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We show in experiments that a long, underdense, relativistic proton bunch propagating in plasma undergoes the oblique instability, which we observe as filamentation. We determine a threshold value for the ratio between the bunch transverse size and plasma skin depth for the instability to occur. At the threshold, the outcome of the experiment alternates between filamentation and self-modulation instability (evidenced by longitudinal modulation into microbunches). Time-resolved images of the bunch density distribution reveal that filamentation grows to an observable level late along the bunch, confirming the spatiotemporal nature of the instability. We provide a rough estimate of the amplitude of the magnetic field generated in the plasma by the instability and show that the associated magnetic energy increases with plasma density.
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Experiments were performed on laser wakefield acceleration in the highly nonlinear regime. With laser powers P<250 TW and using an initial spot size larger than the matched spot size for guiding, we were able to accelerate electrons to energies E_{max}>2.5 GeV, in fields exceeding 500 GV m^{-1}, with more than 80 pC of charge at energies E>1 GeV. Three-dimensional particle-in-cell simulations show that using an oversized spot delays injection, avoiding beam loss as the wakefield undergoes length oscillation. This enables injected electrons to remain in the regions of highest accelerating fields and leads to a doubling of energy gain as compared to results from using half the focal length with the same laser.
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Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, self-modulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma-based accelerators and represent the first characterization of hosing.
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PURPOSE: To firstly examine the pain levels during distraction osteogenesis (DO) with lengthening nails (LN) in a large sample. METHODS: A total of 168 cases underwent DO of the tibia or femur with five different models of LN. Under a standardized medical regime, daily pain levels were noted as nominal rating scale (NRS) score (0-10) during the distraction phase. NRS scores and several potential influence factors (LN model, bone, approach, side, age, gender) were evaluated. RESULTS: The mean distraction length was 39.1 ± 14.4 mm. The average NRS score decreased from postoperative day 1 with 2.84 nonlinearly by 1.03 points (36.3%) over the course of 62 days to an average score of 1.81. The mean decrease during the first thirty days was 0.67(23.6%). Subgroup analysis did not reveal any influence factors. CONCLUSION: Pain levels during the distraction phase are overall low, continuously decreasing, and well manageable with mostly non-opioid analgesics.
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Osteogênese por Distração , Humanos , Fixadores Externos , Unhas , Resultado do Tratamento , Desigualdade de Membros Inferiores/cirurgia , Tíbia/cirurgia , Fêmur/cirurgia , DorRESUMO
Iodine-131 (I-131) radioisotope it causes the formation of free radicals, which lead to the formation of cell lesions and the reduction of cell viability. Thus, the use of radioprotectors, especially those from natural sources, which reduce the effects of radiation to healthy tissues, while maintaining the sensitivity of tumor cells, stands out. The objective of the present study was to evaluate the cytoprotective/radioprotective effects of whole grape juices manufactured from the conventional or organic production systems, whether or not exposed to ultraviolet (UV-C) light irradiation. The results showed that I-131 presented a cytotoxic effect on human hepatocellular cells (HepG2/C3A) at concentrations above 1.85 MBq/mL, after 24 and 48 hours of treatment, though all concentrations (0.0037 to 7.40 MBq/mL) were cytotoxic to non-tumor human lung fibroblast (MCR-5) cells, after 48 hours. However, grape juices (10 and 20 µL/mL) did not interfere with the cytotoxic effect of the therapeutic dose of I-131 on tumor cells within 48 hours of treatment, while protecting the non-tumor cells, probably due to its high antioxidant activity. In accordance with their nutraceutical potential, antioxidant and radioprotective activity, these data stimulate in vivo studies on the use of natural products as radioprotectants, such as grape juice, in order to confirm the positive beneficial potential in living organisms.
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Vitis , Antioxidantes/farmacologia , Humanos , Radioisótopos do Iodo , Compostos RadiofarmacêuticosRESUMO
Citizen science (CS) can help to tackle the emerging and worldwide problem of marine litter (ML), from collecting data to engaging different stakeholders. We reviewed what and how the scientific literature is reporting CS on ML to identify possible gaps to be improved. The 92 search results (separate occasions when 48 different CS initiatives were discussed across 85 publication records) revealed an under-representation of studies in developing regions. Most search results focused on the science of ML, whilst information regarding citizen scientists was commonly vague or missing, preventing critical analysis of good practices on this aspect. The studies concentrated on the shoreline and did not harmonize types and sizes of items collected, thus precluding data meta-analyses. The standardisation of CS methods and approaches and the detailed report of aspects related to citizen scientists are essential to support the science we need for the advances in CS efforts to face ML.
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Ciência do Cidadão , Análise de DadosRESUMO
Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant opportunistic pathogen with a great ability to form biofilms. Herein, the antimicrobial potential of Thymbra capitata essential oil (EO) against MRSA biofilms was investigated. The determination of the minimum inhibitory concentration (MIC) and the minimum lethal concentration (MLC) of the T. capitata EO was first investigated on a group of clinical isolates from septicaemias, diabetic foot ulcers and osteomyelitis. Biofilms were incubated with the EO at the MLC and its anti-biofilm potential was investigated. A strong antimicrobial activity was observed, with MIC and MLC values between 0·32 and 0·64 mg l-1 . However, the concentration of EO necessary for the eradication of planktonic cells was insufficient to significantly reduce the biofilm biomass of some isolates. Nevertheless, cell culturability and overall cellular metabolism was strongly reduced in all biofilms tested, only when the EO was tested. Contrary to the tested antibiotics, T. capitata EO showed a significant antimicrobial activity against MRSA biofilms, by reducing cellular metabolism and cellular culturability.
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Staphylococcus aureus Resistente à Meticilina , Óleos Voláteis , Antibacterianos/farmacologia , Biofilmes , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologiaRESUMO
Urea transporters (UTs) facilitate urea diffusion across cell membranes and play an important role in the urinary concentration mechanisms in the kidney. Herein, we injected cRNAs encoding for c-Myc-tagged murine UT-B, UT-A2 or UT-A3 (versus water-injected control) in Lithobates oocytes and evaluated oocyte surface protein expression with biotinylation and immunoblotting, urea uptake using [14C] counts and water permeability (P f ) by video microscopy. Immunoblots of UT-injected oocyte membranes revealed bands with a molecular weight consistent with that of a UT monomer (34â kDa), and UT-injected oocytes displayed significantly increased and phloretin-sensitive urea uptake and P f when compared to day-matched control oocytes. Subtracting the water-injected urea uptake or P f values from those of UT-injected oocytes yielded UT-dependent values*. We demonstrate for the first time that UT-A2 and UT-A3 can transport water, and we confirm that UT-B is permeable to water. Moreover, the [14C] urea*/P f * ratios fell in the sequence mUT-B>mUT-A2>mUT-A3, indicating that UTs can exhibit selectivity to urea and/or water. It is likely that specific kidney regions with high levels of UTs will exhibit increased urea and/or water permeabilities, directly influencing urine concentration. Furthermore, UT-mediated water transport activity must be considered when developing UT-inhibitors as novel diuretics.This article has an associated First Person interview with the first author of the paper.
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Proteínas de Membrana Transportadoras/metabolismo , Urina/fisiologia , Água/metabolismo , Animais , Anuros , Transporte Biológico , Radioisótopos de Carbono , Camundongos , Modelos Biológicos , Oócitos/metabolismo , Osmose , Permeabilidade , Fatores de Tempo , Ureia/metabolismo , Transportadores de UreiaRESUMO
Differentiation of cultured skeletal myoblasts is induced by extrinsic signals that include reduction in ambient mitogen concentration and increased cell density. Using an established murine myoblast cell line (C2C12), we have found that experimental reduction of the nucleoporin p62 (Nup62) content of myoblasts enhances differentiation in high-mitogen medium, while forced expression of Nup62 inhibits density-induced differentiation. In contrast, differentiation of myoblasts induced by low-mitogen medium was unaffected by ectopic Nup62 expression. Further analyses suggested that Nup62 content affects density-induced myoblast differentiation through a mechanism involving activation of p38 MAP kinase. Nuclear pore complex (NPC) composition, in particular changes in NUP62 content, may be altered during viral infection, differentiation, and in neoplastic growth. The results support a functional role for changes in Nup62 composition in NPCs and density-induced myogenic differentiation, and suggest a link between loss of Nup62 content and induction of an intracellular stress signaling pathways.
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Diferenciação Celular/genética , Desenvolvimento Muscular/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Animais , Linhagem Celular , Células Cultivadas , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Mioblastos/citologia , Mioblastos/metabolismo , Poro Nuclear/genética , Transdução de Sinais/genéticaRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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In this article, we briefly summarize the experiments performed during the first run of the Advanced Wakefield Experiment, AWAKE, at CERN (European Organization for Nuclear Research). The final goal of AWAKE Run 1 (2013-2018) was to demonstrate that 10-20 MeV electrons can be accelerated to GeV energies in a plasma wakefield driven by a highly relativistic self-modulated proton bunch. We describe the experiment, outline the measurement concept and present first results. Last, we outline our plans for the future. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.
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Laser-wakefield accelerators (LWFAs) are high acceleration-gradient plasma-based particle accelerators capable of producing ultra-relativistic electron beams. Within the strong focusing fields of the wakefield, accelerated electrons undergo betatron oscillations, emitting a bright pulse of X-rays with a micrometer-scale source size that may be used for imaging applications. Non-destructive X-ray phase contrast imaging and tomography of heterogeneous materials can provide insight into their processing, structure, and performance. To demonstrate the imaging capability of X-rays from an LWFA we have examined an irregular eutectic in the aluminum-silicon (Al-Si) system. The lamellar spacing of the Al-Si eutectic microstructure is on the order of a few micrometers, thus requiring high spatial resolution. We present comparisons between the sharpness and spatial resolution in phase contrast images of this eutectic alloy obtained via X-ray phase contrast imaging at the Swiss Light Source (SLS) synchrotron and X-ray projection microscopy via an LWFA source. An upper bound on the resolving power of 2.7 ± 0.3 µm of the LWFA source in this experiment was measured. These results indicate that betatron X-rays from laser wakefield acceleration can provide an alternative to conventional synchrotron sources for high resolution imaging of eutectics and, more broadly, complex microstructures.
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ETHNOPHARMACOLOGICAL RELEVANCE: Copaiba oleoresin has been used in folk medicine in the treatment of bronchitis, syphilis, skin diseases and ulcers due to its anti-inflammatory and antiseptic activities, but there is no information about major compounds oral absorption to support the traditional use. AIM OF STUDY: Considering the potential of copalic (CA) and kaurenoic acid (KA) - major biological activity (in vitro) diterpenes found in the oleoresin, this study aimed to evaluate the intestinal permeability of CA and KA using Caco-2 cells model as predictive test for oral drug absorption. MATERIALS AND METHODS: Chemical stability at pH 1.2 and 7.4 and plasma stability were evaluated to mimic physiological conditions of the gastrointestinal tract. The intestinal permeability of CA and KA was evaluated in Caco-2 cells in the presence and absence of the P-glycoprotein inhibitor verapamil. RESULTS: CA and KA were rapidly degraded at pH 1.2 (0.2â¯M Clark-Lubs buffer). At pH 7.4 (0.1â¯M phosphate buffer), CA was stable for up to 24â¯h and KA for up to 6â¯h. In human plasma, CA and KA can be considered stable for 24â¯h and 12â¯h at 37⯰C, respectively. Caco-2 cells were considered viable when incubated with CA or KA in the range of 3.9-250⯵M for 24â¯h. CA and KA exhibited moderate apparent permeability (Papp) of 4.67 (±0.08) ×â¯10-6 cm/s and 4.66 (±0.04) ×â¯10-6 cm/s, respectively. Simultaneous incubation with verapamil showed that P-glycoprotein does not play a relevant role on CA and KA oral absorption, with Papp of 4.48 (±0.26) ×â¯10-6 cm/s and 5.37 (±0.72) ×â¯10-6 cm/s observed for CA and KA, respectively. CONCLUSION: The oral absorption of both CA and KA is driven by mainly passive permeability, is not limited by p-glycoprotein, but enteric-coated dosage forms should be used to avoid chemical instability in the gastric pH.
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Diterpenos/farmacocinética , Fabaceae/química , Preparações de Plantas/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Células CACO-2 , Diterpenos/isolamento & purificação , Estabilidade de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Absorção Intestinal , Permeabilidade , Fatores de Tempo , Verapamil/farmacologiaRESUMO
BACKGROUND: Pharmacokinetic (PK)/pharmacodynamic (PD) modelling offers new insights to design protocols for sedation and analgesia in standing horses. OBJECTIVES: To evaluate the parameters and interactions between detomidine and methadone when given alone or combined in standing horses. STUDY DESIGN: Randomised, placebo-controlled, blinded, crossover. METHODS: Eight adult healthy horses were given six treatments intravenously: saline (SAL); detomidine (5 µg/kg bwt; DET); methadone (0.2 mg/kg bwt; MET) alone or combined with detomidine (2.5 [MLD], 5 [MMD] or 10 [MHD] µg/kg bwt). Venous blood samples were obtained at predetermined times between 0 and 360 min after drug administration. Plasma detomidine and methadone were measured using a single, liquid/liquid extraction technique by liquid chromatography coupled with a triple quadrupole mass spectrometer (LC-MS/MS). Sequential PK/PD modelling compared rival models, with and without PK and PD interaction between drugs, to fit the PD data including height of the head above the ground (HHAG), a visual analogue scale for sedation (VAS), electrical (ET), thermal (TT) and mechanical (MT) nociceptive thresholds and gastrointestinal motility (GIM) [1]. RESULTS: Two and three compartment models best described the PK of detomidine and methadone, respectively. Detomidine decreased its own clearance as well as the clearance of methadone. The interaction of methadone on the effect of detomidine revealed an infra-additive (partial antagonism) effect for HHAG (α = -1.33), VAS (α = -0.98) and GIM (α = -1.05), a positive potentiation for ET (pot = 0.0041) and TT (pot = 0.133) and a synergistic to additive effect for MT (α = 0.78). MAIN LIMITATIONS: This is a small experimental study. CONCLUSIONS: Different PK/PD interactions were demonstrated for each PD parameter and could be modelled in vivo. The modelling of our data will allow us to simulate and predict the effect of constant rate infusions of both drugs for future investigations.
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Analgésicos Opioides/farmacologia , Hipnóticos e Sedativos/farmacologia , Imidazóis/farmacocinética , Metadona/farmacocinética , Analgésicos Opioides/administração & dosagem , Animais , Estudos Cross-Over , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Cavalos , Hipnóticos e Sedativos/administração & dosagem , Imidazóis/administração & dosagem , Imidazóis/sangue , Imidazóis/farmacologia , Metadona/administração & dosagem , Metadona/sangue , Metadona/farmacologia , Distribuição AleatóriaRESUMO
Single-shot absorption measurements have been performed using the multi-keV x rays generated by a laser-wakefield accelerator. A 200 TW laser was used to drive a laser-wakefield accelerator in a mode which produced broadband electron beams with a maximum energy above 1 GeV and a broad divergence of ≈15 mrad FWHM. Betatron oscillations of these electrons generated 1.2±0.2×10^{6} photons/eV in the 5 keV region, with a signal-to-noise ratio of approximately 300â¶1. This was sufficient to allow high-resolution x-ray absorption near-edge structure measurements at the K edge of a titanium sample in a single shot. We demonstrate that this source is capable of single-shot, simultaneous measurements of both the electron and ion distributions in matter heated to eV temperatures by comparison with density functional theory simulations. The unique combination of a high-flux, large bandwidth, few femtosecond duration x-ray pulse synchronized to a high-power laser will enable key advances in the study of ultrafast energetic processes such as electron-ion equilibration.