Development of microcomputer-based mental acuity tests for repeated-measures studies

The purpose of this report is to detail the development of the Automated Performance Test System (APTS), a computer battery of mental acuity tests that can be used to assess human performance in the presence of toxic elements and environmental stressors. There were four objectives in the development of APTS. First, the technical requirements for developing APTS followed the tenets of the classical theory of mental tests which requires that tests meet set criteria like stability and reliability (the lack of which constitutes insensitivity). To be employed in the study of the exotic conditions of protracted space flight, a battery with multiple parallel forms is required. The second criteria was for the battery to have factorial multidimensionality and the third was for the battery to be sensitive to factors known to compromise performance. A fourth objective was for the tests to converge on the abilities entailed in mission specialist tasks. A series of studies is reported in which candidate APTS tests were subjected to an examination of their psychometric properties for repeated-measures testing. From this work, tests were selected that possessed the requisite metric properties of stability, reliability, and factor richness. In addition, studies are reported which demonstrate the predictive validity of the tests to holistic measures of intelligence

Characterizing Morphology and Nonlinear Elastic Properties of Normal and Thermally Stressed Engineered Oral Mucosal Tissues Using Scanning Acoustic Microscopy

This study examines the use of high-resolution ultrasound to monitor changes in the morphology and nonlinear elastic properties of engineered oral mucosal tissues under normal and thermally stressed culture conditions. Nonlinear elastic properties were determined by first developing strain maps from acoustic ultrasound, followed by fitting of nonlinear stress?strain data to a 1-term Ogden model. Testing examined a clinically developed ex vivo produced oral mucosa equivalent (EVPOME). As seeded cells proliferate on an EVPOME surface, they produce a keratinized protective upper layer that fills in and smoothens out surface irregularities. These transformations can also alter the nonlinear stress/strain parameters as EVPOME cells differentiate. This EVPOME behavior is similar to those of natural oral mucosal tissues and in contrast to an unseeded scaffold. If ultrasonic monitoring could be developed, then tissue cultivation could be adjusted in-process to account for biological variations in their development of the stratified cellular layer. In addition to ultrasonic testing, an in-house-built compression system capable of accurate measurements on small (?1.0?1.5?cm2) tissue samples is presented. Results showed a near 2.5-fold difference in the stiffness properties between the unstressed EVPOME and the noncell-seeded acellular scaffold (AlloDerm?). There were also 4?greater differences in root mean square values of the thickness in the unseeded AlloDerm compared to the mature unstressed EVPOME; this is a strong indicator for quantifying surface roughness.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140241/1/ten.tec.2012.0467.pd

Characterization of a Reverse-Phase Perfluorocarbon Emulsion for the Pulmonary Delivery of Tobramycin

Background: Aerosolized delivery of antibiotics is hindered by poor penetration within distal and plugged airways. Antibacterial perfluorocarbon ventilation (APV) is a proposed solution in which the lungs are partially or totally filled with perfluorocarbon (PFC) containing emulsified antibiotics. The purpose of this study was to evaluate emulsion stability and rheological, antibacterial, and pharmacokinetic characteristics. Methods: This study examined emulsion aqueous droplet diameter and number density over 24?hr and emulsion and neat PFC viscosity and surface tension. Additionally, Pseudomonas aeruginosa biofilm growth was measured after 2-hr exposure to emulsion with variable aqueous volume percentages (0.25, 1, and 2.5%) and aqueous tobramycin concentrations (Ca=0.4, 4, and 40?mg/mL). Lastly, the time course of serum and pulmonary tobramycin concentrations was evaluated following APV and conventional aerosolized delivery of tobramycin in rats. Results: The initial aqueous droplet diameter averaged 1.9±0.2??m with little change over time. Initial aqueous droplet number density averaged 3.5±1.7?109 droplets/mL with a significant (p<0.01) decrease over time. Emulsion and PFC viscosity were not significantly different, averaging 1.22±0.03?10?3 Pa·sec. The surface tensions of PFC and emulsion were 15.0±0.1?10?3 and 14.6±0.6?10?3 N/m, respectively, and the aqueous interfacial tensions were 46.7±0.3?10?3 and 26.9±11.0?10?3 N/m (p<0.01), respectively. Biofilm growth decreased markedly with increasing Ca and, to a lesser extent, aqueous volume percentage. Tobramycin delivered via APV yielded 2.5 and 10 times larger pulmonary concentrations at 1 and 4?hr post delivery, respectively, and significantly (p<0.05) lower serum concentrations compared with aerosolized delivery. Conclusions: The emulsion is bactericidal, retains the rheology necessary for pulmonary delivery, is sufficiently stable for this application, and results in increased pulmonary retention of the antibiotic.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140105/1/jamp.2013.1058.pd

Icing: Large-scale inference of immunoglobulin clonotypes

Immunoglobulin (IG) clonotype identification is a fundamental open question in modern immunology. An accurate description of the IG repertoire is crucial to understand the variety within the immune system of an individual, potentially shedding light on the pathogenetic process. Intrinsic IG heterogeneity makes clonotype inference an extremely challenging task, both from a computational and a biological point of view. Here we present icing, a framework that allows to reconstruct clonal families also in case of highly mutated sequences. icing has a modular structure, and it is designed to be used with large next generation sequencing (NGS) datasets, a technology which allows the characterisation of large-scale IG repertoires. We extensively validated the framework with clustering performance metrics on the results in a simulated case. icing is implemented in Python, and it is publicly available under FreeBSD licence at https://github.com/slipguru/icing

Effect of a Gel Retainment Dam on Automated Ultrasound Coverage in a Dual‐Modality Breast Imaging System

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135299/1/jum20102971075.pd

Pulse-Echo Quantitative US Biomarkers for Liver Steatosis: Toward Technical Standardization

Excessive liver fat (steatosis) is now the most common cause of chronic liver disease worldwide and is an independent risk factor for cirrhosis and associated complications. Accurate and clinically useful diagnosis, risk stratification, prognostication, and therapy monitoring require accurate and reliable biomarker measurement at acceptable cost. This article describes a joint effort by the American Institute of Ultrasound in Medicine (AIUM) and the RSNA Quantitative Imaging Biomarkers Alliance (QIBA) to develop standards for clinical and technical validation of quantitative biomarkers for liver steatosis. The AIUM Liver Fat Quantification Task Force provides clinical guidance, while the RSNA QIBA Pulse-Echo Quantitative Ultrasound Biomarker Committee develops methods to measure biomarkers and reduce biomarker variability. In this article, the authors present the clinical need for quantitative imaging biomarkers of liver steatosis, review the current state of various imaging modalities, and describe the technical state of the art for three key liver steatosis pulse-echo quantitative US biomarkers: attenuation coefficient, backscatter coefficient, and speed of sound. Lastly, a perspective on current challenges and recommendations for clinical translation for each biomarker is offered

Alu insertion loci and platyrrhine primate phylogeny

Short INterspersed Elements (SINEs) make very useful phylogenetic markers because the integration of a particular element at a location in the genome is irreversible and of known polarity. These attributes make analysis of SINEs as phylogenetic characters an essentially homoplasy-free affair. Alu elements are primate-specific SINEs that make up a large portion of the human genome and are also widespread in other primates. Using a combination wet-bench and computational approach we recovered 190 Alu insertions, 183 of which are specific to the genomes of nine New World primates. We used these loci to investigate branching order and have produced a cladogram that supports a sister relationship between Atelidae (spider, woolly, and howler monkeys) and Cebidae (marmosets, tamarins, and owl monkeys) and then the joining of this two family clade to Pitheciidae (titi and saki monkeys). The data support these relationships with a homoplasy index of 0.00. In this study, we report one of the largest applications of SINE elements to phylogenetic analysis to date, and the results provide a robust molecular phylogeny for platyrrhine primates. © 2004 Elsevier Inc. All rights reserved

Distinct ligand preferences of Src homology 3 domains from Src, Yes, Abl, Cortactin, p53bp2, PLCgamma, Crk, and Grb2.

Src homology 3 (SH3) domains are conserved protein modules 50-70 amino acids long found in a variety of proteins with important roles in signal transduction. These domains have been shown to mediate protein-protein interactions by binding short proline-rich regions in ligand proteins. However, the ligand preferences of most SH3 domains and the role of these preferences in regulating SH3-mediated protein-protein interactions remain poorly defined. We have used a phage-displayed library of peptides of the form X6PXXPX6 to identify ligands for eight different SH3 domains. Using this approach, we have determined that each SH3 domain prefers peptide ligands with distinct sequence characteristics. Specifically, we have found that the Src SH3 domain selects peptides sharing the consensus motif LXXRPLPXpsiP, whereas Yes SH3 selects psiXXRPLPXLP, Abl SH3 selects PPXthetaXPPPpsiP, Cortactin SH3 selects +PPpsiPXKPXWL, p53bp2 SH3 selects RPXpsiPpsiR+SXP, PLCgamma SH3 selects PPVPPRPXXTL, Crk N-terminal SH3 selects psiPpsiLPpsiK, and Grb2 N-terminal SH3 selects +thetaDXPLPXLP (where psi, theta, and + represent aliphatic, aromatic, and basic residues, respectively). Furthermore, we have compared the binding of phage expressing peptides related to each consensus motif to a panel of 12 SH3 domains. Results from these experiments support the ligand preferences identified in the peptide library screen and evince the ability of SH3 domains to discern subtle differences in the primary structure of potential ligands. Finally, we have found that most known SH3-binding proteins contain proline-rich regions conforming to the ligand preferences of their respective SH3 targets