Synthetic Peroxides Promote Apoptosis of Cancer Cells by Inhibiting P-Glycoprotein ABCB5

This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC₅₀=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma.     

Supermedia-enhanced Internet-based telerobotics

This paper introduces new planning and control methods for supermedia-enhanced real-time telerobotic operations via the Internet. Supermedia is the collection of video, audio, haptic information, temperature, and other sensory feedback. However, when the communication medium used, such as the Internet, introduces random communication time delay, several challenges and difficulties arise. Most importantly, random communication delay causes instability, loss of transparency, and desynchronization in real-time closed-loop telerobotic systems. Due to the complexity and diversity of such systems, the first challenge is to develop a general and efficient modeling and analysis tool. This paper proposes the use of Petri net modeling to capture the concurrency and complexity of Internet-based teleoperation. Combined with the event-based planning and control method, it also provides an efficient analysis and design tool to study the stability, transparency, and synchronization of such systems. In addition, the concepts of event transparency and event synchronization are introduced and analyzed. This modeling and control method has been applied to the design of several supermedia-enhanced Internet-based telerobotic systems, including the bilateral control of mobile robots and mobile manipulators. These systems have been experimentally implemented in three sites test bed consisting of robotic laboratories in the USA, Hong Kong, and Japan. The experimental results have verified the theoretical development and further demonstrated the stability, event transparency, and event synchronization of the systems.     

Ideal amplifier spacing for reduction of Gordon-Haus jitter indispersion-managed soliton communications

Based on a variational analysis, the authors demonstrate that the noise-induced Gordon-Haus timing jitter in a dispersion-managed soliton transmission system can be substantially reduced by appropriate placement of the amplifiers     

The pharmacokinetics and protein-binding of fusidic acid in patients with severe renal failure requiring either haemodialysis or continuous ambulatory peritoneal dialysis

Antibiotic treatment options for Burkholderia cepacia infection are limited because of high intrinsic resistance. The problem is complicated by development of cross-resistance between antibiotics of different classes. We isolated antibiotic-resistant mutants by stepwise exposure to chloramphenicol (Chlor) and to trimethoprim/sulphamethoxazole (T/S) for four B. cepacia strains: ATCC13945, Per (clinical isolate), Cas and D4 (environmental isolates). Chlor(r) mutants did not produce chloramphenicol acetyl-transferase. Cross-resistance, defined as greater than four-fold increase in MIC by microtitre dilution method, was consistently seen in both types of mutants. For chloramphenicol-resistant (Chlor[r]) and trimethoprim/sulphamethoxazole-resistant (Tr/Sr) mutants of B. cepacia ATCC13945 and Cas, no MIC change was seen for piperacillin, ceftazidime, rifampicin, gentamicin, tobramycin, polymyxin B or azithromycin. B. cepacia-Per and -D4 mutants showed cross-resistance to ceftazidime and to piperacillin. Comparison of outer membrane protein (OMP) profiles of B. cepacia and their mutants by SDS-PAGE revealed Tr/Sr) mutants to be deficient in a major OMP (molecular weight 39-47 kDa). Tr/Sr mutants also expressed additional OMPs not found in wild type strains at 75-77 kDa for B. cepacia-ATCC13945 and -Cas, and 20-21 kDa in B. cepacia-D4 and -Per. No OMP changes occurred in Chlor(r) mutants. Lipopolysaccharide (LPS) profiles of each type of mutant showed new high and low molecular weight LPS bands. Cross-resistance seems to be mediated by alterations in porin and LPS for Tr/Sr mutants, but only by LPS in Chlor(r) mutants.     

Context-specific adaptation of vertical vergence to correlates of eye position

Vertical phoria (vertical vergence in the absence of binocular feedback) can be trained to vary with non-visual cues such as vertical conjugate eye position, horizontal conjugate eye position and horizontal vergence. These prior studies demonstrated a low-level association or coupling between vertical vergence and several oculomotor cues. As a test of the potential independence of multiple eye-position cues for vertical vergence, context-specific adaptation experiments were conducted in three orthogonal adapting planes (midsagittal, frontoparallel, and transverse). Four vertical disparities in each of these planes were associated with various combinations of two specific components of eye position. Vertical disparities in the plane were associated with horizontal vergence and vertical conjugate eye position; vertical disparities in the frontoparallel plane were associated with horizontal and vertical conjugate eye position; and vertical disparities in the transverse plane were associated with horizontal vergence and horizontal conjugate eye position. The results demonstrate that vertical vergence can be adapted to respond to specific combinations of two different sources of eye-position information. The results are modeled with an association matrix whose inputs are two classes of eye position and whose weighted output is vertical vergence.     

Measurements of single chain form factors by small-angle neutron scattering from polystyrene blends containing high concentrations of labelled molecules

A series of small angle neutron scattering measurements on blends of normal polystyrene (PSH) and labelled (deuterated) polystyrene (PSD) have been made with concentrations of PSD from 5 to 50 mol %. It is shown that the single chain form factor of the polymer in bulk can be obtained from a single concentration measurement for any concentration of labelled molecules, providing the molecular weights of the parent and labelled molecules are the same and the molecular weight distributions are narrow.