bluuebunny/crossref_metadata_2025 huggingface dataset:
FARADAY ROTATION AND PRIMORDIAL MAGNETIC FIELDS CONSTRAINTS ON ULTRAVIOLET LORENTZ VIOLATION WITH SPACETIME TORSION
Authors: DE ANDRADE L. C. GARCIA
Published: March 2012

Recently Kahniashvili et al.9 presented a unified treatment for ultraviolet Lorentz violation (LV) testing through electromagnetic wave propagation in magnetized plasmas, based on dispersion and rotation measured data. Based on the fact discovered recently by Kostelecky et al., 3 that LV may place constraints on spacetime torsion, in this paper it is shown that on the limit of very low frequency torsion waves, it is possible to constraint torsion from Faraday rotation and CMB on a similar fashion as Minkowski spacetime plus torsion. Here, the Maxwells modified equations are obtained by a perturbative method introduced by de Sabbata and Gasperini [Introduction to Gravitation (World Scientific, 1980)]. Torsion is constraint to Q CMB ≈10-18 GeV which is not so stringent as the 10-31 GeV obtained by Kostelecky et al. However, Gamma-Ray Bursts (GRBs) may lead to the more string value obtained by Kostelecky et al.Another interesting constraint on torsion is shown to be placed by galactic dynamo seed magnetic fields. For torsion effects be compatible with the galactic dynamo seeds, one obtains a torsion constraint of 10-33 GeV which is two orders of magnitude more stringent that the above Kostelecky et al. limit.
THE STOCHASTIC RESETTING AND MASTER NONLINEAR FOKKER–PLANCK IN DISCRETE SPECTROSCOPY OF ULTRATHIN SILICON DIOXIDE FILM
Authors: BAHARI ALI
Published: March 2012

In this paper, we consider a particle (carrier) which is stochastically reset to its initial position at a constant rate r. It leads toward a non-equilibrium stationary state with non-Gaussian fluctuations for the particle position and enhance escape rate of particles through the ultrathin film.

Here we explore strongly-correlated random sequences. It is based on Master — nonlinear Fokker–Planck and chemical reaction equations. In that case compounding moments can set useful constraints to synchrotron radiation spectra of ultrathin film (SRSUTF). This mechanism is explained within a fitting process where both diffusion and reaction occur in discrete cells, and with both Si and O 2 treated as moving and reacting species for the very thin oxides.
SOLITON INTERACTIONS FOR THE GENERALIZED (3+1)-DIMENSIONAL BOUSSINESQ EQUATION
Authors: GAI XIAO-LING , GAO YI-TIAN , YU XIN , SUN ZHI-YUAN
Published: March 2012

Generalized (3+1)-dimensional Boussinesq equation is investigated in this paper. Through the dependent variable transformation and symbolic computation, the one- and two-soliton solutions are obtained. With the one-soliton solution, the coefficient effects in the soliton propagation process are investigated. Through analyzing the two-soliton solution, two kinds of two-soliton interactions are presented: (i) Two solitons merge into a bigger one whose amplitude increases but does not exceed the sum of the two at the moment of the collision; (ii) Two solitons can pass through each other, and their shapes keep unchanged with a phase shift after the separation. In addition, two kinds of analytic solutions are discussed: (i) "Amplitudes" of the two analytic solutions immediately turn to negative (positive) infinity after the "collision"; (ii) Two analytic solutions are fused into a higher peak (valley) at the moment of "collision", whose "amplitudes" change to negative (positive) infinity after the separation.
CONFORMAL GEOMETRY OF ESCORT PROBABILITY AND ITS APPLICATIONS
Authors: OHARA ATSUMI , MATSUZOE HIROSHI , AMARI SHUN-ICHI
Published: March 2012

Escort probability is a certain modification of ordinary probability and a conformally transformed structure can be introduced on the space of its distributions. In this contribution applications of escort probabilities and such a structure are focused on. We demonstrate that they naturally appear and play important roles for computationally efficient method to construct α-Voronoi partitions and analysis of related dynamical systems on the simplex.
IMPURITY EFFECT OF Λ HYPERON ON SHAPE-COEXISTENCE NUCLEUS 44S IN THE ENERGY FUNCTIONAL BASED COLLECTIVE HAMILTONIAN
Authors: MEI H. , LI Z. P. , YAO J. M. , HAGINO K.
Published: March 2012

The nonrelativistic Skyrme energy density functional (EDF) based collective Hamiltonian, that takes into account dynamical correlations related to the restoration of broken symmetries and fluctuations of quadrupole collective variables, is applied to quantitatively study the impurity effect of Λ hyperon on the collectivity of 44 S . Several Skyrme forces for both the nucleon–nucleon (NN) and Λ-nucleon (ΛN) interactions are used. The influence of pairing strengths on the polarization effect of Λ hyperon is also examined. It is found that although these Skyrme forces with different pairing strengths give somewhat different low-lying spectra for 44 S , all of them give similar and generally small size of Λ reduction effect (within 5%) on the collective properties.
DYNAMIC AND GOAL-BASED QUALITY MANAGEMENT FOR HUMAN-BASED ELECTRONIC SERVICES
Authors: KERN ROBERT , THIES HANS , ZIRPINS CHRISTIAN , SATZGER GERHARD
Published: March 2012

Crowdsourcing in the form of human-based electronic services (people services) provides a powerful way of outsourcing tasks to a large crowd of remote workers over the Internet. Research has shown that multiple redundant results delivered by different workers can be aggregated in order to achieve a reliable result. However, basic implementations of this approach are rather inefficient as they multiply the effort for task execution and are not able to guarantee a certain quality level. In this paper, we are addressing these challenges by elaborating on a statistical approach for quality management of people services which we had previously proposed. The approach combines elements of statistical quality management with dynamic group decisions. We present a comprehensive statistical model that enhances our original work and makes it more transparent. We also provide an extendible toolkit that implements our model and facilitates its application to real-time experiments as well as to simulations. A quantitative analysis based on an optical character recognition (OCR) scenario confirms the efficiency and reach of our model.
CHONDROCYTE RESPONSE TO TENSILE AND COMPRESSIVE CYCLIC LOADING MODALITIES
Authors: Kamineni Srinath , Wani Zubair , Luo Zong-Ping , Ruriko Yoshida , An Kai-Nan
Published: March 2012

There is very little data addressing cartilage response to tensile forces, and no literature attempts to correlate compressive with tensile modalities. Our hypothesis was that the cyclic compression and tension modulate chondrocyte matrix proteoglycan synthetic response differently. Porcine chondrocytes cultured to confluence on a flexible membrane were subjected to cyclic compression (Group A: 13 KPa at 1 Hz) or tension (Group C: 10% strain at 1 Hz) for 16 or 32 h; while controls not subjected to any force were kept (Group B). The chondrocytes were then stained with alcian blue and stained areas quantified with confocal microscopy and image processing software. Two-factor ANOVA with post-hoc tests (Scheffe and Bonferroni) statistical analysis were used. Proteoglycan staining covered 46% (range 28%–61%) and 39% (range 26%–49%) of the surface area following 32 and 16 h of compression respectively, 23% (range 15%–49%) for control, and 19% (range 10%–29%) and 16% (range 9%–25%) following 16 and 32 h tension respectively. Proteoglycan content following all compressions was significantly greater than with cyclic tension or control (p < 0.0001). Our data demonstrate that chondrocytes cultured in vitro respond to compression distinctly different from tension and that it is highly sensitive to mechanical loading, with rapid adaptation to its mechanical environment. These results imply that cartilage grown in culture, with the intention of transplantation, may structurally benefit from an environment of cyclic loading at higher frequencies.
India's Palaeoproterozoic legacy
Authors: Santosh M.
Published: March 2012

The Indian lithospheric plate assembles the history of geological events covering almost the entire history of our planet. The proto-Indian continent was an integral part of the Palaeoproterozoic supercontinent Columbia. Global mantle warming beneath this supercontinent triggered rising plumes that led to rifting and the emplacement of mafic dyke swarms and large igneous provinces in many of the major cratons of Peninsular India. Continued rifting and separation of crustal blocks led to the formation of thick passive margin successions. The opening of ocean basins and their eventual closure are recorded in the travelogue of oceanic plates from mid-ocean ridge to the trench in the form of ‘ocean plate stratigraphy’ in Proterozoic belts, including the association of dismembered ophiolites, pelagic sediments and continental margin sequences that were imbricated into accretionary belts such as those in the Aravalli–Delhi domain (Western India Suture), the Central India Tectonic Zone (Central India Suture) and the eastern margin of the East Dharwar Craton (Eastern India Suture). Recent U–Pb zircon chronology from ophiolitic rocks in the eastern margin of the Dharwar Craton shows ages spanning from 1.85 to 1.33 Ga suggesting a prolonged Wilson cycle of subduction–accretion processes before the final collisional event and the extrusion of high-grade metamorphic orogens. The extruded high pressure–temperature (
P–T
) metamorphic belts are often associated with mafic/ultramafic units with an abyssal signature. The available geophysical information from the Indian Palaeoproterozoic belts, particularly deep seismic reflection data, provides important clues on the architecture of these orogens and the subduction polarity. Whereas the Palaeoproterozoic convergent margins in the NW and SE sectors of the Indian peninsula were characterized by the westward subduction of oceanic plates, ocean closure along the Central India Tectonic Zone probably involved a double-sided subduction. The Wilson cycle traces a continuum from Palaeoproterozoic through Mesoproterozoic to Neoproterozoic in some of these belts, with a prolonged subduction–accretion history similar to the ongoing convergent margin processes in the western Pacific region. Peninsular India thus preserves a complete record from Pacific-type accretionary tectonics along the margins of the Columbia supercontinent to Himalayan-style collisional assembly within the Neoproterozoic Rodinia supercontinent.
Mesoarchaean–Palaeoproterozoic stratigraphic record of the Singhbhum crustal province, eastern India: a synthesis
Authors: Mazumder R. , Van Loon A. J. , Mallik L. , Reddy S. M. , Arima M. , Altermann W. , Eriksson P. G. , De S.
Published: March 2012

The Mesoarchaean–Palaeoproterozoic stratigraphic record of the Singhbhum crustal province, eastern India, implies sedimentation and volcanism in a changing tectonic scenario, and thus assumes immense geological significance. Although efforts have been made by many researchers in the past several decades to summarize various geological aspects of the Singhbhum crustal province, a critical synthesis of various stratigraphic issues was long overdue. The present contribution is an updated critical synthesis of the Mesoarchaean–Palaeoproterozoic stratigraphic record of the Singhbhum crustal province. We have pointed out the problematic stratigraphic issues of the Singhbhum crustal province that deserve careful scrutiny in order to gain better insights into the mode of stratigraphic sequence building.
Native iron in the Palaeoproterozoic Chaibasa Formation: primary or secondary?
Authors: Abbott Dallas H. , Mazumder Rajat , Breger Dee
Published: March 2012

Native Fe in the Chaibasa Formation may be the oldest native Fe ever found. The Chaibasa Formation contains pre-1.6 Ga offshore shelf sediments from the Singhbhum Craton in India. The sediments are light green in colour, consistent with a low content of organic matter and a metamorphic grade of greenschist–lower amphibolite facies. The native Fe grains are enclosed in fibrous mica. The native Fe occurs with magnetite crystals, evidence of relatively oxidizing conditions in the Chaibasa Formation during diagenesis. (Mn,Fe)S, a compound characteristic of reducing conditions, is found within the native Fe. The native Fe contains small amounts of native Si. Most grains of native Fe have rough edges. One bulbous grain has smooth edges and an internal wavy structure that is suggestive of a drop of melted iron. The melting temperature of pure Fe is 1535 °C. We also found native Fe with small amounts of carbon in it that appears to have a plate-like, pearlitic structure. Pearlite typically forms at temperatures of 723–500 °C. All of these temperatures are too high to be achieved during greenschist-facies metamorphism. As a result, we infer that the native Fe is primary rather than secondary. Our work and that of others suggests a primary, impact origin for the native Fe.
Metamorphic evolution of the Chotanagpur Granite Gneiss Complex of the East Indian Shield: current status
Authors: Sanyal S. , Sengupta P.
Published: March 2012

Geological information on the Chotanagpur Granite Gneiss Complex (CGGC) has been reviewed with a view to: (a) identifying the different metamorphic episodes; (b) developing an event stratigraphy in the high-grade blocks; and (c) correlating the different metamorphic episodes with the globally extensive orogenic processes. Integrating the existing geological information, the geological evolution of the high-grade block of the CGGC has been divided into four stages associated with four distinct metamorphic events (
M
I
−
M
IV
). The earliest metamorphic event (
M
I
) that is recorded in granulite enclaves in the regionally extensive felsic gneisses culminated in ultrahigh temperatures (>900 °C at
c
. 5–8 kbar) at around 1.87 Ga. In the second stage, voluminous felsic magmas were intruded – the
M
I
granulites – and were metamorphosed to form migmatitic felsic gneisses (
M
II
) within about 1.66–1.55 Ga. The third stage witnessed intrusions of a suite of anorthosite and porphyritic granitoids (
c
. 1.55–1.51 Ga), followed by high-grade metamorphism (700±50 °C, 6.5±1 kbar,
M
III
) during approximately 1.2–0.93 Ga. The fourth stage (
M
IV
) is marked by the intrusion of a suite of mafic dykes, followed by infiltration-driven metamorphism (600–750 °C at 7±1) during 0.87–0.78 Ga. The proposed metamorphic events have been correlated with the supercontinental cycles in the Proterozoic time.
Palaeoproterozoic sedimentation in the Cuddapah Basin, south India and regional tectonics: a review
Authors: Saha Dilip , Tripathy Vikash
Published: March 2012

The Proterozoic Cuddapah Basin of south India hosts a number of unconformity-bound sequences deposited over continental crust. The Palaeoproterozoic Papaghani Group with basal polymict conglomerate unconformably overlies the Archaean Peninsular Gneiss and set the stage for Palaeoproterozoic sedimentation following a long hiatus. Two cycles of fluvial–shallow-marine psammite–carbonate–pelite sedimentation in the western part of the basin (Papaghni sub-basin) is punctuated at different levels by mafic flows, sills and dykes, and less common acidic tuffs. Each of the sedimentation cycles fosters extensive carbonate platforms with dolomitic stromatolites and algal laminites. Emplacement of shallow crustal intrusives at the end of the first cycle was possibly linked to thermal anomalies in the mantle and associated widespread crustal extension in south India. Brittle fault-slip analysis from the western Cuddapah indicates repetitive extensional to strike-slip regimes. This paper proposes a likely late Palaeoproterozoic shallow-marine sedimentary sequence of the Nallamalai Fold Belt as allochthonous, thrusted over the successions of the Papaghni sub-basin and the Kurnool Group in the western part of the basin. Inversion of the Papaghni sub-basin and the development of regional erosional unconformities is discussed in the context of Palaeoproterozoic and early Mesoproterozoic orogenic events at the SE margin of India.
The power of computing; design guidelines in CS education
Authors: Reed Daniel , Guzdial Mark
Published: March 2012

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

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Daniel Reed writes about how computing systems increase human intellect and abilities. Mark Guzdial discusses the need to avoid polarized and extreme positions in education and the trend toward design-based research.
Can services and platform thinking help the U.S. Postal Service?
Authors: Cusumano Michael A.
Published: March 2012

How the U.S. Postal Service might improve the efficiency of its delivery platform.
Information technology and gross national happiness
Authors: Heeks Richard
Published: March 2012

Connecting digital technologies and happiness.
Reading CS classics
Authors: Tekir Selma
Published: March 2012

Revisiting required reading.
Is human mobility tracking a good idea?
Authors: Soper Daniel
Published: March 2012

Considering the trade-offs associated with human mobility tracking.
Why LINQ matters
Authors: Beckman Brian
Published: March 2012

The benefits of composability are becoming clear in software engineering.
Putting the 'smarts' into the smart grid
Authors: Ramchurn Sarvapali D. , Vytelingum Perukrishnen , Rogers Alex , Jennings Nicholas R.
Published: March 2012

A research agenda for making the smart grid a reality.
Probabilistic topic models
Authors: Blei David M.
Published: March 2012

Surveying a suite of algorithms that offer a solution to managing large document archives.
Skeletal muscle fibrosis develops in response to desmin deletion
Authors: Meyer Gretchen A. , Lieber Richard L.
Published: March 2012

Skeletal muscle is a dynamic composite of proteins that responds to both internal and external cues to facilitate muscle adaptation. In cases of disease or altered use, these messages can be distorted resulting in myopathic conditions such as fibrosis. In this work, we describe a mild and progressive fibrotic adaptation in skeletal muscle lacking the cytoskeletal intermediate filament protein desmin. Muscles lacking desmin become progressively stiffer, accumulate increased collagen, and increase expression of genes involved in extracellular matrix turnover. Additionally, in the absence of desmin, skeletal muscle is in an increased state of inflammation and regeneration as indicated by increased centrally nucleated fibers, elevated inflammation and regeneration related gene expression, and increased numbers of inflammatory cells. These data suggest a potential link between increased cellular damage and the development of fibrosis in muscles lacking the cytoskeletal support of the desmin filament network.
Cu/Zn superoxide dismutase (SOD1) induction is implicated in the antioxidative and antiviral activity of acetylsalicylic acid in HCV-expressing cells
Authors: Rivas-Estilla Ana María , Bryan-Marrugo Owen Lloyd , Trujillo-Murillo Karina , Pérez-Ibave Diana , Charles-Niño Claudia , Pedroza-Roldan Cesar , Ríos-Ibarra Clara , Ramírez-Valles Eda , Ortiz-López Rocío , Islas-Carbajal María Cristina , Nieto Natalia , Rincón-Sánchez Ana Rosa
Published: March 2012

We evaluated the participation of oxidative stress in the negative regulation of hepatitis C virus (HCV)-RNA induced by acetylsalicylic acid (ASA). We used the HCV subgenomic replicon cell system that stably expresses HCV-nonstructural proteins (Huh7 HCV replicon cells) and the parental cell line. Cells were exposed to 4 mM ASA at different times (12–72 h), and pyrrolidine dithiocarbamate (PDTC) was used as an antioxidant control. Reactive oxygen species (ROS) production, oxidized protein levels, cytosolic superoxide dismutase (Cu/Zn-SOD), and glutathione peroxidase (GPx) activity were measured to evaluate oxidative stress. In addition, viral RNA and prostaglandin (PGE2) levels were determined. We observed that ASA treatment decreased ROS production and oxidized protein levels in a time-dependent fashion in both parental and HCV replicon cells with a greater extent in the latter. Similar results were found with PDTC exposure. Average GPx activity was decreased, whereas a striking increase was observed in average cytosolic SOD activity at 48 and 72 h in both cells exposed to ASA, compared with untreated cells. HCV replicon cells showed higher levels of Cu/Zn-SOD expression (mRNA and protein) with ASA treatment (48 and 72 h), whereas NS5A protein levels showed decreased expression. In addition, we found that inhibition of SOD1 expression reversed the effect of ASA. Interestingly, PDTC downregulated HCV-RNA expression (55%) and PGE2 (60%) levels, imitating ASA exposure. These results suggest that ASA treatment could reduce cellular oxidative stress markers and modify Cu/Zn-SOD expression, a phenomenon that may contribute to the mechanisms involved in HCV downregulation.
Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2
Authors: Miura Kouichi , Yang Ling , van Rooijen Nico , Ohnishi Hirohide , Seki Ekihiro
Published: March 2012

Inflammatory cell infiltration in the liver is a hallmark of nonalcoholic steatohepatitis (NASH). The chemokine-chemokine receptor interaction induces inflammatory cell recruitment. CC-chemokine receptor (CCR)2 is expressed on hepatic macrophages and hepatic stellate cells. This study aims to investigate the therapeutic potential of CCR2 to NASH. Twenty-two weeks on a choline-deficient amino acid-defined (CDAA) diet induced steatosis, inflammatory cell infiltration, and liver fibrosis with increased CCR2 and monocyte chemoattractant protein (MCP)-1 expression in the wild-type livers. The infiltrated macrophages expressed CD68, CCR2, and a marker of bone marrow-derived monocytes, Ly6C. CCR2−/−mice had less steatosis, inflammatory cell infiltration, and fibrosis, and hepatic macrophages expressing CD68 and Ly6C were decreased. Toll-like receptor (TLR)4−/−, TLR9−/−, and MyD88−/−mice had reduced hepatic macrophage infiltration with decreased MCP-1 and CCR2 expression because TLR signaling is a potent inducer of MCP-1. To assess the role of Kupffer cells at the onset of NASH, Kupffer cells were depleted by liposomal clodronate. The Kupffer cell depletion ameliorated steatohepatitis with a decrease in the MCP-1 expression and recruitment of Ly6C-expressing macrophages at the onset of NASH. Finally, to test the therapeutic potential of targeting CCR2, a CCR2 inhibitor was administered to mice on a CDAA diet. The pharmaceutical inhibition of CCR2 prevented infiltration of the Ly6C-positive macrophages, resulting in an inhibition of liver inflammation and fibrosis. We concluded that CCR2 and Kupffer cells contribute to the progression of NASH by recruiting bone marrow-derived monocytes.
Role of gut nutrient sensing in stimulating appetite and conditioning food preferences
Authors: Sclafani Anthony , Ackroff Karen
Published: March 2012

The discovery of taste and nutrient receptors (chemosensors) in the gut has led to intensive research on their functions. Whereas oral sugar, fat, and umami taste receptors stimulate nutrient appetite, these and other chemosensors in the gut have been linked to digestive, metabolic, and satiating effects that influence nutrient utilization and inhibit appetite. Gut chemosensors may have an additional function as well: to provide positive feedback signals that condition food preferences and stimulate appetite. The postoral stimulatory actions of nutrients are documented by flavor preference conditioning and appetite stimulation produced by gastric and intestinal infusions of carbohydrate, fat, and protein. Recent findings suggest an upper intestinal site of action, although postabsorptive nutrient actions may contribute to flavor preference learning. The gut chemosensors that generate nutrient conditioning signals remain to be identified; some have been excluded, including sweet (T1R3) and fatty acid (CD36) sensors. The gut-brain signaling pathways (neural, hormonal) are incompletely understood, although vagal afferents are implicated in glutamate conditioning but not carbohydrate or fat conditioning. Brain dopamine reward systems are involved in postoral carbohydrate and fat conditioning but less is known about the reward systems mediating protein/glutamate conditioning. Continued research on the postoral stimulatory actions of nutrients may enhance our understanding of human food preference learning.
Impact of partial urethral obstruction on bladder function: time-dependent changes and functional correlates of altered expression of Ca2+ signaling regulators
Authors: Burmeister David , AbouShwareb Tamer , D'Agostino Ralph , Andersson Karl-Erik , Christ George J.
Published: March 2012

In animal models of partial urethral obstruction (PUO), altered smooth muscle function/contractility may be linked to changes in molecules that regulate calcium signaling/sensitization. PUO was created in male rats, and urodynamic studies were conducted 2 and 6 wk post-PUO. Cystometric recordings were analyzed for the presence or absence of nonvoiding contractions [i.e., detrusor overactivity (DO)]. RT-PCR and Western blots were performed on a subpopulation of rats to study the relationship between the expression of RhoA, L-type Ca2+ channels, Rho kinase-1, Rho kinase-2, inositol 1,4,5-trisphosphate, ryanodine receptor, sarco(endo)plasmic reticulum Ca2+-ATPase 2 and protein kinase C (PKC)-potentiated phosphatase inhibitor of 17 kDa, and urodynamic findings in the same animal. Animals displayed DO at 2 (38%) and 6 wk (43%) post-PUO, increases were seen in in vivo pressures at 2 wk, and residual volume at 6 wk. Statistical analysis of RT-PCR and Western blot data at 2 wk, during the compensatory phase of detrusor hypertrophy, documented that expression of molecules that regulate calcium signaling and sensitization was consistently lower in obstructed rats without DO than those with DO or control rats. Among rats with DO at 2 wk, linear regression analysis revealed positive correlations between in vivo pressures and protein and mRNA expression of several regulatory molecules. At 6 wk, in the presence of overt signs of bladder decompensation, no clear or consistent alterations in expression of these same targets were observed at the protein level. These data extend prior work to suggest that molecular profiling of key regulatory molecules during the progression of PUO-mediated bladder dysfunction may shed new light on potential biomarkers and/or therapeutic targets.
JNK-dependent AP-1 activation is required for aristolochic acid-induced TGF-β1 synthesis in human renal proximal epithelial cells
Authors: Rui Hong-liang , Wang Yan-yan , Cheng Hong , Chen Yi-pu
Published: March 2012

Chronic aristolochic acid nephropathy (CAAN) is a chronic and progressive tubulointerstitial nephropathy characterized by extensive interstitial fibrosis. Aristolochic acid (AA) could induce overexpression of transforming growth factor-β1 (TGF-β1) in a human renal proximal tubule epithelial cells line (HKC), which has been implicated in the pathogenesis of CAAN. The present studies in HKC cells showed 1) AA could activate JNK in time- and dose-dependent manners and JNK inhibitor SP600125 could inhibit AA-induced TGF-β1 promoter activity and TGF-β1 synthesis; 2) AA-induced JNK activation and TGF-β1 synthesis were significantly inhibited by kinase-inactive mutants of MEKK4, MKK4, or MKK7; 3) AA could upregulate luciferase activity derived by a wild-type TGF-β1 promoter, but not by an AP-1 binding-deficient TGF-β1 promoter; and 4) AA could upregulate expression of c-Fos, phospho-c-Jun, and phospho-ATF2. The above data suggest AA-induced TGF-β1 overexpression in HKC cells may be mainly mediated by the JNK signaling pathway. Both the upstream kinases of JNK including MEKK4, MKK4, and MKK7, and the downstream transcription factor of JNK, AP-1, may also participate in this process.
Persistent oxidative stress following renal ischemia-reperfusion injury increases ANG II hemodynamic and fibrotic activity
Authors: Basile David P. , Leonard Ellen C. , Beal Alisa G. , Schleuter Devin , Friedrich Jessica
Published: March 2012

ANG II is a potent renal vasoconstrictor and profibrotic factor and its activity is enhanced by oxidative stress. We sought to determine whether renal oxidative stress was persistent following recovery from acute kidney injury (AKI) induced by ischemia-reperfusion (I/R) injury in rats and whether this resulted in increased ANG II sensitivity. Rats were allowed to recover from bilateral renal I/R injury for 5 wk and renal blood flow responses were measured. Post-AKI rats showed significantly enhanced renal vasoconstrictor responses to ANG II relative to sham-operated controls and treatment of AKI rats with apocynin (15 mM, in the drinking water) normalized these responses. Recovery from AKI for 5 wk resulted in sustained oxidant stress as indicated by increased dihydroethidium incorporation in renal tissue slices and was normalized in apocynin-treated rats. Surprisingly, the renal mRNA expression for common NADPH oxidase subunits was not altered in kidneys following recovery from AKI; however, mRNA screening using PCR arrays suggested that post-AKI rats had decreased renal Gpx3 mRNA and an increased expression other prooxidant genes such as lactoperoxidase, myeloperoxidase, and dual oxidase-1. When rats were infused for 7 days with ANG II (100 ng·kg−1·min−1), renal fibrosis was not apparent in sham-operated control rats, but it was enhanced in post-AKI rats. The profibrotic response was significantly attenuated in rats treated with apocynin. These data suggest that there is sustained renal oxidant stress following recovery from AKI that alters both renal hemodynamic and fibrotic responses to ANG II, and may contribute to the transition to chronic kidney disease following AKI.
Resistive exercises, with or without whole body vibration, prevent vertebral marrow fat accumulation during 60 days of head-down tilt bed rest in men
Authors: Trudel Guy , Coletta Elizabeth , Cameron Ian , Belavý Daniel L. , Lecompte Martin , Armbrecht Gabriele , Felsenberg Dieter , Uhthoff Hans K.
Published: March 2012

Fat accumulates in the bone marrow of lumbar vertebrae with bed rest. Exercise with or without whole body vibration may counter this effect. Our objectives were to measure 1) the vertebral fat fraction (VFF) of men subjected to bed rest who performed resistive exercises with (RVE, n = 7) or without whole body vibration(RE, n = 8) or no exercise (CTR, n = 9) using three MRI techniques; and 2) changes in peripheral blood counts. Twenty-four healthy men (age: 20–45 yr) underwent −6° head-down tilt (HDT) bed rest for 60 days. MRI was performed using three techniques (fat saturation, proton spectroscopy, and in and out of phase) to measure the fat fraction of L3, L4, and/or L5 at baseline, mid-HDT, and end-HDT. Erythrocytes and leukocytes were counted at HDT days 19, 33, 47, 54, and 60. The mean absolute VFF was increased in the CTR group at mid-HDT and end-HDT (+3.9 ± 1.3 and +3.6 ± 1.2%, respectively, both P < 0.05). The RE group had a smaller VFF change than the CTR group at mid-HDT (−0.9 ± 1.2 vs. +3.9 ± 1.3%, P < 0.05). The RVE group had a smaller VFF change than the CTR group at end-HDT (−2.6 ± 1.9 vs. +3.5 ± 1.2%, P < 0.05). Erythrocyte counts were increased in all groups at HDT day 19 and HDT day 33 and in the RE group at HDT day 54 (all P < 0.05). Bed rest for 60 days at −6° HDT increased lumbar VFF in men beyond natural involution. RVE and RE regimens effectively prevented VFF accumulation. Higher erythrocyte counts were not altered by RVE or RE. Whole body vibration, along with RE administered to people with prolonged immobility, may prevent fat accumulation in their bone marrow.
Acute impact of intermittent pneumatic leg compression frequency on limb hemodynamics, vascular function, and skeletal muscle gene expression in humans
Authors: Sheldon Ryan D. , Roseguini Bruno T. , Thyfault John P. , Crist Brett D. , Laughlin M. H. , Newcomer Sean C.
Published: March 2012

The mechanisms by which intermittent pneumatic leg compression (IPC) treatment effectively treats symptoms associated with peripheral artery disease remain speculative. With the aim of gaining mechanistic insight into IPC treatment, the purpose of this study was to investigate the effect of IPC frequency on limb hemodynamics, vascular function, and skeletal muscle gene expression. In this two study investigation, healthy male subjects underwent an hour of either high-frequency (HF; 2-s inflation/3-s deflation) or low-frequency (LF; 4-s inflation/16-s deflation) IPC treatment of the foot and calf. In study 1 ( n = 11; 23.5 ± 4.7 yr), subjects underwent both HF and LF treatment on separate days. Doppler/ultrasonography was used to measure popliteal artery diameter and blood velocity at baseline and during IPC treatment. Flow-mediated dilation (FMD) and peak reactive hyperemia blood flow (RHBF) were determined before and after IPC treatment. In study 2 ( n = 19; 22.0 ± 4.6 yr), skeletal muscle biopsies were taken from the lateral gastrocnemius of the treated and control limb at baseline and at 30- and 150-min posttreatment. Quantitative PCR was used to assess mRNA concentrations of genes associated with inflammation and vascular remodeling. No treatment effect on vascular function was observed. Cuff deflation resulted in increased blood flow (BF) and shear rate (SR) in both treatments at the onset of treatment compared with baseline ( P < 0.01). BF and SR significantly diminished by 45 min of HF treatment only ( P < 0.01). Both treatments reduced BF and SR and elevated oscillatory shear index compared with baseline ( P < 0.01) during cuff inflation. IPC decreased the mRNA expression of cysteine-rich protein 61 from baseline and controls ( P <0 .01) and connective tissue growth factor from baseline ( P < 0.05) in a frequency-dependent manner. In conclusion, a single session of IPC acutely impacts limb hemodynamics and skeletal muscle gene expression in a frequency-dependent manner but does not impact vascular function.
Theoretical principles underlying optical stimulation of a channelrhodopsin-2 positive pyramidal neuron
Authors: Foutz Thomas J. , Arlow Richard L. , McIntyre Cameron C.
Published: March 2012

Optogenetics is an emerging field of neuromodulation that permits scaled, millisecond temporal control of the membrane dynamics of genetically targeted cells using light. Optogenetic technology has revolutionized neuroscience research; however, numerous biophysical questions remain on the optical and neuronal factors impacting the modulation of neural activity with photon-sensitive ion channels. To begin to address such questions, we developed a computational tool to explore the underlying principles of optogenetic neural stimulation. This “light-neuron” model consists of theoretical representations of the light dynamics generated by a fiber optic in brain tissue, coupled to a multicompartment cable model of a cortical pyramidal neuron embedded with channelrhodopsin-2 (ChR2) membrane dynamics. Simulations revealed that the large energies required to generate an action potential are primarily due to the limited conductivity of ChR2, and that the major determinants of stimulation threshold are the surface area of illuminated cell membrane and proximity to the light source. Our results predict that the activation threshold is sensitive to many of the properties of ChR2 (density, conductivity, and kinetics), tissue medium (scattering and absorbance), and the fiber-optic light source (diameter and numerical aperture). We also illustrate the impact of redistributing the ChR2 expression density (uniform vs. nonuniform) on the activation threshold. The model system developed in this study represents a scientific instrument to characterize the effects of optogenetic neuromodulation, as well as an engineering design tool to help guide future development of optogenetic technology.
Trace fear conditioning enhances synaptic and intrinsic plasticity in rat hippocampus
Authors: Song Chenghui , Detert Julia A. , Sehgal Megha , Moyer James R.
Published: March 2012

Experience-dependent synaptic and intrinsic plasticity are thought to be important substrates for learning-related changes in behavior. The present study combined trace fear conditioning with both extracellular and intracellular hippocampal recordings to study learning-related synaptic and intrinsic plasticity. Rats received one session of trace fear conditioning, followed by a brief conditioned stimulus (CS) test the next day. To relate behavioral performance with measures of hippocampal CA1 physiology, brain slices were prepared within 1 h of the CS test. In trace-conditioned rats, both synaptic plasticity and intrinsic excitability were significantly correlated with behavior such that better learning corresponded with enhanced long-term potentiation (LTP; r = 0.64, P < 0.05) and a smaller postburst afterhyperpolarization (AHP; r = −0.62, P < 0.05). Such correlations were not observed in pseudoconditioned rats, whose physiological data were comparable to those of poor learners and naive and chamber-exposed control rats. In addition, acquisition of trace fear conditioning did not enhance basal synaptic responses. Thus these data suggest that within the hippocampus both synaptic and intrinsic mechanisms are involved in the acquisition of trace fear conditioning.
The relative importance of retinal error and prediction in saccadic adaptation
Authors: Collins Thérèse , Wallman Josh
Published: March 2012

When saccades systematically miss their visual target, their amplitude adjusts, causing the position errors to be progressively reduced. Conventionally, this adaptation is viewed as driven by retinal error (the distance between primary saccade endpoint and visual target). Recent work suggests that the oculomotor system is informed about where the eye lands; thus not all “retinal error” is unexpected. The present study compared two error signals that may drive saccade adaptation: retinal error and prediction error (the difference between predicted and actual postsaccadic images). Subjects made saccades to a visual target in two successive sessions. In the first session, the target was extinguished during saccade execution if the amplitude was smaller (or, in other experiments, greater) than the running median, thereby modifying the average retinal error subjects experienced without moving the target during the saccade as in conventional adaptation paradigms. In the second session, targets were extinguished at the start of saccades and turned back on at a position that reproduced the trial-by-trial retinal error recorded in the first session. Despite the retinal error in the first and second sessions having been identical, adaptation was severalfold greater in the second session, when the predicted target position had been changed. These results argue that the eye knows where it lands and where it expects the target to be, and that deviations from this prediction drive saccade adaptation more strongly than retinal error alone.
Mislocalization of stationary and flashed bars after saccadic inward and outward adaptation of reactive saccades
Authors: Schnier Fabian , Lappe Markus
Published: March 2012

Recent studies have shown that saccadic inward adaptation (i.e., the shortening of saccade amplitude) and saccadic outward adaptation (i.e., the lengthening of saccade amplitude) rely on partially different neuronal mechanisms. There is increasing evidence that these differences are based on differences at the target registration or planning stages since outward but not inward adaptation transfers to hand-pointing and perceptual localization of flashed targets. Furthermore, the transfer of reactive saccade adaptation to long-duration overlap and scanning saccades is stronger after saccadic outward adaptation than that after saccadic inward adaptation, suggesting that modulated target registration stages during outward adaptation are increasingly used in the execution of saccades when the saccade target is visually available for a longer time. The difference in target presentation duration between reactive and scanning saccades is also linked to a difference in perceptual localization of different targets. Flashed targets are mislocalized after inward adaptation of reactive and scanning saccades but targets that are presented for a longer time (stationary targets) are mislocalized stronger after scanning than after reactive saccades. This link between perceptual localization and adaptation specificity suggests that mislocalization of stationary bars should be higher after outward than that after inward adaptation of reactive saccades. In the present study we test this prediction. We show that the relative amount of mislocalization of stationary versus flashed bars is higher after outward than that after inward adaptation of reactive saccades. Furthermore, during fixation stationary and flashed bars were mislocalized after outward but not after inward adaptation. Thus, our results give further evidence for different adaptation mechanisms between inward and outward adaptation and harmonize some recent research.
Bioanalytical Method Development and Validation of Memantine in Human Plasma by High Performance Liquid Chromatography with Tandem Mass Spectrometry: Application to Bioequivalence Study
Authors: Konda Ravi Kumar , Challa B. R. , Chandu Babu Rao , Chandrasekhar Kothapalli B.
Published: March 2012

A simple, sensitive, and rapid HPLC-MS/MS method was developed and validated for quantitative estimation of memantine in human plasma. Chromatography was performed on Zorbax SB-C18(4.6×75 mm, 3.5 μm) column. Memantine (ME) and internal standard Memantine-d6(MED6) were extracted by using liquid-liquid extraction and analyzed by LC-ESI-MS/MS using multiple-reaction monitoring (MRM) mode. The assay exhibited a linear dynamic range of 50.00–50000.00 pg/ml for ME in human plasma. This method demonstrated an intra- and interday precision within the range of 2.1–3.7 and 1.4–7.8%, respectively. Further intra- and interday accuracy was within the range of 95.6–99.8 and 95.7–99.1% correspondingly. The mean recovery of ME and MED6 was86.07±6.87and80.31±5.70%, respectively. The described method was successfully employed in bioequivalence study of ME in Indian male healthy human volunteers under fasting conditions.
Abdominal Decompression in Children
Authors: Ejike J. Chiaka , Mathur Mudit
Published: March 2012

Abdominal compartment syndrome (ACS) increases the risk for mortality in critically ill children. It occurs in association with a wide variety of medical and surgical diagnoses. Management of ACS involves recognizing the development of intra-abdominal hypertension (IAH) by intra-abdominal pressure (IAP) monitoring, treating the underlying cause, and preventing progression to ACS by lowering IAP. When ACS is already present, supporting dysfunctional organs and decreasing IAP to prevent new organ involvement become an additional focus of therapy. Medical management strategies to achieve these goals should be employed but when medical management fails, timely abdominal decompression is essential to reduce the risk of mortality. A literature review was performed to understand the role and outcomes of abdominal decompression among children with ACS. Abdominal decompression appears to have a positive effect on patient survival. However, prospective randomized studies are needed to fully understand the indications and impact of these therapies on survival in children.
Pharmacokinetics and Pharmacodynamics of Darunavir and Etravirine in HIV-1–Infected, Treatment-Experienced Patients in the Gender, Race, and Clinical Experience (GRACE) Trial
Authors: Kakuda Thomas , Sekar Vanitha , Vis Peter , Coate Bruce , Ryan Robert , Anderson David , De La Rosa Guy , Mrus Joseph
Published: March 2012

Objectives. Evaluation of pharmacokinetics and pharmacodynamics of darunavir and etravirine among HIV-1–infected, treatment-experienced adults from GRACE, by sex and race.Methods. Patients received darunavir/ritonavir 600/100mg twice daily plus other antiretrovirals, which could include etravirine 200mg twice daily. Population pharmacokinetics for darunavir and etravirine were determined over 48 weeks and relationships assessed with virologic response and safety. Rich sampling for darunavir, etravirine, and ritonavir was collected in a substudy at weeks 4, 24, and 48.Results. Pharmacokinetics were estimated in 376 patients for darunavir and 190 patients for etravirine. Median darunavir and were 60,642ng·h/mL and 3624ng/mL, respectively; and for etravirine were 4183ng · h/mL and 280ng/mL, respectively. There were no differences in darunavir or etravirine or by sex or race. Age, body weight, or use of etravirine did not affect darunavir exposure. No relationships were seen between darunavir pharmacokinetics and efficacy or safety. Patients with etravirine exposure in the lowest quartile generally had lower response rates. Rich sampling showed no time-dependent relationship for darunavir, etravirine, or ritonavir exposure over 48 weeks.Conclusions. Population pharmacokinetics showed no relevant differences in darunavir or etravirine exposure by assessed covariates. Lower etravirine exposures were associated with lower response rates.
Rising Intracellular Zinc by Membrane Depolarization and Glucose in Insulin-Secreting Clonal HIT-T15 Beta Cells
Authors: Slepchenko Kira G. , Li Yang V.
Published: March 2012

Zinc (Zn2+) appears to be intimately involved in insulin metabolism since insulin secretion is correlated with zinc secretion in response to glucose stimulation, but little is known about the regulation of zinc homeostasis in pancreatic beta-cells. This study set out to identify the intracellular zinc transient by imaging free cytosolic zinc in HIT-T15 beta-cells with fluorescent zinc indicators. We observed that membrane depolarization by KCl (30–60 mM) was able to induce a rapid increase in cytosolic concentration of zinc. Multiple zinc transients of similar magnitude were elicited during repeated stimulations. The amplitude of zinc responses was not affected by the removal of extracellular calcium or zinc. However, the half-time of the rising slope was significantly slower after removing extracellular zinc with zinc chelator CaEDTA, suggesting that extracellular zinc affect the initial rising phase of zinc response. Glucose (10 mM) induced substantial and progressive increases in intracellular zinc concentration in a similar way as KCl, with variation in the onset and the duration of zinc mobilization. It is known that the depolarization of beta-cell membrane is coupled with the secretion of insulin. Rising intracellular zinc concentration may act as a critical signaling factor in insulin metabolism of pancreatic beta-cells.
A Green Analytical Method Using Ultrasound in Sample Preparation for the Flow Injection Determination of Iron, Manganese, and Zinc in Soluble Solid Samples by Flame Atomic Absorption Spectrometry
Authors: Yebra M. Carmen
Published: March 2012

A simple and rapid analytical method was developed for the determination of iron, manganese, and zinc in soluble solid samples. The method is based on continuous ultrasonic water dissolution of the sample (5–30 mg) at room temperature followed by flow injection flame atomic absorption spectrometric determination. A good precision of the whole procedure (1.2–4.6%) and a sample throughput of ca. 25 samples h–1were obtained. The proposed green analytical method has been successfully applied for the determination of iron, manganese, and zinc in soluble solid food samples (soluble cocoa and soluble coffee) and pharmaceutical preparations (multivitamin tablets). The ranges of concentrations found were 21.4–25.61 μg g-1for iron, 5.74–18.30 μg g-1for manganese, and 33.27–57.90 μg g-1for zinc in soluble solid food samples and 3.75–9.90 μg g-1for iron, 0.47–5.05 μg g-1for manganese, and 1.55–15.12 μg g-1for zinc in multivitamin tablets. The accuracy of the proposed method was established by a comparison with the conventional wet acid digestion method using a pairedt-test, indicating the absence of systematic errors.