The Fermi Bubble as a Source of Cosmic Rays in the Energy Range > 10E15 eV

The {\it Fermi} Large Area Telescope has recently discovered two giant gamma-ray bubbles which extend north and south of the Galactic center with diameters and heights of the order of $H\sim 10$ kpc. We suggest that the periodic star capture processes by the Galactic supermassive black hole Sgr A$^*$, with a capture rate of $\tau_{\rm cap}^{-1}\sim 3\times 10^{-5}$ yr$^{-1}$ and an energy release of $W\sim 3\times 10^{52}$ erg per capture, can result in hot plasma injecting into the Galactic halo at a wind velocity of $u\sim 10^8$ cm s$^{-1}$. The periodic injection of hot plasma can produce a series of shocks. Energetic protons in the bubble are re-accelerated when they interact with these shocks. We show that for energy larger than $E> 10^{15}$ eV, the acceleration process can be better described by the stochastic second-order Fermi acceleration. We propose that hadronic cosmic rays (CRs) within the ``knee'' of the observed CR spectrum are produced by Galactic supernova remnants distributed in the Galactic disk. Re-acceleration of these particles in the Fermi Bubble produces CRs beyond the knee. With a mean CR diffusion coefficient in this energy range in the bubble $D_B\sim 3\times 10^{30}$ cm$^2$ s$^{-1}$, we can reproduce the spectral index of the spectrum beyond the knee and within. The conversion efficiency from shock energy of the bubble into CR energy is about 10\%. This model provides a natural explanation of the observed CR flux, spectral indices, and matching of spectra at the knee.Comment: 43 pages, 8 figues, to be published in the Astrophysical Journal; version 2, 45 pages, 8 figures, added references and corrected typo

Self-Nanoemulsifying Drug Delivery System (SNEDDS) Using Lipophilic Extract of Viscum album subsp. austriacum (Wiesb.) Vollm

Camila Faria de Amorim Pereira,1,* Michelle Nonato de Oliveira Melo,1,* Vania Emerich Bucco de Campos,2 Ivania Paiva Pereira,1 Adriana Passos Oliveira,1 Mariana Souza Rocha,1 João Vitor da Costa Batista,3,4 Valter Paes de Almeida,5 Irailson Thierry Monchak,5 Eduardo Ricci-Júnior,6 Rafael Garrett,7 Aline Gabrielle Alves Carvalho,7 Jane Manfron,5 Stephan Baumgartner,3,8,9 Carla Holandino1,3 1Multidisciplinary Laboratory of Pharmaceutical Sciences, Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 2Department of Pharmacy, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; 3Society for Cancer Research, Hiscia Institute, Arlesheim, Switzerland; 4Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland; 5Postgraduate Program in Pharmaceutical Sciences, Universidade Estadual de Ponta Grossa, Ponta Grossa, Paraná, Brazil; 6Galenic Development Laboratory (LADEG), Department of Drugs and Medicines, Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 7Metabolomics Laboratory, Chemistry Institute, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 8Institute of Integrative Medicine, University of Witten/Herdecke, Herdecke, Germany; 9Institute of Complementary and Integrative Medicine, University of Bern, Bern, Switzerland*These authors contributed equally to this workCorrespondence: Carla Holandino, Multidisciplinary Laboratory of Pharmaceutical Sciences, Universidade Federal do Rio de Janeiro, Faculty of Pharmacy, Block B basement, Room 34, 373, Carlos Chagas Filho Avenue, Cidade Universitária, Rio de Janeiro, RJ, 21941-902, Brazil, Email [email protected] Stephan Baumgartner, Institute of Complementary and Integrative Medicine, University of Bern, Bern, Switzerland, Email [email protected] and Purpose: Natural products are potential sources of anticancer components. Among various species, the lipophilic extract of the Viscum album subsp. austriacum (Wiesb.) Vollm. (VALE) has shown promising therapeutic potential. The present work aimed to qualify the plant source and characterize the extract’s chemical profile. In addition, a self-nanoemulsifying drug delivery system (SNEDDS) containing VALE (SNEDDS-VALE) was developed.Methods: V. album subsp. austriacum histochemistry was performed, and the chemical profile of VALE was analyzed by GC-MS. After the SNEEDS-VALE development, its morphology was visualized by transmission electron microscopy (TEM), while its stability was evaluated by the average droplet size, polydispersity index (PdI) and pH. Lastly, SNEDDS-VALE chemical stability was evaluated by LC-DAD-MS.Results: The histochemical analysis showed the presence of lipophilic compounds in the leaves and stems. The major compound in the VALE was oleanolic acid, followed by lupeol acetate and ursolic acid. SNEDDS was composed of medium chain triglyceride and Kolliphor® RH 40 (PEG-40 hydrogenated castor oil). A homogeneous, isotropic and stable nanoemulsion was obtained, with an average size of 36.87 ± 1.04 nm and PdI of 0.14 ± 0.02, for 14 weeks.Conclusion: This is the first histochemistry analysis of V. album subsp. austriacum growing on Pinus sylvestris L. which provided detailed information regarding its lipophilic compounds. A homogeneous, isotropic and stable SNEDDS-VALE was obtained to improve the low water solubility of VALE. Further, in vitro and in vivo experiments should be performed, in order to evaluate the antitumoral potential of SNEDDS-VALE. Keywords: Viscum album subsp. austriacum, mistletoe, lipophilic extract, oleanolic acid, SNEDD

Domain wall brane in squared curvature gravity

We suggest a thick braneworld model in the squared curvature gravity theory. Despite the appearance of higher order derivatives, the localization of gravity and various bulk matter fields is shown to be possible. The existence of the normalizable gravitational zero mode indicates that our four-dimensional gravity is reproduced. In order to localize the chiral fermions on the brane, two types of coupling between the fermions and the brane forming scalar is introduced. The first coupling leads us to a Schr\"odinger equation with a volcano potential, and the other a P\"oschl-Teller potential. In both cases, the zero mode exists only for the left-hand fermions. Several massive KK states of the fermions can be trapped on the brane, either as resonant states or as bound states.Comment: 18 pages, 5 figures and 1 table, references added, improved version to be published in JHE

The inventory of geological heritage of the state of São Paulo, Brazil: Methodological basis, results and perspectives

An inventory of geological sites based on solid and clear criteria is a first step for any geoconservation strategy. This paper describes the method used in the geoheritage inventory of the State of São Paulo, Brazil, and presents its main results. This inventory developed by the geoscientific community aimed to identify geosites with scientific value in the whole state, using a systematic approach. All 142 geosites representative of 11 geological frameworks were characterised and quantitatively evaluated according to their scientific value and risk of degradation, in order to establish priorities for their future management. An online database of the inventory is under construction, which will be available to be easily consulted and updated by the geoscientific community. All data were made available to the State Geological Institute as the backbone for the implementation of a future state geoconservation strategy.The authors acknowledge the Science Without Borders Programme, Process 075/2012, which supported this study and the São Paulo Research Foundation (FAPESP), Process 2011/17261-6. We also thanks C. Mazoca for his help with maps and figures.info:eu-repo/semantics/acceptedVersio

Spider mite web mediates anti-predator behaviour

Herbivores suffer significant mortality from predation and are therefore subject to natural selection on traits promoting predator avoidance and resistance. They can employ an array of strategies to reduce predation, for example through changes in behaviour, morphology and life history. So far, the anti-predator response studied most intensively in spider mites has been the avoidance of patches with high predation risk. Less attention has been given to the dense web produced by spider mites, which is a complex structure of silken threads that is thought to hinder predators. Here, we investigate the effects of the web produced by the red spider mite, Tetranychus evansi Baker & Pritchard, on its interactions with the predatory mite, Phytoseiulus longipes Evans. We tested whether female spider mites recognize predator cues and whether these can induce the spider mites to produce denser web. We found that the prey did not produce denser web in response to such cues, but laid more eggs suspended in the web, away from the leaf surface. These suspended eggs suffered less from predation by P. longipes than eggs that were laid on the leaf surface under the web. Thus, by altering their oviposition behaviour in response to predator cues, females of T. evansi protect their offspring

Biased-corrected richness estimates for the Amazonian tree flora

Amazonian forests are extraordinarily diverse, but the estimated species richness is very much debated. Here, we apply an ensemble of parametric estimators and a novel technique that includes conspecific spatial aggregation to an extended database of forest plots with up-to-date taxonomy. We show that the species abundance distribution of Amazonia is best approximated by a logseries with aggregated individuals, where aggregation increases with rarity. By averaging several methods to estimate total richness, we confirm that over 15,000 tree species are expected to occur in Amazonia. We also show that using ten times the number of plots would result in an increase to just ~50% of those 15,000 estimated species. To get a more complete sample of all tree species, rigorous field campaigns may be needed but the number of trees in Amazonia will remain an estimate for years to come

The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders

Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes

The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery

The International Human Epigenome Consortium (IHEC) coordinates the generation of a catalog of high-resolution reference epigenomes of major primary human cell types. The studies now presented (see the Cell Press IHEC web portal at http://www.cell.com/consortium/IHEC) highlight the coordinated achievements of IHEC teams to gather and interpret comprehensive epigenomic datasets to gain insights in the epigenetic control of cell states relevant for human health and disease

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health