Photosensitizer Targeting: Mitochondrion-Targeted Photosensitizer Enhances Mitochondrial Reactive Oxygen Species and Mitochondrial Calcium-Mediated Apoptosis

Using laser scanning imaging microscopy, our previous studies have demonstrated visible laser irradiation induced significant generation of mitochondrial reactive oxygen species (mROS) and apoptosis. In addition, photodynamic therapy (PDT) with a mitochondrion-targeted photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), significantly enhanced visible laser irradiation induced mitochondrial dysfunction and apoptosis. To validate the critical role of the mitochondrion as well as how mitochondrial mechanisms were involved in the PDT of BPD-MA, subcellular PDT with BPD-MA were performed using region irradiation and recorded by multi-photon imaging microscopy coupled with mitochondrial specific fluorescent probes in single live C6 glioma cells. Specifically, mROS and mitochondrial free calcium (mCa²⁺) were simultaneously measured from cells received subcellular PDT with BPD-MA in different compartments including the mitochondrion, the cytosol and the nucleus. Results revealed that significant formation of mROS accompanied by elevation of mCa²⁺ was found only in the mitochondrial PDT with BPD-MA. Subsequently, mitochondrial PDT with BPD-MA resulted in severe mitochondrial swelling, plasma membrane blebing and apoptotic death. We conclude that via augmented mROS formation and mCa²⁺ elevation PDT with a mitochondrion-targeted photosensitizer extensively enhances mitochondria-mediated apoptosis and, thus, may provide high eradication efficacy for clinical cancer treatment.     

A VIF-based optimization model to alleviate collinearity problems in multiple linear regression

In this paper, we address data collinearity problems in multiple linear regression from an optimization perspective. We propose a novel linearly constrained quadratic programming model, based on the concept of the variance inflation factor (VIF). We employ the perturbation method that involves imposing a general symmetric non-diagonal perturbation matrix on the correlation matrix. The proposed VIF-based model reduces the largest VIF by minimizing the resulting biases. The VIF-based model can mitigate the harm from data collinearity through the reduction in both the condition number and VIFs, meanwhile improving the statistical significance. The resulting estimator has bounded biases under an iterative framework and hence is termed the least accumulative bias estimator. Certain potential statistical properties can be further considered as the side constraints for the proposed model. Various numerical examples validate the proposed approach.     

Non-equilibrium thermodynamic potential and flux fluctuation theorem

A flux fluctuation theorem proposed recently [Seitaridou, et al., J. Phys. Chem. B 111 (2007) 2288] on the relative probability of direct and reverse diffusion fluxes in a non-equilibrium steady state is related here to a non-equilibrium thermodynamic potential used in extended irreversible thermodynamics. This connection allows one to provide a new derivation of the theorem, which complements the previous one, to generalize it to other fluxes, and illustrates the thermodynamic relevance of this theorem.     

Pyrene-fluorene hybrids containing acetylene linkage as color-tunable emitting materials for organic light-emitting diodes

New blue- to yellow-emitting materials have been developed by incorporating fluorene-based chromophores on pyrene core with acetylene linkage and using multifold palladium-catalyzed cross-coupling reactions. Both mono- and tetrasubstituted derivatives have been synthesized and characterized. The tetrasubstituted derivatives displayed red-shifted emission when compared to the monosubstituted derivative indicative of an extended conjugation in the former. End-capping with a diphenylamine unit further red-shifted the absorption and emission profiles and imparted a weak dipolar character to the molecules. Amine-containing derivatives displayed positive solvatochromism in the fluorescence spectra indicating a more polar excited state due to an efficient charge migration from the diphenylamine donor to the pyrene π-acceptor. All of the derivatives were tested as emitting dopants with host material 4,4'-bis(9H-carbazol-9-yl)biphenyl (CBP) in a multilayered OLED and found to exhibit bright blue or yellow electroluminescence. The device utilizing 1,3,6,8-tetrasubstituted pyrene derivative as a dopant emitter displayed highest maximum luminescence 4630 cd/m(2) with power efficiency 3.8 lm/W and current efficiency 7.1 cd/A at 100 cd/m(2) attributable to the proper alignment of energy levels that led to the efficient harvesting of excitons. All of the devices exhibited color purity over a wide range of operating voltages.     

Robot learning schemes that trade motion accuracy for command simplification

This study was inspired by the human motor control system in its ability to accommodate a wide variety of motions. By contrast, the biologically inspired robot learning controller usually encounters huge learning space problems in many practical applications. A hypothesis for the superiority of the human motor control system is that it may have simplified the motion command at the expense of motion accuracy. This tradeoff provides an insight into how fast and simple control can be achieved when a robot task does not demand high accuracy. Two motion command simplification schemes are proposed in this paper based on the equilibrium-point hypothesis for human motion control. Investigation into the tradeoff between motion accuracy and command simplification reported in this paper was conducted using robot manipulators to generate signatures. Signature generation involves fast handwriting, and handwriting is a human skill acquired via practice. Because humans learn how to sign their names after they learn how to write, in the second learning process, they somehow learn to trade motion accuracy for motion speed and command simplicity, since signatures are simplified forms of original handwriting. Experiments are reported that demonstrate the effectiveness of the proposed schemes.     

Diagnosing the miR-141 prostate cancer biomarker using nucleic acid-functionalized CdSe/ZnS QDs and telomerase

The microRNA, miR-141, is a promising biomarker for prostate cancer. We implement here a two-step sensing platform for the sensitive detection of miR-141. The first step involves the use of semiconductor CdSe/ZnS quantum dots (QDs) modified by FRET quencher-functionalized nucleic acids, that include the recognition sequence for miR-141 and a telomerase primer sequence for the second step of the analytical platform. Subjecting the probe-modified QDs to miR-141, in the presence of duplex specific nuclease, DSN, leads to the formation of a miR-141/probe duplex and to its DSN-mediated cleavage, while regenerating the miR-141. The DSN-induced cleavage of the quencher units leads to the activation of the fluorescence of the QDs, thus allowing the optical detection of miR-141 with a sensitivity corresponding to 1.0 × 10^–12 M. The nucleic acid residues associated with the QDs after cleavage of the probe nucleic acids by DSN act as primers for telomerase. The subsequent telomerase/dNTPs-stimulated elongation of the primer units forms G-quadruplex telomer chains. Incorporation of hemin in the resulting G-quadruplex telomer chains yields horseradish peroxidase-mimicking DNAzyme units, that catalyze the generation of chemiluminescence in the presence of luminol/H₂O₂. The resulting chemiluminescence intensities provide a readout signal for miR-141, DL = 2.8 × 10^–13 M. The first step of the sensing platform is non-selective toward miR-141 and the resulting fluorescence may be considered only as an indicator for the existence of miR-141. The second step in the sensing protocol, involving telomerase, provides a selective chemiluminescence signal for the existence of miR-141. The two-step sensing platform is implemented for the analysis of miR-141 in serum samples from healthy individuals and prostate cancer carriers. Impressive discrimination between healthy individuals and prostate cancer carriers is demonstrated.     

A Stable and Compact Optical Module for Fiber-Optic Gyroscope Application

Abstract

This article introduces a new design for a bi-directional optical sub-assembly for fiber-optic gyroscope applications that integrates a super-luminescent light-emitting diode, a photodiode, a beam splitter, an isolator, a fiber receptacle, and a thermal electric cooler. It is less than 1.5 cm in diameter and 2.5 cm in height. As chip temperature was kept at 30°C under environment temperature of ?35°C, 25°C, and 75°C, the bi-directional optical sub-assembly reached stability at a center wavelength of 1,539 nm and a wavelength shift of 1.5 nm. A 3D simple model with the finite-element method was used to analyze thermal performance.     

Statistical physics and fluctuations in ballistic non-equilibrium systems

In nonequilibrium systems in the ballistic transport regime, every point of the system contains particles arriving from different regions-each of them at different temperatures-and there are only few collisions, in such a way that equilibrium between the different populations will be reached very slowly. Here, we tentatively approach the local distribution function by a superposition of local-equilibrium distribution functions with different temperatures, corresponding to the different starting positions of the particles. In a second-order expansion, we find a distribution function which depends not only on the Hamiltonian H but also on H², and we study the additional contribution to energy fluctuations.     

Turbulent forced convective heat transfer in two-phase evaporating droplet flow through a vertical pipe

A physical model was developed to study heat transfer in turbulent dispersed flow at very high vapor quality in a vertical pipe by numerically solving the coupling governing differential equations for both phases. Major heat transfer mechanisms included in the model were the thermal nonequilibrium effects, droplet vaporization, droplet deposition on the duct wall and thermal radiative transfer. The predicted results indicated that vapor superheating is dominant for the cases with high wall superheat, otherwise droplet vaporization dominates the energy transport processes. Heat transfer during the droplet-wall interaction only exists at low wall superheat but in small amounts.     

Transport of contrast agents in contrast-enhanced magnetic resonance angiography

Contrast-enhanced magnetic resonance angiography (CEMRA) often appears to display vessels with good resolution, but it does not adequately visualize the throat of a tight stenosis. Image quality in CEMRA is also governed by the timing of contrast injection and data acquisition. We developed a numerical technique to predict the image appearance of a target vessel by taking into account the passage of contrast agent. Experiments were conducted on a phantom with both centric and linear ordering. An effort to prolong the duration in which the contrast passes by employing a double injection technique gives a wider window of opportunity to acquire quality images.