391 research outputs found

    Incompressible flow in porous media with fractional diffusion

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    In this paper we study the heat transfer with a general fractional diffusion term of an incompressible fluid in a porous medium governed by Darcy's law. We show formation of singularities with infinite energy and for finite energy we obtain existence and uniqueness results of strong solutions for the sub-critical and critical cases. We prove global existence of weak solutions for different cases. Moreover, we obtain the decay of the solution in LpL^p, for any p2p\geq2, and the asymptotic behavior is shown. Finally, we prove the existence of an attractor in a weak sense and, for the sub-critical dissipative case with α(1,2]\alpha\in (1,2], we obtain the existence of the global attractor for the solutions in the space HsH^s for any s>(N/2)+1αs > (N/2)+1-\alpha

    A maximum principle for the Muskat problem for fluids with different densities

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    We consider the fluid interface problem given by two incompressible fluids with different densities evolving by Darcy's law. This scenario is known as the Muskat problem for fluids with the same viscosities, being in two dimensions mathematically analogous to the two-phase Hele-Shaw cell. We prove in the stable case (the denser fluid is below) a maximum principle for the LL^\infty norm of the free boundary.Comment: 16 page

    Absence of squirt singularities for the multi-phase Muskat problem

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    In this paper we study the evolution of multiple fluids with different constant densities in porous media. This physical scenario is known as the Muskat and the (multi-phase) Hele-Shaw problems. In this context we prove that the fluids do not develop squirt singularities.Comment: 16 page

    Estudio teórico de algunas propiedades termodinámicas de los ácidos grasos obtenidos como destilados en la desodorización de aceites comestibles

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    Nowadays the feasibility of a change of technology in the deodorization stage of edible vegetable oil refining is being investigated. The proposed technology involves a modification in the composition of the distillates coming from the deodorization stage and their further treatment To design the apparatus which are required by the proposed technology it is necessary to study the physical properties of the distillates. The thermodynamic properties of the fatty acids: palmitic, stearic, oleic and linoleic, which are the principal components produced at the deodorization stage have been studied. The properties that have been studied were those corresponding to the critical point (critical temperature, pressure and volume), the vapour pressure-temperature relation and the latent heat of vaporisation. Different methods to estimate the above mentioned properties and some experimental published data have been compared.Estudio teórico de algunas propiedades termodinámicas de los ácidos grasos obtenidos como destilados en la desodorización de aceites comestibles Actualmente se investiga la viabilidad de un cambio en la tecnología de la desodorización de aceites comestibles que afecta a la composición de los destilados que se obtienen en el proceso y al tratamiento de los mismos. El diseño de los equipos que conlleva este cambio de tecnología requiere el estudio de propiedades físicas de los destilados. Se han estudiado algunas propiedades termodinámicas de los ácidos palmítico, esteárico, oleico y linoleico, componentes mayoritarios resultantes del proceso de desodorización. Las propiedades estudiadas han sido las correspondientes al punto crítico (temperatura, presión y volumen críticos), las curvas de presión de vapor en función de la temperatura y el calor latente de vaporización. Se han recogido distintos métodos de estimación de las mencionadas propiedades y algunos datos experimentales, y se han comparado los resultados obtenidos

    The Significance of the Location of Mutations for the Native-State Dynamics of Human Lysozyme

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    The conversion of human lysozyme into amyloid fibrils is associated with a rare but fatal hereditary form of nonneuropathic systemic amyloidosis. The accumulation of large amounts of aggregated protein is thought to be initiated by the formation of transient intermediate species of disease-related lysozyme variants, essentially due to the loss of global cooperativity under physiologically relevant conditions. Interestingly, all five naturally occurring, amyloidogenic, single-point mutations are located in the β-domain of lysozyme, the region that is predominantly unfolded during the formation of the transient intermediate species. Given the lack of known naturally occurring, amyloidogenic, single-point mutations in the α-domain, we chose three specific mutations to address the effects that location may have on native-state dynamics, as studied by hydrogen-deuterium (HD) exchange experiments analyzed by NMR spectroscopy, and mass spectrometry. We compared the effect of a destabilizing α-domain mutation (I23A) with that of the well-characterized I59T β-domain variant. We also investigated the effect of a mutation that has minor effects on native-state stability at the domain interface (I56V) and compared it with that of a variant with similar stability within the C-helix (I89V). We show that when variants have similar reduced native-state stabilities, the location of the mutation (I23A versus I59T) is crucial to the native-state dynamics, with the α-domain mutation having a significantly lower ability to populate transient intermediate species under physiologically relevant conditions. Interestingly, the mutation at the interface (I56V) has a greater effect in facilitating the formation of transient intermediate species at elevated temperatures compared with the variants containing α-domain mutations, even though this mutation results in only minor changes to the native-state stability of lysozyme. These findings reveal that the location of specific mutations is an important factor in determining the native-state dynamical properties of human lysozyme in the context of its propensity to populate the aggregation-prone transient intermediate species associated with pathogenic amyloid formation.This research was supported by the Biotechnology and Biological Sciences Research Council (BB/E019927/1 to C.M.D., C.V.R., and J.R.K.), the Medical Research Council (E.D.G. and C.M.D.), the Belgian Program of Interuniversity Attraction Poles administered by the Federal Office for Scientific Technical and Cultural Affairs (PAI numbers P6/19 and P7144 to C.M.D. and M.D.), the European Union’s Sixth Framework Program (LSHM-CT-2006-037525 to C.M.D. and M.D.), and Programme grants from the Wellcome Trust and the Leverhulme Trust (C.M.D.). It was also supported by a Korean Government Scholarship for Overseas Studies (M.A.), the Winston Churchill Foundation (C.L.H.), and Boerhinger Ingleheim funds (A.D.). The NMR facility at the Department of Chemistry, University of Cambridge, is supported in part by an EPSRC Core Capability grant (EP/K039520/1)

    Solidly Mounted Resonators with Carbon Nanotube Electrodes for Biosensing Applications

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    The work reported here shows a direct experimental comparison of the sensitivities of AlN solidly mounted resonators (SMR)-based biosensors fabricated with standard metal electrodes and with carbon nanotube electrodes. SMRs resonating at frequencies around 1.75 GHz have been fabricated, some devices using a thin film of multi-wall carbon nanotubes (CNTs) as the top electrode material and some identical devices using a chromium/gold electrode. Protein solutions with different concentrations were loaded on the top of the resonators and their responses to mass-load from physically adsorbed coatings were investigated. Results show that resonators using CNTs as the top electrode material exhibited higher frequency change for a given load due to the higher active surface area of a thin film of interconnecting CNTs compared to that of a metal thin film electrode and hence exhibited greater mass loading sensitivity. It is therefore concluded that the use of CNT electrodes on resonators for their use as gravimetric biosensors is viable and worthwhile

    AlN-based BAW resonators with CNT electrodes for gravimetric biosensing

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    Solidly mounted resonators (SMRs) with a top carbon nanotubes (CNTs) surface coating that doubles as an electrode and as a sensing layer have been fabricated. The influence of the CNTs on the frequency response of the resonators was studied by direct comparison to identical devices with a top metallic electrode. It was found that the CNTs introduced significantly less mass load on the resonators and these devices exhibited a greater quality factor, Q (>2000, compared to ∼1000 for devices with metal electrodes), which increases the gravimetric sensitivity of the devices by allowing the tracking of smaller frequency shifts. Protein solutions with different concentrations were loaded on the top of the resonators and their responses to mass-load from physically adsorbed coatings were investigated. Results show that resonators using CNTs as the top electrode exhibited a higher frequency change for a given load (∼0.25 MHz cm2 ng−1) compared to that of a metal thin film electrode (∼0.14 MHz cm2 ng−1), due to the lower mass of the CNT electrodes and their higher active surface area compared to that of a thin film metal electrode. It is therefore concluded that the use of CNT electrodes on resonators for their use as gravimetric biosensors is a significant improvement over metallic electrodes that are normally employed

    Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

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    Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology

    The disruption of JEN1 from Candida albicans impairs the transport of lactate

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    A lactate permease was biochemically identified in Candida albicans RM1000 presenting the following kinetic parameters at pH 5.0: Km 0.33 ± 0.09 mM and Vmax 0.85± 0.06 nmol s-1 mg dry wt-1. Lactate uptake was competitively inhibited by pyruvic and propionic acids; acetic acid behaved as a non-competitive substrate. An ORF homologous to Saccharomyces cerevisiae gene JEN1 was identified (CaJEN1). Deletions of both CaJEN1 alleles of C. albicans (resulting strain CPK2) resulted in the loss of all measurable lactate permease activity. No CaJEN1 mRNA was detectable in glucose-grown cells neither activity for the lactate transporter. In a medium containing lactic acid, CaJEN1 mRNA was detected in the RM1000 strain, and no expression was found in cells of CPK2 strain. In a strain deleted in the CaCAT8 genes the expression of CaJEN1 was significantly reduced, suggesting the role of this gene as an activator for CaJEN1 expression. Both in C. albicans and in S. cerevisiae cells CaJEN1-GFP fusion was expressed and targeted to the plasma membrane. The native CaJEN1 was not functional in a S. cerevisiae jen1Δ strain. Changing ser217-CTG codon (encoding leucine in S. cerevisiae) to a TCC codon restored the permease activity in S. cerevisiae, proving that the CaJEN1 gene codes for a monocarboxylate transporter.Deutsche Forschungsgemeinschaft (SFB 579).Fundação para a Ciência e a Tecnologia (FCT) - Programa Operacional “Ciência, Tecnologia, Inovação” (POCTI) - POCTI/1999/BME/36625 (Eixo 2, Medida 2.3, QCAIII-FEDER) , SFRH/BD/4699/2001 , PRAXIS XXI/BD/18198/98
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