Linear Reference Research Articles

Cilengitide: The First Anti-Angiogenic Small Molecule Drug Candidate. Design, Synthesis and Clinical Evaluation

Cilengitide, a cyclic RGD pentapeptide, is currently in clinical phase III for treatment of glioblastomas and in phase II for several other tumors. This drug is the first anti-angiogenic small molecule targeting the integrins αvβ3, αvβ5 and α5β1. It was developed by us in the early 90s by a novel procedure, the spatial screening. This strategy resulted in c(RGDfV), the first superactive αvβ3 inhibitor (100 to 1000 times increased activity over the linear reference peptides), which in addition exhibited high selectivity against the platelet receptor αIIbβ3. This cyclic peptide was later modified by N-methylation of one peptide bond to yield an even greater antagonistic activity in c(RGDf(NMe)V). This peptide was then dubbed Cilengitide and is currently developed as drug by the company Merck-Serono (Germany). This article describes the chemical development of Cilengitide, the biochemical background of its activity and a short review about the present clinical trials. The positive anti-angiogenic effects in cancer treatment can be further increased by combination with “classical” anti-cancer therapies. Several clinical trials in this direction are under investigation.

Model Following Sliding-Mode Control of a Six-Phase Induction Motor Drive

In this paper an effective direct torque control (DTC) and stator flux control is developed for a quasi six-phase induction motor (QIM) drive with sinusoidally distributed windings. Combining sliding-mode (SM) control and adaptive input-output feedback linearization, a nonlinear controller is designed in the stationary reference frame, which is capable of tracking control of the stator flux and torque independently. The motor controllers are designed in order to track a desired second order linear reference model in spite of motor resistances mismatching. The effectiveness and capability of the proposed method is shown by practical results obtained for a QIM supplied from a voltage source inverter (VSI).

Effect of Transition State Aromaticity and Antiaromaticity on Intrinsic Barriers of Proton Transfers in Aromatic and Antiaromatic Heterocyclic Systems; An ab Initio Study

An ab initio study of two series of carbon-to-carbon proton transfer reactions is reported. The first series refers to the heterocyclic C(4)H(5)X(+)/C(4)H(4)X (X = CH(-), NH, S, O, PH, CH(2), AlH, BH) systems, and the second to the linear [Formula: see text] (X = CH(-), NH, S, PH, O, CH(2), AlH, BH) reference systems . The major objective of this study was to examine to what degree the aromaticity of C(4)H(4)X (X = CH(-), NH, S, O, PH) and the antiaromaticity of C(4)H(4)X (X = AlH, BH) is expressed at the transition state of the proton transfer and how this affects the respective intrinsic barriers. From the differences in the barriers between a given cyclic system and the corresponding linear reference system , ΔΔH(++) = ΔH(++)(cyclic) - ΔH(++)(linear), it was inferred that in the cyclic systems both aromaticity and antiaromaticity lower ΔH(++)(cyclic). This conclusion was based on the assumption that the factors not associated with aromaticity or antiaromaticity such as resonance, inductive and polarizability effects in the protonated species, and charge delocalization occurring along the reaction coordinate affect ΔH(++) for the cyclic and linear systems in a similar way and hence offset each other in ΔΔH(++). The extent by which ΔH(++)(cyclic) is lowered in the aromatic systems correlates quite well with the degree of aromaticity of C(4)H(4)X as measured by aromatic stabilization energies as well as the NICS(1) values of the respective C(4)H(4)X. According to the rules of the principle of nonperfect synchronization (PNS), these results imply a disproportionately large degree of aromaticity at the transition state for the aromatic systems and a disproportionately small degree of transition state antiaromaticity for the antiaromatic systems. These conclusions are consistent with the changes in the NICS(1) values along the reaction coordinate. Other points discussed in the paper include the complex interplay of resonance, inductive, and polarizability effects, along with aromaticity and antiaromaticity on the proton affinities of C(4)H(4)X.

Fast Quantitative Determination of Aroma Volatile Constituents in Melon Fruits by Headspace–Solid-Phase Microextraction and Gas Chromatography–Mass Spectrometry

Since the aroma is one of the essential factors for evaluating fruit quality, a headspace–solid-phase microextraction and gas chromatography–mass spectrometry method for the identification and quantification of the aroma volatile constituents in melon fruits has been developed. Two different varieties of Cucumis melo L., reticulatus and inodorus, have been analyzed and 66 volatile compounds have been identified and quantified; among these, the impact aroma compounds are included too. The volatile compounds have been identified by linear retention index, mass spectra, standard injection, and reference data; the quantification has been carried out by the standard addition technique. The method proposed showed good linearity within the concentration range tested; the precision, CV was <15% for all the components identified, and the limits of quantification was very low for most of the components, for example, 1.7 ng/g for ethyl octanoate and 1.5 ng/g for limonene. The results emphasized each fruit variety could be distinguished by a different qualitative and quantitative volatile fraction composition; as example, reticulatus samples were characterized by a high amount of esters (192.8 μg/Kg), which were present as traces in inodorus. Sensory analysis was performed on the samples and quantitative volatile and sensory data were correlated using multivariate analysis. The developed method allowed us to obtain reliable quantitative data of the melon volatile constituents which are necessary for the fruit quality evaluation since the aroma contribution of a particular substance is assessed by knowledge of the ratio between its amount and odor threshold level.

Five-Level Current-Source Inverters With Buck–Boost and Inductive-Current Balancing Capabilities

This paper presents new five-level current-source inverters (CSIs) with voltage/current buck-boost capability, unlike existing five-level CSIs where only voltage-boost operation is supported. The proposed inverters attain self-inductive-current-balancing per switching cycle at their dc front ends without having to include additional balancing hardware or complex control manipulation. The inverters can conveniently be controlled by using the well-established phase-shifted carrier modulation scheme with only two additional linear references and a mapping logic table needed. Existing modulators can therefore be conveniently retrofitted for controlling the presented inverters. By appropriately coordinating the inverter gating signals, their implementations can be realized by using the least number of components without degrading performance. These enhanced features of the inverters have already been verified in simulation and experimentally using a scaled-down laboratory platform.

Nonlinear Screening Indicators of Drought Resistance at Seedling Stage of Rice Based on Support Vector Machine

Screening indexes for drought resistance in crops is a puzzler characterized with a few samples, multiple indexes, and nonlinear. Rationality of linear regression model and indexes obtained by linear screening based on empirical risk minimization are controversal. On the contrary, support vector machine based on structural risk minimization has the advantages of nonlinear characteristics, fitting for a few samples, avoiding the over-fit, strong generalization ability, and high prediction precision. In this paper, setting the survival percentage under repeated drought condition as the target and support vector regression as the nonlinear screen tool, 6 integrated indexes including plant height, proline content, malondialdehyde content, leaf age, area of the first leaf under the central leaf and ascorbic acid were highlighted from 24 morphological and physiological indexes in 15 paddy rice cultivars. The results showed that support vector regression model with the 6 integrated indexes had a more distinct improvement in fitting and prediction precision than the linear reference models. Considering the simplicity of indexes measurement, the support vector regression model with only 6 morphological indexes including shoot dry weight, area of the second leaf under the central leaf, root shoot ratio, leaf age, leaf fresh weight, and area of the first leaf under the central leaf was also feasible. Furthermore, an explanatory system including the significance of regression model and the importance of single index was established based on support vector regression and F-test.

Control of an Over-Actuated Single-Degree-of-Freedom Excitation System

This paper provides results of a laboratory experiment designed to illustrate the theoretical control considerations for an over-actuated excitation system. The experiment is based on control of a beam pinned at one end providing a single rotational degree of freedom and excited by two electrodynamic actuators. Control is achieved through implementation of two different control reference techniques: (1) reference based on linear acceleration autospectral densities (ASD) and cross-spectral densities (CSD) using linear accelerometer feedback and (2) reference based on an angular acceleration ASD using estimates of angular acceleration as feedback. Correlations to the theoretical based predictions were conducted based on common measurements of both linear acceleration and estimates of angular acceleration acquired during each trial.

Vascular deformation for vascular interventional surgery simulation

Obtaining the expertise to perform minimally vascular interventional surgery (VIS) requires thorough training. Previous VIS simulators have generally assumed that blood vessels are rigid. However, vascular deformation occurs unavoidably in VIS. In this study, the arterial walls were analysed as soft tissue. A mass-spring model (MSM) was applied for vascular deformation simulation. To improve simulation precision, the spring coefficient was derived from a reference model, simulated with a linear finite element method (FEM), which established a link between the spring coefficient and the properties of the vascular materials. In order to evaluate the simulation results, we applied identical external forces to FEM and MSM and calculated their deformations. Additionally, based on the proposed MSM, we designed a VIS simulator to achieve renal artery intervention. Quantitative validation was performed by comparing the simulated catheter position with a reference position, as assessed by 3D rotational angiography imaging. From the simulation results, we could clearly see that MSM deformation was real-time and very close to the linear FEM reference, and MSM was successfully adopted in our renal artery intervention simulator. MSM with a spring coefficient derived from linear FEM was able to produce a realistic deformation simulation of arterial walls. This method could also be extended to model other organ deformations.

Noniterative Approach for Solving the Indirect Problems of Linear Reference Frame Transformations

A linear transformation, including a similarity model and an affine model, plays an important role in reference frame transformation problems. It establishes geometric relations between different reference frames by adopting physically interpretable parameters, and allows one to integrate positional coordinates across various systems. In this study, an analytical noniterative approach for solving the indirect problem (i.e., parameter estimation) of a linear transformation model is proposed. It gives a closed-form solution for the transformation without any prerequisite on the magnitude of parameters. Consequently, neither good initial values nor iterations are required during the parameter estimation process. Through numerical examples, it is illustrated that the proposed approach is capable of giving accurate parameter estimates as a classic least-squares technique does, but with much higher computational efficiency. In a reference frame transformation problem of 1,000 control points, the proposed approa...

Research on Real Time Traffic Information Data Model and Its Data Transmit

Real-time of geographic information system for transportation (GIS-T) is one of the essential conditions to alleviate the traffic jam and guide the traffic flow rationally. In order to make it convenient for sharing and maintaining data, this paper structures the independent real-time traffic information database, seamless merging real-time traffic information and GIS data through data fusion method. In order to realize this purpose, the paper research on baseline network data model, baseline network is composed of base points and baselines. Base points are exclusive locating on the road network, which can be determined in field, and also can be resumed. Baseline is line element, which replaces traffic event, the baseline locate road network by the point, and therefore, it is easy to realize data share for various linear reference system. According to the data model, designing structure and introducing data transmit flow of the Geographic Information System for Transportation. Key words: Data Model; Data Fusion; GIS; Traffic Information This paper is supported by the Department of Instrument Science and Engineering, Southeast University, and professor DE-JUN WAN and professor QING WANG

Jensen-Feynman approach to the statistics of interacting electrons

Faussurier [Phys. Rev. E 65, 016403 (2001)] proposed to use a variational principle relying on Jensen-Feynman (or Gibbs-Bogoliubov) inequality in order to optimize the accounting for two-particle interactions in the calculation of canonical partition functions. It consists of a decomposition into a reference electron system and a first-order correction. The procedure appears to be very efficient in order to evaluate the free energy and the orbital populations. In this work, we present numerical applications of the method and propose to extend it using a reference energy which includes the interaction between two electrons inside a given orbital. This is possible, thanks to our efficient recursion relation for the calculation of partition functions. We also show that a linear reference energy, however, is usually sufficient to achieve a good precision and that the most promising way to improve the approach of Faussurier is to apply Jensen's inequality to a more convenient convex function.

Programmable feedforward linearized CMOS OTA for fully differential continuous‐time filter design

AbstractIn this paper, a feedforward linearization method for programmable CMOS operational transconductance amplifier (OTA) is described. The proposed circuit technique is developed using simple source‐coupled differential pair transconductors, a feedback‐loop amplifier for self‐adjusting transcoductance (gm) and a linear reference resistor (R). As a result, an efficient linearization of a transfer characteristic of the OTA is obtained. SPICE simulations show that for 0.35µm AMS CMOS process with a single +3V power supply, total harmonic distortion at 1 Vpp and temperature range from −30 to +90°C is less than −49.3 dB in comparison with −35.8 dB without linearization. Moreover, the input voltage range of linear operation is increased. Power consumption of the linearized OTA circuit is 0.86 mW. Finally, the OTA is used to design a third‐order elliptic low‐pass filter in high‐frequency range. The cut‐off frequency of the operational transconductance amplifier‐capacitor (OTA‐C) filter is tunable in the range of 322.6 kHz–10 MHz using the feedforward linearized OTAs with the digitally programmable current mirrors. Copyright © 2009 John Wiley &amp; Sons, Ltd.

Shrinking factors of hyperbranched polysaccharide from fungus

The branched structure properties of hyperbranched polysaccharides (TM3a and TM3b), extracted from sclerotia of Pleurotus tuber-regium, were studied by using laser light scattering and viscometry. The configurational shrinking factor ( g) and viscometric shrinking factor ( g′) of TM3a and TM3b were discussed, where curdlan and pullulan were taken as the linear references for derivation of g and g′. The dependences of g factor, g′ factor, and Flory factor ( Φ branched) on weight average molecular weight ( M w) were established to be g = 1.07 × 10 2 M w - 0.48 ± 0.09 , g′ = 3.63 × 10 1 M w - 0.43 ± 0.01 , and Φ branched = 7.08 × 10 20 M w 0.39 ± 0.1 for TM3a in 0.25 M LiCl/DMSO at 25 °C, when curdlan acted as the linear reference. A power law relationship g′ = 2.71 × 10 −1 g −0.61±0.1 for TM3a was found, and the exponent was approximately same to 0.60 established by Kurata et al. for polystyrene star molecules. The dependence of g factor on M w for TM3b was found to be g = 1.99 × 10 2 M w - 0.53 ± 0.02 , when pullulan was used as the linear reference. On the basis of Zimm–Stockmayer equation for tetrafunctional units, molecular weight of branching unit ( M 0) deduced from nonlinear curve fitting of g versus M w was 8739 ± 564 g/mol and 3961 ± 1245 g/mol for TM3a and TM3b, respectively. The effect of different linear reference curves and polydispersity was discussed. This work gave valuable information on branched structure characterization and insights into the biosynthetic pathways of the hyperbranched polysaccharide from fungus.

Stabilisation and altitude tracking of a four-rotor microhelicopter using the lifting operators

The lifting methodology can be used for simplifying the closed-loop stability study of a system in which the measurement data are acquired at different frequencies. This is because the lifting operators allow treating this kind of systems as if there is only one control frequency, which reduces the complexity of the problem in a very important way. The four-rotor microhelicopter designed by the authors, whose control is faced, is a nonlinear plant with sensors operating at two different frequencies. First, the system is linearised cancelling the rotors dynamics. Then, the authors implement a model reference adaptive control structure for identifying the gains of the linear reference plant and performing the adaptive control of the microhelicopter. At this point, the system stability study is carried out by just computing the eigenvalues of the closed-loop states matrix thanks to the lifting operators.

Fuzzy $H_{\infty}$ Tracking Control for Nonlinear Networked Control Systems in T–S Fuzzy Model

This paper investigates the fuzzy tracking control problem for a class of nonlinear networked control systems (NCSs) with a prescribed H(infinity) tracking performance. Such NCSs consist of a nonlinear controlled plant, a tracked plant, sensors, a controller, and an actuator. A Takagi-Sugeno fuzzy model is employed to represent the nonlinear controlled plant in the NCSs, and a tracked plant is described by a linear stable reference model. In transmission, both network-induced delay and packet losses are considered. By the parallel distributed compensation technique, a novel tracking model of the nonlinear NCSs is first established. Based on Lyapunov stability theory, a control design method that guarantees the prescribed H(infinity) tracking performance of the nonlinear NCSs is developed in terms of linear matrix inequalities. Finally, a numerical example is given to illustrate the effectiveness of our result.

A macro-meso constitutive law for concrete having imperfect interface and nonlinear matrix

The overall behavior of concrete depends on its meso structures such as aggregate shape, interface status, and mortar matrix property. The two key meso structure characters of concrete, bond status of interface and nonlinear property of matrix, are considered in focus. The variational structure principle is adopted to establish the macro-meso constitutive law of concrete. Specially, a linear reference composite material is selected to make its effective behavior approach the nonlinear overall behavior of concrete. And the overall property of linear reference composite can be estimated by classical estimation method such as self-consistent estimates method and Mori-Tanaka method. This variational structure method involves an optimum problem ultimately. Finally, the macro-meso constitutive law of concrete is established by optimizing the shear modulus of matrix of the linear reference composite. By analyzing the constitutive relation of concrete established, we find that the brittleness of concrete stems from the imperfect interface and the shear dilation property of concrete comes from the micro holes contained in concrete.

Combining State Route and Local Road Linear Referencing System Information

The Wisconsin Department of Transportation maintains two separate geographic information system databases: one for state roads and one for local roads. Both databases employ linear referencing system (LRS) theory to manage and locate information. Combining data from state and local roads into one system is desirable for the purpose of data management and analysis. This paper's approach combines information from the state route LRS (link ID and offset distance) with information from the local road LRS (node ID) to produce a table that can be employed to transfer data between the systems. A computer program was developed to use this table, along with existing tables in each LRS, to move information from the state route system to the local road system. Quality assurance and quality control techniques are presented along with a long-term implementation approach; both help to update the table bridging these two systems. The approach described does not interfere with the current operation of either system; therefore, no interruption of business practice will occur as this data transfer approach is deployed. Although this approach can transfer any LRS data, a case study of crash data for Dane County, Wisconsin, is used to demonstrate and test the approach. In the case study, crash points on the state routes are combined with local road crashes to produce a complete data set of crashes within the county.

Maximal oxygen uptake versus maximal power output in children

Maximal oxygen uptake ([Vdot]O2max) is considered the optimal method to assess aerobic fitness. The measurement of [Vdot]O2max, however, requires special equipment and training. Maximal exercise testing with determination of maximal power output offers a more simple approach. This study explores the relationship between [Vdot]O2max and maximal power output in 247 children (139 boys and 108 girls) aged 7.9–11.1 years. Maximal oxygen uptake was measured by indirect calorimetry during a maximal ergometer exercise test with an initial workload of 30 W and 15 W · min−1 increments. Maximal power output was also measured. A sample (n = 124) was used to calculate reference equations, which were then validated using another sample (n = 123). The linear reference equation for both sexes combined was: [Vdot]O2max (ml · min−1) = 96 + 10.6 · maximal power + 3.5 · body mass. Using this reference equation, estimated [Vdot]O2max per unit of body mass (ml · min−1 · kg−1) calculated from maximal power correlated closely with the direct measurement of [Vdot]O2max (r = 0.91, P <0.001). Bland-Altman analysis gave a mean limits of agreement of 0.2±2.9 (ml · min−1 · kg−1) (1 s). Our results suggest that maximal power output serves as a good surrogate measurement for [Vdot]O2max in population studies of children aged 8–11 years.

Determining Rail Track Axis Geometry Using Satellite and Terrestrial Geodetic Data

In this paper, a multi-sensor data acquisition system and a method for extracting the track axis geometry of railways are introduced. The rail track surveying system employs GPS and a tracking total station for absolute referencing, aided by a biaxial inclinometer for reducing the data into a common datum in canted sections and a digital odometer for linear referencing. Track axis extraction depends on rail track positional data, whereas its geometric modelling is performed on the basis of design elements using the bearing diagram and the Generalised Least Squares (GLS) method on the horizontal and vertical track layout. In addition, a supplementary algorithm for computing the rail curvature is presented. Extended test runs were conducted to validate the feasibility of the system and the method. The test results show that a directional uncertainty of better than 0.01° in tangent sections and deviations between the actual and computed track radii of better than 1% in curved sections are achievable.

Magnet Reliability in the Fermilab Main Injector and Implications for the ILC

The International Linear Collider reference design requires over 13000 magnets, of approximately 135 styles, which must operate with very high reliability. The Fermilab Main Injector represents a modern machine with many conventional magnet styles, each of significant quantity, that has now accumulated many hundreds of magnet-years of operation. We review here the performance of the magnets built for this machine, assess their reliability and categorize the failure modes, and discuss implications for reliability of similar magnet styles expected to be used at the ILC.