Onset of Telomere Dysfunction and Fusions in Human Ovarian Carcinoma.

Telomere dysfunction has been strongly implicated in the initiation of genomic instability and is suspected to be an early event in the carcinogenesis of human solid tumors. Recent findings have established the presence of telomere fusions in human breast and prostate malignancies; however, the onset of this genomic instability mechanism during progression of other solid cancers is not well understood. Herein, we explored telomere dynamics in patient-derived epithelial ovarian cancers (OC), a malignancy characterized by multiple distinct subtypes, extensive molecular heterogeneity, and widespread genomic instability. We discovered a high frequency of telomere fusions in ovarian tumor tissues; however, limited telomere fusions were detected in normal adjacent tissues or benign ovarian samples. In addition, we found relatively high levels of both telomerase activity and hTERT expression, along with anaphase bridges in tumor tissues, which were notably absent in adjacent normal ovarian tissues and benign lesions. These results suggest that telomere dysfunction may occur early in ovarian carcinogenesis and, importantly, that it may play a critical role in the initiation and progression of the disease. Recognizing telomere dysfunction as a pervasive feature of this heterogeneous malignancy may facilitate the future development of novel diagnostic tools and improved methods of disease monitoring and treatment.

Design and Preclinical Development of a Phage Product for the Treatment of Antibiotic-Resistant Staphylococcus aureus Infections.

Bacteriophages, viruses that only kill specific bacteria, are receiving substantial attention as nontraditional antibacterial agents that may help alleviate the growing antibiotic resistance problem in medicine. We describe the design and preclinical development of AB-SA01, a fixed-composition bacteriophage product intended to treat Staphylococcus aureus infections. AB-SA01 contains three naturally occurring, obligately lytic myoviruses related to Staphylococcus phage K. AB-SA01 component phages have been sequenced and contain no identifiable bacterial virulence or antibiotic resistance genes. In vitro, AB-SA01 killed 94.5% of 401 clinical Staphylococcus aureus isolates, including methicillin-resistant and vancomycin-intermediate ones for a total of 95% of the 205 known multidrug-resistant isolates. The spontaneous frequency of resistance to AB-SA01 was ≤3 × 10-9, and resistance emerging to one component phage could be complemented by the activity of another component phage. In both neutropenic and immunocompetent mouse models of acute pneumonia, AB-SA01 reduced lung S. aureus populations equivalently to vancomycin. Overall, the inherent characteristics of AB-SA01 component phages meet regulatory and generally accepted criteria for human use, and the preclinical data presented here have supported production under good manufacturing practices and phase 1 clinical studies with AB-SA01.

Dynamic iris biometry: a technique for enhanced identification.

BACKGROUND: The iris as a unique identifier is predicated on the assumption that the iris image does not alter. This does not consider the fact that the iris changes in response to certain external factors including medication, disease, surgery as well as longer term ageing changes. It is also part of a dynamic optical system that alters with light level and focussing distance. A means of distinguishing the features that do not alter over time from those that do is needed. This paper applies iris recognition algorithms to a newly acquired database of 186 iris images from four subjects. These images have greater magnification and detail than iris images in existing databases. Iris segmentation methods are tested on the database. A new technique that enhances segmentation is presented and compared to two existing methods. These are also applied to test the effects of pupil dilation in the identification process. FINDINGS: Segmentation results from all the images showed that using the proposed algorithm accurately detected pupil boundaries for 96.2% respectively of the images, which was an increase of 88.7% over the most commonly used algorithm. For the images collected, the proposed technique also showed significant improvement in detection of the limbal boundary compared to the detection rates using existing methods. With regard to boundary displacement errors, only slight errors were found with the proposed technique compared to extreme errors made when existing techniques were applied. As the pupil becomes more dilated, the success of identification is increasingly more dependent on the decision criterion used. CONCLUSIONS: The enhanced segmentation technique described in this paper performs with greater accuracy than existing methods for the higher quality images collected in this study. Implementation of the proposed segmentation enhancement significantly improves pupil boundary detection and therefore overall iris segmentation. Pupil dilation is an important aspect of iris identification; with increasing dilation, there is a greater risk of identification failure. Choice of decision criterion for identification should be carefully reviewed. It needs to be recognised that differences in the quality of images in different databases may result in variations in the performance of iris recognition algorithms.