Developing an Antibody–Drug Conjugate Approach to Selective Inhibition of an Extracellular Protein

Antibody–drug conjugates (ADCs) are a growing class of therapeutics that harness the specificity of antibodies and the cell-killing potency of small-molecule drugs. Beyond cytotoxics, there are few examples of the application of an ADC approach to difficult drug discovery targets. Here, we present the initial development of a non-internalising ADC, with a view to selectively inhibiting an extracellular protein. Employing the wellinvestigated matrix metalloproteinase-9 (MMP-9) as our model, we adapted a broad-spectrum, nonselective MMP inhibitor for conjugation and linked this to a MMP-9-targeting antibody. The resulting ADC fully inhibits MMP-9, and ELISA results suggest antibody targeting can direct a nonselective inhibitor.     

Simulations of amphiphilic fluids using mesoscale lattice-Boltzmann and lattice-gas methods

We compare two recently developed mesoscale models of binary immiscible and ternary amphiphilic fluids. We describe and compare the algorithms in detail and discuss their stability properties. The simulation results for the cases of self-assembly of ternary droplet phases and binary water-amphiphile sponge phases are compared and discussed. Both models require parallel implementation and deployment on large scale parallel computing resources in order to achieve reasonable simulation times for three-dimensional models. The parallelization strategies and performance on two distinct parallel architectures are compared and discussed. Large scale three-dimensional simulation of multiphase fluids requires the extensive use of high performance visualization techniques in order to enable the large quantities of complex data to be interpreted. We report on our experiences with two commercial visualization products: AVS and VTK. We also discuss the application and use of novel computational steering techniques for the more efficient utilization of high performance computing resources. We close the paper with some suggestions for the future development of both models.     

Oscillatory Metastability in Optical Network Synchronizer Circuits

Synchronization of signal packets is required in networks in order to route the packets. Due to changes in the interarrival times of the packets the inputs to the routing circuits may exhibit oscillatory metastability. Oscillatory metastability can be eliminated in optical circuits by the addition of logic signal stretch. This can be done because the propagation time of optics can be precisely controlled. An algorithm for inserting logic signal stretch to eliminate oscillatory metastability is presented herein.     

An investigation of early research experience and research self-efficacy.

Graduate students in psychology typically report that they either love research or hate research. Despite the fact that most doctoral students in psychology enter some type of clinical practice upon graduation, research is a requirement for all students enrolled in scientist-practitioner programs regardless of their career aspirations beyond graduation. Research advances knowledge in the field of psychology and often guides clinical practice, yet very few psychologists conduct research after graduate school (C. J. Gelso, 1993). Efforts have been undertaken to determine factors that contribute to graduate students' research productivity. One such factor may be research self-efficacy. This study examined the influence of early research experience as a factor to bolster research self-efficacy. Results indicated that supportive peers and mentors contributed to positive research experiences. Additionally, positive team research experiences significantly predicted research self-efficacy. Implications for training programs and students are provided. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Announcement

Announcement

Announcement     

AH-64D main transmission accessory drive spur gear installation fault detections

The US Army has launched an aggressive program to implement condition based maintenance on its rotary wing assets. Condition Based Maintenance takes advantage of technology developments in the areas of machinery monitoring, signal processing and fault modeling to reduce the cost of ownership through improved maintenance procedures. Documenting the reduction in maintenance burden, cost savings and increased safety through early detection of helicopter faults is an important step in justifying the program. This paper describes a novel technique used to detect a serious fault in the accessory section of the AH-64D Apache main transmission. The technique determines if the primary or secondary clutch system is driving the aircraft accessories through a tachometer speed ratio. The method has identified three aircraft operating on the secondary system allowing Army maintenance crews to replace the affected transmissions and quickly restore the aircraft to operational status.     

Developing a frame of reference for <Emphasis Type="Italic">ex-ante</Emphasis> IT/IS investment evaluation

Investment appraisal techniques are an integral part of many traditional capital budgeting processes. However, the adoption of Information Systems (IS) and the development of resulting infrastructures are being increasingly viewed on the basis of consumption. Consequently, decision-makers are now moving away from the confines of rigid capital budgeting processes, which have traditionally compared IS with non-IS-related investments. With this in mind, the authors seek to dissect investment appraisal from the broader capital budgeting process to allow a deeper understanding of the mechanics involved with IS justification. This analysis presents conflicting perspectives surrounding the scope and sensitivity of traditional appraisal methods. In contributing to this debate, the authors present taxonomies of IS benefit types and associated natures, and discuss the resulting implications of using traditional appraisal techniques during the IS planning and decision-making process. A frame of reference that can be used to navigate through the variety of appraisal methods available to decision-makers is presented and discussed. Taxonomies of appraisal techniques that are classified by their respective characteristics are also presented. Perspectives surrounding the degree of involvement that financial appraisal should play during decision making and the limitations surrounding investment appraisal techniques are identified.     

Memory loss resulting from fornix and septal damage: Impaired supra-span recall but preserved recognition over a 24-hour delay.

Despite increasing evidence that the fornix is important for memory, uncertainty remains about the exact nature of subsequent impairments arising from damage to this tract. This uncertainty is often created by pathology in additional brain structures. The present study involved a young man, DN, who had almost complete bilateral loss of the rostral columns of the fornix and much of the surrounding septum in the left hemisphere following the surgical removal of a cavernous angioma. Quantitative MRI analyses of structure size, normalized to intracranial volume, showed no difference in any of the additional brain regions measured, apart from those areas removed to expose the tumor. DN showed a marked, stable anterograde memory impairment that was still present 4 years postsurgery. In contrast, DN performed within normal levels on most tests of recognition memory. This sparing was most striking when given a 24-hr delay between study and test of the Warrington Recognition Memory Test. This recall/recognition dissociation provides further evidence for neuroanatomical divisions within recognition memory processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)