Commissioning of the advanced light source dual-axis streak camera

A dual-axis camera, Hamamatsu model C5680, has been installed on the Advanced Light Source photon-diagnostics beam-line to investigate electron-beam parameters. During its commissioning process, the camera has been used to measure single-bunch length vs. current, relative bunch charge in adjacent RF buckets, and bunchphase stability. In this paper the authors describe the visible-light branch of the diagnostics beam-line, the streak-camera installation, and the timing electronics. They will show graphical results of beam measurements taken during a variety of accelerator conditions

Tensile Properties and Microstructures of Laser-Formed Ti-6Al-4V

The room temperature tensile properties of Ti-6Al-4V alloy prepared under two different processing routes were evaluated and compared. One group of samples was prepared by conventional casting-forging-rolling into flat plates. The other group was prepared by using Triton\u27s Laser Free-Form Fabrication (LF3)(TM) processes, i.e., a laser was used to melt pre-alloyed powders of the required metallic composition as they were dropped onto a moveable substrate programmed to move in such a manner as to form a solid alloy plate. Five populations of Ti-6Al-4V were evaluated: a standard wrought form, an as-deposited form, a machined as-deposited form, a heat-treated as-deposited form, and a machined as-deposited and heat-treated form. The poorest mechanical properties occurred with the rough surfaces, likely due to existing microcracks and stress concentrations. The LF3 (TM) as-deposited material had mechanical properties comparable to, if not higher than, the mechanical properties of the wrought material. Further evaluations of the laser-formed material for complex spacecraft piece parts were warranted, specifically in regards to improving the surface finish of the materials

Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria

Here, we describe the discovery of a novel antimalarial agent using phenotypic screening of Plasmodium falciparum asexual blood-stage parasites. Screening a novel compound collection created using diversity-oriented synthesis (DOS) led to the initial hit. Structure–activity relationships guided the synthesis of compounds having improved potency and water solubility, yielding a subnanomolar inhibitor of parasite asexual blood-stage growth. Optimized compound 27 has an excellent off-target activity profile in erythrocyte lysis and HepG2 assays and is stable in human plasma. This compound is available via the molecular libraries probe production centers network (MLPCN) and is designated ML238.Chemistry and Chemical Biolog

Engineered Single-Domain Antibodies with High Protease Resistance and Thermal Stability

The extreme pH and protease-rich environment of the upper gastrointestinal tract is a major obstacle facing orally-administered protein therapeutics, including antibodies. Through protein engineering, several Clostridium difficile toxin A-specific heavy chain antibody variable domains (VHHs) were expressed with an additional disulfide bond by introducing Ala/Gly54Cys and Ile78Cys mutations. Mutant antibodies were compared to their wild-type counterparts with respect to expression yield, non-aggregation status, affinity for toxin A, circular dichroism (CD) structural signatures, thermal stability, protease resistance, and toxin A-neutralizing capacity. The mutant VHHs were found to be well expressed, although with lower yields compared to wild-type counterparts, were non-aggregating monomers, retained low nM affinity for toxin A, albeit the majority showed somewhat reduced affinity compared to wild-type counterparts, and were capable of in vitro toxin A neutralization in cell-based assays. Far-UV and near-UV CD spectroscopy consistently showed shifts in peak intensity and selective peak minima for wild-type and mutant VHH pairs; however, the overall CD profile remained very similar. A significant increase in the thermal unfolding midpoint temperature was observed for all mutants at both neutral and acidic pH. Digestion of the VHHs with the major gastrointestinal proteases, at biologically relevant concentrations, revealed a significant increase in pepsin resistance for all mutants and an increase in chymotrypsin resistance for the majority of mutants. Mutant VHH trypsin resistance was similar to that of wild-type VHHs, although the trypsin resistance of one VHH mutant was significantly reduced. Therefore, the introduction of a second disulfide bond in the hydrophobic core not only increases VHH thermal stability at neutral pH, as previously shown, but also represents a generic strategy to increase VHH stability at low pH and impart protease resistance, with only minor perturbations in target binding affinities. These are all desirable characteristics for the design of protein-based oral therapeutics

More important than guns or grog: The role of television for the health and wellbeing of Australian Aboriginal prisoners

Published online: 30 Nov 2018This article examines the provision of television in the South Australian prison system and its importance to the identity, health, wellbeing and ontological security of Aboriginal prisoners. Existing research has explored the use of broadcast and print media by prisoners in the United Kingdom, United States and Europe and has established that television has an impact on incarcerated audiences far beyond its role as an ‘electronic babysitter’ or a means of filling time. It is also recognised that television plays a significant role in the lives of Aboriginal people (Michaels 1986). However, little is known about television in relation to incarcerated Aboriginal and Torres Strait Islander Australians. This article draws on data concerning in-cell television (‘TV’) among Aboriginal men in prison,1 which found that, when asked to identify the most important factors in the prison environment, 87 per cent of participants identified access to in-cell television as the single most important factor contributing to their congruency with prison accommodation. The article further indicates that access to in-cell television has the potential to reduce incidents of suicide and self-harm and should be adopted as a ‘best-practice’ principle for Aboriginal prisoners in Australian correctional environments.Elizabeth Grant and Yvonne Jewkeshttp://heinonline.org/HOL/Index?index=journals/cicj&collection=journal