NMR Characterization of Changes in the Apparent Diffusion Coefficient of Water Following Transient Cerebral Ischemia

Magnetic resonance imaging (MRI) is a valuable research and clinical imaging modality for the non-invasive detection and characterization of cerebral ischemia. Specifically, diffusion-weighted imaging (DWI), which derives image contrast based on the diffusion of endogenous water molecules, is sensitive to cerebral ischemia within minutes of the onset of stroke. In combination with perfusion-weighted imaging (PWI) and T2-weighted imaging (T2WI), DWI can be used to characterize the temporal and spatial evolution of cerebral ischemia. The primary role of this dissertation is to outline several studies that investigate DWI, PWI, and T2WI changes in a rat stroke model of transient cerebral ischemia. Secondarily, this dissertation will introduce the method and results of an experiment designed to elucidate the relative roles of the intracellular (IC) or extracellular (EC) spaces to the water diffusion coefficient changes that occur as a result of cerebral ischemia. The use of MRI to detect cerebral ischemia is well established; however, the ability to distinguish between reversibly and irreversibly damaged tissues is limited. It has been shown in temporary focal ischemia models that the DWI abnormality (manifested as an image hyperintensity in the DWI) can be resolved if reperfusion is performed soon after the onset of the stroke. Initial studies suggested that the renormalization of water diffusion was associated with permanent restoration of cellular function (i.e., infarction was prevented). However, subsequent studies demonstrated that the disappearance of the acute ischemic lesion following reperfusion is not necessarily permanent and is related to the duration of the transient insult. Following short occlusions [e.g., 10 minutes in a rat middle cerebral artery occlusion (MCAO) model], there is complete tissue renormalization and restoration of normal neurological function. In contrast, following long periods of occlusion (e.g., 90 minutes), there are areas of the brain that do not recover and progress to infarction without delay. Intermediate durations of occlusion (e.g., 30 minutes) exhibit complete renormalization in all regions of ischemia; however, following several hours there is a gradual, secondary decline of the water diffusion coefficient values within the regions initially defined as abnormal. In this dissertation, the significant temporal and spatial heterogeneity in the secondary diffusion changes will be described and evaluated. Ultimately, MR techniques may provide valuable information regarding the response of tissue to transient ischemia as well as potential avenues for therapeutic intervention, which would have major clinical benefit. The significant changes in the apparent diffusion coefficient (ADC) of water that occur in ischemic brain are still not well understood. The leading hypothesis suggests that cellular swelling associated with the failure of the ionic gradient across the cell membrane results in an increase in EC tortuosity of the diffusion paths. Another theory suggests that the influx of fast-diffusing EC water, that occurs during cellular swelling, increases the proportion of water in the IC space, which is more restricted and viscous than the EC space. The final experiment presented herein demonstrates that significant cellular swelling remains in the regions of renormalized of ischemic ADC values that occur following reperfusion in transient ischemia. In short, the changes in the ADC values are not only the result of cellular swelling. Since conventional MR data contains the combined signals from the IC and EC spaces, it is difficult to determine the separate roles of these two compartments to the overall changes in water ADC. First, using a yeast-cell model, a method for separating the NMR signals is introduced. This method utilizes differences in the compartmental relaxation properties to isolate the MR signals from IC and EC spaces, and then secondarily the diffusion coefficients can be calculated. Using a modified version of this method, the experiment was performed in normal and ischemic rat brain. Intracerebroventricular (ICV) infusion of an MR contrast reagent (CR) was used to isolate IC T1, T2, and ADC values in vivo in normal and middle cerebral artery occluded (MCAO) rats using volume-localized, diffusion-weighted inversion-recovery spin-echo (DW-IRSE) spectroscopy and diffusion-weighted echo-planar imaging (DW-EPI). The presence of the EC contrast reagent (CR) selectively enhances the relaxation of water in the EC space and allows the IC and EC signal contributions to be separated based on T1-relaxation time differences between the two compartments. The results presented in this dissertation suggest that the IC ADC value is the major determinant of the overall ADC value measured in the normal rat brain. Further, the data suggests that the ADC decline experienced during acute ischemia is dictated largely by changes in the IC ADC, possibly due to failure of energy-dependent IC microcirculation (cytoplasmic streaming)

Formation of Dark Matter Haloes in a Homogeneous Dark Energy Universe

Several independent cosmological tests have shown evidences that the energy density of the Universe is dominated by a dark energy component, which cause the present accelerated expansion. The large scale structure formation can be used to probe dark energy models, and the mass function of dark matter haloes is one of the best statistical tools to perform this study. We present here a statistical analysis of mass functions of galaxies under a homogeneous dark energy model, proposed in the work of Percival (2005), using an observational flux-limited X-ray cluster survey, and CMB data from WMAP. We compare, in our analysis, the standard Press-Schechter (PS) approach (where a Gaussian distribution is used to describe the primordial density fluctuation field of the mass function), and the PL (Power Law) mass function (where we apply a nonextensive q-statistical distribution to the primordial density field). We conclude that the PS mass function cannot explain at the same time the X-ray and the CMB data (even at 99% confidence level), and the PS best fit dark energy equation of state parameter is $\omega=-0.58$, which is distant from the cosmological constant case. The PL mass function provides better fits to the HIFLUGCS X-ray galaxy data and the CMB data; we also note that the $\omega$ parameter is very sensible to modifications in the PL free parameter, $q$, suggesting that the PL mass function could be a powerful tool to constrain dark energy models.Comment: 4 pages, 2 figures, Latex. Accepted for publication in the International Journal of Modern Physics D (IJMPD)

Influence of Battery Energy Storage Systems on Transmission Grid Operation With a Significant Share of Variable Renewable Energy

The generation mix of Portugal now contains a significant amount of variable renewable energy sources (RES) and the amount of RES is expected to grow substantially. This has led to concerns being raised regarding the security of the supply of the Portuguese electric system as well as concerns relating to system inertia. Deploying and efficiently using various flexibility options is proposed as a solution to these concerns. Among these flexibility options proposed is the use of battery energy storage systems (BESSs) as well as relaxing system inertia constraints such as the system nonsynchronous penetration (SNSP). This article proposes a stochastic mixed-integer linear programming problem formulation, which examines the effects of deploying BESS in a power system. The model is deployed on a real-world test case and results show that the optimal use of BESS can reduce system costs by as much as 10% relative to a baseline scenario and the costs are reduced further when the SNSP constraint is relaxed. The amount of RES curtailment is also reduced with the increased flexibility of the power system through the use of BESS. Thus, the efficiency of the Portuguese transmission system is greatly increased by the use of flexibility measures, primarily the use of BESS.©2021 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.fi=vertaisarvioitu|en=peerReviewed

Hubble Space Telescope Imaging of the CFRS and LDSS Redshift Surveys---III. Field elliptical galaxies at 0.2 < z < 1.0

Surface photometry has been performed on a sample of 46 field elliptical galaxies. These galaxies are described well by a deVaucouleurs R^{1/4} profile. The sample was selected from the combined Canada-France and LDSS redshift surveys and spans the range 0.20 < z < 1.00. The relationship between galaxy half-light radius and luminosity evolves such that a galaxy of a given size is more luminous by Delta M_B=-0.97 \pm 0.14 mag at z=0.92 and the mean rest-frame color shifts blueward by Delta (U-V) =-0.68 \pm 0.11 at z=0.92 relative to the local cluster relations. Approximately 1/3 of these elliptical galaxies exhibit [OII] 3727 emission lines with equivalent widths > 15 angstroms indicating ongoing star formation. Estimated star-formation rates imply that \le 5% of the stellar mass in the elliptical galaxy population has been formed since z=1. We see no evidence for a decline in the space density of early-type galaxies with look-back time. The statistics and a comparison with local luminosity functions are both consistent with the view that the population of massive early-type galaxies was largely in place by z~1. This implies that merging is not required since that time to produce the present-day space density of elliptical galaxies.Comment: 21 pages plus 8 figures plus 5 tables. Accepted by Astrophysical Journa

Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection

Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests. Recent data demonstrate neutralization of Zika virus by monoclonal antibodies or human serum collected early after DENV infection. Whether this finding is true in late DENV convalescence (>6 months after infection) is unknown. We studied late convalescent serum samples from persons with prior DENV or Zika virus exposure. Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was not observed among primary DENV infections. We observed low-frequency (23%) Zika virus cross-neutralization in repeat DENV infections. DENV-immune persons who had Zika virus as a secondary infection had distinct populations of antibodies that neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion experiments. These data suggest that most DENV infections do not induce durable, high-level Zika virus cross-neutralizing antibodies. Zika virus–specific antibody populations develop after Zika virus infection irrespective of prior DENV immunity

Pre-hydrodynamic evolution in large and small systems

We extend our previous investigation of the effects of pre-hydrodynamic evolution on final-state observables in heavy-ion collisions to smaller systems. We use a state-of-the-art hybrid model for the numerical simulations with optimal parameters obtained from a previous Bayesian study. By studying p-Pb collisions, we find that the effects due to the assumption of a conformal evolution in the pre-hydrodynamical stage are even more important in small systems. We also show that this effect depends on the time duration of the pre-equilibrium stage, which is further enhanced in small systems. Finally, we show that the recent proposal of a free-streaming with subluminal velocity for the pre-equilibrium stage, thus effectively breaking conformal invariance, can alleviate the contamination of final state observables. Our study further reinforces the need for moving beyond conformal approaches in pre-equilibrium dynamics modeling, especially when extracting transport coefficients from hybrid models in the high-precision era of heavy-ion collisions.Comment: 15 pages, 14 figure

The effect of intracranial stent implantation on the curvature of the cerebrovasculature

BACKGROUND AND PURPOSE: Recently, the use of stents to assist in the coiling and repair of wide-neck aneurysms has been shown to be highly effective; however, the effect of these stents on the RC of the parent vessel has not been quantified. The purpose of this study was to quantify the effect of intracranial stenting on the RC of the implanted artery using 3D datasets. MATERIALS AND METHODS: Twenty-four patients receiving FDA-approved neurovascular stents to support coil embolization of brain aneurysms were chosen for this study. The stents were located in the ICA, ACA, or MCA. We analyzed C-arm rotational angiography and contrast-enhanced cone beam CT datasets before and after stent implantation, respectively, to ascertain changes in vessel curvature. The images were reconstructed, and the vessel centerline was extracted. From the centerline, the RC was calculated. RESULTS: The average implanted stent length was 25.4 +/- 5.8 mm, with a pre-implantation RC of 7.1 +/- 2.1 mm and a postimplantation RC of 10.7 +/- 3.5 mm. This resulted in a 3.6 +/- 2.7 mm change in the RC due to implantation (P \u3c .0001), more than a 50% increase from the pre-implantation value. There was no difference in the change of RC for the different locations studied. The change in RC was not impacted by the extent of coil packing within the aneurysm. CONCLUSIONS: The implantation of neurovascular stents can be shown to have a large impact on the RC of the vessel. This will lead to a change in the local hemodynamics and flow pattern within the aneurysm

Drosophila Host Model Reveals New Enterococcus faecalis Quorum-Sensing Associated Virulence Factors

Enterococcus faecalis V583 is a vancomycin-resistant clinical isolate which belongs to the hospital-adapted clade, CC2. This strain harbours several factors that have been associated with virulence, including the fsr quorum-sensing regulatory system that is known to control the expression of GelE and SprE proteases. To discriminate between genes directly regulated by Fsr, and those indirectly regulated as the result of protease expression or activity, we compared gene expression in isogenic mutants of V583 variously defective in either Fsr quorum sensing or protease expression. Quorum sensing was artificially induced by addition of the quorum signal, GBAP, exogenously in a controlled manner. The Fsr regulon was found to be restricted to five genes, gelE, sprE, ef1097, ef1351 and ef1352. Twelve additional genes were found to be dependent on the presence of GBAP-induced proteases. Induction of GelE and SprE by GBAP via Fsr resulted in accumulation of mRNA encoding lrgAB, and this induction was found to be lytRS dependent. Drosophila infection was used to discern varying levels of toxicity stemming from mutations in the fsr quorum regulatory system and the genes that it regulates, highlighting the contribution of LrgAB and bacteriocin EF1097 to infection toxicity. A contribution of SprE to infection toxicity was also detected. This work brought to light new players in E. faecalis success as a pathogen and paves the way for future studies on host tolerance mechanisms to infections caused by this important nosocomial pathogen