A Comparison of Cryptographic Methods

While elliptic curve cryptography and quantum cryptography are significantly different branches of cryptography, they provide a suitable reference point for comparison of the value of developing methods used in the present and investing in methods to be used in the future. Elliptic curve cryptography is quite common today, as it is generally secure and efficient. However, as the field of cryptography advances, the value of quantum cryptography’s inherent security from its basic properties should be considered, as a fully realized quantum cryptosystem has the potential to be quite powerful. Ultimately, it is of critical importance to determine the value of investing in strengthening current cryptosystems in comparison to seeking to accelerate the development of new ones. While both are of importance, the question should be asked if one avenue of development will be more effective overall

Orthogonal Synthesis of Indolines and Isoquinolines via Aryne Annulation

Described in this report is the development of two unique methodologies exploiting the reactivity of arynes. Reaction of N-carbamoyl-functionalized enamine derivatives with benzyne affords substituted indolines. An orthogonal reactivity is uncovered when related enamine derivatives are modified as amides, such that isoquinolines are formed as the product of condensation with benzyne. This latter transformation is applied to a concise total synthesis of the opiate alkaloid papaverine

A Comparison of the Fish Populations and Habitat in Open and Closed Salt Marsh Impoundments in East-Central Florida

Historical and recent biological surveys including aerial and ground level photographs reveal gross changes in vegetation and fish habitat associated with impoundment and flooding of salt marshes bordering the Indian River lagoon in east-central Florida. These studies show a depauperate ichthyofauna and floral association in impoundments excluded from estuarine tidal influence. Monthly collections of fishes made during 1979 and 1980 are used to compare two marsh impoundments: one closed to tidal influence from the Indian River lagoon and the other reopened to tidal influence through a single 80 em diameter culvert. The closed impoundment was found to contain a depauperate ichthyofauna consisting of 12 species collected under stressed environmental conditions. Water temperatures ranged from 14 to 34° C, salinities fluctuated widely from 2.0 to 200 ppt and dissolved oxygen was measured as low as 1.2 and as high as 14.2 ppm. The open impoundment contained a far richer ichthyofauna with 41 fish species captured at temperatures of 13.5 to 30° C, salinities of 25 to 38 ppt and dissolved oxygen levels of 2.2 to 7.5 ppm. The open impoundment also demonstrated extensive regrowth of marsh vegetation

CRISPR/Cas9-based editing of a sensitive transcriptional regulatory element to achieve cell type-specific knockdown of the NEMO scaffold protein

The use of alternative promoters for the cell type-specific expression of a given mRNA/protein is a common cell strategy. NEMO is a scaffold protein required for canonical NF-κB signaling. Transcription of the NEMO gene is primarily controlled by two promoters: one (promoter B) drives NEMO transcription in most cell types and the second (promoter D) is largely responsible for NEMO transcription in liver cells. Herein, we have used a CRISPR/Cas9-based approach to disrupt a core sequence element of promoter B, and this genetic editing essentially eliminates expression of NEMO mRNA and protein in 293T human kidney cells. By cell subcloning, we have isolated targeted 293T cell lines that express no detectable NEMO protein, have defined genomic alterations at promoter B, and do not support activation of canonical NF-κB signaling in response to treatment with tumor necrosis factor. Nevertheless, noncanonical NF-κB signaling is intact in these NEMO-deficient cells. Expression of ectopic wildtype NEMO, but not certain human NEMO disease mutants, in the edited cells restores downstream NF-κB signaling in response to tumor necrosis factor. Targeting of the promoter B element does not substantially reduce NEMO expression (from promoter D) in the human SNU423 liver cancer cell line. Thus, we have created a strategy for selectively eliminating cell typespecific expression from an alternative promoter and have generated 293T cell lines with a functional knockout of NEMO. The implications of these findings for further studies and for therapeutic approaches to target canonical NF-κB signaling are discussed.Published versio

Spinal cord grey matter pathology in multiple sclerosis

Background: Traditionally, Multiple Sclerosis (MS) has been considered to be a predominantly white matter (WM) disease. More recent studies have revealed considerable grey matter (GM) involvement in the brain. However there is a paucity of literature examining GM pathology in the spinal cord. Objectives and methods: We use human post-mortem material to explore various aspects of spinal cord GM pathology in MS including (i) the extent and pattern of spinal cord demyelination, (ii) the relative contributions of GM and WM volume loss to spinal cord atrophy, (iii) the extent of neuronal pathology within the spinal cord and (iv) the sensitivity of post-mortem MRI for detecting spinal cord GM plaques. Results: Within the spinal cord, GM demyelination is more extensive than WM demyelination with many lesions showing a novel morphological pattern whereby the plaque borders maintain a strict respect for the GM/WM boundary. Demyelination is more extensive in the spinal cord GM than in other brain regions examined. Post-mortem MR imaging at 4.7 Tesla is highly sensitive for detecting the spinal cord GM plaques. We demonstrate substantial neuronal loss in the spinal cord in MS, observing reductions in both interneuron and motoneuron numbers. This neuronal loss occurs predominantly within GM plaques. We also observe reductions in interneuron size, both within plaques and in the myelinated GM. Despite this, we find no evidence of spinal cord GM atrophy. Conclusions: This study represents the first detailed examination of spinal cord GM involvement in MS. We demonstrate substantial GM pathology in the spinal cord, further challenging the concept that MS is a predominantly WM disease. A greater understanding of this pathology may provide important insights into MS pathogenesis and mechanisms of disability in the disease