bluuebunny/crossref_metadata_2025 huggingface dataset:
The significance of transfusion in the past as a risk for current hepatitis B and hepatitis C infection: a study in endoscopy patients
Authors: Tawk Hani M. , Vickery Karen , Bisset Linda , Lo Sing Kai , Cossart Yvonne E. ,   the Infection in Endoscopy Study Group
Published: April 2005

BACKGROUND: The objective was to determine the contribution of transfusion in the past to the risk of current infection with hepatitis B or C among patients attending a large hospital for endoscopic procedures.

STUDY DESIGN AND METHODS: Blood samples had been tested for hepatitis markers by routine methods. Patients completed a comprehensive risk factor questionnaire and results were analyzed using computer software.

RESULTS: Twenty‐seven percent of the 2120 participants in the study received transfusions in the past. There was no increase in prevalence of hepatitis B among those transfused. Compared with nontransfused participants, recipients of blood before the implementation of hepatitis C virus (HCV) screening in 1990 had a 4.6‐fold increased risk of HCV infection, whereas those transfused with screened blood had a 3‐fold increased risk. The difference between the odds ratios for patients before and after screening was not significant.

CONCLUSIONS: Because screening has almost completely eliminated HCV from the blood supply, our finding of a continuing association of HCV infection with transfusion was unexpected. It implies that there are significant other nosocomial risks for hepatitis C transmission associated with the clinical situations where patients received blood. These should be actively investigated.
A flexible array format for large‐scale, rapid blood group DNA typing
Authors: Hashmi Ghazala , Shariff Tasmia , Seul Michael , Vissavajjhala Prabhakar , Hue‐Roye Kim , Charles‐Pierre Dalisay , Lomas‐Francis Christine , Chaudhuri Asok , Reid Marion E.
Published: April 2005

BACKGROUND: Typing for blood group antigens is currently performed by hemagglutination. The necessary reagents are becoming costly and limited in availability, and the methods are labor‐intensive. The purpose of this study was to determine the feasibility of the use of large‐scale DNA analysis in a microarray as a substitute for blood group typing.

STUDY DESIGN AND METHODS: DNA, extracted from blood samples that had been phenotyped for some of the red blood cell antigens, was analyzed for selected blood group alleles by bead array (BeadChip, BioArray Solutions Ltd., Warren, NJ) and by manual polymerase chain reaction (PCR)‐based assays. Selected alleles were identified by enzyme‐mediated elongation of probes, which were on color‐encoded beads assembled into arrays on silicon chips. The performance of a prototype BeadChip (BLOOD‐1) containing single‐nucleotide polymorphisms (SNPs) for FYA/B, FY‐GATA, DOA/B, COA/B, LWA/B, DIA/B, and SC1/SC2 was verified with DNA from serologically characterized donors. It was then used to analyze more than 400 samples of partially defined phenotype. Samples from Chinese, Ashkenazi, and Thai donors (total n = 227) were tested with BLOOD‐1. An expanded BeadChip with a total of 18 SNPs (36 alleles; SNPs in BLOOD‐1 and M/N, S/s, Lua/Lub, K/k, FY265[for the FyX polymorphism], Jka/Jkb, DO323[for Hy], DO350[for Joa], and HgbS) was then evaluated with a subset of previously tested samples from Chinese, Ashkenazi, and New York blood donors (127) and an additional set of samples from Israeli donors (total n = 188).

RESULTS: Results obtained by BeadChip analysis were concordant with those obtained with the manual PCR‐restriction fragment length polymorphism, allele‐specific PCR, and hemagglutination assays. The frequencies of the alleles in the samples from different ethnic panels were within the expected ranges; however, two new DO alleles were discovered.

CONCLUSION: It has been shown that microarray technology can be used to type DNA and detect new alleles in donor cohorts.*
High‐throughput multiplex single‐nucleotide polymorphism analysis for red cell and platelet antigen genotypes
Authors: Denomme G.A. , Van Oene M.
Published: April 2005

BACKGROUND: Transfusion recipients who become alloimmunized to red cell or platelet (PLT) antigens require antigen‐negative blood to limit adverse transfusion reactions. Blood collection facilities use regulated and unregulated antibodies to phenotype blood, the cost of which can be prohibitive depending on the antisera and demand. An alternative strategy is to screen blood for these antigens with genomic DNA and the associated single‐nucleotide polymorphisms (SNPs).

STUDY DESIGN AND METHODS: A multiplex polymerase chain reaction (PCR)‐oligonucleotide extension assay was developed with genomic DNA and a SNP genotyping platform (GenomeLab SNPstream, Beckman Coulter) to identify SNPs related to D, C/c, E, S/s, K/k, Kpa/b, Fya/b, FY0 (−33 promoter silencing polymorphism), Jka/b, Dia/b, and human PLT antigen (HPA)‐1a/1b. A total of 372 samples were analyzed for 12 SNPs. The genotypes were compared to the blood group and PLT antigen phenotypes.

RESULTS: Individual sample results varied from 98 to 100 percent for 11 of 12 SNPs. D was correctly identified in 292 of 296 (98.6%) D+ donors. The RHCE exon 5 E/e SNP analysis had the lowest concordance (89.5%). Thirty‐three R1R1 and 1 r”r were correctly identified. PCR‐restriction fragment length polymorphism (RFLP) on selected samples confirmed the presence of the FY0 silencing polymorphism in nine donors. Homozygous HPA‐1b/1b was identified in four donors, which was confirmed by PCR‐RFLP (n = 4) and anti‐HPA‐1a serology (n = 2). The two HPA‐1a‐negative donors were recruited into the plateletpheresis program.

CONCLUSION: The platform has the capacity to genotype thousands of samples per day. The suite of SNPs provides genotype data for all blood donors within 36 hours of the start of testing.
Oxaliplatin‐induced immune pancytopenia
Authors: Taleghani Behrouz Mansouri , Fontana Stefano , Meyer Oliver , Ahrens Norbert , Novak Urban , Borner Markus M. , Salama Abdulgabar
Published: April 2005

BACKGROUND: Oxaliplatin, a third‐generation platinum compound, has been implicated in isolated cases of immune hemolytic anemia and/or immune thrombocytopenia. The first case of severe immune pancytopenia related to oxaliplatin is described.

PATIENT AND METHODS: A 79‐year‐old woman with colorectal cancer was initially treated with 5‐fluorouracil and she later received oxaliplatin and leucovorin every 2 to 4 weeks. During the 15th and 17th cycles of chemotherapy she developed thrombocytopenia, hemolysis, and neutropenia. No problems occurred during the 16th cycle without oxaliplatin. Serologic testing including detection of drug‐dependent antibodies and autoantibodies was performed with standard techniques.

RESULTS: Serologic findings included a positive immunoglobulin G direct antiglobulin test; nonreactive red blood cell (RBC) eluates; platelet (PLT)‐bound antibodies to glycophorin (GP) IIb‐IIIa, GPIb‐IX, and GPIa‐IIa; and oxaliplatin‐dependent antibodies to PLTs, RBCs, and neutrophils.

CONCLUSION: Oxaliplatin may lead to the production of ddabs to RBCs, PLTs, and neutrophils. Thus the risk of immune cytopenias should always be considered in patients treated with oxaliplatin.
Specialist Risk Attitudes and the Bid‐Ask Spread
Authors: Prucyk Brian
Published: April 2005

This paper examines the relation between the bid‐ask spread and the risk of the underlying stock. It provides evidence that the specialist is not only sensitive to the absolute level of volatility, but also to changes in the level of volatility. This sensitivity arises because of increased inventory risk for the specialist when volatility is changing. For the sample of very liquid stocks in this paper, the quoted spread and the inventory cost component of the spread are shown to increase significantly during trading periods when volatility is both increasing and decreasing.
Alternative Methods for Projecting Equity Returns: Implications for Evaluating Social Security Reform Proposals
Authors: Sabelhaus John
Published: April 2005

The effect upon future Social Security benefits resulting from the introduction of individual accounts depends on both the potential risks and returns of private equities, yet the historical evidence about the determinants of stock market risks and returns is mixed. In particular, correlations between equity returns and market fundamentals (such as the dividend–price ratio) are weak at annual frequencies, which has led some to conclude that a random returns (fixed mean and variance) model is the preferred specification for simulating the future path of equity returns. Although choosing between the random returns model and models based on market fundamentals does equally well for explaining variation of equity returns in the short run, the distinction is important when projecting equity returns over longer periods, as shown here in the context of a Monte Carlo simulation of Social Security reform. If equity returns are even weakly correlated with market fundamentals then (1) the expected future average return may be a function of the starting values for market fundamentals, and (2) the overall range of cumulative outcomes is narrower than the random returns model suggests.
The Columbia Space Shuttle Tragedy: Third‐Party Liability Implications for the Insurance of Space Losses
Authors: Manikowski Piotr
Published: April 2005

Space flights are no longer rare events, but the commonplace is not necessarily safe. When disaster strikes, as in the Columbia Space Shuttle disaster of 2003, third parties as well as those directly involved are financially affected. This article considers how these issues are treated under international law. It also analyzes what products the insurance markets offer as protection against such third‐party liabilities.
Evaluating the Devolution Revolution1
Authors: Rodgers Harrell
Published: April 2005

This article provides an evaluation of the impact of the Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA) of 1996. The evidence clearly shows that PRWORA has had a major impact on the poverty population and the welfare system. The data analyzed identify those policy areas in which positive changes can be identified, along with implementation and design problems that need reform. The data also show that while some states have made considerable progress in implementing the law, many are lagging.
Innovation in Welfare Policy: Evaluating State Efforts to Encourage Work among Low‐Income Families1
Authors: Bryner Gary , Martin Ryan
Published: April 2005

This article examines what states are doing to help Temporary Assistance to Needy Families (TANF) recipients move into the workforce and become self‐supporting. We first present documentation regarding many different state TANF policies aimed at encouraging work, including benefit structures, time limits, work requirements, sanctions, and work supports. We then discuss how effective these policies are at helping welfare recipients get jobs and increase their income, by reviewing research on each of these elements. We conclude that the TANF program has been effective in increasing employment and decreasing welfare caseloads and expenses, but that this has not resulted in overall income gains for welfare recipients in the long run. We also conclude that the most promising state programs have a strong employment focus combined with focused training and educational opportunities. In addition, we also find that sanctions appear to be harming those most in need of assistance, and therefore that such policies should be reevaluated and refocused.
Plutella xylostella (diamondback moth) and its parasitoid Diadegma semiclausum show different gustatory and longevity responses to a range of nectar and honeydew sugars
Authors: Winkler Karin , Wäckers Felix L. , Stingli Attila , Van Lenteren Joop C.
Published: April 2005

Parasitoids as well as many of their herbivorous hosts, depend on carbohydrate‐rich food during the adult stage. Different types of nectar and honeydew vary with regard to their sugar composition. In order to successfully exploit a food source, the insect must show a positive gustatory response to its component sugars and be able to digest and metabolise them. Here we tested the herbivore Plutella xylostella L. (Lepidoptera: Plutellidae) and its parasitoid Diadegma semiclausum (Hellén) (Ichneumonidae: Campopleginae) with respect to their feeding response and longevity when provided with one of nine sugars (fructose, glucose, lactose, maltose, melibiose, melezitose, raffinose, sucrose, or trehalose). Both species responded to and showed a prolonged life span on a broad range of sugars. The impact of food supply on life span was about sixfold higher for the parasitoid than for the herbivore. In general, there was a good fit between gustatory response and achieved longevity, with some outliers. Both species showed only weak responses to melibiose, which significantly prolonged life span. The parasitoid showed a gustatory response to melezitose, which did not prolong its life span. The parasitoid and its herbivorous host responded differently to trehalose. These differences in gustatory response and longevity show the potential for application of selective sugar sources in conservation biological control. At the same time it also reveals a risk that the indiscriminate application of sugar sources may stimulate herbivory.
Choosy egg parasitoids: Specificity of oviposition‐induced pine volatiles exploited by an egg parasitoid of pine sawflies
Authors: Mumm Roland , Tiemann Tassilo , Varama Martti , Hilker Monika
Published: April 2005

Generalist parasitoids are well‐known to be able to cope with the high genotypic and phenotypic plasticity of plant volatiles by learning odours during their host encounters. In contrast, specialised parasitoids often respond innately to host‐specific cues. Previous studies have shown that females of the specialised egg parasitoid Chrysonotomyia ruforum Krausse (Hymenoptera: Eulophidae) are attracted to volatiles from Pinus sylvestris L. induced by the egg deposition of its host Diprion pini L. (Hymenoptera: Diprionidae), when they have previously experienced pine twigs with host eggs. In this study we investigated by olfactometer bioassays how specifically C. ruforum responded to oviposition‐induced plant volatiles. Furthermore, we studied whether parasitoids show an innate response to oviposition‐induced pine volatiles. Naïve parasitoids were not attracted to oviposition‐induced pine volatiles. The attractiveness of volatiles from pines carrying eggs was shown to be specific for the pine and herbivore species, respectively (species specificity). We also tested whether not only oviposition, but also larval feeding, induces attractive volatiles (developmental stage specificity). The feeding of D. pini larvae did not induce the emission of P. sylvestris volatiles attractive to the egg parasitoid. Our results show that a specialist egg parasitoid does not innately show a positive response to oviposition‐induced plant volatiles, but needs to learn them. Furthermore, the results show that C. ruforum as a specialist does not learn a wide range of volatiles as some generalists do, but instead learns only a very specific oviposition‐induced plant volatile pattern, i.e., a pattern induced by the most preferred host species laying eggs on the most preferred food plant.
Insect feeding preferences and plant phenolic glucosides in the system Gonioctena linnaeana–Salix triandra
Authors: Niemi Lena , Wennström Anders , Ericson Lars
Published: April 2005

The aim of this study was to investigate the preference of a leaf beetle to different Salix clones, and to relate this preference to plant chemistry. The preference of Gonioctena linnaeana Schrank (Coleoptera: Chrysomelidae) was tested in cafeteria experiments using its host Salix triandra L. (Salicaeae) from three Swedish isolated populations and one Russian population from the main distribution range of the host. The leaves from the different host clones were used to analyse the content of phenolic glucosides and the amount of condensed tannins. The larvae did not show any feeding preferences for host clones from the population they originated from, but all Swedish host populations were preferred over the Russian host population. This suggests a preference for regional hosts. We analyzed whether leaf chemistry parameters may explain host plant preferences. Chemical analysis of the leaves showed that the quantities, but not the quality, of the phenolic compounds differed between populations. A Principal Component Analysis of the chemical data also highlighted a difference between the Swedish and Russian host plant populations. The two most important compounds separating Russian from Swedish clones were gallocatechin and salidroside. However, the difference in preference could also be a result of, for example, nutritional quality, water content, or leaf texture. The relative importance of these different factors should be evaluated in future experiments.
Parasitoid exploitation of the seasonal variation in host plant volatile emission for herbivore location
Authors: Rott A.S. , Häckermann J. , Brand N. , Vallat A. , Dorn S.
Published: April 2005

Volatile compounds from the apple, Malus domestica Borkh. (Rosaceae), change considerably as the season progresses, and this is successfully exploited by the female codling moth Cydia pomonella L. (Lepidoptera, Tortricidae), as it searches for oviposition sites. In this study, we investigated the effect of seasonal emissions of apple fruit volatiles on the host location behaviour of a parasitoid of the codling moth larvae, Hyssopus pallidus (Askew) (Hymenoptera: Eulophidae). In dual choice olfactory bioassays, the behaviour of the parasitoid in response to apple cues was observed over the complete 2003 growing season. Our results show that codling moth infested apples evoked a strong response from the parasitoid at the beginning of the season, until July. Then, attraction dropped drastically, increasing again at the beginning of August. At the end of the growing season, just prior to harvest, infested apples hardly evoked any behavioural response. Interestingly enough, mid‐season emissions of healthy apples were per se attractive to the parasitoid, and even preferred over volatiles from infested apples. Simultaneous volatile collections from healthy apples on twigs in the field were analysed throughout the season, showing that the overall quantity of headspace volatiles peaks at the beginning of June and mid‐August. The seasonal volatile emission is correlated with the behaviour of the parasitoid during the fruit ripening stage. The results are discussed in relation to the use of H. pallidus as a potential biocontrol agent, in order to enhance current integrated pest management (IPM) programs.
Leaf age and life history variables of a leafminer: the case of Liriomyza trifolii on potato leaves
Authors: Facknath S.
Published: April 2005

Field observations and laboratory experiments have demonstrated that infestation by the serpentine leaf miner, Liriomyza trifolii Burgess (Diptera: Agromyzidae), begins in the lower leaves of the potato plant, and proceeds through the middle leaves to those of the upper canopy. In choice and no‐choice experiments, mated adult L. trifolii females were given access for 48 h to potato plants, and caged on differently aged leaves. The extent of their feeding and oviposition on the 5–7 leaflets of the upper, middle, and lower leaves were recorded. The life history variables of the next generation were estimated: percentage egg hatch, number of mines formed, larval survival, number of pupae formed, size and weight of pupae, percentage pupation, number of adults formed, percentage emergence, size and weight of adults, sex ratio, adult longevity, and their reproductive performance. The results showed that L. trifolii females laid fewer eggs on the upper leaves, which were poor hosts for larvae. However, a comparison of oviposition behavior between the middle and lower leaves showed that the data did not fit the oviposition preference–offspring performance hypothesis, which postulates that females preferentially oviposit on hosts on which larvae perform best. Females exhibited a preference for the larger, older, lower leaves, although the middle leaves were superior for the growth and development of the young stages. It is hypothesized that adult ovipositional preference for the older, larger, and thicker leaves of the lower foliage may be influenced by factors other than resource quality for larvae.
Mechanisms involved in the control of pheromone production in female moths: recent developments
Authors: Rafaeli Ada
Published: April 2005

Species‐specific pheromone blends of nocturnal female moths, derived from fatty acid precursors, are produced and released for mate‐finding, and are initiated by the circadian, trophic hormone, Pheromone Biosynthesis Activating Neuropeptide (PBAN). PBAN, produced in the sub‐oesophageal ganglion, is a 33 amino acid neuropeptide with a minimum active core in its FXPRLamide C‐terminal. PBAN acts directly on pheromone gland cells of mature females by binding to a specific G‐protein‐coupled membrane receptor (GPCR), and thereby initiating a signal transduction cascade involving calcium and cAMP. This discussion will review recent developments concerning the identification of the PBAN GPCR, its regulation by juvenile hormone (JH), and its mode of action at the level of the pheromone biosynthetic pathway. The discussion will also include recent developments concerning events occurring as a result of the transfer of pheromonostatic compounds of male origin after mating.
Do grains whisper for help? Evidence for herbivore‐induced synomones in wheat grains
Authors: Steidle Johannes L.M. , Fischer André , Gantert Cornelia
Published: April 2005

Thus far, the release of herbivore‐induced synomones (HIS) has almost exclusively been demonstrated in somatic plant tissue. Here we present evidence for the production of HIS from reproductive tissue, i.e., seeds. The study system consisted of wheat grains (Triticum aestivum L., Poaceae) infested by larvae of the granary weevil Sitophilus granarius L. (Coleoptera, Curculionidae), which in turn are attacked by the parasitic wasp Lariophagus distinguendus Förster (Hymenoptera, Pteromalidae). The use of potential chemical signals from the infested grain for host recognition of L. distinguendus was studied with weevil‐infested grains that had developed under a range of humidity conditions. Wasps always performed longer antennal drumming on infested than healthy grains, demonstrating that they were able to recognize infested grains under all humidity conditions. In grains developed at a high humidity (75% r.h.), host recognition is enabled by chemical signals arising from the host faeces which densely cover infested grains. However, in grains from a low humidity (45% r.h.) almost no faeces are present, indicating that other cues are used by the wasp. Control experiments revealed that these other cues are neither chemical signals from faeces contaminations, volatiles from faeces nor host larvae inside the grain, movement of host larvae, or moisture content of infested grains. Therefore, wasp recognition of infested grains in low humidity conditions is probably based on chemical signals from the grain itself that are induced by the feeding of granary weevil larva. Further experiments revealed that infested grains increase their viability when granary weevil larvae are killed by the idiobiont L. distinguendus. This justifies the categorisation of potential signals from the grain as HIS. To our knowledge, this is the only system where potential HIS in plant seeds have been studied. We discuss whether potential HIS are actively produced by infested grains or are a by‐product of grain metabolism.
FINANCING INNOVATIONS AND CAPITAL STRUCTURE CHOICES
Authors: Damodaran Aswath
Published: April 2005

The last two decades have seen a stream of innovation in financial markets, especially in corporate bonds. Some of these innovations—notably, hybrid debt—have provided firms with more flexibility in designing cash flows on borrowings, allowing them to match cash flows on financing more closely to cash flows on assets. In so doing, the use of such innovative securities has increased corporate debt capacity and hence firm value.

But if such changes have been mostly good news for corporate treasurers, the relentless torrent of innovation has sometimes resulted in firms issuing these new securities for the wrong reasons. Some have done so to take advantage of loopholes in the way ratings agencies and regulatory agencies define debt and equity—and others to exploit perceived pricing anomalies—without considering the effect of such securities on the firm's overall risk profile. In this context, it is worth noting that as corporate bonds have become more complex, investment bankers have made themselves indispensable to the process by providing pricing as well as selling support. This article aims to help managers distinguish when financing with complex securities serves their company's interests, and when it can end up hurting them.
RECENT DEVELOPMENTS IN THE HIGH YIELD MARKET
Authors: Bouhuys Henk , Jaeger Stephan
Published: April 2005

After a period of virtually uninterrupted growth stretching from 1994 through the first half of 1998, the high yield market suffered a sudden, jarring setback that led to the widest credit spreads seen since 1991. With the global spread of the Asian flu in August, spreads became so wide that the market for new issues virtually ceased. The most frequently used word to describe conditions in the high yield market during this period was “carnage.”

Then, in response to the Federal Reserve's series of rate cuts beginning in late September, the market staged a modest recovery that carried through the end of the year. Since then, the market has experienced several periods of alternating strength and weak ness, and new issuance has moderated relative to the record levels of a year ago. This article examines last year's volatile new issue environment and analyzes recent developments that can be expected to influence financing opportunities for corporate issuers in the near future.
Determination of Microvessel Permeability and Tissue Diffusion Coefficient of Solutes by Laser Scanning Confocal Microscopy
Authors: Fu Bingmei M. , Adamson Roger H. , Curry Fitz-Roy E.
Published: April 2005

Interstitium contains a matrix of fibrous molecules that creates considerable resistance to water and solutes in series with the microvessel wall. On the basis of our preliminary studies (Adamson et al., 1994, Microcirculation 1(4), pp. 251–265; Fu et al., 1995 Am. J. Physiol. 269(38), pp. H2124–H2140), by using laser-scanning confocal microscopy and a theoretical model for interstitial transport, we determined both microvessel solute permeability (P) and solute tissue diffusion coefficient (Dt) of α-lactalbumin (Stokes radius 2.01nm) from the rate of tissue solute accumulation and the radial concentration gradient around individually perfused microvessel in frog mesentery. Pα‐lactalbumin is 1.7±0.7(SD)×10−6cm∕s(n=6). Dt∕Dfree for α-lactalbumin is 27%±5%(SD)(n=6). This value of Dt∕Dfree is comparable to that for small solute sodium fluorescein (Stokes radius 0.45nm), while Pα‐lactalbumin is only 3.4% of Psodiumfluorescein. Our results suggest that frog mesenteric tissue is much less selective to solutes than the microvessel wall.
Computational Modeling of the Mechanical Behavior of the Cerebrospinal Fluid System
Authors: Kurtcuoglu Vartan , Poulikakos Dimos , Ventikos Yiannis
Published: April 2005

A computational fluid dynamics (CFD) model of the cerebrospinal fluid system was constructed based on a simplified geometry of the brain ventricles and their connecting pathways. The flow is driven by a prescribed sinusoidal motion of the third ventricle lateral walls, with all other boundaries being rigid. The pressure propagation between the third and lateral ventricles was examined and compared to data obtained from a similar geometry with a stenosed aqueduct. It could be shown that the pressure amplitude in the lateral ventricles increases in the presence of aqueduct stenosis. No difference in phase shift between the motion of the third ventricle walls and the pressure in the lateral ventricles because of the aqueduct stenosis could be observed. It is deduced that CFD can be used to analyze the pressure propagation and its phase shift relative to the ventricle wall motion. It is further deduced that only models that take into account the coupling between ventricles, which feature a representation of the original geometry that is as accurate as possible and which represent the ventricle boundary motion realistically, should be used to make quantitative statements on flow and pressure in the ventricular space.
Interpolating Three-Dimensional Kinematic Data Using Quaternion Splines and Hermite Curves
Authors: Coburn James , Crisco Joseph J.
Published: April 2005

Kinematic interpolation is an important tool in biomechanics. The purpose of this work is to describe a method for interpolating three-dimensional kinematic data, minimizing error while maintaining ease of calculation. This method uses cubic quaternion and hermite interpolation to fill gaps between kinematic data points. Data sets with a small number of samples were extracted from a larger data set and used to validate the technique. Two additional types of interpolation were applied and then compared to the cubic quaternion interpolation. Displacement errors below 2% using the cubic quaternion method were achieved using 4% of the total samples, representing a decrease in error over the other algorithms.
Viscoelastic Properties of Single Attached Cells Under Compression
Authors: Peeters Emiel A.G. , Oomens Cees W.J. , Bouten Carlijn V.C. , Bader Dan L. , Baaijens Frank P.T.
Published: April 2005

The viscoelastic properties of single, attached C2C12 myoblasts were measured using a recently developed cell loading device. The device allows global compression of an attached cell, while simultaneously measuring the associated forces. The viscoelastic properties were examined by performing a series of dynamic experiments over two frequency decades (0.1-10Hz) and at a range of axial strains (∼10-40%). Confocal laser scanning microscopy was used to visualize the cell during these experiments. To analyze the experimentally obtained force-deformation curves, a nonlinear viscoelastic model was developed. The nonlinear viscoelastic model was able to describe the complete series of dynamic experiments using only a single set of parameters, yielding an elastic modulus of 2120±900Pa for the elastic spring, an elastic modulus of 1960±1350 for the nonlinear spring, and a relaxation time constant of 0.3±0.12s. To our knowledge, it is the first time that the global viscoelastic properties of attached cells have been quantified over such a wide range of strains. Furthermore, the experiments were performed under optimal environmental conditions and the results are, therefore, believed to reflect the viscoelastic mechanical behavior of cells, such as would be present in vivo.
The Cardiocoil Stent-Artery Interaction
Authors: Brand Moshe , Ryvkin Michael , Einav Shmuel , Slepyan Leonid
Published: April 2005

An analytical approach for the mechanical interaction of the self-expanding Cardiocoil stent with the stenosed artery is presented. The damage factor as the contact stress at the stent-artery interface is determined. The stent is considered as an elastic helical rod having a nonlinear pressure-displacement dependence, while the artery is modeled by an elastic cylindrical shell. An influence of a moderate relative thickness of the shell is estimated. The equations for both the stent and the artery are presented in the stent-associated helical coordinates. The computational efficiency of the model enabled to carry out a parametric study of the damage factor. Comparative examinations are conducted for the stents made of the helical rods with circular and rectangular cross sections. It was found, in particular, that, under same other conditions, the damage factor for the stent with a circular cross section may be two times larger than that for a rectangular one.
Causal Protein-Signaling Networks Derived from Multiparameter Single-Cell Data
Authors: Sachs Karen , Perez Omar , Pe'er Dana , Lauffenburger Douglas A. , Nolan Garry P.
Published: April 2005

Machine learning was applied for the automated derivation of causal influences in cellular signaling networks. This derivation relied on the simultaneous measurement of multiple phosphorylated protein and phospholipid components in thousands of individual primary human immune system cells. Perturbing these cells with molecular interventions drove the ordering of connections between pathway components, wherein Bayesian network computational methods automatically elucidated most of the traditionally reported signaling relationships and predicted novel interpathway network causalities, which we verified experimentally. Reconstruction of network models from physiologically relevant primary single cells might be applied to understanding native-state tissue signaling biology, complex drug actions, and dysfunctional signaling in diseased cells.
Postsecretory Hydrolysis of Nectar Sucrose and Specialization in Ant/Plant Mutualism
Authors: Heil M. , Rattke J. , Boland W.
Published: April 2005

Obligate
Acacia
ant plants house mutualistic ants as a defense mechanism and provide them with extrafloral nectar (EFN). Ant/plant mutualisms are widespread, but little is known about the biochemical basis of their species specificity. Despite its importance in these and other plant/animal interactions, little attention has been paid to the control of the chemical composition of nectar. We found high invertase (sucrose-cleaving) activity in
Acacia
EFN, which thus contained no sucrose. Sucrose, a disaccharide common in other EFNs, usually attracts nonsymbiotic ants. The EFN of the ant acacias was therefore unattractive to such ants. The
Pseudomyrmex
ants that are specialized to live on
Acacia
had almost no invertase activity in their digestive tracts and preferred sucrose-free EFN. Our results demonstrate postsecretory regulation of the carbohydrate composition of nectar.
CD4+T Cells but Not CD8+or γδ+Lymphocytes Are Required for Host Protection againstMycobacterium aviumInfection and Dissemination through the Intestinal Route
Authors: Petrofsky Mary , Bermudez Luiz E.
Published: April 2005

DisseminatedMycobacterium aviuminfection is common in AIDS patients that do not receive anti-AIDS therapy and in patients for whom therapy fails.M. aviumis commonly acquired by ingestion, and a large number of AIDS patients haveM. aviumin their intestinal tracts. To better understand the dynamics of the infection in patients with AIDS, we studied orally infected mice. To determine if immunocompetent mice challenged orally withM. aviumcan develop protection against the infection, and if so, which cell population(s) is responsible for the protection, we exposed wild-type as well as CD4−/−, CD8−/−, and γδ−/−knockout mice to low concentrations ofM. aviumstrain 101 given orally, followed by treatment with azithromycin. After 1 month, the mice were challenged with kanamycin-resistantM. avium104. Only CD4+T cells appeared to be required for protection against the second challenge. Both CD4+and CD8+T cells produced comparable amounts of gamma interferon after the first exposure to the bacterium. Tumor necrosis factor alpha was elevated in CD4+T cells but not in CD8+T cells. Following exposure to a small inoculum of mycobacteria orally, wild-type mice did not develop disseminated infection for approximately 4 months, although viable bacteria could be observed in the mesenteric lymph nodes. The ingestion of small numbers ofM. aviumcells induces a protective immune response in the intestines against subsequent infection. However, the bacteria remain viable in intestinal lymph nodes and might disseminate later.
Trypanosomes Expressing a Mosaic Variant Surface Glycoprotein Coat Escape Early Detection by the Immune System
Authors: Dubois Melissa E. , Demick Karen P. , Mansfield John M.
Published: April 2005

Host resistance to African trypanosomiasis is partially dependent on an early and strong T-independent B-cell response against the variant surface glycoprotein (VSG) coat expressed by trypanosomes. The repetitive array of surface epitopes displayed by a monotypic surface coat, in which identical VSG molecules are closely packed together in a uniform architectural display, cross-links cognate B-cell receptors and initiates T-independent B-cell activation events. However, this repetitive array of identical VSG epitopes is altered during the process of antigenic variation, when former and nascent VSG proteins are transiently expressed together in a mosaic surface coat. Thus, T-independent B-cell recognition of the trypanosome surface coat may be disrupted by the introduction of heterologous VSG molecules into the coat structure. To address this hypothesis, we transformedTrypanosoma brucei rhodesienseLouTat 1 with the 117 VSG gene fromTrypanosoma brucei bruceiMiTat 1.4 in order to produce VSG double expressers; coexpression of the exogenous 117 gene along with the endogenous LouTat 1 VSG gene resulted in the display of a mosaic VSG coat. Results presented here demonstrate that the host's ability to produce VSG-specific antibodies and activate B cells during early infection with VSG double expressers is compromised relative to that during infection with the parental strain, which displays a monotypic coat. These findings suggest a previously unrecognized mechanism of immune response evasion in which coat-switching trypanosomes fail to directly activate B cells until coat VSG homogeneity is achieved. This process affords an immunological advantage to trypanosomes during the process of antigenic variation.
Legionella pneumophilaEvades Gamma Interferon-Mediated Growth Suppression through Interleukin-10 Induction in Bone Marrow-Derived Macrophages
Authors: Yoshizawa Sadako , Tateda Kazuhiro , Matsumoto Tetsuya , Gondaira Fumio , Miyazaki Shuichi , Standiford Theodore J. , Yamaguchi Keizo
Published: April 2005

We examined the roles of Th1-Th2 cytokine cross talk inLegionella pneumophila-infected bone marrow-derived (BM) macrophages in the presence of costimulation with interleukin-12 (IL-12) and IL-18. Treatment with gamma interferon (IFN-γ) alone or treatment with IL-12 in combination with IL-18 resulted in a 3- or 2-log reduction in bacterial numbers, respectively, in BM macrophages, whereas treatment with IL-12 or IL-18 alone had no effect. Significant amounts of IFN-γ were detected in the culture supernatants of infected macrophages stimulated with IL-12 and IL-18 in combination but not independently. Neutralization of IFN-γ by antibody completely abolished the growth inhibitory effects of IL-12 and IL-18. Interestingly, higher infectivity ratios ofL. pneumophilaor the addition of increasing concentrations of heat-killed bacteria (HKB) suppressed the production of IFN-γ, which resulted in the increased intracellular growth of bacteria. Significant amounts of IL-10 were detected in culture supernatants whenLegionella-infected macrophages were cocultured with HKB. Furthermore, neutralization of IL-10 by antibody resulted in an increase in IFN-γ production by infected BM macrophages when cocultured with HKB. Treatment of HKB with trypsin but not polymyxin B attenuated the growth-promoting effects of HKB, suggesting the involvement of a protein component(s) in regulation of the growth ofL. pneumophila. These findings demonstrate a crucial role of Th1-Th2 cross talk inL. pneumophila-infected BM macrophages. Our results also suggest thatL. pneumophilamodulates the cytokine balance from IFN-γ-driven Th1 to more Th2 responses, likely through the induction of IL-10 by a bacterial protein component(s). These data provide new insights not only into the cellular mechanisms of Th1-Th2 cross talk inLegionella-infected macrophages but also into the pathogenesis ofL. pneumophilapneumonia in humans.
Helicobacter pyloriBinds to CD74 on Gastric Epithelial Cells and Stimulates Interleukin-8 Production
Authors: Beswick Ellen J. , Bland David A. , Suarez Giovanni , Barrera Carlos A. , Fan Xuejung , Reyes Victor E.
Published: April 2005

The pathogenesis associated withHelicobacter pyloriinfection requires consistent contact with the gastric epithelium. Although several cell surface receptors have been suggested to play a role in adhesion, the bacterium-host interactions that elicit host responses are not well defined. This study investigated the interaction ofH. pyloriwith the class II major histocompatibility complex (MHC)-associated invariant chain (Ii; CD74), which was found to be highly expressed by gastric epithelial cells. Bacterial binding was increased when CD74 surface expression was increased by gamma interferon (IFN-γ) treatment or by fibroblast cells transfected with CD74, while binding was decreased by CD74 blocking antibodies, enzyme cleavage of CD74, and CD74-coated bacteria.H. pyloriwas also shown to bind directly to affinity-purified CD74 in the absence of class II MHC. Cross-linking of CD74 and the engagement of CD74 were verified to stimulate IL-8 production by unrelated cell lines expressing CD74 in the absence of class II MHC. Increased CD74 expression by cells increased IL-8 production in response toH. pylori, and agents that block CD74 decreased these responses. The binding ofH. pylorito CD74 presents a novel insight into an initial interaction ofH. pyloriwith the gastric epithelium that leads to upregulation of inflammatory responses.
Role of Interleukin-6 in Mortality from and Physiologic Response to Sepsis
Authors: Remick Daniel G. , Bolgos Gerald , Copeland Shannon , Siddiqui Javed
Published: April 2005

Previous studies have suggested that interleukin-6 (IL-6) serves as both a marker and a mediator for the severity of sepsis. We tested whether interleukin 6 knockout (IL-6KO) mice were more susceptible to sepsis mortality induced by cecal ligation and puncture. IL-6KO and wild-type (WT) mice were subjected to increasing degrees of sepsis severity. Physiologic support was given with fluids and appropriate antibiotics. Plasma IL-6 levels were determined 6 h after the onset of sepsis, and a complete hematologic profile was performed on day 2. As expected, increasing sepsis severity resulted in greater and more rapid mortality. However, the mortality was nearly identical in the IL-6KO and WT mice. All WT septic mice had high plasma levels of IL-6 6 h after the onset of sepsis, while IL-6KO were near or below the lower limit of detection. Among the WT mice, mortality was significantly higher in mice with plasma IL-6 >3,000 pg/ml. Both IL-6KO and WT mice destined to die in the early stages of sepsis had substantial and nearly identical weight gain in the first 24 h. However, at later stages the WT mice had significantly greater weight loss than the KO mice. The KO mice failed to develop the characteristic hypothermia within the first 24 h of severe sepsis routinely observed in the WT mice. These data demonstrate that IL-6 serves as a marker of disease severity in sepsis and does modulate some physiologic responses, but complete lack of IL-6 does not does not alter mortality due to sepsis.
The Surface Protein Pls of Methicillin-Resistant
Staphylococcus aureus
Is a Virulence Factor in Septic Arthritis
Authors: Josefsson Elisabet , Juuti Katri , Bokarewa Maria , Kuusela Pentti
Published: April 2005

Pls, a surface protein of certain methicillin-resistant
Staphylococcus aureus
strains, is associated with poor bacterial adherence to solid-phase fibronectin and immunoglobulin G, as well as with reduced invasion of cultured epithelial cells. Here the importance of Pls for the development of septic arthritis and sepsis was investigated by using a mouse model. Mice inoculated with a
pls
knockout mutant developed a much milder arthritis and showed less grave weight reduction than mice infected with the wild-type Pls
+
clinical isolate. Also, the
pls
mutant induced a significantly lower frequency of mortality than the wild-type strain. The bacterial load of the kidneys was larger in mice infected with the Pls
+
strain than in animals challenged with the
pls
mutant. However, there was no evident inflammatory effect due to the Pls molecule alone, as indicated by knee injection of purified Pls. In conclusion, the results show that Pls is a virulence factor for septic arthritis and sepsis.
Identification of Genes Required for Avian
Escherichia coli
Septicemia by Signature-Tagged Mutagenesis
Authors: Li Ganwu , Laturnus Claudia , Ewers Christa , Wieler Lothar H.
Published: April 2005

Infections with avian pathogenic
Escherichia coli
(APEC) cause colibacillosis, an acute and largely systemic disease resulting in significant economic losses in poultry industry worldwide. Although various virulence-associated genes have been identified in APEC, their actual role in pathogenesis is still not fully understood, and, furthermore, certain steps of the infection process have not been related to previously identified factors. Here we describe the application of a signature-tagged transposon mutagenesis (STM) approach to identify critical genes required for APEC infections in vivo. Twenty pools of about 1,800 IMT5155 (O2:H5) mutants were screened in an infection model using 5-week-old chickens, and potentially attenuated mutants were subjected to a secondary screen and in vivo competition assays to confirm their attenuation. A total of 28 genes required for
E. coli
septicemia in chickens were identified as candidates for further characterization. Among these disrupted genes, six encode proteins involved in biosynthesis of extracellular polysaccharides and lipopolysaccharides; two encode iron transporters that have not been previously characterized in APEC in in vivo studies, and four showed similarity to membrane or periplasmic proteins. In addition, several metabolic enzymes, putative proteins with unknown function, and open reading frames with no similarity to other database entries were identified. This genome-wide analysis has identified both novel and previously known factors potentially involved in pathogenesis of APEC infection.
Characterization of
Salmonella
-Induced Cell Death in Human Macrophage-Like THP-1 Cells
Authors: Valle Eulalia , Guiney Donald G.
Published: April 2005

Salmonella
strains are facultative intracellular pathogens that produce marked cytopathology during infection of host cells. Different forms of cytopathic effects have been associated with the virulence systems encoded by the two
Salmonella
pathogenicity islands (SPI-1 and SPI-2) and the
spv
locus. We used
Salmonella enterica
serovar Dublin to investigate the induction of cytopathology during infection of the human macrophage-like cell line THP-1. Analysis of host cells by flow cytometry using a fluorescent terminal deoxynucleotidyltransferase dUTP-biotin nick end labeling (TUNEL) assay revealed that 70% of THP-1 cells showed DNA fragmentation after 4 h of infection, increasing to greater than 90% by 5.5 h. Moreover, the results showed that gentamicin-killed or chloramphenicol-treated bacteria did not induce DNA fragmentation. Serovar Dublin strains with mutations in SPI-1, SPI-2, or
spvB
induced these cytopathic effects similar to wild-type bacteria. In contrast, a mutation in the
phoP
regulatory gene abolished DNA fragmentation in the TUNEL assay. Caspase-3 activation was detected during
Salmonella
infection of THP-1 cells, but caspase-8 and caspase-9 activities were not found. However, inhibition of caspase-3 did not block
Salmonella
-induced DNA fragmentation. These results identify a previously undetected apoptotic effect in
Salmonella
-infected cells that is dependent on
phoP
gene function.