bluuebunny/crossref_metadata_2025 huggingface dataset:
Linkage of the potent leukemogenic activity of Meis1 to cell-cycle entry and transcriptional regulation of cyclin D3
Authors: Argiropoulos Bob , Yung Eric , Xiang Ping , Lo Chao Yu , Kuchenbauer Florian , Palmqvist Lars , Reindl Carola , Heuser Michael , Sekulovic Sanja , Rosten Patty , Muranyi Andrew , Goh Siew-Lee , Featherstone Mark , Humphries R. Keith
Published: March 2010

MEIS1 is a three–amino acid loop extension class homeodomain-containing homeobox (HOX) cofactor that plays key roles in normal hematopoiesis and leukemogenesis. Expression of Meis1 is rate-limiting in MLL-associated leukemias and potently interacts with Hox and NUP98-HOX genes in leukemic transformation to promote self-renewal and proliferation of hematopoietic progenitors. The oncogenicity of MEIS1 has been linked to its transcriptional activation properties. To further reveal the pathways triggered by Meis1, we assessed the function of a novel engineered fusion form of Meis1, M33-MEIS1, designed to confer transcriptional repression to Meis1 target genes that are otherwise up-regulated in normal and malignant hematopoiesis. Retroviral overexpression of M33-Meis1 resulted in the rapid and complete eradication of M33-Meis1–transduced normal and leukemic cells in vivo. Cell-cycle analysis showed that M33-Meis1 impeded the progression of cells from G1-to-S phase, which correlated with significant reduction of cyclin D3 levels and the inhibition of retinoblastoma (pRb) hyperphosphorylation. We identified cyclin D3 as a direct downstream target of MEIS1 and M33-MEIS1 and showed that the G1-phase accumulation and growth suppression induced by M33-Meis1 was partially relieved by overexpression of cyclin D3. This study provides strong evidence linking the growth-promoting activities of Meis1 to the cyclin D-pRb cell-cycle control pathway.
SPIN (Scottish Pregnancy Intervention) study: a multicenter, randomized controlled trial of low-molecular-weight heparin and low-dose aspirin in women with recurrent miscarriage
Authors: Clark Peter , Walker Isobel D. , Langhorne Peter , Crichton Lena , Thomson Andrew , Greaves Mike , Whyte Sonia , Greer Ian A.
Published: March 2010

To assess whether treatment with enoxaparin and low-dose aspirin, along with intensive pregnancy surveillance, reduces rate of pregnancy loss compared with intensive pregnancy surveillance alone in women with history of 2 or more consecutive previous pregnancy losses, a parallel group, multicenter, randomized controlled trial was performed in the United Kingdom and New Zealand. Participants (n = 294) presenting for initial antenatal care at fewer than 7 weeks' gestation with history of 2 or more consecutive previous pregnancy losses at 24 or fewer weeks' gestation and no evidence of anatomic, endocrine, chromosomal, or immunologic abnormality were randomly assigned to receive either enoxaparin 40 mg subcutaneously and 75 mg of aspirin orally once daily along with intense pregnancy surveillance or intense pregnancy surveillance alone from random assignment until 36 weeks' gestation. The primary outcome measure was pregnancy loss rate. Of the 147 participants receiving pharmacologic intervention, 32 (22%) pregnancy losses occurred, compared with 29 losses (20%) in the 147 subjects receiving intensive surveillance alone, giving an odds ratio of 0.91 (95% confidence interval, 0.52-1.59) of having a successful pregnancy with pharmacologic intervention. Thus, we observed no reduction in pregnancy loss rate with antithrombotic intervention in pregnant women with 2 or more consecutive previous pregnancy losses. The trial was registered at http://www.controlled-trials.com as ISRCTN06774126.
Gene regulatory networks modelling using a dynamic evolutionary hybrid
Authors: Maraziotis Ioannis A , Dragomir Andrei , Thanos Dimitris
Published: March 2010

Background

Inference of gene regulatory networks is a key goal in the quest for understanding fundamental cellular processes and revealing underlying relations among genes. With the availability of gene expression data, computational methods aiming at regulatory networks reconstruction are facing challenges posed by the data's high dimensionality, temporal dynamics or measurement noise. We propose an approach based on a novel multi-layer evolutionary trained neuro-fuzzy recurrent network (ENFRN) that is able to select potential regulators of target genes and describe their regulation type.

Results

The recurrent, self-organizing structure and evolutionary training of our network yield an optimized pool of regulatory relations, while its fuzzy nature avoids noise-related problems. Furthermore, we are able to assign scores for each regulation, highlighting the confidence in the retrieved relations. The approach was tested by applying it to several benchmark datasets of yeast, managing to acquire biologically validated relations among genes.

Conclusions

The results demonstrate the effectiveness of the ENFRN in retrieving biologically valid regulatory relations and providing meaningful insights for better understanding the dynamics of gene regulatory networks.

The algorithms and methods described in this paper have been implemented in a Matlab toolbox and are available from: http://bioserver-1.bioacademy.gr/DataRepository/Project_ENFRN_GRN/.
YODA: Software to facilitate high-throughput analysis of chronological life span, growth rate, and survival in budding yeast
Authors: Olsen Brady , Murakami Christopher J , Kaeberlein Matt
Published: March 2010

Background

The budding yeast Saccharomyces cerevisiae is one of the most widely studied model organisms in aging-related science. Although several genetic modifiers of yeast longevity have been identified, the utility of this system for longevity studies has been limited by a lack of high-throughput assays for quantitatively measuring survival of individual yeast cells during aging.

Results

Here we describe the Yeast Outgrowth Data Analyzer (YODA), an automated system for analyzing population survival of yeast cells based on the kinetics of outgrowth measured by optical density over time. YODA has been designed specifically for quantification of yeast chronological life span, but can also be used to quantify growth rate and survival of yeast cells in response to a variety of different conditions, including temperature, nutritional composition of the growth media, and chemical treatments. YODA is optimized for use with a Bioscreen C MBR shaker/incubator/plate reader, but is also amenable to use with any standard plate reader or spectrophotometer.

Conclusions

We estimate that use of YODA as described here reduces the effort and resources required to measure chronological life span and analyze the resulting data by at least 15-fold.
MPprimer: a program for reliable multiplex PCR primer design
Authors: Shen Zhiyong , Qu Wubin , Wang Wen , Lu Yiming , Wu Yonghong , Li Zhifeng , Hang Xingyi , Wang Xiaolei , Zhao Dongsheng , Zhang Chenggang
Published: March 2010

Background

Multiplex PCR, defined as the simultaneous amplification of multiple regions of a DNA template or multiple DNA templates using more than one primer set (comprising a forward primer and a reverse primer) in one tube, has been widely used in diagnostic applications of clinical and environmental microbiology studies. However, primer design for multiplex PCR is still a challenging problem and several factors need to be considered. These problems include mis-priming due to nonspecific binding to non-target DNA templates, primer dimerization, and the inability to separate and purify DNA amplicons with similar electrophoretic mobility.

Results

A program named MPprimer was developed to help users for reliable multiplex PCR primer design. It employs the widely used primer design program Primer3 and the primer specificity evaluation program MFEprimer to design and evaluate the candidate primers based on genomic or transcript DNA database, followed by careful examination to avoid primer dimerization. The graph-expanding algorithm derived from the greedy algorithm was used to determine the optimal primer set combinations (PSCs) for multiplex PCR assay. In addition, MPprimer provides a virtual electrophotogram to help users choose the best PSC. The experimental validation from 2× to 5× plex PCR demonstrates the reliability of MPprimer. As another example, MPprimer is able to design the multiplex PCR primers for DMD (dystrophin gene which caused Duchenne Muscular Dystrophy), which has 79 exons, for 20×, 20×, 20×, 14×, and 5× plex PCR reactions in five tubes to detect underlying exon deletions.

Conclusions

MPprimer is a valuable tool for designing specific, non-dimerizing primer set combinations with constrained amplicons size for multiplex PCR assays.
Large-scale prediction of protein-protein interactions from structures
Authors: Hue Martial , Riffle Michael , Vert Jean-Philippe , Noble William S
Published: March 2010

Background

The prediction of protein-protein interactions is an important step toward the elucidation of protein functions and the understanding of the molecular mechanisms inside the cell. While experimental methods for identifying these interactions remain costly and often noisy, the increasing quantity of solved 3D protein structures suggests thatin silicomethods to predict interactions between two protein structures will play an increasingly important role in screening candidate interacting pairs. Approaches using the knowledge of the structure are presumably more accurate than those based on sequence only. Approaches based on docking protein structures solve a variant of this problem, but these methods remain very computationally intensive and will not scale in the near future to the detection of interactions at the level of an interactome, involving millions of candidate pairs of proteins.

Results

Here, we describe a computational method to predict efficientlyin silicowhether two protein structures interact. This yes/no question is presumably easier to answer than the standard protein docking question, "How do these two protein structures interact?" Our approach is to discriminate between interacting and non-interacting protein pairs using a statistical pattern recognition method known as a support vector machine (SVM). We demonstrate that our structure-based method performs well on this task and scales well to the size of an interactome.

Conclusions

The use of structure information for the prediction of protein interaction yields significantly better performance than other sequence-based methods. Among structure-based classifiers, the SVM algorithm, combined with the metric learning pairwise kernel and the MAMMOTH kernel, performs best in our experiments.
Neuropeptidomic analysis of the embryonic Japanese quail diencephalon
Authors: Scholz Birger , Alm Henrik , Mattsson Anna , Nilsson Anna , Kultima Kim , Savitski Mikhail M , Fälth Maria , Sköld Karl , Brunström Björn , Andren Per E , Dencker Lennart
Published: March 2010

Background

Endogenous peptides such as neuropeptides are involved in numerous biological processes in the fully developed brain but very little is known about their role in brain development. Japanese quail is a commonly used bird model for studying sexual dimorphic brain development, especially adult male copulatory behavior in relation to manipulations of the embryonic endocrine system. This study uses a label-free liquid chromatography mass spectrometry approach to analyze the influence of age (embryonic days 12 vs 17), sex and embryonic day 3 ethinylestradiol exposure on the expression of multiple endogenous peptides in the developing diencephalon.

Results

We identified a total of 65 peptides whereof 38 were sufficiently present in all groups for statistical analysis. Age was the most defining variable in the data and sex had the least impact. Most identified peptides were more highly expressed in embryonic day 17. The top candidates for EE2exposure and sex effects were neuropeptide K (downregulated by EE2in males and females), gastrin-releasing peptide (more highly expressed in control and EE2exposed males) and gonadotropin-inhibiting hormone related protein 2 (more highly expressed in control males and displaying interaction effects between age and sex). We also report a new potential secretogranin-2 derived neuropeptide and previously unknown phosphorylations in the C-terminal flanking protachykinin 1 neuropeptide.

Conclusions

This study is the first larger study on endogenous peptides in the developing brain and implies a previously unknown role for a number of neuropeptides in middle to late avian embryogenesis. It demonstrates the power of label-free liquid chromatography mass spectrometry to analyze the expression of multiple endogenous peptides and the potential to detect new putative peptide candidates in a developmental model.
Bilateral occipital lobe infarction with altitudinal field loss following radiofrequency cardiac catheter ablation
Authors: Luu Susie T , Lee Andrew W , Chen Celia S
Published: March 2010

Background

Bilateral stroke following radiofrequency catheter ablation is an unusual complication and may result in bilateral altitudinal visual field defects. Bilateral altitudinal visual field defects usually result from prechiasmal pathology causing damage to both retinas or optic nerves and rarely from bilateral symmetric damage to the post chiasmal visual pathways.

Case presentation

A 48-year-old man complained of visual disturbance on wakening following radiofrequency catheter ablation. The patient had a CHADS score of 1 pre-operatively and no complications were noted intra-operatively. Examination revealed a bilateral superior altitudinal defect and MRI of the brain showed multifocal areas of infarction predominantly involving the occipital lobes which correlated to with the visual deficits.

Conclusion

While the risk of thromboembolism and perioperative stroke during radiofrequency catheter ablation is small, it is not insignificant.
Role of the VEGF ligand to receptor ratio in the progression of mismatch repair-proficient colorectal cancer
Authors: Eppenberger Manuela , Zlobec Inti , Baumhoer Daniel , Terracciano Luigi , Lugli Alessandro
Published: March 2010

Background

The VEGF family of ligands and receptors are intimately involved in tumor angiogenesis, lymphangiogenesis and metastasis. The evaluation of VEGF ligand/receptor ratios may provide a more profound understanding of the involvement of these proteins in colorectal tumour progression. The aim of this study was to elucidate the role of the VEGF ligand/receptor ratios on tumour progression and metastasis in patients with mismatch repair-proficient colorectal cancer.

Methods

Immunohistochemistry for VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGFR1, VEGFR2 and VEGF3 was carried out on 387 mismatch repair-proficient colorectal cancers using a tissue microarray. Evaluation of immunoreactivity was performed semi-quantitatively and the ligand/receptor expression ratio was obtained.

Results

An increased VEGF-A/VEGFR1 ratio, VEGF-A and VEGFR1 was linked to the presence of peritumoral lymphocytic inflammation at the invasive front (p = 0.032; p = 0.005; p = 0.032, respectively). VEGFR1 expression was related to poorer outcome in multivariable analysis with pT stage, pN stage, vascular invasion, and post-operative therapy. A higher ratio of VEGF-A/VEGFR2 was linked to advanced TNM stage (p = 0.005) while VEGF-A and VEGFR2 were elevated in tumours with an infiltrating tumour growth pattern (p = 0.006; p = 0.014; p = 0.006). No effect of VEGF-A/VEGFR2, VEGF-A or VEGFR2 on survival time was noted.

Conclusions

Our findings highlight an involvement of VEGF-A, VEGR1 and VEGFR2 in events occurring at the invasive tumour front and a potential prognostic role of VEGFR1 expression in mismatch repair-proficient colorectal cancers. The VEGF-A ligand to VEGFR1 or VEGFR2 ratio may represent an alternative evaluation system for identifying patients with poorer clinical outcome.
Socioeconomic deprivation, urban-rural location and alcohol-related mortality in England and Wales
Authors: Erskine Sally , Maheswaran Ravi , Pearson Tim , Gleeson Dermot
Published: March 2010

Background

Many causes of death are directly attributable to the toxic effects of alcohol and deaths from these causes are increasing in the United Kingdom. The aim of this study was to investigate variation in alcohol-related mortality in relation to socioeconomic deprivation, urban-rural location and age within a national context.

Methods

An ecological study design was used with data from 8797 standard table wards in England and Wales. The methodology included using the Carstairs Index as a measure of socioeconomic deprivation at the small-area level and the national harmonised classification system for urban and rural areas in England and Wales. Alcohol-related mortality was defined using the National Statistics definition, devised for tracking national trends in alcohol-related deaths. Deaths from liver cirrhosis accounted for 85% of all deaths included in this definition. Deaths from 1999-2003 were examined and 2001 census ward population estimates were used as the denominators.

Results

The analysis was based on 28,839 deaths. Alcohol-related mortality rates were higher in men and increased with increasing age, generally reaching peak levels in middle-aged adults. The 45-64 year age group contained a quarter of the total population but accounted for half of all alcohol-related deaths. There was a clear association between alcohol-related mortality and socioeconomic deprivation, with progressively higher rates in more deprived areas. The strength of the association varied with age. Greatest relative inequalities were seen amongst people aged 25-44 years, with relative risks of 4.73 (95% CI 4.00 to 5.59) and 4.24 (95% CI 3.50 to 5.13) for men and women respectively in the most relative to the least deprived quintiles. People living in urban areas experienced higher alcohol-related mortality relative to those living in rural areas, with differences remaining after adjustment for socioeconomic deprivation. Adjusted relative risks for urban relative to rural areas were 1.35 (95% CI 1.20 to 1.52) and 1.13 (95% CI 1.01 to 1.25) for men and women respectively.

Conclusions

Large inequalities in alcohol-related mortality exist between sub-groups of the population in England and Wales. These should be considered when designing public health policies to reduce alcohol-related harm.
Antibodies against multiple merozoite surface antigens of the human malaria parasite Plasmodium falciparum inhibit parasite maturation and red blood cell invasion
Authors: Woehlbier Ute , Epp Christian , Hackett Fiona , Blackman Michael J , Bujard Hermann
Published: March 2010

Background

Plasmodium falciparummerozoites expose at their surface a large protein complex, which is composed of fragments of merozoite surface protein 1 (MSP-1; called MSP-183, MSP-130, MSP-138, and MSP-142) plus associated processing products of MSP-6 and MSP-7. During erythrocyte invasion this complex, as well as an integral membrane protein called apical membrane antigen-1 (AMA-1), is shed from the parasite surface following specific proteolysis. Components of the MSP-1/6/7 complex and AMA-1 are presently under development as malaria vaccines.

Methods

The specificities and effects of antibodies directed against MSP-1, MSP-6, MSP-7 on the growth of blood stage parasites were studied using ELISA and the pLDH-assay. To understand the mode of action of these antibodies, their effects on processing of MSP-1 and AMA-1 on the surface of merozoites were investigated.

Results

Antibodies targeting epitopes located throughout the MSP-1/6/7 complex interfere with shedding of MSP-1, and as a consequence prevent erythrocyte invasion. Antibodies targeting the MSP-1/6/7 complex have no effect on the processing and shedding of AMA-1 and, similarly, antibodies blocking the shedding of AMA-1 do not affect cleavage of MSP-1, suggesting completely independent functions of these proteins during invasion. Furthermore, some epitopes, although eliciting highly inhibitory antibodies, are only poorly recognized by the immune system when presented in the structural context of the intact antigen.

Conclusions

The findings reported provide further support for the development of vaccines based on MSP-1/6/7 and AMA-1, which would possibly include a combination of these antigens.
Cytosolic group IVa phospholipase A2 mediates IL-8/CXCL8-induced transmigration of human polymorphonuclear leukocytes in vitro
Authors: Meliton Angelo Y , Muñoz Nilda M , Meliton Lucille N , Binder David C , Osan Christopher M , Zhu Xiangdong , Dudek Steven M , Leff Alan R
Published: March 2010

Background

Cytosolic gIVaPLA2is a critical enzyme in the generation of arachidonate metabolites and in induction of β2-integrin adhesion in granulocytes. We hypothesized that gIVaPLA2activation also is an essential downstream step forpost adhesivemigration of PMNin vitro.

Methods

Migration of PMNs caused by IL-8/CXCL8 was assessed using a transwell migration chamber. PMNs were pretreated with two structurally unrelated inhibitors of gIVaPLA2, arachidonyl trifluoromethylketone (TFMK) or pyrrophenone, prior to IL-8/CXCL8 exposure. The fraction of migrated PMNs present in the lower chamber was measured as total myeloperoxidase content. GIVaPLA2enzyme activity was analyzed using [14C-PAPC] as specific substrate F-actin polymerization and cell structure were examined after rhodamine-phalloidin staining.

Results

IL-8/CXCL8-induced migration of PMNs was elicited in concentration- and time-dependent manner. Time-related phosphorylation and translocation of cytosolic gIVaPLA2to the nucleus was observed for PMNs stimulated with IL-8/CXCL8 in concentration sufficient to cause upstream phosphorylation of MAPKs (ERK-1/2 and p38) and Akt/PKB. Inhibition of gIVaPLA2corresponded to the magnitude of blockade of PMN migration. Neither AA nor LTB4secretion was elicited following IL-8/CXCL8 activation. In unstimulated PMNs, F-actin was located diffusely in the cytosol; however, a clear polarized morphology with F-actin-rich ruffles around the edges of the cell was observed after activation with IL-8/CXCL8. Inhibition of gIVaPLA2blocked change in cell shape and migration caused by IL-8/CXCL8 but did not cause F-actin polymerization or translocation of cytosolic F-actin to inner leaflet of the PMN membrane.

Conclusion

We demonstrate that IL-8/CXCL8 causes a) phosphorylation and translocation of cytosolic gIVaPLA2to the nucleus, b) change in cell shape, c) polymerization of F-actin, and d) chemoattractant/migration of PMN in vitro. Inhibition of gIVaPLA2blocks the deformability and subsequent migration of PMNs caused by IL-8/CXCL8. Our data suggest that activation of gIVaPLA2is an essential step in PMN migrationin vitro.
Kimura's disease with eosinophilic panniculitis - treated with cyclosporine: a case report
Authors: Maleki Davood , Sayyah Alireza , Rahimi-Rad Mohammad Hossein , Gholami Nasrin
Published: March 2010

Kimura's disease is a rare, benign, slow growing chronic inflammatory swelling with a predilection for the head and neck region and almost always with peripheral blood eosinophilia and elevated serum IgE levels. Here, we report a 25-year-old male patient with asthma, Reynaud phenomenon, eosinophilic panniculitis, bilateral inguinal lymphadenopathy and peripheral blood eosinophilia.

He responded initially to oral prednisolone with the subsidence of peripheral blood eosinophilia, asthma and the Reynaud phenomenon. But with tapering of prednisolone symptoms reappeared and hereby he was treated with cyclosporine. He has been symptom free for 6 months of follow up while taking cyclosporine 25 mg orally per day. Eosinophilia has resolved. This case shows that in addition to previously reported associations, Kimura disease may be associated with eosinophilic panniculitis and that cyclosporine could be effective in its treatment.
Choline PET based dose-painting in prostate cancer - Modelling of dose effects
Authors: Niyazi Maximilian , Bartenstein Peter , Belka Claus , Ganswindt Ute
Published: March 2010

Background

Several randomized trials have documented the value of radiation dose escalation in patients with prostate cancer, especially in patients with intermediate risk profile. Up to now dose escalation is usually applied to the whole prostate. IMRT and related techniques currently allow for dose escalation in sub-volumes of the organ. However, the sensitivity of the imaging modality and the fact that small islands of cancer are often dispersed within the whole organ may limit these approaches with regard to a clear clinical benefit. In order to assess potential effects of a dose escalation in certain sub-volumes based on choline PET imaging a mathematical dose-response model was developed.

Methods

Based on different assumptions for α/β, γ50, sensitivity and specificity of choline PET, the influence of the whole prostate and simultaneous integrated boost (SIB) dose on tumor control probability (TCP) was calculated. Based on the given heterogeneity of all potential variables certain representative permutations of the parameters were chosen and, subsequently, the influence on TCP was assessed.

Results

Using schedules with 74 Gy within the whole prostate and a SIB dose of 90 Gy the TCP increase ranged from 23.1% (high detection rate of choline PET, low whole prostate dose, high γ50/ASTRO definition for tumor control) to 1.4% TCP gain (low sensitivity of PET, high whole prostate dose, CN + 2 definition for tumor control) or even 0% in selected cases. The corresponding initial TCP values without integrated boost ranged from 67.3% to 100%. According to a large data set of intermediate-risk prostate cancer patients the resulting TCP gains ranged from 22.2% to 10.1% (ASTRO definition) or from 13.2% to 6.0% (CN + 2 definition).

Discussion

Although a simplified mathematical model was employed, the presented model allows for an estimation in how far given schedules are relevant for clinical practice. However, the benefit of a SIB based on choline PET seems less than intuitively expected. Only under the assumption of high detection rates and low initial TCP values the TCP gain has been shown to be relevant.

Conclusions

Based on the employed assumptions, specific dose escalation to choline PET positive areas within the prostate may increase the local control rates. Due to the lack of exact PET sensitivity and prostate α/β parameter, no firm conclusions can be made. Small variations may completely abrogate the clinical benefit of a SIB based on choline PET imaging.
The internal state of medium spiny neurons varies in response to different input signals
Authors: Qi Zhen , Miller Gary W , Voit Eberhard O
Published: March 2010

Background

Parkinson's disease, schizophrenia, Huntington's chorea and drug addiction are manifestations of malfunctioning neurons within the striatum region at the base of the human forebrain. A key component of these neurons is the protein DARPP-32, which receives and processes various types of dopamine and glutamate inputs and translates them into specific biochemical, cellular, physiological, and behavioral responses. DARPP-32's unique capacity of faithfully converting distinct neurotransmitter signals into appropriate responses is achieved through a complex phosphorylation-dephosphorylation system that evades intuition and predictability.

Results

To gain deeper insights into the functioning of the DARPP-32 signal transduction system, we developed a dynamic model that is robust and consistent with available clinical, pharmacological, and biological observations. Upon validation, the model was first used to explore how different input signal scenarios are processed by DARPP-32 and translated into distinct static and dynamic responses. Secondly, a comprehensive perturbation analysis identified the specific role of each component on the system's signal transduction ability.

Conclusions

Our study investigated the effects of various patterns of neurotransmission on signal integration and interpretation by DARPP-32 and showed that the DARPP-32 system has the capability of discerning surprisingly many neurotransmission scenarios. We also screened out potential mechanisms underlying this capability of the DARPP-32 system. This type of insight deepens our understanding of neuronal signal transduction in normal medium spiny neurons, sheds light on neurological disorders associated with the striatum, and might aid the search for intervention targets in neurological diseases and drug addiction.
Limited educational attainment and radiographic and symptomatic knee osteoarthritis: a cross-sectional analysis using data from the Johnston County (North Carolina) Osteoarthritis Project
Authors: Callahan Leigh F , Shreffler Jack , Siaton Bernadette C , Helmick Charles G , Schoster Britta , Schwartz Todd A , Chen Jiu-Chiuan , Renner Jordan B , Jordan Joanne M
Published: March 2010

Introduction

Applying a cross-sectional analysis to a sample of 2,627 African-American and Caucasian adults aged ≥ 45 years from the Johnston County Osteoarthritis Project, we studied the association between educational attainment and prevalence of radiographic knee osteoarthritis and symptomatic knee osteoarthritis.

Methods

Age- and race-adjusted associations between education and osteoarthritis outcomes were assessed by gender-stratified logistic regression models, with additional models adjusting for body mass index, knee injury, smoking, alcohol use, and occupational factors.

Results

In an analysis of all participants, low educational attainment (<12 years) was associated with higher prevalence of four knee osteoarthritis outcomes (unilateral and bilateral radiographic and symptomatic osteoarthritis). Women with low educational attainment had 50% higher odds of having radiographic knee osteoarthritis and 65% higher odds of symptomatic knee osteoarthritis compared with those with higher educational attainment (≥ 12 years), by using fully adjusted models. In the subset of postmenopausal women, these associations tended to be weaker but little affected by adjustment for hormone replacement therapy. Men with low educational attainment had 85% higher odds of having symptomatic knee osteoarthritis by using fully adjusted models, but the association with radiographic knee osteoarthritis was explained by age.

Conclusions

After adjustment for known risk factors, educational attainment, as an indicator of socioeconomic status, is associated with symptomatic knee osteoarthritis in both men and women and with radiographic knee osteoarthritis in women.
Mechanical ventilation with high tidal volume induces inflammation in patients without lung disease
Authors: Pinheiro de Oliveira Roselaine , Hetzel Marcio Pereira , dos Anjos Silva Mauro , Dallegrave Daniele , Friedman Gilberto
Published: March 2010

Introduction

Mechanical ventilation (MV) with high tidal volumes may induce or aggravate lung injury in critical ill patients. We compared the effects of a protective versus a conventional ventilatory strategy, on systemic and lung production of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in patients without lung disease.

Methods

Patients without lung disease and submitted to mechanical ventilation admitted to one trauma and one general adult intensive care unit of two different university hospitals were enrolled in a prospective randomized-control study. Patients were randomized to receive MV either with tidal volume (VT) of 10 to 12 ml/kg predicted body weight (high VT group) (n = 10) or with VT of 5 to 7 ml/kg predicted body weight (low VT group) (n = 10) with an oxygen inspiratory fraction (FIO2) enough to keep arterial oxygen saturation >90% with positive end-expiratory pressure (PEEP) of 5 cmH2O during 12 hours after admission to the study. TNF-α and IL-8 concentrations were measured in the serum and in the bronchoalveolar lavage fluid (BALF) at admission and after 12 hours of study observation time.

Results

Twenty patients were enrolled and analyzed. At admission or after 12 hours there were no differences in serum TNF-α and IL-8 between the two groups. While initial analysis did not reveal significant differences, standardization against urea of logarithmic transformed data revealed that TNF-α and IL-8 levels in bronchoalveolar lavage (BAL) fluid were stable in the low VT group but increased in the high VT group (P = 0.04 and P = 0.03). After 12 hours, BALF TNF-α (P = 0.03) and BALF IL-8 concentrations (P = 0.03) were higher in the high VT group than in the low VT group.

Conclusions

The use of lower tidal volumes may limit pulmonary inflammation in mechanically ventilated patients even without lung injury.

Trial Registration

Clinical Trial registration: NCT00935896
Resuscitation with low volume hydroxyethylstarch 130 kDa/0.4 is not associated with acute kidney injury
Authors: Boussekey Nicolas , Darmon Raphaël , Langlois Joachim , Alfandari Serge , Devos Patrick , Meybeck Agnes , Chiche Arnaud , Georges Hugues , Leroy Olivier
Published: March 2010

Introduction

Acute kidney injury (AKI) in the ICU is associated with poorer prognosis. Hydroxyethylstarch (HES) solutions are fluid resuscitation colloids frequently used in the ICU with controversial nephrotoxic adverse effects. Our study objective was to evaluate HES impact on renal function and organ failures.

Methods

This observational retrospective study included 363 patients hospitalized for more than 72 hours in our ICU. A hundred and sixty eight patients received HES during their stay and 195 did not. We recorded patients' baseline characteristics on admission and type and volume of fluid resuscitation during the first 3 weeks of ICU stay. We also noted the evolution of urine output, the risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function and end-stage kidney disease (RIFLE) classification and sepsis related organ failure assessment (SOFA) score over 3 weeks.

Results

Patients in the HES group were more severely ill on admission but AKI incidence was similar, as well as ICU mortality. The evolution of urine output (P = 0.74), RIFLE classification (P = 0.44) and SOFA score (P = 0.23) was not different. However, HES volumes administered were low (763+/-593 ml during the first 48 hours).

Conclusions

Volume expansion with low volume HES 130 kDa/0.4 was not associated with AKI.
Sex Differences in Epigenetic Regulation of the Estrogen Receptor-α Promoter within the Developing Preoptic Area
Authors: Kurian Joseph R. , Olesen Kristin M. , Auger Anthony P.
Published: March 2010

Sex differences in the brain are largely organized by a testicular hormone surge that occurs in males shortly after birth. Although this hormone surge is transient, sex differences in brain and behavior are lasting. Here we describe a sex difference in DNA methylation of the estrogen receptor-α (ERα) promoter region within the developing rat preoptic area, with males exhibiting more DNA methylation within the ERα promoter than females. More importantly, we report that simulating maternal grooming, a form of maternal interaction that is sexually dimorphic with males experiencing more than females during the neonatal period, effectively masculinizes female ERα promoter methylation and gene expression. This suggests natural variations in maternal care that are directed differentially at males vs. females can influence sex differences in the brain by creating sexually dimorphic DNA methylation patterns. We also find that the early estradiol exposure may contribute to sex differences in DNA methylation patterns. This suggests that early social interaction and estradiol exposure may converge at the genome to organize lasting sex differences in the brain via epigenetic differentiation.
Human Labor Is Associated with Reduced Decidual Cell Expression of Progesterone, But Not Glucocorticoid, Receptors
Authors: Lockwood C. J. , Stocco C. , Murk W. , Kayisli U. A. , Funai E. F. , Schatz F.
Published: March 2010

Context: Unchanging plasma progesterone (P4) levels suggest that human labor is initiated by reduced P4 receptor (PR) expression, which elicits functional P4 withdrawal. The glucocorticoid receptor (GR) is also implicated in this process.

Objective: Our objective was to compare PR and GR staining in human decidual cells (DCs) and interstitial trophoblasts (ITs) of gestational age-matched pre- and postcontraction specimens and to evaluate steroid effects on PR and GR expression in human DC cultures.

Interventions and Main Outcome Measures: Decidua basalis and parietalis sections were immunostained for PR or GR and then for the cytoplasmic DC and IT markers vimentin and cytokeratin. Western blotting measured PR and GR levels in nuclear extracts of cultured leukocyte-free term DCs after incubation with estradiol-17β (E2) with or without medroxyprogesterone acetate (MPA).

Results: PR histological scores (HSCOREs) were significantly higher in DC nuclei from pre- vs. post-uterine-contraction decidua basalis and parietalis sections with PR immunostaining absent from ITs. In contrast, immunoreactive GR was localized in IT and DC nuclei. GR HSCORES were significantly higher in ITs than DCs but similar in pre- vs. post-uterine-contraction specimens. In term DC monolayers, PR-A and PR-B were enhanced by E2 and inhibited by MPA, whereas E2 plus MPA produced intermediate PR expression. The GR was constitutively expressed.

Conclusions: In post- vs. pre-uterine-contraction specimens, significantly lower HSCOREs in DC nuclei, but not IT, and unchanging GR levels in DCs and ITs suggest that functional P4 withdrawal may occur in DCs and is unlikely to involve the GR. Nuclear extracts from DC monolayer cultures express steroid-regulated PR-A and PR-B and constitutive GR.
Knowledge-based engineering to support aircraft multidisciplinary design and optimization
Authors: La Rocca G , van Tooren M J L
Published: March 2010

This paper discusses structure and functionalities of a knowledge-based engineering (KBE) application, called multimodel generator (MMG), developed to support aircraft multidisciplinary design, analysis, and optimization. Designers can use the MMG as an advanced modelling tool to swiftly generate geometrical models of many and diverse aircraft configurations and variants, by combining and adjusting a limited number of parametric objects, called high-level primitives. Besides capturing the geometric aspects of the design, the MMG also has the capabilities to automate a large part of the lengthy and non-creative pre-processing activities involved in the design verification process. The proposed KBE application has demonstrated to be a valuable solution for some of the critical needs indicated by the multidisciplinary design and optimization community, namely a flexible and robust generative tool to increase the level of automation in aircraft design, including the development of novel configurations; the exploitation of high-fidelity analytical tools already in the early design phase; the management of the design activities across distributed networks of disciplines specialists.
The effect of upstream duct boundary layer growth and compressor blade lean angle variation on an axial compressor performance
Authors: Templalexis I , Pachidis V , Pilidis P , Kotsiopoulos P
Published: March 2010

The compressor of a gas turbine engine is extremely vulnerable on upstream duct-induced flow non-uniformities whether the duct is an engine intake or an interconnecting duct. This is justified by its position being literally an extension of the duct flow path, coupled to the fact that it operates under adverse pressure gradients. In particular, this study focuses on performance deviations between installed and uninstalled compressors. Test results acquired from a test bed installation will differ from those recorded when the compressor operates as an integral part of an engine. The upstream duct, whether an engine intake or an inter-stage duct, will affect the flow-field pattern ingested into the compressor. The case study presented here aims mostly at qualifying the effect of boundary layer growth along the upstream duct wall on compressor performance. Additionally, the compressor performance response on blade lean angle variation is also addressed, with the aim of acquiring an understanding as to how compressor blade lean angle changes interact with intake-induced flow non-uniformities. Such studies are usually conducted as part of the preliminary design phase. Consequently, experimental performance investigation is excluded at this stage of development, and therefore, computer-aided simulation techniques are used if not the only option for compressor performance prediction. Given the fact that many such design parameters need to be assessed under the time pressure exerted by the tight compressor development programme, the compressor flow simulation technique needs to provide reliable results while consuming the least possible computational time. Such a low computational time compressor flow simulation method, among others, is the two-dimensional streamline curvature (SLC) method, being also applied within the frame of reference of the current study. The paper is introduced by a brief discussion on SLC method. Then, a reference is made to the radial equilibrium equation, which is the mathematical basis of SOCRATES, a turbomachinery flow simulation tool that was used in this study. Subsequently, the influence of the upstream duct on the compressor inlet radial flow distribution is being addressed, with the aim of adjusting the compressor blade inlet lean angle, in order to minimize compressor performance deterioration. The paper concludes with a discussion of the results.
Interaction between particle-laden underexpanded twin supersonic jets
Authors: Varun R , Sundararajan T , Usha R , Srinivasan K
Published: March 2010

This paper presents numerical results on the near-field interactions of particle-laden twin supersonic jets operating in underexpanded mode, with special emphasis on the effects of particles on jet flow expansion. Although plane jets have been considered primarily, a few cases of twin round jets have also been simulated for the sake of comparison. Three turbulence models (Spalart—Allmaras, k—ɛ (realizable), and k—ω (sst)) have been considered for incorporating turbulent interaction effects in two-phase supersonic jets. In general, the k—ω (sst) model gives better predictions in the reverse flow as well as in the shock regions. The recirculatory flow is enhanced at high underexpansion (UE) ratios, and the size and strength of the recirculation region are much smaller for twin round jets than those for plane jets. In particle-laden jets, small particles (corresponding to Stokes number less than 0.05) are entrained in the recirculation zone, whereas particles of larger size are not trapped. With large particles, a particle-free zone occurs close to the nozzle wall in the divergent section. Small particles follow the gas phase with negligible non-equilibrium effects, but they also cause higher two-phase drag, resulting in a higher degree of jet UE.
Trajectory tracking controller design using neural networks for a tiltrotor unmanned aerial vehicle
Authors: Kim B-M , Kim B S , Kim N-W
Published: March 2010

This article presents a design of trajectory tracking controller for a tiltrotor unmanned aerial vehicle (UAV). The objective of this design is to control the tiltrotor aircraft with one fixed controller architecture for all flight modes, viz. helicopter mode, conversion mode, and aeroplane mode. The controller is implemented using two time-scale separations, and thus comprises an inner loop for attitude control and an outer loop for trajectory control. The dynamic model inversion (DMI) technique is applied to both the control loops such that the inner-loop and the outer-loop DMIs are driven using the angular equations of motion and the translational equations of motion, respectively. In addition, online adaptive neural networks are employed to compensate for the model inversion errors of the inner loop and the outer loop due to the lack of complete knowledge of tiltrotor aircraft dynamics. The pseudo-control hedging algorithm is adopted to reduce the instability problem caused by the time-delay of control loops, saturation, and rate limit of actuators. The trajectory tracking controller is evaluated using a sophisticated six-degree-of-freedom non-linear simulation programme with an approach and landing scenario including all flight modes of a smart UAV, a tiltrotor UAV.
Large-eddy simulation of kerosene spray combustion in a model scramjet chamber
Authors: Zhang M , Hu Z , He G , Liu P
Published: March 2010

Large-eddy simulation (LES) of kerosene spray combustion in a model supersonic combustor with cavity flame holder is carried out. Kerosene is injected through the ceiling of the cavity. The subgrid-scale (SGS) turbulence stress tensor is closed via the Smagorinsky's eddy-viscosity model, chemical source terms are modelled by a finite rate chemistry (FRC) model, and a four-step reduced kerosene combustion kinetic mechanism is adopted. The chamber wall pressure predicted from the LES is validated by experimental data reported in literature. The test case has a cavity length of 77 mm and a depth of 8 mm. After liquid kerosene is injected through the orifice, most of the droplets are loaded with recirculation fluid momentum inside the cavity. Due to lower velocity of the carrier fluid inside the cavity, sufficient atomization and evaporation take place during the process of droplet transportation, resulting in a rich fuel mixture of kerosene vapour accumulating inside the cavity. These rich fuel mixtures are mixed with fresh air by the approaching mixing layer at the front of the cavity and are thus involved in burning accompanied with the approaching boundary layer separation extending towards upstream. The combustion flame in the downstream impinges onto the rear wall of the cavity and is then reflected back to the front of the cavity. During the recirculation of hot flow, heat is compensated for evaporation of droplets. The circulation processes mentioned above provide an efficient flame-holding mechanism to stabilize the flame. Comparisons with results from a shorter length of cavity (cavity length of 45 mm) show that, due to insufficient atomization and evaporation of the droplets in the short distance inside the cavity, parts of the droplets are carried out of the cavity through the boundary layer fluctuation and evaporated in the hot flame layer, thus resulting in incomplete air fuel mixing and worse combustion performance. The flow structures inside the cavity play an important role in the spray distribution, thus determining the combustion performance.