(R,R)-2,2'-[1,2-ethanediylbis[imino(1-methyl-2,1-ethanediyl)]]- bis[5-nitro-1H-benz[de]isoquinoline-1,3-(2H)-dione] dimethanesulfonate (DMP 840), a novel bis-naphthalimide with potent nonselective tumoricidal activity in vitro

(R,R)-2,2'-[1,2-ethanediylbis[imino(1-methyl-2,1-ethanediyl)]]- bis[5-nitro-1H-benz[de]isoquinoline-1,3-(2H)-dione] dimethanesulfonate (DMP 840), is a bis-naphthalimide anticancer tumoricidal agent currently in phase I clinical trials. DMP 840 exhibits curative activity in human tumor xenografts, where it shows selectivity for human solid tumors over murine leukemias. In contrast to the selectivity found for DMP 840 in vivo, DMP 840 exhibits potent antiproliferative activity in vitro against a variety of human and murine leukemia and solid tumor cell lines in culture, with inhibitory doses that reduce the number of treated cells to one half (IC50) values ranging from 2.3 to 53 nM. DMP 840 was growth inhibitory to three doxorubicin-resistant cell lines with IC50 values also in the nanomolar range. Clonogenic survival experiments showed that DMP 840 was equally cytotoxic to both exponentially growing and quiescent human clone A colon carcinoma cells. A 1-h incubation of DMP 840 (1.22-12 microM) caused 5-log cell kill in KB-3-1 human epidermoid carcinoma, clone A human colon carcinoma, and L1210 murine leukemia cell lines. The rapid cell killing by DMP 840 in clonogenic survival experiments and initial mechanism of action studies was consistent with a DNA-interactive mechanism for DMP 840 cytotoxicity. Mechanism of action studies in L1210 leukemia cells demonstrated that DMP 840 inhibited the incorporation of thymidine and uridine into DNA and RNA with IC50 values of 0.55 and 0.08 microM, respectively. DMP 840 produced DNA single-strand breaks in a dose-dependent manner. Double-strand breaks were not observed with DMP 840 treatment, even at higher concentrations of compound. Chinese hamster ovary (CHO) and P388 cells resistant to camptothecin and containing a mutant form of topoisomerase I were also used to evaluate whether DMP 840 was cross-resistant with agents active against topoisomerase I. While the CHOR line was 163-fold resistant to camptothecin, the CHOR line was only 1.7-fold resistant to DMP 840. In summary, DMP 840 is a DNA-interactive agent that demonstrates excellent antiproliferative activity in vitro against cultured tumor cells from both human and murine sources. Its mechanism of tumoricidal activity may be novel.     

Delaminations at the free edge of a composite laminate

The concept of a fracture process zone where damage takes place is used to analyse the delaminations at the free edges of angle ply laminates under uniaxial tension. The use of a fracture process zone removes the singularity in the interlaminar stresses and enables the initiation and growth of delaminations to be modelled for a perfect laminate without any assumed prior defects. Two different models for the stress displacement relationship in the fracture process zone are examined: a constant stress up to critical displacement and a linear relationship. Finite element analysis shows that there is little difference in the predictions obtained from the two models. An approximate analysis is presented for the constant stress stress-displacement model which is shown to agree with a finite element solution and experimental data. Hence it is argued that the approximate method using a constant stress model for the fracture process zone is sufficient for accurate prediction of delaminations.     

Positive state‐bounding observer for positive interval continuous‐time systems with time delay

This paper is concerned with the problem of positive observer synthesis for positive systems with both interval parameter uncertainties and time delay. Conventional observers may no longer be applicable for such kind of systems due to the positivity constraint on the observers, and they only provide an estimate of the system state in an asymptotic way. A pair of positive observers with state‐bounding feature is proposed to estimate the state of positive systems at all times in this paper. A necessary and sufficient condition for the existence of desired observers is first established, and the observer matrices can be obtained easily through the solutions of a set of linear matrix inequalities (LMIs). Then, to reduce the error signal between the system state and its estimates, an iterative LMI algorithm is developed to compute the optimized state‐bounding observer matrices. Finally, a numerical example is presented to show the effectiveness and applicability of the theoretical results. Copyright © 2011 John Wiley & Sons, Ltd.     

Fast full‐color reflective display via photoluminescent enhancement

Reflective displays are advantageous in applications requiring low power or daylight readability. However, there are no low‐cost reflective technologies capable of displaying bright colors. By employing photoluminescence to more efficiently use ambient light, we created a prototype display that provides bright, full color in a simple, low‐cost architecture. This prototype includes a novel electrokinetic shutter, a layer that incorporates patterned luminescent red, green, and blue sub‐pixel elements, and a novel optical out‐coupling scheme. The luminescent elements convert otherwise‐wasted portions of the incident spectrum to light in the desired color band, resulting in improved color saturation and lightness. This prototype provides a color gamut that is superior to competing reflective display technologies that utilize color filters in single‐layer side‐by‐side sub‐pixel architectures. The current prototype is capable of switching in <0.5 s; future displays based on an alternative electro‐optic shutter technology should achieve video rate operation. A transflective version of this technology has also been prototyped. The transflective version utilizes its backlight with a power efficiency that is at least three times that of a conventional liquid crystal display. These photoluminescence‐based technologies enable a host of applications ranging from low‐power mobile products and retail pricing signage to daylight readable signage for outdoor advertising segments.     

Electrokinetically driven concentration of particles and cells by dielectrophoresis with DC-offset AC electric field

Insulator-based dielectrophoresis (iDEP) has been successfully used for on-chip manipulations of biological samples. Despite its effectiveness, iDEP typically requires high DC voltages to achieve sufficient electric field; this is mainly due to the coupled phenomena among linear electrokinetics: electroosmosis (EO) and electrophoresis (EP) and nonlinear electrokinetics: dielectrophoresis (DEP). This paper presents a microfluidic technique using DC-offset AC electric field for electrokinetic concentration of particles and cells by repulsive iDEP. This technique introduces AC electric field for producing iDEP which is decoupled from electroosmosis (EO) and electrophoresis (EP). The repulsive iDEP is generated in a PDMS tapered contraction channel that induces non-uniform electric field. The benefits of introducing AC electric field component are threefold: (i) it contributes to DEP force acting on particles, (ii) it suppresses EO flow and (iii) it does not cause any EP motion. As a result, the required DC field component that is mainly used to transport particles on the basis of EO and EP can be significantly reduced. Experimental results supported by numerical simulations showed that the total DC-offset AC electric field strength required to concentrate 15-μm particles is significantly reduced up to 85.9% as compared to using sole DC electric field. Parametric experimental studies showed that the higher buffer concentration, larger particle size and higher ratio of AC-to-DC electric field are favorable for particle concentration. In addition, the proposed technique was demonstrated for concentration of yeast cells.     

Optimization and evaluation of reduced graphene oxide hydrogel composite as a demulsifier for heavy crude oil-in-water emulsion

The rising production of produced water from oilfields had been proven to bring detrimental environmental effects. In this study, an efficient, recyclable, and environmental-friendly reduced graphene oxide immobilized κ-Carrageenan hydrogel composite(κCa GO) was fabricated as an alternative sorbent for crude oil-in-water demulsification. Polyethyleneimine(PEI) was employed to form a stable hydrogel composite. The conditions for the immobilization of graphene oxide(GO) on PEI-modified κ-Carrageenan(κC) beads were optimized appropriately. An immobilization yield of 77% was attained at 2% PEI, 2 h immobilization activation time, and p H6.5. Moreover, the synthesized κCa GO is capable of demulsification with an average demulsification efficiency of 70%. It was found that the demulsification efficiency increases with salinity and κCa GO dosage, and it deteriorates under alkaline condition. These phenomena can be attributed to the interfacial interactions between κCa GO and the emulsion. Furthermore, the κCa GO can be recycled to use for up to six cycles without significant leaching and degradation. As such, the synthesized κCa GO could be further developed as a potential sorbent substitute for the separation of crude oil from produced water.     

Effects of Adenine Methylation on the Structure and Thermodynamic Stability of a DNA Minidumbbell

DNA methylation is a prevalent regulatory modification in prokaryotes and eukaryotes. N¹-methyladenine (m¹A) and N⁶-methyladenine (m⁶A) have been found to be capable of altering DNA structures via disturbing Watson–Crick base pairing. However, little has been known about their influences on non-B DNA structures, which are associated with genetic instabilities. In this work, we investigated the effects of m¹A and m⁶A on both the structure and thermodynamic stability of a newly reported DNA minidumbbell formed by two TTTA tetranucleotide repeats. As revealed by the results of nuclear magnetic resonance spectroscopic studies, both m¹A and m⁶A favored the formation of a T·m¹A and T·m⁶A Hoogsteen base pair, respectively. More intriguingly, the m¹A and m⁶A modifications brought about stabilization and destabilization effects on the DNA minidumbbell, respectively. This work provides new biophysical insights into the effects of adenine methylation on the structure and thermodynamic stability of DNA.     

Usher Syndrome in the Inner Ear: Etiologies and Advances in Gene Therapy

Hearing loss is the most common sensory disorder with ~466 million people worldwide affected, representing about 5% of the population. A substantial portion of hearing loss is genetic. Hearing loss can either be non-syndromic, if hearing loss is the only clinical manifestation, or syndromic, if the hearing loss is accompanied by a collage of other clinical manifestations. Usher syndrome is a syndromic form of genetic hearing loss that is accompanied by impaired vision associated with retinitis pigmentosa and, in many cases, vestibular dysfunction. It is the most common cause of deaf-blindness. Currently cochlear implantation or hearing aids are the only treatments for Usher-related hearing loss. However, gene therapy has shown promise in treating Usher-related retinitis pigmentosa. Here we review how the etiologies of Usher-related hearing loss make it a good candidate for gene therapy and discuss how various forms of gene therapy could be applied to Usher-related hearing loss.     

Large-scale in vivo synthesis of the carbohydrate moieties of gangliosides GM1 and GM2 by metabolically engineered Escherichia coli

Two metabolically engineered Escherichia coli strains have been constructed to produce the carbohydrate moieties of gangliosides GM2 (GalNAcbeta-4(NeuAcalpha-3)Galbeta-4Glc; Gal = galactose, Glc = glucose, Ac = acetyl) and GM1 (Galbeta-3GalNAcbeta-4(NeuAcalpha-3)Galbeta-4Glc. The GM2 oligosaccharide-producing strain TA02 was devoid of both beta-galactosidase and sialic acid aldolase activities and overexpressed the genes for CMP-NeuAc synthase (CMP = cytidine monophosphate), alpha-2,3-sialyltransferase, UDP-GlcNAc (UDP = uridine diphosphate) C4 epimerase, and beta-1,4-GalNAc transferase. When this strain was cultivated on glycerol, exogenously added lactose and sialic acid were shown to be actively internalized into the cytoplasm and converted into GM2 oligosaccharide. The in vivo synthesis of GM1 oligosaccharide was achieved by taking a similar approach but using strain TA05, which additionally overexpressed the gene for beta-1,3-galactosyltransferase. In high-cell-density cultures, the production yields for the GM2 and GM1 oligosaccharides were 1.25 g L(-1) and 0.89 g L(-1), respectively.