Boron-Rich Nanoscale Delivery Agents for the Boron Neutron Capture Therapy of Cancer

Nanoscience Poster SessionThe translational research effort in boron neutron capture therapy (BNCT) described below and recently initiated at the University of Missouri International Institute of Nano and Molecular Medicine and the University of Missouri Research Reactor would benefit from collaboration with a research group knowledgeable in modeling human tumors using small animal hosts and cellular biology as it relates to therapeutic results and the treatment of experimental data. The boron-10 (10B) isotope is unique among light elements for its high neutron cross-section and low inherent toxicity. When subjected to relatively benign thermal neutrons, the 10B nucleus undergoes a neutron capture reaction forming an excited 11B species. This unstable nucleus subsequently undergoes essentially instantaneous fission to release 2.4 MeV of kinetic energy in the form of a pair of 7Li3+ and 4He2+ ions, which are confined to the volume of about one cell. Therefore, preferential accumulation of 10B-containing structures within cancerous cells can lead to selective destruction of these cells. This process is more commonly known as Boron Neutron Capture Therapy (BNCT) for cancer. The key to the implementation of this potentially powerful and selective therapy is the delivery of at least 30 parts per million (ppm) of 10B within the tumor tissue while minimizing superfluous 10B within the surrounding healthy tissue. This difference in 10B concentration is often denoted through the boron concentration in tumor to boron concentration in blood ratio, with a higher ratio being preferable. Herein we describe the synthesis and results of biodistribution experiments with two nano-scale boron delivery agents: liposomes and oligomeric phosphate diesters (OPDs). Liposomes, containing both amphiphilic (KC2B9H11(CH2)15CH3, MAC) and hydrophilic (Na3B20H17NH3, TAC) components and ranging in diameter from 30 to 100 nm, showed tumor boron accumulations as high as 50 ppm and tumor to blood ratios over 8. OPDs, ranging in size from 1 to 5 nm in diameter, also exhibited preferential tumor accumulations of 30 ppm at tumor to blood ratios as high as 35 to 1. In both cases, liposomes and OPDs greatly outperformed currently available small boron-containing pharmaceuticals at the same injected dose of 10B. Studies in which OPDs were fluorescently labeled proved their localization within the cellular nucleus, increasing the relative efficacy of these species due to their proximity to the DNA target. In conclusion, both liposomes and OPDs show great promise as nano-sized delivery vehicles for BNCT

A study of long-term potentiation in transgenic mice over-expressing mutant forms of both amyloid precursor protein and presenilin-1

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Synaptic transmission and long-term potentiation (LTP) in the CA1 region of hippocampal slices have been studied during ageing of a double transgenic mouse strain relevant to early-onset familial Alzheimer's disease (AD). This strain, which over-expresses both the 695 amino acid isoform of human amyloid precursor protein (APP) with K670N and M671L mutations and presenilin 1 with the A246E mutation, has accelerated amyloidosis and plaque formation. There was a decrease in synaptic transmission in both wildtype and transgenic mice between 2 and 9 months of age. However, preparing slices from 14 month old animals in kynurenic acid (1 mM) counteracted this age-related deficit. Basal transmission and paired-pulse facilitation was similar between the two groups at all ages (2, 6, 9 and 14 months) tested. Similarly, at all ages LTP, induced either by theta burst stimulation or by multiple tetani, was normal. These data show that a prolonged, substantially elevated level of Aβ are not sufficient to cause deficits in the induction or expression of LTP in the CA1 hippocampal region.Published versio

Multilevel effects in the Rabi oscillations of a Josephson phase qubit

We present Rabi oscillation measurements of a Nb/AlOx/Nb dc superconducting quantum interference device (SQUID) phase qubit with a 100 um^2 area junction acquired over a range of microwave drive power and frequency detuning. Given the slightly anharmonic level structure of the device, several excited states play an important role in the qubit dynamics, particularly at high power. To investigate the effects of these levels, multiphoton Rabi oscillations were monitored by measuring the tunneling escape rate of the device to the voltage state, which is particularly sensitive to excited state population. We compare the observed oscillation frequencies with a simplified model constructed from the full phase qubit Hamiltonian and also compare time-dependent escape rate measurements with a more complete density-matrix simulation. Good quantitative agreement is found between the data and simulations, allowing us to identify a shift in resonance (analogous to the ac Stark effect), a suppression of the Rabi frequency, and leakage to the higher excited states.Comment: 14 pages, 9 figures; minor corrections, updated reference

Challenging the brain disease model of addiction: European launch of the addiction theory network

Challenging the brain disease model of addiction: European launch of the addiction theory networ

UK B.1.1.7 variant exhibits increased respiratory replication and shedding in nonhuman primates.

The continuing emergence of SARS-CoV-2 variants calls for regular assessment to identify differences in viral replication, shedding and associated disease. In this study, African green monkeys were infected intranasally with either a contemporary D614G or the UK B.1.1.7 variant. Both variants caused mild respiratory disease with no significant differences in clinical presentation. Significantly higher levels of viral RNA and infectious virus were found in upper and lower respiratory tract samples and tissues from B.1.1.7 infected animals. Interestingly, D614G infected animals showed significantly higher levels of viral RNA and infectious virus in rectal swabs and gastrointestinal tract tissues. Our results indicate that B.1.1.7 infection in African green monkeys is associated with increased respiratory replication and shedding but no disease enhancement similar to human B.1.1.7 cases. ONE-SENTENCE SUMMARY: UK B.1.1.7 infection of African green monkeys exhibits increased respiratory replication and shedding but no disease enhancement