Identification of Early Biomarkers during Acetaminophen-Induced Hepatotoxicity by Fourier Transform Infrared Microspectroscopy

Acetaminophen is a widely prescribed drug used to relieve pain and fever; however, it is a leading cause of drug-induced liver injury and a burden on public healthcare. In this study, hepatotoxicity in mice post oral dosing of acetaminophen was investigated using liver and sera samples with Fourier Transform Infrared microspectroscopy. The infrared spectra of acetaminophen treated livers in BALB/ mice show decrease in glycogen, increase in amounts of cholesteryl esters and DNA respectively. Rescue experiments using L-methionine demonstrate that depletion in glycogen and increase in DNA are abrogated with pre-treatment, but not post-treatment, with L-methionine. This indicates that changes in glycogen and DNA are more sensitive to the rapid depletion of glutathione. Importantly, analysis of sera identified lowering of glycogen and increase in DNA and chlolesteryl esters earlier than increase in alanine aminotransferase, which is routinely used to diagnose liver damage. In addition, these changes are also observed in C57BL/6 and Nos2(-/-) mice. There is no difference in the kinetics of expression of these three molecules in both strains of mice, the extent of damage is similar and corroborated with ALT and histological analysis. Quantification of cytokines in sera showed increase upon APAP treatment. Although the levels of Tnf alpha and Ifn gamma in sera are not significantly affected, Nos2(-/-) mice display lower Il6 but higher Il10 levels during this acute model of hepatotoxicity. Overall, this study reinforces the growing potential of Fourier Transform Infrared microspectroscopy as a fast, highly sensitive and label-free technique for non-invasive diagnosis of liver damage. The combination of Fourier Transform Infrared microspectroscopy and cytokine analysis is a powerful tool to identify multiple biomarkers, understand differential host responses and evaluate therapeutic regimens during liver damage and, possibly, other diseases.

A spring-mass-lever model, stiffness and inertia maps for single-input, single-output compliant mechanisms

A spring-mass-lever (SML) model is introduced in this paper for a single-input-single-output compliant mechanism to capture its static and dynamic behavior. The SML model is a reduced-order model, and its five parameters provide physical insight and quantify the stiffness and inertia(1) at the input and output ports as well as the transformation of force and displacement between the input and output. The model parameters can be determined with reasonable accuracy without performing dynamic or modal analysis. The paper describes two uses of the SML model: computationally efficient analysis of a system of which the compliant mechanism is a part; and design of compliant mechanisms for the given user-specifications. During design, the SML model enables determining the feasible parameter space of user-specified requirements, assessing the suitability of a compliant mechanism to meet the user-specifications and also selecting and/or re-designing compliant mechanisms from an existing database. Manufacturing constraints, material choice, and other practical considerations are incorporated into this methodology. A micromachined accelerometer and a valve mechanism are used as examples to show the effectiveness of the SML model in analysis and design. (C) 2012 Published by Elsevier Ltd.

Functional maps within a single neuron

Narayanan R, Johnston D. Functional maps within a single neuron. J Neurophysiol 108: 2343-2351, 2012. First published August 29, 2012; doi:10.1152/jn.00530.2012.-The presence and plasticity of dendritic ion channels are well established. However, the literature is divided on what specific roles these dendritic ion channels play in neuronal information processing, and there is no consensus on why neuronal dendrites should express diverse ion channels with different expression profiles. In this review, we present a case for viewing dendritic information processing through the lens of the sensory map literature, where functional gradients within neurons are considered as maps on the neuronal topograph. Under such a framework, drawing analogies from the sensory map literature, we postulate that the formation of intraneuronal functional maps is driven by the twin objectives of efficiently encoding inputs that impinge along different dendritic locations and of retaining homeostasis in the face of changes that are required in the coding process. In arriving at this postulate, we relate intraneuronal map physiology to the vast literature on sensory maps and argue that such a metaphorical association provides a fresh conceptual framework for analyzing and understanding single-neuron information encoding. We also describe instances where the metaphor presents specific directions for research on intraneuronal maps, derived from analogous pursuits in the sensory map literature. We suggest that this perspective offers a thesis for why neurons should express and alter ion channels in their dendrites and provides a framework under which active dendrites could be related to neural coding, learning theory, and homeostasis.

A LOWER INITIAL ABUNDANCE OF SHORT-LIVED Ca-41 IN THE EARLY SOLAR SYSTEM AND ITS IMPLICATIONS FOR SOLAR SYSTEM FORMATION

The short-lived radionuclide Ca-41 plays an important role in constraining the immediate astrophysical environment and the formation timescale of the nascent solar system due to its extremely short half-life (0.1 Myr). Nearly 20 years ago, the initial ratio of Ca-41/Ca-40 in the solar system was determined to be (1.41 +/- 0.14) x 10(-8), primarily based on two Ca-Al-rich Inclusions (CAIs) from the CV chondrite Efremovka. With an advanced analytical technique for isotopic measurements, we reanalyzed the potassium isotopic compositions of the two Efremovka CAIs and inferred the initial ratios of Ca-41/Ca-40 to be (2.6 +/- 0.9) x 10(-9) and (1.4 +/- 0.6) x 10(-9) (2 sigma), a factor of 7-10 lower than the previously inferred value. Considering possible thermal processing that led to lower Al-26/Al-27 ratios in the two CAIs, we propose that the true solar system initial value of Ca-41/Ca-40 should have been similar to 4.2 x 10(-9). Synchronicity could have existed between Al-26 and Ca-41, indicating a uniform distribution of the two radionuclides at the time of CAI formation. The new initial Ca-41 abundance is 4-16 times lower than the calculated value for steady-state galactic nucleosynthesis. Therefore, Ca-41 could have originated as part of molecular cloud materials with a free decay time of 0.2-0.4 Myr. Alternative possibilities, such as a last-minute input from a stellar source and early solar system irradiation, could not be definitively ruled out. This underscores the need for more data from diverse CAIs to determine the true astrophysical origin of Ca-41.

All flavours of El Nino have similar early subsurface origins

The El Nino/Southern Oscillation phenomenon, characterized by anomalous sea surface temperatures and winds in the tropical Pacific, affects climate across the globe(1). El Ninos occur every 2-7 years, whereas the El Nino/Southern Oscillation itself varies on decadal timescales in frequency and amplitude, with a different spatial pattern of surface anomalies(2) each time the tropical Pacific undergoes a regime shift. Recent work has shown that Bjerknes feedback(3,4) (coupling of the atmosphere and the ocean through changes in equatorial winds driven by changes in sea surface temperature owing to suppression of equatorial upwelling in the east Pacific) is not necessary(5) for the development of an El Nino. Thus it is unclear what remains constant through regimes and is crucial for producing the anomalies recognized as El Nino. Here we show that the subsurface process of discharging warm waters always begins in the boreal summer/autumn of the year before the event (up to 18 months before the peak) independent of regimes, identifying the discharge process as fundamental to the El Nino onset. It is therefore imperative that models capture this process accurately to further our theoretical understanding, improve forecasts and predict how the El Nino/Southern Oscillation may respond to climate change.

Full Chemical Kinetic Simulation of Biogas Early Phase Combustion in SI Engines

This paper presents computational work on the biogas early phase combustion in spark ignition (SI) engines using detailed chemical kinetics. Specifically, the early phase combustion is studied to assess the effect of various ignition parameters such as spark plug location, spark energy, and number of spark plugs. An integrated version of the KIVA-3V and CHEMKIN codes was developed and used for the simulations utilizing detailed kinetics involving 325 reactions and 53 species The results show that location of the spark plug and local flow field play an important role. A central plug configuration, which is associated with higher local flow velocities in the vicinity of the spark plug, showed faster initial combustion. Although a dual plug configuration shows the highest rate of fuel consumption, it is comparable to the rate exhibited by the central plug case. The radical species important in the initiation of combustion are identified, and their concentrations are monitored during the early phase of combustion. The concentration of these radicals is also observed to correlate very well with the above-mentioned trend.Thus, the role of these radicals in promoting faster combustion has been clearly established. It is also observed that the minimum ignition energy required to initiate a self-sustained flame depends on the flow field condition in the vicinity of the spark plug.Increasing the methane content in the biogas has shown improved combustion.

Loss ratio of the EDF scheduling policy with early discarding technique

This paper considers a firm real-time M/M/1 system, where jobs have stochastic deadlines till the end of service. A method for approximately specifying the loss ratio of the earliest-deadline-first scheduling policy along with exit control through the early discarding technique is presented. This approximation uses the arrival rate and the mean relative deadline, normalized with respect to the mean service time, for exponential and uniform distributions of relative deadlines. Simulations show that the maximum approximation error is less than 4% and 2% for the two distributions, respectively, for a wide range of arrival rates and mean relative deadlines. (C) 2013 Elsevier B.V. All rights reserved.

MAPS: midline analysis and propagation of segmentation

Scenic word images undergo degradations due to motion blur, uneven illumination, shadows and defocussing, which lead to difficulty in segmentation. As a result, the recognition results reported on the scenic word image datasets of ICDAR have been low. We introduce a novel technique, where we choose the middle row of the image as a sub-image and segment it first. Then, the labels from this segmented sub-image are used to propagate labels to other pixels in the image. This approach, which is unique and distinct from the existing methods, results in improved segmentation. Bayesian classification and Max-flow methods have been independently used for label propagation. This midline based approach limits the impact of degradations that happens to the image. The segmented text image is recognized using the trial version of Omnipage OCR. We have tested our method on ICDAR 2003 and ICDAR 2011 datasets. Our word recognition results of 64.5% and 71.6% are better than those of methods in the literature and also methods that competed in the Robust reading competition. Our method makes an implicit assumption that degradation is not present in the middle row.

Robustness of early warning signals of regime shifts in time-delayed ecological models

Various ecological and other complex dynamical systems may exhibit abrupt regime shifts or critical transitions, wherein they reorganize from one stable state to another over relatively short time scales. Because of potential losses to ecosystem services, forecasting such unexpected shifts would be valuable. Using mathematical models of regime shifts, ecologists have proposed various early warning signals of imminent shifts. However, their generality and applicability to real ecosystems remain unclear because these mathematical models are considered too simplistic. Here, we investigate the robustness of recently proposed early warning signals of regime shifts in two well-studied ecological models, but with the inclusion of time-delayed processes. We find that the average variance may either increase or decrease prior to a regime shift and, thus, may not be a robust leading indicator in time-delayed ecological systems. In contrast, changing average skewness, increasing autocorrelation at short time lags, and reddening power spectra of time series of the ecological state variable all show trends consistent with those of models with no time delays. Our results provide insights into the robustness of early warning signals of regime shifts in a broader class of ecological systems.

Constraints on Be-10 and Ca-41 distribution in the early solar system from Al-26 and Be-10 studies of Efremovka CAIs

Three refractory coarse grained CAIs from the Efremovka CV3 chondrite, one (E65) previously shown to have formed with live Ca-41, were studied by ion microprobe for their Al-26-Mg-26 and Be-10-B-10 systematic in order to better understand the origin of Be-10. The high precision Al-Mg data and the inferred Al-26/Al-27 values attest that the precursors of the three CAIs evolved in the solar nebula over a period of few hundred thousand years before last melting-crystallization events. The initial Be-10/Be-9 ratios and delta B-10 values defined by the Be-10 isochrons for the three Efremovka CAIs are similar within errors. The CAI Be-10 abundance in published data underscores the large range for initial Be-10/Be-9 ratios. This is contrary to the relatively small range of Al-26/Al-27 variations in CAIs around the canonical ratio. Two models that could explain the origin of this large Be-10/Be-9 range are assessed from the collateral variations predicted for the initial delta B-10 values: (i) closed system decay of Be-10 from a ``canonical'' Be-10/Be-9 ratio and (ii) formation of CAIs from a mixture of solid precursors and nebula gas irradiated during up to a few hundred thousand years. The second scenario is shown to be the most consistent with the data. This shows that the major fraction of Be-10 in CAIs was produced by irradiation of refractory grains, while contributions of galactic cosmic rays trapping and early solar wind irradiation are less dominant. The case for Be-10 production by solar cosmic rays irradiation of solid refractory precursors poses a conundrum for Ca-41 because the latter is easily produced by irradiation and should be more abundant than what is observed in CAIs. Be-10 production by irradiation from solar energetic particles requires high Ca-41 abundance in early solar system, however, this is not observed in CAIs. (C) 2013 Elsevier B.V. All rights reserved.

Condition R and proper holomorphic maps between equidimensional product domains

We consider proper holomorphic mappings of equidimensional pseudoconvex domains in complex Euclidean space, where both source and target can be represented as Cartesian products of smoothly bounded domains. It is shown that such mappings extend smoothly up to the closures of the domains, provided each factor of the source satisfies Condition R. It also shown that the number of smoothly bounded factors in the source and target must be the same, and the proper holomorphic map splits as a product of proper mappings between the factor domains. (C) 2013 Elsevier Inc. All rights reserved.

Early osseointegration of a strontium containing glass ceramic in a rabbit model

The most important property of a bone cement or a bone substitute in load bearing orthopaedic implants is good integration with host bone with reduced bone resorption and increased bone regeneration at the implant interface. Long term implantation of metal-based joint replacements often results in corrosion and particle release, initiating chronic inflammation leading onto osteoporosis of host bone. An alternative solution is the coating of metal implants with hydroxyapatite (HA) or bioglass or the use of bulk bioglass or HA-based composites. In the above perspective, the present study reports the in vivo biocompatibility and bone healing of the strontium (Sr)-stabilized bulk glass ceramics with the nominal composition of 4.5SiO(2)-3Al(2)O(3)-1.5P(2)O(5)-3SrO-2SrF(2) during short term implantation of up to 12 weeks in rabbit animal model. The progression of healing and bone regeneration was qualitatively and quantitatively assessed using fluorescence microscopy, histological analysis and micro-computed tomography. The overall assessment of the present study establishes that the investigated glass ceramic is biocompatible in vivo with regards to local effects after short term implantation in rabbit animal model. Excellent healing was observed, which is comparable to that seen in response to a commercially available implant of HA-based bioglass alone. (C) 2013 Elsevier Ltd. All rights reserved.

An early in-situ stress signature of the AlN-Si pre-growth interface for successful integration of nitrides with (111) Si

The integration of Metal Organic Chemical Vapor Deposition (MOCVD) grown group III-A nitride device stacks on Si (111) substrates is critically dependent on the quality of the first AlN buffer layer grown. A Si surface that is both oxide-free and smooth is a primary requirement for nucleating such layers. A single parameter, the AlN layer growth stress, is shown to be an early (within 50 nm), clear (<0.5 GPa versus > 1GPa), and fail-safe indicator of the pre-growth surface, and the AlN quality required for successful epitaxy. Grain coalescence model for stress generation is used to correlate growth stress, the AlN-Si interface, and crystal quality. (C) 2013 AIP Publishing LLC.

Better early osteogenesis of electroconductive hydroxyapatite-calcium titanate composites in a rabbit animal model

In view of the fact that bone healing can be enhanced due to external electric field application, it is important to assess the influence of the implant conductivity on the bone regeneration in vivo. To address this issue, this study reports the in vivo biocompatibility property of multistage spark plasma sintered hydroxyapatite (HA)-80 wt % calcium titanate (CaTiO3) composites and monolithic HA, which have widely different conductivity property (14 orders of magnitude difference). The ability of bone regeneration was assessed by implantation in cylindrical femoral bone defects of rabbit animal model for varying time period of 1, 4, and 12 weeks. The overall assessment of the histology results suggests that the progressive healing of bone defects around HA-80 wt % CaTiO3 is associated with a better efficacy with respect to (w.r.t) early stage neobone formation, which is histomorphometrically around 140% higher than monolithic HA. Overall, this study demonstrates that the in vivo biocompatibility property of HA-80 wt % CaTiO3 with respect to local effects after 12 weeks of implantation is not compromised both qualitatively and quantitatively, and a comparison with control implant (HA) points toward the critical role of electrical conductivity on better early stage bone regeneration. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 842-851, 2014.