Jupiter's X-Ray and UV Dark Polar Region.

We present 14 simultaneous Chandra X-ray Observatory (CXO)-Hubble Space Telescope (HST) observations of Jupiter's Northern X-ray and ultraviolet (UV) aurorae from 2016 to 2019. Despite the variety of dynamic UV and X-ray auroral structures, one region is conspicuous by its persistent absence of emission: the dark polar region (DPR). Previous HST observations have shown that very little UV emission is produced by the DPR. We find that the DPR also produces very few X-ray photons. For all 14 observations, the low level of X-ray emission from the DPR is consistent (within 2-standard deviations) with scattered solar emission and/or photons spread by Chandra's Point Spread Function from known X-ray-bright regions. We therefore conclude that for these 14 observations the DPR produced no statistically significant detectable X-ray signature.

Comparing Jupiter's Equatorial X-Ray Emissions With Solar X-Ray Flux Over 19 Years of the Chandra Mission.

We present a statistical study of Jupiter's disk X-ray emissions using 19 years of Chandra X-Ray Observatory (CXO) observations. Previous work has suggested that these emissions are consistent with solar X-rays elastically scattered from Jupiter's upper atmosphere. We showcase a new pulse invariant (PI) filtering method that minimizes instrumental effects which may produce unphysical trends in photon counts across the nearly two-decade span of the observations. We compare the CXO results with solar X-ray flux data from the Geostationary Operational Environmental Satellites X-ray Sensor for the wavelength band 1-8 Å (long channel), to quantify the correlation between solar activity and Jovian disk counts. We find a statistically significant Pearson's Correlation Coefficient of 0.9, which confirms that emitted Jovian disk X-rays are predominantly governed by solar activity. We also utilize the high spatial resolution of the High Resolution Camera Instrument on-board the CXO to map the disk photons to their positions on Jupiter's surface. Voronoi tessellation diagrams were constructed with the Juno Reference Model through Perijove 9 internal field model overlaid to identify any spatial preference of equatorial photons. After accounting for area and scattering across the curved surface of the planet, we find a preference of Jovian disk emission at 2-3.5 Gauss surface magnetic field strength. This suggests that a portion of the disk X-rays may be linked to processes other than solar scattering: the spatial preference associated with magnetic field strength may imply increased precipitation from the radiation belts, as previously postulated.

Comparison of sporadic and familial behavioral variant frontotemporal dementia (FTD) in a North American cohort.

INTRODUCTION: Behavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments. METHODS: A total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation. RESULTS: Participants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability. DISCUSSION: f-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.

Valley Subband Splitting in Bilayer Graphene Quantum Point Contacts.

We report a study of one-dimensional subband splitting in a bilayer graphene quantum point contact in which quantized conductance in steps of 4e^{2}/h is clearly defined down to the lowest subband. While our source-drain bias spectroscopy measurements reveal an unconventional confinement, we observe a full lifting of the valley degeneracy at high magnetic fields perpendicular to the bilayer graphene plane for the first two lowest subbands where confinement and Coulomb interactions are the strongest and a peculiar merging or mixing of K and K^{'} valleys from two nonadjacent subbands with indices (N,N+2), which are well described by our semiphenomenological model.

The effect of obesity on adverse outcomes and metabolism in pediatric burn patients.

HYPOTHESIS: Obesity influences metabolism and increases the incidence of clinical complications and worsens outcomes in pediatric burn patients. DESIGN: Retrospective, single-center study. SUBJECTS: In all, 592 severely burned pediatric patients who had burns covering more than 30% of the total body surface area and who were treated between 2001 and 2008 were enrolled in this study. Patients were divided into ≥85th percentile (n=277) and normal (n=315) weight groups based on body mass index (BMI) percentiles. RESULTS: Patients stratified below (normal) and ≥85th percentile had similar age, gender distribution and total burn size. No significant differences were detected in the incidence of sepsis (11% for obese vs 10% for normal), the incidence of multiple organ failure (MOF) (21% for obese and 16% for normal) or mortality (11% for obese vs 8% for normal). Compared with the normal group, the ≥85th percentile group had low levels of constitutive proteins (α2macroglobulin and Apolipoprotein A1) (P<0.05 for both) as well as high levels of triglycerides and the acute-phase protein, C-reactive protein (P<0.05 for both) up to 60 days after injury. Patients ≥85th percentile showed a significant higher loss of bone mineral density and lipolysis compared with normal individuals. Stepwise logistic regression analysis revealed that BMI had a positive predictive value towards the maximum DENVER2 score, an index of organ failure (P<0.001). CONCLUSIONS: BMI≥85th percentile altered the post-burn acute phase and catabolic response but did not increase the incidence of sepsis, MOF or mortality in pediatric burn patients. Our results suggest that impaired metabolism and an altered inflammatory response already exists in patients starting at the 85th percentile BMI.

Distinct patterns of brain activity evoked by histamine-induced itch reveal an association with itch intensity and disease severity in atopic dermatitis.

BACKGROUND: Little is known about brain mechanisms supporting the experience of chronic puritus in disease states. OBJECTIVES: To examine the difference in brain processing of histamine-induced itch in patients with active atopic dermatitis (AD) vs. healthy controls with the emerging technique of functional magnetic resonance imaging (fMRI) using arterial spin labelling (ASL). METHODS: Itch was induced with histamine iontophoresis in eight patients with AD and seven healthy subjects. RESULTS: We found significant differences in brain processing of histamine-induced itch between patients with AD and healthy subjects. Patients with AD exhibited bilateral activation of the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), retrosplenial cingulate cortex and dorsolateral prefrontal cortex (DLPFC) as well as contralateral activation of the caudate nucleus and putamen. In contrast, healthy subjects activated the primary motor cortex, primary somatosensory cortex and superior parietal lobe. The PCC and precuneus exhibited significantly greater activity in patients vs. healthy subjects. A significant correlation between percentage changes of brain activation was noted in the activation of the ACC and contralateral insula and histamine-induced itch intensity as well as disease severity in patients with AD. In addition, an association was noted between DLPFC activity and disease severity. CONCLUSIONS: Our results demonstrate that ASL fMRI is a promising technique to assess brain activity in chronic itch. Brain activity of acute itch in AD seems to differ from that in healthy subjects. Moreover, the activity in cortical areas involved in affect and emotion correlated to measures of disease severity.

Pulsed arterial spin-labeled MR imaging evaluation of tuberous sclerosis.

BACKGROUND AND PURPOSE: Tuberous sclerosis presents with characteristic cortical hamartomas and subependymal nodules associated with seizures. The purpose of this study was to use pulsed arterial spin-labeling (PASL) to quantify the perfusion of the cortical hamartomas and correlate the perfusion values with seizure frequency. MATERIALS AND METHODS: A retrospective search yielded 16 MR imaging examinations including conventional MR imaging and PASL perfusion performed in 13 patients (age range, 7 months to 23 years) with a history of tuberous sclerosis. The mean perfusion of each cortical hamartoma greater than 5 mm in size localized with conventional MR imaging sequences was obtained with use of manually drawn regions of interest. Cortical hamartomas were classified as normal, hyperperfused, or hypoperfused on the basis of the mean and SD of the unaffected cortex. Correlation was made between perfusion imaging, conventional imaging, and clinical history. RESULTS: Of the 245 cortical hamartomas, 227 (92.7%) were hypoperfused, 10 (4.1%) were hyperperfused, and 8 (3.3%) were unchanged relative to the mean gray matter. One patient had a subependymal giant cell astrocytoma with a mean perfusion of 93.5 mL/100 g tissue/min. There was a statistically significant positive correlation between seizure frequency and the number of hyperperfused cortical tubers (r = 0.51; n = 16; P = .04), with higher seizure frequency associated with a greater number of hyperperfused cortical tubers. There was no significant correlation, however, between seizure frequency and the overall number of cortical tubers (r = 0.20; n = 16; P = .47). CONCLUSIONS: The PASL technique can assess and quantify the perfusion characteristics of a cortical hamartoma. Most lesions are hypoperfused; however, both normally perfused and hyperperfused lesions occur. The presence of hyperperfused cortical tubers was associated with increased seizure frequency.

Hypercapnia-induced cerebral hyperperfusion: an underrecognized clinical entity.

BACKGROUND AND PURPOSE: The incidence of cerebral hyperperfusion and hypoperfusion, respectively, resulting from hypercapnia and hypocapnia in hospitalized patients is unknown but is likely underrecognized by radiologists and clinicians without routine performance of quantitative perfusion imaging. Our purpose was to report the clinical and perfusion imaging findings in a series of patients confirmed to have hypercapnic cerebral hyperperfusion and hypocapnic hypoperfusion. MATERIALS AND METHODS: Conventional cerebral MR imaging examination was supplemented with arterial spin-labeled (ASL) MR perfusion imaging in 45 patients during a 16-month period at a single institution. Patients presented with an indication of altered mental status, metastasis, or suspected stroke. Images were reviewed and correlated with arterial blood gas (ABG) analysis and clinical history. RESULTS: Patients ranged in age from 1.5 to 85 years. No significant acute findings were identified on conventional MR imaging. Patients with hypercapnia showed global hyperperfusion on ASL cerebral blood flow (CBF) maps, respiratory acidosis on ABG, and diffuse air-space abnormalities on same-day chest radiographs. Regression analysis revealed a significant positive linear relationship between cerebral perfusion and the partial pressure of carbon dioxide (pCO(2); beta, 4.02; t, 11.03; P < .0005), such that rates of cerebral perfusion changed by 4.0 mL/100 g/min for each 1-mm Hg change in pCO(2). CONCLUSIONS: With the inception of ASL as a routine perfusion imaging technique, hypercapnic-associated cerebral hyperperfusion will be recognized more frequently and may provide an alternative cause of unexplained neuropsychiatric symptoms in hospitalized patients. In a similar fashion, hypocapnia may account for a subset of patients with normal MR imaging examinations with poor ASL perfusion signal.

Migraine associated cerebral hyperperfusion with arterial spin-labeled MR imaging.

We present a case series demonstrating abnormal regional cerebral hyperperfusion associated with migraine headache using arterial spin-labeling (ASL). In 3 of 11 patients, regional cortical hyperperfusion was demonstrated during a headache episode that corresponded to previous aura symptoms.

Anoxic injury-associated cerebral hyperperfusion identified with arterial spin-labeled MR imaging.

BACKGROUND AND PURPOSE: Anoxic brain injury is a devastating result of prolonged hypoxia. The goal of this study was to use arterial spin-labeling (ASL) to characterize the perfusion patterns encountered after anoxic injury to the brain. MATERIALS AND METHODS: Sixteen patients with a history of anoxic or hypoxic-ischemic injury ranging in age from 1.5 to 78.0 years (mean, 50.3 years) were analyzed with conventional MR imaging and pulsed ASL 1.0-13.0 days (mean, 4.6 days) after anoxic insult. The cerebral perfusion in each case was quantified by using pulsed ASL as part of the standard stroke protocol. Correlation was made among perfusion imaging, conventional imaging, clinical history, laboratory values, and outcome. RESULTS: Fifteen of the 16 patients showed marked global hyperperfusion, and 1 patient showed unilateral marked hyperperfusion. Mean gray matter (GM) cerebral blood flow (CBF) in these patients was 142.6 mL/100 g of tissue per minute (ranging from 79.9 to 204.4 mL/100 g of tissue per minute). Global GM CBF was significantly higher in anoxic injury subjects, compared with age-matched control groups with and without infarction (F(2,39) = 63.11; P < .001). Three patients had global hyperperfusion sparing areas of acute infarction. Conventional imaging showed characteristic restricted diffusion in the basal ganglia (n = 10) and cortex (n = 13). Most patients examined died (n = 12), with only 4 patients surviving at the 4-month follow-up. CONCLUSION: Pulsed ASL can dramatically demonstrate and quantify the severity of the cerebral hyperperfusion after a global anoxic injury. The global hyperperfusion probably results from loss of autoregulation of cerebral vascular resistance.

Arterial spin-labeling in routine clinical practice, part 3: hyperperfusion patterns.

Arterial spin-labeled (ASL) perfusion imaging can be implemented successfully into a routine clinical neuroimaging protocol and can accurately demonstrate alterations in brain perfusion. We have observed patterns of focal, regional, and global hyperperfusion in a wide variety of disease processes. The causes of hyperperfusion at clinical ASL have not been previously characterized. Focal lesions such as brain tumors and vascular malformations with increased perfusion can be well depicted by ASL. More global causes of hyperperfusion, including postanoxia vasodilation and hypercapnia, may go undetected on conventional MR images, whereas the regional hyperperfusion, which may occur in reversible encephalopathies and luxury perfusion, has been consistently illustrated on ASL cerebral blood flow maps at our institution.

Arterial spin-labeling in routine clinical practice, part 2: hypoperfusion patterns.

Arterial spin-labeling (ASL) is a powerful perfusion imaging technique capable of quickly demonstrating both hypo- and hyperperfusion on a global or localized scale in a wide range of disease states. Knowledge of pathophysiologic changes in blood flow and common artifacts inherent to the sequence allows accurate interpretation of ASL when performed as part of a routine clinical imaging protocol. Patterns of hypoperfusion encountered during routine application of ASL perfusion imaging in a large clinical population have not been described. The objective of this review article is to illustrate our experience with a heterogeneous collection of ASL perfusion cases and describe patterns of hypoperfusion. During a period of 1 year, more than 3000 pulsed ASL procedures were performed as a component of routine clinical brain MR imaging evaluation at both 1.5 and 3T. These images were reviewed with respect to image quality and patterns of hypoperfusion in various normal and disease states.

Arterial spin-labeling in routine clinical practice, part 1: technique and artifacts.

The routine use of arterial spin-labeling (ASL) in a clinical population has led to the depiction of diverse brain pathologic features. Unique challenges in the acquisition, postprocessing, and analysis of cerebral blood flow (CBF) maps are encountered in such a population, and high-quality ASL CBF maps can be generated consistently with attention to quality control and with the use of a dedicated postprocessing pipeline. Familiarity with commonly encountered artifacts can help avoid pitfalls in the interpretation of CBF maps. The purpose of this review was to describe our experience with a heterogeneous collection of ASL perfusion cases with an emphasis on methodology and common artifacts encountered with the technique. In a period of 1 year, more than 3000 pulsed ASL cases were performed as a component of routine clinical brain MR evaluation at both 1.5 and 3T. These ASL studies were analyzed with respect to overall image quality and patterns of perfusion on final gray-scale DICOM images and color Joint Photographic Experts Group (JPEG) CBF maps, and common artifacts and their impact on final image quality were categorized.

Spherical navigator registration using harmonic analysis for prospective motion correction.

Spherical navigators are an attractive approach to motion compensation in Magnetic Resonance Imaging. Because they can be acquired quickly, spherical navigators have the potential to measure and correct for rigid motion during image acquisition (prospectively as opposed to retrospectively). A limiting factor to prospective use of navigators is the time required to estimate the motion parameters. This estimation problem can be separated into a rotational and translational component. Recovery of the rotational motion can be cast as a registration of functions defined on a sphere. Previous methods for solving this registration problem are based on optimization strategies that are iterative and require k-space interpolation. Such approaches have undesirable convergence behavior for prospective use since the estimation complexity depends on both the number of samples and the amount of rotation. We propose and demonstrate an efficient algorithm for recovery of rotational motion using spherical navigators. We decompose the navigator magnitude using the spherical harmonic transform. In this framework, rigid rotations can be recovered from an over-constrained system of equations, leading to a computationally efficient algorithm for prospective motion compensation. The resulting algorithm is compared to existing approaches in simulated and actual navigator data. These results show that the spherical harmonic based estimation algorithm is significantly faster than existing methods and so is suited for prospective motion correction.

Identification of nucleolin as a new L-selectin ligand.

Apart from leucocyte-endothelial interactions, the adhesion molecule L-selectin mediates the homotypic adhesion of leucocytes during recruitment at sites of acute inflammation, as well as intercellular adhesion of haematopoietic progenitor cells during haematopoiesis. There is evidence that, in addition to P-selectin glycoprotein ligand-1, other as-yet-unidentified proteins function as L-selectin ligands on human leucocytes and haematopoietic progenitor cells. In the present study, we show: (i) by affinity chromatography on L-selectin-agarose; (ii) by protein identification using MS; and (iii) by covalent cell-surface labelling with sulphosuccinimidyl-2-(biotinamido)ethyl-1,3-dithiopropionate that the multifunctional nuclear protein nucleolin is partly exposed on the cell surface, and is a ligand of L-selectin in human leucocytes and haematopoietic progenitor cells.

Treatment of traumatized permanent incisors with crown and root fractures: a case report.

A case report of the treatment of permanent incisors with crown and root fractures is presented. A radiolucent lesion at the fracture lines was treated with calcium hydroxide in the coronal fragments for 18 months. Clinically, the teeth became firm and the radiographic results after 2 years showed healing of the lesion and hard tissue filling in the space at the fracture lines.

Targeting of the transcription factor Max during apoptosis: phosphorylation-regulated cleavage by caspase-5 at an unusual glutamic acid residue in position P1.

Max is the central component of the Myc/Max/Mad network of transcription factors that regulate growth, differentiation and apoptosis. Whereas the Myc and Mad genes and proteins are highly regulated, Max expression is constitutive and no post-translational regulation is known. We have found that Max is targeted during Fas-induced apoptosis. Max is first dephosphorylated and subsequently cleaved by caspases. Two specific cleavage sites for caspases in Max were identified, one at IEVE(10) decreasing S and one at SAFD(135) decreasing G near the C-terminus, which are cleaved in vitro by caspase-5 and caspase-7 respectively. Mutational analysis indicates that both sites are also used in vivo. Thus Max represents the first caspase-5 substrate. The unusual cleavage after a glutamic acid residue is observed only with full-length, DNA-binding competent Max protein but not with corresponding peptides, suggesting that structural determinants might be important for this activity. Furthermore, cleavage by caspase-5 is inhibited by the protein kinase CK2-mediated phosphorylation of Max at Ser-11, a previously mapped phosphorylation site in vivo. These findings suggest that Fas-mediated dephosphorylation of Max is required for cleavage by caspase-5. The modifications that occur on Max in response to Fas signalling affect the DNA-binding activity of Max/Max homodimers. Taken together, our findings uncover three distinct processes, namely dephosphorylation and cleavage by caspase-5 and caspase-7, that target Max during Fas-mediated apoptosis, suggesting the regulation of the Myc/Max/Mad network through its central component.

Glyceraldehyde-3-phosphate dehydrogenase is responsible for intranuclear localization of some oligonucleotides.

Nuclear accumulation of ODNs has been associated with their binding to a series of nuclear proteins. These interactions could be responsible for the sequence-independent effects of ODNs as well as for their sequence-specific interactions and their intracellular distribution. Investigation of interaction of ODNs with these proteins may shed light on the mechanisms of cellular uptake and nuclear accumulation of oligonucleotides.

Importin 13: a novel mediator of nuclear import and export.

Importin beta-related receptors mediate translocation through nuclear pore complexes. Co-operation with the RanGTPase system allows them to bind and subsequently release their substrates on opposite sides of the nuclear envelope, which in turn ensures a directed nucleocytoplasmic transport. Here we identify a novel family member from higher eukaryotes that functions primarily, but not exclusively, in import. It accounts for nuclear accumulation of the SUMO-1/sentrin-conjugating enzyme hUBC9 and mediates import of the RBM8 (Y14) protein, and is therefore referred to as importin 13 (Imp13). Unexpectedly, Imp13 also shows export activity towards the translation initiation factor eIF1A and is thus a case where a single importin beta-like receptor transports different substrates in opposite directions. However, Imp13 operates differently from typical exportins in that the binding of eIF1A to Imp13 is only regulated indirectly by RanGTP, and the cytoplasmic release of eIF1A from Imp13 is triggered by the loading of import substrates onto Imp13.

The Rossmann fold of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a nuclear docking site for antisense oligonucleotides containing a TAAAT motif.

The subcellular localisation of oligodeoxynucleotides (ODN) is a major limitation for their use against nuclear targets. In this study we demonstrate that an antisense ODN directed against cytosolic phospholipase A(2) (cPLA2) mRNA is efficiently taken up and accumulates in the nuclei of endothelial cells (HUVEC), human monocytes and HeLa cells. Gel shift experiments and incubation of cells with oligonucleotide derivatives show that the anti-cPLA2 oligo binds a 37 kDa protein in nuclear extracts. The TAAAT sequence was identified as the major binding motif for the nuclear protein in competition experiments with mutated ODNs. Modification of the AAA triplet resulted in an ODN which failed to localise in the nucleus. Moreover, inserting a TAAAT motif into an ODN localising in the cytosol did not modify its localisation. The 37 kDa protein was purified and identified after peptide sequencing as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). It was shown by confocal microscopy that GAPDH co-localises with anti-cPLA2 ODN in the nucleus and commercial GAPDH effectively binds the oligo. Competition experiments with increasing concentration of NAD(+) co-factor indicate that the GAPDH Rossmann fold is a docking site for antisense oligonucleotides containing a TAAAT motif.