bluuebunny/crossref_metadata_2025 huggingface dataset:
Prehistoric seismicity-induced liquefaction along the western segment of the strike-slip Kunlun fault, northern Tibet
Authors: Lin Aiming , Guo Jianming
Published: June 2009

The 2001 M
w
7.8 Kunlun earthquake occurred in northern Tibet, and produced a 450-km-long surface rupture zone along the western segment of the strike-slip Kunlun fault. There are, however, no historic or instrumental records of large earthquakes in this fault segment. Field investigations of liquefaction structures and radiocarbon dating results reveal that at least three large earthquakes, including the 2001 earthquake, occurred in the western segment of the Kunlun fault during the past seven to nine centuries. Liquefaction structures formed in alluvial deposits composed of sand-gravel yielding
14
C ages of 679–901 yr
bp
are observed on the current stream channel which is sinistrally offset 75–82 m, including 3–6 m displacement produced by the 2001 event. On the basis of the field investigations and
14
C dating results, we conclude that the liquefaction structures and subsequent faulting events were caused by at least two large earthquakes of M>7 prior to the 2001 earthquake and the average recurrence interval of large earthquakes is estimated to be about 400 years in the late Holocene.
The Muzaffarabad, Pakistan, earthquake of 8 October 2005: surface faulting, environmental effects and macroseismic intensity
Authors: Ali Zahid , Qaisar Muhammad , Mahmood Tariq , Shah Muhammad Ali , Iqbal Talat , Serva Leonello , Michetti Alessandro M. , Burton Paul W.
Published: June 2009

The Mw 7.6 Muzaffarabad earthquake of 8 October 2005, occurred on a lateral equivalent of the main ramp of the Hymalaia frontal thrust, and is the result of the collision tectonics between the Indian and Eurasian plates. The epicentre was located near the town of Basantkot (Muzaffarabad), and the focal depth was about 13 km. The Muzaffarabad earthquake provides unequivocal evidence about the localization of severe damage, intense ground shaking and secondary environmental effects near the surface expression of the source fault. We analyse its nature, and impact on man-made structures and the physical environment, on the basis of a detailed survey and macroseismic study of the affected areas conducted by the Micro Seismic Studies Programme (MSSP) Team (Ishfaq Ahmad Research Laboratories, Pakistan Atomic Energy Commission) immediately after the mainshock, assisted by a careful review of the subsequent data and literature. In the course of the field survey, the displacement and surface expression of the causative fault, and accompanying secondary environmental effects were observed at a number of places along a capable thrust fault structure. We refer to this structure as the Kashmir Thrust (KT) capable fault following the terminology of local research geologists in Pakistan; the seismological evidence of this structure is already known in the literature as the Indus–Kohistan Seismic Zone. A complex, clearly segmented, at least 112-km-long surface rupture was mapped along the KT. The maximum values of vertical displacement (on the order of 4 to 7 m) were observed mainly between Muzaffarabad and Balakot, along the central segment of the rupture (52 km) associated with maximum slip at depth and a major portion of the energy release. Both the NW Alai segment (38 km) and SE Bagh segment (22 km) are characterized by scattered minor surface ruptures with a few centimetres of displacement, accompanied by extensive surface cracking, landslides and severe damage, concentrated in a narrow belt along the fault trace. A maximum intensity of XI on the Modified Mercalli Intensity (MMI) scale and on the Environmental Seismic Intensity scale (ESI 2007) was recorded in the epicentral area between Muzaffarabad and Balakot. Extremely severe damage and very important secondary environmental effects in the hanging wall adjacent to the trace of the causative fault plane are mainly due to near-fault strong motion and rupture directivity effects. To our knowledge, this is the first study to present field observations over the whole near-field of the earthquake, and to include the intensity map of the entire meizoseismal region.
Subjective Probabilities in Household Surveys
Authors: Hurd Michael D.
Published: June 2009

Subjective probabilities are now collected on a number of large household surveys with the objective of providing data to better understand intertemporal decision making. Comparison of subjective probabilities with actual outcomes shows that the probabilities have considerable predictive power in situations where individuals have considerable private information, such as survival and retirement. In contrast, the subjective probability of a stock market gain varies greatly across individuals even though no one has private information and the outcome is the same for everyone. An explanation is that there is considerable variation in accessing and processing information. Further, the subjective probability of a stock market gain is considerably lower than historical averages, providing an explanation for the relatively low frequency of stock holding. An important research objective will be to understand how individuals form their subjective probabilities.
Organizations and Trade
Authors: Antràs Pol , Rossi-Hansberg Esteban
Published: June 2009

We survey an emerging literature at the intersection of organizational economics and international trade. We argue that a proper modeling of the organizational aspects of production provides valuable insights on the aggregate workings of the world economy. In reviewing the literature, we describe certain predictions of standard models that are affected or even overturned when organizational decisions are brought into the analysis. We also suggest potentially fruitful areas for future research.
Cumulative Knowledge and Progress in Human Factors
Authors: Proctor Robert W. , Vu Kim-Phuong L.
Published: June 2009

This review provides a cumulative perspective on current human factors research by first briefly acknowledging previous Annual Review articles. We show that several recent conceptual advances are an outgrowth of the information-processing approach adopted by the field and present several areas of current research that are built directly on prior work. Topic areas that provide fundamental tools for human factors analyses are summarized, and several current application areas are reviewed. We end by considering alternatives to the information-processing approach that have been proposed and placing those alternatives in context. We argue that the information-processing language provides the foundation that has enabled much of the growth in human factors. This growth reflects a cumulative development of concepts and methods that continues today.
Improved tolerance to sequential glucose loading (Staub-Traugott effect): size and mechanisms
Authors: Bonuccelli Sandra , Muscelli Elza , Gastaldelli Amalia , Barsotti Elisabetta , Astiarraga Brenno D. , Holst Jens J. , Mari Andrea , Ferrannini Ele
Published: June 2009

Improved glucose tolerance to sequential glucose loading (Staub-Traugott effect) is an important determinant of day-to-day glycemic exposure. Its mechanisms have not been clearly established. We recruited 17 healthy volunteers to receive two sequential oral glucose tolerance tests (OGTTs), at time 0 min and 180 min ( Study I). The protocol was repeated on a separate day ( Study II) except that plasma glucose was clamped at 8.3 mmol/l between 60 and 180 min. β-Cell function was analyzed by mathematical modeling of C-peptide concentrations. In a subgroup, glucose kinetics were measured by a triple-tracer technique (infusion of [6,6-2H2]glucose and labeling of the 2 glucose loads with [1-2H]glucose and [U-13C]glucose). In both Studies I and II, the plasma glucose response to the second OGTT equaled 84 ± 2% ( P = 0.003) of the response to the first OGTT. Absolute insulin secretion was lower (37.8 ± 4.3 vs. 42.8 ± 5.1 nmol/m2, P = 0.02), but glucose potentiation (i.e., higher secretion at the same glycemia) was stronger (1.08 ± 0.02- vs. 0.92 ± 0.02-fold, P = 0.006), the increment being higher in Study II (+36 ± 5%) than Study I (+19 ± 6%, P < 0.05). In pooled data, a higher glucose area during the first OGTT was associated with a higher potentiation during the second OGTT (rho=0.60, P = 0.002). Neither insulin clearance nor glucose clearance differed between loads, and appearance of glucose over 3 h totalled 60 ± 6 g for the first load and 52 ± 5 g for the second load ( P = not significant). Fasting endogenous glucose production [13.3 ± 0.6 μmol·min−1·kg fat-free mass (FFM)−1] averaged 6.0 ± 3.8 μmol·min−1·kg FFM−1between 0 and 180 min and 1.7 ± 2.6 between 180 and 360 min ( P < 0.03). Glucose potentiation and stronger suppression of endogenous glucose release are the main mechanisms underlying the Staub-Traugott effect.
Estrogen-dependent facilitation on spinal reflex potentiation involves the Cdk5/ERK1/2/NR2B cascade in anesthetized rats
Authors: Peng Hsien-Yu , Chen Gin-Den , Tung Kwong-Chung , Chien Ya-Wen , Lai Cheng-Yuan , Hsieh Ming-Chun , Chiu Chun-Hsien , Lai Cheng-Hung , Lee Shin-Da , Lin Tzer-Bin
Published: June 2009

Cyclin-dependent kinase-5 (Cdk5), a proline-directed serine/threonine kinase, may alter pain-related neuronal plasticity by regulating extracellular signal-related kinase-1/2 (ERK1/2) activation. This study investigated whether Cdk5-dependent ERK activation underlies the estrogen-elicited facilitation on the repetitive stimulation-induced spinal reflex potentiaton (SRP) that is presumed to be involved in postinflammatory/neuropathic hyperalgesia and allodynia. Reflex activity of the external urethra sphincter electromyogram evoked by pelvic afferent nerve test stimulation (TS; 1 stimulation/30 s for 10 min) and repetitive stimulation (RS; 1 stimulation/1 s for 10 min) was recorded in anesthetized rats. TS evoked a baseline reflex activity, whereas RS produced SRP. Intrathecal (it) β-estradiol facilitated the repetitive stimulation-induced SRP that was reversed by pretreatment with the estrogen receptor anatogonist ICI 182,780 (10 nM, 10 μl it), Cdk5 inhibitor roscovitine (100 nM, 10 μl it), ERK inhibitor (U-0126; 100 μM, 10 μl it) and N-methyl-d-aspartate (NMDA) NR2B subunit antagonist (Co-101244; 100 nM, 10 μl it). Moreover, ERα (propylpyrazoletriol; 100 nM, 10 μl it) and ERβ (diarylpropionitrile; 100 μM, 10 μl it) agonists both facilitated the SRP, similar to results with a β-estradiol injection. In association with the facilitated RS-induced SRP, an intrathecal β-estradiol injection elicited ERK1/2 and NR2B subunit phosphorylation that were both reversed by intrathecal roscovitine and U-0126. These results indicated that the Cdk/ERK cascade, which is activated by ERα and ERβ, may subsequently phosphorylate the NR2B subunit to develop NMDA-dependent postinflammatory hyperalgesia and allodynia to maintain the protective mechanisms of the body.
Quantification of gap junctional intercellular communication based on digital image analysis
Authors: Hofgaard Johannes P. , Mollerup Sarah , Holstein-Rathlou Niels-Henrik , Nielsen Morten Schak
Published: June 2009

Intercellular communication via gap junction channels can be quantified by several methods based on diffusion of fluorescent dyes or metabolites. Given the variation in intercellular coupling of cells, even under untreated control conditions, it is of essence to quantify the coupling between numerous cells to obtain reliable estimates of metabolic coupling. Quantification is often based on manual counting of fluorescent cells, which is time consuming and may include some degree of subjectivity. In this report, we introduce a technique based on digital image analysis, and the software for the analysis is presented together with a detailed protocol in the online supplemental material ( http://bmi.ku.dk/matlab_program/ ). Fluorescent dye was introduced in connexin 43-expressing C6 glioma cells by in situ electroporation, and fluorescence intensity was measured in the electroporated cells and in cells receiving dye by intercellular diffusion. The analysis performed is semiautomatic, and comparison with traditional cell counting shows that this method reliably determines the effect of uncoupling by several interventions. This new method of analysis yields a rapid and objective quantification process with a high degree of reproducibility.
Role of Presynaptic Kainate Receptors at Parallel Fiber–Purkinje Cell Synapses in Induction of Cerebellar LTD: Interplay With Climbing Fiber Input
Authors: Crépel Francis
Published: June 2009

Until recently, except for A1 adenosine, N-methyl-d-aspartate, and cannabinoid receptors, little effort has been made to unravel possible roles of parallel fiber (PF) presynaptic receptors in long-term depression (LTD) of synaptic transmission at PF–Purkinje cell (PC) synapses. Presynaptic kainate (KA) receptors are also present on PFs and might also influence LTD induction by modulating glutamate (Glu) release at PF–PC synapses. This hypothesis was tested by comparing the efficacy of two pairing protocols in inducing LTD in adult wild-type and knock-out mice for the Glu receptor 6 (GluR6) subunit of KA receptors. Activation of presynaptic KA receptors was unnecessary for LTD induction when PF inputs were paired with climbing fiber (CF) stimulation but became crucial when CF input was replaced by direct depolarization of PCs. By comparing basal paired-pulse facilitation of PF-excitatory postsynaptic currents (EPSCs) and depolarization-induced suppression of excitation in adult wild-type and GluR6 knock-out mice, it was shown that the participation of PF presynaptic KA receptors in LTD induction was likely to mainly result from their tonic activation by basal extracellular Glu, rather than from their activation by retrograde release of Glu by PCs during pairing protocols. Finally, this study suggests that, in adult mice, CFs not only participate in LTD induction by depolarizing postsynaptic cells but also by activating postsynaptic mGluR1α metabotropic glutamate receptors at CF–PC synapses.
Visual Efference Neuromodulates Retinal Timing: In Vivo Roles of Octopamine, Substance P, Circadian Phase, and Efferent Activation in Limulus
Authors: Bolbecker Amanda R. , Lim-Kessler Corrinne C. M. , Li Jia , Swan Alicia , Lewis Adrienne , Fleets Jennifer , Wasserman Gerald S.
Published: June 2009

Efferent nerves coursing from the brain to the lateral eye of the horseshoe crab, Limulus polyphemus, increase its nighttime sensitivity to light. They release octopamine, which produces a categorical increase of photoreceptor response duration in vitro. Analogous in vivo timing effects on the electroretinogram (ERG) were demonstrated when octopamine was infiltrated into the eye of an otherwise intact animal; nighttime ERGs were longer than daytime ERGs. Related effects on the ERG were produced by daytime electrical stimulation of efferent fibers. Surprisingly, in a departure from effects predicted solely from in vitro octopamine data, nighttime ERG onsets were also accelerated relative to daytime ERG onsets. Drawing on earlier reports, these remarkable accelerations led to an examination of substance P as another candidate neuromodulator. It demonstrated that infiltrations of either modulator into the lateral eyes of otherwise intact crabs increased the amplitude of ERG responses but that each candidate modulator induced daytime responses that specifically mimicked one of the two particular aspects of the timing differences between day- and nighttime ERGs: octopamine increased the duration of daytime ERGs and substance P infiltrated during the day accelerated response onset. These results indicate that, in addition to octopamine's known role as an efferent neuromodulator that increases nighttime ERG amplitudes, octopamine clearly also affects the timing of photoreceptor responses. But these infiltration data go further and strongly suggest that substance P may also be released into the lateral eye at night, thereby accelerating the ERG's onset in addition to increasing its amplitude.
The Levels of Tumor Necrosis Factor-Alpha and Interleukin-6 in Patients with Isolated Coronary Artery Ectasia
Authors: Aydin Mustafa , Tekin Ishak Ozel , Dogan Sait Mesut , Yildirim Nesligul , Arasli Mehmet , Sayin Muhammet Rasit , Aktop Ziyaettin
Published: June 2009

Background/Aim. Coronary artery ectasia (CAE) is considered as a variant of atherosclerosis. Tumor necrosis factor-alpha (TNF-) and interleukin-6 (IL-6) are among the sensitive markers of systemic inflammation. The aim of this study was to evaluate the plasma levels of the cytokines; TNF- and IL-6 in CAE patients.Methods. Plasma concentrations of TNF- and IL-6 were measured in 36 patients with CAE (28 males, mean age: years), and results were compared with age and sex-matched controls () without coronary artery ectasia. TNF- and IL-6 concentrations in blood were assesed by enzyme-linked immunosorbent assay (ELISA).Results. Baseline characteristics of the two groups were similar. TNF- and IL-6 levels were significantly higher in CAE group than controls ( pg/mL versus  pg/mL, , and versus  , resp.).Conclusion. CAE patients showed increases in TNF- and IL-6 levels compared to the controls. This study provides evidence for alterations in the proinflamatory cytokines which suggest the involvement of the immune system in the pathophysiology of CAE. Further placebo-controlled studies are needed to evaluate the clinical significance of this increase in TNF- and IL-6 levels.
On Numerical Solution of the Incompressible Navier‐Stokes Equations with Static or Total Pressure Specified on Boundaries
Authors: Moshkin N. P. , Yambangwai D.
Published: June 2009

The purpose of this article is to develop and validate a computational method for the solution of viscous incompressible flow in a domain with specified static or total pressure on the flow‐through boundaries (inflow and outflow). The computational algorithm is based on the Finite Volume Method in nonstaggered boundary‐fitted grid. The implementations of the boundary conditions on the flow‐through parts of the boundary are discussed. Test examples illustrate the main features and validity of the proposed method to study viscous incompressible flow through a bounded domain with specified static pressure (or total pressure) on boundary as a part of well‐posed boundary conditions.
Higher Period Stochastic Bifurcation of Nonlinear Airfoil Fluid‐Structure Interaction
Authors: Witteveen Jeroen A. S. , Bijl Hester
Published: June 2009

The higher period stochastic bifurcation of a nonlinear airfoil fluid‐structure interaction system is analyzed
using an efficient and robust uncertainty quantification method for unsteady problems. The computationally efficient numerical approach achieves a constant error with a constant number of samples in time. The robustness of the method is assured by the extrema diminishing concept in probability space. The numerical results demonstrate that the system is even more sensitive to randomness at the higher period bifurcation than in the first bifurcation point. In this isolated point in parameter space
the clear hierarchy of increasing importance of the random nonlinearity parameter, initial condition, and natural frequency ratio, respectively, even suddenly reverses. Disregarding seemingly less important random parameters based on a preliminary analysis can, therefore, be an unreliable approach for reducing the number of relevant random input parameters.
Molecular Characterization and Tissue Localization of an F-Box Only Protein from Silkworm,Bombyx mori
Authors: Shen Yafang , Zhang Tiancheng , Chen Jianqing , Lv Zhengbing , Chen Jian , Wang Dan , Nie Zuoming , He Pingan , Wang Jiang , Zheng Qingliang , Sheng Qing , Wu Xiangfu , Zhang Yaozhou
Published: June 2009

The eukaryotic F-box protein family is characterized by an F-box motif that has been shown to be critical for the controlled degradation of regulatory proteins. We identified a gene encoding an F-box protein from a cDNA library of silkworm pupae, which has an ORF of 1821 bp, encoding a predicted 606 amino acids. Bioinformatic analysis on the amino acid sequence shows that BmFBXO21 has a low degree of similarity to proteins from other species, and may be related to the regulation of cell-cycle progression. We have detected the expression pattern of BmFBXO21 mRNA and protein and performed immunohistochemistry at three different levels. Expression was highest in the spinning stage, and in the tissues of head, epidermis, and genital organs.
Mesothelioma Cells Escape Heat Stress by Upregulating Hsp40/Hsp70 Expression via Mitogen‐Activated Protein Kinases
Authors: Roth Michael , Zhong Jun , Tamm Michael , Szilard John
Published: June 2009

Therapy with hyperthermal chemotherapy in pleural diffuse malignant mesothelioma had limited benefits for patients. Here we investigated the effect of heat stress on heat shock proteins (HSP), which rescue tumour cells from apoptosis. In human mesothelioma and mesothelial cells heat stress (39–42∘C) induced the phosphorylation of two mitogen activated kinases (MAPK) Erk1/2 and p38, and increased Hsp40, and Hsp70 expression. Mesothelioma cells expressed more Hsp40 and were less sensitive to heat stress compared to mesothelial cells. Inhibition of Erk1/2 MAPK by PD98059 or by Erk1 siRNA down‐regulated heat stress‐induced Hsp40 and Hsp70 expression and reduced mesothelioma cell survival. Inhibition of p38MAPK by SB203580 or siRNA reduced Hsp40, but not Hsp70, expression and also increased mesothelioma cell death. Thus hyperthermia combined with suppression of p38 MAPK or Hsp40 may represent a novel approach to improve mesothelioma therapy.
Integrative Gene Cloning and Expression System for Streptomyces sp. US 24 and Streptomyces sp. TN 58 Bioactive Molecule Producing Strains
Authors: Sioud Samiha , Aigle Bertrand , Karray-Rebai Ines , Smaoui Slim , Bejar Samir , Mellouli Lotfi
Published: June 2009

Streptomyces sp. US 24 and Streptomyces sp. TN 58, two strains producing interesting bioactive molecules, were successfully transformed using E. coli ET12567 (pUZ8002), as a conjugal donor, carrying the integrative plasmid pSET152. For the Streptomyces sp. US 24 strain, two copies of this plasmid were tandemly integrated in the chromosome, whereas for Streptomyces sp. TN 58, the integration was in single copy at the attB site. Plasmid pSET152 was inherited every time for all analysed Streptomyces sp. US 24 and Streptomyces sp. TN 58 exconjugants under nonselective conditions. The growth, morphological differentiation, and active molecules production of all studied pSET152 integrated exconjugants were identical to those of wild type strains. Consequently, conjugal transfer using pSET152 integration system is a suitable means of genes transfer and expression for both studied strains. To validate the above gene transfer system, the glucose isomerase gene (xylA) from Streptomyces sp. SK was expressed in strain Streptomyces sp. TN 58. Obtained results indicated that heterologous glucose isomerase could be expressed and folded effectively. Glucose isomerase activity of the constructed TN 58 recombinant strain is of about eighteenfold higher than that of the Streptomyces sp. SK strain. Such results are certainly of importance due to the potential use of improved strains in biotechnological process for the production of high‐fructose syrup from starch.
Triangle of Safety Technique: A New Approach to Laparoscopic Cholecystectomy
Authors: Almutairi Abdulrahman F. M. S. , Hussain Yousef A. M. S.
Published: June 2009

Backgrounds and Study Aims. Common bile duct (CBD) injury is one of the most serious complications of laparoscopic cholecystectomy (LC). Misidentification of the CBD during
dissection of the Calot's triangle can lead to such injuries. The aim of the authors in this study is to present a new safe triangle of dissection. Patients and Method. 501 patients under went LC in the following approach; The cystic artery is identified and mobilized from the gall bladder (GB) medial wall down towards the cystic duct which would simultaneously divide the medial GB peritoneal attachment. This is then followed by dividing the lateral peritoneal attachment. The GB will be unfolded and the borders of the triangle of safety (TST) are achieved: cystic artery medially, cystic duct laterally and the gallbladder wall superiorly. The floor of the triangle is then divided to delineate both cystic duct and artery in an area relatively far from CBD. Results. There were little significant immediate or delayed complications. The mean operating time was 68 minutes, nearly equivalent to the conventional method. Conclusions. Dissection at TST appears to be a safe procedure which clearly demonstrates the cystic duct and may help to reduce the CBD injuries.
Partial Characterization of a Vicilin-Like Glycoprotein from Seeds of Flowering Tobacco (Nicotiana sylvestris)
Authors: Gerlach Jared Q. , Bhavanandan Veer P. , Haynes Paul A. , Joshi Lokesh
Published: June 2009

A vicilin-like glycoprotein from the seeds of Nicotiana sylvestris, flowering tobacco, has been identified using nanoLC/ESI-MS/MS. Sequences from a fragment of protein demonstrated homology with vicilins from other members of the Solanaceae family, notably potato (Solanum demissum). Reducing and nonreducing SDS-PAGE analyses of the identified protein indicated that fragments resulting from in situ proteolytic processing are joined by intrachain disulphide bonds. Staining with Con A lectin was specifically inhibited by mannose suggested the presence of -linked glycosylation which was confirmed by carbohydrate compositional analysis of PVDF-bound protein subunits. HPAEC-PAD analysis of the monosaccharides released from the glycoprotein by acid hydrolysis revealed glucosamine and mannose. -acetylglucosamine termination of attached oligosaccharides was further verified by inhibitable WGA lectin staining. Immunostaining of PVDF-bound N. sylvestris proteins with antibodies against G. max total protein demonstrated cross-staining at masses corresponding to fragments from the proteolytically processed protein subunits.
Strong Convergence of Viscosity Iteration Methods for Nonexpansive Mappings
Authors: Jung Jong Soo
Published: June 2009

We propose a new viscosity iterative scheme for finding fixed points of nonexpansive mappings
in a reflexive Banach space having a uniformly Gâteaux differentiable norm and satisfying that every weakly compact convex subset of the space has the fixed point property for nonexpansive mappings. Certain different control conditions for viscosity iterative scheme are given and strong convergence of viscosity iterative
scheme to a solution of a ceratin variational inequality is established.
Molecular Simulations of Cyclic Loading Behavior of Carbon Nanotubes Using the Atomistic Finite Element Method
Authors: Wang Jianfeng , Gutierrez Marte S.
Published: June 2009

The potential applications of carbon nanotubes (CNT) in many engineered bionanomaterials and electromechanical devices have imposed an urgent need on the understanding of the fatigue behavior and mechanism of CNT under cyclic loading conditions. To date, however, very little work has been done in this field. This paper presents the results of a theoretical study on the behavior of CNT subject to cyclic tensile and compressive loads using quasi‐static molecular simulations. The Atomistic Finite Element Method (AFEM) has been applied in the study. It is shown that CNT exhibited extreme cyclic loading resistance with yielding strain and strength becoming constant within limited number of loading cycles. Viscoelastic behavior including nonlinear elasticity, hysteresis, preconditioning (stress softening), and large strain have been observed. Chiral symmetry was found to have appreciable effects on the cyclic loading behavior of CNT. Mechanisms of the observed behavior have been revealed by close examination of the intrinsic geometric and mechanical features of tube structure. It was shown that the accumulated residual defect‐free morphological deformation was the primary mechanism responsible for the cyclic failure of CNT, while the bond rotating and stretching experienced during loading/unloading played a dominant role on the strength, strain and modulus behavior of CNT.
Ease of Using a Dedicated Percutaneous Closure Device after Inadvertent Cannulation of the Subclavian Artery: Case Report
Authors: Devriendt Arnaud , Tran-Ngoc Emmanuel , Gottignies Philippe , Castro-Rodriguez José , Lomas Oliver , Jamart Sophie , Knecht Sébastien
Published: June 2009

Inadvertent puncture of the subclavian artery is a relatively frequent and potentially disastrous complication of attempted central venous access. Due to its noncompressible location, accidental subclavian arterial cannulation may result in hemorrhage as the sheath is removed. We report a new case of successful percutaneous closure of the subclavian artery which had been inadvertently cannulated, using a closure device based on a collagen plug (Angio-Seal, St. Jude Medical). This was performed in a patient who had received maximal antiplatelet and anticoagulation therapies because of prior coronary stenting in the context of cardiogenic shock. There was no prior angiographic assessment, as arterial puncture was presumed to have been distal to the right common artery and vertebral arteries. No complications were observed in this high-risk patient, suggesting that this technique could be used once the procedure has been evaluated prospectively.
Computational Challenges in miRNA Target Predictions: To Be or Not to Be a True Target?
Authors: Barbato Christian , Arisi Ivan , Frizzo Marcos E. , Brandi Rossella , Da Sacco Letizia , Masotti Andrea
Published: June 2009

All microRNA (miRNA) target—finder algorithms return lists of candidate target genes. How valid is that output in a biological setting? Transcriptome analysis has proven to be a useful approach to determine mRNA targets. Time course mRNA microarray experiments may reliably identify downregulated genes in response to overexpression of specific miRNA. The approach may miss some miRNA targets that are principally downregulated at the protein level. However, the high‐throughput capacity of the assay makes it an effective tool to rapidly identify a large number of promising miRNA targets. Finally, loss and gain of function miRNA genetics have the clear potential of being critical in evaluating the biological relevance of thousands of target genes predicted by bioinformatic studies and to test the degree to which miRNA‐mediated regulation of any “validated” target functionally matters to the animal or plant.
A Biomimetic Approach for the Creation of Two‐Dimensional Microscale Surface Patterns: Creation of Isolated Immunological Synapses
Authors: Stern Eric , Mooney David J. , Fahmy Tarek M.
Published: June 2009

Current efforts in surface functionalization have not produced a robust technique capable of creating specific two‐dimensional microscale geometrical arrays composed of multiple proteins. Such a capability is desirable for engineering substrates in sensing and cell patterning applications where at least two different protein functionalities in a specific configuration are required. Here we introduce a new approach for the creation of arrays of microscale geometries. We demonstrate our approach with a biomimetic structure inspired by the immunological synapse, a cell‐cell interfacial structure characterized by two concentric rings of proteins: an outer adhesion protein structure and an inner recognition ligand core. The power of the technique lies in its ability to pattern any protein in any defined geometry as well as to create arrays in parallel.
The Use of FTIR and Micro-FTIR Spectroscopy: An Example of Application to Cultural Heritage
Authors: La Russa Mauro Francesco , Ruffolo Silvestro Antonio , Barone Germana , Crisci Gino Mirocle , Mazzoleni Paolo , Pezzino Antonino
Published: June 2009

Micro-FTIR and FTIR spectroscopy is useful for the study of degradation forms of cultural heritage. In particular it permits to identify the degradation phases and to establish the structural relationship between them and the substratum. In this paper, we report the results obtained on marble from a Roman sarcophagus, located in the medieval cloister of St. Cosimato Convent (Rome), and on oolitic limestone from the facade of St. Giuseppe Church in Syracuse (Sicily).
The main components found in the samples of both monuments are: gypsum, calcium oxalate, and organic matter due to probably conservation treatments. In particular, the qualitative distribution maps of degradation products, obtained by means of micro-FTIR operating in ATR mode, revealed that the degradation process is present deep inside the stones also if it is not visible macroscopically. This process represents the main cause of crumbling of the substrate.
The results of this research highlight the benefits of the -FTIR analysis providing useful insights on the polishing and consolidation processes of stone materials.
Effect of the Unsteadiness on the Diffuser Flow in a Transonic Centrifugal Compressor Stage
Authors: Bulot N. , Trébinjac I.
Published: June 2009

The study is focused on the analysis of the flow structure within the vaned diffuser of a transonic high‐pressure centrifugal compressor stage. The analyzed time‐dependent flow field comes from unsteady computations of the stage using a 3D Navier‐Stokes code with a phase‐lagged technique, at an operating point close to the design point. A good comparison with available experimental data allowed the use of CFD for investigating the details of the flow in order to assess the effect of the unsteadiness in the diffuser flow development. Applying various data processing techniques, it is shown that the unsteadiness is due to the jet and wake flow structure emerging from the radial impeller and to the pressure waves brought about by the interaction between the vane bow shock wave and the impeller blade. The interaction between the pressure waves and the vane pressure side boundary layer leads to a pulsating behavior of separated bubbles within the diffuser. The pressure waves are similar in shape and strength whatever the blade height. The observed change in the flow field from hub to tip is due to migration of the low momentum fluid contained in the wake toward the pressure side/hub corner.
Bortezomib Alone or in Combination with the Histone Deacetylase Inhibitor JNJ-26481585: Effect on Myeloma Bone Disease in the 5T2MM Murine Model of Myeloma
Authors: Deleu Sarah , Lemaire Miguel , Arts Janine , Menu Eline , Van Valckenborgh Els , Vande Broek Isabelle , De Raeve Hendrik , Coulton Les , Van Camp Ben , Croucher Peter , Vanderkerken Karin
Published: June 2009

The proteasome inhibitor bortezomib (Velcade) is currently approved as second-line treatment of multiple myeloma (MM). MM-related bone disease is one of the most debilitating complications of MM. Besides supportive care with biphosphonates, which have proven efficacy in reducing and delaying skeletal-related events, there is no specific treatment of lytic bone lesions. The present study investigated the effect of bortezomib alone or in combination with a hydroxamate-based histone deacetylase inhibitor, JNJ-26481585 on tumor burden, and MM bone disease in the 5T2MM model. Injection of 5T2MM cells into C57Bl/KaLwRij mice resulted in MM bone disease, characterized by an increase in the percentage osteoclasts, a decrease in osteoblasts, trabecular bone volume, trabecular number, and the development of bone lesions. Treatment of 5T2MM-bearing mice with bortezomib significantly reduced tumor burden, angiogenesis, and MM bone disease. More importantly, the combination of bortezomib with JNJ-26481585 resulted in a more pronounced reduction of osteoclasts and increase of osteoblasts, trabecular bone volume, and trabecular number compared with bortezomib as single agent. These data suggest that bortezomib has bone remodeling properties that can be improved in combination with low dose JNJ-26481585. The study indicates that this combination therapy could be a useful strategy for the treatment of MM patients, especially in those patients with skeletal complications. [Cancer Res 2009;69(13):5307–11]
Murine Gammaherpesvirus 68 Infection of IFNγ Unresponsive Mice: A Small Animal Model for Gammaherpesvirus-Associated B-Cell Lymphoproliferative Disease
Authors: Lee Katherine S. , Groshong Steve D. , Cool Carlyne D. , Kleinschmidt-DeMasters Bette K. , van Dyk Linda F.
Published: June 2009

Gammaherpesviruses are tightly controlled by the host immune response, with gammaherpesvirus-associated malignancies prevalent in immune-suppressed individuals. Previously, infection of IFNγ-unresponsive mice with gammaherpesvirus 68 (γHV68) showed that IFNγ controlled chronic infection, limiting chronic diseases including arteritis and pulmonary fibrosis. Here, we show that γHV68-infected IFNγ receptor–deficient (IFNγR−/−) mice uniformly develop angiocentric inflammatory lesions in the lung. Prolonged infection revealed a range of outcomes, from spontaneous regression to pulmonary lymphoma. By 12 months of infection, 80% of mice had lymphoid hyperplasia or pulmonary lymphoma; 45% of infected mice developed frank tumors between 5 and 12 months postinfection, with some mice showing systemic involvement. Lymphomas were composed of B lymphocytes and contained latently infected cells. Although IFNγR−/− mice control chronic γHV68 infection poorly, both early and late pathologies were indistinguishable between wild-type and reactivation-defective virus infection, indicating that, in contrast with other previously described γHV68-associated pathologies, these chronic diseases were not dependent on the reactivation of latent infection. This distinct combination of latent infection and defined host defect led to a specific and consistent lymphoproliferative disease. Significantly, this mouse model of virus-associated pulmonary B-cell lymphoma closely mimics the full spectrum of human lymphomatoid granulomatosis, an EBV-associated malignancy with no effective treatment. [Cancer Res 2009;69(13):5481–9]
3,3′-Diindolylmethane Enhances Chemosensitivity of Multiple Chemotherapeutic Agents in Pancreatic Cancer
Authors: Banerjee Sanjeev , Wang Zhiwei , Kong Dejuan , Sarkar Fazlul H.
Published: June 2009

Clinical management of pancreatic cancer is a major problem, which is in part due to both de novo and acquired resistance to conventional therapeutics. Here, we present in vitro and in vivo preclinical evidence in support of chemosensitization of pancreatic cancer cells by 3,3-diindolylmethane (DIM), a natural compound that can be easily obtained by consuming cruciferous vegetables. DIM pretreatment of pancreatic cancer cells led to a significantly increased apoptosis (P < 0.01) with suboptimal concentrations of chemotherapeutic agents (cisplatin, gemcitabine, and oxaliplatin) compared with monotherapy. It is known that resistance to chemotherapy in pancreatic cancer is associated with constitutively activated nuclear factor-κB (NF-κB), which becomes further activated by chemotherapeutic drugs. Our data provide mechanistic evidence for the first time showing that DIM potentiates the killing of pancreatic cancer cells by down-regulation of constitutive as well as drug-induced activation of NF-κB and its downstream genes (Bcl-xL, XIAP, cIAP, and survivin). Most importantly, using an orthotopic animal model, we found reduction in tumor size (P < 0.001) when DIM was given in combination with oxaliplatin compared with monotherapy. This was accompanied by loss of phospho-p65 and down-regulation of NF-κB activity and its downstream genes (Bcl-xL, survivin, and XIAP), which correlated with reduced cell proliferation (as assessed by Ki-67 immunostaining of tumor specimens) and evidence of apoptosis [as assessed by poly(ADP-ribose) polymease cleavage and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining]. These results provide strong in vivo evidence in support of our hypothesis that DIM could abrogate chemotherapeutic drug (cisplatin, gemcitabine, and/or oxaliplatin)–induced activation of NF-κB, resulting in the chemosensitization of pancreatic tumors to conventional therapeutics. [Cancer Res 2009;69(13):5592–600]
Changes in Gene Expression Predicting Local Control in Cervical Cancer: Results from Radiation Therapy Oncology Group 0128
Authors: Weidhaas Joanne B. , Li Shu-Xia , Winter Kathryn , Ryu Janice , Jhingran Anuja , Miller Bridgette , Dicker Adam P. , Gaffney David
Published: June 2009

Purpose: To evaluate the potential of gene expression signatures to predict response to treatment in locally advanced cervical cancer treated with definitive chemotherapy and radiation.

Experimental Design: Tissue biopsies were collected from patients participating in Radiation Therapy Oncology Group (RTOG) 0128, a phase II trial evaluating the benefit of celecoxib in addition to cisplatin chemotherapy and radiation for locally advanced cervical cancer. Gene expression profiling was done and signatures of pretreatment, mid-treatment (before the first implant), and “changed” gene expression patterns between pre- and mid-treatment samples were determined. The ability of the gene signatures to predict local control versus local failure was evaluated. Two-group t test was done to identify the initial gene set separating these end points. Supervised classification methods were used to enrich the gene sets. The results were further validated by leave-one-out and 2-fold cross-validation.

Results: Twenty-two patients had suitable material from pretreatment samples for analysis, and 13 paired pre- and mid-treatment samples were obtained. The changed gene expression signatures between the pre- and mid-treatment biopsies predicted response to treatment, separating patients with local failures from those who achieved local control with a seven-gene signature. The in-sample prediction rate, leave-one-out prediction rate, and 2-fold prediction rate are 100% for this seven-gene signature. This signature was enriched for cell cycle genes.

Conclusions: Changed gene expression signatures during therapy in cervical cancer can predict outcome as measured by local control. After further validation, such findings could be applied to direct additional therapy for cervical cancer patients treated with chemotherapy and radiation.
Coadministration of Ritonavir Strongly Enhances the Apparent Oral Bioavailability of Docetaxel in Patients with Solid Tumors
Authors: Oostendorp Roos L. , Huitema Alwin , Rosing Hilde , Jansen Robert S. , ter Heine Rob , Keessen Marianne , Beijnen Jos H. , Schellens Jan H.M.
Published: June 2009

Purpose: To enhance the systemic exposure to oral docetaxel by coadministration of ritonavir, an efficacious inhibitor of CYP 3A4 with minor P-glycoprotein inhibiting effects, in patients with cancer.

Experimental Design: A proof-of-concept study was carried out in 12 patients with solid tumors. The first cohort of patients (n = 4) received 10 mg and the subsequent cohort (n = 8) 100 mg of oral docetaxel, coadministered with 100 mg oral ritonavir randomized simultaneously or ritonavir given 60 minutes before docetaxel on days 1 and 8. On day 15 or 22, patients received 100 mg i.v. docetaxel.

Results: The area under the plasma concentration-time curve in patients who received 10 mg oral docetaxel in combination with ritonavir was low, and the dose could safely be increased to 100 mg. The area under the plasma concentration-time curve in patients who received 100 mg oral docetaxel combined with ritonavir simultaneously or ritonavir given 60 minutes before docetaxel was 2.4 ± 1.5 and 2.8 ± 1.4 mg/h/L, respectively, compared with 1.9 ± 0.4 mg/h/L after i.v. docetaxel. The apparent oral bioavailability of docetaxel combined with ritonavir simultaneously or ritonavir given 60 minutes before docetaxel was 131% ± 90% and 161% ± 91%, respectively. The oral combination of docetaxel and ritonavir was well tolerated.

Conclusion: Coadministration of ritonavir significantly enhanced the apparent oral bioavailability of docetaxel. These data are promising and form the basis for further development of a clinically applicable oral formulation of docetaxel combined with ritonavir.
Phase I Pharmacokinetic and Pharmacodynamic Study of Carboplatin and Topotecan Administered Intravenously Every 28 Days to Patients with Malignant Solid Tumors
Authors: Boss David S. , Siegel-Lakhai Wandena S. , van Egmond-Schoemaker Nadja E. , Pluim Dick , Rosing Hilde , ten Bokkel Huinink Wim W. , Beijnen Jos H. , Schellens Jan H.M.
Published: June 2009

Purpose: Preclinical studies have shown that the combination of topotecan and carboplatin is synergistic. To evaluate the schedule dependency of this interaction, the following phase I trial was designed to determine the safety and maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of carboplatin and topotecan in patients with malignant solid tumors.

Experimental Design: In part 1, patients received carboplatin on day 1 and topotecan on days 1, 2, and 3 (C→T schedule). In part 2, topotecan was administered on days 1, 2, and 3, followed by carboplatin on day 3 (T→C schedule). Pharmacokinetics were determined in plasma and DNA topoisomerase I catalytic activity and Pt-DNA adducts in WBC and tumor tissue.

Results: Forty-one patients were included. Dose-limiting toxicities during the C→T schedule were grade 4 thrombocytopenia and febrile neutropenia (MTD: carboplatin target area under the free carboplatin plasma concentration versus time curve, 4 min mg/mL; topotecan, 0.5 mg/m2/d). Dose-limiting toxicities during the T→C schedule included grade 4 neutropenia, thrombocytopenia, neutropenic fever, and grade 4 nausea and vomiting (MTD: carboplatin target area under the free carboplatin plasma concentration versus time curve, 6 min mg/mL; topotecan, 0.9 mg/m2/d). One complete response and five partial responses were observed. The clearance of and exposure to carboplatin and topotecan did not depend on the sequence of drug administration. No schedule-dependent effects were seen in Pt-DNA levels and DNA topoisomerase I catalytic activity in WBC and tumor tissue. However, myelotoxicity was clearly more evident in the C→T schedule.

Conclusion: The T→C schedule was better tolerated because both hematologic and nonhematologic toxicities were milder. Other pharmacodynamic factors than the ones investigated must explain the schedule-dependent differences in toxicities.