LNA aptamer based multi-modal, Fe3O4-saturated lactoferrin (Fe3O4-bLf) nanocarriers for triple positive (EpCAM, CD133, CD44) colon tumor targeting and NIR, MRI and CT imaging

This is the first ever attempt to combine anti-cancer therapeutic effects of emerging anticancer biodrug bovine lactoferrin (bLf), and multimodal imaging efficacy of Fe3O4 nanoparticles (NPs) together, as a saturated Fe3O4-bLf. For cancer stem cell specific uptake of nanocapsules/nanocarriers (NCs), Fe3O4-bLf was encapsulated in alginate enclosed chitosan coated calcium phosphate (AEC-CP) NCs targeted (Tar) with locked nucleic acid (LNA) modified aptamers against epithelial cell adhesion molecule (EpCAM) and nucleolin markers. The nanoformulation was fed orally to mice injected with triple positive (EpCAM, CD133, CD44) sorted colon cancer stem cells in the xenograft cancer stem cell mice model. The complete regression of tumor was observed in 70% of mice fed on non-targeted (NT) NCs, with 30% mice showing tumor recurrence after 30 days, while only 10% mice fed with Tar NCs showed tumor recurrence indicating a significantly higher survival rate. From tumor tissue analyses of 35 apoptotic markers, 55 angiogenesis markers, 40 cytokines, 15 stem cell markers and gene expression studies of important signaling molecules, it was revealed that the anti-cancer mechanism of Fe3O4-bLf was intervened through TRAIL, Fas, Fas-associated protein with death domain (FADD) mediated phosphorylation of p53, to induce activation of second mitochondria-derived activator of caspases (SMAC)/DIABLO (inhibiting survivin) and mitochondrial depolarization leading to release of cytochrome C. Induction of apoptosis was observed by inhibition of the Akt pathway and activation of cytokines released from monocytes/macrophages and dendritic cells (interleukin (IL) 27, keratinocyte chemoattractant (KC)). On the other hand, the recurrence of tumor in AEC-CP-Fe3O4-bLf NCs fed mice mainly occurred due to activation of alternative pathways such as mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK) and Wnt signaling leading to an increase in expression of survivin, survivin splice variant (survivin 2B) and other anti-apoptotic proteins Bad, Bcl-2 and XIAP. Apart from the promising anti-cancer efficacy and the exceptional tumor targeting ability observed by multimodal imaging using near-infrared (NIR) imaging, magnetic resonance imaging (MRI) and computerized tomographic (CT) techniques, these NCs also maintained the immunomodulatory benefits of bLf as they were able to increase the RBC, hemoglobin, iron calcium and zinc levels in mice.

Modal transformation applied to double three-phase transmission lines

Double three-phase transmission lines are analyzed in this paper using a modal transformation model. The main attribute of this model is the use of a single real transformation matrix based on line geometrical characteristics and the Clarke matrix. Because of this, for any line point, the electrical values can be accessed for phase domain or mode domain using the considered transformation matrix and without convolution methods. For non-transposed symmetrical lines the errors between the model results and the exact modes are insignificant values. The eigenvector and eigenvalue analyses for transposed lines search the similarities among the three analyzed transposition types and the possible simplifications for a non-transposed case.

Modal transformation analyses for double three-phase transmission lines

Eigenvector and eigenvalue analyses are carried out for double three-phase transmission lines, studying the application of a constant and real phase-mode transformation matrix and the errors of this application to mode line models. Employing some line transposition types, exact results are obtained with a single real transformation matrix based on Clarke's matrix and line geometrical characteristics. It is shown that the proposed technique leads to insignificant errors when a nontransposed case is considered. For both cases, transposed and nontransposed, the access to the electrical values (voltage and current, for example) is provided through a simple matrix multiplication without convolution methods. Using this facility, an interesting model for transmission line analysis is obtained even though the nontransposed case errors are not eliminated. The main advantages of the model are related to the transformation matrix: single, real, frequency independent, and identical for voltage and current.

Decomposição modal de linhas de transmissão a partir do uso de duas matrizes de transformação

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alternative Model of Three-Phase Transmission Line Theory-Based Modal Decomposition

In this paper is shown the development of a transmission line, based on discrete circuit elements that provide responses directly in the time domain and phase. This model is valid for ideally transposed rows represent the phases of each of the small line segments are separated in their modes of propagation and the voltage and current are calculated at the modal field. However, the conversion phase-mode-phase is inserted in the state equations which describe the currents and voltages along the line of which there is no need to know the user of the model representation of the theory in the field lines modal.

Alternative proposal for Modal Representation of a Non-transposed Three-Phase Transmission Line with a Vertical Symmetry Plane

The objective of this paper is to show an alternative representation in time domain of a non-transposed three-phase transmission line decomposed in its exact modes by using two transformation matrices. The first matrix is Clarke's matrix that is real, frequency independent, easily represented in computational transient programs (EMTP) and separates the line into quasi-modes a, b and zero. After that, Quasi-modes a and zero are decomposed into their exact modes by using a modal transformation matrix whose elements can be synthesized in time domain through standard curve-fitting techniques. The main advantage of this alternative representation is to reduce the processing time because a frequency dependent modal transformation matrix of a three-phase line has nine elements to be represented in time domain while a modal transformation matrix of a two-phase line has only four elements. This paper shows modal decomposition process and eigenvectors of a non-transposed three-phase line with a vertical symmetry plane whose nominal voltage is 440 kV and line length is 500 km.

An alternative modal representation of a symmetrical nontransposed three-phase transmission line

The objective of this letter is to propose an alternative modal representation of a nontransposed three-phase transmission line with a vertical symmetry plane by using two transformation matrices. Initially, Clarke's matrix is used to separate the line into components a, 0, and zero. Because a and zero components are not exact modes, they can be considered as being a two-phase line that will be decomposed in its exact modes by using a 2 x 2 modal transformation matrix. This letter will describe the characteristics of the two-phase line before mentioned. This modal representation is applied to decouple a nontransposed three-phase transmission line with a vertical symmetry plane whose nominal voltage is 440 kV.

Modal representation of three-phase lines applying two transformation matrices: Evaluation of its eigenvectors

The objective of this paper is to show an alternative representation in time domain of a non-transposed three-phase transmission line decomposed in its exact modes by using two transformation matrices. The first matrix is Clarke's matrix that is real, frequency independent, easily represented in computational transient programs (EMTP) and separates the line into Quasi-modes alpha, beta and zero. After that, Quasi-modes a and zero are decomposed into their exact modes by using a modal transformation matrix whose elements can be synthesized in time domain through standard curve-fitting techniques. The main advantage of this alternative representation is to reduce the processing time because a frequency dependent modal transformation matrix of a three-phase line has nine elements to be represented in time domain while a modal transformation matrix of a two-phase line has only four elements. This paper shows modal decomposition process and eigenvectors of a nontransposed three-phase line with a vertical symmetry plane whose nominal voltage is 440 kV and line length is 500 km.

Modal representation of three-phase lines applying two transformation matrices: Evaluation of its eigenvectors

The objective of this paper is to show an alternative representation in time domain of a non-transposed three-phase transmission line decomposed in its exact modes by using two transformation matrices. The first matrix is Clarke's matrix that is real, frequency independent, easily represented in computational transient programs (EMTP) and separates the line into Quasi-modes α, β and zero. After that, Quasi-modes a and zero are decomposed into their exact modes by using a modal transformation matrix whose elements can be synthesized in time domain through standard curve-fitting techniques. The main advantage of this alternative representation is to reduce the processing time because a frequency dependent modal transformation matrix of a three-phase line has nine elements to be represented in time domain while a modal transformation matrix of a two-phase line has only four elements. This paper shows modal decomposition process and eigenvectors of a non-transposed three-phase line with a vertical symmetry plane whose nominal voltage is 440 kV and line length is 500 km. ©2006 IEEE.

An alternative procedure to decrease the dimension of the frequency dependent modal transformation matrices: Application in three-phase transmission lines with a vertical symmetry plane

The objective of this paper is to show an alternative representation in time domain of a non-transposed three-phase transmission line decomposed in its exact modes by using two transformation matrices. The first matrix is Clarke's matrix that is real, frequency independent, easily represented in computational transient programs (EMTP) and separates the line into Quasi-modes α, β and zero. After that, Quasi-modes α and zero are decomposed into their exact modes by using a modal transformation matrix whose elements can be synthesized in time domain through standard curve-fitting techniques. The main advantage of this alternative representation is to reduce the processing time because a frequency dependent modal transformation matrix of a three-phase line has nine elements to be represented in time domain while a modal transformation matrix of a two-phase line has only four elements. This paper shows modal decomposition process and eigenvectors of a non-transposed three-phase line with a vertical symmetry plane whose nominal voltage is 440 kV and line length is 500 km. © 2006 IEEE.

Modal transformation obtained from Clarke's matrix - Asymmetrical three-phase case

Some constant matrices can be used as phase-mode transformation matrices for transposed three-phase transmission lines. Clarke's matrix is one of these options. Its application as a phase-mode transformation matrix for untransposed three-phase transmission lines has been analyzed through error and frequency scan comparisons. Based on an actual untransposed asymmetrical three-phase transmission line example, a correction procedure is applied searching for better results from the Clarke's matrix applicaton as a phase-mode transformation matrix. The error analyses are carried out using Clarke's matrix and the new transformation matrices obtained from the correction procedure. Applying Clarke's matrix, the relative errors of the eigenvalue matrix elements can be considered negligible and the relative values of the off-diagonal elements are significant. If the the corrected transformation matrices are used, the relative values of the off-diagonal elements are decreased. Based on the results of these analyses, the homopolar mode is more sensitive to the frequency influence than the two other modes related to three-phase lines. © 2007 IEEE.

Mutual coupling modeling in transmission lines directly in the phase domain

This paper describes a computational model based on lumped elements for the mutual coupling between phases in three-phase transmission lines without the explicit use of modal transformation matrices. The self and mutual parameters and the coupling between phases are modeled using modal transformation techniques. The modal representation is developed from the intrinsic consideration of the modal transformation matrix and the resulting system of time-domain differential equations is described as state equations. Thus, a detailed profile of the currents and the voltages through the line can be easily calculated using numerical or analytical integration methods. However, the original contribution of the article is the proposal of a time-domain model without the successive phase/mode transformations and a practical implementation based on conventional electrical circuits, without the use of electromagnetic theory to model the coupling between phases. © 2011 IEEE.

Proposal of a simplified process to correct the phase decoupling using modal analysis

Modal analysis is widely approached in the classic theory of transmission line modeling. This technique is applied to model the three-phase representation of conventional electric systems taking into account their self and mutual electrical parameters. However the methodology has some particularities and inaccuracies for specific applications which are not clearly described in the basic references of this topic. This paper provides a thorough review of modal analysis theory applied to line models followed by an original and simple procedure to overcome the possible errors embedded in the modal decoupling through the three-phase system modeling. © 2012 IEEE.

Development of a simplified transmission line model directly in the phase domain

A transmission line digital model is developed direct in the phase and time domains. The successive modal transformations considered in the three-phase representation are simplified and then the proposed model can be easily applied to several operation condition based only on the previous knowing of the line parameters, without a thorough theoretical knowledge of modal analysis. The proposed model is also developed based on lumped elements, providing a complete current and voltage profile at any point of the transmission system. This model makes possible the modeling of non-linear power devices and electromagnetic phenomena along the transmission line using simple electric circuit components, representing a great advantage when compared to several models based on distributed parameters and inverse transforms. In addition, an efficient integration method is proposed to solve the system of differential equations resulted from the line modeling by lumped elements, thereby making possible simulations of transient and steady state using a wide and constant integration step. © 2012 IEEE.

A distributed-parameters transmission line model developed directly in the phase domain

This article shows a transmission line model developed directly in the phase domain. The proposed model is based on the relationships between the phase currents and voltages at both the sending and receiving ends of a single-phase line. These relationships, established using an ABCD matrix, were extended to multi-phase lines. The proposed model was validated by using it to represent a transmission line during short-and open-circuit tests. The results obtained with the proposed model were compared with results obtained with a classical model based on modal decomposition. These comparisons show that proposed model was correctly developed. © 2013 Taylor and Francis Group, LLC.