Development and clinical performance of high throughput loop-mediated isothermal amplification for detection of malaria.

BACKGROUND: Accurate and efficient detection of sub-microscopic malaria infections is crucial for enabling rapid treatment and interruption of transmission. Commercially available malaria LAMP kits have excellent diagnostic performance, though throughput is limited by the need to prepare samples individually. Here, we evaluate the clinical performance of a newly developed high throughput (HTP) sample processing system for use in conjunction with the Eiken malaria LAMP kit. METHODS: The HTP system utilised dried blood spots (DBS) and liquid whole blood (WB), with parallel sample processing of 94 samples per run. The system was evaluated using 699 samples of known infection status pre-determined by gold standard nested PCR. RESULTS: The sensitivity and specificity of WB-HTP-LAMP was 98.6% (95% CI, 95.7-100), and 99.7% (95% CI, 99.2-100); sensitivity of DBS-HTP-LAMP was 97.1% (95% CI, 93.1-100), and specificity 100% against PCR. At parasite densities greater or equal to 2 parasites/μL, WB and DBS HTP-LAMP showed 100% sensitivity and specificity against PCR. At densities less than 2 p/μL, WB-HTP-LAMP sensitivity was 88.9% (95% CI, 77.1-100) and specificity was 99.7% (95% CI, 99.2-100); sensitivity and specificity of DBS-HTP-LAMP was 77.8% (95% CI, 54.3-99.5) and 100% respectively. CONCLUSIONS: The HTP-LAMP system is a highly sensitive diagnostic test, with the potential to allow large scale population screening in malaria elimination campaigns

Pharmacosynthetic modulation of serotonin networks

Dr. Francis Crick described the brain as an exceedingly cunning combination of precision wiring and associative nets (Crick, 1979). While this explanation is over 30 years old, it accurately describes the complexity of the central nervous system modern neuroscientists are challenged with unraveling. The serotonergic network is an example of this intricate design. It originates from a small number of neurons relatively clustered together, but distributes its projections extensively throughout the entire CNS such that virtually every cell in the brain is in close proximity to a serotonin fiber. Advances using small molecules that augment serotonin concentrations such as serotonin selective reuptake inhibitors (SSRIs) have contributed immensely in constructing the frame work of the serotonin network and characterizing its influence on mammalian physiology and behaviors. Even so, these small molecule approaches are limited due to the global impact they have on serotonergic neurotransmission, making the neuronal mechanisms responsible for their effects difficult to discern. One approach to unraveling the complexity of the serotonin network is to dissect the system into its parts by selectively and reversibly controlling specific serotonin nuclei. In fact, Dr. Crick predicted the need for this approach stating that, to understand a complex biological system one must be able to interfere with it both precisely and delicately at all levels, but especially at the cellular and molecular levels (Crick, 1999). The recently developed chemogenetic technique termed Designer receptors exclusively activated by designer drugs (DREADDs) is ideal for selectively stimulating and inhibiting subpopulations of neurons, thereby demonstrating this delicate and precise approach for elucidating neuronal function at the cellular and molecular levels. In this work, we take advantage of this technique to selectively and remotely control the largest of the serotonergic nuclei, the dorsal raphe, and examined its effects on feeding, anxiety and antidepressant-like behaviors and in turn reveal how this nucleus contributes to the wide ranging effects of the serotonergic system.Doctor of Philosoph

New Optical Methods for Characterization of Materials and Biology

Optical methods, including light and fluorescence microscopies, have seen widespreadapplication in the characterization of materials and biology, but are not equally applicable to allsuch systems. This dissertation aims to describe new developments in select optical methods, andtheir subsequent application to answering scientific questions about material and biologicalsystems that were intractable using previous methodologies. We first develop a novel label-freeinterference-based optical method for characterizing thin films on transparent substrates andsubsequently apply it to reveal reaction dynamics of graphene films in real time. We nextdevelop novel methods in a different optical technique, point-localization super-resolutionfluorescence microscopy. These include the application of spectrally-resolved super-resolutionmicroscopy to organic adlayers on surfaces and the development of a remote focusing techniqueto image oblique planes through thick biological samples. We then combine our developments inoptical methods and super-resolution microscopy to describe a novel correlative super-resolutionimaging methodology, and overview the challenges and opportunities inherent to correlativesuper-resolution methods. We conclude with concrete applications of super-resolutionfluorescence microscopy to biological systems and shed light on long-standing biologicalquestions. These include elucidation of the structure of meiotic chromosome axes in C. Elegans,a mechanism for crossover-interference and crossover-regulation in the same meioticchromosomes, discovery of a novel structural arrangement for nuclear pore complexes in meioticcells, and discovery of a tube-shaped structure spanning the nucleus of breast cancer-like cells

Albuquerque Daily Citizen, 08-03-1899

https://digitalrepository.unm.edu/abq_citizen_news/2879/thumbnail.jp

Albuquerque Citizen, 04-18-1908

https://digitalrepository.unm.edu/abq_citizen_news/3739/thumbnail.jp

Inducing Neural Plasticity and Modulation Using Multisensory Stimulation: Techniques for Sensory Disorder Treatment

University of Minnesota Ph.D. dissertation. June 2017. Major: Biomedical Engineering. Advisor: Hubert Lim. 1 computer file (PDF); xvi, 245 pages.In this dissertation, we characterized the modulatory and plasticity effects of paired multisensory stimulation on neural firing in sensory systems across the brain. In the auditory system, we discovered that electrical somatosensory stimulation can either suppress or facilitate neural firing in the inferior colliculus (IC) and primary auditory cortex (A1) depending stimulation location. We also tested plasticity effects in A1 in response to paired somatosensory and acoustic stimulation with different inter-stimulus delays in anesthetized guinea pigs, and found that plasticity induced by paired acoustic and right mastoid stimulation was consistently suppressive regardless of delay, but paired acoustic and pinna stimulation was timing-dependent, where one inter-stimulus delay was consistently suppressive while other delays induced random changes. These experiments were repeated in awake animals with paired acoustic and pinna stimulation, and two animal groups of different stress levels were used to assess stress effects on plasticity. We found that in low-stress animals, the same inter-stimulus delay was consistently suppressive and a neighboring delay was consistently facilitative across all animals, which matches previous invasive spike-timing dependent plasticity studies (anesthesia may have affected these trends). Meanwhile, high-stress animal results were not consistent with expected time dependence and exhibited no trends across inter-stimulus delays, indicating that stress can have adverse effects on neuromodulation plasticity outcomes. In all other primary sensory cortices, we found that differential effects can be induced with paired sensory stimulation such that the location, amount, type, and timing of plasticity can be controlled by strategically choosing sensory stimulation parameters for modulation of each sensory cortex. We also investigated the ability to target subpopulations of neurons within a brain region and found that by stimulating at levels near activation thresholds, specific subpopulations of IC neurons can be targeted by varying somatosensory stimulation location. Furthermore, acoustic stimulation can excite or modulate specific areas of somatosensory cortex, and we mapped the guinea pig homunculus to characterize this. Overall, these findings illustrate the immense interconnectivity between sensory systems, and multisensory stimulation may provide a noninvasive neuromodulation approach for inducing controlled plasticity to disrupt pathogenic neural activity in neural sensory disorders, such as tinnitus and pain

The Evening Herald (Albuquerque, N.M.), 06-29-1917

https://digitalrepository.unm.edu/abq_eh_news/2067/thumbnail.jp

The degradation of glial scar and enhancement of chronic intracortical recording electrode performance through the local delivery of dexamethasone and chondroitinase

The ability of conducting polymers such as poly(3,4-ethylenedioxythiophene) (PEDOT) to store a drug as a dopant and release it following electrical stimulus make them an intriguing coating possibility for intracortical electrodes, along with their ability to reduce electrode impedance. The mechanism allows for the release of an assortment of useful agents, including anti-inflammatory drugs and neuromodulatory chemicals. We evaluated the release capabilities of a multi-walled carbon nanotube (MWCNT)-doped PEDOT coating incorporating the anti-inflammatory steroid dexamethasone in vitro using sputtered-gold macroelectrodes, and then applied the coating to half of the electrodes within 16-shank platinum/iridium floating microelectrode arrays for chronic in vivo evaluation in rat visual cortex. Impedance measurement, neurophysiological recording, and cyclic voltammetric release stimulus (-0.9 V to 0.6 V, 1 V/s, 20 cycles) was performed daily to all channels. On the 11th day, histology was performed to quantitatively characterize inflammatory tissue response using OX42 (microglia) and GFAP (astroglia). Equivalent circuit analysis was performed to assist the interpretation of impedance data. Our results indicated that the MWCNT/PEDOT-coated gold macroelectrodes released double the amount of dexamethasone using passive release followed by CV stimulation (10 sets of 20 cycles) compared to passive release alone. Coatings applied to Pt/Ir microelectrodes reduced 1 kHz impedance in PBS by approximately 38%. Coated probes in vivo exhibited a significant decrease in 1 kHz impedance for the initial three days of implantation followed by an increase, between days 4 and 7, to values equivalent to those exhibited by uncoated probes. Neurophysiological recording performance of coated and uncoated probes remained equivalent for the duration of the experiment, in terms of signal-to-noise ratio and noise amplitude. Histology revealed no significant difference in tissue inflammatory response to coated and uncoated electrodes. Explant imaging revealed the presence of a membranous film enveloping coated electrodes, and equivalent circuit analysis suggested that the day 4-7 increase in 1 kHz impedance of coated electrodes was due to a decrease in effective surface area of the coatings as well as the core electrodes. Additional work was also performed developing a model for the in vivo microinjection of the enzyme Chondroitinase ABC into tissue surrounding implanted microelectrodes

A New framework for an electrophotographic printer model

Digital halftoning is a printing technology that creates the illusion of continuous tone images for printing devices such as electrophotographic printers that can only produce a limited number of tone levels. Digital halftoning works because the human visual system has limited spatial resolution which blurs the printed dots of the halftone image, creating the gray sensation of a continuous tone image. Because the printing process is imperfect it introduces distortions to the halftone image. The quality of the printed image depends, among other factors, on the complex interactions between the halftone image, the printer characteristics, the colorant, and the printing substrate. Printer models are used to assist in the development of new types of halftone algorithms that are designed to withstand the effects of printer distortions. For example, model-based halftone algorithms optimize the halftone image through an iterative process that integrates a printer model within the algorithm. The two main goals of a printer model are to provide accurate estimates of the tone and of the spatial characteristics of the printed halftone pattern. Various classes of printer models, from simple tone calibrations, to complex mechanistic models, have been reported in the literature. Existing models have one or more of the following limiting factors: they only predict tone reproduction, they depend on the halftone pattern, they require complex calibrations or complex calculations, they are printer specific, they reproduce unrealistic dot structures, and they are unable to adapt responses to new data. The two research objectives of this dissertation are (1) to introduce a new framework for printer modeling and (2) to demonstrate the feasibility of such a framework in building an electrophotographic printer model. The proposed framework introduces the concept of modeling a printer as a texture transformation machine. The basic premise is that modeling the texture differences between the output printed images and the input images encompasses all printing distortions. The feasibility of the framework was tested with a case study modeling a monotone electrophotographic printer. The printer model was implemented as a bank of feed-forward neural networks, each one specialized in modeling a group of textural features of the printed halftone pattern. The textural features were obtained using a parametric representation of texture developed from a multiresolution decomposition proposed by other researchers. The textural properties of halftone patterns were analyzed and the key texture parameters to be modeled by the bank were identified. Guidelines for the multiresolution texture decomposition and the model operational parameters and operational limits were established. A method for the selection of training sets based on the morphological properties of the halftone patterns was also developed. The model is fast and has the capability to continue to learn with additional training. The model can be easily implemented because it only requires a calibrated scanner. The model was tested with halftone patterns representing a range of spatial characteristics found in halftoning. Results show that the model provides accurate predictions for the tone and the spatial characteristics when modeling halftone patterns individually and it provides close approximations when modeling multiple halftone patterns simultaneously. The success of the model justifies continued research of this new printer model framework