Major Loop Research Articles

The membrane topology of vitamin K epoxide reductase is conserved between human isoforms and the bacterial enzyme.

The membrane topology of vitamin K epoxide reductase (VKOR) is controversial with data supporting both a three transmembrane and a four transmembrane model. The positioning of the transmembrane domains and the loops between these domains is critical if we are to understand the mechanism of vitamin K oxidation and its recycling by members of the thioredoxin family of proteins and the mechanism of action of warfarin, an inhibitor of VKOR. Here we show that both mammalian VKOR isoforms adopt the same topology, with the large loop between transmembrane one and two facing the lumen of the endoplasmic reticulum (ER). We used a redox sensitive green fluorescent protein (GFP) fused to the N- or C-terminus to show that these regions face the cytosol, and introduction of glycosylation sites along with mixed disulfide formation with thioredoxin-like transmembrane protein (TMX) to demonstrate ER localization of the major loop. The topology is identical with the bacterial homologue from Synechococcussp., for which the structure and mechanism of recycling has been characterized. Our results provide a resolution to the membrane topology controversy and support previous results suggesting a role for members of the ER protein disulfide isomerase (PDI) family in recycling VKOR.

Comprehensive study of the influence of aging on the hysteresis behavior of a lithium iron phosphate cathode-based lithium ion battery – An experimental investigation of the hysteresis

In this work a detailed investigation of the hysteresis behavior of the open circuit voltage (OCV) in a lithium iron phosphate (LiFePO4) cathode-based lithium-ion cell is presented. For the first time the hysteresis behavior of the OCV in a LiFePO4 cell is investigated in detail, taking the aging state of the cells into account as a fundamental factor. Tests were carried out in a time window of more than two years on cells in different aging states. The dependency of the major and minor loops of the OCV on temperature, current rate, short-term history and aging are shown and deeply discussed. The results show that the characteristics of the hysteresis of the OCV change completely during battery lifetime, not only concerning the major OCV boundaries but also regarding the single minor loops obtained through partial charge/discharge processes. The paper discusses the results considering different approaches presented in the literature published by date, and addresses the necessity of understanding the physic-chemical behavior of the cell in order to correctly determine the battery state in the application.

Statistical magnetometry on isolated NiCo nanowires and nanowire arrays: a comparative study

The first-order reversal curve (FORC) method can be used to extract information about the interaction and switching field distribution of ferromagnetic nanowire arrays, yet it remains challenging to acquire reliable values. Within ordered pores of anodic alumina templates we electrochemically synthesize eight different NixCo1−x samples with x varying between 0.05 and 1. FORC diagrams are acquired using vibrating sample magnetometry. By dissolving the template and using the magneto-optical Kerr effect, we measure the hysteresis loops of up to 100 different and isolated nanowires for each sample to gain precise information about the intrinsic switching field distribution. Values of the interaction field are extracted from a deshearing of the major hysteresis loop. We present a comparative study between all methods in order to evaluate and reinforce current FORC theory with experimental findings.

The Time Lags Effects of Innovation Input on Output in National Innovation Systems: The Case of China

This paper investigates the time lags effects of innovation input on output in the national innovation systems (NIS). Firstly, we analyze the intrinsic properties of China’s NIS based on the conceptual framework and the causal loop diagram. Secondly, we construct a time lags distribution calculation model and employ the main innovation input indicators to measure the specific characteristics of time lags effects of innovation input on output for China in the period 2000–2012. The results indicate that there are considerable time lags in the four major feedback loops, and the distribution of time lags is various according to the characteristics of innovation input and influencing factors in the internal transformation. The trends of time lags from R&D personnel and industry-academia-research collaboration show steady growth, and the trends of time lags from R&D expenditure and government’s macro-control take inverted U-shaped pattern. Finally, we combine the estimation results of lags distribution calculation model with the analysis results of the causal loop diagram (including positive loops and negative loops) to provide some innovation policy suggestions. This study provides important implications for our understanding of the long-term complex lags effects of innovation input on output as well as for policy-makers designing and implementing the innovation strategies.

Role of RNA secondary structure in emergence of compartment specific hepatitis B virus immune escape variants.

AIMTo investigate the role of subgenotype specific RNA secondary structure in the compartment specific selection of hepatitis B virus (HBV) immune escape mutations.METHODSThis study was based on the analysis of the specific observation of HBV subgenotype A1 in the serum/plasma, while subgenotype A2 with G145R mutation in the peripheral blood leukocytes (PBLs). Genetic variability found among the two subgenotypes was used for prediction and comparison of the full length pregenomic RNA (pgRNA) secondary structure and base pairings. RNA secondary structures were predicted for 37 °C using the Vienna RNA fold server, using default parameters. Visualization and detailed analysis was done using RNA shapes program.RESULTSIn this analysis, using similar algorithm and conditions, entirely different pgRNA secondary structures for subgenotype A1 and subgenotype A2 were predicted, suggesting different base pairing patterns within the two subgenotypes of genotype A, specifically, in the HBV genetic region encoding the major hydrophilic loop. We observed that for subgenotype A1 specific pgRNA, nucleotide 358U base paired with 1738A and nucleotide 587G base paired with 607C. However in sharp contrast, in subgenotype A2 specific pgRNA, nucleotide 358U was opposite to nucleotide 588G, while 587G was opposite to 359U, hence precluding correct base pairing and thereby lesser stability of the stem structure. When the nucleotides at 358U and 587G were replaced with 358C and 587A respectively (as observed specifically in the PBL associated A2 sequences), these nucleotides base paired correctly with 588G and 359U, respectively.CONCLUSIONThe results of this study show that compartment specific mutations are associated with HBV subgenotype specific alterations in base pairing of the pgRNA, leading to compartment specific selection and preponderance of specific HBV subgenotype with unique mutational pattern.

Contourite drifts as indicators of Cenozoic bottom water intensity in the eastern Agulhas Ridge area, South Atlantic

High-resolution multichannel seismic reflection profiles acquired in the Agulhas Ridge area (eastern sub-polar South Atlantic) were used in conjunction with multibeam bathymetry and Ocean Drilling Program Leg 177 borehole data to characterise deep water contourite formation in the area of the northeastern Agulhas Ridge and the Cape Rise seamounts. The transverse ridge separates the Cape Basin from the Agulhas Basin and controls the exchange of water masses between these two basins. Small scale buried drifts, moats and sheet like deposits indicate that sedimentation was controlled by bottom currents since the late Eocene. After a pronounced early Oligocene erosional event resulting from the onset of Lower Circumpolar Deep Water (LCDW) flow, drift formation intensified. The type, position and formation history of the interpreted drifts suggest that the pathways of LCDW flow have undergone little change during the last ~33Ma and followed roughly today's 4900m depth contour. Northwest of the Cape Rise seamount we found a mounded drift with an oval shape, a height of ~400m and a width of ~50–60km indicating a clockwise circulating bottom water gyre in that area. Extensive drifts in the Cape Basin occur as features confined between the Agulhas Ridge and Cape Rise seamounts and as mounded and sheeted drifts further to the west. The confined drifts show erosional features on both flanks suggesting a west setting bottom water flow along the northern flank of the Agulhas Ridge and an opposing eastward directed flow along the southern rim of the Cape Rise seamount group. In contrast to the large drift deposits in the Cape Basin smaller, confined drifts showing more erosional features are found south of the Agulhas Ridge. Together these findings suggest that the deepest LCDW flowed anticlockwise around the Agulhas Ridge before taking a major clockwise loop in the Cape Basin. The returning bottom water then flowed around the Cape Rise seamounts before entering the Indian Ocean.

Hysteresis Compensation Based on Controlled Current Pulses for Magnetoresistive Sensors

This paper presents a novel hysteresis compensation method for increasing the measurement accuracy of magnetoresistive (MR) sensors such as anisotropic magnetoresistance (AMR), giant magnetoresistance (GMR), and tunnel magnetoresistance (TMR) sensors. A coil consisting of one winding is processed on top of the sensor element. This configuration allows short current pulses (positive and negative) to generate a defined magnet field, which should be much stronger than the field to be measured. In this case, the MR sensors can always be kept in the same magnetic loop (major loop) during the measurement cycle. By demodulating or averaging the output signal of the sensor, the influence of the sensors hysteresis can be largely reduced. A mixed signal circuit consisting of a field-programmable gate array, analog-to-digital converters and analog switches is used to generate the pulses. AMR, GMR, and TMR current sensors are chosen as examples in the experiment. Current measurements with and without controlled magnetic field pulse are compared. A hysteresis reduction to nearly 20% of the original value, by using the novel hysteresis compensation method, is reached.

Criteria for saturated magnetization loop

Proper estimation of magnetization curve parameters is vital in studying magnetic systems. In the present article, criteria for discrimination non-saturated (minor) from saturated (major) hysteresis loops are proposed. These employ the analysis of (i) derivatives of both ascending and descending branches of the loop, (ii) remanent magnetization curves, and (iii) thermomagnetic curves. Computational simulations are used in order to demonstrate their validity. Examples illustrating the applicability of these criteria to well-known real systems, namely Fe3O4 and Ni fine particles, are provided. We demonstrate that the anisotropy-field value estimated from a visual examination of an only apparently major hysteresis loop could be more than two times lower than the real one.

Magnetic characterisation of microstructural feature distribution in P9 and T22 steels by major and minor BH loop measurements

This paper investigates the magnetic properties and parameters measured from major/minor loops and used to characterise different microstructural feature distributions in P9 and T22 steel in different heat treatment or service conditions. The present study introduces a non-destructive way of selecting microstructural features of interest and/or excluding those of little relevance by examination of minor loop measurements at a selected range of applied fields and discusses the fundamental mechanism in terms of domain processes. There is remarkable consistency in magnetic behaviours and properties such as initial/incremental permeability values between the measurements by different techniques. This behaviour has been ascribed to the similar underlying domain processes and hence similar selected microstructural features that are affecting the domain processes.

Numerical investigation of symmetry breaking and multi-loop hysteresis phenomena in a symmetric supersonic combustor

AbstractNumerical investigations are performed to study the features of symmetry breaking phenomena in a symmetric supersonic combustor. By changing the fuel equivalence ratio, the symmetry breaking phenomena are numerically observed. Further, the hysteresis behaviours are observed along with the phenomena of symmetry breaking by increasing and then decreasing the the fuel equivalence ratio. Furthermore, more complex hysteresis phenomenon, i.e., multi-loop hysteresis, is observed numerically. The multi-loop hysteresis consists of both major and minor loops, and is associated with the interaction between multiple flow structures. Due to the fact that different flow structures would result in different flow conditions, the findings regarding the existence of hysteresis behaviours can significantly affect the combustion process and even the performance of the engine. It is hoped that the observation of the (multi-loop) hysteresis phenomenon may bring it to the attention of those investigators whose experiments maybe affected by its occurrence.

Hysteresis Model of Magnetically Controlled Shape Memory Alloy Based on a PID Neural Network

Magnetically controlled shape memory alloys(MSMA) are a new kind of smart material that can be used in micro-displacement and micro-positioning applications. However, the hysteresis nonlinearity of this material is an obstacle to achieve high precision accuracy [1]. The hysteresis nonlinearity of MSMA can be described by the relationship between the input and output signal which is called hysteresis loop [2]. As shown in figure 1(a), hysteresis loops can be divided into major and minor hysteresis loops. The input and output signals have the same phase at the extrema and the phase of the output signal lags behind the input signal at all other times. A major hysteresis loop takes shape when the input signal rises from an initial value to a maximum value before decreasing to a minimum value (which is same as the initial value). Minor hysteresis loops occur when the input signal rises from a local minimum value (which is different from the overall minimum value) to a local maximum value (which is different from the overall maximum value) before decreasing to a local minimum value.

Enhancement of magnetic domain topologies in Co/Pt thin films by fine tuning the magnetic field path throughout the hysteresis loop

We have studied the influence of magnetic history on the topology of perpendicular magnetic domains in a thin ferromagnetic film made of [Co(8Å)/Pt(7Å)]50 multilayers. More specifically, we have followed the morphological changes in the domain pattern when applying a magnetic field perpendicular to the layer, throughout minor and major magnetization loops, and in the resulting remanent state. We carried out this study by using MFM microscopy with an in-situ magnetic field. We find that the morphology of the magnetic domain pattern is greatly influenced by the magnetic history of the material and that some features, such as the degree of bubbliness (i.e., the extent of bubble domain formation) and density of isolated domains can be enhanced by fine tuning the magnetic field path within the major hysteresis loop towards different remanent states. In particular, we see how hysteresis is correlated to irreversible changes in the domain morphology. More interestingly, we find that the magnetic domain morphology at remanence can be changed from an interconnected labyrinthine stripe state to a state of many separated bubble domains by fine tuning the magnitude of the field previously applied to the material. These results agree well with other findings, such as the magnetic reversal behavior and magnetic memory effects in Co/Pt multilayers, and provide opportunities for potential technological applications.

Epitopes in α8β1 and other RGD-binding integrins delineate classes of integrin-blocking antibodies and major binding loops in α subunits.

Identification of epitopes for integrin-blocking monoclonal antibodies (mAbs) has aided our understanding of structure-function relationship of integrins. We mapped epitopes of chicken anti-integrin-α8-subunit-blocking mAbs by mutational analyses, examining regions that harboured all mapped epitopes recognized by mAbs against other α-subunits in the RGD-binding-integrin subfamily. Six mAbs exhibited blocking function, and these mAbs recognized residues on the same W2:41-loop on the top-face of the β-propeller. Loop-tips sufficiently close to W2:41 (<25 Å) contained within a footprint of the mAbs were mutated, and the loop W3:34 on the bottom face was identified as an additional component of the epitope of one antibody, clone YZ5. Binding sequences on the two loops were conserved in virtually all mammals, and that on W3:34 was also conserved in chickens. These indicate 1) YZ5 binds both top and bottom loops, and the binding to W3:34 is by interactions to conserved residues between immunogen and host species, 2) five other blocking mAbs solely bind to W2:41 and 3) the α8 mAbs would cross-react with most mammals. Comparing with the mAbs against the other α-subunits of RGD-integrins, two classes were delineated; those binding to “W3:34 and an top-loop”, and “solely W2:41”, accounting for 82% of published RGD-integrin-mAbs.

A combined Preisach–Hyperbolic Tangent model for magnetic hysteresis of Terfenol-D

This study presents a new model using the combination of Preisach and Hyperbolic Tangent models, to predict the magnetic hysteresis of Terfenol-D at different frequencies. Initially, a proper experimental setup was fabricated and used to obtain different magnetic hysteresis curves of Terfenol-D; such as major, minor and reversal loops. Then, it was shown that the Hyperbolic Tangent model is precisely capable of modeling the magnetic hysteresis of the Terfenol-D for both rate-independent and rate-dependent cases. Empirical equations were proposed with respect to magnetic field frequency which can calculate the non-dimensional coefficients needed by the model. These empirical equations were validated at new frequencies of 100Hz and 300Hz. Finally, the new model was developed through the combination of Preisach and Hyperbolic Tangent models. In the combined model, analytical relations of the Hyperbolic Tangent model for the first order reversal loops determined the weighting function of the Preisach model. This model reduces the required experiments and errors due to numerical differentiations generally needed for characterization of the Preisach function. In addition, it can predict the rate-dependent hysteresis as well as rate-independent hysteresis.

Accurate mean-field modeling of the Barkhausen noise power in ferromagnetic materials, using a positive-feedback theory of ferromagnetism

A mean-field positive-feedback (PFB) theory of ferromagnetism is used to explain the origin of Barkhausen noise (BN) and to show why it is most pronounced in the irreversible regions of the hysteresis loop. By incorporating the ABBM-Sablik model of BN into the PFB theory, we obtain analytical solutions that simultaneously describe both the major hysteresis loop and, by calculating separate expressions for the differential susceptibility in the irreversible and reversible regions, the BN power response at all points of the loop. The PFB theory depends on summing components of the applied field, in particular, the non-monotonic field-magnetization relationship characterizing hysteresis, associated with physical processes occurring in the material. The resulting physical model is then validated by detailed comparisons with measured single-peak BN data in three different steels. It also agrees with the well-known influence of a demagnetizing field on the position and shape of these peaks. The results could form the basis of a physics-based method for modeling and understanding the significance of the observed single-peak (and in multi-constituent materials, multi-peak) BN envelope responses seen in contemporary applications of BN, such as quality control in manufacturing, non-destructive testing, and monitoring the microstructural state of ferromagnetic materials.

Hysteresis in single and polycrystalline iron thin films: Major and minor loops, first order reversal curves, and Preisach modeling

Hysteretic behavior was studied in a series of Fe thin films, grown by molecular beam epitaxy, having different grain sizes and grown on different substrates. Major and minor loops and first order reversal curves (FORCs) were collected to investigate magnetization mechanisms and domain behavior under different magnetic histories. The minor loop coefficient and major loop coercivity increase with decreasing grain size due to higher defect concentration resisting domain wall movement. First order reversal curves allowed estimation of the contribution of irreversible and reversible susceptibilities and switching field distribution. The differences in shape of the major loops and first order reversal curves are described using a classical Preisach model with distributions of hysterons of different switching fields, providing a powerful visualization tool to help understand the magnetization switching behavior of Fe films as manifested in various experimental magnetization measurements.

Abstract A34: GDC-0980, a dual PI3K/mTOR inhibitor, selectively inhibits NF2 mutant malignant mesothelioma (MM) cells and inhibits TOR signaling without activating Akt or ERK

Abstract Purpose: Inactivation of Merlin/NF2 is common, occurring in 45-60% of mesotheliomas. Merlin loss leads to hyperactivation of TOR signaling and dysregulation of this pathway drives tumor development and growth. Cytostatic inhibition of TOR with rapamycin in MM cells has limited impact (Lopez-Lago Mol Cell Biol 2009). Rapamycin releases two major negative feedback loops that restrain Akt-TOR signaling, thereby leading to hyperactivation of both Akt and ERK. Effective growth inhibition likely requires dual inhibition of PI3K and mTOR. We therefore sought to assess the activity of the potent and selective dual PI3K/mTOR inhibitor GDC-0980 in MM cells with respect to cell proliferation and hyperactivation of Akt and ERK. Experimental Procedures: NF2 mutant cell lines, VAMT and JMN, and NF2 wild type cell lines, H-Meso and 211-H, were cultured in the presence of increasing concentrations of GDC-0980 for 48 hours and subjected to MTT assay. Values were normalized to untreated samples at day 0. Meso 33 and JMN malignant mesothelioma cell lines were treated with increasing doses of GDC-0980 for 2 hours and subjected to immunoblotting for P-S6, P-4E-BP1, P-Akt (S473), P-ERK, and ERK2. Results: GDC-0980 effectively inhibited proliferation of the NF2 mutant cell lines by 40% but had little or no effect on NF2 wild type cell lines (statistically significant difference at 80 nM with p&amp;lt;0.006). 100 nM GDC-0980 completely suppresses activation of TOR as assessed by phosphorylation of S6 and 4E-BP1 in Meso-33 cells. Higher concentrations were required for these events in JMN cells. However, in both Meso-33 and JMN cells, these effects were not associated with overactivation of Akt or ERK. Conclusions: GDC-0980 is a potent inhibitor of proliferation in MM cells with NF2 mutations and does not cause hyperactivation of Akt and ERK. Along with our ongoing preclinical work with cell lines and xenograft mouse models, the data from a recent phase I clinical trial with an expansion cohort in mesothelioma (NCT00854152) provide a strong rationale for the development of biomarker-driven clinical trials of GDC-0980 and other PI3K/mTOR inhibitors in mesothelioma. This work was supported in part by Genentech. Citation Format: Marjorie G. Zauderer, Kamalika Moulik, Jonathan Cooper, Lee M. Krug, Filippo Giancotti. GDC-0980, a dual PI3K/mTOR inhibitor, selectively inhibits NF2 mutant malignant mesothelioma (MM) cells and inhibits TOR signaling without activating Akt or ERK. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A34.

Development of a candidate influenza vaccine based on virus-like particles displaying influenza M2e peptide into the immunodominant loop region of hepatitis B core antigen: Insertion of multiple copies of M2e increases immunogenicity and protective efficiency

The extracellular domain of the transmembrane protein M2 (M2e) of influenza A virus is a promising target for the development of “universal” vaccines against influenza. M2e is a poor immunogen by itself; however, when M2e is linked to an appropriate carrier, such as hepatitis B virus core (HBc) particles, it becomes highly immunogenic. Insertions of target peptides into the surface-exposed major immunodominant loop region (MIR) of the HBc antigen are especially immunogenic, but such insertions often affect the protein folding and formation of recombinant virus-like particles. To facilitate an appropriate conformation of the M2e insert, we introduced flexible linkers at the junction points between the insert and flanking HBc sequences. This approach allowed the construction of recombinant HBc particles carrying 1, 2 and 4 copies of M2e in the MIR region. These particles were produced in Escherichia coli and purified to homogeneity. The immune response and protective activity of hybrid HBc particles in mice correlated with the number of inserted M2e peptides: the highest immunogenicity and complete protection of mice against the lethal challenge by influenza virus was observed with particles carrying four copies of M2e. The possibility of the simultaneous presentation of M2e peptides from several important influenza strains on a single HBc particle could also facilitate the development of a broad-specificity vaccine efficient not only against influenza A strains of human origin but also for newly emerging strains of animal origin, such as the avian influenza.

Kinetic effects on double hysteresis in spin crossover molecular magnets analyzed with first order reversal curve diagram technique

In this paper, we analyze two types of hysteresis in spin crossover molecular magnets compounds in the framework of the First Order Reversal Curve (FORC) method. The switching between the two stable states in these compounds is accompanied by hysteresis phenomena if the intermolecular interactions are higher than a threshold. We have measured the static thermal hysteresis (TH) and the kinetic light induced thermal hysteresis (LITH) major loops and FORCs for the polycrystalline Fe(II) spin crossover compound [Fe1−xZnx(bbtr)3](ClO4)2 (bbtr = 1,4-di(1,2,3-triazol-1-yl)butane), either in a pure state (x = 0) or doped with Zn ions (x = 0.33) considering different sweeping rates. Here, we use this method not only to infer the domains distribution but also to disentangle between kinetic and static components of the LITH and to estimate the changes in the intermolecular interactions introduced by dopants. We also determined the qualitative relationship between FORC distributions measured for TH and LITH.

Study on classical and excess eddy currents losses of Terfenol-D

In the present paper, classical and excess eddy currents losses of Terfenol-D are studied and effects of magnetic field frequency, peak of magnetic flux density and diameter of Terfenol-D on the eddy currents losses are investigated. To provide reliable data for the purpose of the paper, an experimental laboratory is fabricated and used to obtain major and minor hysteresis loops of Terfenol-D at different frequencies. In theoretical study, initially an analytical model based on uniform distribution of magnetic flux is developed which yields to calculation of classical eddy currents losses. Then, another eddy currents model based on non-uniform distribution of magnetic flux and nonlinear diffusion of electromagnetic fields is presented. The difference between output values of the two models is identified as excess eddy currents losses. Obtained results show that the values of excess losses are generally larger than classical losses and applying just classical model leads to wrong calculation of actual value of eddy currents losses. For the results obtained from two above models, empirical models with respect to the magnetic field frequency and the peak value of magnetic flux density are achieved which can predict the eddy currents losses precisely. To validate the empirical relations, experiments are repeated at a new frequency and values of power losses calculated from analytical equations are compared with the predicted values of the empirical models. The results point towards possibility to use the obtained empirical relations in order to calculate the classical and excess eddy currents losses of Terfenol-D at the frequencies below 200Hz and different values of magnetic flux density.