bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluid structure interaction of patient specific abdominal aortic aneurysms: a comparison with solid stress models
Authors: Leung James H , Wright Andrew R , Cheshire Nick , Crane Jeremy , Thom Simon A , Hughes Alun D , Xu Yun
Published: May 2006

Background

Abdominal aortic aneurysm (AAA) is a dilatation of the aortic wall, which can rupture, if left untreated. Previous work has shown that, maximum diameter is not a reliable determinant of AAA rupture. However, it is currently the most widely accepted indicator. Wall stress may be a better indicator and promising patient specific results from structural models using static pressure, have been published. Since flow and pressure inside AAA are non-uniform, the dynamic interaction between the pulsatile flow and wall may influence the predicted wall stress. The purpose of the present study was to compare static and dynamic wall stress analysis of patient specific AAAs.

Method

Patient-specific AAA models were created from CT scans of three patients. Two simulations were performed on each lumen model, fluid structure interaction (FSI) model and static structural (SS) model. The AAA wall was created by dilating the lumen with a uniform 1.5 mm thickness, and was modeled as a non-linear hyperelastic material. Commercial finite element code Adina 8.2 was used for all simulations. The results were compared between the FSI and SS simulations.

Results

Results are presented for the wall stress patterns, wall shear stress patterns, pressure, and velocity fields within the lumen. It is demonstrated that including fluid flow can change local wall stresses slightly. However, as far as the peak wall stress is concerned, this effect is negligible as the difference between SS and FSI models is less than 1%.

Conclusion

The results suggest that fully coupled FSI simulation, which requires considerable computational power to run, adds little to rupture risk prediction. This justifies the use of SS models in previous studies.
HIV-1 associated dementia: symptoms and causes
Authors: Ghafouri Mohammad , Amini Shohreh , Khalili Kamel , Sawaya Bassel E
Published: May 2006

Despite the use of highly active antiretroviral therapy (HAART), neuronal cell death remains a problem that is frequently found in the brains of HIV-1-infected patients. HAART has successfully prevented many of the former end-stage complications of AIDS, however, with increased survival times, the prevalence of minor HIV-1 associated cognitive impairment appears to be rising among AIDS patients. Further, HIV-1 associated dementia (HAD) is still prevalent in treated patients as well as attenuated forms of HAD and CNS opportunistic disorders. HIV-associated cognitive impairment correlates with the increased presence in the CNS of activated, though not necessarily HIV-1-infected, microglia and CNS macrophages. This suggests that indirect mechanisms of neuronal injury and loss/death occur in HIV/AIDS as a basis for dementia since neurons are not themselves productively infected by HIV-1. In this review, we discussed the symptoms and causes leading to HAD. Outcome from this review will provide new information regarding mechanisms of neuronal loss in AIDS patients.
A paradox of immunodeficiency and inflammation in human aging: lessons learned from apoptosis
Authors: Gupta Sudhir , Agrawal Anshu , Agrawal Sudhanshu , Su Houfen , Gollapudi Sastry
Published: May 2006

Aging is associated with a paradox of immunodeficiency and inflammation (an evidence of hyperactive immune system). Apoptosis is associated with cellular depletion and suppression of inflammatory response. In this brief review, we will present evidence for the role of increased apoptosis in immunodeficiency and paradoxical increased inflammation associated with human aging. In particular, a role of apoptotic cells in failure to generate anti-inflammatory responses and directly activating inflammatory responses will be discussed.
A nucleolar localizing Rev binding element inhibits HIV replication
Authors: Michienzi Alessandro , De Angelis Fernanda G , Bozzoni Irene , Rossi John J
Published: May 2006

The Rev protein of the human immunodeficiency virus (HIV) facilitates the nuclear export of intron containing viral mRNAs allowing formation of infectious virions. Rev traffics through the nucleolus and shuttles between the nucleus and cytoplasm. Rev multimerization and interaction with the export protein CRM1 takes place in the nucleolus. To test the importance of Rev nucleolar trafficking in the HIV-1 replication cycle, we created a nucleolar localizing Rev Response Element (RRE) decoy and tested this for its anti-HIV activity. The RRE decoy provided marked inhibition of HIV-1 replication in both the CEM T-cell line and in primary CD34+ derived monocytes. These results demonstrate that titration of Rev in the nucleolus impairs HIV-1 replication and supports a functional role for Rev trafficking in this sub-cellular compartment.
The association of psychological stress and health related quality of life among patients with stroke and hypertension in Gaza Strip
Authors: Baune BT , Aljeesh Y
Published: May 2006

Background

The study was performed to investigate the association of psychological stress and quality of life (QOL) among patients with the cardiovascular disease (CVD) of hypertension plus stroke or hypertension only.

Methods

The WHOQOL-BREF questionnaire was applied to 112 hypertensive patients with hypertension plus stroke and 224 hypertensive patients without stroke. Psychological stress was assessed with SCL-90. Means scale scores were compared using student-t-test and predictors of QOL were calculated with covariance analysis.

Results

Patients with stroke had a significant lower QOL than patients without stroke and a significantly higher level of stress (p < 0.01). In analyses of covariance psychological stress was significantly correlated to all domains of QOL among non-stroke patients. The same psychological and sociodemographic factors showed little impact on the stroke patients in these multivariable analyses. In these models psychological stress had a significant impact on the global domain of QOL among stroke patients. Income and gender were the only sociodemographic factors being significantly associated with the physical (education) and social (gender) domains of QOL in stroke patients.

Conclusion

Psychological stress was strongly correlated with all domains of QOL in patients without stroke and was only partly associated with QOL among patients with stroke. Future studies should investigate if psychological stress is a factor suitable for educational and psychological interventions aiming at stress reduction in CVD patients which might substantially contribute to better health related quality of life in these patients.
Estimating Downtime in Loss Modeling
Authors: Comerio Mary C.
Published: May 2006

Downtime includes the time necessary to plan, finance, and complete repairs on facilities damaged in earthquakes or other disasters. It is an essential component of loss modeling, because it is one measure of operational failure in lifelines and business interruption in buildings. Data from building repairs after the Loma Prieta and Northridge earthquakes, together with institutional risk management projections are used to define the rational and irrational components of downtime for buildings. Rational components include construction costs and time. Irrational situation-specific components take into account the time needed to mobilize for repairs and include financing, relocation of functions, workforce availability, regulatory changes, and economic uncertainty. To quantify these factors, the pace of recovery can be linked to the scale of damage in a stock of buildings in the affected region.
Analytical Models for the Seismic Performance of Gypsum Drywall Partitions
Authors: Kanvinde Amit M. , Deierlein Gregory G.
Published: May 2006

Gypsum drywall partitions may contribute significantly to the lateral strength and stiffness of woodframe structures, whether or not the walls are explicitly designed for that purpose. This paper proposes analytical models to determine the lateral shear strength and initial elastic stiffness of wood-framed gypsum wall panels, taking into account the effects of wall geometry, door and window openings, connector type and spacing, and wall boundary conditions. The strength and stiffness models are incorporated in a multilinear curve to describe the monotonic lateral shear versus deformation response of the walls. Additional parameters to calibrate the response of a peak-oriented hysteretic cyclic model are also proposed, thus making the models suitable for nonlinear time-history simulations of woodframe buildings. The models are developed and validated using published data from 16 shear tests of full-scale gypsum wall panels.
Effects of Fling Step and Forward Directivity on Seismic Response of Buildings
Authors: Kalkan Erol , Kunnath Sashi K.
Published: May 2006

This paper investigates the consequences of well-known characteristics of near-fault ground motions on the seismic response of steel moment frames. Additionally, idealized pulses are utilized in a separate study to gain further insight into the effects of high-amplitude pulses on structural demands. Simple input pulses were also synthesized to simulate artificial fling-step effects in ground motions originally having forward directivity. Findings from the study reveal that median maximum demands and the dispersion in the peak values were higher for near-fault records than far-fault motions. The arrival of the velocity pulse in a near-fault record causes the structure to dissipate considerable input energy in relatively few plastic cycles, whereas cumulative effects from increased cyclic demands are more pronounced in far-fault records. For pulse-type input, the maximum demand is a function of the ratio of the pulse period to the fundamental period of the structure. Records with fling effects were found to excite systems primarily in their fundamental mode while waveforms with forward directivity in the absence of fling caused higher modes to be activated. It is concluded that the acceleration and velocity spectra, when examined collectively, can be utilized to reasonably assess the damage potential of near-fault records.
The Reinforced Cut Wall (RCW): A Low-Cost Base Dissipator for Masonry Buildings
Authors: Sassu Mauro
Published: May 2006

The design criteria for a new, low-cost base dissipation technique for simple masonry buildings are presented together with the results of some numerical analyses. The proposed apparatus, termed the “reinforced cut wall” (RCW), is made up of a layer of weak mortar (50 mm) and a 4- mm-thick elastomer membrane sheath laid between the foundation and base of the wall, which is further reinforced by a series of vertical steel rods (8–12 mm in diameter) connecting it to the foundation. Experimental trials have been performed on a sample set of dissipators in order to establish their mechanical properties and define suitable assembly techniques. Numerical simulations, consisting of incremental nonlinear static analyses, of several types of masonry buildings highlight the system's efficient performance in terms of force-displacement law. For moderate horizontal actions, the RCW does not cause relevant foundation-base displacement. However, when a prescribed force limit is exceeded, friction behavior of the weak layers of the RCW permit inelastic deformation along both horizontal directions, while the vertical steel rods ensure an elastic restoring force for rocking movements as well. Furthermore, the RCW provides the added benefit of isolating the structure from ground humidity.
Ground Motion Intensity Measures for Liquefaction Hazard Evaluation
Authors: Kramer Steven L. , Mitchell Robert A.
Published: May 2006

The requirements of performance-based earthquake engineering place increasing importance on the optimal characterization of earthquake ground motions. With respect to liquefaction hazard evaluation, ground motions have historically been characterized by a combination of peak acceleration and earthquake magnitude, and more recently by Arias intensity. This paper introduces a new ground motion intensity measure, CAV5, and shows that excess pore pressure generation in potentially liquefiable soils is considerably more closely related to CAV5 than to other intensity measures, including peak acceleration and Arias intensity. CAV5 is shown to be an efficient, sufficient, and predictable intensity measure for rock motions used as input to liquefaction hazard evaluations. An attenuation relationship for CAV5 is presented and used in an example that illustrates the benefits of scaling bedrock motions to a particular value of CAV5, rather than to the historical intensity measures, for performance-based evaluation of liquefaction hazards.
The Recognition of Phonologically Assimilated Words Does Not Depend on Specific Language Experience
Authors: Mitterer Holger , Csépe Valéria , Honbolygo Ferenc , Blomert Leo
Published: May 2006

In a series of 5 experiments, we investigated whether the processing of phonologically assimilated utterances is influenced by language learning. Previous experiments had shown that phonological assimilations, such as /lean#bacon/→ [leam bacon], are compensated for in perception. In this article, we investigated whether compensation for assimilation can occur without experience with an assimilation rule using automatic event‐related potentials. Our first experiment indicated that Dutch listeners compensate for a Hungarian assimilation rule. Two subsequent experiments, however, failed to show compensation for assimilation by both Dutch and Hungarian listeners. Two additional experiments showed that this was due to the acoustic properties of the assimilated utterance, confirming earlier reports that phonetic detail is important in compensation for assimilation. Our data indicate that compensation for assimilation can occur without experience with an assimilation rule, in line with phonetic‐phonological theories that assume that speech production is influenced by speech‐perception abilities.
With the Future Behind Them: Convergent Evidence From Aymara Language and Gesture in the Crosslinguistic Comparison of Spatial Construals of Time
Authors: Núñez Rafael E. , Sweetser Eve
Published: May 2006

Cognitive research on metaphoric concepts of time has focused on differences between moving Ego and moving time models, but even more basic is the contrast between Ego‐ and temporal‐reference‐point models. Dynamic models appear to be quasi‐universal cross‐culturally, as does the generalization that in Ego‐reference‐point models, FUTURE IS IN FRONT OF EGO and PAST IS IN BACK OF EGO. The Aymara language instead has a major static model of time wherein FUTURE IS BEHIND EGO and PAST IS IN FRONT OF EGO; linguistic and gestural data give strong confirmation of this unusual culture‐specific cognitive pattern. Gestural data provide crucial information unavailable to purely linguistic analysis, suggesting that when investigating conceptual systems both forms of expression should be analyzed complementarily. Important issues in embodied cognition are raised: how fully shared are bodily grounded motivations for universal cognitive patterns, what makes a rare pattern emerge, and what are the cultural entailments of such patterns?
The Coordinated Interplay of Scene, Utterance, and World Knowledge: Evidence From Eye Tracking
Authors: Knoeferle Pia , Crocker Matthew W.
Published: May 2006

Two studies investigated the interaction between utterance and scene processing by monitoring eye movements in agent–action–patient events, while participants listened to related utterances. The aim of Experiment 1 was to determine if and when depicted events are used for thematic role assignment and structural disambiguation of temporarily ambiguous English sentences. Shortly after the verb identified relevant depicted actions, eye movements in the event scenes revealed disambiguation. Experiment 2 investigated the relative importance of linguistic/world knowledge and scene information. When the verb identified either only the stereotypical agent of a (nondepicted) action, or the (nonstereotypical) agent of a depicted action as relevant, verb‐based thematic knowledge and depicted action each rapidly influenced comprehension. In contrast, when the verb identified both of these agents as relevant, the gaze pattern suggested a preferred reliance of comprehension on depicted events over stereotypical thematic knowledge for thematic interpretation. We relate our findings to language comprehension and acquisition theories.
Memory and Mystery: The Cultural Selection of Minimally Counterintuitive Narratives
Authors: Norenzayan Ara , Atran Scott , Faulkner Jason , Schaller Mark
Published: May 2006

We hypothesize that cultural narratives such as myths and folktales are more likely to achieve cultural stability if they correspond to a minimally counterintuitive (MCI) cognitive template that includes mostly intuitive concepts combined with a minority of counterintuitive ones. Two studies tested this hypothesis, examining whether this template produces a memory advantage, and whether this memory advantage explains the cultural success of folktales. In a controlled laboratory setting, Study 1 found that an MCI template produces a memory advantage after a 1‐week delay, relative to entirely intuitive or maximally counterintuitive cognitive templates. Using archival methods, Study 2 examined the cognitive structure of Grimm Brothers folktales. Compared to culturally unsuccessful folktales, those that were demonstrably successful were especially likely to fit an MCI template. These findings highlight the role of human memory processes in cultural evolution.
A Hierarchical Bayesian Model of Human Decision‐Making on an Optimal Stopping Problem
Authors: Lee Michael D.
Published: May 2006

We consider human performance on an optimal stopping problem where people are presented with a list of numbers independently chosen from a uniform distribution. People are told how many numbers are in the list, and how they were chosen. People are then shown the numbers one at a time, and are instructed to choose the maximum, subject to the constraint that they must choose a number at the time it is presented, and any choice below the maximum is incorrect. We present empirical evidence that suggests people use threshold‐based models to make decisions, choosing the first currently maximal number that exceeds a fixed threshold for that position in the list. We then develop a hierarchical generative account of this model family, and use Bayesian methods to learn about the parameters of the generative process, making inferences about the threshold decision models people use. We discuss the interesting aspects of human performance on the task, including the lack of learning, and the presence of large individual differences, and consider the possibility of extending the modeling framework to account for individual differences. We also use the modeling results to discuss the merits of hierarchical, generative and Bayesian models of cognitive processes more generally.
Arrows in Comprehending and Producing Mechanical Diagrams
Authors: Heiser Julie , Tversky Barbara
Published: May 2006

Mechanical systems have structural organizations—parts, and their relations—and functional organizations—temporal, dynamic, and causal processes—which can be explained using text or diagrams. Two experiments illustrate the role of arrows in diagrams of mechanical systems. In Experiment 1, people described diagrams with or without arrows, interpreting diagrams without arrows as conveying structural information and diagrams with arrows as conveying functional information. In Experiment 2, people produced sketches of mechanical systems from structural or functional descriptions. People spontaneously used arrows to indicate functional processes in diagrams. Arrows can play a powerful role in augmenting structural diagrams to convey dynamic, causal, or functional information.
Functional Expression of Mouse Relaxin and Mouse Relaxin-3 in the Lung from an Ebola Virus Glycoprotein-Pseudotyped Lentivirus via Tracheal Delivery
Authors: Silvertown Josh D. , Walia Jagdeep S. , Summerlee Alastair J. , Medin Jeffrey A.
Published: May 2006

The peptide hormone relaxin is a known modulator of connective tissue and the extracellular matrix by virtue of its ability to regulate matrix metalloproteinases (MMPs). Relaxin knockout mice exhibit age-related pulmonary fibrosis, and delivery of recombinant human H2 relaxin ameliorates fibrotic-like conditions in the mouse lung. We investigated whether lentiviral vectors (LVs) engineering the expression of murine relaxins could induce MMP activity in the mouse lung. Mouse relaxin and mouse relaxin-3 peptides engineered by recombinant LVs were biologically active as shown by stimulation of cAMP from both THP-1 and 293T cells stably expressing relaxin receptor LGR7 and by up-regulation of MMP-2 activity from primary C57BL/6 lung cell cultures. To provide the virions with enhanced tropism for the lung, LVs were pseudotyped with the Zaire strain of the Ebola virus glycoprotein (EboZ GP) and delivered by endotracheal intubation. LVs engineering luciferase pseudotyped with EboZ GP, but not with vesicular stomatitis virus glycoprotein resulted in successful LV transduction and transgene expression in C57BL/6 mouse lung by as early as d 4. Mice treated via tracheal delivery with EboZ GP pseudotyped LVs that engineered expression of mouse relaxins exhibited increased MMP-2 and MMP-9 activity in lung tissue up until the end of our study at d 21. Taken together, this study provides proof-of- principle that relaxin gene expression targeted to the mouse lungs can result in enhanced MMP activity offering potential for alleviating disease conditions characterized by dysregulation of extracellular matrix protein accumulation.
Derivatives of Z-Bisdehydrodoisynolic Acid Provide a New Description of the Binding-Activity Paradox and Selective Estrogen Receptor Modulator Activity
Authors: Adler Molly , Hou Yuqing , Sandrock Paul , Meyers Cal Y. , Winters Todd A. , Banz William J. , Adler Stuart
Published: May 2006

Z-Bisdehydrodoisynolic acid [(±)-Z-BDDA], an estrogenic carboxylic acid, is highly active in vivo yet binds poorly to estrogen receptors (ERs). Studies of Z-BDDA and its enantiomers demonstrate therapeutic potential as selective ER modulators; however, the activity vs. binding paradox has remained. One possible explanation is that the carboxylic acid group of Z-BDDA may be modified in vivo to an ester or amide. Synthesis of these derivatives showed the relative binding affinity (RBA) of the methyl ester for ERα and ERβ was increased approximately 14- and 20-fold, respectively, relative to the parent compound. Yet, this increased affinity did not result in increased reporter gene expression. In contrast, the amide showed an unexpected approximately 4-fold decrease in RBA to both ERs compared with the parent. The relationship among the RBAs of ester, acid, and amide is consistent with their predicted polarity, suggesting the carboxylic acid, and not the carboxylate of BDDA, binds to ERs. Studies at pH 6.5, 7.4, and 8.0 were consistent with a simple acid-base equilibrium model, with BDDA binding as the undissociated acid and with affinity equal to or exceeding that of estradiol, consistent with high in vivo potency. Furthermore, the alcohol BDD-OH also demonstrated high affinity and increased activity in gene expression assays. In addition to suggesting a resolution to the decades-old binding/activity paradox, these studies may provide a direction for definitive in vivo metabolic and pharmacokinetic studies and provide additional insight into the chemical and metabolic determinants of BBDA’s unique tissue selectivity and selective ER modulator activities.
SIM1 Overexpression Partially Rescues Agouti Yellow and Diet-Induced Obesity by Normalizing Food Intake
Authors: Kublaoui Bassil M. , Holder J. Lloyd , Tolson Kristen P. , Gemelli Terry , Zinn Andrew R.
Published: May 2006

Single-minded 1 (SIM1) mutations are associated with obesity in mice and humans. Haploinsufficiency of mouse Sim1 causes hyperphagic obesity with increased linear growth and enhanced sensitivity to a high-fat diet, a phenotype similar to that of agouti yellow and melanocortin 4 receptor knockout mice. To investigate the effects of increased Sim1 dosage, we generated transgenic mice that overexpress human SIM1 and examined their phenotype. Compared with wild-type mice, SIM1 transgenic mice had no obvious phenotype on a low-fat chow diet but were resistant to diet-induced obesity on a high-fat diet due to reduced food intake with no change in energy expenditure. The SIM1 transgene also completely rescued the hyperphagia and partially rescued the obesity of agouti yellow mice, in which melanocortin signaling is abrogated. Our results indicate that the melanocortin 4 receptor signals through Sim1 or its transcriptional targets in controlling food intake but not energy expenditure.
Role and Regulation of Nodal/Activin Receptor-Like Kinase 7 Signaling Pathway in the Control of Ovarian Follicular Atresia
Authors: Wang Hongmei , Jiang Jin-Yi , Zhu Cheng , Peng Chun , Tsang Benjamin K.
Published: May 2006

Although the role of the TGF β superfamily members in the regulation of ovarian folliculogenesis has been extensively studied, their involvement in follicular atresia is not well understood. In the present study, we have demonstrated for the first time that Nodal, a member of the TGF β superfamily, is involved in promoting follicular atresia as evidenced by the following: 1) colocalization of Nodal and its type I receptor Activin receptor-like kinase 7 (ALK7) proteins in the granulosa cells was only observed in atretic antral follicles, whereas they were present in theca cells and granulosa cells of healthy follicles, respectively; 2) addition of recombinant Nodal or overexpression of Nodal by adenoviral infection induced apoptosis of otherwise healthy granulosa cells; 3) constitutively active ALK7 (ALK7-ca) overexpression mimicked the function of Nodal in the induction of granulosa cell apoptosis. Furthermore, overexpression of Nodal or ALK7-ca increased phosphorylation and nuclear translocation of Smad2, decreased X-linked inhibitor of apoptotic proteins (Xiap) expression at both mRNA and protein level and phospho-Akt content, as well as triggered mitochondrial release of death proteins Smac/DIABLO, Omi/HtrA2, and cytochrome c in the granulosa cells. Dominant-negative Smad2 significantly attenuated ALK7-ca-induced down-regulation of Xiap and thus rescued granulosa cells from undergoing apoptosis. In addition, whereas up-regulation of Xiap significantly attenuated ALK7-ca-induced apoptosis, down-regulation of Xiap sensitized granulosa cells to ALK7-ca-induced apoptosis. Furthermore, ALK7-ca-induced apoptosis was significantly attenuated by forced expression of activated Akt, and Akt rescued granulosa cells from undergoing apoptosis via proteasome-mediated ALK7 degradation. Taken together, Nodal plays an atretogenic role in the ovary where it induces granulosa cell apoptosis through activation of Smad2, down-regulation of the key survival molecules Xiap and phospho-Akt, as well as the activation of mitochondrial death pathway.
Turkey and the European Union
Authors: Payne Donald M.
Published: May 2006

Donald M. Payne is a member of the US House of Representatives and is a senior member of the International Relations Committee. He is the ranking Democrat on the Subcommittee on Africa, Global Human Rights, and International Operations.
Modernity and Economic Nationalism in the Formation of Turkish Nationalism
Authors: Yilmaz Cevdet , Şahin Mustafa
Published: May 2006

Cevdet Yilmaz is general director of the European Union Directorate, State Planning Organization, Turkey. Mustafa Şahin is the former head of the European Studies Department, Center for Eurasian Strategic Studies, Turkey.
Protease Analysis by Neoepitope Approach Reveals the Activation of MMP-9 Is Achieved Proteolytically in a Test Tissue Cartilage Model Involved in Bone Formation
Authors: Lee Eunice R. , Lamplugh Lisa , Kluczyk Beata , Mort John S. , Leblond Charles Philippe
Published: May 2006

A principle of regulation of matrix metalloproteinase (MMP) activity has been introduced as the cysteine-switch mechanism of activation ( Springman et al. 1990 ). According to this mechanism, a critical Cys residue found in the auto-inhibitory propeptide domain of latent proenzyme is important to determine whether or not activation is turned on or off. The mechanism further allows for multiple modes of activation. To determine whether or not activation is accomplished proteolytically within a rat test cartilage model, protease analysis by the neoepitope approach, which relies upon a set of antibodies, was applied. One is used to identify the MMP-9 proenzyme bearing the critical cysteine residue, the other to identify any enzyme present bearing a new NH2-terminus 89FQTFD. This is indicative of MMP-9 lacking the cysteine switch. The antibody set has been applied to frozen tissue sections and analyzed by light and electron microscopic methods. Results reveal that activation of the MMP-9 protease involves limited proteolysis resulting in propeptide domain release. Here we report the observed changes of protease form to indigenous cells and extracellular matrix, thereby making it possible to uncover the features of MMP-9 activation within a specified set of tissue circumstances where a cartilage model is transformed into definitive bone. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.
A Novel Fluorescent Probe That Is Brain Permeable and Selectively Binds to Myelin
Authors: Wu Chunying , Tian Donghua , Feng Yue , Polak Paul , Wei Jingjun , Sharp Adam , Stankoff Bruno , Lubetzki Catherine , Zalc Bernard , Mufson Elliott J. , Gould Robert M. , Feinstein Douglas L. , Wang Yanming
Published: May 2006

Myelin is a multilayered glial cell membrane that forms segmented sheaths around large-caliber axons of both the central nervous system (CNS) and peripheral nervous system (PNS). Myelin covering insures rapid and efficient transmission of nerve impulses. Direct visual assessment of local changes of myelin content in vivo could greatly facilitate diagnosis and therapeutic treatments of myelin-related diseases. Current histologic probes for the visualization of myelin are based on antibodies or charged histochemical reagents that do not enter the brain. We have developed a series of chemical compounds including ( E,E)-1,4-bis(4′-aminostyryl)-2-dimethoxy-benzene termed BDB and the subject of this report, which readily penetrates the blood-brain barrier and selectively binds to the myelin sheath in brain. BDB selectively stains intact myelinated regions in wild-type mouse brain, which allows for delineation of cuprizone-induced demyelinating lesions in mouse brain. BDB can be injected IV into the brain and selectively detect demyelinating lesions in cuprizone-treated mice in situ. These studies justified further investigation of BDB as a potential myelin-imaging probe to monitor myelin pathology in vivo.
Breast Cancer Resistance Protein (BCRP/ABCG2) Is Expressed by Progenitor Cells/Reactive Ductules and Hepatocytes and Its Expression Pattern Is Influenced by Disease Etiology and Species Type: Possible Functional Consequences
Authors: Borght Sara Vander , Libbrecht Louis , Katoonizadeh Aezam , Pelt Jos van , Cassiman David , Nevens Frederik , Lommel Alfons Van , Petersen Bryon E. , Fevery Johan , Jansen Peter L. , Roskams Tania A.
Published: May 2006

Breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette transport protein that is expressed in several organs including the liver. Previous studies have shown that ABC transport proteins play an important pathophysiological role in several liver diseases. However, to date, expression pattern and possible role of BCRP in human liver diseases and animal models have not been studied in detail. Here we investigated the expression pattern of BCRP in normal liver, chronic parenchymal and biliary human liver diseases, and parallel in different rat models of liver diseases. Expression was studied by immunohistochemistry and additionally by RT-PCR analysis in Thy-1-positive rat oval cells. Bile ducts, hepatic progenitor cells, reactive bile ductules, and blood vessel endothelium were immunoreactive for BCRP in normal liver and all types of human liver diseases and in rat models. BCRP was expressed by the canalicular membrane of hepatocytes in normal and diseased human liver, but never in rat liver. Remarkably, there was also expression of BCRP at the basolateral pole of human hepatocytes, and this was most pronounced in chronic biliary diseases. In conclusion, BCRP positivity in the progenitor cells/reactive ductules could contribute to the resistance of these cells to cytotoxic agents and xenotoxins. Basolateral hepatocytic expression in chronic biliary diseases may be an adaptive mechanism to pump bile constituents back into the sinusoidal blood. Strong differences between human and rat liver must be taken into account in future studies with animal models.
Expression of the Human Copper Influx Transporter 1 in Normal and Malignant Human Tissues
Authors: Holzer Alison K. , Varki Nissi M. , Le Quynh T. , Gibson Michael A. , Naredi Peter , Howell Stephen B.
Published: May 2006

The major copper influx transporter, copper transporter 1 (hCTR1), controls the cellular accumulation of cisplatin in mammalian cells. The goal of this study was to determine the pattern of hCTR1 expression in normal and malignant human tissues. Tissue arrays were stained with an antibody specific for hCTR1 using standard immunohistochemical techniques. Particularly strong staining was noted in the α cells of the pancreatic islets, enteroendocrine cells of the gastric mucosa and bronchioles, C cells of the thyroid, and a subset of cells in the anterior pituitary. Frequency and intensity of hCTR1 staining in malignant tissues reflected the levels found in their normal tissue counterparts. For example, neither normal prostate nor prostate cancers expressed hCTR1, whereas it was commonly expressed in both normal colonic epithelium and in colon carcinomas. Strong staining was observed in a limited number of cases of carcinoid tumors, Ewing's sarcoma, and undifferentiated carcinomas. Although all tissues require copper, expression of hCTRI was highly variable among normal tissues and among the major human malignancies, with the highest levels found in enteroendocrine cells. No hCTR1 expression was found in several common types of cancer, suggesting that hCTR1 expression is not commonly enhanced by transformation.
Gc-Globulin: Roles in Response to Injury
Authors: Meier Ursula , Gressner Olav , Lammert Frank , Gressner Axel M
Published: May 2006

Background: Gc-globulin (vitamin D–binding protein) appears to have important functions in addition to its role as a carrier of vitamin D.

Approach: We reviewed recent studies focusing on the pathophysiologic functions and clinical significance of Gc-globulin.

Results: Serum concentrations of Gc-globulin, as determined by immunoassay techniques, are decreased in severe injury. The extent of the decrease may have prognostic significance for patient outcomes. Clinical studies and animal models have shown that Gc-globulin has an important role in the clearance of procoagulant actin from the circulation after its release during cell necrosis and tissue injury. Gc-globulin has other potential roles in responses to acute tissue injury through conversion to a macrophage-activating factor, neutrophil chemotactic activity, and enhancement of C5a-mediated signaling.

Conclusion: Considering the important physiologic roles of Gc-globulin in responses to tissue injury, such as clearance of actin, measurement of Gc-globulin may have value in directing the care of patients in many clinical disorders.
Nanodiagnostics: A New Frontier for Clinical Laboratory Medicine
Authors: Azzazy Hassan ME , Mansour Mai MH , Kazmierczak Steven C
Published: May 2006

Background: The use of nanotechnologies for diagnostic applications shows great promise to meet the rigorous demands of the clinical laboratory for sensitivity and cost-effectiveness. New nanodiagnostic tools include quantum dots (QDs), gold nanoparticles, and cantilevers. QDs, which are the most promising nanostructures for diagnostic applications, are semiconductor nanocrystals characterized by high photostability, single-wavelength excitation, and size-tunable emission. QDs and magnetic nanoparticles can be used for barcoding of specific analytes. Gold and magnetic nanoparticles are key components of the bio-barcode assay, which has been proposed as a future alternative to the PCR.

Methods: We examined articles published over the past 10 years investigating the use of QDs, gold nanoparticles, cantilevers, and other nanotechnologies in promising diagnostic applications.

Results: Several nanodiagnostic assays have been developed, including a QD-based assay capable of detecting biotinylated prostate-specific antigen (PSA) at 0.38 ng/L, a bio-barcode assay capable of detecting 30 amol/L PSA in a 10-μL sample, and another able to detect 50 molecules of the Alzheimer marker amyloid β-derived diffusible ligand in 10 μL of cerebrospinal fluid.

Conclusions: Nanodiagnostics promise increased sensitivity, multiplexing capabilities, and reduced cost for many diagnostic applications as well as intracellular imaging. Further work is needed to fully optimize these diagnostic nanotechnologies for clinical laboratory setting and to address the potential health and environmental risks related to QDs.
Material Behavior of Dredged Contaminated Sediments from Simple Laboratory and Oedometer Tests
Authors: Holme JK , Dokter L , Eek E , Jensen TG , Loken T , Breedveld GD
Published: May 2006

Contaminated sediments, near urbanized areas, usually have a high content of organic matter and therefore a high water content and low shear strength. During dredging, additional water is mixed with the sediment, increasing the water content even further. The resulting dredged material that has to be disposed will be very soft with a very low shear strength. As a result, capping of a disposal site with clean sediments will be a challenge and put restrictions on the thickness of the cap and the used placement technique. Simple laboratory tests have been conducted to evaluate the transition of newly dredged material from being a fluid to behaving like a continuum. The performed tests show that it is possible to put a sand layer on top of dredged material after a short initial consolidation phase. This indicates that dredged material at this stage is by definition a continuum. Results from special oedometer tests revealed that the time needed for primary consolidation for contaminated clay from the Bjørvika area in Oslo (Norway), was approximately 30 h. The undrained shear strength of dredged material after consolidation under the influence of a thin sand layer is difficult to measure using traditional methods. A simple laboratory test with a transparent cylinder and a tilting table was conducted to force a failure mechanism. From these results, the undrained shear strength can be back calculated. For Bjørvika clay, test results, using a 2–3 cm sand cap, indicated a shear strength of approximately 0.10–0.15 kPa after three days of consolidation. Thin sand layers will increase the shear strength of the dredged material and act as draining layers of excess pore pressure during disposal site operation. This will improve the stability of the final cap after site closure.
Seawater Quality, Suspended Solids, and Settling Particles in the Wood Pool Area of Shimizu Port, Japan
Authors: Sato Y , Fukue M , Yasuda K , Kita K , Sawamoto S , Miyata Y
Published: May 2006

The transport and contamination of suspended solids in a wood pool were quantitatively studied as a case study for the environmental assessment of an enclosed sea area. To assess the present contamination of Shimizu Port (Japan), seawater, suspended solids, and settling particles were collected from three rivers, the wood pool, and Shimizu Port. Physical and chemical properties of the samples were analyzed. In addition, tidal currents were observed to investigate the transport process of chemical substances by suspended solids. The results showed that the amount of lithogenic particles discharged into Shimizu Port was approximately 12 000 kg/day. Suspended solids discharged from rivers and the biological particles produced in the port caused a reduction in seawater transparency and an increase in chemical oxygen demand. Trace metals, such as Mn, Co, and Pb, were highly concentrated in suspended solids. Tributyltin adsorbed onto settling particles was approximately 300 µg/kg. Concentration factors for Mn, Fe, Cd, and Pb from water and settling particles are comparable to those of plankton. Hydroxides were found in suspended solids from the wood pool, which locates in the inner part of Shimizu Port. The results showed that these suspended particles could accumulate metals from seawater as effectively as biogenic particles. After particle deposition, trace metals are regenerated into seawater under anaerobic conditions. This process plays an important role in the accumulation of chemicals in seawater and sediments, especially in enclosed sea areas.
Applicability of Cement-Stabilized Mud Soil as Embankment Material
Authors: Tani S , Fukushima S , Kitajima A , Nishimoto K
Published: May 2006

Although conventional improved soil using cement has high strength, a maximum strength can be induced by a small strain, causing cracks. Thus, such improved soil is not considered to be fit for core materials (i.e., impervious materials) for earth dam embankments. We have developed a method to repair embankments with crushed and compacted soil utilizing earth dam mud soil. This method enables embankments which rarely crack to be constructed. The improved soil was produced in the following manner. First, the stabilized soil was cured for a few days. The soil was then crushed, plowed, compacted, and re-stabilized, resulting in an improved soil that, although it had lower strength, at the maximum strength can only be generated by a large strain. In this paper, mechanical tests for soil specimens prepared in a laboratory and obtained from actual embankments were used to obtain the curing times till crushing, and the strength and deformation characteristics of the crushed-compacted soil. In addition, we carried out a dry-wet cycling test for endurance for the crushed-compacted soil, and examined the mechanical characteristics. Finally, we describe some actual examples where the present method has been applied.
What Is The Pride Of Halicarnassus?
Authors: Gagné Renaud
Published: May 2006

Abstract This paper proposes a general analysis of the structure and imagery of the Salmacis epigram, a late Hellenistic verse inscription recently found in Bodrum which relates the foundation of Halicarnassus and lists the achievements of the city's authors. Focusing on the first part of the poem, I argue that the epigram can be seen to trace a complex symbolic map of the city in space and time. On a first level of reference the poem's episodes of foundation are consistently represented as the aitia of ritual events. Superimposed on the catalogue of foundation episodes is a catalogue of the ritual events that commemorated them, and our epigram uses this level of reference to ground its portrait of Halicarnassus in the contemporary ritual life of the polis. In this way the poem is able to locate the city in the space of cult and to inscribe the linear time of primordial origins in the recurrent present of ritual practice. On a complementary level of reference, finally, the different episodes of foundation also function as so many statements of kinship—every founder effectively ties the city to another region and another people. As a parallel to the local space of ritual, then, the combination of these statements of kinship is made to locate the city in the wider space of ethnic geography. Behind a seemingly simple catalogic form, the Salmacis epigram actually combines two levels of reference to achieve a significant and multifaceted representation of a late Hellenistic city's cultural memory.
Falling into Time in Homer'sIliad
Authors: Purves Alex
Published: May 2006

Abstract This paper addresses the question of the relation between mortal and immortal time in the Iliad as it is represented by the physical act of falling. I begin by arguing that falling serves as a point of reference throughout the poem for a concept of time that is specifically human. It is well known that mortals fall at the moment of death in the poem, but it has not been recognized that the movement of the fall is also connected with the time of birth, aging, and generation. In light of the significance of falling for mortals, I then go on to examine the problematic case of two particular immortals who fall in the Iliad. When Hephaestus tumbles down to earth from Olympus, and when Ares is knocked flat on the battlefield, both gods, I argue, also “fall into” human time. This complicates their status as ageless and eternal beings, and draws into question the different temporal registers at work in the narrative (such as repetition, “long time,” and time that is steady or continuous [empedos]). The single action of falling brings together several key concepts in the poem which hinge on the issue of the separation between the mortal and immortal spheres in the Iliad.
Justice, Geography and Empire in Aeschylus'Eumenides
Authors: Kennedy Rebecca Futo
Published: May 2006

Abstract This paper argues that Aeschylus' Eumenides presents a coherent geography that, when associated with the play's judicial proceedings, forms the basis of an imperial ideology. The geography of Eumenides constitutes a form of mapping, and mapping is associated with imperial power. The significance of this mapping becomes clear when linked to fifth-century Athens' growing judicial imperialism. The creation of the court inEumenides, in the view of most scholars, refers only to Ephialtes' reforms of 462 BC. But in the larger context, Athenian courts in the mid-fifth century are a form of imperial control. When geographically specific jurisdiction combines with new courts, it supports and even creates a developing imperial ideology. Moreover, the figure of Athena and the role she gives the Athenian jury emphasizes a passionate pro-Athenian nationalism, a nationalism that the text connects to Athens' geographic and judicial superiority. This imperial ideology did not spring from Aeschylus' imagination fully formed; it reflects a trend in Athens of promoting her own cultural superiority. This sense of cultural superiority in fact disguises the realities of Athens' developing power and increasingly harsh subjection of her former allies.