Evaluation of HA-fibrin-based hydrogel for restoration of degenerated intervertebral disc

Introduction: Intervertebral disc degeneration is associated with loss of nucleus pulposus (NP) tissue and reduced disc height[1]. A number of therapies, including synthetic and natural biomaterials, have been developed to restore full disc function and to minimize the pain and disability caused by this disease. Fibrin-based biomaterials are used as a replacement for NP or as a cell carrier for tissue engineering approaches[2]. While the behavior of such gels is well-characterized from a material point of view, little is known about their contribution to intervertebral disc (IVD) restoration under dynamic loads. The aim of the present study is the evaluation of a hyaluronic acid fibrin-based hydrogel (ProCore) used to repair an in vitro model of disc degeneration under dynamic loading. Methods: In vitro model of disc degeneration was induced in intact coccygeal bovine IVD by papain digestion of the NP as previously described[3]. In order to characterize fibrin hydrogels, four experimental groups were considered: 1) intact IVD (control), 2) IVD injected with PBS, 3) injection of hydrogels in degenerative IVD and 4) injection of hydrogels in combination with human bone marrow-derived mesenchymal stem cells (MSC) in degenerative IVD. All of the groups were subjected to dynamic loading protocols consisting of 0.2MPa static compression superimposed with ±2° torsion at 0.2Hz for 8h per day and maintained for 7 days. Additionally, one group consisted of degenerative IVD injected with hydrogel and subjected to static compression. Disc heights were monitored after the duration of the loading and compared to the initial disc height. The macrostructure of the formed tissue and the cellular distribution was evaluated by histological means. Results: After one week of loading, the degenerative IVD filled with hydrogel in combination with MSC (dynamic load), hydrogels (dynamic load) and hydrogels (static load) showed a reduction in height by 30%, 15% and 20%, respectively, as compared to their initial disc height. Histological sections showed that the HA-fibrin gel fully occupied the nucleotomized region of the disc and that fibrin was effective in filling the discontinuities of the cavity region. Furthermore, the cells were homogenously distributed along the fibrin hydrogels after 7 days of loading. Discussion: In this study, we showed that fibrin hydrogels showed a good integration within the papain-induced model of disc degeneration and can withstand the applied loads. Fibrin hydrogels can contribute to disc restoration by possibly maintaining adequate stiffness of the tissue and thus preventing disorganization of the surrounding IVD. References: 1. Jarman, J.P., Arpinar, V.E., Baruah, D., Klein, A.P., Maiman, D.J., and Tugan Muftuler, L. (2014). Intervertebral disc height loss demonstrates the threshold of major pathological changes during degeneration. Eur Spine J . 2. Colombini, A., Ceriani, C., Banfi, G., Brayda-Bruno, M., and Moretti, M. (2014). Fibrin in intervertebral disc tissue engineering. Tissue Eng Part B Rev . 3. Chan, S.C., Bürki, A., Bonél, H.M., Benneker, L.M., and Gantenbein-Ritter, B. (2013). Papain-induced in vitro disc degeneration model for the study of injectable nucleus pulposus therapy. Spine J 13, 273-283. Acknowledgement We thank the Swiss National Science Foundation SNF #310030_153411 for funding.

Repair of Annulus fibrosus with Genipin-enhanced Fibrin Hydrogel and silk membrane- fleece

Introduction Low back pain is often caused by a trauma causing disc herniation and /or disc degeneration. Although there are some promising approaches for nucleus pulposus repair, the inner tissue of the intervertebral disc (IVD) so far no treatment or repair is available for annulus fibrosus (AF) injuries. Here we aimed to develop a new method to seal and repair AF injuries by using a silk fleece composite and a genipin enhanced hydrogel. Methods Bovine (b) IVDs were harvested under aseptic conditions and kept in free swelling conditions for 24h in high-glucose DMEM containing 5% bovine serum for equilibration (1). A circular 2mm biopsy punch (Polymed Medical Center, Switzerland) was used to form a reproducible defect in the AF. For filling the defect and keeping the silk composite in place a human-derived fibrin gel (Baxter Tisseel, Switzerland) enhanced with 4.2mg/ml of the cross linker genipin (Wako Chemicals GmbH, Germany) was used. The silk composite consists of a mesh- and a membrane side (Spintec Engineering GmbH, Germany); the membrane is facing outwards to form a seal. bIVDs were cultured in vitro for 14 days either under dynamic load in a custom-built bioreactor under physiological conditions (0.2MPa load and ±2° torsion at 0.2Hz for 8h/day) or static diurnal load of 0.2MPa (2). At the end of culture discs were checked for seal failure, disc height, metabolic activity, cell death by necrosis (LDH assay), DNA content and glycosaminoglycan content. Results Silk composite maintained its position throughout the 14 days of culture under loaded conditions. Although repaired discs performed slightly lower in cell activity, DNA and GAG content were in the range of the control. Also LDH resulted in similar values compared to control discs (Fig 1). Height loss in repaired discs was in the same range as for static diurnal loaded control samples. For dynamically loaded samples the decrease was comparable to the injured, unrepaired discs. Fig 1 LDH of repaired discs compared to control disc after 24h in free swelling conditions for equilibration and first three loading cycles. Conclusions Silk-genipin-fibrin reinforced hydrogel is a promising approach to close AF defects as tested by two degree of freedom loading. In further experiments cytocompatibility of genipin has to be investigated. References 1. Chan SC, Gantenbein-Ritter B. Preparation of intact bovine tail intervertebral discs for organ culture. J Vis Exp 2012, Feb 2;60(60):e3490. 2. Walser J, Ferguson SJ, Gantenbein-Ritter B. Design of a mechanical loading device to culture intact bovine caudal motional segments of the spine under twisting motion. In: Davies J, editors. Replacing animal models: a practical guide to creating and using biomimetic alternatives. Chichester, UK: John Wiley & Sons, Ltd.; 2012. p. 89-105. Acknowledgements This project is funded by the Gerbert Rüf Stiftung project # GRS-028/13 and the Swiss National Science Project SNF #310030_153411.

A combined biomaterial and cellular approach for annulus fibrosus rupture repair

Recurrent intervertebral disc (IVD) herniation and degenerative disc disease have been identified as the most important factors contributing to persistent pain and disability after surgical discectomy. An annulus fibrosus (AF) closure device that provides immediate closure of the AF rupture, restores disc height, reduces further disc degeneration and enhances self-repair capacities is an unmet clinical need. In this study, a poly(trimethylene carbonate) (PTMC) scaffold seeded with human bone marrow derived mesenchymal stromal cells (MSCs) and covered with a poly(ester-urethane) (PU) membrane was assessed for AF rupture repair in a bovine organ culture annulotomy model under dynamic load for 14 days. PTMC scaffolds combined with the sutured PU membrane restored disc height of annulotomized discs and prevented herniation of nucleus pulposus (NP) tissue. Implanted MSCs showed an up-regulated gene expression of type V collagen, a potential AF marker, indicating in situ differentiation capability. Furthermore, MSCs delivered within PTMC scaffolds induced an up-regulation of anabolic gene expression and down-regulation of catabolic gene expression in adjacent native disc tissue. In conclusion, the combined biomaterial and cellular approach has the potential to hinder herniation of NP tissue, stabilize disc height, and positively modulate cell phenotype of native disc tissue.

Esperienza vissuta e scrittura nella poesia di Bassani

Seguendo le tracce della metologia proposta da Dilthey fino a Heidegger riguardo il concetto di Erlebnis (esperienza vissuta), si rintracciano i rapporti tra vita e opera nella produzione poetica di Giorgio Bassani che si prolunga dal 1939 al 1982. La ricerca evidenzia le conessioni della dinamica tra biografia e produzione artistica e il conseguente processo d’interiorizzazione psicologica che il percorso autobiografico dell’ autore rivela nella sua poesia. L’ impatto sul piano psicologico che lo spazio autorappresentato ha nello stesso autore, diventa nei testi proposti spazi di sperienze interiori [Fremont 1976]. Le proposte metodologiche sopra esposte possono essere un utile riferimento per un’analisi critica della poesia bassaniana, che può essere letta o come esperienza autonoma, con una sua originalità di stile e una sua ampiezza d’occasioni, o come laboratorio di temi e nodi che avranno uno sviluppo narrativo, una volta scorporati dalla matrice originaria e amplificati nella loro carica dinamica di proiezioni e figurazioni.

StreamCloud: An Elastic Parallel-Distributed Stream Processing Engine

In recent years, applications in domains such as telecommunications, network security or large scale sensor networks showed the limits of the traditional store-then-process paradigm. In this context, Stream Processing Engines emerged as a candidate solution for all these applications demanding for high processing capacity with low processing latency guarantees. With Stream Processing Engines, data streams are not persisted but rather processed on the fly, producing results continuously. Current Stream Processing Engines, either centralized or distributed, do not scale with the input load due to single-node bottlenecks. Moreover, they are based on static configurations that lead to either under or over-provisioning. This Ph.D. thesis discusses StreamCloud, an elastic paralleldistributed stream processing engine that enables for processing of large data stream volumes. Stream- Cloud minimizes the distribution and parallelization overhead introducing novel techniques that split queries into parallel subqueries and allocate them to independent sets of nodes. Moreover, Stream- Cloud elastic and dynamic load balancing protocols enable for effective adjustment of resources depending on the incoming load. Together with the parallelization and elasticity techniques, Stream- Cloud defines a novel fault tolerance protocol that introduces minimal overhead while providing fast recovery. StreamCloud has been fully implemented and evaluated using several real word applications such as fraud detection applications or network analysis applications. The evaluation, conducted using a cluster with more than 300 cores, demonstrates the large scalability, the elasticity and fault tolerance effectiveness of StreamCloud. Resumen En los útimos años, aplicaciones en dominios tales como telecomunicaciones, seguridad de redes y redes de sensores de gran escala se han encontrado con múltiples limitaciones en el paradigma tradicional de bases de datos. En este contexto, los sistemas de procesamiento de flujos de datos han emergido como solución a estas aplicaciones que demandan una alta capacidad de procesamiento con una baja latencia. En los sistemas de procesamiento de flujos de datos, los datos no se persisten y luego se procesan, en su lugar los datos son procesados al vuelo en memoria produciendo resultados de forma continua. Los actuales sistemas de procesamiento de flujos de datos, tanto los centralizados, como los distribuidos, no escalan respecto a la carga de entrada del sistema debido a un cuello de botella producido por la concentración de flujos de datos completos en nodos individuales. Por otra parte, éstos están basados en configuraciones estáticas lo que conducen a un sobre o bajo aprovisionamiento. Esta tesis doctoral presenta StreamCloud, un sistema elástico paralelo-distribuido para el procesamiento de flujos de datos que es capaz de procesar grandes volúmenes de datos. StreamCloud minimiza el coste de distribución y paralelización por medio de una técnica novedosa la cual particiona las queries en subqueries paralelas repartiéndolas en subconjuntos de nodos independientes. Ademas, Stream- Cloud posee protocolos de elasticidad y equilibrado de carga que permiten una optimización de los recursos dependiendo de la carga del sistema. Unidos a los protocolos de paralelización y elasticidad, StreamCloud define un protocolo de tolerancia a fallos que introduce un coste mínimo mientras que proporciona una rápida recuperación. StreamCloud ha sido implementado y evaluado mediante varias aplicaciones del mundo real tales como aplicaciones de detección de fraude o aplicaciones de análisis del tráfico de red. La evaluación ha sido realizada en un cluster con más de 300 núcleos, demostrando la alta escalabilidad y la efectividad tanto de la elasticidad, como de la tolerancia a fallos de StreamCloud.

StreamCloud: An elastic and scalable data streaming system

Many applications in several domains such as telecommunications, network security, large scale sensor networks, require online processing of continuous data lows. They produce very high loads that requires aggregating the processing capacity of many nodes. Current Stream Processing Engines do not scale with the input load due to single-node bottlenecks. Additionally, they are based on static con?gurations that lead to either under or over-provisioning. In this paper, we present StreamCloud, a scalable and elastic stream processing engine for processing large data stream volumes. StreamCloud uses a novel parallelization technique that splits queries into subqueries that are allocated to independent sets of nodes in a way that minimizes the distribution overhead. Its elastic protocols exhibit low intrusiveness, enabling effective adjustment of resources to the incoming load. Elasticity is combined with dynamic load balancing to minimize the computational resources used. The paper presents the system design, implementation and a thorough evaluation of the scalability and elasticity of the fully implemented system.

Amplificación del efecto destructivo de los desprendimientos rocosos por deslizamiento sobre suelos volcánicos (Tenerife y Madeira)

This work provides geomorphological and geotechnical observations on the amplification of the destructive behaviour of rock falls developed in rocky slopes with a soil rich in organic matter, which are both exposed to high rainfall regimes. The determinant factor of this process would be related to the low geotechnical quality that the organic matter gives to the soil, which experience a sudden change in its fabric related to the dynamic load, similar to those observed in the quick clays in the fjords of Norway.

Leakage and temperature aware server control for improving energy efficiency in data centers

Reducing the energy consumption for computation and cooling in servers is a major challenge considering the data center energy costs today. To ensure energy-efficient operation of servers in data centers, the relationship among computa- tional power, temperature, leakage, and cooling power needs to be analyzed. By means of an innovative setup that enables monitoring and controlling the computing and cooling power consumption separately on a commercial enterprise server, this paper studies temperature-leakage-energy tradeoffs, obtaining an empirical model for the leakage component. Using this model, we design a controller that continuously seeks and settles at the optimal fan speed to minimize the energy consumption for a given workload. We run a customized dynamic load-synthesis tool to stress the system. Our proposed cooling controller achieves up to 9% energy savings and 30W reduction in peak power in comparison to the default cooling control scheme.

Smart aeronautical structures: development and experimental validation of a structural health monitoring system for damage detection

En muchas áreas de la ingeniería, la integridad y confiabilidad de las estructuras son aspectos de extrema importancia. Estos son controlados mediante el adecuado conocimiento de danos existentes. Típicamente, alcanzar el nivel de conocimiento necesario que permita caracterizar la integridad estructural implica el uso de técnicas de ensayos no destructivos. Estas técnicas son a menudo costosas y consumen mucho tiempo. En la actualidad, muchas industrias buscan incrementar la confiabilidad de las estructuras que emplean. Mediante el uso de técnicas de última tecnología es posible monitorizar las estructuras y en algunos casos, es factible detectar daños incipientes que pueden desencadenar en fallos catastróficos. Desafortunadamente, a medida que la complejidad de las estructuras, los componentes y sistemas incrementa, el riesgo de la aparición de daños y fallas también incrementa. Al mismo tiempo, la detección de dichas fallas y defectos se torna más compleja. En años recientes, la industria aeroespacial ha realizado grandes esfuerzos para integrar los sensores dentro de las estructuras, además de desarrollar algoritmos que permitan determinar la integridad estructural en tiempo real. Esta filosofía ha sido llamada “Structural Health Monitoring” (o “Monitorización de Salud Estructural” en español) y este tipo de estructuras han recibido el nombre de “Smart Structures” (o “Estructuras Inteligentes” en español). Este nuevo tipo de estructuras integran materiales, sensores, actuadores y algoritmos para detectar, cuantificar y localizar daños dentro de ellas mismas. Una novedosa metodología para detección de daños en estructuras se propone en este trabajo. La metodología está basada en mediciones de deformación y consiste en desarrollar técnicas de reconocimiento de patrones en el campo de deformaciones. Estas últimas, basadas en PCA (Análisis de Componentes Principales) y otras técnicas de reducción dimensional. Se propone el uso de Redes de difracción de Bragg y medidas distribuidas como sensores de deformación. La metodología se validó mediante pruebas a escala de laboratorio y pruebas a escala real con estructuras complejas. Los efectos de las condiciones de carga variables fueron estudiados y diversos experimentos fueron realizados para condiciones de carga estáticas y dinámicas, demostrando que la metodología es robusta ante condiciones de carga desconocidas. ABSTRACT In many engineering fields, the integrity and reliability of the structures are extremely important aspects. They are controlled by the adequate knowledge of existing damages. Typically, achieving the level of knowledge necessary to characterize the structural integrity involves the usage of nondestructive testing techniques. These are often expensive and time consuming. Nowadays, many industries look to increase the reliability of the structures used. By using leading edge techniques it is possible to monitoring these structures and in some cases, detect incipient damage that could trigger catastrophic failures. Unfortunately, as the complexity of the structures, components and systems increases, the risk of damages and failures also increases. At the same time, the detection of such failures and defects becomes more difficult. In recent years, the aerospace industry has done great efforts to integrate the sensors within the structures and, to develop algorithms for determining the structural integrity in real time. The ‘philosophy’ has being called “Structural Health Monitoring” and these structures have been called “smart structures”. These new types of structures integrate materials, sensors, actuators and algorithms to detect, quantify and locate damage within itself. A novel methodology for damage detection in structures is proposed. The methodology is based on strain measurements and consists in the development of strain field pattern recognition techniques. The aforementioned are based on PCA (Principal Component Analysis) and other dimensional reduction techniques. The use of fiber Bragg gratings and distributed sensing as strain sensors is proposed. The methodology have been validated by using laboratory scale tests and real scale tests with complex structures. The effects of the variable load conditions were studied and several experiments were performed for static and dynamic load conditions, demonstrating that the methodology is robust under unknown load conditions.

Novo procedimento para a realização de análise capwap no ensaio de carregamento dinâmico em estacas pré-moldadas.

Desde a década de 1980 diversos autores apresentaram correlações entre provas de carga estática e ensaios de carregamento dinâmico em estacas. Para uma boa correlação é fundamental que os testes sejam bem executados e que atinjam a ruptura segundo algum critério, como o de Davisson, por exemplo, além de levar em conta o intervalo de tempo entre a execução da prova de carga estática e do ensaio dinâmico, face ao efeito \"set up\". Após a realização do ensaio dinâmico realiza-se a análise CAPWAP que permite a determinação da distribuição do atrito lateral em profundidade, a carga de ponta e outros parâmetros dos solos tais como quakes e damping. A análise CAPWAP é realizada por tentativas através do procedimento \"signal matching\", isto é, o melhor ajuste entre os sinais de força medido pelos sensores e o calculado. É relativamente fácil mostrar que a mesma solução pode ser obtida através de dados de entrada diferentes. Isso significa que apesar de apresentarem cargas mobilizadas próximas o formato da curva da simulação de prova de carga estática, obtida pelo CAPWAP, assim como a distribuição do atrito lateral, podem ser diferentes, mesmo que as análises apresentem \"match quality\" (MQWU) satisfatórios. Uma forma de corrigir o formato da curva simulada do CAPWAP, assim como a distribuição do atrito lateral, é através da comparação com provas de carga estática (PCE). A sobreposição das duas curvas, a simulada e a \"real\", permite a determinação do quake do fuste através do trecho inicial da curva carga-recalque da prova de carga estática, que por sua vez permite uma melhor definição da distribuição do atrito lateral e da reação de ponta. Neste contexto surge o conceito de \"match quality de recalques\" (MQR). Quando a PCE não está disponível, propõe-se efetuar um carregamento estático utilizando o peso próprio do martelo do bate-estaca (CEPM). Mostra-se, através de dois casos de obra, em que estavam disponíveis ensaios de carregamento dinâmico e PCEs, que esse procedimento permite obter uma melhor solução do ponto de vista físico, isto é consistente com as características do subsolo e com a curva carga-recalque da PCE, e não apenas matemático, através da avaliação do \"match quality\" (MQWU).

A Unique Prestressed Concrete Pedestrian Bridge in Spain

This paper describes the so-called Kiss Bridge. This structure resembles a kiss, a subtle touch of structures. The beams have been structurally designed to adapt the Japanese art of paper folding called "origami." The material used for constructing the floating beams is white reinforced concrete in the form of folded shells. The two geometrically different parts have distinct structural behaviors. The length of the main pathway of both structures is over 60 m. The pedestrian bridge crosses an artificial rainwater channel with a skew of 45° with respect to the referred channel. The joint between the cantilever structure and the Y-shaped one is located over the middle of the channel. Each stretch has different transversal sections. The pedestrian bridge is made with prestressed self-compacting reinforced concrete of 60 MPa. The foundation is shallow, comprising footings and footing beams made of 25 MPa conventional concrete. The cantilever structure with its foundations is designed as a semi-integral bridge whereas the Y-shaped one is an integral structure. The dynamic behavior of the structure was carefully studied to ensure that the dynamic loads generated by pedestrians do not cause excessive vibrations, especially to the cantilever structure, which could present dynamic interactions with the pedestrians walking. The bridge was recognized, in the 2014 edition of the fib Awards for Outstanding Concrete Structures, for having made a valuable contribution to the image and promotion of concrete structures.

Parallel partitioning of unstructured meshes

A method is outlined for optimising graph partitions which arise in mapping un- structured mesh calculations to parallel computers. The method employs a combination of iterative techniques to both evenly balance the workload and minimise the number and volume of interprocessor communications. They are designed to work efficiently in parallel as well as sequentially and when combined with a fast direct partitioning technique (such as the Greedy algorithm) to give an initial partition, the resulting two-stage process proves itself to be both a powerful and flexible solution to the static graph-partitioning problem. The algorithms can also be used for dynamic load-balancing and a clustering technique can additionally be employed to speed up the whole process. Experiments indicate that the resulting parallel code can provide high quality partitions, independent of the initial partition, within a few seconds.

Computational tool for three-point hitch geometry optimization

The weight-transfer effect, consisting of the change in dynamic load distribution between the front and the rear tractor axles, is one of the most impairing phenomena for the performance, comfort, and safety of agricultural operations. Excessive weight transfer from the front to the rear tractor axle can occur during operation or maneuvering of implements connected to the tractor through the three-point hitch (TPH). In this respect, an optimal design of the TPH can ensure better dynamic load distribution and ultimately improve operational performance, comfort, and safety. In this study, a computational design tool (The Optimizer) for the determination of a TPH geometry that minimizes the weight-transfer effect is developed. The Optimizer is based on a constrained minimization algorithm. The objective function to be minimized is related to the tractor front-to-rear axle load transfer during a simulated reference maneuver performed with a reference implement on a reference soil. Simulations are based on a 3-degrees-of-freedom (DOF) dynamic model of the tractor-TPH-implement aggregate. The inertial, elastic, and viscous parameters of the dynamic model were successfully determined through a parameter identification algorithm. The geometry determined by the Optimizer complies with the ISO-730 Standard functional requirements and other design requirements. The interaction between the soil and the implement during the simulated reference maneuver was successfully validated against experimental data. Simulation results show that the adopted reference maneuver is effective in triggering the weight-transfer effect, with the front axle load exhibiting a peak-to-peak value of 27.1 kN during the maneuver. A benchmark test was conducted starting from four geometries of a commercially available TPH. As result, all the configurations were optimized by above 10%. The Optimizer, after 36 iterations, was able to find an optimized TPH geometry which allows to reduce the weight-transfer effect by 14.9%.

Feasibility Study of Dynamic Overload and Ultimate Load Tests of Full-Scale Highway Bridges, HR-160, 1973

As a result of the construction of the Saylorville Dam and Reservoir on the Des Moines River, six highway bridges are scheduled for removal. Five of these are old high-truss single-lane bridges, each bridge having several simple spans. The other bridge is a fairly modern (1955) double 4-span continuous beam-and-slab composite highway bridge. The availability of these bridges affords an unusual opportunity for study of the behavior of full-scale bridges. Because of the magnitude of the potential testing program, a feasibility study was initiated and the results are presented in this two-part final report. Part I summarizes the findings and Part II presents the supporting detailed information.

Spectral analysis of the electromyograph of the erector spinae muscle before and after a dynamic manual load-lifting test

The aim of the present study was to assess the spectral behavior of the erector spinae muscle during isometric contractions performed before and after a dynamic manual load-lifting test carried out by the trunk in order to determine the capacity of muscle to perform this task. Nine healthy female students participated in the experiment. Their average age, height, and body mass (± SD) were 20 ± 1 years, 1.6 ± 0.03 m, and 53 ± 4 kg, respectively. The development of muscle fatigue was assessed by spectral analysis (median frequency) and root mean square with time. The test consisted of repeated bending movements from the trunk, starting from a 45º angle of flexion, with the application of approximately 15, 25 and 50% of maximum individual load, to the stand up position. The protocol used proved to be more reliable with loads exceeding 50% of the maximum for the identification of muscle fatigue by electromyography as a function of time. Most of the volunteers showed an increase in root mean square versus time on both the right (N = 7) and the left (N = 6) side, indicating a tendency to become fatigued. With respect to the changes in median frequency of the electromyographic signal, the loads used in this study had no significant effect on either the right or the left side of the erector spinae muscle at this frequency, suggesting that a higher amount and percentage of loads would produce more substantial results in the study of isotonic contractions.