Polymeric prodrugs of mitomycin C designed for tumour tropism and sustained activation

Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents.     

Molecular cloning of human Frizzled-6

The Frizzled genes encode receptors for WNTs, secreted glycoproteins implicated in development as well as in carcinogenesis. In this paper, we report molecular cloning of Hfz6, the human homologue of Mfz6. Nucleotide sequence analysis showed that the Hfz6 gene encodes the 706 amino-acid protein with seven transmembrane domains, a cystein-rich domain in the N-terminal extracellular region, two N-linked glycosylation sites, and two cystein residues in the second and third extracellular loops. Hfz6 mRNA 4.4-kb in size was detected in various normal adult and fetal tissues, and a larger amount of Hfz6 mRNA was detected in both fetal lung and fetal kidney. The Hfz6 gene has been mapped to human chromosome 8q22.3-q23.1. In conclusion, we have cloned Hfz6, which encodes a seven-transmembrane receptor with the cystein-rich domain in the N-terminal extracellular region, but without the Ser/Thr-X-Val motif in the C-terminus.     

Fabrication of 1.55 μm VCSELs on Si using metallic bonding

Using AuGeNiCr multilayered metals as the wafer bonding medium, long-wavelength GaInAsP/InP vertical cavity surface emitting lasers employing Al-oxide/Si as the upper and lower distributed Bragg reflectors were fabricated on Si substrate with the bonding interface formed outside the vertical cavity surface emitting laser cavity. Laser emission at 1.545 μm was measured under pulsed operations near room temperature. The low-temperature metallic bonding process demonstrates a great potential in device fabrication     

Development of a recurrent Sigma-Pi neural network rainfall forecasting system in Hong Kong

At the moment, weather forecasting is still an art — the experience and intuition of forecasters play a significant role in determining the quality of forecasting. This paper describes the development of a new approach to rainfall forecasting using neural networks. It deals with the extraction of information from radar images and an evaluation of past rain gauge records to provide shortterm rainfall forecasting. All of the meteorological data were provided by the Royal Observatory of Hong Kong (ROHK). Preprocessing procedures were essential for this neural network rainfall forecasting. The forecast of the rainfall was performed every half an hour so that a storm warning signal can be delivered to the public in advance. The network architecture is based on a recurrent Sigma-Pi network. The results are very promising, and this neural-based rainfall forecasting system is capable of providing a rain storm warning signal to the Hong Kong public one hour ahead.     

Spontaneous disappearance of traumatic macular holes in young patients

PURPOSE: To report the disappearance of traumatic macular hole in three eyes of three patients. METHODS: Clinical data of the patients were reviewed. RESULTS: The three patients were relatively young, ranging in age from 12 to 18 years old. In one eye of each patient, a small traumatic macular hole was observed at the first visit. Visual acuities ranged from 20/100 to 20/40. The macular holes resolved spontaneously 3 to 4 months after the trauma, and final visual acuity improved to 20/20 in all patients. CONCLUSION: Small traumatic macular holes in young patients can resolve spontaneously, and this can be associated with good visual recovery.     

Estimation of deformation gradient and strain from cine-PC velocity data

Phase contrast magnetic resonance imaging (MRI) can provide in vivo myocardial velocity field measurements. These data allow densely spaced material points to be tracked throughout the whole heart cycle using, for example, the Fourier tracking algorithm. To process the tracking results for myocardial deformation and strain quantification, we developed a method that is based on fitting the tracking results to an appropriate local deformation model. We further analyzed the accuracy and precision of the method and provided performance predictions for several local models. In order to validate the method and the theoretical performance analysis, we conducted controlled computer simulations and a phantom study. The results agreed well with expectations. Human heart data were also acquired and analyzed, and provided encouraging results. At the signal-to-noise ratio (SNR) level and spatial resolution expected in clinical settings, the study predicts strain quantification accuracy and precision that may allow the technique to become a practical and powerful noninvasive approach for the study of cardiac function, although clinically acceptable data acquisition strategies for three-dimensional (3-D) data are still a challenge.