independent growth
Authors: Zhang Xing , Xu Li-hua , Yu Qiang
Published: January 2010

Background

Apoptosis caused by inadequate or inappropriate cell-matrix interactions is defined as anoikis. Although transformed cells are known to be anoikis-resistant, the underlying mechanisms have not been well understood. We investigated the mechanisms of anoikis resistance of tumor cells.

Results

We observed that cell aggregation in suspension promoted cell survival and proliferation. We demonstrated a correlation between tumor cell aggregation in suspension and cell growth in soft agar. Analysis of tyrosine kinase-mediated cell survival and growth signaling pathways revealed increased levels of tyrosine-phosphorylation of PECAM-1 and Pyk2 in cell aggregates. We also showed that PECAM-1 and Pyk2 physically interact with each other, and that PECAM-1 carrying a deletion of exons 11-16 could no longer bind to Pyk2. Furthermore, RNA interference-mediated reduction of Pyk2 and PECAM-1 protein levels reduced cell aggregation and inhibited the growth of tumor cells in soft agar.

Conclusions

The data demonstrated that Pyk2 and PECAM-1 were critical mediators of both anchorage-independent growth and anoikis resistance in tumor cells.
The mechanism of dietary cholesterol effects on lipids metabolism in rats
Authors: Wang Yu-Ming , Zhang Bei , Xue Yong , Li Zhao-Jie , Wang Jing-Feng , Xue Chang-Hu , Yanagita Teruyoshi
Published: January 2010

Background

Cholesterol administration has been reported to influence hepatic lipid metabolism in rats. In the present study, the effect of dietary cholesterol on hepatic activity and mRNA expression of the enzymes involved in lipid metabolism were investigated. Fourteen male Wistar rats were randomly divided into 2 groups and fed 1% cholesterol or cholesterol free AIN76 diets for 4 weeks.

Results

The serum triglyceride and high density lipoprotein cholesterol levels were significantly decreased but the total cholesterol and non high density lipoprotein cholesterol levels were significantly increased in the cholesterol-fed rats compared with the control rats. And the concentrations of the hepatic total cholesterol and triglyceride increased about 4-fold and 20-fold separately by dietary cholesterol. The activities of hepatic malic enzyme, glucose-6-phosphate dehydrogenase, fatty acid synthase, phosphatidate phophatase and carnitine palmitoyl transferase were depressed by the cholesterol feeding (40%, 70%, 50%, 15% and 25% respectively). The results of mRNA expression showed that fatty acid synthase, carnitine palmitoyl transferase 1, carnitine palmitoyl transferase 2, and HMG-CoA reductase were down-regulated (35%, 30%, 50% and 25% respectively) and acyl-CoA: cholesterol acyltransferase and cholesterol 7α-hydroxylase were up regulated (1.6 and 6.5 folds) in liver by the cholesterol administration.

Conclusions

The dietary cholesterol increased the triglyceride accumulation in liver, but did not stimulate the activity and the gene expression of hepatic enzymes related to triglyceride and fatty acid biosynthesis.
Transient oligoarthritis of the lower extremity following influenza B virus infection: Case report
Authors: Bruck Normi , Gahr Manfred , Pessler Frank
Published: January 2010

A 12-year-old girl developed influenza B virus infection proven by typical symptoms and detection of the virus in a nasopharyngeal swab by culture and PCR. Two weeks later she developed an otherwise unexplained transient oligoarthritis of small joints of the left foot. Influenza viruses may be a hitherto underappreciated cause of a post-infectious arthritis.
Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype
Authors: Dirscherl Konstantin , Karlstetter Marcus , Ebert Stefanie , Kraus Dominik , Hlawatsch Julia , Walczak Yana , Moehle Christoph , Fuchshofer Rudolf , Langmann Thomas
Published: January 2010

Background

Luteolin, a plant derived flavonoid, exerts a variety of pharmacological activities and anti-oxidant properties associated with its capacity to scavenge oxygen and nitrogen species. Luteolin also shows potent anti-inflammatory activities by inhibiting nuclear factor kappa B (NFkB) signaling in immune cells. To better understand the immuno-modulatory effects of this important flavonoid, we performed a genome-wide expression analysis in pro-inflammatory challenged microglia treated with luteolin and conducted a phenotypic and functional characterization.

Methods

Resting and LPS-activated BV-2 microglia were treated with luteolin in various concentrations and mRNA levels of pro-inflammatory markers were determined. DNA microarray experiments and bioinformatic data mining were performed to capture global transcriptomic changes following luteolin stimulation of microglia. Extensive qRT-PCR analyses were carried out for an independent confirmation of newly identified luteolin-regulated transcripts. The activation state of luteolin-treated microglia was assessed by morphological characterization. Microglia-mediated neurotoxicity was assessed by quantifying secreted nitric oxide levels and apoptosis of 661W photoreceptors cultured in microglia-conditioned medium.

Results

Luteolin dose-dependently suppressed pro-inflammatory marker expression in LPS-activated microglia and triggered global changes in the microglial transcriptome with more than 50 differentially expressed transcripts. Pro-inflammatory and pro-apoptotic gene expression was effectively blocked by luteolin. In contrast, mRNA levels of genes related to anti-oxidant metabolism, phagocytic uptake, ramification, and chemotaxis were significantly induced. Luteolin treatment had a major effect on microglial morphology leading to ramification of formerly amoeboid cells associated with the formation of long filopodia. When co-incubated with luteolin, LPS-activated microglia showed strongly reduced NO secretion and significantly decreased neurotoxicity on 661W photoreceptor cultures.

Conclusions

Our findings confirm the inhibitory effects of luteolin on pro-inflammatory cytokine expression in microglia. Moreover, our transcriptomic data suggest that this flavonoid is a potent modulator of microglial activation and affects several signaling pathways leading to a unique phenotype with anti-inflammatory, anti-oxidative, and neuroprotective characteristics. With the identification of several novel luteolin-regulated genes, our findings provide a molecular basis to understand the versatile effects of luteolin on microglial homeostasis. The data also suggest that luteolin could be a promising candidate to develop immuno-modulatory and neuroprotective therapies for the treatment of neurodegenerative disorders.
Pancreatic intraductal papillary mucinous neoplasm with concomitant heterotopic pancreatic cystic neoplasia of the stomach: a case report and review of the literature
Authors: Tsapralis Dimitrios , Charalabopoulos Alexandros , Karamitopoulou Eva , Schizas Dimitrios , Charalabopoulos Konstantinos , Liakakos Theodoros , Macheras Anastasios
Published: January 2010

A 60-year-old Caucasian male underwent a total pancreatectomy for a mixed type pancreatic intraductal papillary mucinous neoplasm (IPMN) arising in the main and secondary pancreatic ducts. During surgery, a subserosal polypoid mass was noted at the greater curvature of the gastric antrum and was enucleated. This mass was proven to be heterotopic pancreatic tissue with cystic neoplasia of the IPMN histologic subtype. Through an extensive search of the literature, we found that this is the first case ever reported with simultaneous existence of IPMN changes, in the main and secondary ducts of the orthotopic pancreas and in the heterotopic pancreatic tissue of the gastric wall.
Extensive proteomic screening identifies the obesity-related NYGGF4 protein as a novel LRP1-interactor, showing reduced expression in early Alzheimer's disease
Authors: Kajiwara Yuji , Franciosi Sonia , Takahashi Nagahide , Krug Lisa , Schmeidler James , Taddei Kevin , Haroutunian Vahram , Fried Ulrik , Ehrlich Michelle , Martins Ralph N , Gandy Samuel , Buxbaum Joseph D
Published: January 2010

Background

The low-density lipoprotein receptor related protein 1 (LRP1) has been implicated in Alzheimer's disease (AD) but its signalling has not been fully evaluated. There is good evidence that the cytoplasmic domain of LRP1 is involved in protein-protein interactions, important in the cell biology of LRP1.

Results

We carried out three yeast two-hybrid screens to identify proteins that interact with the cytoplasmic domain of LRP1. The screens included both conventional screens as well as a novel, split-ubiquitin-based screen in which an LRP1 construct was expressed and screened as a transmembrane protein. The split-ubiquitin screen was validated in a screen using full-length amyloid protein precursor (APP), which successfully identified FE65 and FE65L2, as well as novel interactors (Rab3a, Napg, and ubiquitin b). Using both a conventional screen as well as the split-ubiquitin screen, we identified NYGGF4 as a novel LRP1 interactor. The interaction between LRP1 and NYGGF4 was validated using two-hybrid assays, coprecipitation and colocalization in mammalian cells. Mutation analysis demonstrated a specific interaction of NYGGF4 with an NPXY motif that required an intact tyrosine residue. Interestingly, while we confirmed that other LRP1 interactors we identified, including JIP1B and EB-1, were also able to bind to APP, NYGGF4 was unique in that it showed specific binding with LRP1. Expression of NYGGF4 decreased significantly in patients with AD as compared to age-matched controls, and showed decreasing expression with AD disease progression. Examination of Nyggf4 expression in mice with different alleles of the human APOE4 gene showed significant differences in Nyggf4 expression.

Conclusions

These results implicate NYGGF4 as a novel and specific interactor of LRP1. Decreased expression of LRP1 and NYGGF4 over disease, evident with the presence of even moderate numbers of neuritic plaques, suggests that LRP1-NYGGF4 is a system altered early in disease. Genetic and functional studies have implicated both LRP1 and NYGGF4 in obesity and cardiovascular disease and the physical association of these proteins may reflect a common mechanism. This is particularly interesting in light of the dual role of ApoE in both cardiovascular risk and AD. The results support further studies on the functional relationship between NYGGF4 and LRP1.
How the Federal Trade Commission Is Fighting Cancer Treatment Scams
Authors: Kando-Pineda Carol
Published: January 2010

A cancer diagnosis can tempt a patient to turn to miraculous cancer-fighting products, but the Federal Trade Commission says it is good to be skeptical—most of these products are scams.
Cost Effectiveness of Evidence-Based Treatment Guidelines for the Treatment of Non–Small-Cell Lung Cancer in the Community Setting
Authors: Neubauer Marcus A. , Hoverman J. Russell , Kolodziej Michael , Reisman Lonny , Gruschkus Stephen K. , Hoang Susan , Alva Albert A. , McArthur Marilyn , Forsyth Michael , Rothermel Todd , Beveridge Roy A.
Published: January 2010

Results of this study suggest that treating patients according to evidence-based guidelines is a cost-effective strategy for delivering care to those with non–small-cell lung cancer treated in the outpatient community setting.
Understanding the Role of Physician Assistants in Oncology
Authors: Ross Alicia C. , Polansky Maura N. , Parker Patricia A. , Palmer J. Lynn
Published: January 2010

A descriptive study using a Web-based questionnaire was undertaken to understand the deployment of physician assistants in oncology, as we face a significant shortage of oncology providers by 2020.
Practical Model for Psychosocial Care
Authors: Hendrick Susan S. , Cobos Everardo
Published: January 2010

The delivery of economically feasible psychosocial care is critical for patients with cancer and their families. Creative partnering enables such comprehensive care to be provided effectively and efficiently.
Basic Steps to Building a Research Program
Authors: Baer Allison , Bechar Naftali , Cohen Gary , Devine Susan
Published: January 2010

Establishing a clinical trial infrastructure is an important step when developing a successful research program. Two areas required for success include financial oversight and a qualified research team.
Genetic modeling of Li-Fraumeni syndrome in zebrafish
Authors: Parant John M. , George Stephen A. , Holden Joseph A. , Yost H. Joseph
Published: January 2010

Li-Fraumeni syndrome (LFS) is a highly penetrant, autosomal dominant, human familial cancer predisposition. Although a key role for the tumor suppressor p53 has been implicated in LFS, the genetic and cellular mechanisms underpinning this disease remain unknown. Therefore, modeling LFS in a vertebrate system that is accessible to both large-scale genetic screens and in vivo cell biological studies will facilitate the in vivo dissection of disease mechanisms, help identify candidate genes, and spur the discovery of therapeutic compounds. Here, we describe a forward genetic screen in zebrafish embryos that was used to identify LFS candidate genes, which yielded a p53 mutant (p53I166T) that as an adult develops tumors, predominantly sarcomas, with 100% penetrance. As in humans with LFS, tumors arise in heterozygotes and display loss of heterozygosity (LOH). This report of LOH indicates that Knudson’s two-hit hypothesis, a hallmark of human autosomal dominant cancer syndromes, can be modeled in zebrafish. Furthermore, as with some LFS mutations, the zebrafish p53I166T allele is a loss-of-function allele with dominant-negative activity in vivo. Additionally, we demonstrate that the p53 regulatory pathway, including Mdm2 regulation, is evolutionarily conserved in zebrafish, providing a bona fide biological context in which to systematically uncover novel modifier genes and therapeutic agents for human LFS.
Cardiac preconditioning for ischaemia: lost in translation
Authors: Ludman Andrew J. , Yellon Derek M. , Hausenloy Derek J.
Published: January 2010

Coronary heart disease (CHD) is the leading cause of death worldwide. The development of novel treatment strategies for protecting the myocardium against the detrimental effects of acute ischaemia-reperfusion injury, termed cardioprotection, and for improving clinical outcomes in patients with CHD requires the use of appropriate animal disease models. The concept of cardioprotection was first conceived in the late 1960s and has evolved to include the endogenous cardioprotective phenomenon of ischaemic conditioning, a concept in which the heart can be protected from an episode of acute lethal ischaemia-reperfusion injury by applying brief non-lethal episodes of ischaemia and reperfusion either to the heart itself or to an organ or tissue that is remote from the heart. The brief conditioning episodes of ischaemia and reperfusion can be applied prior to the index ischaemic episode (ischaemic preconditioning), after the onset of the index ischaemic episode (ischaemic perconditioning), or at the onset of reperfusion (ischaemic postconditioning). Elucidation of the signal transduction pathways underlying ischaemic conditioning has identified a variety of pharmacological agents that are capable of reproducing its cardioprotective actions. Despite a wealth of preclinical, experimental animal data demonstrating clear cardioprotective benefits with these treatment strategies, their translation into clinical therapy has been hugely disappointing. This review explores the potential reasons behind this failure; it will focus primarily on the inadequacy of the experimental animal disease models that are currently being used to investigate novel cardioprotective strategies, which on the whole are not adequately representative of the clinical scenario, and finally, we will discuss potential solutions to remedy this problem.
Postconditioning: from experimental proof to clinical concept
Authors: Mewton Nathan , Ivanès Fabrice , Cour Martin , Ovize Michel
Published: January 2010

The therapeutic strategies for acute myocardial infarction in the last decade have, among other therapeutic targets, focused on myocardial reperfusion injury, which accounts for a significant part of the final infarct size. Although several experiments in the last 20 years have reported that pharmacological interventions at reperfusion might reduce myocardial reperfusion injury, this could not be consistently confirmed in animal models or human studies. An alternative to chemical modifiers, postconditioning (brief repeated periods of ischemia applied at the onset of reperfusion) is the first method proven to be efficient in different animal models and to be confirmed in a recent human study. This simple method, applied in the first minute of reperfusion, reduces the final infarct size by 30–50%. This review will focus on the postconditioning technique and show how the data from different animal models and experimental settings have advanced our understanding of both the mechanisms and the definition of an accurate protocol that is easily applicable in human patients in the setting of acute myocardial infarction.
Evaluation of residual stress assessment methods using a repair weld benchmark
Authors: Keppas L K , Wimpory R C , Katsareas D E , Anifantis N K , Youtsos A G
Published: January 2010

A simple design of a letterbox-type repair weld on a plate is evaluated as a benchmark problem. Residual stresses are recorded using the non-destructive neutron diffraction technique and compared with predictions by full three-dimensional finite element modelling. The comparison is performed over a number of path lines in an attempt to evaluate both methods as potential residual stress assessment tools, for weld repairs. The proposed finite element methodology is based on uncoupled quasi-static thermoelasticity and incorporates the element activation–deactivation technique for simulating weld deposition. Sensitivity analysis indicates that the effect of heat loss due to radiation on predicted residual stresses is negligible, whereas incorporation of full annealing into the model is recommended. The diffractometer used, is STRESS-SPEC, located at the FRMII research reactor (Munich, Germany) and comprises a highly flexible monochromator arrangement and a two-dimensional position-sensitive 3He detector. The success of the repair weld benchmark design is illustrated by not only the satisfactory correlation between experimental and computational results in the form of residual stress but also temperature history data.
Fuzzy feedback scheduling algorithm based on central processing unit utilization for a software-based computer numerical control system
Authors: Wan J , Li D , Yan H , Zhang P
Published: January 2010

The tasks of a software-based computer numerical control (CNC) system are characterized by concurrency, hybridization, and correlation, which makes system implementation difficult. The uncertainty factors when running real-time tasks affect control performance by degrading manufacturing accuracy as a result of restrictions on system resources and processor use. To address the technical difficulty of embedded system implementation, a novel fuzzy feedback scheduling algorithm based on CPU utilization for a software-based CNC system is proposed herein. Time characteristics such as sampling jitter, input—output jitter, and non-schedulability are discussed, followed by quantification through simulations of the impact of time characteristics on manufacturing accuracy. On the basis of this research, fuzzy feedback scheduling based on the loop-up table method is designed for a software-based CNC system in order to reduce mismachining tolerance. The simulated results show that machining precision rises by an order of magnitude or more, proving that the presented algorithm is effective. Moreover, the algorithm is independent of task execution times and is easy to implement while incurring only a small overhead.
Finite element method study of incremental sheet forming for complex shape and its improvement
Authors: Nguyen D-T , Park J-G , Lee H-J , Kim Y-S
Published: January 2010

In order to improve the incremental sheet forming process for the product of complex shape (e.g. human face), a combination of both computer-aided manufacturing (CAM) and finite-element modelling (FEM) simulation, is implemented and evaluated from the histories of stress and strain value by means of finite-element analysis. Here, the results, using ABAQUS/Explicit finite-element code, are compared with forming limit curve at fracture in order to predict and improve the forming conditions by changing process variables of tool radius, tool down-step, and friction coefficient according to the orthogonal array of Taguchi's method. First, the CAM simulation is used to create cutter location data. This data are then calculated, modified, and exported to the input file format required by ABAQUS through using MATLAB programming. The FEM results are implemented for negative incremental sheet forming and then investigated by experiment.
An integrated performance analysis for a small axial-flow fan
Authors: Lin S-C , Tsai M-L
Published: January 2010

Owing to the high system resistance and space limitations on computer devices, many researchers have begun to pay more attention to developing high-performance axial-flow fans. Evidently, evaluating the fan performance under different operating conditions is essential for both designer and practical engineering applications. However, previous studies do not provide a detailed flow-field analysis, torque prediction, efficiency estimation at various operating points, and qualitative numerical prediction of sound generation. Thus, this comprehensive study was performed with the aim to offer the aforementioned technical information and completely evaluate the fan performance. In this study, computational fluid dynamics (CFD) simulations and experimental measurements are utilized to perform flow visualization, torque calculation, efficiency estimation, and noise analysis. For demonstration purposes, a 120 mm-diameter axial-flow fan is designed and fabricated via computer numerical control (CNC) to serve as the research subject. The result indicates that the P— Q curve and the sound pressure level (SPL) spectrum of the experiment are in agreement with those of numerical simulations. The numerical deviations in maximum volumetric flowrate and static pressure are approximately 7 per cent and 13 per cent, respectively. Regarding the acoustic characteristics, the overall SPLs for measured spectra and large eddy simulation (LES) calculation are 51.3 dB and 48.1 dB, respectively. Consequently, this study establishes an integrated aerodynamic, acoustic, and electro-mechanical evaluation approach that can be used as an important tool for fan designers.
Condition monitoring studies on ball bearings considering solid contaminants in the lubricant
Authors: Hariharan V , Srinivasan P S S
Published: January 2010

Rolling element bearings are common in any rotating machinery. They are subject to failure under continuous running. Therefore they have received a great deal of attention in the field of condition monitoring. In rolling element bearings, contamination of lubricant grease by solid particles is one of the several reasons for an early bearing failure. In this context, this article investigates the effect of contamination of lubricant by solid particles on the dynamic behaviour of rolling bearings. Silica powder at three concentration levels and different particle sizes was used to contaminate the lubricant. Experimental tests have been performed on the ball bearings lubricated with grease, and the trends in the amount of vibration affected by the contamination of the grease were determined. The contaminant concentration as well as the particle size is varied. Vibration signatures were analysed in terms of root mean square (RMS) values. From the results, some fruitful conclusions are made about the bearing performance. The effects of contaminant and the bearing vibration are studied for both good and defective bearings. The results show significant variation in the RMS velocity values on varying the contaminant concentration and particle size.
The effect of conduction—radiation on the oscillating natural convection boundary layer flow of viscous incompressible fluid along a vertical plate
Authors: Roy N C , Hossain M A
Published: January 2010

The natural convection boundary layer flow with conduction—radiation interaction of a viscous incompressible fluid along a vertical plate to surface temperature oscillations has been studied. Three distinct methods are used in the investigation, namely (a) the perturbation method for low frequency range and the asymptotic series expansion method for high frequency range, (b) the direct finite difference method for primitive variable formulations, and (c) the implicit finite difference method for stream-function formulation together with the Keller-box elimination technique for the entire frequency range. The effects of varying the Prandtl number Pr, the conduction—radiation parameter Rd, and the surface temperature parameter θw, are discussed in terms of amplitude and phase of the rate of heat transfer for fluid having the Prandtl number equal to 0.1. Also the effects of these parameters on the amplitude of oscillation of the transient skin-friction and transient heat transfer have been investigated.
The principles and practice of magnetic instrumentation for natural orifice transluminal endoscopic surgery and other limited access surgical operations
Authors: Cahill R A , Lewin R P , Mortensen N J , Jones H
Published: January 2010

Natural orifice transluminal endoscopic surgery (NOTES) is viewed as a means of breaking one of the physical barriers associated with invasive abdominal operation by decoupling body wall injury from the surgical intervention. However, although the global concept has been clearly elucidated, there remains many separate components that still need piecing together before its routine practice can be realized. In particular, NOTES, in common with other confined access approaches such as single-port laparoscopic surgery, imposes marked constraints on the range and fluidity of operator instrument movement. Therefore, at present, these techniques possess significant limitations on their capacity for ensuring sufficient instrument triangulation as well as the appropriate degrees of tissue positioning and tensioning for facilitating efficient dissection. These technical considerations have recently reinvigorated the investigation of the utility of magnets in affecting surgical operation. The majority of work to date has however focused solely on permanent magnets due to their ease of manufacture and handling, despite the significant limitations inherent in their physical qualities. This review considers these issues and presents the potential engineering solution achievable by employing high-temperature superconducting electromagnets to impose the required physical forces for effective surgical operation in place of conventional rigid assistance instrumentation.
A numerical investigation of transient electro-osmotic flow in rectangular microchannels: A comparison of different models
Authors: Kamali R , Eslami M
Published: January 2010

Transient electro-osmotic flow in rectangular microchannels is investigated numerically in this article. The complete Poisson—Boltzmann equation along with the time-dependent momentum equation is solved using the finite-difference method. Moreover, linearized equations based on the Debye—Huckle assumption are also solved to compare with the available analytical approximate solutions. The effects of different parameters such as wall zeta potential, non-dimensional electrokinetic width, and channel aspect ratio are also studied. It is shown that the Debye—Huckle approximation is not only valid for small values of zeta potential, but also the channel hydraulic diameter should be large enough with respect to electrical double layer (EDL) thickness. In addition, the flow behaviour at higher values of zeta potential is shown to be completely different from what available analytical solutions predict. Effective parameters on the transition period from the start time to the steady-state condition are also discussed. On the other hand, a comparison between the present numerical solution and the results of slip velocity approximation reveals that the slip model could be only used for very large values of non-dimensional electro-kinetic width. Finally, velocity distributions in channels of different aspect ratios are provided and discussed.
Autonomous spatial orientation of robots using chaotic cognition and geometric cues
Authors: Yu X-L , Sun Y , Liu J , Xiang W
Published: January 2010

In this paper an innovative methodology for geometrical orientation and robot control is proposed. The innovative method exploits the use of multisensory integration applied to a chaotic cognitive system for a mobile robot which is able to be controlled in real-time towards less complex orbits, such as periodic orbits or equilibrium points, considered as perceptive orbits. The strategy is inspired by the olfactory bulb neural activity observed in rabbits subjected to external stimuli. These are subject to real-time modifications on the basis of environmental changes acquired through a distributed sensory system. The mathematical details of the approach are given including simulation results in different geometric environments. The obtained results also demonstrate the significant impact of different geometric cues on reorientation performance as well as spatial updating performance for autonomous robots. Furthermore, the robot's reorientation performance is approximately inversely proportional to the rotational symmetry of the environment, whereas the spatial updating performance is equally good in angular environments but worse in a circular environment.
Stability analysis for delayed Hopfield neural networks
Authors: Ahn C K
Published: January 2010

In this paper, an
Probabilistic risk assessment framework for software propagation analysis of failures
Authors: Wei Y , Rodriguez M , Smidts C S
Published: January 2010

Probabilistic risk assessment (PRA) is a methodology consisting of techniques to assess the probability of failure or success of a system. It has been proven to be a systematic, logical, and comprehensive methodology for risk assessment. However, the contribution of software to risk has not been well studied. To address this shortcoming, recent research has focused on the development of an approach to systematically integrate software risk contributions into the PRA framework. The latter research has identified as key the need to quantify various major software-failure-related contributions to risk. Of these contributions, the quantification of input failures is the topic of this paper. An input failure consists of a failure of a system component directly or indirectly connected to a software component, which reaches the software input and propagates through the software component. The paper studies and quantifies the impact of input failures on the software component and then further on in the system, and outlines a framework to systematically conduct such an analysis. An application to a safety-critical system is also provided that illustrates the application of the concepts introduced in the paper.
HIV risk and prevention behaviours, intentions, perceptions and knowledge among youth in Goa, India
Authors: Gong J , Saxena V , Mathur A , Li X , Stanton B , Kaljee L , Kamat D
Published: January 2010

Summary

In order to examine the association between HIV/AIDS knowledge and perceptions, and risk intentions and behaviours among adolescents in Goa, India, cross-sectional data from 942 youth were collected and assessed. The prevalence rates in the past six months for fighting, smoking, drinking and drug use were 16.5%, 3.8%, 17.8% and 1.1%, respectively; 5.2% acknowledged ever having engaged in sex. Prior risk involvement was significantly correlated with future risk intention (odds ratio [OR]: 9.7–19.7), and those involved in one risk behaviour were more likely to engage in other risk behaviours (OR: 1.3–23.5). The findings suggest the importance of targeted interventions for youth engaging or intending to engage in risk behaviours and universal interventions regarding basic facts and skills for all youth in Goa.
Early syphilis mimicking tuberculous meningoencephalitis in an HIV-positive patient
Authors: Farazmand P , Alvarez-Uria G , Higgins S P , Vilar J F
Published: January 2010

A man previously treated for tuberculous arthritis presented with acute meningoencephalitis. Cerebrospinal fluid tests suggested infection with Mycobacterium tuberculosis, but a diagnosis of early neurosyphilis was subsequently made.