Studio, analisi e progettazione di un prototipo di infrastructure as code

La tesi inserita in un periodo di forte transizione dai sistemi On­premises a sistemi Cloud ha avuto l'esigenza di risolvere alcune problematiche legate alla definizione delle infrastrutture. Come poter scalare le risorse all'evenienza ricreando gli stessi ambienti, monitorandoli e mettendo in sicurezza i dati critici delle applicazioni? La tesi ha risposto proprio a questa domanda definendo un nuovo paradigma nel concepire le infrastrutture chiamato Infrastructure as Code. La tesi ha approfondito le pratiche e le metodologie che si sono legate maggiormente all'Infrastructure as Code tra le quali Version Control, Configuration Management, Continuous Integration e Continuous Delivery. La tesi inoltre ha previsto la realizzazione di un prototipo finale nato dallo studio del flusso di sviluppo software aziendale, definendo gli ambienti in accordo ai sistemi di Version Control e Configuration Management, applicando pratiche di integrazione continua per giungere ad una deployment pipeline funzionale.

Análisis de mecanismos de integración de herramientas para Suministro Continuo (Continuous Delivery)

Las empresas actuales centran sus esfuerzos en conseguir una buena calidad del software que desarrollan, haciendo uso de metodologías, procedimientos y estándares adecuados para poder desarrollar y lanzar un producto software de calidad con la suficiente certeza de obtener un menor coste y riesgo finales. Es por ello que se han establecido nuevos paradigmas de organización que proponen el uso de nuevas tecnologías y procesos para permitir una puesta en producción ágil y menos arriesgada. Este trabajo se centra en la implementación de una de estas técnicas, el Suministro Continuo (Continuous Delivery - CD). La implantación de esta técnica se basa en llevar a cabo la automatización de todos los pasos entre el desarrollo y la puesta en producción de software. Dentro de las tareas necesarias para implementar esta técnica, este trabajo lleva a cabo la identificación de las herramientas básicas que permiten el Suministro Continuo y el estudio de mecanismos de integración de todas estas herramientas, automatizando todo el proceso de desarrollo software desde la construcción del proyecto hasta su puesta en producción. Posibilitando así un proceso de Suministro Continuo, en el que se lleven a cabo despliegues del producto software diarios que permitan recoger realimentación más rápidamente de los usuarios y poder reaccionar ágilmente a los cambios de necesidad de estos.

Continuous Delivery : Utmaningar ett förvaltningsuppdrag kan stå inför vid en övergång till Continuous Delivery

Continuous delivery (CD) is a software engineering approach where the focus lays on creating a short delivery cycle by automating parts of the deployment pipeline which includes build, deploy-, test and release process. CD is based on that during development should be possible to always automatically generate a release based on the source code in its current state. One of CD's many advantages is that through continuous releases it allows you to get a quick feedback loop leading to faster and more efficient implementation of new functions, at the same time fixing errors. Although CD has many advantages, there are also several challenges a maintenance management project must manage in the transition to CD. These challenges may differ depending on the maturity level for a maintenance management project and what strengths and weaknesses the project has. Our research question was: "What challenges can a maintenance management project face in transition to Continuous delivery?" The purpose of this study is to describe Continuous delivery and the challenges a maintenance management project may face during a transition to Continuous delivery. A descriptive case study has been carried out with the data collection methods of interviews and documents. A situation analysis was created based on the collected data in a shape of a process model that represent the maintenance management projects release process. The processmodel was used as the basis of SWOT analysis and analysis by Rehn et al's Maturity Model. From these analyzes we found challenges of a maintenance management project may face in the transition to CD. The challenges are about customers and the management's attitude towards a transition to CD. But the biggest challenge is about automation of the deployment pipeline steps.

Effects of local continuous release of brain derived neurotrophic factor (BDNF) on peripheral nerve regeneration in a rat model

The purpose of this study was to evaluate the effect of continuously released BDNF on peripheral nerve regeneration in a rat model. Initial in vitro evaluation of calcium alginate prolonged-release-capsules (PRC) proved a consistent release of BDNF for a minimum of 8 weeks. In vivo, a worst case scenario was created by surgical removal of a 20-mm section of the sciatic nerve of the rat. Twenty-four autologous fascia tubes were filled with calcium alginate spheres and sutured to the epineurium of both nerve ends. The animals were divided into 3 groups. In group 1, the fascial tube contained plain calcium alginate spheres. In groups 2 and 3, the fascial tube contained calcium alginate spheres with BDNF alone or BDNF stabilized with bovine serum albumin, respectively. The autocannibalization of the operated extremity was clinically assessed and documented in 12 additional rats. The regeneration was evaluated histologically at 4 weeks and 10 weeks in a blinded manner. The length of nerve fibers and the numbers of axons formed in the tube was measured. Over a 10-week period, axons have grown significantly faster in groups 2 and 3 with continuously released BDNF compared to the control. The rats treated with BDNF (groups 2 and 3) demonstrated significantly less autocannibalization than the control group (group 1). These results suggest that BDNF may not only stimulate faster peripheral nerve regeneration provided there is an ideal, biodegradable continuous delivery system but that it significantly reduces the neuropathic pain in the rat model.

A proposal for a model-based approach for adapting software configuration to runtime environments

Las metodologías de desarrollo ágiles han sufrido un gran auge en entornos industriales durante los últimos años debido a la rapidez y fiabilidad de los procesos de desarrollo que proponen. La filosofía DevOps y específicamente las metodologías derivadas de ella como Continuous Delivery o Continuous Deployment promueven la gestión completamente automatizada del ciclo de vida de las aplicaciones, desde el código fuente a las aplicaciones ejecutándose en entornos de producción. La automatización se ve como un medio para producir procesos repetibles, fiables y rápidos. Sin embargo, no todas las partes de las metodologías Continuous están completamente automatizadas. En particular, la gestión de la configuración de los parámetros de ejecución es un problema que ha sido acrecentado por la elasticidad y escalabilidad que proporcionan las tecnologías de computación en la nube. La mayoría de las herramientas de despliegue actuales pueden automatizar el despliegue de la configuración de parámetros de ejecución, pero no ofrecen soporte a la hora de fijar esos parámetros o de validar los ficheros que despliegan, principalmente debido al gran abanico de opciones de configuración y el hecho de que el valor de muchos de esos parámetros es fijado en base a preferencias expresadas por el usuario. Esto hecho hace que pueda parecer que cualquier solución al problema debe estar ajustada a una aplicación específica en lugar de ofrecer una solución general. Con el objetivo de solucionar este problema, propongo un modelo de configuración que puede ser inferido a partir de instancias de configuración existentes y que puede reflejar las preferencias de los usuarios para ser usado para facilitar los procesos de configuración. El modelo de configuración puede ser usado como la base de un proceso de configuración interactivo capaz de guiar a un operador humano a través de la configuración de una aplicación para su despliegue en un entorno determinado o para detectar cambios de configuración automáticamente y producir una configuración válida que se ajuste a esos cambios. Además, el modelo de configuración debería ser gestionado como si se tratase de cualquier otro artefacto software y debería ser incorporado a las prácticas de gestión habituales. Por eso también propongo un modelo de gestión de servicios que incluya información relativa a la configuración de parámetros de ejecución y que además es capaz de describir y gestionar propuestas arquitectónicas actuales tales como los arquitecturas de microservicios. ABSTRACT Agile development methodologies have risen in popularity within the industry in recent years due to the speed and reliability of the processes they propose. The DevOps philosophy and specifically the methodologies derived from it such as Continuous Delivery and Continuous Deployment push for a totally automated management of the application lifecycle, from the source code to the software running in production environment. Automation in this regard is used as a means to produce repeatable, reliable and fast processes. However, not all parts of the Continuous methodologies are completely automatized. In particular, management of runtime parameter configuration is a problem that has increased its impact in deployment process due to the scalability and elasticity provided by cloud technologies. Most deployment tools nowadays can automate the deployment of runtime parameter configuration, but they offer no support for parameter setting o configuration validation, as the range of different configuration options and the fact that the value of many of those parameters is based on user preference seems to imply that any solution to the problem will have to be tailored to a specific application. With the aim to solve this problem I propose a configuration model that can be inferred from existing configurations and reflect user preferences in order to ease the configuration process. The configuration model can be used as the base of an interactive configuration process capable of guiding a human operator through the configuration of an application for its deployment in a specific environment or to automatically detect configuration changes and produce valid runtime parameter configurations that take into account those changes. Additionally, the configuration model should be managed as any other software artefact and should be incorporated into current management practices. I also propose a service management model that includes the configuration information and that is able to describe and manage current architectural practices such as the microservices architecture.

Hypoxic/ischemic models in newborn piglet: Comparison of constant FiO(2) versus variable FiO(2) delivery

A comparison of a constant (continuous delivery of 4% FiO(2)) and a variable (initial 5% FiO(2) with adjustments to induce low amplitude EEG (LAEEG) and hypotension) hypoxic/ischemic insult was performed to determine which insult was more effective in producing a consistent degree of survivable neuropathological damage in a newborn piglet model of perinatal asphyxia. We also examined which physiological responses contributed to this outcome. Thirty-nine 1-day-old piglets were subjected to either a constant hypoxic/ischemic insult of 30- to 37-min duration or a variable hypoxic/ischemic insult of 30-min low peak amplitude EEG (LAEEG < 5 mu V) including 10 min of low mean arterial blood pressure (MABP < 70% of baseline). Control animals (n = 6) received 21% FiO(2) for the duration of the experiment. At 72 h, the piglets were euthanased, their brains removed and fixed in 4% paraformaldehyde and assessed for hypoxic/ischemic injury by histological analysis. Based on neuropathology scores, piglets were grouped as undamaged or damaged; piglets that did not survive to 72 h were grouped separately as dead. The variable insult resulted in a greater number of piglets with neuropathological damage (undamaged = 12.5%, damaged = 68.75%, dead = 18.75%) while the constant insult resulted in a large proportion of undamaged piglets (undamaged = 50%, damaged = 22.2%, dead = 27.8%). A hypoxic insult varied to maintain peak amplitude EEG < 5 mu V results in a greater number of survivors with a consistent degree of neuropathological damage than a constant hypoxic insult. Physiological variables MABP, LAEEG, pH and arterial base excess were found to be significantly associated with neuropathological outcome. (c) 2006 Elsevier B.V. All rights reserved.

A silicone elastomer vaginal ring for HIV prevention containing two microbicides with different mechanisms of action

Vaginal rings are currently being developed for the long-term (at least 30 days) continuous delivery of microbicides against human immunodeficiency virus (HIV). Research to date has mostly focused on devices containing a single antiretroviral compound, exemplified by the 25 mg dapivirine ring currently being evaluated in a Phase III clinical study. However, there is a strong clinical rationale for combining antiretrovirals with different mechanisms of action in a bid to increase breadth of protection and limit the emergence of resistant strains. Here we report the development of a combination antiretroviral silicone elastomer matrix-type vaginal ring for simultaneous controlled release of dapivirine, a non-nucleoside reverse transcriptase inhibitor, and maraviroc, a CCR5-targeted HIV-1 entry inhibitor. Vaginal rings loaded with 25 mg dapivirine and various quantities of maraviroc (50– 400 mg) were manufactured and in vitro release assessed. The 25 mg dapivirine and 100 mg maraviroc formulation was selected for further study. A 24-month pharmaceutical stability evaluation was conducted, indicating good product stability in terms of in vitro release, content assay, mechanical properties and related substances. This combination ring product has now progressed to Phase I clinical testing.

Nitrifying and denitrifying bacterial communities in the sediment and rhizosphere of a free water surface constructed wetland

La contínua descàrrega de nutrients, sobretot fosfats i nitrogen, és la major causa d'eutrofització dels ecosistemes aquàtics. Els sistemes de tractament basats en aiguamolls construïts s'han emprat per reduir ells nivells de nitrogen a l'aigua com a alternativa de baix cost als mètodes de depuració convencionals. L'eliminació del nitrogen a aquests sistemes depèn en bona part de la vegetació, i l'alternança de condicions aeròbiques i anaeròbiques per promoure els processos de nitrificació i desnitrificació. En aquest treball hem volgut investigar les activitats microbianes de nitrificació i desnitrificació en relació a dues espècies de plantes macròfites en un sistema d'aiguamolls de tractament de flux superficial (FS-SAC), dissenyat per minimitzar l'impacte de l'alliberament d'aigua carregada de nutrients a la reserva natural dels Aiguamolls de l'Empordà (Girona, Espanya).

Mathematical modelling of competitive LDL/VLDL binding and uptake by hepatocytes

Elevated levels of low-density-lipoprotein cholesterol (LDL-C) in the plasma are a well-established risk factor for the development of coronary heart disease. Plasma LDL-C levels are in part determined by the rate at which LDL particles are removed from the bloodstream by hepatic uptake. The uptake of LDL by mammalian liver cells occurs mainly via receptor-mediated endocytosis, a process which entails the binding of these particles to specific receptors in specialised areas of the cell surface, the subsequent internalization of the receptor-lipoprotein complex, and ultimately the degradation and release of the ingested lipoproteins' constituent parts. We formulate a mathematical model to study the binding and internalization (endocytosis) of LDL and VLDL particles by hepatocytes in culture. The system of ordinary differential equations, which includes a cholesterol-dependent pit production term representing feedback regulation of surface receptors in response to intracellular cholesterol levels, is analysed using numerical simulations and steady-state analysis. Our numerical results show good agreement with in vitro experimental data describing LDL uptake by cultured hepatocytes following delivery of a single bolus of lipoprotein. Our model is adapted in order to reflect the in vivo situation, in which lipoproteins are continuously delivered to the hepatocyte. In this case, our model suggests that the competition between the LDL and VLDL particles for binding to the pits on the cell surface affects the intracellular cholesterol concentration. In particular, we predict that when there is continuous delivery of low levels of lipoproteins to the cell surface, more VLDL than LDL occupies the pit, since VLDL are better competitors for receptor binding. VLDL have a cholesterol content comparable to LDL particles; however, due to the larger size of VLDL, one pit-bound VLDL particle blocks binding of several LDLs, and there is a resultant drop in the intracellular cholesterol level. When there is continuous delivery of lipoprotein at high levels to the hepatocytes, VLDL particles still out-compete LDL particles for receptor binding, and consequently more VLDL than LDL particles occupy the pit. Although the maximum intracellular cholesterol level is similar for high and low levels of lipoprotein delivery, the maximum is reached more rapidly when the lipoprotein delivery rates are high. The implications of these results for the design of in vitro experiments is discussed.

VEGF incorporated into calcium phosphate ceramics promotes vascularisation and bone formation in vivo

Bone formation and osseointegration of biomaterials are dependent on angiogenesis and vascularization. Angiogenic growth factors such as vascular endothelial growth factor (VEGF) were shown to promote biomaterial vascularization and enhance bone formation. However, high local concentrations of VEGF induce the formation of malformed, nonfunctional vessels. We hypothesized that a continuous delivery of low concentrations of VEGF from calcium phosphate ceramics may increase the efficacy of VEGF administration.VEGF was co-precipitated onto biphasic calcium phosphate (BCP) ceramics to achieve a sustained release of the growth factor. The co-precipitation efficacy and the release kinetics of the protein were investigated in vitro. For in vivo investigations BCP ceramics were implanted into critical size cranial defects in Balb/c mice. Angiogenesis and microvascularization were investigated over 28 days by means of intravital microscopy. The formation of new bone was determined histomorphometrically. Co-precipitation reduced the burst release of VEGF. Furthermore, a sustained, cell-mediated release of low concentrations of VEGF from BCP ceramics was mediated by resorbing osteoclasts. In vivo, sustained delivery of VEGF achieved by protein co-precipitation promoted biomaterial vascularization, osseointegration, and bone formation. Short-term release of VEGF following superficial adsorption resulted in a temporally restricted promotion of angiogenesis and did not enhance bone formation. The release kinetics of VEGF appears to be an important factor in the promotion of biomaterial vascularization and bone formation. Sustained release of VEGF increased the efficacy of VEGF delivery demonstrating that a prolonged bioavailability of low concentrations of VEGF is beneficial for bone regeneration.

(Table 1) Minor and trace element concentrations in interstitial waters from ODP Leg 166 sites

Concentrations of minor and trace elements (Li, Rb, Sr, Ba, Fe, and Mn) in interstitial water (IW) were found in samples collected during Ocean Drilling Program (ODP) Leg 166 from Sites 1005, 1006, and 1007 on the western flank of the Great Bahama Bank (GBB). Concentrations of Li range from near-seawater values immediately below the sediment/water interface to a maximum of 250 µM deep in Site 1007. Concentrations determined during shore-based studies are substantially lower than the shipboard data presented in the Leg 166 Initial Reports volume (range of 28-439 µM) because of broad-band interferences from high dissolved Sr concentrations in the shipboard analyses. Rubidium concentrations of 1.3-1.7 µM were measured in IW from Site 1006 when salinity was less than 40 psu. A maximum of 2.5 µM is reached downhole at a salinity of 50 psu. Shipboard and shore-based concentrations of Sr2+ are in excellent agreement and vary from 0.15 mM near the sediment water interface to 6.8 mM at depth. The latter represent the highest dissolved Sr2+ concentrations observed to date in sediments cored during the Deep Sea Drilling Project (DSDP) or ODP. Concentrations of Ba2+ span three orders of magnitude (0.1-227µM). Concentrations of Fe (<0.1-14 µM) and Mn (0.1-2 µM) exhibit substantially greater fluctuations than other constituents. The concentrations of minor and trace metals in pore fluids from the GBB transect sites are mediated principally by changes in pore-water properties resulting from early diagenesis of carbonates associated with microbial degradation of organic matter, and by the abundance of detrital materials that serve as a source of these elements. Downcore variations in the abundance of detrital matter reflect differences in carbonate production during various sea-level stands and are more evident at the more proximal Site 1005 than at the more pelagic Site 1006. The more continuous delivery of detrital matter deep in Site 1007 and throughout all of Site 1006 is reflected in a greater propensity to provide trace elements to solution. Concentrations of dissolved Li+ derive principally from (1) release during dissolution of biogenic carbonates and subsequent exclusion during recrystallization and (2) release from partial dissolution of Li-bearing detrital phases, especially ion-exchange reactions with clay minerals. A third but potentially less important source of Li+ is a high-salinity brine hypothesized to exist in Jurassic age (unsampled) sediments underlying those sampled during Leg 166. The source of dissolved Sr2+ is almost exclusively biogenic carbonate, particularly aragonite. Concentrations of dissolved Sr2+ and Ba2+ are mediated by the solubility of their sulfates. Barite and detrital minerals appear to be the more important source of dissolved Ba2+. Concentrations of Fe and Mn2+ in anoxic pore fluids are mediated by the relative insolubility of pyrite and incorporation into diagenetic carbonates. The principal sources of these elements are easily reduced Fe-Mn-rich phases including Fe-rich clays found in lateritic soils and aoelian dust.

Future glucose-lowering drugs for type 2 diabetes

The multivariable and progressive natural history of type 2 diabetes limits the effectiveness of available glucose-lowering drugs. Constraints imposed by comorbidities (notably cardiovascular disease and renal impairment) and the need to avoid hypoglycaemia, weight gain, and drug interactions further complicate the treatment process. These challenges have prompted the development of new formulations and delivery methods for existing drugs alongside research into novel pharmacological entities. Advances in incretin-based therapies include a miniature implantable osmotic pump to give continuous delivery of a glucagon-like peptide-1 receptor agonist for 6-12 months and once-weekly tablets of dipeptidyl peptidase-4 inhibitors. Hybrid molecules that combine the properties of selected incretins and other peptides are at early stages of development, and proof of concept has been shown for small non-peptide molecules to activate glucagon-like peptide-1 receptors. Additional sodium-glucose co-transporter inhibitors are progressing in development as well as possible new insulin-releasing biological agents and small-molecule inhibitors of glucagon action. Adiponectin receptor agonists, selective peroxisome proliferator-activated receptor modulators, cellular glucocorticoid inhibitors, and analogues of fibroblast growth factor 21 are being considered as potential new approaches to glucose lowering. Compounds that can enhance insulin receptor and post-receptor signalling cascades or directly promote selected pathways of glucose metabolism have suggested opportunities for future treatments. However, pharmacological interventions that are able to restore normal β-cell function and β-cell mass, normalise insulin action, and fully correct glucose homoeostasis are a distant vision.

Continuous and High-Level In Vivo Delivery of Endostatin From Recombinant Cells Encapsulated in TheraCyte (R) Immunoisolation Devices

Endostatin (ES) is a potent inhibitor of angiogenesis and tumor growth. Continuous ES delivery of ES improves the efficacy and potency of the antitumoral therapy. The TheraCyte (R) system is a polytetrafluoroethylene (PTFE) semipermeable membrane macroencapsulation system for implantation of genetically engineered cells specially designed for the in vivo delivery of therapeutic proteins, such as ES, which circumvents the problem of limited half-life and variation in circulating levels. In order to enable neovascularization at the tissues adjacent to the devices prior to ES secretion by the cells inside them, we designed a scheme in which empty TheraCyte (R) devices were preimplanted SC into immunodeficient mice. Only after healing (17 days later) were Chinese hamster ovary cells expressing ES injected into the preimplanted devices. In another model for device implantation, the cells expressing ES where loaded into the immunoisolation devices prior to implantation into the animals, and the TheraCyte (R) were then immediately implanted SC into the mice. Throughout the 2-month study, constant high ES levels of up to 3.7 mu g/ml were detected in the plasma of the mice preimplanted with the devices, while lower but also constant levels of ES (up to 2.1 mu g/ml plasma) were detected in the mice that had received devices preloaded with the ES-expressing cells. Immunohistochemistry using anti-ES antibody showed reaction within the device and outside it, demonstrating that ES, secreted by the confined recombinant cells, permeated through the membrane and reached the surrounding tissues.

A cache-based mobility-aware scheme for real-time continuous media delivery in wireless networks

Providing real-time or continuous media (CM) application services in wireless networks poses a significant challenge, as it requires timely delivery of data in a best-effort network. In this paper, we propose a cache-based scheme for mobility-aware, CM applications. The proposed scheme exploits a previously proposed caching strategy to complement Mobile-IP by placing services closer to migrated mobile nodes. The central idea of this work is based on the migration of sessions in order to facilitate uninterrupted delivery of CM in mobile environments. The performance of the proposed scheme is investigated by simulation studies. In particular, the effect of the proposed scheme on several QoS parameters under varying conditions of mobility and CM data is measured.

Application of continuous positive airway pressure in the delivery room: a multicenter randomized clinical trial

This study evaluated whether the use of continuous positive airway pressure (CPAP) in the delivery room alters the need for mechanical ventilation and surfactant during the first 5 days of life and modifies the incidence of respiratory morbidity and mortality during the hospital stay. The study was a multicenter randomized clinical trial conducted in five public university hospitals in Brazil, from June 2008 to December 2009. Participants were 197 infants with birth weight of 1000-1500 g and without major birth defects. They were treated according to the guidelines of the American Academy of Pediatrics (APP). Infants not intubated or extubated less than 15 min after birth were randomized for two treatments, routine or CPAP, and were followed until hospital discharge. The routine (n=99) and CPAP (n=98) infants studied presented no statistically significant differences regarding birth characteristics, complications during the prenatal period, the need for mechanical ventilation during the first 5 days of life (19.2 vs 23.4%, P=0.50), use of surfactant (18.2 vs 17.3% P=0.92), or respiratory morbidity and mortality until discharge. The CPAP group required a greater number of doses of surfactant (1.5 vs 1.0, P=0.02). When CPAP was applied to the routine group, it was installed within a median time of 30 min. We found that CPAP applied less than 15 min after birth was not able to reduce the need for ventilator support and was associated with a higher number of doses of surfactant when compared to CPAP applied as clinically indicated within a median time of 30 min.