Molecular and spin dynamics in solid state nuclear magnetic resonance spectroscopy

Thesis: Ph. D., Massachusetts Institute of Technology, Dept. of Chemistry, 1996Cataloged from PDF of thesis. Microfiche contains the reproduction of the print thesis.Includes bibliographical references (page 152).Nuclear Magnetic Resonance (NMR) spectroscopic data often involve spatial and spin dynamics and interference phenomena between the two. Experimental results are presented which demonstrate several of these phenomena and exploitation of these anomalies to acquire and improve knowledge regarding relevant chemistry. In some cases numerical analysis of such data are illustrated for obtaining quantitative rates of molecular dynamics. First, the dynamics of methyls bonded to the metals Tungsten and Tantalum are examined. In the case of Tungsten. an interference between methyl dynamics and proton decoupling is studied, whereas in the Tantalum instance, interference between molecular dynamics and Magic Angle Spinning (MAS) is examined. Agostic interactions had been hypothesized to exist in both compounds, but the unusual molecular dynamics are explainable without invoking a relation to such interactions. Further, no evidence is found to support the existence agostic bonds from examination of X-ray crystal data. Next. the spin dynamics in high resolution solid state proton systems diluted by deuterium is examined. In this case techniques such as Rotational Resonance and Radio-Frequency driven Dipolar Recoupling (RFDR) are employed to counteract the averaging of dipole couplings induced by MAS. The numerical analysis of such data in systems in which internuclear distances of interest are not identical but rather statistically distributed is discussed. Finally, a technique which may improve the sensitivity of NMR experiments is demonstrated. Dynamic Nuclear Polarization (DNP) is adapted to solid state MAS experiments and shown to enhance the signal intensity of a biomolecule, T4-lysozyme, by a factor of ~50. The necessary conditions for application of this technique to solid state NMR is discussed.by Douglas C. Maus.Ph. D.Ph.D. Massachusetts Institute of Technology, Dept. of Chemistr

A Neurological Cause of Recurrent Choking During Sleep

We describe a case of nocturnal choking episodes caused by insular seizures. Recurrent choking spells from sleep showed no response to treatment for sleep apnea or gastroesophageal reflux. Laryngoscopy revealed no abnormalities. Although continuous EEG monitoring during events was normal, ictal SPECT imaging showed increased radiotracer uptake in the left insular region, an area involved in sensation of the upper gastrointestinal tract. The episodes remitted after initiation of an antiepileptic drug. Obstructive sleep apnea is the most common cause for presentation to a sleep center, but seizures should remain in the differential diagnosis of nocturnal choking episodes

On-demand EEG education through competition – A novel, app-based approach to learning to identify interictal epileptiform discharges

Objective: Misinterpretation of EEGs harms patients, yet few resources exist to help trainees practice interpreting EEGs. We therefore sought to evaluate a novel educational tool to teach trainees how to identify interictal epileptiform discharges (IEDs) on EEG. Methods: We created a public EEG test within the iOS app DiagnosUs using a pool of 13,262 candidate IEDs. Users were shown a candidate IED on EEG and asked to rate it as epileptiform (IED) or not (non-IED). They were given immediate feedback based on a gold standard. Learning was analyzed using a parametric model. We additionally analyzed IED features that best correlated with expert ratings. Results: Our analysis included 901 participants. Users achieved a mean improvement of 13% over 1,000 questions and an ending accuracy of 81%. Users and experts appeared to rely on a similar set of IED morphologic features when analyzing candidate IEDs. We additionally identified particular types of candidate EEGs that remained challenging for most users even after substantial practice. Conclusions: Users improved in their ability to properly classify candidate IEDs through repeated exposure and immediate feedback. Significance: This app-based learning activity has great potential to be an effective supplemental tool to teach neurology trainees how to accurately identify IEDs on EEG

Organ-Specific Mechanisms of Transendothelial Neutrophil Migration in the Lung, Liver, Kidney, and Aorta

Immune responses are dependent on the recruitment of leukocytes to the site of inflammation. The classical leukocyte recruitment cascade, consisting of capture, rolling, arrest, adhesion, crawling, and transendothelial migration, is thoroughly studied but mostly in model systems, such as the cremasteric microcirculation. This cascade paradigm, which is widely accepted, might be applicable to many tissues, however recruitment mechanisms might substantially vary in different organs. Over the last decade, several studies shed light on organ-specific mechanisms of leukocyte recruitment. An improved awareness of this matter opens new therapeutic windows and allows targeting inflammation in a tissue-specific manner. The aim of this review is to summarize the current understanding of the leukocyte recruitment in general and how this varies in different organs. In particular we focus on neutrophils, as these are the first circulating leukocytes to reach the site of inflammation. Specifically, the recruitment mechanism in large arteries, as well as vessels in the lungs, liver, and kidney will be addressed

Insights from immuno-oncology: the Society for Immunotherapy of Cancer Statement on access to IL-6-targeting therapies for COVID-19.

The following statement was posted on March 24, 2020 and updated April 2, 2020. It has been accepted for upcoming publication in the Journal for ImmunoTherapy of Cancer (JITC)

Microscale Physiological Events on the Human Cortical Surface

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit