bluuebunny/crossref_metadata_2025 huggingface dataset:
Interlinked nonlinear subnetworks underlie the formation of robust cellular patterns in Arabidopsis epidermis: a dynamic spatial model
Authors: Benítez Mariana , Espinosa-Soto Carlos , Padilla-Longoria Pablo , Alvarez-Buylla Elena R
Published: November 2008

Background

Dynamical models are instrumental for exploring the way information required to generate robust developmental patterns arises from complex interactions among genetic and non-genetic factors. We address this fundamental issue of developmental biology studying the leaf and root epidermis ofArabidopsis. We propose an experimentally-grounded model of gene regulatory networks (GRNs) that are coupled by protein diffusion and comprise a meta-GRN implemented on cellularised domains.

Results

Steady states of the meta-GRN model correspond to gene expression profiles typical of hair and non-hair epidermal cells. The simulations also render spatial patterns that match the cellular arrangements observed in root and leaf epidermis. As in actual plants, such patterns are robust in the face of diverse perturbations. We validated the model by checking that it also reproduced the patterns of reported mutants. The meta-GRN model shows that interlinked sub-networks contribute redundantly to the formation of robust hair patterns and permits to advance novel and testable predictions regarding the effect of cell shape, signalling pathways and additional gene interactions affecting spatial cell-patterning.

Conclusion

The spatial meta-GRN model integrates available experimental data and contributes to further understanding of theArabidopsisepidermal system. It also provides a systems biology framework to explore the interplay among sub-networks of a GRN, cell-to-cell communication, cell shape and domain traits, which could help understanding of general aspects of patterning processes. For instance, our model suggests that the information needed for cell fate determination emerges from dynamic processes that depend upon molecular components inside and outside differentiating cells, suggesting that the classical distinction of lineageversuspositional cell differentiation may be instrumental but rather artificial. It also suggests that interlinkage of nonlinear and redundant sub-networks in larger networks is important for pattern robustness. Pursuing dynamic analyses of larger (genomic) coupled networks is still not possible. A repertoire of well-characterised regulatory modules, like the one presented here, will, however, help to uncover general principles of the patterning-associated networks, as well as the peculiarities that originate diversity.
Lack of association of genetic variants in genes of the endocannabinoid system with anorexia nervosa
Authors: Müller Timo Dirk , Reichwald Kathrin , Brönner Günter , Kirschner Jeanette , Nguyen Thuy Trang , Scherag André , Herzog Wolfgang , Herpertz-Dahlmann Beate , Lichtner Peter , Meitinger Thomas , Platzer Matthias , Schäfer Helmut , Hebebrand Johannes , Hinney Anke
Published: November 2008

Background

Several lines of evidence indicate that the central cannabinoid receptor 1 (CNR1) as well as the major endocannabinoid degrading enzymes fatty acid amide hydrolase (FAAH), N-acylethanolamine-hydrolyzing acid amidase (NAAA) and monoglyceride lipase (MGLL) are implicated in mediating the orexigenic effects of cannabinoids. The aim of this study was to analyse whether nucleotide sequence variations in the CNR1, FAAH, NAAA and MGLL genes are associated with anorexia nervosa (AN).

Methods

We analysed the association of a previously described (AAT)n repeat in the 3' flanking region of CNR1 as well as a total of 15 single nucleotide polymorphisms (SNPs) representative of regions with restricted haplotype diversity in CNR1, FAAH, NAAA or MGLL in up to 91 German AN trios (patient with AN and both biological parents) using the transmission-disequilibrium-test (TDT). One SNP was additionally analysed in an independent case-control study comprising 113 patients with AN and 178 normal weight controls. Genotyping was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, ARMS-PCR or using 3730xl capillary sequencers.

Results

The TDT revealed no evidence for association for any of the SNPs or the (AAT)n repeat with AN (all two-sided uncorrected p-values > 0.05). The lowest p-value of 0.11 was detected for the A-allele of the CNR1 SNP rs1049353 for which the transmission rate was 59% (95% confidence interval 47%...70%). Further genotyping of rs1049353 in 113 additional independent patients with AN and 178 normal weight controls could not substantiate the initial trend for association (p = 1.00).

Conclusion

As we found no evidence for an association of genetic variation in CNR1, FAAH, NAAA and MGLL with AN, we conclude that genetic variations in these genes do not play a major role in the etiology of AN in our study groups.
Determining the impact of alternative splicing events on transcriptome dynamics
Authors: Wilhelm Emmanuelle , Pellay François-Xavier , Benecke Arndt , Bell Brendan
Published: November 2008

Background

The complete sequencing of the human genome and its subsequent analysis revealed a predominant role for alternative splicing in the generation of proteome diversity. Splice switching oligonucleotides (SSOs) are a powerful and specific tool to experimentally control alternative splicing of endogenous messenger RNAs in living cells. SSOs also have therapeutic potential to treat diseases that are caused by aberrant splicing. The assignment of biological roles to alternative splicing events of currently unknown function promises to provide a largely untapped source of potential new therapeutic targets. Here we have developed a protocol that combines high sensitivity microarrays with the transfection of SSOs to monitor global changes in gene expression downstream of alternate, endogenous splice events.

Results

When applied to a well-characterized splicing event in the Bcl-x gene, the application of high sensitivity microarrays revealed a link between the induction of the Bcl-xS isoform and the repression of genes involved in protein synthesis.

Conclusion

The strategy introduced herein provides a useful approach to define the biological impact of any given alternative splicing event on global gene expression patterns. Furthermore, our data provide the first link between Bcl-xS expression and the repression of ribosomal protein gene expression.
Structural insights into phenylethanolamines high-affinity binding site in NR2B from binding and molecular modeling studies
Authors: Ng Fui-Mee , Geballe Matthew T , Snyder James P , Traynelis Stephen F , Low Chian-Ming
Published: November 2008

Background

Phenylethanolamines selectively bind to NR2B subunit-containingN-methyl-D-aspartate-subtype of ionotropic glutamate receptors and negatively modulate receptor activity. To investigate the structural and functional properties of the ifenprodil binding domain on the NR2B protein, we have purified a soluble recombinant rat NR2B protein fragment comprising the first ~400 amino acid amino-terminal domain (ATD2B) expressed inE. coli. Spectral measurements on refolded ATD2B protein demonstrated specific binding to ifenprodil. We have used site-directed mutagenesis, circular dichroism spectroscopy and molecular modeling to obtain structural information on the interactions between critical amino acid residues and ifenprodil of our soluble refolded ATD2B proteins. Ligand-induced changes in protein structure were inferred from changes in the circular dichroism spectrum, and the concentration dependence of these changes was used to determine binding constants for ifenprodil and its analogues.

Results

Ligand binding of ifenprodil, RO25,6981 and haloperidol on soluble recombinant ATD2B determined from circular dichroism spectroscopy yielded low-to-high micromolar equilibrium constants which concurred with functional IC50measurement determined in heterologously expressed NR1/NR2B receptors inXenopusoocytes. Amino acid residue substitutions of Asp101, Ile150 and Phe176 with alanine residue within the ATD2B protein altered the recombinant protein dissociation constants for ifenprodil, mirroring the pattern of their functional phenotypes. Molecular modeling of ATD2B as a clam-shell-like structure places these critical residues near a putative ligand binding site.

Conclusion

We report for the first time biochemical measurements show that the functional measurements actually reflect binding to the ATD of NR2B subunit. Insights gained from this study help advance the theory that ifenprodil is a ligand for the ATD of NR2B subunit.
Malignant mesothelioma of the tunica vaginalis of the testis without exposure to asbestos
Authors: Goel Ashish , Agrawal Akansha , Gupta Rajiv , Hari Smriti , Dey A B
Published: November 2008

Introduction

Mesotheliomas are rare tumours that usually are seen in the pleura after asbestos exposure. Mesotheliomas have been reported around the testicular region but are even rarer following trauma, herniorrhaphy and long term hydrocoele.

Case presentation

An elderly male farmer presented to us with an insidious onset of painless swelling in his left lower limb which gradually progressive. At the time of presentation it had involved his entire limb. A hard palpable mass of size 5 * 4 cms was detected in the left iliac fossa and a testicular enlargement was noted on the left side. The ultrasound of the testes showed that the left testis was enlarged 3.9*3*3.2 cms showing diffusely heterogenous echo-texture and irregular nodular surface with irregular hypoechoic thickening of the scrotal wall with left sided hydrocele. A separate hypoechoic *1.2 cms lesion was visualized in the anterior scrotal wall. FNAC from the scrotal mass showed tumour cells of simialr morphology present singly in monolayered sheets and in three dimensional fragments. The overall immunomorphological features suggested a malignant mesothelioma likely to have arisen from the tunica vaginalis.

Conclusion

In conclusion, though a rare tumor, malignant mesothelioma of the tunica vaginalis of the testis should be considered whenever a paratesticular mass lesion is seen even without a history of trauma or asbestos exposure as is highlighted in this case. Ultrasound findings are helpful and fine needle aspiration of the tumor may assist in arrival at a diagnosis. Surgical orchidectomy remains the modality of treatment.
Primary hepatic carcinoid; a diagnostic dilemma: a case report
Authors: Touloumis Zisis , Delis Spiros G , Triantopoulou Charikleia , Giannakou Nikoletta , Avgerinos Costas , Dervenis Christos
Published: November 2008

Introduction

Primary hepatic carcinoid tumours (PHCTs) are extremely rare neuroendocrine neoplasms. Only 58 cases have been reported in the literature and less than 10 cases were functional.

Case presentation

We present a case of a 65 years old, Caucasian female with a large unresectable primary hepatic carcinoid tumor secreting 5-hydroxyindoleacetic acid (5-HIAA), presented with flushing and diarrhoea and treated with trans-catheter arterial embolization (TACE) and subsequent administration of lanreotide (long acting somatostatin analogue).

Conclusion

The diagnosis of PHCTs is difficult due to their common radiologic characteristics with other liver lesions. Their diagnosis is based on the exclusion of other sites of disease and the histologic confirmation. Although the mainstay of treatment when is technically feasible is surgical resection with optimal 5-year survival and low recurrence rate, in cases of unresectable disease palliation with combination of TACE and administration of somatostatin analogues have good results in controlling the disease and the patients symptoms.
Therapeutic efficacy of intra-articular adrenomedullin injection in antigen-induced arthritis in rabbits
Authors: Okura Toshiyuki , Marutsuka Kousuke , Hamada Hiroaki , Sekimoto Tomohisa , Fukushima Tsuyoshi , Asada Yujiro , Kitamura Kazuo , Chosa Etsuo
Published: November 2008

Introduction

Adrenomedullin is a potent vasodilatory and hypotensive peptide as well as an endogenous immunomodulatory factor with predominantly anti-inflammatory effects. The purpose of the present study was to evaluate the therapeutic effects of adrenomedullin in rabbits with antigen-induced arthritis, an experimental model of rheumatoid arthritis.

Methods

Following the induction of arthritis in both knee joints by ovalbumin injection into the joint spaces of pre-immunized rabbits, increasing daily doses of adrenomedullin were injected into the knee joint spaces or saline was injected into the contralateral knee joint spaces as the control. For time-course experiments, adrenomedullin and saline were injected into the knee joint spaces daily for 7 days and 20 days. The degree of joint swelling and the histological change in the knee joints injected with adrenomedullin were compared with the control knee joints. Histological evaluation of the infrapatellar fat pads and synovial tissue was performed. TNFα, IL-6, vascular endothelial growth factor and transforming growth factor-beta mRNA levels in the synovial tissue were measured using real-time quantitative PCR.

Results

Daily injections of adrenomedullin into the knee joint spaces of rabbits with antigen-induced arthritis decreased joint swelling. Histological examination revealed that adrenomedullin reduced edematous changes and the infiltration of inflammatory cells in the synovial tissues. Analysis of mRNA levels showed that adrenomedullin significantly reduced TNFα mRNA expression by 21% to 49% in a dose-dependent manner, and dose-dependently increased IL-6 mRNA expression by 45% to 121%.

Conclusions

These results suggest that daily injections of adrenomedullin into the knee joint spaces of rabbits with antigen-induced arthritis ameliorated the inflammatory response in arthritic joints. Adrenomedullin may thus be useful as a treatment for rheumatoid arthritis; however, the effect of adrenomedullin on IL-6 production in the synovial tissue may be an undesirable adverse effect in rheumatoid arthritis therapy.
Collagen-specific T-cell repertoire in blood and synovial fluid varies with disease activity in early rheumatoid arthritis
Authors: Ria Francesco , Penitente Romina , De Santis Maria , Nicolò Chiara , Di Sante Gabriele , Orsini Massimiliano , Arzani Dario , Fattorossi Andrea , Battaglia Alessandra , Ferraccioli Gian Franco
Published: November 2008

Introduction

Type II collagen is a DR4/DR1 restricted target of self-reactive T cells that sustain rheumatoid arthritis. The aim of the present study was to analyze the T-cell receptor repertoire at the onset of and at different phases in rheumatoid arthritis.

Methods

We used the CDR3 BV-BJ spectratyping to study the response to human collagen peptide 261–273 in 12 patients with DR4+ rheumatoid arthritis (six at the onset of disease and six during the course of disease) and in five healthy DR4+ relatives.

Results

The collagen-specific T-cell repertoire is quite restricted at the onset of disease, involving approximately 10 rearrangements. Within the studied collagen-specific rearrangements, nearly 75% is shared among patients. Although the size of the repertoire used by control individuals is comparable to that of patients, it is characterized by different T-cell receptors. Part of the antigen-specific T-cell repertoire is spontaneously enriched in synovial fluid. The specific T-cell repertoire in the periphery was modulated by therapy and decreased with the remission of the disease. Failure of immunoscopy to detect this repertoire was not due to suppression of collagen-driven proliferation in vitro by CD4+ CD25+ T cells. Clinical relapse of the disease was associated with the appearance of the original collagen-specific T cells.

Conclusions

The collagen-specific T-cell receptor repertoire in peripheral blood and synovial fluid is restricted to a limited number of rearrangements in rheumatoid arthritis. The majority of the repertoire is shared between patients with early rheumatoid arthritis and it is modulated by therapy.
Proteomics studies confirm the presence of alternative protein isoforms on a large scale
Authors: Tress Michael L , Bodenmiller Bernd , Aebersold Ruedi , Valencia Alfonso
Published: November 2008

Background

Alternative splicing of messenger RNA permits the formation of a wide range of mature RNA transcripts and has the potential to generate a diverse spectrum of functional proteins. Although there is extensive evidence for large scale alternative splicing at the transcript level, there have been no comparable studies demonstrating the existence of alternatively spliced protein isoforms.

Results

Recent advances in proteomics technology have allowed us to carry out a comprehensive identification of protein isoforms in Drosophila. The analysis of this proteomic data confirmed the presence of multiple alternative gene products for over a hundred Drosophila genes.

Conclusions

We demonstrate that proteomics techniques can detect the expression of stable alternative splice isoforms on a genome-wide scale. Many of these alternative isoforms are likely to have regions that are disordered in solution, and specific proteomics methodologies may be required to identify these peptides.
Escherichia colitype 1 pili trigger late IL-8 production by neutrophil-like differentiated PLB-985 cells through a Src family kinase- and MAPK-dependent mechanism
Authors: Sémiramoth Nicolas , Gleizes Aude , Turbica Isabelle , Sandré Catherine , Gorges Roseline , Kansau Imad , Servin Alain , Chollet-Martin Sylvie
Published: November 2008

The innate immune response to enteropathogenic bacteria includes chemokine-induced polymorphonuclear neutrophil (PMN) migration across mucosal epithelia leading to bacterial clearance and resolution of infection. Among these bacteria, diffusely adherent Escherichia coli expressing Afa/Dr fimbriae (Afa/Dr DAEC), causing childhood diarrhea, can promote IL-8-dependent PMN transmigration across cultured intestinal epithelial cell monolayers via MAPK pathway activation. However, interactions between PMN and Afa/Dr DAEC are poorly documented and constitute the aim of the present study. Using the human PLB-985 cell line differentiated into fully mature PMN, we described the coordinated response to various E. coli. The rapid and strong release of reactive oxygen species and preformed intragranular mediators (myeloperoxidase and IL-8) is followed by a later TNF-α, IL-1β, and IL-8 synthesis. The use of wild-type (IH11128, C1845, LF82), control (AAEC185), and recombinant (AAEC185 bearing Dr or F1845 fimbriae, AdLF82, or type 1 pili) bacterial strains allowed us to demonstrate that late IL-8 hyperproduction is triggered by type 1 pili but not by Dr or F1845 fimbriae; MAPKs (p38, ERK, Src) and NF-κB activations are implicated in this response. Thus, in the course of Afa/Dr DAEC intestinal infection, epithelium- and neutrophil-derived IL-8 could, at least in part, control the flow of neutrophils through the lamina propria. Afa/Dr DAEC-induced IL-8 hyperproduction by PMN might thus be important for inducing and perpetuating local inflammation, and this self-amplifying loop might play a role in the pathogenesis of inflammatory bowel diseases such as Crohn’s disease.
Relationship of Treatment-Related Cytopenias and Response to Lenalidomide in Patients With Lower-Risk Myelodysplastic Syndromes
Authors: Sekeres Mikkael A. , Maciejewski Jaroslaw P. , Giagounidis Aristotle A.N. , Wride Kenton , Knight Robert , Raza Azra , List Alan F.
Published: November 2008

Purpose

Patients with myelodysplastic syndromes (MDS) often require treatment with growth factors (GFs) or non-GF therapies. One non-GF drug, lenalidomide, is particularly effective at achieving transfusion independence (TI) in patients with lower-risk MDS with the del(5q) cytogenetic abnormality. However, approximately half of del(5q) patients and one quarter of non–del(5q) patients treated with lenalidomide experience significant cytopenias. Lenalidomide-induced cytopenias occurring early in treatment may serve as a surrogate marker of clonal suppression and, therefore, may be predictive of a TI response.

Patients and Methods

We analyzed 362 low-risk, transfusion-dependent patients with MDS, with or without the del(5q) abnormality, enrolled in two phase II studies (MDS-003 and MDS-002) to determine whether treatment-related cytopenias are correlated with lenalidomide response. Cytopenias were assessed during the first 8 weeks of therapy, and response was defined as TI; response predictors were explored in univariate and multivariate analyses.

Results

Among patients with del(5q), 70% of those whose platelet count decreased by ≥ 50% achieved TI, as compared with 42% of those whose platelet count remained stable or declined by less than 50% (P = .01). Among patients without baseline neutropenia, 82% of those whose absolute neutrophil count (ANC) decreased by ≥ 75% achieved TI, as compared with 51% whose ANC remained stable or decreased by less than 75% (P = .02). These relationships were consistent in multivariate analyses. No relationship between the development of cytopenias and response could be established for lower-risk patients with MDS without del(5q).

Conclusion

These findings support the hypothesis that a direct cytotoxic effect of lenalidomide specific to the del(5q) clone may be indicative of a TI response.
Phase I/II Study of Ipilimumab for Patients With Metastatic Melanoma
Authors: Weber Jeffrey S. , O’Day Steven , Urba Walter , Powderly John , Nichol Geoff , Yellin Michael , Snively Jolie , Hersh Evan
Published: November 2008

Purpose

The primary objective of this phase I/II study was to determine the safety and pharmacokinetic profile of either transfectoma- or a hybridoma-derived ipilimumab. Secondary objectives included determination of a maximum-tolerated dose and assessment of clinical activity.

Patients and Methods

Eighty-eight patients with unresectable stage III or IV melanoma with at least one measurable lesion were treated. Mean age was 59 years, with 65% male and 35% female patients, and 79% of patients had received prior systemic therapy. Single doses of ipilimumab up to 20 mg/kg (group A, single dose), multiple doses up to 5 mg/kg (group A, multiple dose), and multiple doses up to 10 mg/kg (group B) were administered.

Results

Single dosing up to 20 mg/kg of transfectoma antibody was well tolerated, as were multiple doses up to 10 mg/kg without a maximum-tolerated dose. In group B, dose-limiting toxicity was seen in six of 23 melanoma patients. Grade 3 or 4 immune-related adverse events (irAEs) were observed in 14% of patients (12 of 88 patients), and grade 1 or 2 irAEs were seen in an additional 58%. The half-life of ipilimumab was 359 hours. In group B, there was one partial response (23+ months), one complete response (21+ months), and seven patients with stable disease (SD), for a disease control rate of 39%. Two patients in group B with SD had slow, steady decline in tumor burden that was ongoing at 1 year of observation.

Conclusion

Ipilimumab has activity in patients with metastatic melanoma. Late responses were observed in patients with prolonged SD.
[18F]Fluorodeoxyglucose Positron Emission Tomography in Nonseminomatous Germ Cell Tumors After Chemotherapy: The German Multicenter Positron Emission Tomography Study Group
Authors: Oechsle Karin , Hartmann Michael , Brenner Winfried , Venz Stephan , Weissbach Lothar , Franzius Christiane , Kliesch Sabine , Mueller Stephan , Krege Susanne , Heicappell Ruediger , Bares Roland , Bokemeyer Carsten , de Wit Maike
Published: November 2008

Purpose

In patients with metastatic nonseminomatous germ cell cancer (NSGCT), residual masses after chemotherapy (CTX) can consist of vital carcinoma, mature teratoma, or necrosis. This prospective trial has evaluated the accuracy of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the prediction of histology compared with computed tomography (CT) and serum tumor markers (STM).

Patients and Methods

A total of 121 patients with stage IIC or III NSGCT scheduled for secondary resection after cisplatin-based CTX were included. FDG-PET was performed after completion of CTX. All results were confirmed by histopathology and correlated to STM and CT.

Results

Prediction of tumor viability with FDG-PET was correct in 56%, which did not reach the expected clinically relevant level of 70%, and was not better than the accuracy of CT (55%) or STM (56%). Sensitivity and specificity of FDG-PET were 70% and 48%. The positive predictive values were not significantly different (55%, 61%, and 59% for CT, STM, and PET, respectively). Judging only vital carcinoma as a true malignant finding, the negative predictive value increased to 83% for FDG-PET.

Conclusion

The presence of vital carcinoma and mature teratoma is common (55%) in residual masses in patients with NSGCT, and CT and STM cannot reliably predict absence of disease. In contrast to prior studies, this prospective trial, which is the only with histologic confirmation in all patients, demonstrated that FDG-PET is unable to give a clear additional clinical benefit to the standard diagnostic procedures, CT and STM, in the prediction of tumor viability in residual masses.
Using computational fluid dynamic/rigid body dynamic results to generate aerodynamic models for projectile flight simulation
Authors: Costello M , Sahu J
Published: November 2008

A method to efficiently generate a complete aerodynamic description for projectile flight dynamic modelling is described. At the core of the method is an unsteady, time accurate computational fluid dynamic simulation that is tightly coupled to a rigid projectile flight dynamic simulation. A set of short time snippets of simulated projectile motion at different Mach numbers is computed and employed as baseline data. For each time snippet, aerodynamic forces and moments and the full rigid body state vector of the projectile are known. With time synchronized air loads and state vector information, aerodynamic coefficients can be estimated with a simple fitting procedure. By inspecting the condition number of the fitting matrix, it is straightforward to assess the suitability of the time history data to predict a selected set of aerodynamic coefficients. The technique it is exercised on an exemplar fin-stabilized projectile with good results.
Taxi planner optimization: A management tool
Authors: Marín Á , Salmerón J
Published: November 2008

This work introduces taxi planning optimization (TPO) as a methodology to guide airport surface management operations. The optimization model represents competing aircraft using limited ground resources. TPO improves aircraft taxiing routes and their schedule in situations of congestion, minimizing overall taxiing time (TT), and helping taxi planners to meet prespecified goals such as compliance with take-off windows, TT limits, and trajectory conflicts. By considering all simultaneous trajectories during a given planning horizon, TPO's estimation of TT from the stand to the runways improves over current planning methods. The operational optimization model is a large-scale space-time multi-commodity network with capacity constraints. In addition to its natural use as a real-time taxi planning tool, a number of TPO variants can be used for design purposes, such as expansion of new infrastructure. TPO is demonstrated using Madrid-Barajas as test airport.
Synchronization with particular application to the control of a chaotic electromagnetic system
Authors: Chang S C , Lin H P
Published: November 2008

This study confirms the chaotic motion of an electromagnetic dynamic system and then elucidates the application of synchronization to an electromagnetic system to control the chaos. A bifurcation diagram reveals rich non-linear behaviour over a range of parameter values. Next, the Lyapunov exponent procedure is employed to show the occurrence of chaotic motion and to verify the results of numerical simulation. Finally, a continuous feedback control approach based on the synchronization characteristics is developed to control a chaotic electromagnetic system. Simulation results demonstrate the feasibility of the proposed method.
Aerodynamic shape optimization of a near-sonic passenger plane using computational fluid dynamics
Authors: Watanabe T , Matsushima K , Nakahashi K
Published: November 2008

In this article, aerodynamic optimization of a near-sonic passenger plane was conducted, starting with a conventional tail configuration. The genetic algorithm (GA) combined with the Euler simulations were used to maximize the lift-to-drag ratio ( L/ D) at Mach 0.95. First, the wing planform shape, twist, and thickness ratios were optimized. As a result, information about the aerodynamic design parameters was obtained and the optimal individual was designed with high inboard sweep angle, long chord length at the root, and less outboard aerofoil thickness. Then, the point of junction was optimized by applying the optimized wing and fuselage. Through the optimization process, the incidence angles of the wing were reduced, and the shapes of the root leading edge were then sharpened to reduce the interference drag. By its aerodynamic performance, the optimized wing/body configuration showed the aerodynamic feasibility of near-sonic flight.
An experimental study of the fibre orientation and laminate sequencing effects on mechanical properties of Glare
Authors: Sadighi M , Dariushi S
Published: November 2008

Glare (glass-reinforced aluminium laminate) is a new class of fibre metal laminates and has been selected as a suitable substitute for metal structures, especially in aerospace structural applications. It is a hybrid composite consisting of alternating thin layers of aluminium sheets and glass-reinforced epoxy prepreg. In this study, the mechanical properties of this attractive material including impact, tensile, and bending strength and the effect of fibre orientation on them are investigated. Test results show that glass fibre sheet with zero orientation in laminate considerably improves the mechanical properties. Comparing similar specimens with different layer arrangement shows the importance of fibre orientation and its arrangement on the mechanical properties. Aluminium layers have higher role on these properties. Moreover, the difference of orientations for two glass layers in the laminate helps better resistance against various loads, and these types of specimens present more suitable performance. Finally, statistical analysis of data shows the effect of the independent variables and interactions with their relative significance on the mechanical behaviour.
Non-linear free vibration analysis of laminated composite cylindrical/hyperboloid shell panels based on higher-order shear deformation theory using non-linear finite-element method
Authors: Panda S K , Singh B N
Published: November 2008

In this article, the non-linear free vibration analysis of the laminated composite shallow cylindrical/hyperboloid shell panels is attempted by taking geometric non-linearity in Green—Lagrange sense. A higher-order shear deformation theory is employed to model the shell panel flexure. A set of non-linear governing equations is derived using a variational approach. A non-linear finite-element model is proposed and applied to obtain discretized non-linear equations. Typical numerical examples have been solved using a direct iterative technique. Effects of lamination schemes, modular ratio, amplitude ratio, thickness ratio, and various boundary conditions on the frequency ratio (non-linear frequency to linear frequency) are examined in detail. The results are compared with those available in the literature. These show the importance and necessity of the Green—Lagrange-type non-linearity especially when the shell panel undergoes large deformation.
A study of speed ratio affecting the performance of a contra-rotating axial compressor
Authors: Chen Y-Y , Liu B , Xuan Y , Xiang X-R
Published: November 2008

The performance and detailed flow structure of a counter-rotating compressor under different rotating speed and typical working condition were experimentally and numerically investigated. Numerical results preliminarily showed that the total pressure ratio performance agreed well with experimental data, when the calculated peak efficiency was a little bigger than the experimental one. With optimized speed ratio, the peak isentropic efficiency can be increased with minor reduction of the total pressure ratio and safe margin. Flow reversal fist occurred at the start section of the outlet guide vane and it covered nearly 40 per cent area of the whole flow at the stall point when the rotational speed ratio of rotor 1 and rotor 2 were greater than or equal to 1, and it caused the compressor operate in the stall point. First, however, the flow separation and great range low-energy flow occurred at the 30 per cent span range of s rotor blade-tip near stall point, which was the main reason for the compressor stall when the speed ratio is less than 1. Rotor 2 worked at a greater incidence angle because of the separation at the trailing edge of rotor 1.
Effect of corner rounding on the performance of the double offset Y-shaped aircraft intake duct
Authors: Singh R K , Singh S N , Seshadri V
Published: November 2008

A Y-shaped intake duct is a crucial component of a modern combat aircraft having a single engine. The flow analyses in these ducts have been done using renormalization group k- turbulence model. The present study attempts to demonstrate the effect of corner rounding on the performance and the flow characteristics of a double offset Y-shaped aircraft intake duct having a semi-elliptical inlet and a circular exit with an area ratio of 2, and uniform wall roughness. It is seen that the performance and the flow characteristics of the Y-shaped intake duct improve significantly with rounding of the sharp corners up to an arc radius ( r/ Dh) of 0.14.
High-strength porous titanium diboride ceramics: Microstructure and mechanical properties
Authors: Hong C Q , Han J C , Zhang X H , Meng S H
Published: November 2008

Porous TiB2 ceramics have been fabricated by compacting TiB2 powders with cold isostatical pressing, followed by pressureless sintering. The microstructural feature, relative density, flexural strength, and fracture toughness were investigated. The experimental results revealed that the porosity of the fabricated porous TiB2 was controllable between ∼ 50 and ∼ 84 per cent depending on the sintering temperature and initial compacted pressures. The flexural strength and fracture toughness were improved with the increased relative density. The improved mechanical properties of the sintered porous TiB2 were attributed to the enhanced neck bonding and growth.
Optimization Support for Senior Design Project Assignments
Authors: Lopes Leo , Aronson Meredith , Carstensen Gary , Smith Cole
Published: November 2008

Each year, the College of Engineering at the University of Arizona offers senior design projects to approximately 300 seniors. Sponsors provide the university with potential student projects; three to six students from various disciplines must collaborate on each project. Students give the university a rank ordering of their preferred projects. The program manager then selects a subset of the projects, assigns students to projects according to their preferences, and manages other requirements, such as matching sponsor-requested skills and minimizing deviations in team average GPAs. The task of assigning students to projects used to consume untold hours and Post-it notes as the program manager tried to solve the problem manually. Invariably, some students were unhappy because they did not understand why they had been assigned to less-desirable projects. In this paper, we discuss a pragmatic mixed-integer program (MIP) to optimize the solution to this problem. We cover both the modeling challenges and all aspects from design to implementation that were necessary to ensure the system's successful deployment; these include testing, interaction with business processes, user interfaces, and integration. We report the practical benefits the university derived from using our system, and summarize some of the lessons, which we learned as part of our development life cycle, that may be applicable to the development of MIP-based decision-support systems.
Standardized or simple effect size: What should be reported?
Authors: Baguley Thom
Published: November 2008

It is regarded as best practice for psychologists to report effect size when disseminating quantitative research findings. Reporting of effect size in the psychological literature is patchy – though this may be changing – and when reported it is far from clear that appropriate effect size statistics are employed. This paper considers the practice of reporting point estimates of standardized effect size and explores factors such as reliability, range restriction and differences in design that distort standardized effect size unless suitable corrections are employed. For most purposes simple (unstandardized) effect size is more robust and versatile than standardized effect size. Guidelines for deciding what effect size metric to use and how to report it are outlined. Foremost among these are: (i) a preference for simple effect size over standardized effect size, and (ii) the use of confidence intervals to indicate a plausible range of values the effect might take. Deciding on the appropriate effect size statistic to report always requires careful thought and should be influenced by the goals of the researcher, the context of the research and the potential needs of readers.
JNK Activity Is Essential for Atf4 Expression and Late-Stage Osteoblast Differentiation
Authors: Matsuguchi Tetsuya , Chiba Norika , Bandow Kenjiro , Kakimoto Kyoko , Masuda Akio , Ohnishi Tomokazu
Published: November 2008

Osteoblasts differentiate from mesodermal progenitors and play a pivotal role in bone formation and mineralization. Several transcription factors including runt-related transcription factor 2 (RUNX2), Osterix (OSX), and activating transcription factor4 (ATF4) are known to be crucial for the process, whereas the upstream signal transduction controlling the osteoblast differentiation sequence is largely unknown. Here, we explored the role of c-jun N-terminal kinase (JNK) in osteoblast differentiation using in vitro differentiation models of primary osteoblasts and MC3T3-E1 cells with ascorbic acid/β-glycerophosphate treatment. Terminal osteoblast differentiation, represented by matrix mineralization, was significantly inhibited by the inactivation of JNK with its specific inhibitor and exogenous overexpression of MKP-M (MAP kinase phosphatase isolated from macrophages), which preferentially inactivates JNK. Conversely, enhanced mineral deposition was observed by inducible overexpression of p54JNK2, whereas it was not observed by the overexpression of p46JNK1 or p46JNK2, indicating a distinct enhancing role of p54JNK2 in osteoblast differentiation. Inactivation of JNK significantly inhibited late-stage molecular events of osteoblast differentiation, including gene expression of osteocalcin (Ocn) and bone sialoprotein (Bsp). In contrast, earlier differentiation events including alkaline phosphatase (ALP) activation and osteopontin (Opn) expression were not inhibited by JNK inactivation. Although the expression levels of two transcription factor genes, Runx2 and Osx, were not significantly affected by JNK inactivation, induction of Atf4 mRNA during osteoblast differentiation was significantly inhibited. Taken together, these data indicate that JNK activity is specifically required for the late-stage differentiation events of osteoblasts.
Hip Fractures and the Contribution of Cortical Versus Trabecular Bone to Femoral Neck Strength
Authors: Holzer Gerold , von Skrbensky Gobert , Holzer Lukas A , Pichl Wolfgang
Published: November 2008

Osteoporotic fractures are caused by both cortical thinning and trabecular bone loss. Both are seen to be important for bone fragility. The relative contributions of cortical versus trabecular bone have not been established. The aim of this study was to test the contribution of cortical versus trabecular bone to femoral neck stability in bone strength. In one femur from each pair of 18 human cadaver femurs (5 female; 4 male), trabecular bone was completely removed from the femoral neck, providing one bone with intact and the other without any trabecular structure in the femoral neck. Geometrical, X-ray, and DXA measurements were carried out before biomechanical testing (forces to fracture). Femoral necks were osteotomized, slices were analyzed for cross-sectional area (CSA) and cross-sectional moment of inertia (CSMI), and results were compared with biomechanical testing data. Differences between forces needed to fracture excavated and intact femurs (ΔF/F mean) was 7.0% on the average (range, 4.6–17.3%). CSA of removed spongiosa did not correlate with difference of fracture load (ΔF/F mean), nor did BMD. The relative contribution of trabecular versus cortical bone in respect to bone strength in the femoral neck seems to be marginal and seems to explain the subordinate role of trabecular bone and its changes in fracture risk and the effects of treatment options in preventing fractures.
Denosumab, a Fully Human Monoclonal Antibody to RANKL, Inhibits Bone Resorption and Increases BMD in Knock-In Mice That Express Chimeric (Murine/Human) RANKL
Authors: Kostenuik Paul J , Nguyen Hung Q , McCabe James , Warmington Kelly S , Kurahara Carol , Sun Ning , Chen Ching , Li Luke , Cattley Russ C , Van Gwyneth , Scully Shelia , Elliott Robin , Grisanti Mario , Morony Sean , Tan Hong Lin , Asuncion Frank , Li Xiaodong , Ominsky Michael S , Stolina Marina , Dwyer Denise , Dougall William C , Hawkins Nessa , Boyle William J , Simonet William S , Sullivan John K
Published: November 2008

RANKL is a TNF family member that mediates osteoclast formation, activation, and survival by activating RANK. The proresorptive effects of RANKL are prevented by binding to its soluble inhibitor osteoprotegerin (OPG). Recombinant human OPG-Fc recognizes RANKL from multiple species and reduced bone resorption and increased bone volume, density, and strength in a number of rodent models of bone disease. The clinical development of OPG-Fc was discontinued in favor of denosumab, a fully human monoclonal antibody that specifically inhibits primate RANKL. Direct binding assays showed that denosumab bound to human RANKL but not to murine RANKL, human TRAIL, or other human TNF family members. Denosumab did not suppress bone resorption in normal mice or rats but did prevent the resorptive response in mice challenged with a human RANKL fragment encoded primarily by the fifth exon of the RANKL gene. To create mice that were responsive to denosumab, knock-in technology was used to replace exon 5 from murine RANKL with its human ortholog. The resulting “huRANKL” mice exclusively express chimeric (human/murine) RANKL that was measurable with a human RANKL assay and that maintained bone resorption at slightly reduced levels versus wildtype controls. In young huRANKL mice, denosumab and OPG-Fc each reduced trabecular osteoclast surfaces by 95% and increased bone density and volume. In adult huRANKL mice, denosumab reduced bone resorption, increased cortical and cancellous bone mass, and improved trabecular microarchitecture. These huRANKL mice have potential utility for characterizing the activity of denosumab in a variety of murine bone disease models.
Durkheim and Criminology: Reconstructing the Legacy
Authors: Smith Philip
Published: November 2008

The article offers an overview of Emile Durkheim's substantial and surprisingly diverse legacy for criminology. This is shown to run the gamut from positivism through to social constructivism. Further, it includes insights into deviance, social control and the law. Although broad in scope and often brilliant, his contribution is perhaps insufficiently acknowledged. Reasons for this oversight are given, as are some indications of future directions for Durkheimian criminology.
The Heritability of HbA1c and Fasting Blood Glucose in Different Measurement Settings
Authors: Simonis-Bik Annemarie M. C. , Eekhoff Elisabeth M. W. , Diamant Michaela , Boomsma Dorret I. , Heine Rob J. , Dekker Jacqueline M. , Willemsen Gonneke , van Leeuwen Marieke , de Geus Eco J. C.
Published: November 2008

In an extended twin study we estimated the heritability of fasting HbA1c and blood glucose levels. Blood glucose was assessed in different settings (at home and in the clinic). We tested whether the genetic factors influencing fasting blood glucose levels overlapped with those influencing HbA1c and whether the same genetic factors were expressed across different settings. Fasting blood glucose was measured at home and during two visits to the clinic in 77 healthy families with same-sex twins and siblings, aged 20 to 45 years. HbA1c was measured during the first clinic visit. A 4-variate genetic structural equation model was used that estimated the heritability of each trait and the genetic correlations among traits. Heritability explained 75% of the variance in HbA1c. The heritability of fasting blood glucose was estimated at 66% at home and lower in the clinic (57% and 38%). Fasting blood glucose levels were significantly correlated across settings (0.34 <r< 0.54), mostly due to a common set of genes that explained between 53% and 95% of these correlations. Correlations between HbA1c and fasting blood glucoses were low (0.11 <r< 0.23) and genetic factors influencing HbA1c and fasting glucose were uncorrelated. These results suggest that in healthy adults the genes influencing HbA1c and fasting blood glucose reflect different aspects of the glucose metabolism. As a consequence these two glycemic parameters can not be used interchangeably in diagnostic procedures or in studies attempting to find genes for diabetes. Both contribute unique (genetic) information.
Effects of Densification on Permeable Friction Course Mixtures
Authors: Alvarez Allex E. , Martin Amy Epps , Estakhri Cindy
Published: November 2008

Compaction of permeable or porous friction course (PFC) mixtures is generally considered a process without major issues, and field density requirements (or corresponding total air voids [AV] content) are not currently specified for this type of hot mix asphalt. However, proper densification is one of the most important aspects to control during construction to prevent raveling, the distress most frequently reported as the cause of failure in these mixtures. This paper presents an evaluation of the effect of densification on PFC mixtures. This evaluation included both the study of the internal structure of compacted mixtures and a comparison of performance based on macroscopic response. Results from this study showed that differences encountered in the internal structure of road cores and specimens compacted using the Superpave Gyratory Compactor limit the use of these laboratory compacted specimens in durability and functionality evaluations of PFC mixtures. In addition, changes in densification, after reaching stone-on-stone contact, modified the mixture properties and performance. The magnitude of these modifications provided evidence of the ease of verifying not only stone-on-stone contact during mix design, but also of the importance of controlling the density during construction to ensure an equilibrium density that guarantees the balance between mixture durability and mixture functionality.