Extending the capability of forensic electrochemistry to the novel psychoactive substance benzylpiperazine.

Benzylpiperazine (BZP) is a novel psychoactive substance that is commonly abused in tablet form as an 'ecstasy-type' drug. Electroanalysis offers genuine potential for field testing of bulk drug samples. This research is the first to investigate the viability of voltammetric analysis of BZP. Initial cyclic voltammetry in 0.1 M KCl showed an oxidative peak at a glassy carbon electrode for BZP at approximately 0.8 V (scan rate 205 mV s− 1). Next an optimised electrode/electrolyte combination (viz. 80:20 W:W glassy carbon beads:nujol and pH 9.5, 40 mM, Britton-Robinson buffer) was developed using K3Fe(CN)6 to test the electrode material. The oxidation of BZP involves two electrons and two protons and a mechanism has been proposed. An anodic stripping square wave voltammetric method was optimised by factorial design with the conditions of deposition: − 0.8 V for 135 s, and stripping: step height 10 mV, amplitude 50 mV and frequency 13 Hz. A limit of detection of 6 μM was achieved. The resolution against 3,4-methylenedioxymethylamphetamine (MDMA) was also verified

System requirements analysis and technological support for the Ballistic Missile Defense System (BMDS): FY07 progress report

Engineering of the Ballistic Missile Defense System (BMDS) requires one to take a holistic approach that includes the physical modeling and analysis of the missile defense operating environment, development of metrics and techniques to analyze the communication requirements of the net-centric Ballistic Missile Defense warfare, and the use of architectural patterns and other software technologies to shape the emergent behavior of the BMDS taking into account of the system's interoperability, composability, extensibility, and dynamic reconfigurability. This report summarizes the work in FY07 to investigate new technologies to support the development of the BMDS. We developed new scoring functions for the fusion of sensor data, an algorithm for multiple hypothesis tracking, a distributed medium access control protocol and data dissemination algorithm for wireless networks of cooperative radar systems, simulation models for network-centric electronic warfare metrics study and for the prediction of the over the horizon radar system footprints, technologies for the correct specification and validation of temporal behaviors in a Service-Oriented Architecture (SOA) based system-of-systems, runtime verification of system-level requirements of distributed reactive systems using MSC-Assertions, and safety assurance of reconfigurable and selfreconfigurable systems. We also evaluated the effectiveness of the real-time Java technology for BMDS software and the potential impact of integrating the Air Force YAL-1A Attack Laser into the BMDS.Approved for public release; distribution is unlimited

G.O.2: Mutations in LMOD3 cause severe nemaline myopathy by disrupting thin filament organisation in skeletal muscle

Nemaline myopathy (NM) is a disorder of the skeletal muscle thin filament characterised by muscle dysfunction and electron-dense protein accumulations (nemaline bodies). Pathogenic mutations have been described in nine genes to date, but the genetic basis remains unknown in many cases. We used whole exome sequencing (WES) in two families with NM and subsequent gene sequencing in over 540 additional genetically unresolved NM patients to identify and characterise a new genetic cause of NM. We developed a knock-down zebrafish model of this condition and used immunohistochemistry, western blotting, single-fibre contractility studies and recombinant protein studies to characterise the expression, localisation and biochemical functions of the new disease-related protein. We identified homozygous or compound heterozygous variants in LMOD3, which encodes leiomodin-3 (Lmod3) in 21 patients from 14 families. Affected individuals had severe generalised weakness and hypotonia, and most affected individuals died in the neonatal period. We demonstrated that Lmod3 is expressed from early muscle differentiation, localises to thin filaments with enrichment at the pointed ends, and has strong actin nucleating activity. Loss of Lmod3 in patient muscle results in shortening and disorganisation of thin filaments. Knockdown of lmod3 in the zebrafish replicates this phenotype. These findings define a new genetic subtype of congenital myopathy and demonstrate an essential, previously unrecognised role for Lmod3 in the regulation of sarcomeric thin filaments in skeletal muscle