RESIK and RHESSI observations of the 20 September 2002 flare

Soft X-ray spectra 3.33 A - 6.15 A from the RESIK instrument on CORONAS-F constitute a unique database for the study of the physical conditions of solar flare plasmas, enabling the calculation of differential emission measures. The two RESIK channels for the shortest wavelengths overlap with the lower end of RHESSI spectral energy range, which is located around 3 keV, making it possible to compare both data sets. We aim to compare observations from RESIK and RHESSI spectrometers and cross-correlate these instruments. Observations are compared with synthetic spectra calculated based on the results of one-dimensional hydrodynamical (1D-HD) modelling. The analysis was performed for the flare on 20 September 2002. We estimated the geometry of the flaring loop, necessary for 1D-HD modelling, based on images from RHESSI and SOHO/EIT. The distribution of non-thermal electrons (NTEs) was determined from RHESSI spectra. The 1D-HD model assumes that non-thermal electrons with a power-law spectrum were injected at the apex of the flaring loop. The NTEs then heat and evaporate the chromosphere, filling the loop with hot and dense plasma radiating in soft X-rays. The total energy of electrons was constrained by comparing observed and calculated fluxes from GOES 1 - 8 A data. We determined the temperature and density at every point of the flaring loop throughout the evolution of the flare, calculating the resulting X-ray spectra. The synthetic spectra calculated based on the results of hydrodynamic modelling for the 20 September 2002 flare are consistent within a factor of two with the observed RESIK spectra during most of the duration of the flare. This discrepancy factor is probably related to the uncertainty on the cross-calibration between RESIK and RHESSI instruments

Heterogeneous electrocatalysis in porous cathodes of solid oxide fuel cells

A general physics-based model is developed for heterogeneous electrocatalysis in porous electrodes and used to predict and interpret the impedance of solid oxide fuel cells. This model describes the coupled processes of oxygen gas dissociative adsorption and surface diffusion of the oxygen intermediate to the triple phase boundary, where charge transfer occurs. The model accurately captures the Gerischer-like frequency dependence and the oxygen partial pressure dependence of the impedance of symmetric cathode cells. Digital image analysis of the microstructure of the cathode functional layer in four different cells directly confirms the predicted connection between geometrical properties and the impedance response. As in classical catalysis, the electrocatalytic activity is controlled by an effective Thiele modulus, which is the ratio of the surface diffusion length (mean distance from an adsorption site to the triple phase boundary) to the surface boundary layer length (square root of surface diffusivity divided by the adsorption rate constant). The Thiele modulus must be larger than one in order to maintain high surface coverage of reaction intermediates, but care must be taken in order to guarantee a sufficient triple phase boundary density. The model also predicts the Sabatier volcano plot with the maximum catalytic activity corresponding to the proper equilibrium surface fraction of adsorbed oxygen adatoms. These results provide basic principles and simple analytical tools to optimize porous microstructures for efficient electrocatalysis

Antioxidant status in the vitreous of eyes with rhegmatogenous retinal detachment with and without proliferative vitreoretinopathy, macular hole and epiretinal membrane

(1) Background: The aim of the study was to test the hypothesis that the antioxidant status in the vitreous body of eyes, which had been vitrectomized due to rhegmatogenous retinal detachment (RRD) with or without proliferative vitreoretinopathy (PVR), is higher than in eyes vitrectomized due to other retinal diseases. (2) Methods: four patient groups were analyzed: 22 eyes of patients with RRD without PVR, 27 eyes with RRD and PVR, 22 eyes with macular hole (MH) and 10 eyes with epiretinal membrane (ERM). Spectrophotometric methods were used to determine the total antioxidant status (TAS) values as well as superoxide dismutase (SOD) and glutathione reductase (GR) activities in the vitreous fluid samples. (3) Results: no significant differences in TAS values and antioxidant enzyme activities were observed among patient with RRD with and without PVR and with MH and ERM. The longer the duration of RRD leading to PVR and better postoperative visual acuity, the higher the TAS level. No significant differences were found between “macula on” and “macula off” subgroups within the RRD group and the RRD combined with PVR group. (4) Conclusions: The preliminary results do not support the thesis that the antioxidant status of vitrectomized eyes is different in patients with RRD with or without PVR in comparison to patients with MH and ERM. In patients with RRD, PVR presence and detached macula do not affect the values of TAS, SOD and GR in the vitreous fluid. The duration of the disease influences TAS in the vitreous in eyes with RRD complicated with PVR

Direct mass measurements of 19B, 22C, 29F, 31Ne, 34Na and other light exotic nuclei

We report on direct time-of-flight based mass measurements of 16 light neutron-rich nuclei. These include the first determination of the masses of the Borromean drip-line nuclei $^{19}$B, $^{22}$C and $^{29}$F as well as that of $^{34}$Na. In addition, the most precise determinations to date for $^{23}$N and $^{31}$Ne are reported. Coupled with recent interaction cross-section measurements, the present results support the occurrence of a two-neutron halo in $^{22}$C, with a dominant $\nu2s_{1/2}^2$ configuration, and a single-neutron halo in $^{31}$Ne with the valence neutron occupying predominantly the 2$p_{3/2}$ orbital. Despite a very low two-neutron separation energy the development of a halo in $^{19}$B is hindered by the 1$d_{5/2}^2$ character of the valence neutrons.Comment: 5 page

Phase Ib study of CP-868,596, a PDGFR inhibitor, combined with docetaxel with or without axitinib, a VEGFR inhibitor

BACKGROUND: Tumoural interstitial hypertension, possibly modulated by platelet-derived and vascular endothelial growth factor receptors (PDGFR and VEGFR), may mediate resistance to chemotherapy. METHODS: Forty-eight patients with advanced solid tumours received oral PDGFR inhibitor CP-868,596 (60-100 mg twice daily (BID)) and docetaxel (75-100 mg m⁻²), or CP-868,596 (60 mg BID), docetaxel (75 mg m⁻²), and VEGFR inhibitor axitinib (5 mg BID). RESULTS: The CP-868,596/docetaxel was escalated as above. The CP-868,596/docetaxel/axitinib was not dose escalated because of increased incidence of mucositis-like adverse events (AEs) with concurrent neutropenia relative to that expected for docetaxel. All tested regimens were tolerable, including 100 mg BID CP-868,596 (recommended phase II dose) plus 100 mg m⁻² docetaxel (maximum approved dose). Most treatment-emergent AEs were mild-moderate and reversible, commonly including nausea, diarrhoea, vomiting, constipation, fatigue, and anaemia (CP-868,596/docetaxel), and hypertension, lethargy, diarrhoea, and fatigue (CP-868,596/docetaxel/axitnib). Pharmacokinetics were unaffected by co-administration. Twenty-one patients achieved stable disease, including all seven evaluable on CP-868,596/docetaxel/axitinib. All nine CP-868,596/docetaxel/axitinib patients received therapy for a median of six (range, 3-16) cycles. CONCLUSIONS: The CP-868,596/docetaxel was well tolerated, but increased efficacy was not observed. Addition of axitinib delivered greater benefits than expected in the number of patients achieving prolonged stable disease with a moderate increase in AEs

Cancer cell differentiation heterogeneity and aggressive behavior in solid tumors

The differentiation stage of tumors is a central aspect in the histopathological classification of solid malignancies. The differentiation stage is strongly associated with tumor behavior, and generally an immature tumor is more aggressive than the more differentiated counterpart. While this is common knowledge in surgical pathology, the contribution of differentiation-related gene expression and functions to tumor behavior is often overlooked in the experimental, tumor biological setting. The mechanisms by which tumor cell differentiation stages are perturbed or affected are poorly explored but have recently come into focus with the introduction.of the tumor stem cell concept. While developmental biologists view the differentiation as a unidirectional event, pathologists and tumor biologists have introduced the concept of dedifferentiation to explain phenotypic changes occurring in solid tumors. In this review we discuss the impact of the tumor cell differentiation stage as used in surgical pathology. We further discuss knowledge gained from exploring the molecular basis of the differentiation and dedifferentiation processes in neuroblastoma and breast cancer, two tumor forms where the tumor cell differentiation concept is used in the clinical diagnostic work and where the tumor stem cell theory has been applied

Metabolic state alters economic decision making under risk in humans

Background: Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. Methodology/Principal Findings: We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. Conclusions/Significance: We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has significant implications for both real-world economic transactions and for aberrant decision-making in eating disorders and obesity

Urgent vitrectomy with vancomycin infusion, silicone oil endotamponade, and general antibiotic treatment in multiple cases of endophthalmitis from a single day of intravitreal injections—case series

The aim of this study was to report on the anatomical and functional results of surgical management of seven cases of endophthalmitis related to a single day of intravitreal aflibercept injections. Patients with signs of endophthalmitis who underwent aflibercept injections (seven eyes) performed on the same day were retrospectively evaluated. The data of visual acuity and optical coherence tomography (OCT) within nine months of the follow-up and the treatment and results of microbiological cultures are reported. Four of the total seven cases had a positive bacterial culture outcome (Streptococcus mitis). All patients underwent vitrectomy combined with phacoemulsification when the eyes were not pseudophakic, vancomycin infusion, and silicone oil tamponade within 24 h; additionally, systemic antibiotics were administered intravenously. The final best-corrected visual acuity (BCVA) after the treatment was finger counting or light perception in all cases, and all eyes were saved with disruption of the inner retinal layers and stabilization of the retina in regard to changes related to the wet age-related macular degeneration (AMD). Although the retinal anatomy was mostly preserved, most of the patients affected by Streptococcus mitis-induced endophthalmitis did not regain baseline vision after the therapy

Platelet-derived growth factor receptor-β, carrying the activating mutation D849N, accelerates the establishment of B16 melanoma

<p>Abstract</p> <p>Background</p> <p>Platelet-derived growth factor (PDGF)-BB and PDGF receptor (PDGFR)-β are mainly expressed in the developing vasculature, where PDGF-BB is produced by endothelial cells and PDGFR-β is expressed by mural cells, including pericytes. PDGF-BB is produced by most types of solid tumors, and PDGF receptor signaling participates in various processes, including autocrine stimulation of tumor cell growth, recruitment of tumor stroma fibroblasts, and stimulation of tumor angiogenesis. Furthermore, PDGF-BB-producing tumors are characterized by increased pericyte abundance and accelerated tumor growth. Thus, there is a growing interest in the development of tumor treatment strategies by blocking PDGF/PDGFR function. We have recently generated a mouse model carrying an activated PDGFR-β by replacing the highly conserved aspartic acid residue (D) 849 in the activating loop with asparagine (N). This allowed us to investigate, in an orthotopic tumor model, the role of increased stromal PDGFR-β signaling in tumor-stroma interactions.</p> <p>Methods</p> <p>B16 melanoma cells lacking PDGFR-β expression and either mock-transfected or engineered to express PDGF-BB, were injected alone or in combination with matrigel into mice carrying the activated PDGFR-β (D849N) and into wild type mice. The tumor growth rate was followed and the vessel status of tumors, i.e. total vessel area/tumor, average vessel surface and pericyte density of vessels, was analyzed after resection.</p> <p>Results</p> <p>Tumors grown in mice carrying an activated PDGFR-β were established earlier than those in wild-type mice. In this early phase, the total vessel area and the average vessel surface were higher in tumors grown in mice carrying the activated PDGFR-β (D849N) compared to wild-type mice, whereas we did not find a significant difference in the number of tumor vessels and the pericyte abundance around tumor vessels between wild type and mutant mice. At later phases of tumor progression, no significant difference in tumor growth rate was observed between wild type mice and mutant mice, although the pericyte coverage was higher around tumor vessels from mutant mice.</p> <p>Conclusion</p> <p>Our findings suggest that the activated PDGFR-β (D849N) in the host animal increased the total vessel area and the average vessel surface even in PDGF-negative tumors, resulting in a shorter lag phase during tumor establishment.</p