Linear Architecture Research Articles

HPMA copolymer-doxorubicin conjugates: The effects of molecular weight and architecture on biodistribution and in vivo activity

The molecular weight and molecular architecture of soluble polymer drug carriers significantly influence the biodistribution and anti‐tumour activities of their doxorubicin (DOX) conjugates in tumour-bearing mice. Biodistribution of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-DOX conjugates of linear and star architectures were compared in EL4 T-cell lymphoma-bearing mice. Biodistribution, including tumour accumulation, and anti‐tumour activity of the conjugates strongly depended on conjugate molecular weight (MW), polydispersity, hydrodynamic radius (Rh) and molecular architecture. With increasing MW, renal clearance decreased, and the conjugates displayed extended blood circulation and enhanced tumour accumulation. The linear conjugates with flexible polymer chains were eliminated by kidney clearance more quickly than the highly branched star conjugates with comparable MWs. Interestingly, the data suggested different mechanisms of renal filtration for star and linear conjugates. Only star conjugates with MWs below 50,000g.mo−1 were removed by kidney filtration, while linear polymer conjugates with MWs near 70,000g.mol−1, exceeding the generally accepted limit for renal elimination, were detected in the urine 36–96h after injection. Additionally, survival of tumour-bearing mice was strongly dependent on molecular weight and polymer conjugate architecture. Treatment of mice with the lower MW conjugate at a dose of 10mg DOX eq./kg resulted in 12% long-term surviving animals, while treatment with the corresponding star conjugate enabled 75% survival of animals.

Prediction of e-Learning Efficiency by Neural Networks

Abstract A model for prediction of the outcome indicators of e-Learning, based on Balanced ScoreCard (BSC) by Neural Networks (NN) is proposed. In the development of NN models the problem of a small sample size of the data arises. In order to reduce the number of variables and increase the examples of the training sample, preprocessing of the data with the help of the methods Interpolation and Principal Component Analysis (PCA) is performed. A method for optimizing the structure of the neural network is applied over linear and nonlinear neural network architectures. The highest accuracy of prognosis is obtained applying the method of Optimal Brain Damage (OBD) over the nonlinear neural network. The efficiency and applicability of the method suggested is proved by numerical experiments on the basis of real data.

Power Allocation in Two-Hop Amplify-and-Forward MIMO Relay Systems With QoS Requirements

The problem of minimizing the total power consumption while satisfying different quality-of-service (QoS) requirements in a two-hop multiple-input multiple-output network with a single non-regenerative relay is considered. As shown by Y. Rong in [1], the optimal processing matrices for both linear and non-linear transceiver architectures lead to the diagonalization of the source-relay-destination channel so that the power minimization problem reduces to properly allocating the available power over the established links. Unfortunately, finding the solution of this problem is numerically difficult as it is not in a convex form. To overcome this difficulty, existing solutions rely on the computation of upper- and lower-bounds that are hard to obtain or require the relaxation of the QoS constraints. In this work, a novel approach is devised for both linear and non-linear transceiver architectures, which allows to closely approximate the solutions of the non-convex power allocation problems with those of convex ones easy to compute in closed-form by means of multi-step procedures of reduced complexity. Computer simulations are used to assess the performance of the proposed approach and to make comparisons with alternatives.

Computationally efficient neuro-dynamic programming approximation method for the capacitated re-entrant line scheduling problem

This paper presents a computationally efficient neuro-dynamic programming approximation method for the capacitated re-entrant line scheduling problem by reducing the number of feature functions. The method is based on a statistical assessment of the significance of the various feature functions. This assessment can be made by combining the weighted principal components with a thresholding algorithm. The efficacy of the new feature functions selected is tested by numerical experiments. The results indicate that the feature selection method presented here can extract a small number of significant features with the potential capability of providing a compact representation of the target value function in a neuro-dynamic programming framework. Moreover, the linear parametric architecture considered holds considerable promise as a way to provide effective and computationally efficient approximations for an optimal scheduling policy that consistently outperforms the heuristics typically employed.

Linear aromatic amide foldamer-derived supramolecular architectures and materials

Intramolecular hydrogen bonding in oligomeric aromatic amides may induce the backbones to adopt folded, zigzag, or other extended conformations, depending on the positions of the amide units and the hydrogen-bonding sites on the aromatic rings. This article summarizes our efforts in exploring the applications of this family of preorganized oligomers in supramolecular and materials chemistry. Several series of preorganized frameworks or foldamers have been developed as efficient acyclic receptors for binding both neutral and ionic guests. The backbones have been modified with discrete functional groups from the ends or the side chains. The resulting molecules have been applied for designing new molecular tweezers, assembling ordered supramolecular architectures (organogels and vesicles), and directing the formation of complicated macrocyclic and capsular systems. When the hydrogen-bonded folded segments are connected to n-butyl methacrylate copolymers as cross-links, the resulting copolymers display unique reversible mechanical properties owing to the breaking and recovering of the intramolecular hydrogen bonds. When the folded segments are incorporated into the dumbbell components of the donor–acceptor interaction-based pseudo[2]rotaxanes and [2]rotaxanes, they are capable of tuning the slippage/deslippage and switching of the ring component between the discrete “stations” in their dumbbell component.

Design and Implementation of FPGA based Low Power Digital FIR Filter

Abstract : Finite impulse response (FIR) filters are widely used in various DSP applications. The low-power or low-area techniques developed specifically for digital filters can be found in. Many applications in digital communication (channel equalization, frequency channelization), speech processing (adaptive noise cancelation), seismic signal processing (noise elimination), and several other areas of signal processing require large order FIR filters ,since the number of multiply - accumulate (MAC) operations required per filter output increases linearly with th e filter order, real - time implementation of these filters of large orders is a challenging task. This paper presents the methods to reduce dynamic power consumption of a digital Finite Impulse Response (FIR) filter these methods include low power serial multiplier and serial adder, combinational booth multiplier, shift/add multipliers, folding transformation in linear phase architecture and applied to fir filters to power consumption reduced thus reduce power consumption due to glitches is also reduced. This paper is implemented using XILINX ISE and hardware used is Spartan-3E and family is XC2S200E.

A Detailed Nonlinear Dynamic Model of a 3-DOF Laboratory Helicopter for Control Design

AbstractThis work investigates the model of a 3-DOF laboratory helicopter, which constitutes a highly nonlinear system. For this model, advanced control concepts are developed and applied. In the beginning, the equations of motion are derived from a physical modeling approach. The modeling procedure yields highly nonlinear differential equations, from which linear state space systems are derived for arbitrary operating points. The major part of this work consists of the development of different linear and non-linear control architectures. At first, a classic state vector feedback controller with integration of the control error is implemented. Based on the system parameters of the linearized model, a gain scheduling approach is developed using one of the degrees of freedom as scheduling parameter. The gain scheduling application uses both discrete operating points as well as one possible continuous scheduling through interpolation. Additionally, a flatness-based feedforward controller architecture is added for transient set point changes using linear and nonlinear inverse dynamics. The control performance is validated in its dynamical and steady-state behavior. Finally, the previously derived approaches are tested on the actual helicopter.

Systolic Architecture for Implementation of 2-D Discrete Sine Transform

In this paper, a recursive algorithm and two linear systolic architectures for realizing the one-dimensional discrete sine transform (DST) are presented. By using some mathematical techniques, any general length DST can be converted into a recursive equation. The recursive algorithms apply to arbitrary length algorithms and are appropriate for VLSI implementation. These two linear arrays have been utilised for designing a bilayer structure for computing the 2-D DST. This bilayer structure does not require any hardware / time for the transposition of the intermediate results. The desired transposition is achieved by orthogonal alignment of the linear array of the upper layer with respect to those of the lower layer.

Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution

BackgroundCationic copolymers consisting of polycations linked to nonionic amphiphilic block polymers have been evaluated as nonviral gene delivery systems, and a large number of different polymers and copolymers of linear, branched, and dendrimeric architectures have been tested in terms of their suitability and efficacy for in vitro and in vivo transfection. However, the discovery of new potent materials still largely relies on empiric approaches rather than a rational design. The authors investigated the relationship between the polymers’ structures and their biological performance, including DNA compaction, toxicity, transfection efficiency, and the effect of cellular uptake.MethodsThis article reports the synthesis and characterization of a series of cationic copolymers obtained by grafting polyethyleneimine with nonionic amphiphilic surfactant polyether-Pluronic® consisting of hydrophilic ethylene oxide and hydrophobic propylene oxide blocks. Transgene expression, cytotoxicity, localization of plasmids, and cellular uptake of these copolymers were evaluated following in vitro transfection of HeLa cell lines with various individual components of the copolymers.ResultsPluronics can exhibit biological activity including effects on enhancing DNA cellular uptake, nuclear translocation, and gene expression. The Pluronics with a higher hydrophilic-lipophilic balance value lead to homogeneous distribution in the cytoplasm; those with a lower hydrophilic-lipophilic balance value prefer to localize in the nucleus.ConclusionThis Pluronic-polyethyleneimine system may be worth exploring as components in the cationic copolymers as the DNA or small interfering RNA/microRNA delivery system in the near future.

Structure–activity effects in peptide self-assembly and gelation – Dendritic versus linear architectures

We demonstrate that linear-dendritic shape-isomerism can have an impact on the gelation potential of peptides based on lysine, but the architectural effects can be inverted depending on the choice of functional groups, with the nature of these protecting groups dominating the gelation ability.

Hierarchical microphase separation in bicontinuous ternary polymer blends

We describe the phase behavior of a ternary blend of poly(ethylene-alt-propylene) (P), poly(cyclohexylethylene-b-ethylene-b-cyclohexylethylene) (CEC), and a CECEC–P amphiphilic hexablock where both CEC and CECEC–P are ordered in the bulk. In this system, designed to mimic A/B/A–B ternary polymer blends, CEC and P were mixed with CECEC–P along the 50 : 50 CEC/P volumetric isopleth, and the phase behavior of select blend compositions was probed with a combination of rheology, SANS, TEM and SEM. At low volume fractions of CECEC–P and above the TODT of CEC, the phase behavior is very similar to that of A/B/A–B systems, with a progression from swollen lamellae to microemulsion phases. Cooling through the TODT of CEC yields a striking change in morphology, precipitating a transition to microemulsion phases at a broader range of blend compositions. Within the CEC-rich domain of such a bicontinuous microemulsion, we identify alternating C–E lamellae which are oriented perpendicularly to the CEC/P interface. SEM images of porous templates of this phase created by selective removal of P confirm the bicontinuous structure. The mechanical properties of these templates are poor due to the alignment of C–E lamellae across the CEC-rich domain. These results illustrate the generalizability of A/B/A–B ternary blend phase behavior to significantly more complex linear architectures containing multiple ordering transitions, and offer a route for templating functional multiblock copolymers with the bicontinuous microemulsion morphology.

Uranyl Ion Complexes with Ammoniobenzoates as Assemblers for Cucurbit[6]uril Molecules

The crystal structures of the complexes formed under hydrothermal conditions by uranyl ions with 4-aminobenzoic (HL1), 4-amino-3-methylbenzoic (HL2), 4-(aminomethyl)benzoic (HL3), and 3-amino-5-hydroxybenzoic (HL4) acids, in the presence of cucurbit[6]uril (CB6), have been determined. These ligands have been chosen because, in their zwitterionic form, they display both a metal-complexing carboxylate group and an ammonium group able to associate with CB6 through ion-dipole and hydrogen bonding interactions. The complexes [H2NMe2]2[(UO2)2(L1)2O(OH)(H2O)]2·CB6·15H2O (1) and [H2NMe2]2[(UO2)2(L2)2O(OH)(H2O)]2·CB6·17H2O (2) were obtained in the presence of dimethylformamide, which gives dimethylammonium ions in situ. The latter are held at the CB6 portals, while the tetranuclear uranyl complex with the aminobenzoate anions is not bound to CB6. The neutral, ammonium-containing form of the ligand is present in [UO2(HL3)(OH)(HCOO)(H2O)]2·2CB6·2DMF·14H2O (3), in which the di(μ2-hydroxo)-bridged, dinuclear uranyl complex displays two diverging, monodentate HL3 ligands. The latter are associated with two CB6 molecules to give a dumbbell-shaped supramolecular assembly. Three CB6 molecules are assembled around a tetranuclear uranyl complex in [(UO2)4(HL3)2(L3)O2(OH)2(H2O)4]·2CB6·0.5CB8·HL3·NO3·20H2O (4), with two of them being bridging and giving rise to a one-dimensional, linear supramolecular architecture. Finally, the 3-amino substituted ligand HL4 gives the highly symmetric complex [UO2(HL4)(L4)2]·3CB6·16H2O (5), in which the uranyl ion is chelated by three carboxylate groups. Three CB6 molecules are assembled around the planar complex to give a triangular, discrete species. In compounds 3–5, the usual packing of CB6 molecules into columns or layers is not retained as it is frequently in the presence of uranyl complexes. This is due to the CB6-assembling role of the heterodifunctional ligands, which hold the CB6 molecules at the periphery of mono-, di-, or tetranuclear uranyl complexes of quite usual, planar geometry.

Coherent Versus Noncoherent

In this article, we investigate the design philosophies of the existing space-time (ST) block codes (STBCs) in the open literature, namely the orthogonal approach and layered method, followed by the introduction of the generalized linear dispersion architecture. We will demonstrate that the powerful linear dispersion structure is capable of unifying the entire suite of existing schemes and, as a further benefit, it offers extra design flexibility so that diverse system requirements can be satisfied. Furthermore, after characterizing the fundamental relationship between STBCs and differential STBCs (DSTBCs), we highlight the benefits of noncoherently detected schemes, which are capable of exploiting the advantages of multiple antennas, while circumventing the potentially excessive burden of multiantenna channel estimation. Additionally, the linear dispersion structure can also be applied in systems, where the multiantenna array is formed in a distributed fashion by multiple single-antenna-aided cooperating mobile stations. Hence, the design of colocated and cooperative multiple-input-multiple-output (MIMO) systems aiming for achieving diversity is linked from a linear dispersion perspective.

First Complete Mitochondrial Genome Sequence from a Box Jellyfish Reveals a Highly Fragmented Linear Architecture and Insights into Telomere Evolution

Animal mitochondrial DNAs (mtDNAs) are typically single circular chromosomes, with the exception of those from medusozoan cnidarians (jellyfish and hydroids), which are linear and sometimes fragmented. Most medusozoans have linear monomeric or linear bipartite mitochondrial genomes, but preliminary data have suggested that box jellyfish (cubozoans) have mtDNAs that consist of many linear chromosomes. Here, we present the complete mtDNA sequence from the winged box jellyfish Alatina moseri (the first from a cubozoan). This genome contains unprecedented levels of fragmentation: 18 unique genes distributed over eight 2.9- to 4.6-kb linear chromosomes. The telomeres are identical within and between chromosomes, and recombination between subtelomeric sequences has led to many genes initiating or terminating with sequences from other genes (the most extreme case being 150 nt of a ribosomal RNA containing the 5′ end of nad2), providing evidence for a gene conversion–based model of telomere evolution. The silent-site nucleotide variation within the A. moseri mtDNA is among the highest observed from a eukaryotic genome and may be associated with elevated rates of recombination.

Comparison of the Stem-Loop and Linear Probe-Based Electrochemical DNA Sensors by Alternating Current Voltammetry and Cyclic Voltammetry

Here we systematically characterized the sensor performance of the stem-loop probe (SLP) and linear probe (LP) electrochemical DNA sensors using alternating current voltammetry (ACV) and cyclic voltammetry (CV), with the goal of generating the set of operational criteria that best suits each sensor architecture, in addition to elucidating the signaling mechanism behind these sensors. Although the LP sensor shows slightly better % signal suppression (SS) upon hybridization with the perfect match target at 10 Hz, our frequency-dependent study suggests that it shows optimal % SS only in a very limited AC frequency range. Similar results are observed in CV studies in which the LP sensor, when compared to the SLP sensor, displays a narrower range of voltammetric scan rates where the optimal % SS can be achieved. More importantly, the difference between the two sensors' performance is particularly pronounced if the change in integrated charge (Q) upon target hybridization, rather than the peak current (I), is measured in CV. The temperature-dependent study further highlights the differences between the two sensors, where the LP sensor, owing to the flexible linear probe architecture, is more readily perturbed by temperature changes. Both SLP and LP sensors, however, show a loss of % SS when operated at elevated temperatures, despite the significant improvement in the hybridization kinetics. In conjunction with the ACV, CV, and temperature-dependent studies, the electron-transfer kinetics study provides further evidence in support of the proposed signaling mechanism of these two sensors, in which the SLP sensor's signaling efficiency and sensor performance is directly linked to the hybridization-induced conformational change in the redox-labeled probe, whereas the performance of the LP sensor relies on the hybridization-induced change in probe dynamics.

Multiobjective optimization of parallel kinematic mechanisms by the genetic algorithms

SUMMARYIt is well known that Parallel Kinematic Mechanisms (PKMs) have an intrinsic dynamic potential (very high speed and acceleration) with high precision and high stiffness. Nevertheless, the choice of optimal dimensions that provide the best performances remains a difficult task, since performances strongly depend on dimensions. On the other hand, there are many criteria of performance that must be taken into account for dimensional synthesis, and which are sometimes antagonist. This paper presents an approach of multiobjective optimization for PKMs that takes into account several criteria of performance simultaneously that have a direct impact on the dimensional synthesis of PKMs. We first present some criteria of performance such as the workspace, transmission speeds, stiffness, dexterity, precision, as well as dynamic dexterity. Secondly, we present the problem of dimensional synthesis, which will be defined as a multiobjective optimization problem. The method of genetic algorithms is used to solve this type of multiobjective optimization problem by means of NSGA-II and SPEA-II algorithms. Finally, based on a linear Delta architecture, we present an illustrative application of this methodology to a 3-axis machine tool in the context of manufacturing of automotive parts.

Understanding the Effect of Polylysine Architecture on DNA Binding Using Molecular Dynamics Simulations

Polycations with varying chemistries and architectures have been synthesized and used in DNA transfection. In this paper we connect poly-L-lysine (PLL) architecture to DNA-binding strength, and in turn transfection efficiency, since experiments have shown that graft-type oligolysine architectures [e.g., poly(cyclooctene-g-oligolysine)] exhibit higher transfection efficiency than linear PLL. We use atomistic molecular dynamics simulations to study structural and thermodynamic effects of polycation-DNA binding for linear PLL and grafted oligolysines of varying graft lengths. Structurally, linear PLL binds in a concerted manner, while each oligolysine graft binds independently of its neighbors in the grafted architecture. Additionally, the presence of a hydrophobic backbone in the grafted architecture weakens binding to DNA compared to linear PLL. The binding free energy varies nonmonotonically with the graft length primarily due to entropic contributions. The binding free energy normalized to the number of bound amines is similar between the grafted and linear architectures at the largest (Poly5) and smallest (Poly2) graft length and stronger than the intermediate graft lengths (Poly3 and Poly4). These trends agree with experimental results that show higher transfection efficiency for Poly3 and Poly4 grafted oligolysines than for Poly5, Poly2, and linear PLL.

Making the Golden Connection: Reversible Mechanochemical and Vapochemical Switching of Luminescence from Bimetallic Gold–Silver Clusters Associated through Aurophilic Interactions

Aiming at the development of new architectures within the context of the quest for strongly luminescent materials with tunable emission, we utilized the propensity of the robust bimetallic clusters [Au₂Ag₂(R(I)/R(II))₄] (R(I) = 4-C₆F₄I, R(II) = 2-C₆F₄I) for self-assembly through aurophilic interactions. With a de novo approach that combines the coordination and halogen-bonding potential of aromatic heteroperhalogenated ligands, we have generated a family of remarkably luminescent bimetallic materials that provide grounds to address the relevance, relative effects, and synergistic action of the two interactions in the underlying photophysics. By polymerizing the green-emitting (λ(max)(em) = 540 nm) monomer [Au₂Ag₂R(II)₄(tfa)₂]²⁻ (tfa = trifluoroacetate) to a red-emitting (λ(max)(em) = 660 nm) polymer [Au₂Ag₂R(II)₄(MeCN)₂](n), we demonstrate herein that the degree of cluster association in these materials can be effectively and reversibly switched simply by applying mechanochemical and/or vapochemical stimuli in the solid state as well as by solvatochemistry in solution, the reactions being coincident with a dramatic switching of the intense, readily perceptible photoluminescence. We demonstrate that the key event in the related equilibrium is the evolution of a metastable yellow emitter (λ(max)(em) = 580 nm) for which the structure determination in the case of the ligand R(II) revealed a dimeric nonsolvated topology [Au₂Ag₂R(II)₄]₂. Taken together, these results reveal a two-stage scenario for the aurophilic-driven self-assembly of the bimetallic clusters [Au₂Ag₂(R(I)/R(II))₄]: (1) initial association of the green-emitting monomers to form metastable yellow-emitting dimers and desolvation followed by (2) resolvation of the dimers and their self-assembly to form a red-emitting linear architecture with delocalized frontier orbitals and a reduced energy gap. The green emission from [Au₂Ag₂R(II)₄(tfa)₂]²⁻ (λ(max)(em) = 540 nm) exceeds the highest energy observed for [Au₂Ag₂]-based structures to date, thereby expanding the spectral slice for emission from related structures beyond 140 nm, from the green region to the deep-red region.

Dendritic and Linear Macromolecular Architectures for Photovoltaics: A Photoinduced Charge Transfer Investigation

Dendritic and Linear Macromolecular Architectures for Photovoltaics: A Photoinduced Charge Transfer Investigation

Post-silicon Validation Procedure for a PWL ASIC Microprocessor Architecture

In this paper, we present the environment set for validation and testing a particular ASIC that implements a piecewise linear (PWL) architecture. Description for a package debug propose is included. Methodologies for power consumption and maximum operation frequency estimation, based on laboratory measurements, are described.