Side Chain Structure Determines Unique Physiologic and Therapeutic Properties of norUrsodeoxycholic Acid in Mdr2(-/-) Mice

24-norursodeoxycholic acid (norUDCA), a side chain-modified ursodeoxycholic acid derivative, has dramatic therapeutic effects in experimental cholestasis and may be a promising agent for the treatment of cholestatic liver diseases. We aimed to better understand the physiologic and therapeutic properties of norUDCA and to test if they are related to its side chain length and/or relative resistance to amidation. For this purpose, Mdr2-/- mice, a model for sclerosing cholangitis, received either a standard diet or a norUDCA-, tauro norursodeoxycholic acid (tauro- norUDCA)-, or di norursodeoxycholic acid (di norUDCA)-enriched diet. Bile composition, serum biochemistry, liver histology, fibrosis, and expression of key detoxification and transport systems were investigated. Direct choleretic effects were addressed in isolated bile duct units. The role of Cftr for norUDCA-induced choleresis was explored in Cftr-/- mice. norUDCA had pharmacologic features that were not shared by its derivatives, including the increase in hepatic and serum bile acid levels and a strong stimulation of biliary HCO3- -output. norUDCA directly stimulated fluid secretion in isolated bile duct units in a HCO3- -dependent fashion to a higher extent than the other bile acids. Notably, the norUDCA significantly stimulated HCO 3- -output also in Cftr-/- mice. In Mdr2-/- mice, cholangitis and fibrosis strongly improved with norUDCA, remained unchanged with tauro- norUDCA, and worsened with di norUDCA. Expression of Mrp4, Cyp2b10, and Sult2a1 was increased by norUDCA and di norUDCA, but was unaffected by tauro- norUDCA. Conclusion:The relative resistance of norUDCA to amidation may explain its unique physiologic and pharmacologic properties. These include the ability to undergo cholehepatic shunting and to directly stimulate cholangiocyte secretion, both resulting in a HCO3- -rich hypercholeresis that protects the liver from cholestatic injury.

Intraplate Response to the Great 2004 Sumatra-Andaman Earthquake: A Study from the Andaman Segment

The 1300-km rupture of the 2004 interplate earthquake terminated at around 15 degrees N, in the northernmost segment of the Andaman-Nicobar subduction zone. This part of the plate boundary is noted for its generally lower level seismicity, compared with the southern segments. Based on the Global Centroid Moment Tensor (CMT) and National Earthquake Information Center (NEIC) data, most of the earthquakes of M-w >= 4.5 prior to 2004 were associated with the Andaman Spreading Ridge (ASR), and a few events were located within the forearc basin. The 2004 event was followed by an upward migration of hypocenters along the subducting plate, and the Andaman segment experienced a surge of aftershock activity. The continuing extensional faulting events, including the most recent earthquake (10 August 2009; M-w 7.5) in the northern end of the 2004 rupture, suggest the reduction of compressional strain associated with the interplate event. The style of faulting of the intraplate events before and after a great plate boundary earthquake reflects the relative influences of the plate-driving forces. Here we discuss the pattern of earthquakes in the Andaman segment before and after the 2004 event to appraise the spatial and temporal relation between large interplate thrust events and intraplate deformation. This study suggests that faulting mechanisms in the outer-ridge and outer-rise regions could be indicative of the maturity of interplate seismic cycles.

The effect of grain size on the high-strain, high-strain-rate behavior of copper

Copper with four widely differing grain sizes was subjected to high-strain-rate plastic deformation in a special experimental arrangement in which high shear strains of approximately 2 to 7 were generated. The adiabatic plastic deformation produced temperature rises in excess of 300 K, creating conditions favorable for dynamic recrystallization, with an attendant change in the mechanical response. Preshocking of the specimens to an amplitude of 50 GPa generated a high dislocation density; twinning was highly dependent on grain size, being profuse for the 117- and 315-mu m grain-size specimens and virtually absent for the 9.5-mu m grain-size specimens. This has a profound effect on the subsequent mechanical response of the specimens, with the smaller grain-size material undergoing considerably more hardening than the larger grain-size material. A rationale is proposed which leads to a prediction of the shock threshold stress for twinning as a function of grain size. The strain required for localization of plastic deformation was dependent on the combined grain size/shock-induced microstructure, with the large grain-size specimens localizing more readily. The experimental results obtained are rationalized in terms of dynamic recrystallization, and a constitutive equation is applied to the experimental results; it correctly predicts the earlier onset of localization for the large grain-size specimens. It is suggested that the grain-size dependence of shock response can significantly affect the performance of shaped charges.

Connectivity-aware Routing in Sensor Networks

Sensor network applications such as environmental monitoring demand that the data collection process be carried out for the longest possible time. Our paper addresses this problem by presenting a routing scheme that ensures that the monitoring network remains connected and hence the live sensor nodes deliver data for a longer duration. We analyze the role of relay nodes (neighbours of the base-station) in maintaining network connectivity and present a routing strategy that, for a particular class of networks, approaches the optimal as the set of relay nodes becomes larger. We then use these findings to develop an appropriate distributed routing protocol using potential-based routing. The basic idea of potential-based routing is to define a (scalar) potential value at each node in the network and forward data to the neighbor with the highest potential. We propose a potential function and evaluate its performance through simulations. The results show that our approach performs better than the well known lifetime maximization policy proposed by Chang and Tassiulas (2004), as well as AODV [Adhoc on demand distance vector routing] proposed by Perkins (1997).

The June 2010 Nicobar Earthquake: Fault Reactivation on the Subducting Oceanic Plate

The similar to 1300-km-long rupture zone of the 2004 Andaman-Sumatra megathrust earthquake continues to generate a mix of thrust, normal, and strike-slip faulting events. The 12 June 2010 M(w) 7.5 event on the subducting plate is the most recent large earthquake on the Nicobar segment. The left-lateral faulting mechanism of this event is unusual for the outer-rise region, considering the stress transfer processes that follow great underthrusting earthquakes. Another earthquake (M(w) 7.2) with a similar mechanism occurred very close to this event on 24 July 2005. These earthquakes and most of their aftershocks on the subducting plate were generated by left-lateral strike-slip faulting on north-northeast-south-southwest oriented near-vertical faults, in response to north-northwest-south-southeast directed compression. Pre-2004 earthquake faulting mechanisms on the subducting oceanic plate are consistent with this pattern. Post-2004, left-lateral faulting on the subducting oceanic plate clusters between 5 degrees N and 9 degrees N, where the 90 degrees E ridge impinges the trench axis. Our study observes that the subducting plate off the Sumatra and Nicobar segments behaves similarly to a chip of the India-Australia plate, deforming in response to a generally northwest-southeast oriented compression, an aspect that must be factored into the plate deformation models.

Geoarchaeological Evidence of a Chola-Period Tsunami from an Ancient Port at Kaveripattinam on the Southeastern Coast of India

Literature of the ancient Chola Dynasty (A.D. 9th-11th centuries) of South India and recent archaeological excavations allude to a sea flood that crippled the ancient port at Kaveripattinam, a trading hub for Southeast Asia, and probably affected the entire South Indian coast, analogous to the 2004 Indian Ocean tsunami impact. We present sedimentary evidence from an archaeological site to validate the textual references to this early medieval event. A sandy layer showing bed forms representing high-energy conditions, possibly generated by a seaborne wave, was identified at the Kaveripattinam coast of Tamil Nadu, South India. Its sedimentary characteristics include hummocky cross-stratification, convolute lamination with heavy minerals, rip-up clasts, an erosional contact with the underlying mud bed, and a landward thinning geometry. Admixed with 1000-year-old Chola period artifacts, it provided an optically stimulated luminescence age of 1091 perpendicular to 66 yr and a thermoluminescence age of 993 perpendicular to 73 yr for the embedded pottery sherds. The dates of these proxies converge around 1000 yr B. P., correlative of an ancient tsunami reported from elsewhere along the Indian Ocean coasts. (C) 2011 Wiley Periodicals, Inc.

Optical diffraction of second-harmonic signals in the LiBO2-Nb2O5 glasses induced by self-organized LiNbO3 crystallites

The nanocrystallites ( ≈ 3 nm) of LiNbO3, evolved in the (100−x)LiBO2-xNb2O5 (5x20, in molar ratio) glass system exhibited intense second-harmonic signals in transmission mode when exposed to infrared (IR) light at λ = 1064 nm. The second-harmonic waves were found to undergo optical diffraction which was attributed to the presence of self-organized submicrometer-sized LiNbO3 crystallites that were grown within the glass matrix along the parallel damage fringes created by the IR laser radiation. Micro-Raman studies carried out on the laser-irradiated samples confirmed the self-organized crystallites to be LiNbO3.

Relaxor behavior of K0.5La0.5Bi2Nb2O9 ceramics

K0.5La0.5Bi2Nb2O9, a relaxor, was synthesized and the structural studies confirmed it to be an n = 2 member of the Aurivillius oxides. The ½{h00} and ½{hk0} types of superlattice reflections in the electron diffraction patterns reflected the presence of ordered polar regions. A broad dielectric peak with frequency dependent dielectric maximum temperature was observed. The dielectric relaxation obeyed the Vogel-Fulcher relation wherein Ea = 0.04 eV, Tf = 428 K,and ωo = 1010 Hz. The diffuseness parameter γ = 2.003 established the relaxor nature and it was attributed to the A-site cationic disorder. The piezoelectric d31 coefficient was 0.5 pC/N at 300 K and 2 pC/N at 480 K.

Relaxor characteristics of layered Ba1-(3/2)xLaxBi2Nb2O9 ceramics

Barium lanthanum bismuth niobate Ba1−(3/2)xLaxBi2Nb2O9 (x = 0, 0.05, 0.1, and 0.15) powders have been prepared via solid state reaction route. The monophasic layered perovskite nature of each composition of these was confirmed by x-ray diffraction studies. A continuous decrease in the lattice parameter c of parent BaBi2Nb2O9 with increase in La3+ doping level was noteworthy. A decrease in dielectric constant maximum (εm), a shift in dielectric anomaly to lower temperatures (from 488 to 382 K), and an increase in the diffuseness (γ) (from 1.58 to 1.84) of dielectric anomaly were encountered on increasing x from 0 to 0.15. Vogel-Fulcher analyses showed a decrease in freezing temperature (Tf) (from 157 to 40 K) and an increase in the activation energy (0.53 to 1.12 eV) for frequency dispersion with increase in La3+ content. A downward shift in the peak position of the pyroelectric coefficient with increasing La3+ doping level was observed. The observed changes in the above physical properties were attributed to the increase in A-site chemical heterogeneity as a result of aliovalent La3+ doping on Ba2+ sites and associated A-site vacancy formation.

Andaman Postseismic Deformation Observations: Still Slipping after All These Years?

More than six years after the great (M-w 9.2) Sumatra-Andaman earthquake, postevent processes responsible for relaxation of the coseismic stress change remain controversial. Modeling of Andaman Islands Global Positioning System (GPS) displacements indicated early near-field motions were dominated by slip down-dip of the rupture, but various researchers ascribe elements of relaxation to dominantly poroelastic, dominantly viscoelastic, and dominantly fault slip processes, depending primarily on their measurement sampling and modeling tools used. After subtracting a pre-2004 interseismic velocity, significant transient motion during the 2008.5-2010.5 epoch confirms that postseismic relaxation processes continue in Andaman. Modeling three-component velocities as viscoelastic flow yields a weighted root-mean-square (wrms) misfit that always exceeds the wrms of the measured signal (26.3 mm/yr). The best-fitting models are those that yield negligible deformation, indicating the model parameters have no real physical meaning. GPS velocities are well fit (wrms 4.0 mm/yr) by combining a viscoelastic flow model that best fits the horizontal velocities with similar to 50 cm/yr thrust slip down-dip of the coseismic rupture. Both deep slip and flow respond to stress changes, and each can significantly change stress in the realm of the other; it therefore is reasonable to expect that both transient deep slip and viscoelastic flow will influence surface deformation long after a great earthquake.

LOCAL TWO-DIMENSIONAL PARTICLE-IN-CELL SIMULATIONS OF THE COLLISIONLESS MAGNETOROTATIONAL INSTABILITY

The magnetorotational instability (MRI) is a crucial mechanism of angular momentum transport in a variety of astrophysical accretion disks. In systems accreting at well below the Eddington rate, such as the central black hole in the Milky Way (Sgr A*), the plasma in the disk is essentially collisionless. We present a nonlinear study of the collisionless MRI using first-principles particle-in-cell plasma simulations. We focus on local two-dimensional (axisymmetric) simulations, deferring more realistic three-dimensional simulations to future work. For simulations with net vertical magnetic flux, the MRI continuously amplifies the magnetic field, B, until the Alfven velocity, v(A), is comparable to the speed of light, c (independent of the initial value of v(A)/c). This is consistent with the lack of saturation of MRI channel modes in analogous axisymmetric MHD simulations. The amplification of the magnetic field by the MRI generates a significant pressure anisotropy in the plasma (with the pressure perpendicular to B being larger than the parallel pressure). We find that this pressure anisotropy in turn excites mirror modes and that the volume-averaged pressure anisotropy remains near the threshold for mirror mode excitation. Particle energization is due to both reconnection and viscous heating associated with the pressure anisotropy. Reconnection produces a distinctive power-law component in the energy distribution function of the particles, indicating the likelihood of non-thermal ion and electron acceleration in collisionless accretion disks. This has important implications for interpreting the observed emission-from the radio to the gamma-rays-of systems such as Sgr A*.

The study of dielectric, pyroelectric and piezoelectric properties on hot pressed PZT-PMN systems

Hot uniaxial pressing technique has been adopted for the densification of PZT-PMN system with an aim to yield dense ceramics and to lower the sintering temperature and time for achieving better and reproducible electronic properties. The ceramics having >97% theoretical density and micron size grains are investigated for their dielectric, pyroelectric and piezoelectric properties. The effect of Li and Mn addition has also been studied. Copyright 2012 Author(s). This article is distributed under a Creative Commons Attribution 3.0 Unported License. http://dx.doi.org/10.1063/1.4769889]

Constraining large earthquakes along the Andaman trench using deepwater turbidites: prospects and challenges

The 2004 Sumatra-Andaman earthquake was unprecedented in terms of its magnitude (M-w 9.2), rupture length along the plate boundary (1300 km) and size of the resultant tsunami. Since 2004, efforts are being made to improve the understanding of the seismic hazard in the Sumatra-Andaman subduction zone in terms of recurrence patterns of major earthquakes and tsunamis. It is reasonable to assume that previous earthquake events in the Myanmar Andaman segment must be preserved in the geological record in the form of seismo-turbidite sequences. Here we present the prospects of conducting deep ocean palaeoseismicity investigations in order to refine the quantification of the recurrence pattern of large subduction-zone earthquakes along the Andaman-Myanmar arc. Our participation in the Sagar Kanya cruise SK-273 (in June 2010) was to test the efficacy of such a survey. The primary mission of the cruise, along a short length (300 km) of the Sumatra Andaman subduction front was to collect bathymetric data of the ocean floor trenchward of the Andaman Islands. The agenda of our piggyback survey was to fix potential coring sites that might preserve seismo-turbidite deposits. In this article we present the possibilities and challenges of such an exercise and our first-hand experience of such a preliminary survey. This account will help future researchers with similar scientific objectives who would want to survey the deep ocean archives of this region for evidence of extreme events like major earthquakes.