Reduced-basis Output Bound Methods for Parametrised Partial Differential Equations

An efficient and reliable method for the prediction of outputs of interest of partial differential equations with affine parameter dependence is presented. To achieve efficiency we employ the reduced-basis method: a weighted residual Galerkin-type method, where the solution is projected onto low-dimensional spaces with certain problem-specific approximation properties. Reliability is obtained by a posteriori error estimation methods - relaxations of the standard error-residual equation that provide inexpensive but sharp and rigorous bounds for the error in outputs of interest. Special affine parameter dependence of the differential operator is exploited to develop a two-stage off-line/on-line blackbox computational procedure. In the on-line stage, for every new parameter value, we calculate the output of interest and an associated error bound. The computational complexity of the on-line stage of the procedure scales only with the dimension of the reduced-basis space and the parametric complexity of the partial differential operator; the method is thus ideally suited for the repeated and rapid evaluations required in the context of parameter estimation, design, optimization, and real-time control. The theory and corroborating numerical results are presented for: symmetric coercive problems (e.g. problems in conduction heat transfer), parabolic problems (e.g. unsteady heat transfer), noncoercive problems (e.g. the reduced-wave, or Helmholtz, equation), the Stokes problem (e.g flow of highly viscous fluids), and certain nonlinear equations (e.g. eigenvalue problems)

Biofluid modeling of the coupled eye-brain system and insights into simulated microgravity conditions

This work aims at investigating the interactions between the flow of fluids in the eyes and the brain and their potential implications in structural and functional changes in the eyes of astronauts, a condition also known as spaceflight associated neuro-ocular syndrome (SANS). To this end, we propose a reduced (0-dimensional) mathematical model of fluid flow in the eyes and brain, which is embedded into a simplified whole-body circulation model. In particular, the model accounts for: (i) the flows of blood and aqueous humor in the eyes; (ii) the flows of blood, cerebrospinal fluid and interstitial fluid in the brain; and (iii) their interactions. The model is used to simulate variations in intraocular pressure, intracranial pressure and blood flow due to microgravity conditions, which are thought to be critical factors in SANS. Specifically, the model predicts that both intracranial and intraocular pressures increase in microgravity, even though their respective trends may be different. In such conditions, ocular blood flow is predicted to decrease in the choroid and ciliary body circulations, whereas retinal circulation is found to be less susceptible to microgravity-induced alterations, owing to a purely mechanical component in perfusion control associated with the venous segments. These findings indicate that the particular anatomical architecture of venous drainage in the retina may be one of the reasons why most of the SANS alterations are not observed in the retina but, rather, in other vascular beds, particularly the choroid. Thus, clinical assessment of ocular venous function may be considered as a determinant SANS factor, for which astronauts could be screened on earth and in-flight

Deep-water macroalgae from the Canary Islands: new records and biogeographical relationships

Due to the geographical location and paleobiogeography of the Canary Islands, the seaweed flora contains macroalgae with different distributional patterns. In this contribution, the biogeographical relations of several new records of deep-water macroalgae recently collected around the Canarian archipelago are discussed. These are Bryopsidella neglecta (Berthotd) Rietema,Discosporangium mesarthrocarpum (Meneghini) Hauck, Hincksia onslowensis (Amsler et Kapraun)P.C. Silva, Syringoderma floridana Henry, Peyssonnelia harveyana J. Agardh, Cryptonemia seminervis(C. Agardh) J. Agardh, Botryodadia wynnei Ballantine, Gloiocladia blomquistii (Searles) R. E.Norris, PIahchrysis peltata (W. R. Taylor) P. Huv4 et H. Huv4, Leptofauchea brasiliensis Joly, and Sarcodiotheca divaricata W. R. Taylor. These new records, especially those in the Florideophyceae,support the strong affinity of the Canary Islands seaweed flora with the warm-temperate Mediterranean-Atlantic region. Some species are recorded for the first time from the east coast of the Atlantic Ocean, enhancing the biogeographic relations of the Canarian marine flora with that of the western Atlantic regions

Interfacial Strength and Physical Properties of Functionalized Graphene - Epoxy Nanocomposites

The toughness and coefficient of thermal expansion of a series of functionalized graphene sheet - epoxy nanocomposites are investigated. Functionalized graphene sheets are produced by splitting graphite oxide into single graphene sheets through a rapid thermal expansion process. These graphene sheets contain approx. 10% oxygen due to the presence of hydroxide, epoxide, and carboxyl functional groups which assist in chemical bond formation with the epoxy matrix. Intrinsic surface functionality is used to graft alkyl amine chains on the graphene sheets, and the addition of excess hardener insures covalent bonding between the epoxide matrix and graphene sheets. Considerable improvement in the epoxy dimensional stability is obtained. An increase in nanocomposite toughness is observed in some cases

Tween® preserves enzyme activity and stability in PLGA nanoparticles

Enzymes, as natural and potentially long-term treatment options, have become one of the most sought-after pharmaceutical molecules to be delivered with nanoparticles (NPs); however, their instability during formulation often leads to underwhelming results. Various molecules, including the Tween® polysorbate series, have demonstrated enzyme activity protection but are often used uncontrolled without optimization. Here, poly(lactic-co-glycolic) acid (PLGA) NPs loaded with β-glucosidase (β-Glu) solutions containing Tween® 20, 60, or 80 were compared. Mixing the enzyme with Tween® pre-formulation had no effect on particle size or physical characteristics, but increased the amount of enzyme loaded. More importantly, NPs made with Tween® 20:enzyme solutions maintained significantly higher enzyme activity. Therefore, Tween® 20:enzyme solutions ranging from 60:1 to 2419:1 mol:mol were further analyzed. Isothermal titration calorimetry analysis demonstrated low affinity and unquantifiable binding between Tween® 20 and β-Glu. Incorporating these solutions in NPs showed no effect on size, zeta potential, or morphology. The amount of enzyme and Tween® 20 in the NPs was constant for all samples, but a trend towards higher activity with higher molar rapports of Tween® 20:β-Glu was observed. Finally, a burst release from NPs in the first hour with Tween®:β-Glu solutions was the same as free enzyme, but the enzyme remained active longer in solution. These results highlight the importance of stabilizers during NP formulation and how optimizing their use to stabilize an enzyme can help researchers design more efficient and effective enzyme loaded NPs

Microfluidic technology for the production of hybrid nanomedicines

Microfluidic technologies have recently been applied as innovative methods for the production of a variety of nanomedicines (NMeds), demonstrating their potential on a global scale. The capacity to precisely control variables, such as the flow rate ratio, temperature, total flow rate, etc., allows for greater tunability of the NMed systems that are more standardized and automated than the ones obtained by well-known benchtop protocols. However, it is a crucial aspect to be able to obtain NMeds with the same characteristics of the previously optimized ones. In this study, we focused on the transfer of a production protocol for hybrid NMeds (H-NMeds) consisting of PLGA, Cholesterol, and Pluronic® F68 from a benchtop nanoprecipitation method to a microfluidic device. For this aim, we modified parameters such as the flow rate ratio, the concentration of core materials in the organic phase, and the ratio between PLGA and Cholesterol in the feeding organic phase. Outputs analysed were the chemico–physical properties, such as size, PDI, and surface charge, the composition in terms of %Cholesterol and residual %Pluronic® F68, their stability to lyophilization, and the morphology via atomic force and electron microscopy. On the basis of the results, even if microfluidic technology is one of the unique procedures to obtain industrial production of NMeds, we demonstrated that the translation from a benchtop method to a microfluidic one is not a simple transfer of already established parameters, with several variables to be taken into account and to be optimized

Classification of qualitative fieldnotes collected during quantitative sensory testing: a step towards the development of a new mixed methods approach in pain rseearch

Purpose: Quantitative sensory testing (QST) is a standardized method to assess somatosensory function. The collection of qualitative information, during the QST procedure, could be an interesting way to facilitate the characterization of altered sensory perception and the identification of different pain phenotypes. The aims of this study were 1) to classify qualitative fieldnotes of sensory abnormalities collected during an independent QST study, and 2) to generate a qualitative interview guide that could be included in the traditional QST procedure as a step towards the implementation of a mixed methods approach. Patients and Methods: QST data were collected from 48 chronic neuropathic pain patients treated with spinal cord stimulation (SCS). Three body areas, with or without SCS, were tested: the painful limb targeted by SCS, the contralateral area, and the ipsilateral upper limb. After each trial of each QST modality, patients were encouraged to report any sensory abnormalities they could identify with a pain quality scale or using their own words. Results: Qualitative self-reported sensory abnormalities were dichotomized into two groups: altered sensory intensities and altered sensory perceptions. Altered sensory intensities were classified as sensory loss or sensory gain subgroups. Altered sensory perceptions were classified as paresthesia and dysesthesia subgroups Overall, 630 qualitative fieldnotes of altered sensations were collected: 385 on the painful limb, 173 at the contralateral area, and 72 at the ipsilateral upper limb. Based on these qualitative data, we propose a standardized method to collect qualitative data involving 9 open- and close-ended questions and 21 codes. Conclusion: Our findings have highlighted the value of qualitative sensory evaluation during QST and constitute an important milestone in the development of a mixed methods protocol in phenotyping research

Knowledge translation to fitness trainers: A systematic review

<p>Abstract</p> <p>Background</p> <p>This study investigates approaches for translating evidence-based knowledge for use by fitness trainers. Specific questions were: Where do fitness trainers get their evidence-based information? What types of interventions are effective for translating evidence-based knowledge for use by fitness trainers? What are the barriers and facilitators to the use of evidence-based information by fitness trainers in their practice?</p> <p>Methods</p> <p>We describe a systematic review of studies about knowledge translation interventions targeting fitness trainers. Fitness trainers were defined as individuals who provide exercise program design and supervision services to the public. Nurses, physicians, physiotherapists, school teachers, athletic trainers, and sport team strength coaches were excluded.</p> <p>Results</p> <p>Of 634 citations, two studies were eligible for inclusion: a survey of 325 registered health fitness professionals (66% response rate) and a qualitative study of 10 fitness instructors. Both studies identified that fitness trainers obtain information from textbooks, networking with colleagues, scientific journals, seminars, and mass media. Fitness trainers holding higher levels of education are reported to use evidence-based information sources such as scientific journals compared to those with lower education levels, who were reported to use mass media sources. The studies identified did not evaluate interventions to translate evidence-based knowledge for fitness trainers and did not explore factors influencing uptake of evidence in their practice.</p> <p>Conclusion</p> <p>Little is known about how fitness trainers obtain and incorporate new evidence-based knowledge into their practice. Further exploration and specific research is needed to better understand how emerging health-fitness evidence can be translated to maximize its use by fitness trainers providing services to the general public.</p

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution