81 research outputs found
Inducing vortices in a Bose-Einstein condensate using holographically produced light beams
In this paper we demonstrate a technique that can create out-of-equilibrium
vortex configurations with almost arbitrary charge and geometry in a
Bose-Einstein condensate. We coherently transfer orbital angular momentum from
a holographically generated light beam to a Rubidium 87 condensate using a
two-photon stimulated Raman process. Using matter wave interferometry, we
verify the phase pattern imprinted onto the atomic wave function for a single
vortex and a vortex-antivortex pair. In addition to their phase winding, the
vortices created with this technique have an associated hyperfine spin texture.Comment: 4 pages, 5 figure
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Culture bag systems for clinical applications of adult human neural crest-derived stem cells
Introduction
Facing the challenging treatment of neurodegenerative diseases as well as complex craniofacial injuries such as those common after cancer therapy, the field of regenerative medicine increasingly relies on stem cell transplantation strategies. Here, neural crest-derived stem cells (NCSCs) offer many promising applications, although scale up of clinical-grade processes prior to potential transplantations is currently limiting. In this study, we aimed to establish a clinical-grade, cost-reducing cultivation system for NCSCs isolated from the adult human nose using cGMP-grade Afc-FEP bags.
Methods
We cultivated human neural crest-derived stem cells from inferior turbinate (ITSCs) in a cell culture bag system using Afc-FEP bags in human blood plasma-supplemented medium. Investigations of viability, proliferation and expression profile of bag-cultured ITSCs were followed by DNA-content and telomerase activity determination. Cultivated ITSCs were introduced to directed in vitro differentiation assays to assess their potential for mesodermal and ectodermal differentiation. Mesodermal differentiation was determined using an enzyme activity assay (alkaline phosphatase, ALP), respective stainings (Alizarin Red S, Von Kossa and Oil Red O), and RT-PCR, while immunocytochemistry and synaptic vesicle recycling were applied to assay neuroectodermal differentiation of ITSCs.
Results
When cultivated within Afc-FEP bags, ITSCs grew three-dimensionally in a human blood plasma-derived matrix, thereby showing unchanged morphology, proliferation capability, viability and expression profile in comparison to three dimensionally-cultured ITSCs growing in standard cell culture plastics. Genetic stability of bag-cultured ITSCs was further accompanied by unchanged telomerase activity. Importantly, ITSCs retained their potential to differentiate into mesodermal cell types, particularly including ALP-active, Alizarin Red S-, and Von Kossa-positive osteogenic cell types, as well as adipocytes positive in Oil Red O assays. Bag culture further did not affect the potential of ITSCs to undergo differentiation into neuroectodermal cell types coexpressing β-III-tubulin and MAP2 and exhibiting the capability for synaptic vesicle recycling.
Conclusions
Here, we report for the first time the successful cultivation of human NCSCs within cGMP-grade Afc-FEP bags using a human blood plasma-supplemented medium. Our findings particularly demonstrate the unchanged differentiation capability and genetic stability of the cultivated NCSCs, suggesting the great potential of this culture system for future medical applications in the field of regenerative medicine
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1,8-cineol potentiates IRF3-mediated antiviral response in human stem cells and an ex vivo model of rhinosinusitis
Common cold is one of the most frequent human inflammatory diseases caused by viruses and can facilitate bacterial super-infections resulting in sinusitis or pneumonia. The active ingredient of the drug Soledum, 1,8-cineole, is commonly applied for treating inflammatory diseases of the respiratory tract. However, the potential of 1,8-cineole for treating primary viral infections of the respiratory tract remains unclear.
In the present study, we demonstrate for the first time that 1,8-cineole potentiates Poly(I:C)-induced activity of the anti-viral transcription factor Interferon Regulatory Factor 3, while simultaneously reducing pro-inflammatory NF-κB-activity in human cell lines, inferior turbinate stem cells (ITSCs) and ex vivo cultivated human nasal mucosa. Co-treatment of cell lines with Poly(I:C) and 1,8-cineole resulted in significantly increased IRF3 reporter gene activity compared to Poly(I:C) alone, whereas NF-κB-activity was reduced. Accordingly, 1,8-cineole- and Poly(I:C)-treatment led to increased nuclear translocation of IRF3 in ITSCs and a human ex vivo model of rhinosinusitis compared to the Poly(I:C)-treated approach. Nuclear translocation of IRF3 was significantly increased in ITSCs and slice cultures treated with LPS and 1,8-cineole compared to the LPS-treated cells mimicking bacterial infection. Our findings strongly suggest that 1,8-cineole potentiates the antiviral activity of IRF3 in addition to its inhibitory effect on pro-inflammatory NF-κB-signalling and may thus broaden its field of application
The epidemiological impact of childhood influenza vaccination using live-attenuated influenza vaccine (LAIV) in Germany: predictions of a simulation study
Rose MA, Damm O, Greiner W, et al. The epidemiological impact of childhood influenza vaccination using live-attenuated influenza vaccine (LAIV) in Germany: predictions of a simulation study. BMC Infectious Diseases. 2014;14(1): 40.Background
Routine annual influenza vaccination is primarily recommended for all persons aged 60 and above and for people with underlying chronic conditions in Germany. Other countries have already adopted additional childhood influenza immunisation programmes. The objective of this study is to determine the potential epidemiological impact of implementing paediatric influenza vaccination using intranasally administered live-attenuated influenza vaccine (LAIV) in Germany.
Methods
A deterministic age-structured model is used to simulate the population-level impact of different vaccination strategies on the transmission dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate the effects of adding a LAIV-based immunisation programme targeting children 2 to 17 years of age to the existing influenza vaccination policy. The data used in the model is based on published evidence complemented by expert opinion.
Results
In our model, additional vaccination of children 2 to 17 years of age with LAIV leads to the prevention of 23.9 million influenza infections and nearly 16 million symptomatic influenza cases within 10 years. This reduction in burden of disease is not restricted to children. About one third of all adult cases can indirectly be prevented by LAIV immunisation of children.
Conclusions
Our results demonstrate that vaccinating children 2–17 years of age is likely associated with a significant reduction in the burden of paediatric influenza. Furthermore, annual routine childhood vaccination against seasonal influenza is expected to decrease the incidence of influenza among adults and older people due to indirect effects of herd protection. In summary, our model provides data supporting the introduction of a paediatric influenza immunisation programme in Germany
Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis
Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis
Elastic SCAD as a novel penalization method for SVM classification tasks in high-dimensional data
<p>Abstract</p> <p>Background</p> <p>Classification and variable selection play an important role in knowledge discovery in high-dimensional data. Although Support Vector Machine (SVM) algorithms are among the most powerful classification and prediction methods with a wide range of scientific applications, the SVM does not include automatic feature selection and therefore a number of feature selection procedures have been developed. Regularisation approaches extend SVM to a feature selection method in a flexible way using penalty functions like LASSO, SCAD and Elastic Net.</p> <p>We propose a novel penalty function for SVM classification tasks, Elastic SCAD, a combination of SCAD and ridge penalties which overcomes the limitations of each penalty alone.</p> <p>Since SVM models are extremely sensitive to the choice of tuning parameters, we adopted an interval search algorithm, which in comparison to a fixed grid search finds rapidly and more precisely a global optimal solution.</p> <p>Results</p> <p>Feature selection methods with combined penalties (Elastic Net and Elastic SCAD SVMs) are more robust to a change of the model complexity than methods using single penalties. Our simulation study showed that Elastic SCAD SVM outperformed LASSO (<it>L</it><sub>1</sub>) and SCAD SVMs. Moreover, Elastic SCAD SVM provided sparser classifiers in terms of median number of features selected than Elastic Net SVM and often better predicted than Elastic Net in terms of misclassification error.</p> <p>Finally, we applied the penalization methods described above on four publicly available breast cancer data sets. Elastic SCAD SVM was the only method providing robust classifiers in sparse and non-sparse situations.</p> <p>Conclusions</p> <p>The proposed Elastic SCAD SVM algorithm provides the advantages of the SCAD penalty and at the same time avoids sparsity limitations for non-sparse data. We were first to demonstrate that the integration of the interval search algorithm and penalized SVM classification techniques provides fast solutions on the optimization of tuning parameters.</p> <p>The penalized SVM classification algorithms as well as fixed grid and interval search for finding appropriate tuning parameters were implemented in our freely available R package 'penalizedSVM'.</p> <p>We conclude that the Elastic SCAD SVM is a flexible and robust tool for classification and feature selection tasks for high-dimensional data such as microarray data sets.</p
Electrospun PLLA Nanofiber Scaffolds and Their Use in Combination with BMP-2 for Reconstruction of Bone Defects
Introduction
Adequate migration and differentiation of mesenchymal stem cells is essential for regeneration of large bone defects. To achieve this, modern graft materials are becoming increasingly important. Among them, electrospun nanofiber scaffolds are a promising approach, because of their high physical porosity and potential to mimic the extracellular matrix (ECM).
Materials and Methods
The objective of the present study was to examine the impact of electrospun PLLA nanofiber scaffolds on bone formation in vivo, using a critical size rat calvarial defect model. In addition we analyzed whether direct incorporation of bone morphogenetic protein 2 (BMP-2) into nanofibers could enhance the osteoinductivity of the scaffolds. Two critical size calvarial defects (5 mm) were created in the parietal bones of adult male Sprague-Dawley rats. Defects were either (1) left unfilled, or treated with (2) bovine spongiosa, (3) PLLA scaffolds alone or (4) PLLA/BMP-2 scaffolds. Cranial CT-scans were taken at fixed intervals in vivo. Specimens obtained after euthanasia were processed for histology, histomorphometry and immunostaining (Osteocalcin, BMP-2 and Smad5).
Results
PLLA scaffolds were well colonized with cells after implantation, but only showed marginal ossification. PLLA/BMP-2 scaffolds showed much better bone regeneration and several ossification foci were observed throughout the defect. PLLA/BMP-2 scaffolds also stimulated significantly faster bone regeneration during the first eight weeks compared to bovine spongiosa. However, no significant differences between these two scaffolds could be observed after twelve weeks. Expression of osteogenic marker proteins in PLLA/BMP-2 scaffolds continuously increased throughout the observation period. After twelve weeks osteocalcin, BMP-2 and Smad5 were all significantly higher in the PLLA/BMP-2 group than in all other groups.
Conclusion
Electrospun PLLA nanofibers facilitate colonization of bone defects, while their use in combination with BMP-2 also increases bone regeneration in vivo and thus combines osteoconductivity of the scaffold with the ability to maintain an adequate osteogenic stimulus
Quantum-centric Supercomputing for Materials Science: A Perspective on Challenges and Future Directions
Computational models are an essential tool for the design, characterization,
and discovery of novel materials. Hard computational tasks in materials science
stretch the limits of existing high-performance supercomputing centers,
consuming much of their simulation, analysis, and data resources. Quantum
computing, on the other hand, is an emerging technology with the potential to
accelerate many of the computational tasks needed for materials science. In
order to do that, the quantum technology must interact with conventional
high-performance computing in several ways: approximate results validation,
identification of hard problems, and synergies in quantum-centric
supercomputing. In this paper, we provide a perspective on how quantum-centric
supercomputing can help address critical computational problems in materials
science, the challenges to face in order to solve representative use cases, and
new suggested directions.Comment: 60 pages, 14 figures; comments welcom
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