Induction of placental heme oxygenase-1 is protective against TNFα-induced cytotoxicity and promotes vessel relaxation

Background: Pregnancy is characterized by an inflammatory-like process and this may be exacerbated in preeclampsia. The heme oxygenase (HO) enzymes generate carbon monoxide (CO) that induces blood vessel relaxation and biliverdin that acts as an endogenous antioxidant. Materials and Methods: We examined the expression and localization of HO-1 and HO-2 in normal and preeclamptic placenta using reverse transcription polymerase chain reaction (RT-PCR), RNase protection assay, immunoblotting and immunohistochemistry. In addition, the effect of HO activation on tumor necrosis factor-alpha (TNF) induced placental damage and on feto-placental circulation was studied. Results: We provide the first evidence for the role of HO as an endogenous placental factor involved with cytoprotection and placental blood vessel relaxation. HO-1 was significantly higher at term, compared with first trimester placentae indicating its role in placental vascular development and regulation. HO-1 predominantly localized in the extravascular connective tissue that forms the perivascular contractile sheath around the developing blood vessels. HO-2 was localized in the capillaries, as well as the villous stroma, with weak staining of trophoblast. Induction of HO-1 caused a significant attenuation of TNF-mediated cellular damage in placental villous explants, as assessed by lactate dehydrogenase leakage (p 0.01). HO-1 protein was significantly reduced in placentae from pregnancies complicated with preeclampsia, compared with gestationally matched normal pregnancies. This suggests that the impairment of HO-1 activation may compromise the compensatory mechanism and predispose the placenta to cellular injury and subsequent maternal endothelial cell activation. Isometric contractility studies showed that hemin reduced vascular tension by 61% in U46619-preconstricted placental arteries. Hemininduced vessel relaxation and CO production was inhibited by HO inhibitor, tin protoporphyrin IX. Conclusions: Our findings establish HO-1 as an endogenous system that offers protection against cytotoxic damage in the placenta, identifies the HO-CO pathway to regulate feto-placental circulation and provides a new approach to study the disease of preeclampsia.

Energy-based damage and fracture framework for viscoelastic asphalt concrete

A framework based on the continuum damage mechanics and thermodynamics of irreversible processes using internal state variables is used to characterize the distributed damage in viscoelastic asphalt materials in the form of micro-crack initiation and accumulation. At low temperatures and high deformation rates, micro-cracking is considered as the source of nonlinearity and thus the cause of deviation from linear viscoelastic response. Using a non-associated damage evolution law, the proposed model shows the ability to describe the temperature-dependent processes of micro-crack initiation, evolution and macro-crack formation with good comparison to the material response in the Superpave indirect tensile (IDT) strength test.

Industrial districts, inward foreign investment and regional development

This article compares the importance of agglomerations of local firms, and inward FDI as drivers of regional development. The empirical analysis exploits a unique panel dataset of the Italian manufacturing sector at the regional and industry levels. We explore whether FDI and firm agglomeration can be drivers of total factor productivity (separately and jointly), with this effect being robust to different estimators, and different assumptions about inter-regional effects. In particular, we isolate one form of firm agglomeration that is especially relevant in the Italian context, industrial districts, in order to ascertain their impact on productivity. In so doing, we distinguish standard agglomeration and localization economies from industrial districts to understand what additional impact the latter has on standard agglomeration effects. Interaction effects between FDI spillovers and different types of agglomeration economies shed some light on the heterogeneity of regional development patterns as well as on the opportunity to fine tune policy measures to specific regional contexts.

A hierarchical localization scheme for large scale underwater wireless sensor networks

In this paper, we study the localization problem in large-scale Underwater Wireless Sensor Networks (UWSNs). Unlike in the terrestrial positioning, the global positioning system (GPS) can not work efficiently underwater. The limited bandwidth, the severely impaired channel and the cost of underwater equipment all makes the localization problem very challenging. Most current localization schemes are not well suitable for deep underwater environment. We propose a hierarchical localization scheme to address the challenging problems. The new scheme mainly consists of four types of nodes, which are surface buoys, Detachable Elevator Transceivers (DETs), anchor nodes and ordinary nodes. Surface buoy is assumed to be equipped with GPS on the water surface. A DET is attached to a surface buoy and can rise and down to broadcast its position. The anchor nodes can compute their positions based on the position information from the DETs and the measurements of distance to the DETs. The hierarchical localization scheme is scalable, and can be used to make balances on the cost and localization accuracy. Initial simulation results show the advantages of our proposed scheme. © 2009 IEEE.

Enclosing the behavior of a hybrid system up to and beyond a Zeno point

Even simple hybrid systems like the classic bouncing ball can exhibit Zeno behaviors. The existence of this type of behavior has so far forced simulators to either ignore some events or risk looping indefinitely. This in turn forces modelers to either insert ad hoc restrictions to circumvent Zeno behavior or to abandon hybrid modeling. To address this problem, we take a fresh look at event detection and localization. A key insight that emerges from this investigation is that an enclosure for a given time interval can be valid independently of the occurrence of a given event. Such an event can then even occur an unbounded number of times, thus making it possible to handle certain types of Zeno behavior.

Age-related macular degeneration is associated with increased vascular endothelial growth factor, hemorheology and endothelial dysfunction

OBJECTIVE: To investigate laboratory evidence of abnormal angiogenesis, hemorheologic factors, endothelial damage/dysfunction, and age-related macular degeneration (ARMD). DESIGN: Comparative cross-sectional study. PARTICIPANTS: We studied 78 subjects (26 men and 52 women; mean age 74 years; standard deviation [SD] 9.0) with ARMD attending a specialist referral clinic. Subjects were compared with 25 healthy controls (mean age, 71 years; SD, 11). INTERVENTION AND OUTCOME MEASURES: Levels of vascular endothelial growth factor (VEGF, an index of angiogenesis), hemorheologic factors (plasma viscosity, hematocrit, white cell count, hemoglobin, platelets), fibrinogen (an index of rheology and hemostasis), and von Willebrand factor (a marker of endothelial dysfunction) were measured. RESULTS: Median plasma VEGF (225 vs. 195 pg/ml, P = 0.019) and mean von Willebrand factor (124 vs. 99 IU/dl, P = 0.0004) were greater in ARMD subjects than the controls. Mean plasma fibrinogen and plasma viscosity levels were also higher in the subjects (both P < 0.0001). There were no significant differences in other indices between cases and controls. When "dry" (drusen, atrophy, n = 28) and "exudative" (n = 50) ARMD subjects were compared, there was no significant differences in VEGF, fibrinogen, viscosity, or von Willebrand factor levels. There were no significant correlations between the measured parameters. Stepwise multiple regression analysis did not demonstrate any significant clinical predictors (age, gender, smoking, body mass index, history of vascular disease, or hypertension) for plasma VEGF or fibrinogen levels, although smoking status was a predictor of plasma von Willebrand factor levels (P < 0.05). CONCLUSIONS: This study suggests an association between markers of angiogenesis (VEGF), hemorheologic factors, hemostasis, endothelial dysfunction, and ARMD. The interaction between abnormal angiogenesis and the components of Virchow's triad for thrombogenesis may in part contribute to the pathogenesis of ARMD.

Enclosing the behavior of a hybrid automaton up to and beyond a Zeno point

Even simple hybrid automata like the classic bouncing ball can exhibit Zeno behavior. The existence of this type of behavior has so far forced a large class of simulators to either ignore some events or risk looping indefinitely. This in turn forces modelers to either insert ad-hoc restrictions to circumvent Zeno behavior or to abandon hybrid automata. To address this problem, we take a fresh look at event detection and localization. A key insight that emerges from this investigation is that an enclosure for a given time interval can be valid independent of the occurrence of a given event. Such an event can then even occur an unbounded number of times. This insight makes it possible to handle some types of Zeno behavior. If the post-Zeno state is defined explicitly in the given model of the hybrid automaton, the computed enclosure covers the corresponding trajectory that starts from the Zeno point through a restarted evolution.

Interpretation of the Superpave IDT strength test using a viscoelastic-damage constitutive model

This paper presents a new interpretation for the Superpave IDT strength test based on a viscoelastic-damage framework. The framework is based on continuum damage mechanics and the thermodynamics of irreversible processes with an anisotropic damage representation. The new approach introduces considerations for the viscoelastic effects and the damage accumulation that accompanies the fracture process in the interpretation of the Superpave IDT strength test for the identification of the Dissipated Creep Strain Energy (DCSE) limit from the test result. The viscoelastic model is implemented in a Finite Element Method (FEM) program for the simulation of the Superpave IDT strength test. The DCSE values obtained using the new approach is compared with the values obtained using the conventional approach to evaluate the validity of the assumptions made in the conventional interpretation of the test results. The result shows that the conventional approach over-estimates the DCSE value with increasing estimation error at higher deformation rates.

Retromer controls epithelial cell polarity by trafficking the apical determinant crumbs

The evolutionarily conserved apical determinant Crumbs (Crb) is essential for maintaining apicobasal polarity and integrity of many epithelial tissues [1]. Crb levels are crucial for cell polarity and homeostasis, yet strikingly little is known about its trafficking or the mechanism of its apical localization. Using a newly established, liposome-based system described here, we determined Crb to be an interaction partner and cargo of the retromer complex. Retromer is essential for the retrograde transport of numerous transmembrane proteins from endosomes to the trans-Golgi network (TGN) and is conserved between plants, fungi, and animals [2]. We show that loss of retromer function results in a substantial reduction of Crb in Drosophila larvae, wing discs, and the follicle epithelium. Moreover, loss of retromer phenocopies loss of crb by preventing apical localization of key polarity molecules, such as atypical protein kinase C (aPKC) and Par6 in the follicular epithelium, an effect that can be rescued by overexpression of Crb. Additionally, loss of retromer results in multilayering of the follicular epithelium, indicating that epithelial integrity is severely compromised. Our data reveal a mechanism for Crb trafficking by retromer that is vital for maintaining Crb levels and localization. We also show a novel function for retromer in maintaining epithelial cell polarity.

Face context interferes with local part processing in a prosopagnosic patient

We investigated the role of local and global information on perceptual encoding of faces in patient HJA, who shows prosopagnosia and visual agnosia following occipito-temporal damage. HJA and an age-matched control were tested in a simultaneous matching task which focused on detection of local changes in faces: the inversion of central parts (eyes and mouth) relative to their context (as in the Thatcher illusion). Same-different judgements were made to normal, “thatcherised” and mixed type face pairs. Whole faces (Experiment 1), or face parts (Experiment 2), were presented in upright and inverted orientations. Compared to the control, HJA was severely impaired at matching whole faces, but he improved dramatically when face parts were presented in isolation. This suggests an inhibitory influence of face context on HJAs processing of local parts and a relatively intact ability to process part-based information from a face (when context cannot interfere). Face inversion did not affect HJAs performance. A control experiment (Experiment 3) with non-face stimuli (houses) suggested that the inhibitory influence of context on HJAs performance was restricted to faces. These results indicate that contextual information in a face can have an adverse influence on the processing of local part-based information in prosopagnosia.

Characterization of tissue transglutaminase in human osteoblast-like cells

Tissue transglutaminase (tTG) is a calcium-dependent and guanosine 5'-triphosphate (GTP) binding enzyme, which catalyzes the post-translational modification of proteins by forming intermolecular ε(ϒ-glutamyl)lysine cross-links. In this study, human osteoblasts (HOBs) isolated from femoral head trabecular bone and two osteosarcoma cell lines (HOS and MG-63) were studied for their expression and localization of tTG. Quantitative evaluation of transglutaminase (TG) activity determined using the [1,414C]-putrescine incorporation assay showed that the enzyme was active in all cell types. However, there was a significantly higher activity in the cell homogenates of MG-63 cells as compared with HOB and HOS cells (p <0.001). There was no significant difference between the activity of the enzyme in HOB and HOS cells. All three cell types also have a small amount of active TG on their surface as determined by the incorporation of biotinylated cadaverine into fibronectin. Cell surface-related tTG was further shown by preincubation of cells with tTG antibody, which led to inhibition of cell attachment. Western blot analysis clearly indicated that the active TG was tTG and immunocytochemistry showed it be situated in the cytosol of the cells. In situ extracellular enzyme activity also was shown by the cell-mediated incorporation of fluorescein cadaverine into extracellular matrix (ECM) proteins. These results clearly showed that MG-63 cells have high extracellular activity, which colocalized with the ECM protein fibronectin and could be inhibited by the competitive primary amine substrate putrescine. The contribution of tTG to cell surface/matrix interactions and to the stabilization of the ECM of osteoblast cells therefore could by an important factor in the cascade of events leading to bone differentiation and mineralization.

Random distributed feedback fibre lasers

The concept of random lasers exploiting multiple scattering of photons in an amplifying disordered medium in order to generate coherent light without a traditional laser resonator has attracted a great deal of attention in recent years. This research area lies at the interface of the fundamental theory of disordered systems and laser science. The idea was originally proposed in the context of astrophysics in the 1960s by V.S. Letokhov, who studied scattering with "negative absorption" of the interstellar molecular clouds. Research on random lasers has since developed into a mature experimental and theoretical field. A simple design of such lasers would be promising for potential applications. However, in traditional random lasers the properties of the output radiation are typically characterized by complex features in the spatial, spectral and time domains, making them less attractive than standard laser systems in terms of practical applications. Recently, an interesting and novel type of one-dimensional random laser that operates in a conventional telecommunication fibre without any pre-designed resonator mirrors-random distributed feedback fibre laser-was demonstrated. The positive feedback required for laser generation in random fibre lasers is provided by the Rayleigh scattering from the inhomogeneities of the refractive index that are naturally present in silica glass. In the proposed laser concept, the randomly backscattered light is amplified through the Raman effect, providing distributed gain over distances up to 100km. Although an effective reflection due to the Rayleigh scattering is extremely small (~0.1%), the lasing threshold may be exceeded when a sufficiently large distributed Raman gain is provided. Such a random distributed feedback fibre laser has a number of interesting and attractive features. The fibre waveguide geometry provides transverse confinement, and effectively one-dimensional random distributed feedback leads to the generation of a stationary near-Gaussian beam with a narrow spectrum. A random distributed feedback fibre laser has efficiency and performance that are comparable to and even exceed those of similar conventional fibre lasers. The key features of the generated radiation of random distributed feedback fibre lasers include: a stationary narrow-band continuous modeless spectrum that is free of mode competition, nonlinear power broadening, and an output beam with a Gaussian profile in the fundamental transverse mode (generated both in single mode and multi-mode fibres).This review presents the current status of research in the field of random fibre lasers and shows their potential and perspectives. We start with an introductory overview of conventional distributed feedback lasers and traditional random lasers to set the stage for discussion of random fibre lasers. We then present a theoretical analysis and experimental studies of various random fibre laser configurations, including widely tunable, multi-wavelength, narrow-band generation, and random fibre lasers operating in different spectral bands in the 1-1.6μm range. Then we discuss existing and future applications of random fibre lasers, including telecommunication and distributed long reach sensor systems. A theoretical description of random lasers is very challenging and is strongly linked with the theory of disordered systems and kinetic theory. We outline two key models governing the generation of random fibre lasers: the average power balance model and the nonlinear Schrödinger equation based model. Recently invented random distributed feedback fibre lasers represent a new and exciting field of research that brings together such diverse areas of science as laser physics, the theory of disordered systems, fibre optics and nonlinear science. Stable random generation in optical fibre opens up new possibilities for research on wave transport and localization in disordered media. We hope that this review will provide background information for research in various fields and will stimulate cross-disciplinary collaborations on random fibre lasers. © 2014 Elsevier B.V.

Mechanistic modeling of fracture in asphalt mixtures under compressive loading

When an asphalt mixture is subjected to a destructive compressive load, it experiences a sequence of three deformation stages, as follows: the (1) primary, (2) secondary, and (3) tertiary stages. Most literature research focuses on plastic deformation in the primary and secondary stages, such as prediction of the flow number, which is in fact the initiation of the tertiary stage. However, little research effort has been reported on the mechanistic modeling of the damage that occurs in the tertiary stage. The main objective of this paper is to provide a mechanistic characterizing method for the damage modeling of asphalt mixtures in the tertiary stage. The preliminary study conducted by the writers illustrates that deformation during the tertiary flow of the asphalt mixtures is principally caused by the formation and propagation of cracks, which was signaled by the increase of the phase angle in the tertiary phase. The strain caused by the growth of cracks is the viscofracture strain, which can be obtained by conducting the strain decomposition of the measured total strain in the destructive compressive test. The viscofracture strain is employed in the research reported in this paper to mechanistically characterize the time-dependent fracture (viscofracture) of asphalt mixtures in compression. By using the dissipated pseudostrain energy-balance principle, the damage density and true stress are determined and both are demonstrated to increase with load cycles in the tertiary stage. The increased true stress yields extra viscoplastic strain, which is the reason why the permanent deformation is accelerated by the occurrence of cracks. To characterize the evolution of the viscofracture in the asphalt mixtures in compression, a pseudo J-integral Paris' law in terms of damage density is proposed and the material constants in the Paris' law are determined, which can be employed to predict the fracture of asphalt mixtures in compression. © 2013 American Society of Civil Engineers.

Quantum dot materials for terahertz generation applications

Compact and tunable semiconductor terahertz sources providing direct electrical control, efficient operation at room temperatures and device integration opportunities are of great interest at the present time. One of the most well-established techniques for terahertz generation utilises photoconductive antennas driven by ultrafast pulsed or dual wavelength continuous wave laser systems, though some limitations, such as confined optical wavelength pumping range and thermal breakdown, still exist. The use of quantum dot-based semiconductor materials, having unique carrier dynamics and material properties, can help to overcome limitations and enable efficient optical-to-terahertz signal conversion at room temperatures. Here we discuss the construction of novel and versatile terahertz transceiver systems based on quantum dot semiconductor devices. Configurable, energy-dependent optical and electronic characteristics of quantum-dot-based semiconductors are described, and the resonant response to optical pump wavelength is revealed. Terahertz signal generation and detection at energies that resonantly excite only the implanted quantum dots opens the potential for using compact quantum dot-based semiconductor lasers as pump sources. Proof-of-concept experiments are demonstrated here that show quantum dot-based samples to have higher optical pump damage thresholds and reduced carrier lifetime with increasing pump power.