The complex circumstellar environment of supernova 2023ixf.

The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare1,2, followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating3. Early serendipitous observations2,4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants.

The effect of krill oil supplementation on skeletal muscle function and size in older adults: A randomised controlled trial.

BACKGROUND & AIMS: The aim of this study was to determine the effect of krill oil supplementation, on muscle function and size in healthy older adults. METHODS: Men and women, aged above 65 years, with a BMI less than 35kg/m2, who participated in less than 1h per week of structured self-reported exercise, were enrolled in the study (NCT04048096) between March 2018 and March 2020. Participants were randomised to either control or krill oil supplements (4g/day) for 6 months in this double blind randomised controlled trial. At baseline, 6 weeks and 6 months, knee extensor maximal torque was measured as the primary outcome of the study. Secondary outcomes measured were grip strength, vastus lateralis muscle thickness, short performance physical battery test, body fat, muscle mass, blood lipids, glucose, insulin, and C-Reactive Protein, neuromuscular (M-Wave, RMS and voluntary activation), and erythrocyte fatty acid composition. RESULTS: A total of 102 men and women were enrolled in the study. Ninety-four participants (krill group (26 women and 23 men) and placebo group (27 women and 18 men)) completed the study (mean (SD): age 71.2 (5.1) years and weight 71.8 (12.3) kg). Six months supplementation with krill oil resulted in, an increase in knee extensor maximal torque, grip strength and vastus lateralis muscle thickness, relative to control (p<0.05). The 6-month treatment effects were 9.3% (95%CI: 2.8, 15.8%), 10.9% (95%CI: 8.3, 13.6%) and 3.5% (95%CI: 2.1, 4.9%) respectively. Increases in erythrocyte fatty acid profile were seen with krill oil for EPA 214% (95%CI: 166, 262%), DHA 36% (95%CI: 24, 48%) and the omega-3 index 61% (95%CI: 49, 73%), relative to control (p < 0.05). Krill oil resulted in an increased, relative to control (p < 0.05), M-Wave of 17% (95%CI: 12.7, 38.1%) but there was no effect of krill oil on RMS, voluntary activation, or on any other secondary outcomes such as performance of the short performance physical battery test or quality of life. CONCLUSION: Krill oil supplementation for 6 months results in statistically and clinically significant increases in muscle function and size in healthy older adults. GOV IDENTIFIER: NCT04048096.

A prospective study of weekly intensity modulated radiation therapy plan adaptation for head and neck cancer: improved target coverage and organ at risk sparing.

This prospective study of weekly CT scanning and plan adaption during H&N IMRT reports on the frequency of plan adaptations based on dosimetric differences between original and re-optimised IMRT plans. The volumetric and geometric change occurring in target volumes and salivary glands is also described. Ten H&N cancer patients underwent weekly planning CT imaging and re-optimisation of the IMRT plan if PTV or OAR coverage was unacceptable. Comparisons of PTV and parotid gland dosimetry between the original and adaptive plans were made. Parotid and submandibular gland volume changes and shift were calculated. Eight of ten patients required one or more plan adaptations, with 41% of adaptations occurring by fraction ten. Salivary glands reduced in volume, with a medial shift of the lateral border of the parotid gland and a superior shift of the submandibular gland. Change in PTV coverage did not correlate with weight loss or nutritional score. Inadequate PTV coverage, requiring plan adaptation, occurs early in the course of IMRT. A weekly Adaptive RT (ART) protocol results in significant improvement of PTV coverage. Implementation of a clinical ART protocol should include imaging and dose calculation within the first ten fractions.

Ultrastructural Characteristics of the Testicular Interstitial Endocrinocytes of Adult Rats Subjected to Total Sialoadenectomy.

The major salivary glands of rats release into the saliva and blood a wide spectrum of bioactive substances, essential for many organs, including the testes. Sialoadenectomy leads to the development of degenerative changes in the cells of the twisted testicular tubules. However, the effects of bioactive factors released by the major salivary glands on the morphology and function of Leydig cells remain little studied. Sialoadenectomy in adult rats led (in 1-4 weeks) to a decrease in the nuclear and cytoplasmatic areas of Leydig cells, violation of the plasmalemma integrity, dilatation of perinuclear space and agranular endoplasmatic reticulum vesicles, and to destruction of the mitochondria. Ultrastructural changes caused by sialoadenectomy completely resolved by week 6 of the experiment at the expense of compensatory activation of the synthesis of the major salivary gland factors by other sources in the organism of rats.

iPTF16geu: A multiply imaged, gravitationally lensed type Ia supernova.

We report the discovery of a multiply imaged, gravitationally lensed type Ia supernova, iPTF16geu (SN 2016geu), at redshift z = 0.409. This phenomenon was identified because the light from the stellar explosion was magnified more than 50 times by the curvature of space around matter in an intervening galaxy. We used high-spatial-resolution observations to resolve four images of the lensed supernova, approximately 0.3 arc seconds from the center of the foreground galaxy. The observations probe a physical scale of ~1 kiloparsec, smaller than is typical in other studies of extragalactic gravitational lensing. The large magnification and symmetric image configuration imply close alignment between the lines of sight to the supernova and to the lens. The relative magnifications of the four images provide evidence for substructures in the lensing galaxy.

Comparative Effects of CT Imaging Measurement on RECIST End Points and Tumor Growth Kinetics Modeling.

Quantitative assessments of tumor burden and modeling of longitudinal growth could improve phase II oncology trials. To identify obstacles to wider use of quantitative measures we obtained recorded linear tumor measurements from three published lung cancer trials. Model-based parameters of tumor burden change were estimated and compared with similarly sized samples from separate trials. Time-to-tumor growth (TTG) was computed from measurements recorded on case report forms and a second radiologist blinded to the form data. Response Evaluation Criteria in Solid Tumors (RECIST)-based progression-free survival (PFS) measures were perfectly concordant between the original forms data and the blinded radiologist re-evaluation (intraclass correlation coefficient = 1), but these routine interrater differences in the identification and measurement of target lesions were associated with an average 18-week delay (range, -20 to 55 weeks) in TTG (intraclass correlation coefficient = 0.32). To exploit computational metrics for improving statistical power in small clinical trials will require increased precision of tumor burden assessments.

ULTRASTRUCTURAL DIFFERENCES OF PRESPORES DEVELOPMENTAL STAGES AND MEIOSPORES OF SPECIES OF CLOSELY RELATED MICROSPORIDIA OF GENERA AMBLYOSPORA AND TRICHOCTOSPOREA (AMBLYOSPORIDAE: MICROSPORIDIA) FROM BLOOD-SUKING MOSQUITOES OF THE GENUS AEDES (DIPTERA: CULICIDAE).

Ultrastructure of prespore developmental stages, with emphasis on meiospores, has been examined in closely related genera of Microsporidia, Amblyospora and Trichoctosporea, isolated from larvae adipose tissue of mosquitoes Aedes in order to compare morphology of these parasites. Ultrastructural differences between Amblyospora and Trichoctosporea have been found to concern the secret filling episporal space of sporophorous vesicle, wall of mature spores, the polaroplast and membranes of thin coils of polar tubes. The episporal secret contributes to formation of meiospore wall and its structure is one of key systematic features to be considered in the identification of microsporidia.

Amine oxidase activity of ß-amyloid precursor protein modulates systemic and local catecholamine levels.

The catecholamines dopamine (DA), norepinephrine (NE) and epinephrine (E) are neurotransmitters and hormones that mediate stress responses in tissues and plasma. The expression of ß-amyloid precursor protein (APP) is responsive to stress and is high in tissues rich in catecholamines. We recently reported that APP is a ferroxidase, subsuming, in neurons and other cells, the iron-export activity that ceruloplasmin mediates in glia. Here we report that, like ceruloplasmin, APP also oxidizes synthetic amines and catecholamines catalytically (K(m) NE=0.27 mM), through a site encompassing its ferroxidase motif and selectively inhibited by zinc. Accordingly, APP knockout mice have significantly higher levels of DA, NE and E in brain, plasma and select tissues. Consistent with this, these animals have increased resting heart rate and systolic blood pressure as well as suppressed prolactin and lymphocyte levels. These findings support a role for APP in extracellular catecholaminergic clearance.

Electron microscopy of rat liver after intravenous injection of nanosized magnetite suspension.

Rat liver was examined by transmission electron microscopy after a single intravenous injection of nanosized magnetite suspension (0.1 g (Fe(3)O(4))/kg body weight). Magnetite particles were found in Kupffer's cells and hepatocytes. Accumulation of the particles by these two cell types was different. Morphometry of magnetite-containing granules in Kupffer's cells and nanoparticle agglomerations in hepatocytes was carried out. The ultrastructure of Kupffer's cell granules was described and the mechanism of penetration of nanosized magnetite particles into the cells was suggested. Nanosized magnetite particles were not completely eliminated over 40 days after a single injection.

The relative contribution of efflux and target gene mutations to fluoroquinolone resistance in recent clinical isolates of Pseudomonas aeruginosa.

The clinical utility of fluoroquinolones (FQs) for the treatment of Pseudomonas aeruginosa (PA) and other serious Gram-negative infections is currently decreasing due to the rapid emergence of resistance. Because previous studies have shown that efflux is a common mechanism contributing to FQ resistance in PA, one suggested approach to extend the longevity of this class of drugs is combination therapy with an efflux pump inhibitor (EPI). In order to determine the viability of this approach, it is necessary to understand the relative contribution of efflux- vs. target-mediated mechanisms of FQ resistance in the clinic. A set of 26 recent PA clinical isolates were characterized for antibiotic resistance profiles, efflux pump expression, topoisomerase mutations, and FQ susceptibility with and without an EPI. The contribution of OprM to the overall antibiotic resistance was assessed in a subset of these strains. Our results suggest that the co-administration of an EPI with FQs or other antibiotics currently in use would not be sufficient to combat the complexity of resistance mechanisms now present in many clinical isolates.

Supernova 2007bi as a pair-instability explosion.

Stars with initial masses such that 10M[symbol: see text] or= 140M[symbol: see text] (if such exist) develop oxygen cores with masses, M(core), that exceed 50M[symbol: see text], where high temperatures are reached at relatively low densities. Conversion of energetic, pressure-supporting photons into electron-positron pairs occurs before oxygen ignition and leads to a violent contraction which triggers a nuclear explosion that unbinds the star in a pair-instability supernova. Transitional objects with 100M[symbol: see text] < M(initial) < 140M[symbol: see text] may end up as iron-core-collapse supernovae following violent mass ejections, perhaps as a result of brief episodes of pair instability, and may already have been identified. Here we report observations of supernova SN 2007bi, a luminous, slowly evolving object located within a dwarf galaxy. We estimate the exploding core mass to be M(core) approximately 100M[symbol: see text], in which case theory unambiguously predicts a pair-instability supernova. We show that >3M[symbol: see text] of radioactive (56)Ni was synthesized during the explosion and that our observations are well fitted by models of pair-instability supernovae. This indicates that nearby dwarf galaxies probably host extremely massive stars, above the apparent Galactic stellar mass limit, which perhaps result from processes similar to those that created the first stars in the Universe.

[Use of the OTE-staining method for ultrathin sections on the example of microsporidia (Protozoa: Microsporidia)].

A novel method for staining ultrathin sections and examining organelles of taxonomic importance in microsporidian parasites was evaluated using oolong tea extract (OTE) and compared with traditional staining with uranyl acetate (UA). All basic intracellular structures of taxonomic significance were effectively stained with the OTE-staining method and additional layers of the polar filament with more clear boundaries between them were revealed. However, greater resolution and higher general contrast of several structures including membranes, layers of the envelope of mature spores, the structure of rough endoplasmic reticulum, Golgi complex, and nuclear chromatin were achieved with traditional UA-staining. The OTE-staining method has the advantage of being safe and preparations can be stored in light at room temperature with no loss in staining properties. However, greater staining time is required. We conclude that the OTE-staining method may be used as an alternative to traditional staining with UA with successful results.

Reduction of cerebral infarct volume by apocynin requires pretreatment and is absent in Nox2-deficient mice.

BACKGROUND AND PURPOSE: Reactive oxygen species (ROS) derived from Nox2-containing reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity is reportedly detrimental in cerebrovascular disease. However, ROS generation by other Nox isoforms may have a physiological role. No Nox2-selective inhibitors have yet been identified, and thus it is unclear whether isoform non-selective Nox inhibitors would necessarily improve outcome after stroke. We assessed the effect of apocynin on cerebrovascular ROS production and also on outcome following cerebral ischaemia when administered either before ischaemia or after cerebral reperfusion. The involvement of Nox2-containing NADPH oxidase in the effects of apocynin was assessed using Nox2(-/-) mice. EXPERIMENTAL APPROACH: Transient cerebral ischaemia was induced by 0.5 h middle cerebral artery occlusion followed by 23.5 h reperfusion. Mice received apocynin (2.5 mg.kg(-1), i.p.) either 0.5 h before ischaemia or 1 h after reperfusion. In situ superoxide production after cerebral ischaemia-reperfusion was measured in brain sections of wild-type mice at 24 h using dihydroethidium fluorescence. KEY RESULTS: Treatment with apocynin 0.5 h before ischaemia reduced total infarct volume, neurological impairment and mortality in wild-type but not Nox2(-/-) mice. Conversely, treatment with apocynin 1 h after initiation of reperfusion had no protective effect. Cerebral ischaemia and reperfusion increased superoxide production in the brain at 24 h, and pretreatment but not posttreatment with apocynin reduced superoxide levels. CONCLUSIONS AND IMPLICATIONS: Apocynin improves outcome following stroke when administered before ischaemia in wild-type but not Nox2(-/-) mice.

Mechanisms of augmented vasoconstriction induced by 5-hydroxytryptamine in aortic rings from spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: To test whether development of enhanced vasoconstriction to 5-hydroxytryptamine (5-HT; serotonin) in SHR was temporally related to hypertension, elevated vascular superoxide (O(2)(-)) levels, decreased NO bioavailability, or increased contractile effects of cyclooxygenase or rho-kinase and/or PKC. EXPERIMENTAL APPROACH: We examined systolic blood pressure (SBP), vascular O(2)(-), and 5-HT-induced contractile responses of aortic segments from 4- and 8-week-old WKY and SHR. KEY RESULTS: SBP was 35% higher in SHR than WKY at 4 weeks and 60% higher at 8 weeks. Contractile responses to 5-HT were similar in WKY and SHR at 4 weeks, but were markedly augmented in SHR at 8 weeks. The NO synthase inhibitor, L-NAME, enhanced contractile responses to 5-HT markedly in both strains at 4 weeks and in WKY at 8 weeks, but only very modestly in SHR at 8 weeks. These functional differences were associated with higher O(2)(-) levels in SHR versus WKY at 8 weeks, but not at 4 weeks. The rho-kinase inhibitor, Y-27632, and the PKC inhibitor, Ro 31-8220, each only modestly attenuated contractions in WKY and SHR in each age group, and their effects in each strain were more pronounced at 8 weeks. The cyclooxygenase inhibitor, indomethacin, had no effect on contractile responses. CONCLUSIONS AND IMPLICATIONS: Development of augmented vascular contractile responses to 5-HT in SHR is preceded by hypertension. It is associated with increased vascular O(2)(-) levels and reduced modulatory effects of NO, and is unlikely to be due to enhanced activity of rho-kinase, PKC or cyclooxygenase.

An equatorial oscillation in Saturn's middle atmosphere.

The middle atmospheres of planets are driven by a combination of radiative heating and cooling, mean meridional motions, and vertically propagating waves (which originate in the deep troposphere). It is very difficult to model these effects and, therefore, observations are essential to advancing our understanding of atmospheres. The equatorial stratospheres of Earth and Jupiter oscillate quasi-periodically on timescales of about two and four years, respectively, driven by wave-induced momentum transport. On Venus and Titan, waves originating from surface-atmosphere interaction and inertial instability are thought to drive the atmosphere to rotate more rapidly than the surface (superrotation). However, the relevant wave modes have not yet been precisely identified. Here we report infrared observations showing that Saturn has an equatorial oscillation like those found on Earth and Jupiter, as well as a mid-latitude subsidence that may be associated with the equatorial motion. The latitudinal extent of Saturn's oscillation shows that it obeys the same basic physics as do those on Earth and Jupiter. Future highly resolved observations of the temperature profile together with modelling of these three different atmospheres will allow us determine the wave mode, the wavelength and the wave amplitude that lead to middle atmosphere oscillation.

Temperature and composition of Saturn's polar hot spots and hexagon.

Saturn's poles exhibit an unexpected symmetry in hot, cyclonic polar vortices, despite huge seasonal differences in solar flux. The cores of both vortices are depleted in phosphine gas, probably resulting from subsidence of air into the troposphere. The warm cores are present throughout the upper troposphere and stratosphere at both poles. The thermal structure associated with the marked hexagonal polar jet at 77 degrees N has been observed for the first time. Both the warm cyclonic belt at 79 degrees N and the cold anticyclonic zone at 75 degrees N exhibit the hexagonal structure.

Jupiter cloud composition, stratification, convection, and wave motion: a view from new horizons.

Several observations of Jupiter's atmosphere made by instruments on the New Horizons spacecraft have implications for the stability and dynamics of Jupiter's weather layer. Mesoscale waves, first seen by Voyager, have been observed at a spatial resolution of 11 to 45 kilometers. These waves have a 300-kilometer wavelength and phase velocities greater than the local zonal flow by 100 meters per second, much higher than predicted by models. Additionally, infrared spectral measurements over five successive Jupiter rotations at spatial resolutions of 200 to 140 kilometers have shown the development of transient ammonia ice clouds (lifetimes of 40 hours or less) in regions of strong atmospheric upwelling. Both of these phenomena serve as probes of atmospheric dynamics below the visible cloud tops.

A phase II trial of imatinib (ST1571) in patients with c-kit expressing relapsed small-cell lung cancer: a CALGB and NCCTG study.

BACKGROUND: The aim of the present study was to evaluate the clinical activity of imatinib mesylate in patients with recurrent and refractory c-kit-expressing small-cell lung cancer. PATIENTS AND METHODS: Patients with c-kit-expressing SCLC (> or =1+ by immunohistochemistry) were enrolled in two groups. Arm A included patients with disease progression <3 months and arm B included patients with disease progression > or =3 months after previous treatment. Imatinib was administered at a dose of 400 mg b.i.d. continuously, with a cycle length of 28 days. A single stage Simon design with a planned interim analysis was used to evaluate the 16-week progression free rate in each arm. RESULTS: A total of 29 evaluable patients were entered into the study (seven in arm A, median age 68; 22 in arm B, median age 64.5). Median number of treatment cycles was one in both arms. Grade 3+ non-hematologic adverse events were seen in 15 (52%) patients, with nausea, vomiting, dyspnea, fatigue, anorexia and dehydration each occurring in at least 10% of patients. Median survival was 3.9 and 5.3 months and median time to progression was 1 and 1.1 months for arms A and B, respectively. Enrollment to arm A was temporarily suspended prior to reaching interim analysis due to striking early disease progression (29%), early deaths (29%) and patient refusal (42%). No objective responses and no confirmed stable disease > or =6 weeks were seen in either arm. Accrual was permanently terminated to both arms as only one patient was progression-free at 16 weeks. CONCLUSION: Imatinib failed to demonstrate any clinical activity in spite of patient selection for c-kit-expressing SCLC. Our results strengthen the collective evidence that prediction of efficacy of novel therapeutic agents based on target expression, rather than pathway activation (for example, through activating mutations), may not be a valid paradigm for drug development.

Titan's atmospheric temperatures, winds, and composition.

Temperatures obtained from early Cassini infrared observations of Titan show a stratopause at an altitude of 310 kilometers (and 186 kelvin at 15 degrees S). Stratospheric temperatures are coldest in the winter northern hemisphere, with zonal winds reaching 160 meters per second. The concentrations of several stratospheric organic compounds are enhanced at mid- and high northern latitudes, and the strong zonal winds may inhibit mixing between these latitudes and the rest of Titan. Above the south pole, temperatures in the stratosphere are 4 to 5 kelvin cooler than at the equator. The stratospheric mole fractions of methane and carbon monoxide are (1.6 +/- 0.5) x 10(-2) and (4.5 +/- 1.5) x 10(-5), respectively.