bluuebunny/crossref_metadata_2025 huggingface dataset:
Force- and Ca2+-dependent internalization of integrins in cultured endothelial cells
Authors: Kiyoshima Daisuke , Kawakami Keisuke , Hayakawa Kimihide , Tatsumi Hitoshi , Sokabe Masahiro
Published: November 2011

The effects of mechanical force applied to the integrin clusters at focal contacts were examined in cultured human umbilical vein endothelial cells. When a fibronectin-coated glass bead was attached to the apical cell surface, focal contacts formed beneath the bead that became linked to focal contacts at the basal cell membrane by actin stress fibers in 5 minutes. Integrin dynamics at the basal focal contacts were monitored in live cells in response to a localized mechanical stimulus generated by displacing the glass bead. Traction force transmitted to the basal focal contacts through the stress fibers was monitored by measuring the deformation of the polyacrylamide gel substratum. The force declined in a few seconds, probably owing to decreases in the elastic modulus of the stress fibers. This transient mechanical stimulus caused the dephosphorylation of paxillin and disassembly of integrin clusters at the basal cell membrane in 20 minutes. The disassembly was mediated mainly by clathrin-dependent endocytosis of integrins. The integrin internalization was inhibited in Ca2+- and K+-free solution, and by phenylarsine oxide, a phosphatase inhibitor. These results suggest that a transient mechanical stimulus applied to focal contacts induces Ca2+-dependent dephosphorylation of some proteins, including paxillin, and facilitates clathrin-dependent endocytosis of integrins.
Dynamics of CENP-N kinetochore binding during the cell cycle
Authors: Hellwig Daniela , Emmerth Stephan , Ulbricht Tobias , Döring Volker , Hoischen Christian , Martin Ronny , Samora Catarina P. , McAinsh Andrew D. , Carroll Christopher W. , Straight Aaron F. , Meraldi Patrick , Diekmann Stephan
Published: November 2011

Accurate chromosome segregation requires the assembly of kinetochores, multiprotein complexes that assemble on the centromere of each sister chromatid. A key step in this process involves binding of the constitutive centromere-associated network (CCAN) to CENP-A, the histone H3 variant that constitutes centromeric nucleosomes. This network is proposed to operate as a persistent structural scaffold for assembly of the outer kinetochore during mitosis. Here, we show by fluorescence resonance energy transfer (FRET) that the N-terminus of CENP-N lies in close proximity to the N-terminus of CENP-A in vivo, consistent with in vitro data showing direct binding of CENP-N to CENP-A. Furthermore, we demonstrate in living cells that CENP-N is bound to kinetochores during S phase and G2, but is largely absent from kinetochores during mitosis and G1. By measuring the dynamics of kinetochore binding, we reveal that CENP-N undergoes rapid exchange in G1 until the middle of S phase when it becomes stably associated with kinetochores. The majority of CENP-N is loaded during S phase and dissociates again during G2. We propose a model in which CENP-N functions as a fidelity factor during centromeric replication and reveal that the CCAN network is considerably more dynamic than previously appreciated.
Effect ofFerula hermonisroot extract on rat skeletal muscle adaptation to exercise
Authors: Allouh Mohammed Z
Published: November 2011

Ferula hermonis Boiss. is an aphrodisiac plant that grows in the Mediterranean region. It has been reported that treatment with acetonic extract from the root of this plant acutely increases serum testosterone in the rat. This study investigated the effects of F. hermonis extract alone or combined with exercise on rat skeletal muscle fibers. Adult male rats were divided into four groups: control-sedentary (CS) that had no treatment or exercise; ferula-sedentary (FS) that was orally treated with ferula extract at a dose of 60 mg/kg/rat every other day over a period of 20 d; control-exercised (CE) that was trained by swimming for 40 min every other day; and ferula-exercised (FE) that received ferula and performed exercise. At the end of experiments, the fiber diameter and number of muscle nuclei of tibialis anterior were measured by using immunofluorescent techniques and software analyses. The FE group showed significant increases in muscle weight, fiber size and nuclear number compared with the other groups. However, no significant changes in the aforementioned parameters were found among the CS, FS and CE groups. Ferula treatment and exercise were additive to each other. In conclusion, short-term exercise combined with administration of F. hermonis extract was more effective in enhancing the growth of skeletal muscle fibers than exercise alone.
Role of CXCR4 internalization in the anti-HIV activity of stromal cell-derived factor-1αprobed by a novel synthetically and modularly modified-chemokine analog
Authors: Dong Chang-Zhi , Tian Shaomin , Madani Navid , Choi Won-Tak , Kumar Santosh , Liu Dongxiang , Sodroski Joseph G , Huang Ziwei , An Jing
Published: November 2011

The natural ligands of two major human immunodeficiency virus type 1 (HIV-1) co-receptors, CXCR4 and CCR5, can profoundly inhibit the replication of HIV-1 that uses these co-receptors for entry into the target cells. It has been postulated that these natural chemokines inhibit HIV-1 infection by blocking common binding sites on CXCR4 or CCR5 that are required for HIV-1 envelope glycoprotein gp120 interaction with its co-receptor and/or by inducing receptor internalization. To investigate whether receptor internalization caused by stromal cell-derived factor (SDF)-1 α, a natural ligand of CXCR4, plays a role in its anti-HIV activity, we applied the SMM (synthetically and modularly modified)-chemokine approach to generate a functional probe of SDF-1 α that retains significant CXCR4 binding but does not induce CXCR4 internalization. The antiviral study of this functional probe analog versus wild-type SDF-1 α showed that, despite the significant CXCR4 binding activity, this probe analog displayed a complete loss of effect in causing CXCR4 internalization and greatly diminished antiviral activity. Interestingly, this new analog also showed a decreased number of overlapping binding sites with HIV-1 on CXCR4 transmembrane and extracellular domains. The correlation of the decrease in the anti-HIV activity with the loss of CXCR4 internalization observed with this probe molecule suggests that receptor internalization may play an important role in the anti-HIV activity of SDF-1 α and possibly other natural chemokines. This further implies that any modifications in SDF-1 α that result in a reduction or loss of internalization activity may result in analogs that are not suitable as effective HIV-1 inhibitors that target CXCR4, unless such modifications also result in improved CXCR4 interaction with increased number of overlapping binding sites with HIV-1, thus leading to more effective steric hindrance against HIV-1.
Determinants of the cytotoxicity of PrrC anticodon nuclease and its amelioration by tRNA repair
Authors: Meineke Birthe , Shuman Stewart
Published: November 2011

Breakage of tRNALys(UUU) by the Escherichia coli anticodon nuclease PrrC (EcoPrrC) underlies a host antiviral response to phage T4 infection that is ultimately thwarted by a virus-encoded RNA repair system. PrrC homologs are prevalent in other bacteria, but their activities and substrates are not defined. We find that induced expression of EcoPrrC is toxic in Saccharomyces cerevisiae and E. coli, whereas the Neisseria meningitidis PrrC (NmePrrC) is not. PrrCs consist of an N-terminal NTPase module and a C-terminal nuclease module. Domain swaps identified the EcoPrrC nuclease domain as decisive for toxicity when linked to either the Eco or Nme NTPase. Indeed, a single arginine-to-tryptophan change in the NmePrrC nuclease domain (R316W) educed a gain-of-function and rendered NmePrrC toxic to yeast, with genetic evidence for tRNALys(UUU) being the relevant target. The reciprocal Trp-to-Arg change in EcoPrrC (W335R) abolished its toxicity. Further mutagenesis of the EcoPrrC nuclease domain highlighted an ensemble of 15 essential residues and distinguished between hypomorphic alleles and potential nuclease-nulls. We report that the RNA repair phase of the bacterial virus-host dynamic is also portable to yeast, where coexpression of the T4 enzymes Pnkp and Rnl1 ameliorated the toxicity of NmePrrC-R316W. Plant tRNA ligase AtRNL also countered NmePrrC-R316W toxicity, in a manner that depended on AtRNL's 5′-kinase and ligase functions.
Revised Delivery-Time Quotation in Scheduling with Tardiness Penalties
Authors: Steiner George , Zhang Rui
Published: November 2011

There are many situations in supply chain scheduling when the supplier finds it impossible to meet the promised due dates for some orders. We present a model for the rescheduling of orders with simultaneous assignment of attainable revised due dates to minimize due date escalation and tardiness penalties for the supplier. We show that the problem is equivalent to minimizing the total tardiness with rejection with respect to the original due dates. We prove that the problem is 𝒩𝒫-hard and present a pseudopolynomial algorithm for it. We also present a fully polynomial time approximation scheme for the problem. Finally, we discuss the implications of our solution for setting fair tardiness penalties when due dates have to be renegotiated because of the delays.
Optimal Selection of Airport Runway Configurations
Authors: Bertsimas Dimitris , Frankovich Michael , Odoni Amedeo
Published: November 2011

We present a mixed integer programming (MIP) model to solve the problems of (i) selecting an airport's optimal sequence of runway configurations and (ii) determining the optimal balance of arrivals and departures to be served at any moment. These problems, the runway configuration management (RCM) problem and the arrival/departure runway balancing (ADRB) problem, respectively, are of critical importance in minimizing the delay of both in-flight and on-the-ground aircraft along with their associated costs. We show that under mild assumptions on the time required to change between configurations, large realistic problem instances can be solved within several seconds. Furthermore, as assumptions are relaxed, optimal solutions are still found within several minutes. Comparison with a sophisticated baseline heuristic reveals that in many cases the potential reduction in cost from using the method is significant and could be expected to be of the order of at least 10%. Finally, we present an extension of the MIP model to solve these two problems for a group of airports in a metropolitan area such as New York (metroplex), where operations at each airport within the metroplex might have an impact on operations at some of the other airports due to limitations in shared airspace.
Convexity Results for the Erlang Delay and Loss Formulae When the Server Utilization Is Held Constant
Authors: Harel Arie
Published: November 2011

This paper proves a long-standing conjecture regarding the optimal design of the M/M/s queue. The classical Erlang delay formula is shown to be a convex function of the number of servers when the server utilization is held constant. This means that when the server utilization is held constant, the marginal decrease in the probability that all servers are busy in the M/M/s queue brought about by the addition of two extra servers is always less than twice the decrease brought about by the addition of one extra server. As a consequence, a method of marginal analysis yields the optimal number of servers that minimize the waiting and service costs when the server utilization is held constant. In addition, it is shown that the expected number of customers in the queue and in the system, as well as the expected waiting time and sojourn in the M/M/s queue, are convex in the number of servers when the server utilization is held constant. These results are useful in design studies involving capacity planning in service operations. The classical Erlang loss formula is also shown to be a convex function of the number of servers when the server utilization is held constant.
Stem cells for cardiac regeneration and possible roles of the transforming growth factor-β superfamily
Authors: Kawaguchi Nanako
Published: November 2011

Heart failure is a leading cause of death worldwide. Studies of stem cell biology are essential for developing efficient treatments. Recently, we established and characterized c-kit-positive cardiac stem cells from the adult rat heart. Using a MethoCult culture system with a methyl-cellulose-based medium, stem-like left-atrium-derived pluripotent cells could be regulated to differentiate into skeletal/cardiac myocytes or adipocytes with almost 100% purity. Microarray and pathway analyses of these cells showed that transforming growth factor-β1 (TGF-β1) and noggin were significantly involved in the differentiation switch. Furthermore, TGF-β1 may act as a regulator for this switch because it simultaneously inhibits adipogenesis and activates myogenesis in a dose-dependent manner. However, the effect of TGF-β varies with developmental stage, dosage, and timing of treatment. In the present review, the findings of recent studies, in particular the use of c-kit-positive cardiac stem cells, are discussed. The effects of the TGF-β superfamily on differentiation, especially on adipogenesis and/or myogenesis, have important implications for future regenerative medicine.
Implementation of standardization in clinical practice: not always an easy task
Authors: Panteghini Mauro
Published: November 2011

As soon as a new reference measurement system is adopted, clinical validation of correctly calibrated commercial methods should take place. Tracing back the calibration of routine assays to a reference system can actually modify the relation of analyte results to existing reference intervals and decision limits and this may invalidate some of the clinical decision-making criteria currently used. To maintain the accumulated clinical experience, the quantitative relationship to the previous calibration system should be established and, if necessary, the clinical decision-making criteria should be adjusted accordingly. The implementation of standardization should take place in a concerted action of laboratorians, manufacturers, external quality assessment scheme organizers and clinicians. Dedicated meetings with manufacturers should be organized to discuss the process of assay recalibration and studies should be performed to obtain convincing evidence that the standardization works, improving result comparability. Another important issue relates to the surveillance of the performance of standardized assays through the organization of appropriate analytical internal and external quality controls. Last but not least, uncertainty of measurement that fits for this purpose must be defined across the entire traceability chain, starting with the available reference materials, extending through the manufacturers and their processes for assignment of calibrator values and ultimately to the final result reported to clinicians by laboratories.
Pharmacokinetic interaction of intramammary ceftriaxone and oral polyherbal drug (Fibrosin®) in goats
Authors: Sar Tapas Kumar , Patra Pabitra Hriday , Dash Jeevan Ranjan , Mandal Tapan Kumar
Published: November 2011

Background: The aim of the present study was to determine pharmacokinetic interaction of ceftriaxone and polyherbal drug (Fibrosin®) in lactating goats following single dose intramammary administration of ceftriaxone with 1 h pre-single dose oral administration of Fibrosin®.

Methods: Pharmacokinetic interaction of ceftriaxone and Fibrosin® was evaluated in lactating goats following single dose intramammary administration of ceftriaxone at 50 mg/kg with 1 h pre-single dose oral administration of Fibrosin® (1.9 g). Estimation of ceftriaxone and its metabolite, ceftizoxime, was determined by high performance liquid chromatography.

Results: Fibrosin® treated goats showed a typical absorption-reabsorption phase of ceftriaxone in plasma following intramammary administration. Neither ceftriaxone nor ceftizoxime was detected in the plasma and urine of goats without Fibrosin® treatment, however, ceftriaxone persisted for 36 h and ceftizoxime was present from 48 h to 72 h in the plasma of Fibrosin® treated goats. Ceftizoxime was also available from 72 h to 360 h post-dosing in milk in the presence of Fibrosin® following intramammary administration of ceftriaxone suggesting the polyherbal drug played a major role in the penetration of ceftriaxone from milk to systemic circulation. Furthermore, the polyherbal drug increased the bioavailability of ceftizoxime in milk following the metabolism of ceftriaxone.

Conclusions: Polyherbal drug (Fibrosin®) plays a major role in the penetration of ceftriaxone from milk to systemic circulation and may be responsible for increased bioavailability of its metabolite in the mammary gland resulting in higher concentration and longer persistence of the drug in milk.
Variation and evolution of the ABC transporter genes ABCB1, ABCC1, ABCG2, ABCG5 and ABCG8: implication for pharmacogenetics and disease
Authors: Silverton Latoya , Dean Michael , Moitra Karobi
Published: November 2011

The ATP-binding cassette (ABC) transporter genes are ubiquitous in the genomes of all vertebrates. Some of these transporters play a key role in xenobiotic defense and are endowed with the capacity to efflux harmful toxic substances. A major role in the evolution of the vertebrate ABC genes is played by gene duplication. Multiple gene duplication and deletion events have been identified in ABC genes, resulting in either gene birth or gene death indicating that the process of gene evolution is still ongoing in this group of transporters. Additionally, polymorphisms in these genes are linked to variations in expression, function, drug disposition and drug response. Single nucleotide polymorphisms in the ABC genes may be considered as markers of individual risk for adverse drug reactions or susceptibility to complex diseases as they can uniquely influence the quality and quantity of gene product. As the ABC genes continue to evolve, globalization will yield additional migration and racial admixtures that will have far reaching implications for the pharmacogenetics of this unique family of transporters in the context of human health.
Huntingtin Aggregation Kinetics and Their Pathological Role in aDrosophilaHuntington’s Disease Model
Authors: Weiss Kurt R , Kimura Yoko , Lee Wyan-Ching Mimi , Littleton J Troy
Published: November 2011

Huntington’s disease is a neurodegenerative disorder resulting from expansion of a polyglutamine tract in the Huntingtin protein. Mutant Huntingtin forms intracellular aggregates within neurons, although it is unclear whether aggregates or more soluble forms of the protein represent the pathogenic species. To examine the link between aggregation and neurodegeneration, we generated Drosophila melanogaster transgenic strains expressing fluorescently tagged human huntingtin encoding pathogenic (Q138) or nonpathogenic (Q15) proteins, allowing in vivo imaging of Huntingtin expression and aggregation in live animals. Neuronal expression of pathogenic Huntingtin leads to pharate adult lethality, accompanied by formation of large aggregates within the cytoplasm of neuronal cell bodies and neurites. Live imaging and Fluorescence Recovery After Photobleaching (FRAP) analysis of pathogenic Huntingtin demonstrated that new aggregates can form in neurons within 12 hr, while preexisting aggregates rapidly accumulate new Huntingtin protein within minutes. To examine the role of aggregates in pathology, we conducted haplo-insufficiency suppressor screens for Huntingtin-Q138 aggregation or Huntingtin-Q138–induced lethality, using deficiencies covering ∼80% of the Drosophila genome. We identified two classes of interacting suppressors in our screen: those that rescue viability while decreasing Huntingtin expression and aggregation and those that rescue viability without disrupting Huntingtin aggregation. The most robust suppressors reduced both soluble and aggregated Huntingtin levels, suggesting toxicity is likely to be associated with both forms of the mutant protein in Huntington’s disease.
A Conserved Transcriptional Regulator Governs Fungal Morphology in Widely Diverged Species
Authors: Cain Christopher W , Lohse Matthew B , Homann Oliver R , Sil Anita , Johnson Alexander D
Published: November 2011

Fungi exhibit a large variety of morphological forms. Here, we examine the functions of a deeply conserved regulator of morphology in three fungal species: Saccharomyces cerevisiae, Candida albicans, and Histoplasma capsulatum. We show that, despite an estimated 600 million years since those species diverged from a common ancestor, Wor1 in C. albicans, Ryp1 in H. capsulatum, and Mit1 in S. cerevisiae are transcriptional regulators that recognize the same DNA sequence. Previous work established that Wor1 regulates white–opaque switching in C. albicans and that its ortholog Ryp1 regulates the yeast to mycelial transition in H. capsulatum. Here we show that the ortholog Mit1 in S. cerevisiae is also a master regulator of a morphological transition, in this case pseudohyphal growth. Full-genome chromatin immunoprecipitation experiments show that Mit1 binds to the control regions of the previously known regulators of pseudohyphal growth as well as those of many additional genes. Through a comparison of binding sites for Mit1 in S. cerevisiae, Wor1 in C. albicans, and Wor1 ectopically expressed in S. cerevisiae, we conclude that the genes controlled by the orthologous regulators overlap only slightly between these two species despite the fact that the DNA binding specificity of the regulators has remained largely unchanged. We suggest that the ancestral Wor1/Mit1/Ryp1 protein controlled aspects of cell morphology and that movement of genes in and out of the Wor1/Mit1/Ryp1 regulon is responsible, in part, for the differences of morphological forms among these species.
Fine-Scale Estimation of Location of Birth from Genome-Wide Single-Nucleotide Polymorphism Data
Authors: Hoggart Clive J , O’Reilly Paul F , Kaakinen Marika , Zhang Weihua , Chambers John C , Kooner Jaspal S , Coin Lachlan J M , Jarvelin Marjo-Riitta
Published: November 2011

Systematic nonrandom mating in populations results in genetic stratification and is predominantly caused by geographic separation, providing the opportunity to infer individuals’ birthplace from genetic data. Such inference has been demonstrated for individuals’ country of birth, but here we use data from the Northern Finland Birth Cohort 1966 (NFBC1966) to investigate the characteristics of genetic structure within a population and subsequently develop a method for inferring location to a finer scale. Principal component analysis (PCA) shows that while the first PCs are particularly informative for location, there is also location information in the higher-order PCs, but it cannot be captured by a linear model. We introduce a new method, pcLOCATE, which is able to exploit this information to improve the accuracy of location inference. pcLOCATE uses individuals’ PC values to estimate the probability of birth in each town and then averages over all towns to give an estimated longitude and latitude of birth using a fully Bayesian model. We apply pcLOCATE to the NFBC1966 data to estimate parental birthplace, testing with successively more PCs and finding the model with the top 23 PCs most accurate, with a median distance of 23 km between the estimated and the true location. pcLOCATE predicts the most recent residence of NFBC1966 individuals to a median distance of 47 km. We also apply pcLOCATE to Indian individuals from the London Life Sciences Prospective Population Study (LOLIPOP) data, and find that birthplace is predicated to a median distance of 54 km from the true location. A method with such accuracy is potentially valuable in population genetics and forensics.
Inferring the History of Interchromosomal Gene Transposition in Drosophila Using n-Dimensional Parsimony
Authors: Han Mira V , Hahn Matthew W
Published: November 2011

Gene transposition puts a new gene copy in a novel genomic environment. Moreover, genes moving between the autosomes and the X chromosome experience change in several evolutionary parameters. Previous studies of gene transposition have not utilized the phylogenetic framework that becomes possible with the availability of whole genomes from multiple species. Here we used parsimonious reconstruction on the genomic distribution of gene families to analyze interchromosomal gene transposition in Drosophila. We identified 782 genes that have moved chromosomes within the phylogeny of 10 Drosophila species, including 87 gene families with multiple independent movements on different branches of the phylogeny. Using this large catalog of transposed genes, we detected accelerated sequence evolution in duplicated genes that transposed when compared to the parental copy at the original locus. We also observed a more refined picture of the biased movement of genes from the X chromosome to the autosomes. The bias of X-to-autosome movement was significantly stronger for RNA-based movements than for DNA-based movements, and among DNA-based movements there was an excess of genes moving onto the X chromosome as well. Genes involved in female-specific functions moved onto the X chromosome while genes with male-specific functions moved off the X. There was a significant overrepresentation of proteins involving chromosomal function among transposed genes, suggesting that genetic conflict between sexes and among chromosomes may be a driving force behind gene transposition in Drosophila.
Fixation Probability in a Two-Locus Model by the Ancestral Recombination–Selection Graph
Authors: Lessard Sabin , Kermany Amir R
Published: November 2011

We use the ancestral influence graph (AIG) for a two-locus, two-allele selection model in the limit of a large population size to obtain an analytic approximation for the probability of ultimate fixation of a single mutant allele A. We assume that this new mutant is introduced at a given locus into a finite population in which a previous mutant allele B is already segregating with a wild type at another linked locus. We deduce that the fixation probability increases as the recombination rate increases if allele A is either in positive epistatic interaction with B and allele B is beneficial or in no epistatic interaction with B and then allele A itself is beneficial. This holds at least as long as the recombination fraction and the selection intensity are small enough and the population size is large enough. In particular this confirms the Hill–Robertson effect, which predicts that recombination renders more likely the ultimate fixation of beneficial mutants at different loci in a population in the presence of random genetic drift even in the absence of epistasis. More importantly, we show that this is true from weak negative epistasis to positive epistasis, at least under weak selection. In the case of deleterious mutants, the fixation probability decreases as the recombination rate increases. This supports Muller’s ratchet mechanism to explain the accumulation of deleterious mutants in a population lacking recombination.
MicroRNA Transgene Overexpression Complements Deficiency-Based Modifier Screens in Drosophila
Authors: Szuplewski Sébastien , Kugler Jan-Michael , Lim Sing Fee , Verma Pushpa , Chen Ya-Wen , Cohen Stephen M
Published: November 2011

Dosage-sensitive modifier screening is a powerful tool for linking genes to biological processes. Use of chromosomal deletions permits sampling the effects of removing groups of genes related by position on the chromosome. Here, we explore the use of inducible microRNA transgenes as a complement to deficiency-based modifier screens. miRNAs are predicted to have hundreds of targets. miRNA overexpression provides an efficient means to reduces expression of large gene sets. A collection of transgenes was prepared to allow overexpression of 89 miRNAs or miRNA clusters. These transgenes and a set of genomic deficiencies were screened for their ability to modify the bristle phenotype of the cell-cycle regulator minus. Sixteen miRNAs were identified as dominant suppressors, while the deficiency screen uncovered four genomic regions that contain a dominant suppressor. Comparing the genes uncovered by the deletions with predicted miRNA targets uncovered a small set of candidate suppressors. Two candidates were identified as suppressors of the minus phenotype, Cullin-4 and CG5199/Cut8. Additionally, we show that Cullin-4 acts through its substrate receptor Cdt2 to suppress the minus phenotype. We suggest that inducible microRNA transgenes are a useful complement to deficiency-based modifier screens.
Resistance of alkali-activated slag mortar to abrasion and fire
Authors: Karahan Okan , Yakupoğlu Aslan
Published: November 2011

This study investigates the durability of alkali-activated slag mortar exposed to abrasion and fire. Alkali-activated slag mortar is made by activating ground-granulated blast furnace slag with sodium hydroxide, sodium carbonate, sodium metasilicate and sodium silicate without adding Portland cement. Mortars were made with CEN reference sand, ground granulated blast-furnace slag, alkali-activator and natural spring water. The sand–slag and water–slag materials ratios were 3·0 and 0·50 for all mixtures, respectively. At 28 days, the specimens were exposed to horizontal Böhme abrasion and vertical grinding abrasion tests and to an elevated temperature of 1000°C for a fire test. The highest abrasion resistance was observed from the slag mortar activated by sodium silicate and sodium metasilicate. Sodium hydroxide showed superior fire resistance when compared with Portland cement mortar and other alkali-activated slag mortars.
Effect of size fraction on composition and pozzolanic activity of high calcium fly ash
Authors: Zhang Tong-sheng , Yu Qi-jun , Wei Jiang-xiong , Zhang Ping-ping
Published: November 2011

To improve the properties of fly ash-incorporating Portland cement and utilise fly ash more efficiently, a high calcium fly ash was classified into several fractions by an air classifier. The composition, morphology, water requirement and activity index of different fly ash fractions were examined in the present study. Pozzolanic activity of fly ash fractions in simulative pore solution of Portland cement paste was determined. The experimental results show that the chemical and mineral compositions of fly ash particles vary with particle size. Fine fly ash fractions present high amounts of alkali, un-burnt carbon, CaO, SO3 and glass phase, whereas coarse fly ash fractions have more crystalline phases. In addition, the fly ash fractions with mean size under 8 μm show significantly higher pozzolanic activity and higher compressive activity index than coarse fractions. Thus, these fractions are recommended to serve as supplementary cementitious material for Portland cement-based materials.
Influence of chloride ion on the hydration reaction of C3A in presence of gypsum and lime
Authors: Ahmed Doaa A. , Mohammed Maha R.
Published: November 2011

The hydration reactions of the systems C3A, C3A +gypsum (1 : 1·5 mole ratio) and C3A + gypsum + lime (1 : 1·5 : 1 mole ratio) in 0·1 and 1 molar solutions of sodium chloride at room temperature were studied. The hydration products formed after 2 min and up to 7 days were investigated using X-ray diffraction analysis. The filtered solutions were also analysed for sulfate, chloride, aluminium and calcium contents and the pH values of these solutions were determined. X-ray diffraction analysis indicated the formation of the chloro-compound known as Friedel's salt in all the studied systems. The ettringite phase and Friedel's salt appeared in systems containing gypsum and lime. Increasing the concentration of NaCl solution increased the rate of formation of both compounds.
Safety in large-scale manufacturing of nanoparticles for bio-medical use
Authors: Serguei Maksimov K. , Nikolai Soukhov D. , Kirill Maksimov S.
Published: November 2011

Nanoparticles offer significant advantages but also great risks. Risks associated with nanoparticles are problems faced by all technologies, but they increase in many folds in nanotechnologies. Adequate methods for real-time production inspection are necessary to solve the problem of risks. Existing safety standards result from a principle of ‘maximum permissible concentrations or MPC’. This principle is not applicable to nanoparticles, but a safety standard reflecting risks inherent in nanoparticles does not exist. Possible approaches for safety standards of nanoparticles are reflected in many publications, but conventional inspection methods cannot provide its realization and this gap is an obstacle to assumption of similar solutions. Therefore, the development of nanoparticle industry as a whole (also development of the pharmacology industry in particular) is impossible without the creation of an adequate inspection method. There are newly suggested inspection methods that have been based on new physical principles and are satisfying to meet the adequate safety standards for handling nanoparticles. These methods demonstrate that the creation of acceptable safety standards and the real-time production inspection in large-scale manufacturing of nanoparticles are solvable problems. However, there is a large gap between the physical principles and its actual implementation and a transition from the principle to the hardware demands significant intellectual and material costs. Therefore, it is desirable to call the attention of the public at large to the necessity of urgent expansion of investigations associated with real time inspections in nanoparticle technologies.
Formation and evolution of water menisci in unsaturated granular media
Authors: LOURENçO S.D.N. , GALLIPOLI D. , AUGARDE C.E. , TOLL D.G. , FISHER P.C. , CONGREVE A.
Published: November 2011

Loose particles in moist granular materials, such as unsaturated soils, are held together by capillary forces acting at the interparticle contacts. The magnitude of these capillary forces depends on the surface tension and on the radius of curvature of the menisci, which in turn depends on the contact angle of the air/water interface against the surface of the solid particles. Menisci are usually assumed to be predominantly concave on the side of the air with negative water pressure (relative to the atmosphere). Evidence for this comes from direct observations at the millimetre scale or from theoretical assumptions. This note presents data from environmental scanning electron microscopy of particles at the micrometre scale that contradict this assumption and show for the first time that, for a given water content, the contact angle between air/water interfaces and grains can give rise to a variety of meniscus shapes, with curvatures not all concave on the side of air. It was found that the curvature of water menisci, in both idealised and natural granular materials with variable particle sizes, shapes and nature, could vary along the border of a single meniscus or differ from one point to another separated at the micrometre scale, and is also dependent on the nature of materials and wetting history. Menisci can have both predominantly convex shapes (corresponding to compressive capillary pressure) and predominantly concave shapes (corresponding to tensile capillary water pressure). These observations confirm the importance of surface tension in the air/water interfaces (often also referred to as ‘contractile skin') in holding particles together.
Students' views on their education and the future
Authors: Bather Mike
Published: November 2011

Today's students are tomorrow's civil engineers. If today's pace of change continues then they will face many new challenges. How do they prepare for an uncertain future? Along with industry, the professional bodies and academia, students are important stakeholders in the provision of civil engineering degree courses. It is right that their views should be known. Research was undertaken with civil engineering students from the final and penultimate years of the University of Bolton BSc(Hons) degree course using small discussion groups and mini focus groups. The results of this small-scale research are interesting and raise questions about, firstly, the immense benefits of practical experience for students undertaking degree courses and, secondly, the direction and management of the lifelong learning of all professional engineers (particularly in support of younger engineers). The key benefit of this work is the chance for policy makers to briefly see the world of civil engineering education through the eyes of undergraduate students from a modern university in a northern working town.
Civil engineering degrees: fit for the future?
Authors: Mills Peter John
Published: November 2011

Much has been written about the skills that current engineers need and the desired attributes of the so-called twenty-first century engineer. There is always debate around how much theoretical understanding a graduate engineer needs and how much practical application is required. This paper unpacks the requirements of twenty-first century engineers, from a UK perspective, and questions whether current civil engineering degrees are meeting such requirements. The requirements of existing professional bodies in the UK are critically reviewed. A key question is whether a post-modernist view of engineering should be adopted and the education aligned accordingly. A review of post-modernism, from a coastal engineering perspective, is presented and parallels are drawn with civil engineering. It is concluded that civil engineering degrees do adopt a post-modernist approach and are fit for the future based on current professional body requirements. It is further argued that to be even better prepared for the future, civil engineering educators and professional bodies should be cognisant of educational theories.
Criticality of intelligent clients in the infrastructure sector
Authors: Emuze Fidelis , Smallwood John
Published: November 2011

Intelligence in the form of skills that depend on tacit and explicit knowledge gained through formal and informal learning assists in informed decision-making, which is necessary for project execution. However, literature related to project failures attributes poor performance in construction to the level of skills of project stakeholders. The central issue here is the seemingly inadequate technical and management skills domiciled in public works departments of developing countries. In fact, anecdotal evidence suggests that this inadequacy marginalises the realisation of infrastructure development in sub-Saharan Africa. Therefore, using South Africa as an example, the paper reports on the consequences associated with skills inadequacies and future skills requirements. The report is therefore based on an extensive review of related literature, and an empirical study undertaken in South Africa. The research findings indicate that skills shortages in public sector departments may be responsible for a range of project failings such as unnecessary delays in contract award after tender submission, which in turn hamper project performance. Therefore, the study suggests that in order to deliver future infrastructure projects adequately, attention should be given to the development of management, project management and technical skills.
UK rail transport: a review of demand and supply
Authors: Ison Stephen , Frost Matthew , Watson Robert
Published: November 2011

Over recent years the UK railway industry has seen unprecedented growth in the number of passengers and the amount of freight carried. Expansion in network capacity, however, has not kept pace with this growth. This has led to significant overcrowding and little or no capacity left to run more trains within existing stock or track provision. The UK government however has stated that as part of achieving ‘best value' it wants to further increase rail traffic, and has recently set out a strategy to optimise this. This paper reviews the issues associated with the growth in passengers, the demand placed on the network and the policy developed to accommodate and manage it. It identifies the capacity constraints and options identified for capacity enhancement. The paper concludes that while privatisation has made coherent decision-making difficult there is significant experience to be gained in the development of policy and route utilisation strategies.
A Prospective Study of the Associations Between Treated Diabetes and Cancer Outcomes
Authors: Yeh Hsin-Chieh , Platz Elizabeth A. , Wang Nae-Yuh , Visvanathan Kala , Helzlsouer Kathy J. , Brancati Frederick L.
Published: November 2011

OBJECTIVE

To quantify the association of treated diabetes with cancer incidence and cancer mortality as well as cancer case fatality and all-cause mortality in adults who subsequently develop cancer and to calculate attributable fractions due to diabetes on various cancer outcomes.

RESEARCH DESIGN AND METHODS

Prospective data on 599 diabetic and 17,681 nondiabetic adults from the CLUE II (Give Us a Clue to Cancer and Heart Disease) cohort in Washington County, Maryland, were analyzed. Diabetes was defined by self-reported use of diabetes medications at baseline. Cancer incidence was ascertained using county and state cancer registries. Mortality data were obtained from death certificates.

RESULTS

From 1989 to 2006, 116 diabetic and 2,365 nondiabetic adults developed cancer, corresponding to age-adjusted incidence of 13.25 and 10.58 per 1,000 person-years, respectively. Adjusting for age, sex, education, BMI, smoking, hypertension treatment, and high cholesterol treatment using Cox proportional hazards regression, diabetes was associated with a higher risk of incident cancer (hazard ratio 1.22 [95% CI 0.98–1.53]) and cancer mortality (1.36 [1.02–1.81]). In individuals who developed cancer, adults with diabetes had a higher risk of cancer case fatality (1.34 [1.002–1.79]) and all-cause mortality (1.61 [1.29–2.01]). For colorectal, breast, and prostate cancers, the attributable fractions resulting from diabetes were larger for cancer fatality and mortality than cancer incidence.

CONCLUSIONS

In this prospective cohort, diabetes appears to exert a greater influence downstream on the risk of mortality in people with cancer than on upstream risk of incident cancer.
Overwhelmed Patients
Authors: Bohlen Krista , Scoville Elizabeth , Shippee Nathan D. , May Carl R. , Montori Victor M.
Published: November 2011

OBJECTIVE

Patients with diabetes may experience high burden of treatment (BOT), including treatment-related effects and self-care demands. We examined whether patients with type 2 diabetes and their clinicians discuss BOT, the characteristics of their discussions, and their attempts to address BOT during visits.

RESEARCH DESIGN AND METHODS

Two coders independently reviewed videos of 46 primary care visits obtained during a practice-based trial and identified utterances concerning BOT, classifying them by topic and by whether BOT was addressed (i.e., whether statements emerged aimed at alleviating BOT).

RESULTS

Of the 46 visits, 43 (93.5%) contained BOT discussions. Both coders identified 83 discussions: 12 involving monitoring, 28 treatment administration, 19 access, and 24 treatment effects. BOT was unambiguously addressed only 30% of the time.

CONCLUSIONS

BOT discussions usually arise during visits but rarely beget problem-solving efforts. These discussions represent missed opportunities for reducing treatment-related disruptions in the lives of patients with diabetes, which may affect adherence and well-being.
Processed and Unprocessed Red Meat Consumption and Incident Type 2 Diabetes Among French Women
Authors: Lajous Martin , Tondeur Laura , Fagherazzi Guy , de Lauzon-Guillain Blandine , Boutron-Ruaualt Marie-Christine , Clavel-Chapelon Françoise
Published: November 2011

OBJECTIVE

To evaluate the relation of processed and unprocessed red meat and incident type 2 diabetes.

RESEARCH DESIGN AND METHODS

We conducted a prospective study among 66,118 disease-free French women with dietary information from a validated questionnaire. Between 1993 and 2007, we identified 1,369 cases of incident diabetes. Multivariate analyses were adjusted for age, education, region, smoking, BMI, hypertension, hypercholesterolemia, physical activity, parental history of diabetes, menopause, hormone replacement therapy, alcohol, calories, n-3 fatty acids, carbohydrates, coffee, fiber, and fruits and vegetables.

RESULTS

Comparing the highest category of processed meat intake, ≥5 servings/week (median, 48 g/day), to the lowest, <1 serving/week (median, 5 g/day), processed meat was significantly associated with incident diabetes (hazard ratio 1.30 [95% CI 1.07–1.59], P trend = 0.0007; for 1 serving/day, 1.29 [1.14–1.45]). Unprocessed red meat was not associated with diabetes.

CONCLUSIONS

In this large prospective cohort of French women, a direct association was observed only for processed red meat and type 2 diabetes.
William Blake'sMilton/A Poemand the Miltonic Matrix of 1791–1810
Authors: Paley Morton D.
Published: November 2011

From the time when ‘Milton lovd me in childhood & shewd me his face,’ William Blake felt a special relationship with John Milton. He would therefore have felt a great interest in the extraordinary spate of publishing and pictorial activity (sometimes both together) that occurred in the last decade of the eighteenth century and the early years of the nineteenth. He was, indeed, mentioned as a participant in two major Milton projects planned during this period, but neither materialized. His own Milton/A Poem, completed c. 1811, addresses two major subjects of previous discussion: Milton's political commitment and his relations with the women in his life. Characteristically, Blake does not adopt any prior positions, but renders his own views, which are different from any of them.
Blake and the Banknote Crises of 1797, 1800, and 1818
Authors: Crosby Mark
Published: November 2011

On 5 April 1797, Blake signed a certificate attesting to the efficacy of Alexander Tilloch's method for producing forge-proof banknotes. Tilloch's scheme was designed to obviate the human cost of forgery, which was a capital offence. Predicated on a stereotype printing process, Tilloch's method was technically and conceptually analogous to Blake's experiments in illuminated printing. While motivated by different political, economic, and aesthetic ideals, both men used experimental engraving/etching technologies to challenge systemic repression. This essay examines an overlooked context for Blake's poetic responses to repression, documents a previously unrecorded manuscript certificate dated 5 April 1797 containing Blake's signature, as well as two hitherto unrecorded instances of Blake's name being published in connection with Tilloch's 1797 scheme, and suggests another context for the ‘black net’ that Blake describes smothering London in 1800. The trial records show that those convicted of banknote forgery had access to engraving equipment. As an engraver with a copperplate rolling press, Blake would have come under suspicion when large quantities of counterfeit notes were discovered in 1797, 1800, and 1818.
Remember Me! Customs and Costumes of Blake's Gift Book
Authors: Bentley G.E.
Published: November 2011

The gift book Remember Me! with Blake's wonderful engraving of the ‘Hiding of Moses’ was more remarkable for its decorations than for its literary contents. Of the twenty-four copies recorded, each differs from the others in the pattern of binding, colour of fore-edges, endpapers, and the decorated sleeve-case. Despite this varied elegance, the work had only a modest sale, and the same sheets were re-issued in 1825 for the 1826 gift-giving season. This paucity of sales may be related to the fact that the publisher John Poole had little experience of book distribution. His speciality was as a maker of Marble Paper and Fancy Pocket-Books, not in selling them.