Strategies for the Controlled Synthesis of Oligomeric Natural Products

1 - Total Syntheses of Helicterin B, Helisorin, and Helisterculin A - The total synthesis of three members of the helicterin family of natural products, helicterin B, helisorin and helisterculin A, was completed from a common, non-biomimetic intermediate. This work featured the development of a complex retro Diels-Alder/Diels-Alder sequence, a Friedel-Crafts ring closure resulting in a highly strained ring-system, an acid-catalyzed hydroxyketone rearrangement, a Lewis acid-promoted dimerization of a bicyclooctene monomer, and the use of a novel phenol protecting group. 2 - Synthetic Studies of an Alternative Diels-Alder Approach Towards the Helicterin and the Yunnaneic Acid Families of Natural Products - Efforts towards the development of an enantioselective synthesis of the helicterin natural products are presented. Given the failure of known methods to achieve this goal, a novel Diels-Alder approach based on a revised biosynthetic proposal was explored. This method achieved a bicyclooctene framework with good stereoselectivity, but its conversion to the natural product core proved challenging. Additionally, a Diels-Alder approach to the core of the yunnaneic acids was developed, one in which the effective reversal of the regiochemical preference of the reaction was achieved. 3 - Small Molecule Inhibitors of Cell Death in a Huntington's Disease Model - A compound based on the core of the helicterin natural products with the ability to prevent cell death in a Huntington's Disease model system was identified. Although its mechanism of action is unknown, its cellular target appears to be distinct from that of prior inhibitors. A number of analogs based on this initial hit were synthesized, and structure-activity relationships were explored. 4 - Synthetic Studies Towards a Biomimetic Approach to the Myrmicarin Alkaloids - The shortest and highest yielding synthesis of the monomeric myrmicarin alkaloids to date has been completed, and the stereochemical complexity of the upper half of the dimeric myrmicarin 430A has been achieved for the first time. Although the dienamine building blocks readily afforded the monomeric natural products under presumed biological conditions, the results of synthetic and theoretical experiments suggest that their dimers are either non-biomimetic or that enzymes are required in the biosynthesis of the higher-order myrmicarins. 5 - Studies on The Mechanism of the Knorr Pyrrole Cyclization - A mechanistic study of the Knorr pyrrole cyclization of an indolizidine-based dienamine to myrmicarin 215B was completed. This cyclization was found to occur exclusively in polar protic solvents, and two solvent molecules were required in the rate-determining step. A revised mechanism for this cyclization is proposed, in which a slow ketone protonation step precedes the cyclization and dehydration steps

Advanced control strategies toward achieving nearly-zero energy consumption in buildings

In this paper the main concept and results of the PEBBLE Project are presented: PEBBLE is an ongoing FP7 Project aiming at the development of advanced ICT tools to support the operation of nearly-zero- and positive energy buildings. In the design and operation of such buildings a pragmatic target is maximization of the actual net energy produced (NEP) by intelligently shaping demand to perform generation-consumption matching. With the belief that maximization of the NEP for Positive-Energy Buildings is attained thru Better ControL decisions (PEBBLE), a control and optimization ICT methodology that combines model-based predictive control and cognitive-based adaptive optimization is presented. There are three essential ingredients to the PEBBLE system: a) thermal simulation models; b) sensors, actuators, and user interfaces; and c), generic control and optimization tools. The potential for energy savings using advanced control strategies is illustrated using simulation-based studies: there are significant benefits in terms of energy-performance of using advanced control strategies, compared to traditional rule-based ones. Ongoing work about demonstration and evaluation of the PEBBLE system in three real world buildings is described

Comparing the impact of different thermal comfort constraints on a model-assisted control design process

In the design of supervisory controllers for managing energy in buildings, modelbased control design approaches have recently attracted significant attention. The control-design problem in these cases is typically posed as a constrained minimization problem: given a simulation model acting as a surrogate of the building, identify a controller that minimizes a cost function, say energy, subject to the constraint that thermal comfort stays within acceptable levels. The use of a thermal comfort model can be the means for estimating comfort so that the mathematical programming problem can be formulated. In the present paper, we investigate how the choice of thermal comfort model affects the quality of the resulting controller. We consider a building simulated in EnergyPlus and design, under the same conditions, controllers using three different thermal comfort models: the model of Fanger, the two-node Pierce model, and the KSU two-node model. A comparative study is performed to draw conclusions upon the effects that this selection has with respect to the performance of the resulting controller

Strategies for the Controlled Synthesis of Oligomeric Natural Products

1 - Total Syntheses of Helicterin B, Helisorin, and Helisterculin A - The total synthesis of three members of the helicterin family of natural products, helicterin B, helisorin and helisterculin A, was completed from a common, non-biomimetic intermediate. This work featured the development of a complex retro Diels-Alder/Diels-Alder sequence, a Friedel-Crafts ring closure resulting in a highly strained ring-system, an acid-catalyzed hydroxyketone rearrangement, a Lewis acid-promoted dimerization of a bicyclooctene monomer, and the use of a novel phenol protecting group. 2 - Synthetic Studies of an Alternative Diels-Alder Approach Towards the Helicterin and the Yunnaneic Acid Families of Natural Products - Efforts towards the development of an enantioselective synthesis of the helicterin natural products are presented. Given the failure of known methods to achieve this goal, a novel Diels-Alder approach based on a revised biosynthetic proposal was explored. This method achieved a bicyclooctene framework with good stereoselectivity, but its conversion to the natural product core proved challenging. Additionally, a Diels-Alder approach to the core of the yunnaneic acids was developed, one in which the effective reversal of the regiochemical preference of the reaction was achieved. 3 - Small Molecule Inhibitors of Cell Death in a Huntington's Disease Model - A compound based on the core of the helicterin natural products with the ability to prevent cell death in a Huntington's Disease model system was identified. Although its mechanism of action is unknown, its cellular target appears to be distinct from that of prior inhibitors. A number of analogs based on this initial hit were synthesized, and structure-activity relationships were explored. 4 - Synthetic Studies Towards a Biomimetic Approach to the Myrmicarin Alkaloids - The shortest and highest yielding synthesis of the monomeric myrmicarin alkaloids to date has been completed, and the stereochemical complexity of the upper half of the dimeric myrmicarin 430A has been achieved for the first time. Although the dienamine building blocks readily afforded the monomeric natural products under presumed biological conditions, the results of synthetic and theoretical experiments suggest that their dimers are either non-biomimetic or that enzymes are required in the biosynthesis of the higher-order myrmicarins. 5 - Studies on The Mechanism of the Knorr Pyrrole Cyclization - A mechanistic study of the Knorr pyrrole cyclization of an indolizidine-based dienamine to myrmicarin 215B was completed. This cyclization was found to occur exclusively in polar protic solvents, and two solvent molecules were required in the rate-determining step. A revised mechanism for this cyclization is proposed, in which a slow ketone protonation step precedes the cyclization and dehydration steps

Co-simulation setup for online model-assisted control design

For reduction of energy intensity of the building sector, effective and parsimonious use of energy resources and climate control systems is a prerequisite. Intelligent Building Energy Management Systems (BEMS) can be key ingredients towards achieving this goal; the incorporation of forecast data into the decision process can help achieve improved performance compared to existing state-of-the-art approaches. In the present paper, the potential of model-based supervisory control design algorithms for automatically designing BEMS is evaluated by performing experiments in a real building. A co-simulation setup is implemented where the thermal simulation model of the building is warmed up using past sensed data and then, given weather and occupancy forecasts, a controller is designed by solving a constrained minimization problem. A stochastic optimization algorithm is used to intelligently search the controller parameter space and identify a controller that minimizes an energy-related cost function, subject to thermal comfort constraints. A middleware solution is deployed in the building to facilitate two-way communication between the building (sensing and actuation) layer and the algorithmic layer

Simulation-time reduction techniques for a retrofit planning tool

The design of retrofitted energy efficient buildings is a promising option towards achieving a cost-effective improvement of the overall building sector’s energy performance. With the aim of discovering the best design for a retrofitting project in an automatic manner, a decision making (or optimization) process is usually adopted, utilizing accurate building simulation models towards evaluating the candidate retrofitting scenarios. A major factor which affects the overall computational time of such a process is the simulation execution time. Since high complexity and prohibitive simulation execution time are predominantly due to the full-scale, detailed simulation, in this work, the following simulation-time reduction methodologies are evaluated with respect to accuracy and computational effort in a test building: Hierarchical clustering; Koopman modes; and Meta-models. The simplified model that would be the outcome of these approaches, can be utilized by any optimization approach to discover the best retrofitting option

Προστασία προσωπικών δεδομένων και ασφάλεια ηλεκτρονικής συνταγογράφησης και πληροφοριακών συστημάτων υγείας: Συστηματική ανασκόπηση

Σήμερα παγκοσμίως αναγνωρίζεται η ανάγκη για προστασία της ιδιωτικότητας, των προσωπικών δεδομένων και της ασφάλειας των ΠΣ και επικοινωνιών. Ακόμα πιο μεγάλη είναι η ανάγκη αυτή στον χώρο της Υγείας, ένα κατεξοχήν πολύπλοκο και ευαίσθητο χώρο, που καθίσταται ακόμα πιο σύνθετος από την είσοδο των νεών ΤΠΕ σε όλο το φάσμα υπηρεσιών και λειτουργιών του. Σκοπός της εισόδου αυτής είναι να τον υποστηρίξουν, να τον εξελίξουν, αλλά και να τον ελέγξουν. Προς αυτή την κατεύθυνση πρέπει και λαμβάνονται πλήθος μέτρων, τόσο σε θεωρητικό όσο και σε πρακτικό επίπεδο. Από την άλλη προβλέπεται ότι το κυβερνοέγκλημα θα αναπτύσσεται παγκοσμίως και το κόστος για τις επιχειρήσεις θα είναι τεράστιο. Αυτό σημαίνει ότι η ευρωπαϊκή και η παγκόσμια κοινότητα, θα πρέπει να δραστηριοποιηθεί και να επενδύσει σε θέματα ασφάλειας ΠΣ. Η ανάγκη για σχετική με τις παράνομες πράξεις νομοθεσία σε διεθνές επίπεδο είναι πάντα απαραίτητη, αλλά ακόμη πιο απαραίτητη είναι στην περίπτωση της ψηφιακής τεχνολογίας μιας και τα ψηφιακά σύνορα είναι πιο δύσκολο να ανιχνευθούν και να ελέγχθουν από τον μέσο άνθρωπο. Πρωτόκολλα και νομοθετικές διατάξεις έχουν οπωσδήποτε θεσπιστεί από δεκαετίες παράλληλα με την εξέλιξη της ψηφιακής τεχνολογίας και συνεχώς ανανεώνονται και αναθεωρούνται σε ένα κατεξοχήν δυναμικό και αναπτυσσόμενο περιβάλλον, όπως είναι η εισαγωγή ΤΠΕ σε όλες τις κοινωνικές δομές και στο χώρο της υγείας ειδικότερα. Αντικείμενο της διπλωματικής, είναι να περιγράψει τις απειλές, το νομοθετικό πλαίσιο, τη διαχείριση κινδύνου, και τα τεχνικά μέτρα που πρέπει να λαμβάνονται υπ΄όψιν προκειμένου να τεθεί σε τάξη η ασφάλεια στην ψηφιακή υγεία, με σκοπό την προστασία της δημόσιας υγείας και των κοινωνικών αξιών γενικότερα. Αυτό θα αυξήσει το αίσθημα της εμπιστοσύνης των ανθρώπων στη χρήση και επέκταση των νέων ψηφιακών τεχνολογιών στην Υγεία, που είναι και το τελικό ζητούμενο. Για το σκοπό της διπλωματικής μελέτης, χρησιμοποιήθηκαν μηχανές αναζήτησης, όπως η Google scholar η Pubmed και η ΙEEExplore και σχετικές με το θέμα λέξεις κλειδιά, όπως επίσης μελετήθηκαν εκτεταμένα και ιστότοποι σχετικών εθνικών, ευρωπαϊκών, διεθνών οργανισμών, και επιχειρήσεων.Τhe need for the protection of privacy and personal information, and for the security of information systems is universally acknowledged in our time, as of extreme importance. This becomes more imperative in Healthcare as it is a profoundly complex and sensitive environment, which with the introduction of modern information and communication technologies in every aspect of its spectrum, becomes even more complex. Τhe reason for the introduction of IT technologies in the Healthcare sector is to support, improve and also control the sector. To this end multiple measures should be considered and addressed both in theoretical and practical level. Cybercrime is expected to rise in numbers world-wide, and the expected cost for businesses to be enormous. Τhis means that both Europe and the global community will have to adjust and invest in IT security fields. The need for relevant legislation against illegal actions in an international level is always necessary, but even more so in the case of digital technologies, as the digital borders are even harder to be monitored and controlled from the average person. For this purpose and for decades now in accordance with the evolution of IT, relative technical protocols, legislative acts are endorsed and are being continuously updated in a dynamic and constantly developing environment, as is the introduction of IT in all aspects of society and in Healthcare in particular. This will be the object of this thesis, to outline the threats, the legal aspects, the risk-management, and the technical measures that must be considered in order to place digital health security under control, and thus protect both public health and society values. This in the end will increase trust in the use and development of new digital technologies in Healthcare, which is the main objective. For this research, search engines like Google Scholar, PubMed, and IEEExplore were searched using relevant to the subject Keywords and also official business, national and international websites of important relevant organisations were visited

Functional and technological definition of BIM-aware services to assess, predict and optimize energy performance of buildings

There are a number of important elements in designing of building energy management systems – when data collection, aggregation and management is usually well addressed by existing building management systems, actual analytical components allowing to diagnose energy-prone and/or user comfort compromising behaviors are far less mature. It is not only about developing algorithms for such tools, but also proper design of a hosting platform and its viability – it should not only enable access to sensor readings, but also provide access to other building data like Building Information Models and allow collaboration and interconnection of such analytics. BaaS project calls such tools Assess, Predict and Optimize services. Developing a smart platform supporting these services naturally leads to a concept of the building as a service ecosystem (BaaS) where any new tool can be plugged in the system and can benefit from already existing components. In the present work, the high level architecture of the BaaS platform is presented and the ability of BaaS system to act as a platform enabling the building contextual data as well as dynamic data (sensor readings) to software modules is demonstrated through a use-case example on a simple one zone office building

Sense‐Think‐Act Framework for Intelligent Building Energy Management

The realization of smart and energetically efficient buildings is contingent upon the successful implementation of two tasks that occur on distinct phases of the building life cycle: in the design and subsequent retrofitting phases, the selection and implementation of an effective energy concept, and, during the operation phase, the actuation of energy systems to ensure parsimonious energy use while retaining acceptable end‐user thermal comfort. Operational efficiencies are achieved through the use of Building Energy Management Systems tasked to deliver core Sense, Think, Act (STA) functionalities: Sense, using sensing modalities installed in the building; Think, utilizing, typically a rule‐based decision system; and Act, by sending actuation commands to controllable building elements. Providing the intelligence in this STA process can be a formidable task due to the complex interplay of many systems and occurrence of disturbances. In this article, an architectural and algorithmic framework is presented to provide streamlined implementation of this process. Important ingredients in this framework are: (S) a data access component capable of collecting and aggregating information from a number of heterogeneous sources (sensors, weather stations, weather forecasts); (T) a model‐based optimization methodology to generate intelligent operational decisions; and (A) an assessment and actuation component. An illustrative application of the proposed methodology in an office building is provided