A study on the sharp knee and fine structures of cosmic ray spectra

The paper investigates the overall and detailed features of cosmic ray (CR) spectra in the knee region using the scenario of nuclei-photon interactions around the acceleration sources. Young supernova remnants can be the physical realities of such kind of CR acceleration sites. The results show that the model can well explain the following problems simultaneously with one set of source parameters: the knee of CR spectra and the sharpness of the knee, the detailed irregular structures of CR spectra, the so-called "component B" of Galactic CRs, and the electron/positron excesses reported by recent observations. The coherent explanation serves as evidence that at least a portion of CRs might be accelerated at the sources similar to young supernova remnants, and one set of source parameters indicates that this portion mainly comes from standard sources or from a single source.Comment: 13 pages, 4 figures, accepted for publication in SCIENCE CHINA Physics, Mechanics & Astronomy

Fluid flow in the osteocyte mechanical environment : a fluid-structure interaction approach

Osteocytes are believed to be the primary sensor of mechanical stimuli in bone, which orchestrate osteoblasts and osteoclasts to adapt bone structure and composition to meet physiological loading demands. Experimental studies to quantify the mechanical environment surrounding bone cells are challenging, and as such, computational and theoretical approaches have modelled either the solid or fluid environment of osteocytes to predict how these cells are stimulated in vivo. Osteocytes are an elastic cellular structure that deforms in response to the external fluid flow imposed by mechanical loading. This represents a most challenging multi-physics problem in which fluid and solid domains interact, and as such, no previous study has accounted for this complex behaviour. The objective of this study is to employ fluid–structure interaction (FSI) modelling to investigate the complex mechanical environment of osteocytes in vivo. Fluorescent staining of osteocytes was performed in order to visualise their native environment and develop geometrically accurate models of the osteocyte in vivo. By simulating loading levels representative of vigorous physiological activity (3,000με compression and 300 Pa pressure gradient), we predict average interstitial fluid velocities (∼60.5μ m/s ) and average maximum shear stresses (∼11 Pa ) surrounding osteocytes in vivo. Interestingly, these values occur in the canaliculi around the osteocyte cell processes and are within the range of stimuli known to stimulate osteogenic responses by osteoblastic cells in vitro. Significantly our results suggest that the greatest mechanical stimulation of the osteocyte occurs in the cell processes, which, cell culture studies have indicated, is the most mechanosensitive area of the cell. These are the first computational FSI models to simulate the complex multi-physics mechanical environment of osteocyte in vivo and provide a deeper understanding of bone mechanobiology

The CALorimetric Electron Telescope (CALET) for high-energy astroparticle physics on the International Space Station

The CALorimetric Electron Telescope (CALET) is a space experiment, currently under development by Japan in collaboration with Italy and the United States, which will measure the flux of cosmic-ray electrons (and positrons) up to 20 TeV energy, of gamma rays up to 10 TeV, of nuclei with Z from 1 to 40 up to 1 PeV energy, and will detect gamma-ray bursts in the 7 keV to 20 MeV energy range during a 5 year mission. These measurements are essential to investigate possible nearby astrophysical sources of high energy electrons, study the details of galactic particle propagation and search for dark matter signatures. The main detector of CALET, the Calorimeter, consists of a module to identify the particle charge, followed by a thin imaging calorimeter (3 radiation lengths) with tungsten plates interleaving scintillating fibre planes, and a thick energy measuring calorimeter (27 radiation lengths) composed of lead tungstate logs. The Calorimeter has the depth, imaging capabilities and energy resolution necessary for excellent separation between hadrons, electrons and gamma rays. The instrument is currently being prepared for launch (expected in 2015) to the International Space Station ISS, for installation on the Japanese Experiment Module - Exposure Facility (JEM-EF)

Aquatic therapy for boys with Duchenne muscular dystrophy (DMD): an external pilot randomised controlled trial

Background: Standard treatment of Duchenne muscular dystrophy (DMD) includes regular physiotherapy. There are no data to show whether adding aquatic therapy (AT) to land-based exercises helps maintain motor function. We assessed the feasibility of recruiting and collecting data from boys with DMD in a parallel-group pilot randomised trial (primary objective), also assessing how intervention and trial procedures work. Methods: Ambulant boys with DMD aged 7–16 years established on steroids, with North Star Ambulatory Assessment (NSAA) score ≥8, who were able to complete a 10-m walk test without aids or assistance, were randomly allocated (1:1) to 6 months of either optimised land-based exercises 4 to 6 days/week, defined by local community physiotherapists, or the same 4 days/week plus AT 2 days/week. Those unable to commit to a programme, with >20% variation between NSAA scores 4 weeks apart, or contraindications to AT were excluded. The main outcome measures included feasibility of recruiting 40 participants in 6 months from six UK centres, clinical outcomes including NSAA, independent assessment of treatment optimisation, participant/therapist views on acceptability of intervention and research protocols, value of information (VoI) analysis and cost-impact analysis. Results: Over 6 months, 348 boys were screened: most lived too far from centres or were enrolled in other trials; 12 (30% of the targets) were randomised to AT (n = 8) or control (n = 4). The mean change in NSAA at 6 months was −5.5 (SD 7.8) in the control arm and −2.8 (SD 4.1) in the AT arm. Harms included fatigue in two boys, pain in one. Physiotherapists and parents valued AT but believed it should be delivered in community settings. Randomisation was unattractive to families, who had already decided that AT was useful and who often preferred to enrol in drug studies. The AT prescription was considered to be optimised for three boys, with other boys given programmes that were too extensive and insufficiently focused. Recruitment was insufficient for VoI analysis. Conclusions: Neither a UK-based RCT of AT nor a twice weekly AT therapy delivered at tertiary centres is feasible. Our study will help in the optimisation of AT service provision and the design of future research. Trial registration: ISRCTN4100295

Innate Synchronous Oscillations in Freely-Organized Small Neuronal Circuits

BACKGROUND: Information processing in neuronal networks relies on the network's ability to generate temporal patterns of action potentials. Although the nature of neuronal network activity has been intensively investigated in the past several decades at the individual neuron level, the underlying principles of the collective network activity, such as the synchronization and coordination between neurons, are largely unknown. Here we focus on isolated neuronal clusters in culture and address the following simple, yet fundamental questions: What is the minimal number of cells needed to exhibit collective dynamics? What are the internal temporal characteristics of such dynamics and how do the temporal features of network activity alternate upon crossover from minimal networks to large networks? METHODOLOGY/PRINCIPAL FINDINGS: We used network engineering techniques to induce self-organization of cultured networks into neuronal clusters of different sizes. We found that small clusters made of as few as 40 cells already exhibit spontaneous collective events characterized by innate synchronous network oscillations in the range of 25 to 100 Hz. The oscillation frequency of each network appeared to be independent of cluster size. The duration and rate of the network events scale with cluster size but converge to that of large uniform networks. Finally, the investigation of two coupled clusters revealed clear activity propagation with master/slave asymmetry. CONCLUSIONS/SIGNIFICANCE: The nature of the activity patterns observed in small networks, namely the consistent emergence of similar activity across networks of different size and morphology, suggests that neuronal clusters self-regulate their activity to sustain network bursts with internal oscillatory features. We therefore suggest that clusters of as few as tens of cells can serve as a minimal but sufficient functional network, capable of sustaining oscillatory activity. Interestingly, the frequencies of these oscillations are similar those observed in vivo

Suppression of AP1 Transcription Factor Function in Keratinocyte Suppresses Differentiation

Our previous study shows that inhibiting activator protein one (AP1) transcription factor function in murine epidermis, using dominant-negative c-jun (TAM67), increases cell proliferation and delays differentiation. To understand the mechanism of action, we compare TAM67 impact in mouse epidermis and in cultured normal human keratinocytes. We show that TAM67 localizes in the nucleus where it forms TAM67 homodimers that competitively interact with AP1 transcription factor DNA binding sites to reduce endogenous jun and fos factor binding. Involucrin is a marker of keratinocyte differentiation that is expressed in the suprabasal epidermis and this expression requires AP1 factor interaction at the AP1-5 site in the promoter. TAM67 interacts competitively at this site to reduce involucrin expression. TAM67 also reduces endogenous c-jun, junB and junD mRNA and protein level. Studies with c-jun promoter suggest that this is due to reduced transcription of the c-jun gene. We propose that TAM67 suppresses keratinocyte differentiation by interfering with endogenous AP1 factor binding to regulator elements in differentiation-associated target genes, and by reducing endogenous c-jun factor expression

Emergence of a Small-World Functional Network in Cultured Neurons

The functional networks of cultured neurons exhibit complex network properties similar to those found in vivo. Starting from random seeding, cultures undergo significant reorganization during the initial period in vitro, yet despite providing an ideal platform for observing developmental changes in neuronal connectivity, little is known about how a complex functional network evolves from isolated neurons. In the present study, evolution of functional connectivity was estimated from correlations of spontaneous activity. Network properties were quantified using complex measures from graph theory and used to compare cultures at different stages of development during the first 5 weeks in vitro. Networks obtained from young cultures (14 days in vitro) exhibited a random topology, which evolved to a small-world topology during maturation. The topology change was accompanied by an increased presence of highly connected areas (hubs) and network efficiency increased with age. The small-world topology balances integration of network areas with segregation of specialized processing units. The emergence of such network structure in cultured neurons, despite a lack of external input, points to complex intrinsic biological mechanisms. Moreover, the functional network of cultures at mature ages is efficient and highly suited to complex processing tasks

Soroprevalência de anticorpos do vírus SARS-CoV-2 em escolares no município de São Paulo, 2020

OBJECTIVE: To estimate seroprevalence of SARS-CoV-2 antibodies in schoolchildren aged 4 to 14 years living in the city of São Paulo, according to clinical, demographic, epidemiological, and social variables, during the school closure period as a measure against covid-19 spread. METHODS: A serological survey was made in September 2020 with a random sample stratified by school system (municipal public, state public and private) type. A venous blood sample was collected using the Wondfo SARS-CoV-2 Antibody Test (lateral flow method) for detection of total SARS-CoV-2 virus antibodies. Semi-structured questionnaires were applied to collect clinical, demographic, social, and epidemiological data. RESULTS: Seroprevalence of SARS-CoV-2 antibodies in schoolchildren was of 16.6% (95%CI 15.4–17.8). The study found higher seroprevalence in the municipal (18.5%; 95%CI 16.6–20.6) and state (16.2%; 95%CI 14.4–18.2) public school systems compared to the private school system (11.7; 95%CI 10.0–13.7), among black and brown students (18.4%; 95%CI 16.8–20.2) and in the most vulnerable social stratum (18.5 %;95%CI 16.9–20.2). Lower seroprevalence was identified in schoolchildren who reported following the recommended protective measures against covid-19. CONCLUSION: Seroprevalence of SARS-CoV-2 antibodies is found mainly in the most socially vulnerable schoolchildren. This study can contribute to support public policies that reinforce the importance of suspending face-to-face classes and developing strategies aimed at protective measures and monitoring of the serological status of those who have not yet been included in the vaccination schedule.OBJETIVO: Estimar a soroprevalência de anticorpos do vírus SARS-CoV-2 em escolares de quatro a 14 anos de idade residentes no município de São Paulo, segundo variáveis clínicas, demográficas, epidemiológicas e sociais, durante o período de fechamento das escolas como medida de controle da covid-19. MÉTODOS: Realizou-se um inquérito sorológico em setembro de 2020 com amostra aleatória estratificada por tipo de rede de ensino (pública municipal, pública estadual e privada). Foi coletada amostra de sangue venoso utilizando-se o teste de imunoensaio de fluxo lateral da fabricante Wondfo para detecção de anticorpos totais contra o vírus SARS-CoV-2. Aplicaram-se questionários semiestruturados para o levantamento de dados clínicos, demográficos, sociais e epidemiológicos. RESULTADOS: A soroprevalência de anticorpos do vírus SARS-CoV-2 em escolares foi de 16,6% (IC95% 15,4–17,8). O estudo encontrou soroprevalências mais elevadas na rede pública municipal (18,5%; IC95% 16,6–20,6) e estadual (16,2%; IC95% 14,4–18,2) em relação à rede privada (11,7; IC95% 10,0–13,7) e entre escolares da raça/cor preta e parda (18,4%; IC95% 16,8–20,2) e no estrato social mais vulnerável (18,5%; IC95% 16,9–20,2). A pesquisa identificou menores soroprevalências nos escolares que relataram seguir as medidas recomendadas de proteção contra a covid-19. CONCLUSÃO: A soroprevalência de anticorpos contra o vírus SARS-CoV-2 atinge principalmente os escolares socialmente mais vulneráveis. Este estudo pode contribuir para embasar políticas públicas que reforcem a importância da suspensão das aulas presenciais e da necessidade de estratégias de medidas de proteção e acompanhamento do status sorológico daqueles que ainda não foram contemplados no calendário vacinal

Requirements for F-BAR Proteins TOCA-1 and TOCA-2 in Actin Dynamics and Membrane Trafficking during Caenorhabditis elegans Oocyte Growth and Embryonic Epidermal Morphogenesis

The TOCA family of F-BAR–containing proteins bind to and remodel lipid bilayers via their conserved F-BAR domains, and regulate actin dynamics via their N-Wasp binding SH3 domains. Thus, these proteins are predicted to play a pivotal role in coordinating membrane traffic with actin dynamics during cell migration and tissue morphogenesis. By combining genetic analysis in Caenorhabditis elegans with cellular biochemical experiments in mammalian cells, we showed that: i) loss of CeTOCA proteins reduced the efficiency of Clathrin-mediated endocytosis (CME) in oocytes. Genetic interference with CeTOCAs interacting proteins WSP-1 and WVE-1, and other components of the WVE-1 complex, produced a similar effect. Oocyte endocytosis defects correlated well with reduced egg production in these mutants. ii) CeTOCA proteins localize to cell–cell junctions and are required for proper embryonic morphogenesis, to position hypodermal cells and to organize junctional actin and the junction-associated protein AJM-1. iii) Double mutant analysis indicated that the toca genes act in the same pathway as the nematode homologue of N-WASP/WASP, wsp-1. Furthermore, mammalian TOCA-1 and C. elegans CeTOCAs physically associated with N-WASP and WSP-1 directly, or WAVE2 indirectly via ABI-1. Thus, we propose that TOCA proteins control tissues morphogenesis by coordinating Clathrin-dependent membrane trafficking with WAVE and N-WASP–dependent actin-dynamics

The CALorimetric Electron Telescope (CALET) for high-energy astroparticle physics on the International Space Station

The CALorimetric Electron Telescope (CALET) is a space experiment, currently under development by Japan in collaboration with Italy and the United States, which will measure the flux of cosmic-ray electrons (and positrons) up to 20 TeV energy, of gamma rays up to 10 TeV, of nuclei with Z from 1 to 40 up to 1 PeV energy, and will detect gamma-ray bursts in the 7 keV to 20 MeV energy range during a 5 year mission. These measurements are essential to investigate possible nearby astrophysical sources of high energy electrons, study the details of galactic particle propagation and search for dark matter signatures. The main detector of CALET, the Calorimeter, consists of a module to identify the particle charge, followed by a thin imaging calorimeter (3 radiation lengths) with tungsten plates interleaving scintillating fibre planes, and a thick energy measuring calorimeter (27 radiation lengths) composed of lead tungstate logs. The Calorimeter has the depth, imaging capabilities and energy resolution necessary for excellent separation between hadrons, electrons and gamma rays. The instrument is currently being prepared for launch (expected in 2015) to the International Space Station ISS, for installation on the Japanese Experiment Module - Exposure Facility (JEM-EF)