Understanding the role of CAP proteins in the polarization process of C. elegans

La division cellulaire asymétrique est un processus crucial dans le développement des organismes multicellulaires puisqu’elle permet la génération de la diversité cellulaire. Les cellules qui se divisent de façon asymétrique doivent tout d’abord se polariser et correctement orienter leur fuseau mitotique pour ségréger des déterminants cellulaires en deux entités distinctes. L’embryon du nématode C. elegans est un modèle robuste et largement utilisé pour étudier la division cellulaire asymétrique. Dans cet embryon, le point d'entrée du spermatozoïde détermine l'axe de polarité antéro-postérieur. Suite à la fécondation, le cortex embryonnaire est uniformément contractile et un complexe conservé formé des protéines PAR-3, PAR-6 et PKC-3 (nommé complexe PAR-3 ci-dessous) est localisé sur l'ensemble du cortex. La complétion de la méiose maternelle induit une relaxation corticale au postétieur et un flux cortical vers l’antérieur de l’embryon. Ces contractions corticales asymétriques mènent à la formation d'un domaine antérieur contenant le complexe PAR-3, tandis que le cortex postérieur, dont le complexe PAR-3 s’est délocalisé, est enrichi avec les protéines PAR-2 et PAR-1. Par conséquent, les domaines formés par les protéines PAR définissent un pôle antérieur et un pôle postérieur dans l'embryon suite au remodelage du cytosquelette. Les protéines PAR-4 et PAR-5 restent localisées de façon uniforme dans l'embryon. Curieusement, les protéines PAR exercent une régulation par rétroaction sur la contractilité corticale. Il a été montré qu’une des protéines PAR récemment identifiée, PAR-5, est orthologue à la protéine adaptatrice 14-3-3 et joue un rôle important dans la contractilité corticale. En dépit de son rôle central dans la contractilité corticale et le processus de polarisation cellulaire, le mécanisme par lequel PAR-5 régule la contractilité corticale n’est pas bien compris. Le but de ce projet est de mieux comprendre comment PAR-5 et ses interacteurs contrôlent la régulation des contractions corticales et, de ce fait, la polarité cellulaire. Dans un essai de capture de la protéine GST (GST pull-down), nous avons identifié plusieurs nouveaux interacteurs de PAR-5. Parmi ceux-ci, nous avons trouvé CAP-2 (protéine de coiffage de l'actine), qui a été identifiée dans des éxpériences de capture de 14-3-3 dans trois systèmes modèles différents. CAP-2 est un hétérodimère des protéines CAP, qui sont impliquées dans la régulation de l'actine. Nous avons trouvé que la déplétion des protéines CAP par interférence à l’ARN dans des vers de type sauvage mène à une augmentation létalité embryonnaire, ce qui suggère que ces protéines jouent un rôle important dans le développement embryonnaire. L'imagerie en temps réel d'embryons déplétés pour les protéines CAP montre qu’ils ont une diminution des contractions corticales avec un sillon de pseudoclivage mois stable, suggérant un défaut dans la régulation du cytosquelette d'actine-myosine. Ceci a également été confirmé par la diminution de la vitesse et du nombre de foci de NMY-2::GFP. En outre, ces embryons montrent une légère diminution de la taille du croissant cortical de PAR-2 lors de la phase d’établissement de la polarité. Les embryons déplétés en CAP-2 montrent également un retard dans la progression du cycle cellulaire, mais le lien entre ce phénotype et la régulation des contractions corticales reste à être précisé. La caractérisation des protéines CAP, des régulateurs du remodelage du cytosquelette, permettra d'améliorer notre compréhension des mécanismes qui sous-tendent l'établissement et le maintien de la polarité cellulaire, et donc la division cellulaire asymétrique.

Understanding the role of CAP proteins in the polarization process of C. elegans

La division cellulaire asymétrique est un processus crucial dans le développement des organismes multicellulaires puisqu’elle permet la génération de la diversité cellulaire. Les cellules qui se divisent de façon asymétrique doivent tout d’abord se polariser et correctement orienter leur fuseau mitotique pour ségréger des déterminants cellulaires en deux entités distinctes. L’embryon du nématode C. elegans est un modèle robuste et largement utilisé pour étudier la division cellulaire asymétrique. Dans cet embryon, le point d'entrée du spermatozoïde détermine l'axe de polarité antéro-postérieur. Suite à la fécondation, le cortex embryonnaire est uniformément contractile et un complexe conservé formé des protéines PAR-3, PAR-6 et PKC-3 (nommé complexe PAR-3 ci-dessous) est localisé sur l'ensemble du cortex. La complétion de la méiose maternelle induit une relaxation corticale au postétieur et un flux cortical vers l’antérieur de l’embryon. Ces contractions corticales asymétriques mènent à la formation d'un domaine antérieur contenant le complexe PAR-3, tandis que le cortex postérieur, dont le complexe PAR-3 s’est délocalisé, est enrichi avec les protéines PAR-2 et PAR-1. Par conséquent, les domaines formés par les protéines PAR définissent un pôle antérieur et un pôle postérieur dans l'embryon suite au remodelage du cytosquelette. Les protéines PAR-4 et PAR-5 restent localisées de façon uniforme dans l'embryon. Curieusement, les protéines PAR exercent une régulation par rétroaction sur la contractilité corticale. Il a été montré qu’une des protéines PAR récemment identifiée, PAR-5, est orthologue à la protéine adaptatrice 14-3-3 et joue un rôle important dans la contractilité corticale. En dépit de son rôle central dans la contractilité corticale et le processus de polarisation cellulaire, le mécanisme par lequel PAR-5 régule la contractilité corticale n’est pas bien compris. Le but de ce projet est de mieux comprendre comment PAR-5 et ses interacteurs contrôlent la régulation des contractions corticales et, de ce fait, la polarité cellulaire. Dans un essai de capture de la protéine GST (GST pull-down), nous avons identifié plusieurs nouveaux interacteurs de PAR-5. Parmi ceux-ci, nous avons trouvé CAP-2 (protéine de coiffage de l'actine), qui a été identifiée dans des éxpériences de capture de 14-3-3 dans trois systèmes modèles différents. CAP-2 est un hétérodimère des protéines CAP, qui sont impliquées dans la régulation de l'actine. Nous avons trouvé que la déplétion des protéines CAP par interférence à l’ARN dans des vers de type sauvage mène à une augmentation létalité embryonnaire, ce qui suggère que ces protéines jouent un rôle important dans le développement embryonnaire. L'imagerie en temps réel d'embryons déplétés pour les protéines CAP montre qu’ils ont une diminution des contractions corticales avec un sillon de pseudoclivage mois stable, suggérant un défaut dans la régulation du cytosquelette d'actine-myosine. Ceci a également été confirmé par la diminution de la vitesse et du nombre de foci de NMY-2::GFP. En outre, ces embryons montrent une légère diminution de la taille du croissant cortical de PAR-2 lors de la phase d’établissement de la polarité. Les embryons déplétés en CAP-2 montrent également un retard dans la progression du cycle cellulaire, mais le lien entre ce phénotype et la régulation des contractions corticales reste à être précisé. La caractérisation des protéines CAP, des régulateurs du remodelage du cytosquelette, permettra d'améliorer notre compréhension des mécanismes qui sous-tendent l'établissement et le maintien de la polarité cellulaire, et donc la division cellulaire asymétrique.

Internationalization process of TUBOFURO

The central objective of this case study was to formulate the strategy of internationalization of Tubofuro®, discriminating relevant points from its design to its implementation. This is a company located in Leiria, Ortigosa parish, which operates, among others, in the Portuguese PVC pipes industry for which currently the domestic market is clearly insufficient, given the oversupply compared to demand. Being Tubofuro® an exporting company since 2004, the work here developed specifically intended to increase sales to the foreign market, with this representing 45% of total company's business in 2018 increasing of the number of markets through new partners to enable the positioning of Tubofuro® among the main players in each market, particularly in South American markets, North African and European. To achieve the above objectives presented a case study was applied, centred on Tubofuro® company, target of the internationalization strategy. The search carried out for the formulation of the strategy has been supported on a thorough analysis of the external environment and internal characteristics of the company, for which were crossed different types of data, quantitative, qualitative, secondary data and primary data. From this work resulted the development of internationalization and international marketing plan for the next three years, whose objectives are based on entrance and consequent growth in new markets, including the market Chilean, Peruvian, Mexican, Argentine, Algerian and German, as well growth in the presence and turnover in the markets for which Tubofuro® already exports regularly, for example Spain, France, Tunisia and Morocco. Based on the production capacity of Tubofuro® company, which will not suffer any kind of investment for incrementing but only to update, it is expected that the appropriate response capacity for the company is 8 regular markets, and could eventually arise sporadic exports to other markets not interfering with the normal production capacity of the company. The suggestion of the presented markets resulted from the study of the final price based on the one that local customers purchase a product equal or similar to Tubofuro® and the number of potential existing customers in each market. The internationalization model known as Uppsala Model corresponds to the strategy adopted by the company to its internationalization process, taking into account the philosophy of senior management and the risk aversion of them. The sales team Tubofuro® demand for each market, export a full container registering customer feedback, including quality and flow capacity in the market in order to seek a partnership agreement with a local distributor, which allows the Tubofuro® go to step two above mentioned model. The partnership agreement is based on mutual commitment to technical cooperation and trade between the Tubofuro® and partner, in order to increase the performance capacity among local customers. Only if the market presents a greater demand to our supply capacity and be justified by cost / benefit ratio, the entry into this market through a joint venture or subsidiary is that the decision will be taken. Although this is a case study, which means that is adjusted to the concrete case Tubofuro® preventing generalization of findings, we believe that this work can be a useful example for other companies in the internationalization process or the methodology adopted in formulating strategy or the outputs and conclusions drawn.

Person, community, Tian: the emergence of order and harmony in Chinese philosophy

This thesis clarifies how the concept of tian functions in Chinese thought, and what tianren heyi (the continuity between tian and humans) means in the Chinese context. With a new interpretation about tianren heyi, I provide a new contribution for understanding these Chinese concepts for an English speaking audience. Tian is not a fixed concept like the idea of heaven, rather, it can be the principle for one’s immanent world. The meaning of the term changes depending on the context it is being used in, and can also be neutral when necessary. Continuity means that there is a resonance and reciprocity in the way these aspects of cosmology emerge together. Humans and tian are not being unified or connected—there is simply continuity between them. What happens is that a productive relationship between them produces depth, harmony, and enhanced significance. Through the interaction between humanity and tian, the human world gains order, and from the perspective of tian, gains harmony. This different understanding the continuity between humanity and tian leads to a new understanding of timing or the appropriateness in li. In the process of practice and self cultivation, it is seen that li is also an idea that is not fixed to one single interpretation as it is connected with timing and appropriateness. The Classical Chinese concept of “Person” (ren 人), as the concrete context of li, is the centre of this practice. Because of the unfixed natures of tian and li, one needs to be flexible in order to cater to their demands. This embodies the freedom of the subject in Chinese thought. As the outcome of li, the social and political structure is shaped in this process, the examples being the models of “great union” and “small tranquillity” (Chapter 3) in Chinese tradition.

Women's experiences of how their recovery process is promoted after a first myocardial infarction : Implications for cardiac rehabilitation care

Background: After a myocardial infarction and discharge from the hospital a recovery process follows for the women. In order to facilitate their recovery, both a preventive and promotive perspective should be taken into consideration. Despite this, today´s healthcare focuses more on prevention and thus research into the promotion of women’s recovery process is needed. Aim: To explore how women’s recovery processes are promoted after a first myocardial infarction Methods: The study had an explorative and descriptive design based on qualitative content analysis. Findings: The women’s recovery process was promoted through using external and internal resources as well as embracing behaviour, social and psychological dimensions. The women embraced these dimensions to a varying extent and this process led to them being able to take in a new perspective on life. Conclusions: The women’s personal recovery is a multidirectional process with a desire to develop and approach a new perspective on life. It is important for cardiac rehabilitation nurses to not only focus on lifestyle changes and social support, but also on working actively with the women’s inner strength in order to promote the personal recovery of the women. Furthermore, it would be interesting to investigate men’s experiences of how their recovery process after a first Myocardial infarction is promoted.

Teaching / learning process through the case method in the law degree

This project in teaching innovation and improvement aims to disseminate the case method as one of the most innovative educational instruments inteaching of Law in general, and specifically with regard to Family and Inheritance Law. The methodology used ensures learning through a legal conflict, which must be resolved by the students themselves from different viewpoints as legal agents. This is an activity in teaching innovation, in which students become the protagonists. Participation is voluntary, and the main aim is student motivation. The subject's aim is for students to learn public speaking skills fundamental to the profession while familiarising themselves with judicial practice. Theteacher sets up a legal conflict in order for students to resolve the dispute as legal agents with divergent viewpoints - in other words, as judges, attorneys, lawyers and so on. The project seeks alternatives to traditional teaching methods and is an innovative teaching method aimed at professionally training future lawyers as well as being a model that involves students more in their own learning.

Caracterización de las condiciones de salud y de trabajo y su relación con lesiones cutáneas en los orfebres artesanales de Mompox Bolivar-Colombia 2015

INTRODUCCIÓN Las alteraciones de la salud relacionadas con el trabajo (enfermedades y accidentes), pueden prevenirse desde las actividades bien enfocadas del Sistema de Gestión de Seguridad y Salud en el Trabajo (SGSST), realizando la identificación y control de los agentes causales en el ambiente de trabajo y la vigilancia de la salud de la población trabajadora. El proyecto desarrollado va dirigido a un grupo específico de artesanos orfebres en la ciudad de Mompox, Bolivar, en la que esta labor artesanal se centra en el arte de la filigrana, transmitido generacionalmente desde antaño En esta ciudad los artesanos orfebres, aunque corresponden a un sector informal de la economía, se encuentran agremiados principalmente en tres asociaciones ubicadas en la cabecera municipal. En el desempeño de sus labores, estos profesionales del arte de la filigrana manipulan agentes químicos como el ácido nítrico, el ácido sulfúrico, la plata y el mercurio, los cuales se utilizan en las diferentes etapas del proceso que incluye técnicas propias de esta labor. Teniendo en cuenta que la información disponible en la literatura científica describe principalmente los efectos de agentes químicos en otros oficios diferentes a la población orfebre y conociendo que la exposición a estas sustancias químicas puede generar variados efectos en el organismo, el interés de este proyecto se centra específicamente en las alteraciones cutáneas posiblemente relacionadas con las condiciones de trabajo de esta población del sector informal. MATERIALES Y METODOS La presente investigación es un estudio de corte trasversal, el cual realizó una selección por conveniencia de 114 trabajadores de orfebres Momposinos con el fin de identificar la relación de las condiciones de trabajo con la presencia de alteraciones cutáneas de los trabajadores que laboran en la orfebrería artesanal en la ciudad de Mompox, departamento de Bolívar, en el año 2015, de tal manera que dejando a consideración la descripción de los hallazgos encontrados, se posibiliten futuras y precisas investigaciones e intervenciones en este colectivo de trabajadores. Los instrumentos empleados para la recolección de la información y para el cumplimento de los objetivos fueron la encuesta Nacional de Condiciones de Trabajo del Instituto Nacional de Seguridad e Higiene en el trabajo de España (INSHT) que permite recolectar información sobre la caracterización de la población a nivel sociodemográfico y ocupacional, y para la determinación de patologías dermatológicas relacionadas con el trabajo se utilizó el Cuestionario NOSQ-2002 Nórdico- Enfermedades Cutáneas de origen Laboral, en su versión validada en español. Se describieron las variables categóricas con porcentajes y las continuas (cuantitativas) con medidas de tendencia central y dispersión La asociación entre los hallazgos de exposición ocupacional y los síntomas y signos en piel, fue estimada mediante riesgos relativos. RESULTADOS El 75,4% del total de la población correspondió al género masculino y el 67,5% reportó realizar sus labores como trabajadores independientes. Respecto a la identificación de condiciones de salud, la percepción por parte de los orfebres fue positiva, reportando muy buena salud en el 34% de los mismos. El 8% de la población manifestó alteraciones dermatológicas tipo eczema en los últimos seis meses y el 11% las presentó principalmente en manos. Respecto de la iniciación del eczema, el 97% de los trabajadores reportó que se iniciaba al contacto con sustancias químicas y el 98,7% manifestó que se encontraban realizando la labor de orfebrería cuando inició el eczema. La lesión prevalente fue mancha roja sin edema (8%), seguida de ronchas o manchas y ampollas pequeñas (3%) y de piel seca con escamas (2%). CONCLUSIONES Los resultados de la presente investigación mostraron la prevalencia de alteraciones cutáneas principalmente en las manos, tipo eczema (manchas rojas) o prurito (picor). Se recomienda la disminución de los tiempos de exposición, adecuación de jornadas y tiempos de descanso, sistemas de protección personal adecuados y la implementación de un programa de educación y participación para el control integral del riesgo.

Contribución de la misión de naciones unidas en Guatemala – Minugua, a la promoción, defensa y garantía de los derechos de la población indígena guatemalteca (1994 a 2004)

El conflicto armado en Guatemala se originó por el abuso de poder, la desigualdad, la exclusión y la profunda discriminación, sobre todo hacia la población indígena, a la que se le han desconocido históricamente sus derechos y que fue la más afligida durante el conflicto. Lo que desembocó en el nacimiento de grupos al margen de la ley, cuyo propósito fue reivindicar los derechos de la población, así como la equidad y justicia social. El conflicto se caracterizó por la formación de grupos paramilitares, la violación al Derecho Internacional Humanitario, el elevado número de víctimas del conflicto, mayoritariamente indígenas y porque más del 85% de las violaciones a los derechos humanos fueron perpetradas por el Estado. Gracias a la voluntad política, al respaldo de la comunidad internacional, especialmente de la Organización de Naciones Unidas -ONU, y a los buenos oficios de la Comisión Nacional de Reconciliación – CNR, se lograron firmar los Acuerdos de Paz y dar fin a este cruento conflicto de más de 36 años. Las partes firmantes vieron la necesidad de que un ente autónomo e imparcial de Naciones Unidas, verificara el cumplimiento de La Misión de Naciones Unidas en Guatemala - MINUGUA contribuyó a la promoción, defensa y garantía de los derechos de la población indígena guatemalteca. Específicamente, incidió en el cumplimiento de los compromisos contenidos en el Acuerdo sobre Identidad y Derechos de los Pueblos Indígenas guatemaltecos –AIDPI, que fue suscrito el 31 de marzo de 1995, asimismo, contribuyó a la garantía del derecho a la justicia de la población indígena, lo que se evidenció en las acciones y el papel que desempeñó en los componentes de verdad, justicia y reparación.

Dynamical modeling of biogas production supported by an experimental anaerobic digestion process

This paper presents the development of a combined experimental and numerical approach to study the anaerobic digestion of both the wastes produced in a biorefinery using yeast for biodiesel production and the wastes generated in the preceding microbial biomass production. The experimental results show that it is possible to valorise through anaerobic digestion all the tested residues. In the implementation of the numerical model for anaerobic digestion, a procedure for the identification of its parameters needs to be developed. A hybrid search Genetic Algorithm was used, followed by a direct search method. In order to test the procedure for estimation of parameters, first noise-free data was considered and a critical analysis of the results obtain so far was undertaken. As a demonstration of its application, the procedure was applied to experimental data.

Trandisciplinarity and Design: Comparative Review and Synthesis for the Design Process

Transdisciplinarity gained importance in the 1970s, with the initial signs of weakness of both multi- and interdisciplinary approaches. This weakness was felt due to the increased complexity in the social and technological landscapes. Generally, discussion over the transdisciplinary topic is centred in social and health sciences. Therefore, the major challenge in this research is to adapt design research to the emerging transdisciplinary discussion. Based on a comparative and critical review of several engineering and design models for the design process, we advocate the importance of collaboration and conceptualisation for these disciplines. Therefore, a transdisciplinary and conceptual cooperation between engineering and industrial design disciplines is considered as decisive to create breakthroughs. Furthermore, a synthesis is proposed, in order to foster the cooperation between engineering and industrial design.

Reaching the unreached: de-mystifying the role of ICT in the process of doctoral research

Information and Communication Technology (ICT) has become a necessary element of academic practice in higher education today. Under normal circumstances, PhD students from all disciplines have to use ICT in some form throughout the process of their research, including the preparation, fieldwork, analysis and writing phases of their studies. Nevertheless, there has been little research to date that explores PhD students’ first-hand experiences of using various ICT to support their research practices. This paper brings together the findings and the key points from a review of significant parts of the existing literature associated with the role played by ICT in the processes PhD students use in doctoral research. The review is based on 27 papers appearing in international peer-reviewed journals published from 2005 to 2014. The study seeks to address the under-researched area in the current literature of how ICT plays a role in the processes of doctoral research. While there are many contributions taking the ‘institutional’ or ‘teaching’ perspectives, papers focusing on ‘student’ perspective, or the viewpoint of engaging ICT in daily study routine, are relatively fewer. As far as research methodology is concerned, this review found that many of the papers that were examined were mostly based on perception data such as surveys or interviews, while actual practice data were rarely present. With their ready access to technologies, PhD students are well positioned to take advantage of a range of technologies in order to carry out their research efficiently (in terms of means to an end) and effectively (in terms of reaching goals within a task). This review reveals that in the literature, this important area is under-represented.

High-strength steels manufactured via Laser Powder Bed Fusion: effect of post-process heat treatments and surface finishing on microstructure and mechanical properties

Laser Powder Bed Fusion (LPBF) permits the manufacturing of parts with optimized geometry, enabling lightweight design of mechanical components in aerospace and automotive and the production of tools with conformal cooling channels. In order to produce parts with high strength-to-weight ratio, high-strength steels are required. To date, the most diffused high-strength steels for LPBF are hot-work tool steels, maraging and precipitation-hardening stainless steels, featuring different composition, feasibility and properties. Moreover, LPBF parts usually require a proper heat treatment and surface finishing, to develop the desired properties and reduce the high roughness resulting from LPBF. The present PhD thesis investigates the effect of different heat treatments and surface finishing on the microstructure and mechanical properties of a hot-work tool steel and a precipitation-hardening stainless steel manufactured via LPBF. The bibliographic section focuses on the main aspects of LPBF, hot-work tool steels and precipitation-hardening stainless steels. The experimental section is divided in two parts. Part A addresses the effect of different heat treatments and surface finishing on the microstructure, hardness, tensile and fatigue behaviour of a LPBF manufactured hot-work tool steel, to evaluate its feasibility for automotive and racing components. Results indicated the possibility to achieve high hardness and strength, comparable to the conventionally produced steel, but a great sensitivity of fatigue strength on defects and surface roughness resulting from LPBF. Part B investigates the effect of different heat treatments on the microstructure, hardness, tensile and notch-impact behaviour of a LPBF produced precipitation-hardening stainless steel, to assess its feasibility for tooling applications. Results indicated the possibility to achieve high hardness and strength also through a simple Direct Aging, enabling heat treatment simplification by exploiting the microstructural features resulting from LPBF.

Optimization of a polyhydroxyalkanoates production process using a halotolerant mixed microbial culture

The rate at which petroleum based plastics are being produced, used and thrown away is increasing every year because of an increase in the global population. Polyhydroxyalkanoates can represent a valid alternative to petroleum based plastics. They are biodegradable polymers that can be produced by some microorganisms as intracellular reserves. The actual problem is represented by the production cost of these bioplastics, which is still not competitive if compared to the one of petroleum based plastics. Mixed microbial cultures can be fed with substrates obtained from the acidogenic fermentation of carbon rich wastes, such as cheese whey, municipal effluents and various kinds of food wastes, that have a low or sometimes even inexisting cost and in this way wastes can be valorized instead of being discharged. The process consists of three phases: acidogenic fermentation in which the substrate is obtained, culture selection in which a PHA-storing culture is selected and enriched eliminating organisms that do not show this property and accumulation, in which the culture is fed until reaching the maximum storage capacity. In this work the possibility to make the process cheaper was explored trying to couple the selection and accumulation steps and a halotolerant culture collected from seawater was used and fed with an artificially salted synthetic substrated made of an aqueous solution containing a mixture of volatile fatty acids in order to explore also if its performance can allow to use it to treat substrates derived from saline effluents, as these streams cannot be treated properly by bacterias found in activated sludge plants due to inhibition caused by high salt concentrations. Generating and selling the produced PHAs obtained from these bacterias it could be possible to lower, nullify or even overcome the costs associated to the new section of a treating plant dedicated to saline effluents.

Analytic Network Process (ANP) a supporto della scelta della strategia produttiva: sviluppo e test di un approccio decisionale

Di fronte alla concorrenza globale, la sopravvivenza di un'azienda manifatturiera dipende sempre più da come essa può progettare, gestire e strutturare al meglio il proprio sistema di produzione per far fronte alla diversità dei prodotti, per migliorare l'affidabilità di consegna e anche per ridurre i costi. In questo contesto, le aziende manifatturiere utilizzano spesso sistemi di produzione diversi, in base a ciò che richiede il mercato. Molto in generale, i sistemi produttivi possono essere classificati in due categorie principali: make-to-stock (MTS) e make-to-order (MTO), in base alla politica di risposta alla domanda del mercato. Nel nuovo contesto competitivo le aziende si sono trovate a dover produrre costantemente prodotti specifici e di alta qualità con costi unitari bassi e livelli di servizio elevati (ossia, tempi di consegna brevi). È chiaro, dunque, che una delle principali decisioni strategiche da prendere da parte delle aziende sia quella relativa alla ripartizione dei prodotti in MTS/MTO, ovvero quale prodotto o famiglia di prodotti può essere fabbricato per essere stoccato a magazzino (MTS), quale può essere prodotto su ordinazione (MTO) e quale dovrebbe essere fabbricato in base alla politica di produzione ibrida MTS/MTO. Gli ultimi anni hanno mostrato una serie di cambiamenti nella politica di produzione delle aziende, che si stanno gradualmente spostando sempre più verso la modalità̀ di produzione ibrida MTS/MTO. In particolare, questo elaborato si concentrerà sul delayed product differentiation (DPD), una particolare strategia produttiva ibrida, e ne verrà proposto un modello decisionale basato sul funzionamento dell’Analytic Network Process (ANP) implementato attraverso il software Superdecisions.

The Applicability Of Ordered Mesoporous Sba-15 And Its Hydrophobic Glutaraldehyde-bridge Derivative To Improve Ibuprofen-loading In Releasing System.

The mesoporous SBA-15 silica with uniform hexagonal pore, narrow pore size distribution and tuneable pore diameter was organofunctionalized with glutaraldehyde-bridged silylating agent. The precursor and its derivative silicas were ibuprofen-loaded for controlled delivery in simulated biological fluids. The synthesized silicas were characterized by elemental analysis, infrared spectroscopy, (13)C and (29)Si solid state NMR spectroscopy, nitrogen adsorption, X-ray diffractometry, thermogravimetry and scanning electron microscopy. Surface functionalization with amine containing bridged hydrophobic structure resulted in significantly decreased surface area from 802.4 to 63.0 m(2) g(-1) and pore diameter 8.0-6.0 nm, which ultimately increased the drug-loading capacity from 18.0% up to 28.3% and a very slow release rate of ibuprofen over the period of 72.5h. The in vitro drug release demonstrated that SBA-15 presented the fastest release from 25% to 27% and SBA-15GA gave near 10% of drug release in all fluids during 72.5 h. The Korsmeyer-Peppas model better fits the release data with the Fickian diffusion mechanism and zero order kinetics for synthesized mesoporous silicas. Both pore sizes and hydrophobicity influenced the rate of the release process, indicating that the chemically modified silica can be suggested to design formulation of slow and constant release over a defined period, to avoid repeated administration.