Sign Patterns of J-orthogonal Matrices

This thesis builds upon the results in “G-matrices, J-orthogonal matrices, and their sign patterns”, Czechoslovak Math. J. 66 (2016), 653-670, by Hall and Rozloˇzn ́ık. Some general results about the sign patterns of J-orthogonal matrices are proved, including about block diagonal matrices. It is shown that every full 4 × 4 sign pattern allows J -orthogonality and as a result that, for n ≤ 4, all n × n full sign patterns allow a J-orthogonal matrix as well as a G-matrix. The 3 × 3 sign patterns of the J -orthogonal matrices which have zero entires are also characterized

Pay Toll with Coins: Looking Back on FBAR Penalties and Prosecutions to Inform the Future of Cryptocurrency Taxation

Cryptocurrencies are gaining a foothold in the globaleconomy, and the government wants its cut. However, fewpeople are reporting cryptocurrency transactions on their taxreturns. How will the IRS solve its cryptocurrencynoncompliance problem? Its response so far bears manysimilarities to the government’s campaign to increase Reportsof Foreign Bank and Financial Accounts (FBARs). FBARnoncompliance penalties are notoriously harsh, and thegovernment has pursued them vigorously. This Note exploresthe connections and differences between cryptocurrencyreporting and foreign bank account reporting in an effort topredict the future regime of cryptocurrency tax compliance

Mitigating Emergency Department Crowding With Stochastic Population Models

Environments such as shopping malls, airports, or hospital emergency departments often experience crowding, with many people simultaneously requesting service. Crowding is highly noisy, with sudden overcrowding "spikes". Past research has either focused on average behavior or used context-specific non-generalizable models. Here we show that a stochastic population model, previously applied to a broad range of natural phenomena, can aptly describe hospital emergency-department crowding, using data from five-year minute-by-minute emergency-department records. The model provides reliable forecasting of the crowding distribution. Overcrowding is highly sensitive to the patient arrival-flux and length-of-stay: a 10% increase in arrivals triples the probability of overcrowding events. Expediting patient exit-rate to shorten the typical length-of-stay by just 20 minutes (8.5%) reduces severe overcrowding events by 50%. Such forecasting is crucial in prevention and mitigation of breakdown events. Our results demonstrate that despite its high volatility, crowding follows a dynamic behavior common to many natural systems.Comment: 21 pages, 6 figures + Supplementary informatio

Dendritic Spine Shape Analysis: A Clustering Perspective

Functional properties of neurons are strongly coupled with their morphology. Changes in neuronal activity alter morphological characteristics of dendritic spines. First step towards understanding the structure-function relationship is to group spines into main spine classes reported in the literature. Shape analysis of dendritic spines can help neuroscientists understand the underlying relationships. Due to unavailability of reliable automated tools, this analysis is currently performed manually which is a time-intensive and subjective task. Several studies on spine shape classification have been reported in the literature, however, there is an on-going debate on whether distinct spine shape classes exist or whether spines should be modeled through a continuum of shape variations. Another challenge is the subjectivity and bias that is introduced due to the supervised nature of classification approaches. In this paper, we aim to address these issues by presenting a clustering perspective. In this context, clustering may serve both confirmation of known patterns and discovery of new ones. We perform cluster analysis on two-photon microscopic images of spines using morphological, shape, and appearance based features and gain insights into the spine shape analysis problem. We use histogram of oriented gradients (HOG), disjunctive normal shape models (DNSM), morphological features, and intensity profile based features for cluster analysis. We use x-means to perform cluster analysis that selects the number of clusters automatically using the Bayesian information criterion (BIC). For all features, this analysis produces 4 clusters and we observe the formation of at least one cluster consisting of spines which are difficult to be assigned to a known class. This observation supports the argument of intermediate shape types.Comment: Accepted for BioImageComputing workshop at ECCV 201

Distinct roles of NMDA receptors at different stages of granule cell development in the adult brain.

NMDA receptor (NMDAR)-dependent forms of synaptic plasticity are thought to underlie the assembly of developing neuronal circuits and to play a crucial role in learning and memory. It remains unclear how NMDAR might contribute to the wiring of adult-born granule cells (GCs). Here we demonstrate that nascent GCs lacking NMDARs but rescued from apoptosis by overexpressing the pro-survival protein Bcl2 were deficient in spine formation. Insufficient spinogenesis might be a general cause of cell death restricted within the NMDAR-dependent critical time window for GC survival. NMDAR loss also led to enhanced mushroom spine formation and synaptic AMPAR activity throughout the development of newborn GCs. Moreover, similar elevated synapse maturation in the absence of NMDARs was observed in neonate-generated GCs and CA1 pyramidal neurons. Together, these data suggest that NMDAR operates as a molecular monitor for controlling the activity-dependent establishment and maturation rate of synaptic connections between newborn neurons and others

Esmolol is noninferior to metoprolol in achieving a target heart rate of 65 beats/min in patients referred to coronary CT angiography: A randomized controlled clinical trial.

BACKGROUND: Coronary CT angiography (CTA) is an established tool to rule out coronary artery disease. Performance of coronary CTA is highly dependent on patients' heart rates (HRs). Despite widespread use of beta-blockers for coronary CTA, few studies have compared various agents used to achieve adequate HR control. OBJECTIVE: We sought to assess if the ultrashort-acting beta-blocker intravenous esmolol is at least as efficacious as the standard of care intravenous metoprolol for HR control during coronary CTA. METHODS: Patients referred to coronary CTA with a HR >65 beats/min despite oral metoprolol premedication were enrolled in the study. We studied 412 patients (211 male; mean age, 57 +/- 12 years). Two hundred four patients received intravenous esmolol, and 208 received intravenous metoprolol with a stepwise bolus administration protocol. HR and blood pressure were recorded at arrival, before, during, immediately after, and 30 minutes after the coronary CTA scan. RESULTS: Mean HRs of the esmolol and metoprolol groups were similar at arrival (78 +/- 13 beats/min vs 77 +/- 12 beats/min; P = .65) and before scan (68 +/- 7 beats/min vs 69 +/- 7 beats/min; P = .60). However, HR during scan was lower in the esmolol group vs the metoprolol group (58 +/- 6 beats/min vs 61 +/- 7 beats/min; P < .0001), whereas HRs immediately and 30 minutes after the scan were higher in the esmolol group vs the metoprolol group (68 +/- 7 beats/min vs 66 +/- 7 beats/min; P = .01 and 65 +/- 8 beats/min vs 63 +/- 8 beats/min; P < .0001; respectively). HR </=65 beats/min was reached in 182 of 204 patients (89%) who received intravenous esmolol vs 162 of 208 of the patients (78%) who received intravenous metoprolol (P < .05). Of note, hypotension (systolic BP <100 mm Hg) was observed right after the scan in 19 patients (9.3%) in the esmolol group and in 8 patients (3.8%) in the metoprolol group (P < .05), whereas only 5 patients (2.5%) had hypotension 30 minutes after the scan in the esmolol group compared to 8 patients (3.8%) in the metoprolol group (P = .418). CONCLUSION: Intravenous esmolol with a stepwise bolus administration protocol is at least as efficacious as the standard of care intravenous metoprolol for HR control in patients who undergo coronary CTA

Investigating Sub-Spine Actin Dynamics in Rat Hippocampal Neurons with Super-Resolution Optical Imaging

Morphological changes in dendritic spines represent an important mechanism for synaptic plasticity which is postulated to underlie the vital cognitive phenomena of learning and memory. These morphological changes are driven by the dynamic actin cytoskeleton that is present in dendritic spines. The study of actin dynamics in these spines traditionally has been hindered by the small size of the spine. In this study, we utilize a photo-activation localization microscopy (PALM)–based single-molecule tracking technique to analyze F-actin movements with ∼30-nm resolution in cultured hippocampal neurons. We were able to observe the kinematic (physical motion of actin filaments, i.e., retrograde flow) and kinetic (F-actin turn-over) dynamics of F-actin at the single-filament level in dendritic spines. We found that F-actin in dendritic spines exhibits highly heterogeneous kinematic dynamics at the individual filament level, with simultaneous actin flows in both retrograde and anterograde directions. At the ensemble level, movements of filaments integrate into a net retrograde flow of ∼138 nm/min. These results suggest a weakly polarized F-actin network that consists of mostly short filaments in dendritic spines

Spine neck plasticity regulates compartmentalization of synapses

Dendritic spines have been proposed to transform synaptic signals through chemical and electrical compartmentalization. However, the quantitative contribution of spine morphology to synapse compartmentalization and its dynamic regulation are still poorly understood. We used time-lapse super-resolution stimulated emission depletion (STED) imaging in combination with fluorescence recovery after photobleaching (FRAP) measurements, two-photon glutamate uncaging, electrophysiology and simulations to investigate the dynamic link between nanoscale anatomy and compartmentalization in live spines of CA1 neurons in mouse brain slices. We report a diversity of spine morphologies that argues against common categorization schemes and establish a close link between compartmentalization and spine morphology, wherein spine neck width is the most critical morphological parameter. We demonstrate that spine necks are plastic structures that become wider and shorter after long-term potentiation. These morphological changes are predicted to lead to a substantial drop in spine head excitatory postsynaptic potential (EPSP) while preserving overall biochemical compartmentalization

Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism

The process of axonal and dendritic development establishes the synaptic circuitry of the central nervous system (CNS) and is the result of interactions between intrinsic molecular factors and the external environment. One growth factor that has a compelling function in neuronal development is the neurotrophin brain-derived neurotrophic factor (BDNF). BDNF participates in axonal and dendritic differentiation during embryonic stages of neuronal development, as well as in the formation and maturation of dendritic spines during postnatal development. Recent studies have also implicated vesicular trafficking of BDNF via secretory vesicles, and both secretory and endosomal trafficking of vesicles containing synaptic proteins, such as neurotransmitter and neurotrophin receptors, in the regulation of axonal and dendritic differentiation, and in dendritic spine morphogenesis. Several genes that are either mutated or deregulated in neurodevelopmental disorders associated with mental retardation have now been identified, and several mouse models of these disorders have been generated and characterized. Interestingly, abnormalities in dendritic and synaptic structure are consistently observed in human neurodevelopmental disorders associated with mental retardation, and in mouse models of these disorders as well. Abnormalities in dendritic and synaptic differentiation are thought to underlie altered synaptic function and network connectivity, thus contributing to the clinical outcome. Here, we review the roles of BDNF and vesicular trafficking in axonal and dendritic differentiation in the context of dendritic and axonal morphological impairments commonly observed in neurodevelopmental disorders associated with mental retardation