On the consequences of bi-Maxwellian plasma distributions for parallel electric fields

The objective is to use the measurements of the equatorial particle distributions to obtain the parallel electric field structure and the evolution of the plasma distribution function along the field line. Appropriate uses of kinetic theory allows us to use the measured ( and inferred) particle distributions to obtain the electric field, and hence the variation on plasma density along the magnetic field line. The approach, here, is to utilize the adiabatic invariants, and assume the plasma distributions are in equilibrium

Epitope mapping using mRNA display and a unidirectional nested deletion library

In vitro selection targeting an anti-polyhistidine monoclonal antibody was performed using mRNA display with a random, unconstrained 27-mer peptide library. After six rounds of selection, epitope-like peptides were identified that contain two to five consecutive, internal histidines and are biased for arginine residues, without any other identifiable consensus. The epitope was further refined by constructing a high-complexity, unidirectional fragment library from the final selection pool. Selection by mRNA display minimized the dominant peptide from the original selection to a 15-residue functional sequence (peptide Cmin: RHDAGDHHHHHGVRQ; K-D = 38 nM). Other peptides recovered from the fragment library selection revealed a separate consensus motif (ARRXA) C-terminal to the histidine track. Kinetics measurements made by surface plasmon resonance, using purified Fab (antigen-binding fragment) to prevent avidity effects, demonstrate that the selected peptides bind with 10- to 75-fold higher affinities than a hexahistidine peptide. The highest affinity peptides (K-D approximate to 10 nM) encode both a short histidine track and the ARRXA motif, suggesting that the motif and other flanking residues make important contacts adjacent to the core polyhistidine-binding site and can contribute > 2.5 kcal/mol of binding free energy. The fragment library construction methodology described here is applicable to the development of high-complexity protein or cDNA expression libraries for the identification of protein-protein interaction domains

Single-particle levitation system for automated study of homogeneous solute nucleation

We present an instrument that addresses two critical requirements for quantitative measurements of the homogeneous crystal nucleation rate in supersaturated aqueous solution. First, the need to perform repeated measurements of nucleation incubation times is met by automating experiments to enable programmable cycling of thermodynamic conditions. Second, the need for precise and robust control of the chemical potential in supersaturated aqueous solution is met by implementing a novel technique for regulating relative humidity. The apparatus levitates and weighs micron-sized samples in an electric field, providing access to highly supersaturated states. We report repeated observations of the crystal nucleation incubation time in a supersaturated aqueous sodium chloride droplet, from which we infer the nucleation rate

Microfluidic Selection of Aptamers towards Applications in Precision Medicine

Precision medicine represents a shift in medicine where large datasets are gathered for massive patient groups to draw correlations between disease cohorts. An individual patient can then be compared to these large datasets to determine the best treatment strategy. While electronic health records and next generation sequencing techniques have enabled much of the early applications for precision medicine, the human genome only represents a fraction of the information present and important to a person’s health. A person’s proteome (peptides and proteins) and glycome (glycans and glycosylation patterns) contain biomarkers that indicate health and disease; however, tools to detect and analyze such biomarkers remain scarce. Thus, precision medicine databases are lacking a major source of phenotypic data due to the absence of available methods to explore these domains, despite the potential of such data to allow further stratification of patients and individualized therapeutic strategies. Available methods to detect non-nucleic acid biomarkers are currently not well suited to address the needs of precision medicine. Mass spectrometry techniques, while capable of generating high throughput data, lack standardization, require extensive preparative steps, and have many sources of errors. Immunoassays rely on antibodies which are time consuming and expensive to produce for newly discovered biomarkers. Aptamers, analogous to antibodies but composed of nucleotides and isolated through in vitro methods, have potential to identify non-nucleic acid biomarkers but methods to isolate aptamers remain labor and resource intensive and time consuming. Recently, microfluidic technology has been applied to the aptamer discovery process to reduce the aptamer development time, while consuming smaller amounts of reagents. Methods have been demonstrated that employ capillary electrophoresis, magnetic mixers, and integrated functional chambers to select aptamers. However, these methods are not yet able to fully integrate the entire aptamer discovery process on a single chip and must rely on off-chip processes to identify aptamers. In this thesis, new approaches for aptamer selection are developed that aim to integrate the entire process for aptamer discovery on a single chip. These approaches are capable of performing efficient aptamer selection and polymerase chain reaction based amplification while utilizing highly efficient bead-based reactions. The approaches use pressure driven flow, electrokinetic flow or a combination of both to transfer aptamer candidates through multiple rounds of affinity selection and PCR amplification within a single microfluidic device. As such, the approaches are capable of isolating aptamer candidates within a day while consuming <500 µg of a target molecule. The utility of the aptamer discovery approach is then demonstrated with examples in precision medicine over a broad spectrum (small molecule to protein) of molecular targets. Seeking to demonstrate the potential of the device to generate probes capable of accessing the human glycome (an emerging source of precision medicine biomarkers), aptamers are isolated against gangliosides GM1, GM3, and GD3, and a glycosylated peptide. Finally, personalized, patient specific aptamers are isolated against a multiple myeloma patient serum sample. The aptamers have high affinity only for the patient derived antibody

The Value of Knowing: Public Lands Monitoring by Non-Agency Groups

It is generally recognized that in order to make informed federal land management decisions, such decisions need to be based on information gathered from monitoring of those lands. While some monitoring is being conducted by federal land management agencies, it is happening too infrequently and is often inadequate for properly informing land management decisions. In an attempt to fill this gap non-agency groups have begun monitoring federal public lands themselves. It appears that through recent congressional authorizations, policy reforms, and agency initiatives monitoring by non-agency groups is being supported at every government level. While theoretically this transfer of responsibility from the federal agencies to non-agency groups looks good on paper in reality there are considerable barriers. This has many groups gathering data that ends up never being used in the decision making process. Despite this barrier, however, non-agency groups continue to monitor while the topic itself garners increased attention. As it stands, our understanding of how non-agency monitoring can affect land management decision making is seen as fairly black and white; data from monitoring is either used by the agency to make decisions or it is not. This study suggests that such a view of monitoring by non-agency groups is too narrow. The values associated with monitoring on federal public lands can be seen as having an internal or external benefit. Internal benefits, such as engaging youth or leveraging funding, are those that primarily only affect the monitoring group. External benefits, such as filling in gaps of agency monitoring or informing adaptive management within the agency, are those that may lead to either directly or indirectly influencing land management decision making. Ultimately, directly influencing federal land management decision making is difficult and may be out of reach for many non-agency groups. However those benefits that affect the group itself may be easier to achieve and could act as a starting point for groups wanting to start monitoring. Over time external benefits can be realized such as building relationships with agency staff, building public support, or informing NEPA reports that can lead to indirectly influencing federal land management decision making. Furthermore, there are differences between how single-interest groups and multi-interest groups value monitoring. Combined, these insights can assist groups in focusing their monitoring goals in order to increase the longevity and success of monitoring activity

Homotaurine, a safe blood-brain barrier permeable GABAA-R-specific agonist, ameliorates disease in mouse models of multiple sclerosis.

There is a need for treatments that can safely promote regulatory lymphocyte responses. T cells express GABA receptors (GABAA-Rs) and GABA administration can inhibit Th1-mediated processes such as type 1 diabetes and rheumatoid arthritis in mouse models. Whether GABAA-R agonists can also inhibit Th17-driven processes such as experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), is an open question. GABA does not pass through the blood-brain barrier (BBB) making it ill-suited to inhibit the spreading of autoreactivity within the CNS. Homotaurine is a BBB-permeable amino acid that antagonizes amyloid fibril formation and was found to be safe but ineffective in long-term Alzheimer's disease clinical trials. Homotaurine also acts as GABAA-R agonist with better pharmacokinetics than that of GABA. Working with both monophasic and relapsing-remitting mouse models of EAE, we show that oral administration of homotaurine can (1) enhance CD8+CD122+PD-1+ and CD4+Foxp3+ Treg, but not Breg, responses, (2) inhibit autoreactive Th17 and Th1 responses, and (3) effectively ameliorate ongoing disease. These observations demonstrate the potential of BBB-permeable GABAA-R agonists as a new class of treatment to enhance CD8+ and CD4+ Treg responses and limit Th17 and Th1-medaited inflammation in the CNS

Learning Styles as Predictors of Problem-Based Learning Success in the Information Systems Classroom

Problem-Based Learning (PBL) is increasingly used as a mode of instruction to more fully engage students, while at the same time promote self-learning and retention. For many students, PBL is a welcome change from traditional professorial lecture approach. In practice, however, some students do not thrive in this less structured environment. We utilize theories of learning styles to shed light on this apparent tension. This paper develops an approach to arrive at a predictive model of how learning styles determine student acceptance of problem-based learning. First, a chronological view of PBL and the learning style literature is provided. This is followed by a discussion of the research constructs, methodology, and survey instruments to be used to predict the efficacy of PBL techniques, based on learning styles. We use Felder and Solomon’s (1996) freely available and widely validated instrument to assess student learning styles, and develop this predictive model through data analysis using Principle Least Squares (PLS). This model will be used to form specific hypotheses which can be tested further. A discussion of how the results from this study may aid professors, and thus benefit students, is then presented

Understanding Events, Critical Incidents, and Punctuation in Process Theories

Paradigmatic diversity in information systems research has increased as process theorizing from case studies has become increasingly popular. Central to process theorizing is the identification of events, or critical incidents that mark the evolution of a process over time. In this paper, we present a way of understanding events while building on process models which have been described in the IS literature. Specifically, we outline the interplay between punctuations, critical incidents, and incremental adaptations using a visual mapping strategy. We argue that a more precise understanding of these elements will strengthen the rigor and adoption of process research methods