Here, we test whether early visual and OCT rod energy-linked biomarkers indicating pathophysiology in nicotinamide nucleotide transhydrogenase (Nnt)-null 5xFAD mice also occur in Nnt-intact 5xFAD ...mice and whether these biomarkers can be pharmacologically treated. Four-month-old wild-type or 5xFAD C57BL/6 substrains with either a null (B6J) Nnt or intact Nnt gene (B6NTac) and 5xFAD B6J mice treated for one month with either R-carvedilol + vehicle or only vehicle (0.01% DMSO) were studied. The contrast sensitivity (CS), external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness (a proxy for low pH-triggered water removal), profile shape of the hyperreflective band just posterior to the ELM (i.e., the mitochondrial configuration within photoreceptors per aspect ratio MCP/AR), and retinal laminar thickness were measured. Both wild-type substrains showed similar visual performance indices and dark-evoked ELM-RPE contraction. The lack of a light-dark change in B6NTac MCP/AR, unlike in B6J mice, is consistent with relatively greater mitochondrial efficiency. 5xFAD B6J mice, but not 5xFAD B6NTac mice, showed lower-than-WT CS. Light-adapted 5xFAD substrains both showed abnormal ELM-RPE contraction and greater-than-WT MCP/AR contraction. The inner retina and superior outer retina were thinner. Treating 5xFAD B6J mice with R-carvedilol + DMSO or DMSO alone corrected CS and ELM-RPE contraction but not supernormal MCP/AR contraction or laminar thinning. These results provide biomarker evidence for prodromal photoreceptor mitochondrial dysfunction/oxidative stress/oxidative damage, which is unrelated to visual performance, as well as the presence of the Nnt gene. This pathophysiology is druggable in 5xFAD mice.
Abstract
BACKGROUND
High-grade gliomas are the most frequent and deadliest type of primary brain tumors in adults; despite the significant advances in understanding tumor biology, life expectancy of ...these patients is still limited. The aim of our study was to analyse blood cells counts and ratios as systemic inflammatory markers in newly diagnosed glioblastoma, to correlate these data with the radiological parameters and to identify their role as prognostic factors.
MATERIAL AND METHODS
A retrospective analysis was performed in 112 patients who underwent surgery for glioblastoma between 2016 and 2021. MRI for radiological features was available in all patients. Preoperative blood tests (neutrophils N, lymphocytes L, monocytes M, platelets PLT) were available in 105 patients. Inflammatory markers/ratios (NLR, LMR and PLR) were calculated.
RESULTS
Significant cut-offs for survival in inflammatory ratios were identified. Significant predictors for survival in Cox regression analysis were NLR > 2.3, LMR < 3 and high platelets counts. We then evaluated relationship with radiological parameters: midline location was statistically significantly correlated with higher N and PLT levels as well as NLR and PLR and with lower L levels; insular location with lower L and higher NLR and PLR; the involvement of more than one lobe with higher N and NLR, midline shift with higher N, NLR and PLR and lower L. The correlation with inflammatory markers was confirmed for tumor volume in FLAIR, associated with higher N, NLR and PLR and lower L, contrast-enhanced volume, associated with higher PLR, and necrosis volume, associated with higher N, NLR and PLR and PLT. Significant predictors in univariate Cox regression analysis were midline and insular location, involvement of more than 1 lobe and multifocality. In the multivariate analysis multifocality had the greater impact on survival (HR 2, p = 0.037) while contrast-enhanced volume and necrosis volume had a significant but lower impact on survival (HR 1.04 and 0.94, respectively); a LMR > 3 was associated with a benefit in survival (HR 0.56, p = 0.041), while increasing platelets were associated with poor outcome, even if with a lower impact (HR 1.01, p < 0.001).
CONCLUSION
We identified potential markers of systemic inflammation in gliobastoma patients calculated as ratios of preoperative blood cells counts (NLR, LMR, PLR) and proposed cut-points with significant impact on overall survival. We established a relationship between counts and ratios and radiological features, particularly tumor location, mass effect and volumes. We also identified a “trend” in blood cells counts and inflammatory markers correlated with those radiological features with a significant impact on survival. We identified platelets and lymphocytes (in the ratio relative to monocytes) as the inflammatory markers with the most significant effect on survival.
Erbium quinolinolates, commonly assumed to be mononuclear species with octahedral co‐ordination geometry, have been proposed as promising materials for photonic devices but difficulties in obtaining ...well defined products have so far limited their use. We report here the conditions to obtain in high yields three different kinds of pure neutral erbium quinolinolates by mixing an erbium salt with 8‐quinolinol (HQ) and 5,7‐dihalo‐8‐quinolinol (H5,7XQ: X = Cl and Br): i) the trinuclear complex Er3Q9 (1) which is obtained with HQ deprotonated by NH3 in water or ethanol/water mixtures; ii) the already known dimeric complexes based on the unit Er(5,7XQ)3(H2O)2 X = Cl (2) and Br (3); iii) the mononuclear Er(5,7XQ)2(H5,7XQ)2Cl X = Cl (4) and Br (5) complexes, obtained in organic solvents without base addition, where the ion results coordinated to four ligands, two deprotonated chelating, and two as zwitterionic monodentate oxygen donors. These results represent a further progress with respect to a recent reinvestigation on this reaction, which has shown that obtaining pure and anhydrous octahedral ErQ3, the expected reaction product, is virtually impossible, but failed in the isolation of 1 and of the neutral tetrakis species based on H5,7XQ ligands. Structural data provide a detailed description of the molecules and of their packing which involves short contacts between quinoxaline ligands, due to π–π interactions. Electronic and vibrational studies allow to select the fingerprints to distinguish the different products and to identify the presence of water. The structure/property relationship furnishes a satisfactory interpretation of the photo‐physical properties. Experimental evidence confirms that the most important quenchers for the erbium emission are the coordinated water molecules and shows that the ligand emission is significantly affected by the π–π interactions.
The structure/property relationship on the class of erbium‐quinolinolates furnishes a satisfactory interpretation of the photo‐physical properties and allows to revise literature data. Experimental evidence confirms that the most important quenchers for the erbium emission are the coordinated water molecules and shows that the ligand emission is significantly affected by the π–π interactions.
We compare Jupiter observations made around 27 August 2016 by Juno's JunoCam, Jovian Infrared Auroral Mapper (JIRAM), MicroWave Radiometer (MWR) instruments, and NASA's Infrared Telescope Facility. ...Visibly dark regions are highly correlated with bright areas at 5 µm, a wavelength sensitive to gaseous NH3 gas and particulate opacity at p ≤5 bars. A general correlation between 5‐µm and microwave radiances arises from a similar dependence on NH3 opacity. Significant exceptions are present and probably arise from additional particulate opacity at 5 µm. JIRAM spectroscopy and the MWR derive consistent 5‐bar NH3 abundances that are within the lower bounds of Galileo measurement uncertainties. Vigorous upward vertical transport near the equator is likely responsible for high NH3 abundances and with enhanced abundances of some disequilibrium species used as indirect indicators of vertical motions.
Key Points
A high correlation between visibly dark clouds and 5‐micron radiation extends only partially to microwave radiation
Five‐micron spectroscopy and microwave radiometry yield a 5‐bar NH3 abundance not inconsistent with Galileo results
Meridional dependence of deep atmospheric opacity is dynamically consistent with most other vertical‐motion tracers
Plain Language Summary
Comparison of observations of Jupiter by different Juno and ground‐based instruments verified some long‐standing relationships, such as those between visibly dark regions and clear, dry parts of the atmosphere. But Juno saw significant exceptions. Different instrument results for the abundance of ammonia gas, a condensate similar to water in the Earth's atmosphere, at 5 bars of pressure were self‐consistent and within the uncertainty of Galileo results. The substantial upwelling of ammonia detected by the Microwave Radiometer from great depth near the equator is consistent with other indirect tracers of vertical winds.
Today, the workflows that are involved in industrial assembly and production activities are becoming increasingly complex. To efficiently and safely perform these workflows is demanding on the ...workers, in particular when it comes to infrequent or repetitive tasks. This burden on the workers can be eased by introducing smart assistance systems. This article presents a scalable concept and an integrated system demonstrator designed for this purpose. The basic idea is to learn workflows from observing multiple expert operators and then transfer the learnt workflow models to novice users. Being entirely learning-based, the proposed system can be applied to various tasks and domains. The above idea has been realized in a prototype, which combines components pushing the state of the art of hardware and software designed with interoperability in mind. The emphasis of this article is on the algorithms developed for the prototype: 1) fusion of inertial and visual sensor information from an on-body sensor network (BSN) to robustly track the user's pose in magnetically polluted environments; 2) learning-based computer vision algorithms to map the workspace, localize the sensor with respect to the workspace and capture objects, even as they are carried; 3) domain-independent and robust workflow recovery and monitoring algorithms based on spatiotemporal pairwise relations deduced from object and user movement with respect to the scene; and 4) context-sensitive augmented reality (AR) user feedback using a head-mounted display (HMD). A distinguishing key feature of the developed algorithms is that they all operate solely on data from the on-body sensor network and that no external instrumentation is needed. The feasibility of the chosen approach for the complete action-perception-feedback loop is demonstrated on three increasingly complex datasets representing manual industrial tasks. These limited size datasets indicate and highlight the potential of the chosen technology as a combined entity as well as point out limitations of the system.
Dawn storms are among the brightest events in the Jovian aurorae. Up to now, they had only been observed from Earth‐based observatories, only showing the Sun‐facing side of the planet. Here, we show ...for the first time global views of the phenomenon, from its initiation to its end and from the nightside of the aurora onto the dayside. Based on Juno's first 20 orbits, some patterns now emerge. Small short‐lived spots are often seen a couple of hours before the main emission starts to brighten and evolve from a straight arc to a more irregular one in the midnight sector. As the whole feature rotates dawn‐ward, the arc then separates into two arcs with a central initially void region that is progressively filled with emissions. A gap in longitude then often forms before the whole feature dims. Finally, it transforms into an equatorward‐moving patch of auroral emissions associated with plasma injection signatures. Some dawn storms remain weak and never fully develop. We also found cases of successive dawn storms within a few hours. Dawn storms thus share many fundamental features with the auroral signatures of the substorms at Earth, despite the substantial differences between the dynamics of the magnetosphere at the two planets.
Plain Language Summary
Polar aurorae are a direct consequence of the dynamics of the plasma in the magnetosphere. The sources of mass and energy differ between the Earth's and Jupiter's magnetospheres, leading to fundamentally distinct auroral morphologies and very different responses to solar wind variations. Here, we report on the imaging of all development stages of spectacular auroral events at Jupiter, called dawn storms, including, for the first time, their initiation on the nightside. Our results reveal surprising similarities with auroral substorms at Earth, which are auroral events stemming from explosive magnetospheric reconfigurations. These findings demonstrate that, whatever their sources, mass and energy do not always circulate smoothly in planetary magnetospheres. Instead they often accumulate until the magnetospheres reconfigure and generate substorm‐like responses in the planetary aurorae, although the temporal and spatial scales are different for different planets.
Key Points
Juno's observations provide the first global description of dawn storms in Jupiter's aurorae, from their initiation to their end
Examples of nonisolated dawn storms and smaller events named pseudo‐dawn storms have been identified
Jovian dawn storms and terrestrial auroral substorms share many morphological and temporal characteristics
Almost 30% of the sunitinib-treated patients for metastatic renal carcinoma (mRCC) do not receive a clinical benefit. Convincing evidences demonstrated a cross talk between the VEGF and CXCR4 ...pathways. It was hypothesized that CXCR4 expression in primary renal cancer could predict sunitinib responsiveness.
In this exploratory study sixty-two mRCC patients receiving sunitinib as first-line treatment were evaluated for CXCR4 expression through immunohistochemistry (IHC). Correlations between CXCR4 expression, baseline patients and tumour characteristics were studied by contingency tables and the chi-square test. Univariable analysis was performed with the log-rank test, and the Cox model was applied for multivariable analysis.
The objective response rate of sunitinib first-line therapy was 35.5% (22/62) with a disease control rate (response and stable disease) of 62.9% (39/62). CXCR4 expression was absent/low in 30 (48.4%), moderate in 17 (27.4%), and high in 15 (24.2%) tumors respectively. Low or absent CXCR4 expression predicted response to sunitinib therapy. Moreover, Fuhrman grading and concomitant, CXCR4 and Fuhrman grading, strongly predicted sunitinib first line therapy responsiveness on progression-free survival and overall survival.
High CXCR4 expression correlates with sunitinib poor response in metastatic renal cancer.
The present study investigates some sampling strategies for the estimation of abundance and canopy cover of trees outside forest (TOF) over large areas. A collection of about 53 000 TOF units in ...Central Italy was acquired by visual, on-screen interpretation of aerial orthophotos and was taken as the reference population with the purpose of investigating: (i) one-phase inventories with sample points located by means of the tessellation stratified sampling (TSS), which involves covering the study region by a grid of regular polygons of equal sizes and randomly and independently selecting a point in each of them; (ii) two-phase inventories with the one-per-stratum stratified sampling adopted in the second phase to select a sample of polygons from the grid and then visit only the points contained in those polygons. Uniform random sampling is also considered in the first phase as a benchmark for tessellation stratified sampling. The sampling schemes adopted to select TOF units at the sample points are as follows: (i) point sampling, (ii) centroid-based plot sampling with plot radius of 50 m (CPLS50) or 100 m, and (iii) plot intersect sampling with plot radius of 50 or 100 m. CPLS50 under single-phase TSS proves to be a promising strategy to large-scale TOF inventories.
Background & Aims Insulin contributes to vascular homeostasis in peripheral circulation, but the effects of insulin in liver microvasculature have never been explored. The aim of this study was to ...assess the vascular effects of insulin in the healthy and fatty liver. Methods Wistar rats were fed a control or a high fat diet (HFD) for 3 days, while treated with a placebo, the insulin-sensitizer metformin, or the iNOS inhibitor 1400W. Vascular responses to insulin were evaluated in the isolated liver perfusion model. Insulin sensitivity at the sinusoidal endothelium was tested by endothelium-dependent vasodilation in response to acetylcholine in the presence or absence of insulin and by the level of liver P-eNOS after an insulin injection. Results Rats from the HFD groups developed liver steatosis. Livers from the control group showed a dose-dependent hepatic vasodilation in response to insulin, which was blunted in livers from HFD groups. Metformin restored liver vascular insulin-sensitivity. Pre-treatment with insulin enhanced endothelium-dependent vasodilation of the hepatic vasculature and induced hepatic eNOS phosphorylation in control rats but not in HFD rats. Treatment with metformin or 1400W restored the capacity of insulin to enhance endothelium dependent vasodilation and insulin induced eNOS phosphorylation in HFD rats. Conclusions The administration of a HFD induces insulin resistance in the liver sinusoidal endothelium, which is mediated, at least in part, through iNOS upregulation and can be prevented by the administration of metformin. Insulin resistance at the hepatic vasculature can be detected earlier than inflammation or any other sign of advanced NALFD.
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