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.     

On-demand learning for a wireless campus

The current Internet and wireless networks are harsh environments for transporting high-bandwidth multimedia data. We examine the technical issues involved, and describe an end-to-end solution to support a Web-based learn-on-demand system that operates in a wireless campus environment.     

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     

Structure and stability of an immunoglobulin superfamily domain from twitchin, a muscle protein of the nematode Caenorhabditis elegans

The NMR solution structure of an immunoglobulin superfamily module of twitchin (Ig 18') has been determined and the kinetic and equilibrium folding behaviour characterised. Thirty molecular coordinates were calculated using a hybrid distance geometry-simulated annealing protocol based on 1207 distance and 48 dihedral restraints. The atomic rms distributions about the mean coordinate for the ensemble of structures is 0.55( +/- 0.09) A for backbone atoms and 1.10( +/- 0.08) A for all heavy atoms. The protein has a topology very similar to that of telokin and the titin Ig domains and thus it falls into the I set of the immunoglobulin superfamily. The close agreement between the predicted and observed structures of Ig 18' demonstrates clearly that the I set profile can be applied in the structure prediction of immunoglobulin-like domains of diverse modular proteins. Folding studies reveal that the protein has relatively low thermodynamic stability, deltaG(H2O)U-F = 4.0 kcal mol(-1) at physiological pH. Unfolding studies suggest that the protein has considerable kinetic stability, the half life of the unfolding is greater than 40 minutes in the absence of denaturant.     

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.     

Effect of Wall Surface Properties at Different Drying Kinetics on the Deposition Problem in Spray Drying

Current methods in alleviating the wall deposition problem in spray drying emphasize mainly controlling the stickiness of the drying particles and less attention is placed on the properties of the dryer wall. In this experimental study, the effect of wall surface properties on the deposition mechanism has been investigated. Properties considered in classifying different wall materials were surface energy, roughness, and dielectric properties. The model solution contained sucrose, representing low-molecular-weight sugars commonly encountered in spray drying of fruit and vegetable juices. The effect of wall properties on deposition was explored at different drying rates producing particles of different surface rigidity. Larger surface roughness produced higher deposition fluxes for particles with high impact velocity and moisture. Surface energy and surface roughness were found to have no significant effect for dry rigid particles at the middle and bottom elevation of the drying chamber. However, material with lower surface energy (Teflon) exhibited less deposition for rubbery particles at such elevations. Analysis shows that dielectric wall material (Teflon) tends to enhance deposition of dry particles because of attrition at the surface. Higher wall temperature was found to produce slightly more deposition. The results of this work give a general indication of the effect of wall material on the deposition problem and provide the fundamental understanding for further studies along this line. Proper selection of dryer wall material will provide potential alternatives for reducing the deposition problem.     

Robust State Feedback Control Through Actuators With Generalized Sector Nonlinearities And Saturation

In control systems, actuators often have nonlinear characteristics that can not be neglected. For linear systems driven by actuators satisfying the generalized sector condition, a robust state feedback controller synthesis method is proposed to achieve the ultimate boundedness control. The method is based on the linear matrix inequality approach and is easy to apply. As an important special case of the generalized sector condition, the saturation characteristic of actuators is discussed separately, and non‐conservative results are obtained.     

Nonoperative management of esophageal perforations. Is it justified?

OBJECTIVE: Experiences obtained with nonoperative treatment (NOT), i.e. total prohibition of per oral food intake for a minimum of 7 days, administration of combinations of broad-spectrum antibiotics, and parenteral hyperalimentation, are described in the management of esophageal perforations. SUMMARY BACKGROUND DATA: The place, value, and indication of NOT in the management of esophageal perforation has not yet been unequivocally defined. As a result, contradictory data have been published regarding the outcome of NOT. METHODS: During the past 15 years (1979 to 1994), 20 of 86 patients (23.3%) with esophageal perforation have been treated nonoperatively from the outset. In this group, perforations were located to the upper, middle, and lower third of the esophagus in 50%, 30%, and 20%, respectively. In the operative management group (OT)--in which conservative (drainage, endeprothesis), reconstructive (suture, reinforced suture), and radical (resection) surgical methods were applied--lesions were preponderantly located in the lower one third of the esophagus (56.1%--37/66). As to the interval between the perforation and the onset of treatment, 14 patients had been diagnosed within 24 hours, whereas in 6 cases treatment had been begun beyond 24 hours. RESULTS: NOT could be successfully carried out in 16 patients; the decision to use NOT had to be revised in 4 other cases (Table 1). Two patients were lost; the mortality rate was 10% (2 of 20). The rate of complications was lower in the NOT group (20%, or 4 of 20) than in the OT group (50%, or 33 of 66). CONCLUSIONS: NOT can be suggested for the treatment of intramural perforations. In the case of transmural perforation, this approach should be taken into consideration if the esophageal lesion is circumscribed, is not in neoplastic tissue, is not in the abdominal cavity, and is not accompanied by simultaneous obstructive esophageal disease; in addition, symptoms and signs of septicemia should be absent.     

Gordon-Haus timing jitter reduction in dispersion-managed solitoncommunications

An analytic theory is presented which demonstrates that the noise induced Gordon-Haus timing jitter in arbitrary dispersion-managed transmission systems is reduced by the power-enhancement factor required to support a dispersion-managed solitons provided the path-average soliton period is much greater than the dispersion-map period. The analysis further predicts the behaviour of the amplitude, width, and quadratic chirp fluctuations due to the amplified spontaneous emission (ASE) noise