Daunorubicin‐Loaded DNA Origami Nanostructures Circumvent Drug‐Resistance Mechanisms in a Leukemia Model

Many cancers show primary or acquired drug resistance due to the overexpression of efflux pumps. A novel mechanism to circumvent this is to integrate drugs, such as anthracycline antibiotics, with nanoparticle delivery vehicles that can bypass intrinsic tumor drug‐resistance mechanisms. DNA nanoparticles serve as an efficient binding platform for intercalating drugs (e.g., anthracyclines doxorubicin and daunorubicin, which are widely used to treat acute leukemias) and enable precise structure design and chemical modifications, for example, for incorporating targeting capabilities. Here, DNA nanostructures are utilized to circumvent daunorubicin drug resistance at clinically relevant doses in a leukemia cell line model. The fabrication of a rod‐like DNA origami drug carrier is reported that can be controllably loaded with daunorubicin. It is further directly verified that nanostructure‐mediated daunorubicin delivery leads to increased drug entry and retention in cells relative to free daunorubicin at equal concentrations, which yields significantly enhanced drug efficacy. Our results indicate that DNA origami nanostructures can circumvent efflux‐pump‐mediated drug resistance in leukemia cells at clinically relevant drug concentrations and provide a robust DNA nanostructure design that could be implemented in a wide range of cellular applications due to its remarkably fast self‐assembly (≈5 min) and excellent stability in cell culture conditions.     

Robust fault detection using Luenberger-type unknown input observers-a parametric approach

A new parametric observer-based approach for robust fault detection in multivariable linear systems with unknown disturbances is proposed. The residual is generated through utilizing a Luenberger function observer. By using a parametric solution to a class of generalized Sylvester matrix equations, a parametrization is proposed for the residual generator on the basis of a Luenberger function observer. By further properly constraining the design parameters provided in the Luenberger observer design, the effect of the unknown disturbance is decoupled from the residual signal. The proposed approach provides all the degrees of freedom and is demonstrated to be simple and effective.     

Mixed time- and frequency-domain robust eigenstructure assignment

This paper considers robust eigenstructure assignment for multivariable systems. The time-domain performance specifications provided by eigenstructure assignment and robust performance specifications in the frequency domain considered by H infinity control are combined to realize joint optimal robust control design. A parametric expression for state-feedback eigenstructure assignment is introduced on the basis of a set of free parameters. The mixed performance index used as the cost function consists of two parts: robustness in the frequency domain; and system eigenstructure constraints in the time domain. The analytical gradient calculation of the cost function with respect to the free parameters is derived for optimal robust eigenstructure assignment using gradientbased optimization. The mixed time- and frequency-domain robust eigenstructure assignment is demonstrated in the design of a mode-decoupled roll-yaw autopilot.     

A study on neuro-fuzzy systems for fault diagnosis

Fault diagnosis can be facilitated by using either quantitative or qualitative information of the system monitored. This paper presents a novel approach to integrate quantitative and qualitative information in fault-diagnosis, based on the use of neuro-fuzzy systems. In this approach the diagnostic signals (residuals) are generated and evaluated via a B-Spline functions network. The configuration adopted allows the designer to both extract and include symbolic knowledge from the trained network to provide reliable diagnostic information. The effectiveness of the proposed diagnosis strategy is illustrated through a simulation study of a nonlinear two-tank system.     

Being bicultural: A mixed-methods study of adolescents' implicitly and explicitly measured multiethnic identities.

Understanding how ethnic identities develop in adolescence is currently limited by a reliance on self-report paper-and-pencil measures. This mixed-methods study presents a novel response time measure, the Multiethnic Identities Processing Task (MIPT), to quantify bicultural adolescents' implicit identifications with ethnic and racial identity labels. Eighty-four adolescents (age 14–21 years) of diverse ethnic and racial backgrounds self-identified as bicultural or not bicultural and described their ethnic identities, pride, and ethnic centrality during a brief interview. Participants were assigned to complete either the interview (self-prime) or the MIPT (no prime) first. Results indicate that bicultural adolescents readily endorsed a variety of ethnic and racial labels in the MIPT, reflecting their multifaceted identities. Younger bicultural adolescents showed a large inhibited response to the label “White,” indicating some hesitation in deciding whether the label was “like me” or “not like me.” Heart rate monitoring and qualitative analyses of interviews provide some insight into this pattern of results. Findings are discussed with respect to developmental theory, and the strengths of using both implicit and explicit measures to understand multiethnic identity development in adolescence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Consider Multiple Solutions

Design teams rarely consider multiple solution ideas before committing to one. They often forget that an even better idea could be just around the corner, and consider alternative ideas only when they don't like the current one. Using sketchboarding, design studio, or a combination of these two techniques can let teams quickly ideate over many solutions. They then have a chance to arrive at a solution that no one individual had thought of.     

Factors related to the formation of cytoplasmic crescents on milk fat globules

Cytoplasm from lactating cells is included with some milk fat globules at secretion. The objective was to search for factors causing this phenomenon. Globules bearing crescents of cytoplasm were selectively stained with the fluorescent dye, acridine orange, and their proportion in the globule population was obtained by counting from photomicrographs. Incidence of crescents on fat globules in milk samples of 50 human donors ranged from 1 to 29%, and the mean was 7.2%. Two bovine milk samples, both representing over 100 animals, contained 1% or less of globules with crescents. Globules in individual milkings of five beef cows showed the same low proportion of crescents. In addition to species, genetic and diurnal factors influenced numbers of crescents. Two sisters showed evidence within and between lactations of a persistent high proportion (greater than 25%) of globules with crescents. Samples collected in the a.m. contained a lower percentage of globules with crescents (6.5%) than those obtained in the p.m. (9.7%). Crescent incidence was not correlated with lipid or protein content of human milk, interval within a milking, days in lactation, or the donor's age. Evidence is presented to suggest that the concentration, distribution, and acylation of butyrophilin and xanthine oxidase, coat proteins of the apical plasma membrane, are important factors in globule crescent formation.