Miniaturization of Chemical Analysis Tools: Micro-Solid Phase Extraction Tips for Protein Extractions and Development of a Miniaturized Glow Discharge Source for Elemental Analysis

An increased interest has been placed on the miniaturization of chemical processes. Focus is placed on rapid chemical analysis, decreased operation cost, minimal generation of chemical waste, and reduced sample size. Presented here is an approached the goal of \u27miniaturization\u27 through two distinct areas of analytical chemistry: 1) employing capillary-channeled polymer (C-CP) fibers as a stationary phase in micro-SPE (solid phase extraction) tips for the extraction of proteins from buffered solutions (i.e. biofluids) with analysis by mass spectrometry (MS) and 2) the development of the liquid sampling-atmospheric pressure glow discharge (LS-APGD) as an excitation source for elemental analysis. Determination of proteins in biological matrices is vital for the identification of disease-specific biomarkers. With this in mind, research efforts have grown tremendously for protein analysis in biofluids. More importantly, research has focused on development of extraction/separation techniques necessary for performance on miniaturized levels (i.e. low volume aliquots/concentrations) prior to analysis with mass spectrometry (MS). MS is commonly used for detection due to its sensitivity and the abundant chemical information it provides on analysis. However, buffered species (i.e. salts and biofluids) can be detrimental to MS analysis due to mechanisms such as co-ionization. Presented here, is the use of C-CP fibers as a stationary phase for the extraction of proteins from these matrices. These C-CP mirco-SPE tips have shown to be effective for extraction of nanogram quantities of proteins from buffered species. More importantly, extractions have been optimized to be performed with samples sizes of ~1 µL compared to commercially available tips which require up to 100 µL of sample. Investigations of fiber packing density, tip length, loading capacities, and load/elution volumes were performed to improve the efficiency of C-CP tips for the extraction of proteins. After optimization, C-CP tips were utilized for extracting nanogram quantities of proteins (\u3c5 \u3eµL aliquots) from urine matrices. Additionally, there is a need to design spectrochemical instruments with lower power consumption, reduced sample sizes, compact footprint, and the ability to be operated under ambient conditions. In this dissertation the liquid sampling-atmospheric pressure glow discharge (LS-APGD) is employed as a miniaturized approach towards elemental analysis focusing on the determination of plasma characteristics (i.e. plasma temperatures) under parametric evaluations for elemental analysis of solutions and the use of the LS-APGD source as a secondary excitation/ionization source following laser ablation of solid materials. Excitation, rotation, and ionization temperatures along with electron number density and robustness characteristics of the LS-APGD were studied under parametric evaluation. It was determined that the LS-APGD show great promise in terms of handling complex samples (liquid and laser ablated particles) without presenting matrix effects. Both directions demonstrate promising results with regards to miniaturization of chemical analysis techniques in hopes of developing rapid procedures that require small quantities of sample while operating at low costs and producing little to zero chemical waste

Principals\u27 early career instructional leadership experiences in rural schools

I reported on findings from a phenomenological study intended to investigate the leadership experiences of 12 novice, rural public school principals in a Midwestern state. I utilized data from semi-structured interviews to analyze how novice, rural principals engaged in instructional leadership activities in a rural setting. I also focused on how new principals managed the challenges of leadership as they transitioned into their new positions in a rural setting. Framed by sensemaking, I situated the analysis within existing research on instructional leadership, particularly the context of principals’ work and how they thought about and prioritized instructional leadership goals. My findings indicated that novice, rural principals wear multiple hats while juggling all that expected of a building principal. Although the principals spoke eloquently about their understanding of their role as an instructional leader, their day-to-day experiences are met with demands and expectations peripheral to instructional leadership. Keywords: Instructional leadership, novice principals, rural school, principal development

Monitoring/Verification using DMS: TATP Example

Field-rugged and field-programmable differential mobility spectrometry (DMS) networks provide highly selective, universal monitoring of vapors and aerosols at detectable levels from persons or areas involved with illicit chemical/biological/explosives (CBE) production. CBE sensor motes used in conjunction with automated fast gas chromatography with DMS detection (GC/DMS) verification instrumentation integrated into situational operations-management systems can be readily deployed and optimized for changing application scenarios. The feasibility of developing selective DMS motes for a “smart dust” sampling approach with guided, highly selective, fast GC/DMS verification analysis is a compelling approach to minimize or prevent the illegal use of explosives or chemical and biological materials. DMS is currently one of the foremost emerging technologies for field separation and detection of gas-phase chemical species. This is due to trace-level detection limits, high selectivity, and small size. Fast GC is the leading field analytical method for gas phase separation of chemical species in complex mixtures. Low-thermal-mass GC columns have led to compact, low-power field systems capable of complete analyses in 15–300 seconds. A collaborative effort optimized a handheld, fast GC/DMS, equipped with a non-rad ionization source, for peroxide-based explosive measurements

Chemical, Biological, and Explosive Sensors for Field Measurements

Special Technologies Laboratory (STL) is developing handheld chemical, biological, and explosive (CBE) detection systems and sensor motes for wireless networked field operations. The CBE sensors are capable of detecting and identifying multiple targeted toxic industrial chemicals (TICs) and high-explosive vapor components. The CBE devices are based on differential mobility spectrometry (DMS) coupled with fast gas chromatography (GC) or mass spectrometry. The systems all include the concepts of: 1. Direct air/particulate “smart” sampling 2. Selective, continuous real-time (~1 sec) alert monitoring using DMS 3. Highly selective, rapid dual technology separation/verification analysis The biosensor technology is based on Raman aerosol particle flow cytometry for target detection and identification. Monitoring and identifying trace level chemical vapors directly from ambient air will allow First Responders to quickly adapt situational response strategies and personal protective equipment needs to the specific response scenario being encountered. First Responders require great confidence in the measurements and ability of a given system to detect CBE below threshold levels without interferences. The concept of determining the background matrix in near real-time to allow subsequent automated field-programmable method selection and cueing of high-value assets in a wide range of environs will be presented. This provides CBE information for decisions prior to First Responders entering the response site or sending a portable mobile unit for a remote site survey of the hazards. The focus is on real-time information needed by those responsible for emergency response and national security

Modulating effect of COMT genotype on the brain regions underlying proactive control process during inhibition

peer reviewedIntroduction. Genetic variability related to the catechol-O-methyltransferase (COMT) gene (Val158Met polymorphism) has received increasing attention as a possible modulator of cognitive control functions. Methods. In an event-related fMRI study, a modified version of the Stroop task was administered to three groups of 15 young adults according to their COMT Val158Met genotype [Val/Val (VV), Val/Met (VM) and Met/Met (MM)]. Based on the theory of dual mechanisms of control (Braver, et al., 2007), the Stroop task has been built to induce proactive or reactive control processes according to the task context. Results. Behavioral results did not show any significant group differences for reaction times but Val allele carriers individuals are less accurate in the processing of incongruent items. fMRI results revealed that proactive control is specifically associated with increased activity in the anterior cingulate cortex (ACC) in carriers of the Met allele, while increased activity is observed in the middle frontal gyrus (MFG) in carriers of the Val allele. Conclusion. These observations, in keeping with a higher cortical dopamine level in MM individuals, support the hypothesis of a COMT Val158Met genotype modulation of the brain regions underlying proactive control, especially in frontal areas as suggested by Braver et al

Longitudinal change in executive function is associated with impaired top-down frontolimbic regulation during reappraisal in older adults

Networks in the prefrontal cortex (PFC) that are important for executive function are also engaged in adaptive responding to negative events. These networks are particularly vulnerable to age-related structural atrophy and an associated loss of executive function, yet existing evidence suggests preserved emotion processing ability in ageing. Using longitudinally acquired data from a battery of cognitive tasks, we defined a metric for the rate of decline of executive function. With this metric, we investigated relationships between changes in executive function and emotion reappraisal ability and brain structure, in 34 older adults, using functional and structural MRI. During task-based fMRI, participants were asked to cognitively reappraise negatively valenced images. We hypothesised one of two associations with decreasing executive function over time: 1) a decreased ability to reappraise reflected in decreased PFC and increased amygdala activation, or 2) a neural compensation mechanism characterised by increased PFC activation but no differential amygdala activation. Structurally, for a decreased reappraisal ability, we predicted a decrease in grey matter in PFC and/or a decrease of white matter integrity in amygdala-PFC pathways. Neither of the two hypotheses relating to brain function were completely supported, with the findings indicating a steeper decline in executive function associated with both increased PFC and increased left amygdala activity when reappraising negative stimuli. In addition, white matter integrity of the uncinate fasciculus, a primary white matter tract connecting the amygdala and ventromedial areas of PFC, was lower in those individuals who demonstrated a greater decrease in executive function. These findings highlight the association of diminishing cognitive ability with brain structure and function linked to emotion regulation

In vivo imaging of synaptic loss in Alzheimer’s disease with [18F]UCB-H Positron Emission Tomography

IUAP - Interuniversity Attraction Poles Programme (IUAP 7/11); ARC - Actions de recherche concertées (ARC 12/17-01); Special Research Funds classical grant 2016 (Faculty of Medicine, University of Liege, Belgium), FRS-FNR

Ion mobility spectrometry-mass spectrometry (IMS-MS) of small molecules: separating and assigning structures to ions

The phenomenon of ion mobility (IM), the movement/transport of charged particles under the influence of an electric field, was first observed in the early 20th Century and harnessed later in ion mobility spectrometry (IMS). There have been rapid advances in instrumental design, experimental methods, and theory together with contributions from computational chemistry and gas-phase ion chemistry, which have diversified the range of potential applications of contemporary IMS techniques. Whilst IMS-mass spectrometry (IMS-MS) has recently been recognized for having significant research/applied industrial potential and encompasses multi-/cross-disciplinary areas of science, the applications and impact from decades of research are only now beginning to be utilized for "small molecule" species. This review focuses on the application of IMS-MS to "small molecule" species typically used in drug discovery (100-500 Da) including an assessment of the limitations and possibilities of the technique. Potential future developments in instrumental design, experimental methods, and applications are addressed. The typical application of IMS-MS in relation to small molecules has been to separate species in fairly uniform molecular classes such as mixture analysis, including metabolites. Separation of similar species has historically been challenging using IMS as the resolving power, R, has been low (3-100) and the differences in collision cross-sections that could be measured have been relatively small, so instrument and method development has often focused on increasing resolving power. However, IMS-MS has a range of other potential applications that are examined in this review where it displays unique advantages, including: determination of small molecule structure from drift time, "small molecule" separation in achiral and chiral mixtures, improvement in selectivity, identification of carbohydrate isomers, metabonomics, and for understanding the size and shape of small molecules. This review provides a broad but selective overview of current literature, concentrating on IMS-MS, not solely IMS, and small molecule applications. © 2012 Wiley Periodicals, Inc

Impairments in Episodic-Autobiographical Memory and Emotional and Social Information Processing in CADASIL during Mid-Adulthood

Staniloiu A, Woermann FG, Markowitsch HJ. Impairments in Episodic-Autobiographical Memory and Emotional and Social Information Processing in CADASIL during Mid-Adulthood. Frontiers in Behavioral Neuroscience. 2014;8: 227.Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) – is the most common genetic source of vascular dementia in adults, being caused by a mutation in NOTCH3 gene. Spontaneous de novo mutations may occur, but their frequency is largely unknown. Ischemic strokes and cognitive impairments are the most frequent manifestations, but seizures affect up to 10% of the patients. Herein, we describe a 47-year-old male scholar with a genetically confirmed diagnosis of CADASIL (Arg133Cys mutation in the NOTCH3 gene) and a seemingly negative family history of CADASIL illness, who was investigated with a comprehensive neuropsychological testing battery and neuroimaging methods. The patient demonstrated on one hand severe and accelerated deteriorations in multiple cognitive domains such as concentration, long-term memory (including the episodic-autobiographical memory domain), problem solving, cognitive flexibility and planning, affect recognition, discrimination and matching, and social cognition (theory of mind). Some of these impairments were even captured by abbreviated instruments for investigating suspicion of dementia. On the other hand the patient still possessed high crystallized (verbal) intelligence and a capacity to put forth a façade of well-preserved intellectual functioning. Although no definite conclusions can be drawn from a single case study, our findings point to the presence of additional cognitive changes in CADASIL in middle adulthood, in particular to impairments in the episodic-autobiographical memory domain and social information processing (e.g., social cognition). Whether these identified impairments are related to the patient’s specific phenotype or to an ascertainment bias (e.g., a paucity of studies investigating these cognitive functions) requires elucidation by larger scale research