bluuebunny/crossref_metadata_2025 huggingface dataset:
IL-7 and IL-15 allow the generation of suicide gene–modified alloreactive self-renewing central memory human T lymphocytes
Authors: Kaneko Shin , Mastaglio Sara , Bondanza Attilio , Ponzoni Maurilio , Sanvito Francesca , Aldrighetti Luca , Radrizzani Marina , La Seta-Catamancio Simona , Provasi Elena , Mondino Anna , Nagasawa Toshiro , Fleischhauer Katharina , Russo Vincenzo , Traversari Catia , Ciceri Fabio , Bordignon Claudio , Bonini Chiara
Published: November 2008

Long-term clinical remissions of leukemia, after allogeneic hematopoietic stem cell transplantation, depend on alloreactive memory T cells able to self-renew and differentiate into antileukemia effectors. This is counterbalanced by detrimental graft-versus-host disease (GVHD). Induction of a selective suicide in donor T cells is a current gene therapy approach to abrogate GVHD. Unfortunately, genetic modification reduces alloreactivity of lymphocytes. This associates with an effector memory (TEM) phenotype of gene-modified lymphocytes and may limit antileukemia effect. We hypothesized that alloreactivity of gene-modified lymphocytes segregates with the central memory (TCM) phenotype. To this, we generated suicide gene–modified TCM lymphocytes with a retroviral vector after CD28 costimulation and culture with IL-2, IL-7, or a combination of IL-7 and IL-15. In vitro, suicide gene–modified TCM cells self-renewed upon alloantigen stimulation and resisted activation-induced cell death. In a humanized mouse model, only suicide gene–modified T cells cultured with IL-7 and IL-15 persisted, differentiated in TEM cells, and were as potent as unmanipulated lymphocytes in causing GVHD. GVHD was halted through the activation of the suicide gene machinery. These results warrant the use of suicide gene–modified TCM cells cultured with IL-7 and IL-15 for the safe exploitation of the alloreactive response against cancer.
Foxn1 is required to maintain the postnatal thymic microenvironment in a dosage-sensitive manner
Authors: Chen Lizhen , Xiao Shiyun , Manley Nancy R.
Published: November 2008

The postnatal thymus is the primary source of T cells in vertebrates, and many if not all stages of thymocyte development require interactions with thymic epithelial cells (TECs). The Foxn1 gene is a key regulator of TEC differentiation, and is required for multiple aspects of fetal TEC differentiation. Foxn1 is also expressed in the postnatal thymus, but its function after birth is unknown. We generated a Foxn1 allele with normal fetal expression and thymus development, but decreased expression in the postnatal thymus. This down-regulation causes rapid thymic compartment degeneration and reduced T-cell production. TEC subsets that express higher Foxn1 levels are most sensitive to its down-regulation, in particular MHCIIhiUEA-1hi medullary TECs. The requirement for Foxn1 is extremely dosage sensitive, with small changes in Foxn1 levels having large effects on thymus phenotypes. Our results provide the first evidence that Foxn1 is required to maintain the postnatal thymus. Furthermore, the similarities of this phenotype to accelerated aging-related thymic involution support the possibility that changes in Foxn1 expression in TECs during aging contribute to the mechanism of involution.
Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells
Authors: Hulleman Esther , Kazemier Karin M. , Holleman Amy , VanderWeele David J. , Rudin Charles M. , Broekhuis Mathilde J. C. , Evans William E. , Pieters Rob , Den Boer Monique L.
Published: November 2008

Treatment failure in pediatric acute lymphoblastic leukemia (ALL) is related to cellular resistance to glucocorticoids (eg, prednisolone). Recently, we demonstrated that genes associated with glucose metabolism are differentially expressed between prednisolone-sensitive and prednisolone-resistant precursor B-lineage leukemic patients. Here, we show that prednisolone resistance is associated with increased glucose consumption and that inhibition of glycolysis sensitizes prednisolone-resistant ALL cell lines to glucocorticoids. Treatment of prednisolone-resistant Jurkat and Molt4 cells with 2-deoxy-D-glucose (2-DG), lonidamine (LND), or 3-bromopyruvate (3-BrPA) increased the in vitro sensitivity to glucocorticoids, while treatment of the prednisolone-sensitive cell lines Tom-1 and RS4; 11 did not influence drug cytotoxicity. This sensitizing effect of the glycolysis inhibitors in glucocorticoid-resistant ALL cells was not found for other classes of antileukemic drugs (ie, vincristine and daunorubicin). Moreover, down-regulation of the expression of GAPDH by RNA interference also sensitized to prednisolone, comparable with treatment with glycolytic inhibitors. Importantly, the ability of 2-DG to reverse glucocorticoid resistance was not limited to cell lines, but was also observed in isolated primary ALL cells from patients. Together, these findings indicate the importance of the glycolytic pathway in glucocorticoid resistance in ALL and suggest that targeting glycolysis is a viable strategy for modulating prednisolone resistance in ALL.
TLR2-dependent eosinophil interactions with mycobacteria: role of α-defensins
Authors: Driss Virginie , Legrand Fanny , Hermann Emmanuel , Loiseau Sylvie , Guerardel Yann , Kremer Laurent , Adam Estelle , Woerly Gaëtane , Dombrowicz David , Capron Monique
Published: November 2008

Peripheral blood and tissue eosinophilia are a prominent feature in allergic diseases and during helminth infections. Eosinophil recruitment also frequently occurs upon mycobacterial infections, particularly in lung granuloma. However, the mechanism by which eosinophils interact with mycobacteria remains largely unknown. Because eosinophils recently have been shown to be involved in innate immune responses, we investigated the direct interactions of eosinophils with Mycobacterium bovis BCG as a study model. We show that live BCG attracts human eosinophils and induces reactive oxygen species (ROS) synthesis, granule protein release, and tumor necrosis factor (TNF)–α secretion. Using anti-TLR2 neutralizing antibodies before exposure of eosinophils to BCG, we showed a critical role of TLR2 signaling in ROS and eosinophil peroxidase release. BCG-induced eosinophil activation is mediated through the p38 mitogen-activated protein (MAP) kinase and nuclear factor (NF)–κB pathways. In addition, a mycobacterial wall component, lipomannan, induced a TLR2-dependent eosinophil activation. In addition, we showed that eosinophils express and produce α-defensins upon stimulation with BCG and lipomannan and that α-defensins could inhibit mycobacterial growth in synergy with eosinophil cationic protein. These results suggest a role for human eosinophils as direct effectors in TLR2-mediated innate immunity against mycobacteria and confer to these cells potent cytotoxic functions through defensin and eosinophil cationic protein production.
A distinctive subtype of t(14;18)-negative nodal follicular non-Hodgkin lymphoma characterized by a predominantly diffuse growth pattern and deletions in the chromosomal region 1p36
Authors: Katzenberger Tiemo , Kalla Jörg , Leich Ellen , Stöcklein Heike , Hartmann Elena , Barnickel Sandra , Wessendorf Swen , Ott M. Michaela , Müller-Hermelink Hans Konrad , Rosenwald Andreas , Ott German
Published: November 2008

Follicular lymphoma (FL) is a morphologically and genetically well-characterized B-cell non-Hodgkin lymphoma that can show predominantly follicular, combined follicular and diffuse, or predominantly diffuse growth patterns. Although approximately 85% of FLs harbor the translocation t(14;18)(q32;q21) and consistently display a follicular growth pattern, predominantly diffuse FLs are less well characterized on the phenotypical, molecular, and clinical level. We studied 35 predominantly diffuse FL by immunohistochemistry, classical chromosome banding analysis, fluorescence in situ hybridization (FISH), and gene expression profiling. A total of 28 of 29 analyzable cases lacked t(14;18), and 27 of 29 cases revealed a unifying chromosomal aberration, a deletion in 1p36. Morphologically, 12 FLs were grade 1 and 23 were grade 2, and the immunophenotype with frequent expression of CD10, BCL6, and CD23 was in line with a germinal center B-cell phenotype. The gene expression profiles of 4 predominantly diffuse FLs fell into the spectrum of typical FL, with a unique enrichment of specific gene signatures. Remarkably, patients with diffuse FL frequently presented with low clinical stage and large but localized inguinal tumors. These results suggest that predominantly diffuse FL represent a distinct subtype of t(14;18)-negative nodal FL with a unifying genetic alteration (deletion of 1p36) and characteristic clinical features.
QuantPrime – a flexible tool for reliable high-throughput primer design for quantitative PCR
Authors: Arvidsson Samuel , Kwasniewski Miroslaw , Riaño-Pachón Diego Mauricio , Mueller-Roeber Bernd
Published: November 2008

Background

Medium- to large-scale expression profiling using quantitative polymerase chain reaction (qPCR) assays are becoming increasingly important in genomics research. A major bottleneck in experiment preparation is the design of specific primer pairs, where researchers have to make several informed choices, often outside their area of expertise. Using currently available primer design tools, several interactive decisions have to be made, resulting in lengthy design processes with varying qualities of the assays.

Results

Here we present QuantPrime, an intuitive and user-friendly, fully automated tool for primer pair design in small- to large-scale qPCR analyses. QuantPrime can be used online through the internet http://www.quantprime.de/ or on a local computer after download; it offers design and specificity checking with highly customizable parameters and is ready to use with many publicly available transcriptomes of important higher eukaryotic model organisms and plant crops (currently 295 species in total), while benefiting from exon-intron border and alternative splice variant information in available genome annotations. Experimental results with the model plant Arabidopsis thaliana, the crop Hordeum vulgare and the model green alga Chlamydomonas reinhardtii show success rates of designed primer pairs exceeding 96%.

Conclusion

QuantPrime constitutes a flexible, fully automated web application for reliable primer design for use in larger qPCR experiments, as proven by experimental data. The flexible framework is also open for simple use in other quantification applications, such as hydrolyzation probe design for qPCR and oligonucleotide probe design for quantitative in situ hybridization. Future suggestions made by users can be easily implemented, thus allowing QuantPrime to be developed into a broad-range platform for the design of RNA expression assays.
Evolutionary conservation of dual Sec translocases in the cyanelles of Cyanophora paradoxa
Authors: Yusa Fumie , Steiner Jürgen M , Löffelhardt Wolfgang
Published: November 2008

Background

Cyanelles, the peptidoglycan-armored plastids of glaucocystophytes, occupy a unique bridge position in between free-living cyanobacteria and chloroplasts. In some respects they side with cyanobacteria whereas other features are clearly shared with chloroplasts. The Sec translocase, an example for "conservative sorting" in the course of evolution, is found in the plasma membrane of all prokaryotes, in the thylakoid membrane of chloroplasts and in both these membrane types of cyanobacteria.

Results

In this paper we present evidence for a dual location of the Sec translocon in the thylakoid as well as inner envelope membranes of the cyanelles from Cyanophora paradoxa, i. e. conservative sorting sensu stricto. The prerequisite was the generation of specific antisera directed against cyanelle SecY that allowed immunodetection of the protein on SDS gels from both membrane types separated by sucrose density gradient floatation centrifugation. Immunoblotting of blue-native gels yielded positive but differential results for both the thylakoid and envelope Sec complexes, respectively. In addition, heterologous antisera directed against components of the Toc/Tic translocons and binding of a labeled precursor protein were used to discriminate between inner and outer envelope membranes.

Conclusion

The envelope translocase can be envisaged as a prokaryotic feature missing in higher plant chloroplasts but retained in cyanelles, likely for protein transport to the periplasm. Candidate passengers are cytochrome c
6 and enzymes of peptidoglycan metabolism. The minimal set of subunits of the Toc/Tic translocase of a primitive plastid is proposed.
Phase-dependent preference of thermosensation and chemosensation during simultaneous presentation assay in Caenorhabditis elegans
Authors: Adachi Ryota , Osada Hiroshi , Shingai Ryuzo
Published: November 2008

Background

Multi-sensory integration is necessary for organisms to discriminate different environmental stimuli and thus determine behavior. Caenorhabditis elegans has 12 pairs of amphid sensory neurons, which are involved in generating behaviors such as thermotaxis toward cultivation temperature, and chemotaxis toward chemical stimuli. This arrangement of known sensory neurons and measurable behavioral output makes C. elegans suitable for addressing questions of multi-sensory integration in the nervous system. Previous studies have suggested that C. elegans can process different chemoattractants simultaneously. However, little is known about how these organisms can integrate information from stimuli of different modality, such as thermal and chemical stimuli.

Results

We studied the behavior of a population of C. elegans during simultaneous presentation of thermal and chemical stimuli. First, we examined thermotaxis within the radial temperature gradient produced by a feedback-controlled thermoregulator. Separately, we examined chemotaxis toward sodium chloride or isoamyl alcohol. Then, assays for simultaneous presentations of 15°C (colder temperature than 20°C room temperature) and chemoattractant were performed with 15°C-cultivated wild-type worms. Unlike the sum of behavioral indices for each separate behavior, simultaneous presentation resulted in a biased migration to cold regions in the first 10 min of the assay, and sodium chloride-regions in the last 40 min. However, when sodium chloride was replaced with isoamyl alcohol in the simultaneous presentation, the behavioral index was very similar to the sum of separate single presentation indices. We then recorded tracks of single worms and analyzed their behavior. For behavior toward sodium chloride, frequencies of forward and backward movements in simultaneous presentation were significantly different from those in single presentation. Also, migration toward 15°C in simultaneous presentation was faster than that in 15°C-single presentation.

Conclusion

We conclude that worms preferred temperature to chemoattractant at first, but preferred the chemoattractant sodium chloride thereafter. This preference was not seen for isoamyl alcohol presentation. We attribute this phase-dependent preference to the result of integration of thermosensory and chemosensory signals received by distinct sensory neurons.
Investigation of Swedish cases reveals an outbreak of cryptosporidiosis at a Norwegian hotel with possible links to in-house water systems
Authors: Hajdu Agnes , Vold Line , Østmo Torild A , Helleve Anna , Helgebostad Sigrid R , Krogh Truls , Robertson Lucy , de Jong Birgitta , Nygård Karin
Published: November 2008

Background

In March 2007, the Norwegian Institute of Public Health was notified of Swedish individuals diagnosed with cryptosporidiosis after staying at a Norwegian hotel. In Norway, cryptosporidiosis is not reportable, and human infections are rarely diagnosed.

Methods

A questionnaire on illness and exposure history was e-mailed to seven organised groups who had visited the hotel in March. Cases were defined as persons with diarrhoea for more than two days or laboratory-confirmed cryptosporidiosis during or within two weeks of the hotel visit. The risk factor analysis was restricted to two groups with the highest attack rates (AR) and same hotel stay period. Local food safety authorities conducted environmental investigations.

Results

In total, 25 diarrhoeal cases (10 laboratory-confirmed) were identified among 89 respondents. Although environmental samples were negative, epidemiological data suggest an association with in-house water consumption. In one group, the AR was higher amongst consumers of water from hotel dispenser (relative risk [RR] = 3.0; 95% confidence interval [CI]: 0.9–9.8), tap water (RR = 2.3; CI: 0.9–5.8), and lower amongst commercial bottled water drinkers (RR = 0.6; CI: 0.4–1.0). Consumption of ice cubes was a risk-factor (RR = 7.1; CI: 1.1–45.7) in the two groups combined.

Conclusion

This outbreak would probably have remained undetected without the alert from Swedish health authorities, illustrating the difficulties in outbreak detection due to low health care seeking behaviour for diarrhoea and limited parasite diagnostics in Norway. Awareness of cryptosporidiosis should be raised amongst Norwegian medical personnel to improve case and outbreak detection, and possible risks related to in-house water systems should be assessed.
Development and validation of an enzyme-linked immunosorbent assay for antibodies against Mycobacterium bovisin european wild boar
Authors: Aurtenetxe Olaia , Barral Marta , Vicente Joaquín , de la Fuente José , Gortázar Christian , Juste Ramón A
Published: November 2008

Background

Bovine tuberculosis (bTB) remains a significant problem in some parts of Spain largely because of contacts between cattle and wildlife reservoirs in extensive grazing systems. European Wild boar (Sus scrofa) is one of the species involved in the transmission of the disease to other species. Fast and simple detection methods would be critical for assessing infection prevalence, study the mechanisms of pathogen transmission and monitoring the effects of TB control measures.

Results

An enzyme-linked immunosorbent assay (ELISA) to detect antibodies against Mycobacterium bovis in wild boar serum was developed and validated on 185 sera from TB positive and negative wild boar. Based on antigen inoculation of captive animals as well as tuberculosis compatible lesions, culture results and molecular analysis of hunted individuals, animals were allocated into two groups: tuberculosis positive group and tuberculosis negative group. After optimization of the positive to negative ratio using different combinations of serum dilutions and conjugate concentrations, the test yielded a sensitivity of 72.60% and a specificity of 96.43% for the best cut-off.

Conclusion

Although some negative group animals showed an ELISA positive reaction (< 3%), this assay showed a high potential for accurate diagnosis of TB in wild boar, as its large dynamic range supported a good discriminatory power and a satisfactory balance between sensitivity and specificity.
Molecular and geographic analyses of vampire bat-transmitted cattle rabies in central Brazil
Authors: Kobayashi Yuki , Sato Go , Mochizuki Nobuyuki , Hirano Shinji , Itou Takuya , Carvalho Adolorata AB , Albas Avelino , Santos Hamilton P , Ito Fumio H , Sakai Takeo
Published: November 2008

Background

Vampire bats are important rabies virus vectors, causing critical problems in both the livestock industry and public health sector in Latin America. In order to assess the epidemiological characteristics of vampire bat-transmitted rabies, the authors conducted phylogenetic and geographical analyses using sequence data of a large number of cattle rabies isolates collected from a wide geographical area in Brazil.

Methods

Partial nucleoprotein genes of rabies viruses isolated from 666 cattle and 18 vampire bats between 1987 and 2006 were sequenced and used for phylogenetic analysis. The genetic variants were plotted on topographical maps of Brazil.

Results

In this study, 593 samples consisting of 24 genetic variants were analyzed. Regional localization of variants was observed, with the distribution of several variants found to be delimited by mountain ranges which served as geographic boundaries. The geographical distributions of vampire-bat and cattle isolates that were classified as the identical phylogenetic group were found to overlap with high certainty. Most of the samples analyzed in this study were isolated from adjacent areas linked by rivers.

Conclusion

This study revealed the existence of several dozen regional variants associated with vampire bats in Brazil, with the distribution patterns of these variants found to be affected by mountain ranges and rivers. These results suggest that epidemiological characteristics of vampire bat-related rabies appear to be associated with the topographical and geographical characteristics of areas where cattle are maintained, and the factors affecting vampire bat ecology.
Analysis of the precision and sensitivity to change of different approaches to assess cartilage loss by quantitative MRI in a longitudinal multicentre clinical trial in patients with knee osteoarthritis
Authors: Raynauld Jean-Pierre , Martel-Pelletier Johanne , Abram François , Dorais Marc , Haraoui Boulos , Choquette Denis , Bias Peter , Emmert Karl H , Laufer Stefan , Pelletier Jean-Pierre
Published: November 2008

Introduction

Cartilage thickness and volume loss measurements using quantitative magnetic resonance imaging (qMRI) are suggested to detect significant cartilage changes over short time intervals. We aimed to compare these two different approaches looking at the global knee and subregions, using data from an osteoarthritis (OA) multicentre randomised clinical trial.

Methods

Three hundred and fifty-five patients with symptomatic knee OA were recruited for a two-year, double-blind, randomised clinical trial evaluating the effect of 200 mg licofelone twice daily and 500 mg naproxen twice daily on cartilage loss, and 301 patients had baseline MRI. MRIs were performed at baseline, 6, 12 and 24 months. Cartilage volume and thickness in the global joint, medial and lateral compartments, and central weight-bearing subregions of the medial and lateral femoral condyles and tibial plateaus were analysed. Data were analysed for the mean value imputed for intent-to-treat (ITT-MVI) and statistical analyses were performed using two-sample Student's t-test.

Results

Cartilage mean thickness loss in the global joint, lateral and medial compartments, as well as in medial compartments stratified according to patients with or without meniscal extrusion, was significantly less in the licofelone compared with the naproxen group at 12 and 24 months. Interestingly, these data were similar to those found when using cartilage volume loss as an outcome. Although greater cartilage volume and mean thickness loss was seen in central weight-bearing subregions of the medial and lateral compartments compared with the whole compartment and also in patients with meniscal lesions/extrusion, suggesting good sensitivity to change, its high standard deviation precluded for the condyles a high statistical power and abrogated statistically significant differences between the treatment groups.

Conclusions

These data demonstrate that both the measurement of cartilage thickness and that of cartilage volume provide the same level of sensitivity to estimate cartilage loss in a clinical trial. However, the potential of gaining statistical power with the use of thickness/volume change in knee subregions as an outcome seems negated by high inter-patient variability. Moreover, there is no superiority in statistical power by selecting patients with meniscal extrusion.
Approach to the Patient with a Cytologically Indeterminate Thyroid Nodule
Authors: Alexander Erik K.
Published: November 2008

Background: Fine-needle aspiration remains the primary diagnostic intervention for the evaluation of most thyroid nodules larger than 1–1.5 cm. Although most aspirates provide diagnostic cytology, approximately 15–25% will be classified indeterminate (often referred to as follicular neoplasm, suspicious for carcinoma, or atypical). In such cases, abnormal cellular findings preclude interpretation of benignity, although only a minority will prove cancerous upon final histopathology. Nonetheless, patients with indeterminate aspirates are commonly referred for consideration of hemi- or near-total thyroidectomy. Recently, improved understanding and novel investigation of clinical, radiological, cytological, and molecular factors has allowed improved stratification of cancer risk.

Conclusion: Although surgery continues to be commonly recommended, strategies for such patients should increasingly seek to define treatment based on the estimation of an individual’s thyroid cancer risk in comparison with associated operative risk and morbidity. In doing so, the rate of unnecessary surgical procedures and associated complications can be reduced.
Dialogue on Post-Capitalism
Authors: Huibin Li , Dirlik Arif
Published: October 2008

The influential marketing analyst Peter Drucker's idea of post-capitalism has attracted considerable attention in recent years in the People's Republic of China. One of its proponents is Professor Li Huibin of the Contemporary Marxism Institute of the Central Compilation and Translation Bureau of the Communist Party of China, who has written extensively on questions of economics and philosophy. The dialogue was initiated at the invitation of Professor Li when Professor Arif Dirlik of the Chinese University of Hong Kong was a visiting scholar with the Contemporary Marxism Institute during the summer of 2006. The dialogue takes up questions of the relationship between Drucker's theory and Marxist theories of capitalism, the intellectual usefulness of “post-capitalism” in understanding contemporary developments in capitalism, and its possible relevance to the developmental strategy of “socialism with Chinese characteristics.”
Of Accumulation: The Collected Poems of Robert Creeley
Authors: Lerner Ben
Published: October 2008

This essay attempts to take the measure of Robert Creeley's some sixty-year commitment to poetry as a medium for tracking the processes of thinking and speaking, not for the production of finished thoughts. By reading Creeley against Wallace Stevens, I hope to both identify the significant formal signatures of Creeley's poetry and to document how a projectivist poetics attempted to distinguish itself from an influential modernist predecessor, a poetic reorientation inseparable from the history of boundary 2.
Sarcomeric actin organization is synergistically promoted by tropomodulin, ADF/cofilin, AIP1 and profilin in C. elegans
Authors: Yamashiro Sawako , Cox Elisabeth A. , Baillie David L. , Hardin Jeff D. , Ono Shoichiro
Published: November 2008

Sarcomeric organization of thin and thick filaments in striated muscle is important for the efficient generation of contractile forces. Sarcomeric actin filaments are uniform in their lengths and regularly arranged in a striated pattern. Tropomodulin caps the pointed end of actin filaments and is a crucial regulator of sarcomere assembly. Here, we report unexpected synergistic functions of tropomodulin with enhancers of actin filament dynamics in Caenorhabditis elegans striated muscle. Pointed-end capping by tropomodulin inhibited actin filament depolymerization by ADF/cofilin in vitro. However, in vivo, the depletion of tropomodulin strongly enhanced the disorganization of sarcomeric actin filaments in ADF/cofilin mutants, rather than antagonistically suppressing the phenotype. Similar phenotypic enhancements by tropomodulin depletion were also observed in mutant backgrounds for AIP1 and profilin. These in vivo effects cannot be simply explained by antagonistic effects of tropomodulin and ADF/cofilin in vitro. Thus, we propose a model in which tropomodulin and enhancers of actin dynamics synergistically regulate elongation and shortening of actin filaments at the pointed end.
Mechanism and rate of glucose absorption differ between an Australian honeyeater (Meliphagidae) and a lorikeet (Loriidae)
Authors: Napier Kathryn R. , McWhorter Todd J. , Fleming Patricia A.
Published: October 2008

Efficient mechanisms of glucose absorption are necessary for volant animals as a means of reducing mass during flight: they speed up gut transit time and require smaller volume and mass of gut tissue. One mechanism that may be important is absorption via paracellular (non-mediated) pathways. This may be particularly true for nectarivorous species which encounter large quantities of sugar in their natural diet. We investigated the extent of mediated and non-mediated glucose absorption in red wattlebirds Anthochaera carunculata (Meliphagidae) and rainbow lorikeets Trichoglossus haematodus (Loriidae) to test the hypothesis that paracellular uptake accounts for a significant proportion of total glucose uptake in these species. We found that routes of glucose absorption are highly dynamic in both species. In lorikeets, absorption of l-glucose(non-mediated uptake) is slower than that of d-glucose (mediated and non-mediated uptake), with as little as 10% of total glucose absorbed by the paracellular pathway initially (contrasting previous indirect estimates of∼0%). Over time, however, more glucose may be absorbed via the paracellular route. Glucose absorption by both mediated and non-mediated mechanisms in wattlebirds occurred at a faster rate than in lorikeets, and wattlebirds also rely substantially on paracellular uptake. In wattlebirds, we recorded higher bioavailability of l-glucose (96±3%)compared with d-glucose (57±2%), suggesting problems with the in vivo use of radiolabeled d-glucose. Further trials with 3-O-methyl-d-glucose revealed high bioavailability in wattlebirds (90±5%). This non-metabolisable glucose analogue remains the probe of choice for measuring uptake rates in vivo, especially in birds in which absorption and metabolism occur extremely rapidly.
Production degrees of freedom as manufacturing system reconfiguration potential measures
Authors: Farid A M , McFarlane D C
Published: November 2008

In recent years, many design approaches have been developed for automated manufacturing systems in the fields of reconfigurable manufacturing systems (RMSs), holonic manufacturing systems (HMSs), and multi-agent systems (MASs). One of the principle reasons for these developments has been to enhance the reconfigurability of a manufacturing system, allowing it to adapt readily to changes over time. However, to date, reconfigurability assessment has been limited. Hence, the efficacy of these design approaches remains inconclusive. This paper is the first of two in this issue to address reconfigurability measurement. Specifically, it seeks to address ‘reconfiguration potential’ by analogy. Mechanical degrees of freedom have been used in the field of mechanics as a means of determining the independent directions of motion of a mechanical system. By analogy, manufacturing degrees of freedom can be used to determine independent ways of production. Furthermore, manufacturing degrees of freedom can be classified into their production and product varieties. This paper specifically focuses on the former to measure the product-independent aspects of manufacturing system ‘reconfiguration potential’. This approach will be added to complementary work on the measurement of ‘reconfiguration ease’ so as to form an integrated reconfigurability measurement process described elsewhere [1—5].
Ant Colony Optimization for Design of Space Trusses
Authors: Kaveh A. , Azar B. Farhmand , Talatahari S.
Published: November 2008

This paper presents two mechanisms to improve Ant Colony Optimization (ACO) for design of truss structures. The Sub-Optimization Mechanism causes the reduction in the search space, the size of the trail matrix and the decision vector; consequently, the optimization process is performed in smaller time. The Scatter Memory Mechanism introduces a matrix for saving the best scatter order and enables the ACO-based algorithms to reduce the number of ants and intensity of the analyses. The proposed mechanisms applied to ACS and ASrank are tested on two benchmark trusses from literature. The results for different algorithms demonstrate the efficiency of the proposed mechanisms.
Membrane Buckling Patterns and Secondary Buckling Analysis
Authors: Yunliang Li , Huifeng Tan , Changguo Wang , yu Lu Ming
Published: November 2008

In this paper, the shear wrinkles of a rectangular membrane under the pretension were analyzed firstly. A critical shear distance was then obtained based on the tension field theory. An expression between the wavelength and the amplitude of the membrane wrinkles were developed using the Von Karman large deflection formula. The simulation flow of the membrane wrinkles were also established using the nonlinear post-buckling analytical method. The results indicated that the wrinkle was firstly generated on both sides of the membrane and then extended to the center. The wrinkle amplitude increased with the shear distance increases. The wrinkle formation and expansion were effectively resisted by increasing the initial pretension. Buckling mode of the shear membrane was unstable in the post-buckling process and the secondary buckling phenomenon was obviously observed. The theoretical and numerical results were compared to verify the rationality of the theoretical and simulation results.
On Generalized Reciprocal Diagrams for Self-Stressed Frameworks
Authors: Micheletti Andrea
Published: November 2008

We present the duality between edge lengths and axial forces in self-stressed frameworks, upon which are based reciprocal diagrams, introduced by Maxwell and Cremona in the nineteenth century. The main concepts and principles are simplified by using a graph theoretic approach. We describe some unusual orthogonality relations, involving lengths, axial forces and their rates of change.

Reciprocal diagrams, which exist for frameworks with underlying planar graph, are extended also to the non-planar case by introducing a new criterion. When this criterion can be applied, different reciprocals can be obtained as symmetric frameworks. The same criterion can also be applied to planar cases giving new reciprocals as a result.

Although reciprocal diagrams cannot be obtained for all self-stressed frameworks, the presented duality always holds and it provides useful insights for design and form-finding purposes.
On the Roundness of Polyhedra for Soccer Ball Design
Authors: Geiger Adél , Lengyel András
Published: November 2008

Most soccer balls are made of stitched leather or synthetic flat panels with a bladder inside. The initial flat configuration is represented by polyhedra in 3-space. This paper studies polyhedra related to different symmetry groups in order to find the optimal topology and the optimal dimensions for soccer ball design. A number of polyhedra obtained from regular ones by truncation are investigated. Two mathematical quantities are introduced to measure the sphericity of the ball. They are surface integrals of expressions of the coordinates: the first one expresses moments around the origin of the coordinate system, and the other measures the deviation of a surface from the perfect sphere. We set up a ranking for different ball designs and the results are compared to those of previous studies in this field. Our mathematical approach is applicable to inflated balls with curved surface.
A Strategy of Numerical Analysis of Space Truss Connections with Stamped Bar Ends
Authors: Souza A. S. C. , Gonçalves R. M. , De Nardin S. , Calado L.
Published: November 2008

This paper describes a strategy for numerical simulation using the Finite Elements Method to analyze connections in steel space trusses composed of circular section bars with stamped ends. This type of space truss is widely used in Brazil and the bar ends are stamped to compose the connection. This is an inexpensive solution, but poses several structural problems, thus requiring studies to establish criteria and limits for its use. The most important variables of connections and structural behavior, such as eccentricities, section variation at the bar ends, and physical and geometrical nonlinearity were introduced into the numerical model. The interaction between the bars (relative displacement and sliding in the nodal region) was simulated by means of contact elements. The numerical analysis involved modeling of a complete joining of the structure with shell elements, which were inserted at different points of the space truss. The results were satisfactory, enabling us to evaluate how the behavior of the connections affects the strength and collapse mode of the space trusses.
Molecular characterization of human Argonaute-containing ribonucleoprotein complexes and their bound target mRNAs
Authors: Landthaler Markus , Gaidatzis Dimos , Rothballer Andrea , Chen Po Yu , Soll Steven Joseph , Dinic Lana , Ojo Tolulope , Hafner Markus , Zavolan Mihaela , Tuschl Thomas
Published: November 2008

microRNAs (miRNAs) regulate the expression of mRNAs in animals and plants through miRNA-containing ribonucleoprotein particles (RNPs). At the core of these miRNA silencing effector complexes are the Argonaute (AGO) proteins that bind miRNAs and mediate target mRNA recognition. We generated HEK293 cell lines stably expressing epitope-tagged human AGO proteins and other RNA silencing-related proteins and used these cells to purify miRNA-containing RNPs. Mass spectrometric analyses of the proteins associated with different AGO proteins revealed a common set of helicases and mRNA-binding proteins, among them the three trinucleotide repeat containing proteins 6 (TNRC6A,-B,-C). mRNA microarray analyses of these miRNA-associated RNPs revealed that AGO and TNRC6 proteins bind highly similar sets of transcripts enriched in binding sites for highly expressed endogenous miRNAs, indicating that the TNRC6 proteins are a component of the mRNA-targeting miRNA silencing complex. Together with the very similar proteomic composition of each AGO complex, this result suggests substantial functional redundancy within families of human AGO and TNRC6 proteins. Our results further demonstrate that we have developed an effective biochemical approach to identify physiologically relevant human miRNA targets.
Numerical Solution of Linear Equations Arising in Markov Chain Models
Authors: Heyman Daniel P. , Reeves Alyson
Published: October 2008

We examine several methods for numerically solving linear equations that arise in the study of Markov chains. These methods are Gaussian elimination, state-reduction, closed-form matrix solutions, and some hybrid methods. The emphasis is on moments of first-passage times and times to absorption. We compare the methods on the basis of accuracy and computation. We conclude that state-reduction is the most accurate and that the matrix solutions have the least computation time.

INFORMS Journal on Computing, ISSN 1091-9856, was published as ORSA Journal on Computing from 1989 to 1995 under ISSN 0899-1499.
Strategies for Creating Advanced Bases for Large-Scale Linear Programming Problems
Authors: Maros István , Mitra Gautam
Published: October 2008

The performance of the revised sparse simplex method, or its variants, for the solution of large scale linear programming problems can be considerably enhanced if an advanced starting basis is introduced instead of the traditional all-logical initial basis. We consider three such procedures known as crash procedures to obtain advanced starting points for the revised sparse simplex: 1) We extend traditional crash procedures whereby triangularity of the basis is always maintained and take advantage of the problem characteristics; we apply additional criteria for determining the entering structural variables and their position in the basis. 2) We allow the triangularity to be slightly “violated,” and make some cheap pivot steps to find a better basis. 3) We use the iterative successive-over-relaxation technique to compute a non-extreme point solution and make a crossover to a basic solution. In this article, we first review the work done by other researchers. Then we present an analysis of issues, followed by a description of the techniques and our computational experience.
Column Generation Methods for Probabilistic Logic
Authors: Jaumard Brigitte , Hansen Pierre , Poggi de Aragão Marcus
Published: October 2008

Nilsson recently introduced a rigorous semantic generalization of logic in which the truth values of sentences are probability values. This led to state precisely several basic problems of artificial intelligence, a paradigm of which is probabilistic satisfiability (PSAT): determine, given a set of clauses and probabilities that these clauses are true, whether these probabilities are consistent. We consider several extensions of this model involving intervals on probability values, conditional probabilities and minimal modifications of probability values to ensure satisfiability. Investigating further an approach of G. Georgakopoulos, D. Kavvadias and C. H. Papadimitriou, we propose a column generation algorithm which allows to solve exactly all these extensions. Computational experience shows that large problems, with up to 140 variables and 300 clauses, may be solved in reasonable time.

INFORMS Journal on Computing, ISSN 1091-9856, was published as ORSA Journal on Computing from 1989 to 1995 under ISSN 0899-1499.
Incremental Linear Constraint Solving and Detection of Implicit Equalities
Authors: Stuckey Peter J.
Published: October 2008

The incremental linear constraint satisfaction problem consists of repeatedly solving the satisfiability problem for a growing set of linear constraints. This problem is important to constraint logic programming systems where constraints are discovered one at a time and added to a current constraint set, and the satisfiability of this constraint set must be known at all times. Implicit equalities of a system of constraints are inequality constraints that are satisfied as an equality in all solutions of the system of constraints. Detecting implicit equalities is important in determining the minimal (canonical) representation of a system of linear constraints. In incremental constraint solving systems detecting implicit equalities provides information that can simplify further constraint solving. We present an algorithm which efficiently solves the incremental linear constraint satisfaction problem and detects all the implicit equalities present in the constraints. The algorithm forms a basis for the inequality constraint solver in the CLP(ℜ) system.

INFORMS Journal on Computing, ISSN 1091-9856, was published as ORSA Journal on Computing from 1989 to 1995 under ISSN 0899-1499.
Fast Heuristics for Large Geometric Traveling Salesman Problems
Authors: Reinelt Gerhard
Published: October 2008

Very frequently in practical applications we are faced with large or very large scale traveling salesman problems where the number of cities may range from several hundreds or thousands up to even millions. Due to timing restrictions in the production process there may be situations where good approximative solutions to an instance of the traveling salesman problem have to be found very fast, and where it is not feasible to call even O(n2) time procedures too often. In this paper we discuss several ideas to handle such large traveling salesman problems under time restrictions. We will consider Euclidean traveling salesman problems in the plane and show how their geometric structure can be exploited to derive fast heuristics.

INFORMS Journal on Computing, ISSN 1091-9856, was published as ORSA Journal on Computing from 1989 to 1995 under ISSN 0899-1499.
Optimal Balanced Assignments and a Parallel Database Application
Authors: Ghandeharizadeh Shahram , Meyer Robert R. , Schultz Gary L. , Yackel Jonathan
Published: October 2008

In parallel database systems, distribution of the data among the processors has a significant impact on the response time and throughput of the system. The benefits of parallelism (using multiple processors to execute a query) must be balanced against its costs (communication, startup, and termination overhead). We formalize the problem of minimizing overhead while partitioning data uniformly across the processors. We derive lower bounds on these combinatorial problems and demonstrate how processors may be optimally assigned so as to achieve these lower bounds for a number of problem classes.

INFORMS Journal on Computing, ISSN 1091-9856, was published as ORSA Journal on Computing from 1989 to 1995 under ISSN 0899-1499.
Commentary—A Survival Guide for Parallel Simulation
Authors: Bagrodia Rajive
Published: October 2008

The comprehensive article by Fujimoto clearly outlines the path that parallel simulation must follow in the future. To paraphrase a winning slogan from the recent presidential elections—“The tools, stupid.” This paper elaborates on Fujimoto's insightful observations on what is required to make parallel simulation more accessible to the discrete event simulation community and presents experiences derived from the author's research to reinforce the conclusions.

INFORMS Journal on Computing, ISSN 1091-9856, was published as ORSA Journal on Computing from 1989 to 1995 under ISSN 0899-1499.
Commentary—The Silver Bullet
Authors: Reynolds Paul F.
Published: October 2008

When addressing acceptance of a parallel computing technology by the general simulation community, the issue of performance cannot be overlooked and is difficult to overexaggerate. So, how does this relate to Fujimoto's paper? Fujimoto identifies “easing the amount of work and expertise required to parallelize simulation applications” as his primary point of departure and focuses on four silver bullets. “Alleviating concerns about performance” is not among them. Yet, if there is a silver bullet, this is it.

What I mean by “alleviating performance concerns” is this: if an environment existed where simulationists could develop parallel simulations with automated support for difficult tasks such as synchronization and communication, and the acceptability of the performance of the resulting simulation execution did not hinge on the performance of the automated portions, then performance concerns have been alleviated. Ideally, the performance of the entire simulation would be acceptable, but programmers can be finicky. Later I employ a borrowed virtual memory analogy to clarify my goal.

The difference between what Fujimoto and I consider important is not a matter of content as much as it is a matter of focus. I propose an ideal environment, where the environment is a vehicle for expressing my goals about alleviating performance concerns. Fujimoto discusses languages and identifies requirements that would make the languages better. Both of us conclude by pinpointing similar needs for different reasons. I contend that Fujimoto's presentation leaves the reader with too vague a focus. Many of the issues about languages, application libraries and the like can wait. The research focus needs to be on one central issue: alleviate performance concerns. Solve that and the rest will follow.

In the remainder of this commentary, I discuss the limitations of Fujimoto's silver bullets as goals unto themselves and then elaborate on the issues involved in addressing performance concerns and discuss why this issue is central.

INFORMS Journal on Computing, ISSN 1091-9856, was published as ORSA Journal on Computing from 1989 to 1995 under ISSN 0899-1499.