Ir(III) and Ru(II) Complexes in Photoredox Catalysis and Photodynamic Therapy: A New Paradigm towards Anticancer Applications

Individually, photoredox catalysis (PC) and photodynamic therapy (PDT) are well-established concepts that have experienced a remarkable resurgence in recent years, leading to significant progress in organic synthesis for PC and clinical approval of anticancer drugs for PDT. But, very recently, new photoredox catalyst systems based on Ir(III) and Ru(II) complexes have garnered significant interest because they can simultaneously be used as PDT agents apart from their demonstrated PC activity. This highlight discusses the unique PC behavior of emerging Ir(III)- and Ru(II)-based systems while also examining their potential PDT activity in cancer treatment.     

On the synergy between electrical and photonic switching

This article focuses on the values of electrical switching vs. photonic switching in the context of telecom transport networks. In particular, we show that the requirement of providing agility at the optical layer in the face of traffic forecast uncertainties is served better through photonic switching. On the other hand, some of the network-level functions, such as fast protection, subwavelength aggregation, and flexible client connectivity, require electrical switching. We further argue that additional values are achieved with hybrid photonic and electrical switching, which do not exist when either of these options is used in isolation.     

Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

Unexplained physical symptoms: outcome, utilization of medical care and associated factors

BACKGROUND: Measurement of intracardiac hemodynamic parameters has been limited to brief periods in the acute care setting. We developed and evaluated an implantable hemodynamic monitor that is capable of measuring chronic right ventricular oxygen saturation and pulmonary artery pressure. METHODS AND RESULTS: The device consists of an electronic controller placed subcutaneously and two transvenous leads placed in the right ventricle (reflectance oximeter) and pulmonary artery (variable capacitance pressure sensor). Implantation was performed in 10 patients with severe left ventricular dysfunction. Average implant pulmonary artery pressures were systolic, 52 +/- 16 mm Hg; diastolic, 29 +/- 11 mm Hg; and mean, 40 +/- 12 mm Hg. The mean right ventricular oxygen saturation at implant was 51%. Provocative maneuvers, including postural changes, sublingual nitroglycerin, and bicycle exercise, demonstrated expected changes in measured oxygen saturation and pulmonary artery pressures over time. At follow-up of 0.5 to 15.5 months, there were no significant differences between pulmonary artery pressures or oxygen saturation values transmitted from the device and simultaneous measurement with balloon flotation catheters. Four of the pulmonary artery leads dislodged and three demonstrated sensor drift, whereas two of the oxygen saturation sensors failed. Four patients died and four received transplants. Pathological study did not demonstrate injury to the right ventricular outflow tract or pulmonic valve. CONCLUSIONS: Chronic measurement of hemodynamic parameters in the outpatient setting with implantable sensor technology appears to be feasible. The devices are well tolerated without significant untoward effects, and the sensors generally function well over time, providing reliable information. Clinical usefulness remains to be established.     

Design of sample adaptive product quantizers for noisy channels

Channel-optimized vector quantization (COVQ) has proven to be an effective joint source-channel coding technique that makes the underlying quantizer robust to channel noise. Unfortunately, COVQ retains the high encoding complexity of the standard vector quantizer (VQ) for medium-to-high quantization dimensions and moderate-to-good channel conditions. A technique called sample adaptive product quantization (SAPQ) was recently introduced by Kim and Shroff to reduce the complexity of the VQ while achieving comparable distortions. In this letter, we generalize the design of SAPQ for the case of memoryless noisy channels by optimizing the quantizer with respect to both source and channel statistics. Numerical results demonstrate that the channel-optimized SAPQ (COSAPQ) achieves comparable performance to the COVQ (within 0.2 dB), while maintaining considerably lower encoding complexity (up to half of that of COVQ) and storage requirements. Robustness of the COSAPQ system against channel mismatch is also examined.     

The effects of a monetary alternative on marijuana self-administration

We have used a variety of methods to characterize the genome of the archaeon Methanosarcina thermophila TM-1. Pulsed-field gel analysis indicates a genome size of 2.8 Mb. We have constructed a bacterial artificial chromosome (BAC) library of M. thermophila and have used it to generate physical maps for this organism. The library is made up of 384 clones with an average insert size of 58 kb representing 8.0 genome equivalents. The utility of the library for low-resolution physical mapping was shown by identifying NotI linking clones and using these to order the NotI macrorestriction fragments of M. thermophila into a 2.8 Mb map. Hybridization of nine single copy genes and a 16S rRNA sequence to these macrorestriction fragments forms the basis for the first genetic map in this organism. High-resolution physical maps, consisting of overlapping clones, have been created using HindIII fingerprints of BAC clones. In this way, we identified a minimal path of five clones that span a 270 kb NotI fragment. The ease of manipulating BAC clones makes the BAC system an excellent choice for the construction of low-resolution and high-resolution physical and genetic maps of archaeal genomes. It also provides a substrate for future genome-sequencing efforts.     

Effect of crosslinking agent content, monomer functionality, and repeat unit chemistry on properties of unfilled resins

Seven mechanical/physical properties were used to evaluate 10 unfilled resins: eight aromatic dimethacrylates and two urethane dimethacrylates. Physical property tests included compressive strength, Young's modulus in compression, uniaxial tensile strength, intrinsic yield point, toothbrush abrasion, Knoop hardness, and water sorption. Controlled changes were made in the following four material parameters: amount of crosslinking diluent present in the uncured monomer, functionality of the monomer, repeat unit chemistry of the monomer (urethane vs. aromatic structure) and mode of activation (chemical vs. visible light). Polymers containing a high concentration of crosslinking agent (50 wt%) were found to be tougher and to possess lower hardness than materials containing lesser amounts of crosslinking agent. This was attributed to the flexible nature of the triethylene glycol dimethacrylate crosslinking molecule. Exposure to water plasticized the highly crosslinked materials to the degree that the yield point and elastic modulus were effectively lowered. Most of the tested properties were unaffected by differences in functionality except resistance to toothbrush abrasion, which was enhanced for polymers derived from high functionality monomers. The urethane-based polymers sorbed substantially more water than the aromatic-based materials, which presumably resulted in lower values for surface hardness. However, the urethane resins were very tough, and excellent resistance to toothbrush abrasion was observed. Property differences caused by differences in activation mode were small, although the visible light materials did sorb more water.