Innovation in conceptual design of chemical processes

Nowadays, the chemical industry has reached significant goals to produce essential components for human being. The growing competitiveness of the market caused an important acceleration in R&D activities, introducing new opportunities and procedures for the definition of process improvement and optimization. In this dynamicity, sustainability is becoming one of the key aspects for the technological progress encompassing economic, environmental protection and safety aspects. With respect to the conceptual definition of sustainability, literature reports an extensive discussion of the strategies, as well as sets of specific principles and guidelines. However, literature procedures are not completely suitable and applicable to process design activities. Therefore, the development and introduction of sustainability-oriented methodologies is a necessary step to enhance process and plant design. The definition of key drivers as support system is a focal point for early process design decisions or implementation of process modifications. In this context, three different methodologies are developed to support design activities providing criteria and guidelines in a sustainable perspective. In this framework, a set of key Performance Indicators is selected and adopted to characterize the environmental, safety, economic and energetic aspects of a reference process. The methodologies are based on heat and material balances and the level of detailed for input data are compatible with available information of the specific application. Multiple case-studies are defined to prove the effectiveness of the methodologies. The principal application is the polyolefin productive lifecycle chain with particular focus on polymerization technologies. In this context, different design phases are investigated spanning from early process feasibility study to operative and improvements assessment. This flexibility allows to apply the methodologies at any level of design, providing supporting guidelines for design activities, compare alternative solutions, monitor operating process and identify potential for improvements.

L'edilizia residenziale nell'era dell'economia circolare. Modelli e paradigmi per la rigenerazione delle periferie urbane

Il patrimonio residenziale italiano ammonta a 12,2 milioni di edifici, di cui il 57,5% ha più di 50 anni ed è stato costruito in assenza di normative specifiche, in termini di sicurezza sismica, resistenza al fuoco, efficienza energetica e accessibilità, e manifesta un’avanzata obsolescenza. Agire su questo patrimonio significa operare tramite le due macro categorie di intervento: demolizione/ricostruzione o riqualificazione energetica. Questa ricerca dottorale vuole indagare la demolizione/ricostruzione di comparti urbani periferici, costruiti tra 1945-1965, quale strategia di rigenerazione urbana, integrandola in un modello edilizio basato sui criteri dell’economia circolare. Vengono definite le caratteristiche costruttive e i principi di questo modello di progettazione ecosistemica, denominato Integrho, che coniuga i criteri di ecodesign nel ciclo di vita (Building in Layers, Design for Disassembly e il Design out Waste) con quelli di bioclimaticità e di adattabilità funzionale. Il lavoro è stato improntato secondo due livelli gerarchici, scala urbana e scala edilizia, tra loro correlate mediante quella intermedia dell’isolato, al fine di ottenere un obiettivo di natura metodologica: definire uno strumento di supporto decisionale, capace di indirizzare tra le categorie di intervento attraverso parametri oggettivi, valutati con analisi comparative speditive. Tale metodologia viene applicata al contesto di Bologna, e si fonda sulla creazione di un’approfondita base conoscitiva attraverso la catalogazione delle 8.209 pratiche edilizie di nuova costruzione presentate tra 1945 e il 1965. Tale strumento georeferenziato, contenente informazioni tipologiche, costruttive ecc., è impiegato per valutare in modo quantitativo e speditivo i consumi energetici, i materiali incorporati, gli impatti ambientali e i costi economici dei differenti scenari di intervento nel ciclo di vita. Infine, l’applicazione del modello edilizio Integrho e del paradigma Ri-Costruire per Ri-Generare ad uno degli isolati periferici selezionati, è impiegata come esemplificazione dell’intero processo, dalla fase conoscitiva a quella strumentale, al fine di verificarne l’attendibilità e l’applicabilità su larga scala.

Fatigue Design Challenges of Transition Pieces from Decommissioned Platforms for Offshore Wind Energy

All structures are subjected to various loading conditions and combinations. For offshore structures, these loads include permanent loads, hydrostatic pressure, wave, current, and wind loads. Typically, sea environments in different geographical regions are characterized by the 100-year wave height, surface currents, and velocity speeds. The main problems associated with the commonly used, deterministic method is the fact that not all waves have the same period, and that the actual stochastic nature of the marine environment is not taken into account. Offshore steel structure fatigue design is done using the DNVGL-RP-0005:2016 standard which takes precedence over the DNV-RP-C203 standard (2012). Fatigue analysis is necessary for oil and gas producing offshore steel structures which were first constructed in the Gulf of Mexico North Sea (the 1930s) and later in the North Sea (1960s). Fatigue strength is commonly described by S-N curves which have been obtained by laboratory experiments. The rapid development of the Offshore wind industry has caused the exploration into deeper ocean areas and the adoption of new support structural concepts such as full lattice tower systems amongst others. The optimal design of offshore wind support structures including foundation, turbine towers, and transition piece components putting into consideration, economy, safety, and even the environment is a critical challenge. In this study, fatigue design challenges of transition pieces from decommissioned platforms for offshore wind energy are proposed to be discussed. The fatigue resistance of the material and structural components under uniaxial and multiaxial loading is introduced with the new fatigue design rules whilst considering the combination of global and local modeling using finite element analysis software programs.

Development and testing of a safety module for diagnostics and protection from hazards in secondary woodworking machinery

The main theme covered by this dissertation is safety, set in the context of automatic machinery for secondary woodworking. The thesis describes in detail the project of a software module for CNC machining centers to protect the operator against hazards and to report errors in the machine safety management. Its design has been developed during an internship at SCM Group technical department. The development of the safety module is addressed step by step in a detailed way: first the company and the reference framework are introduced and then all the design choices are explained and justified. The discussion begins with a detailed analysis of the standards concerning woodworking machines and safety-related software. In this way, a clear and linear procedure can be established to develop and implement the internal structure of the module, its interface, and its application to specific safety-critical conditions. Afterwards, particular attention is paid to software testing, with the development of a comprehensive test procedure for the module, and to diagnostics, especially oriented towards signal management in IoT mode. Finally, the safety module is used as an anti-regression tool to initiate a design improvement of the machine control program. The refactoring steps performed in the process are explained in detail and the SCENT approach is introduced to test the result.

Design and management of a supply chain: a joint location-inventory problem under uncertainty (Part A)

In this paper, a joint location-inventory model is proposed that simultaneously optimises strategic supply chain design decisions such as facility location and customer allocation to facilities, and tactical-operational inventory management and production scheduling decisions. All this is analysed in a context of demand uncertainty and supply uncertainty. While demand uncertainty stems from potential fluctuations in customer demands over time, supply-side uncertainty is associated with the risk of “disruption” to which facilities may be subject. The latter is caused by external factors such as natural disasters, strikes, changes of ownership and information technology security incidents. The proposed model is formulated as a non-linear mixed integer programming problem to minimise the expected total cost, which includes four basic cost items: the fixed cost of locating facilities at candidate sites, the cost of transport from facilities to customers, the cost of working inventory, and the cost of safety stock. Next, since the optimisation problem is very complex and the number of evaluable instances is very low, a "matheuristic" solution is presented. This approach has a twofold objective: on the one hand, it considers a larger number of facilities and customers within the network in order to reproduce a supply chain configuration that more closely reflects a real-world context; on the other hand, it serves to generate a starting solution and perform a series of iterations to try to improve it. Thanks to this algorithm, it was possible to obtain a solution characterised by a lower total system cost than that observed for the initial solution. The study concludes with some reflections and the description of possible future insights.

Calibration of design strength values of Wire and Arc Additive Manufacturing inclined bars and intersections

Although being studied only for few years, Wire and Arc Additive Manufacturing (WAAM) will become the predominant way of producing stainless-steel elements in a near-like future. The analysis and study of such elements has yet to be defined in a proper way, but the projects regarding this subject are innovating more and more thanks to the findings discovered by the latter. This thesis is focused on an initial stage on the analysis of mechanical and geometrical properties of such stainless-steel elements produced by MX3D laboratories in Amsterdam, and to perform a calibration of the design strength values by means of Annex D of Eurocode 0, which talks about the analysis of the semi-probabilistic safety factors, hence the definition of characteristic values. Moreover, after testing the stainless-steel specimens by means of strain gauges and after obtaining mechanical and geometrical properties, a statistical analysis of such properties and an evaluation of characteristic values is performed. After this, there is to execute the calibration of design strength values of WAAM inclined bars and intersections.

Data analysis and hydrological modelling of rainfall and discharge extremes along the Tione River: implications for the design of water structures

There are many natural events that can negatively affect the urban ecosystem, but weather-climate variations are certainly among the most significant. The history of settlements has been characterized by extreme events like earthquakes and floods, which repeat themselves at different times, causing extensive damage to the built heritage on a structural and urban scale. Changes in climate also alter various climatic subsystems, changing rainfall regimes and hydrological cycles, increasing the frequency and intensity of extreme precipitation events (heavy rainfall).  From an hydrological risk perspective, it is crucial to understand future events that could occur and their magnitude in order to design safer infrastructures. Unfortunately, it is not easy to understand future scenarios as the complexity of climate is enormous.  For this thesis, precipitation and discharge extremes were primarily used as data sources. It is important to underline that the two data sets are not separated: changes in rainfall regime, due to climate change, could significantly affect overflows into receiving water bodies. It is imperative that we understand and model climate change effects on water structures to support the development of adaptation strategies.   The main purpose of this thesis is to search for suitable water structures for a road located along the Tione River. Therefore, through the analysis of the area from a hydrological point of view, we aim to guarantee the safety of the infrastructure over time.   The observations made have the purpose to underline how models such as a stochastic one can improve the quality of an analysis for design purposes, and influence choices.

Design, Synthesis And Biological Evaluation Of Hybrid Bioisoster Derivatives Of N-acylhydrazone And Furoxan Groups With Potential And Selective Anti-trypanosoma Cruzi Activity.

Hybrid bioisoster derivatives from N-acylhydrazones and furoxan groups were designed with the objective of obtaining at least a dual mechanism of action: cruzain inhibition and nitric oxide (NO) releasing activity. Fifteen designed compounds were synthesized varying the substitution in N-acylhydrazone and in furoxan group as well. They had its anti-Trypanosoma cruzi activity in amastigotes forms, NO releasing potential and inhibitory cruzain activity evaluated. The two most active compounds (6, 14) both in the parasite amastigotes and in the enzyme contain the nitro group in para position of the aromatic ring. The permeability screening in Caco-2 cell and cytotoxicity assay in human cells were performed for those most active compounds and both showed to be less cytotoxic than the reference drug, benznidazole. Compound 6 was the most promising, since besides activity it showed good permeability and selectivity index, higher than the reference drug. Thereby the compound 6 was considered as a possible candidate for additional studies.

Study Of The Homogeneity Of Drug Loaded In Polymeric Films Using Near-infrared Chemical Imaging And Split-plot Design.

Split-plot design (SPD) and near-infrared chemical imaging were used to study the homogeneity of the drug paracetamol loaded in films and prepared from mixtures of the biocompatible polymers hydroxypropyl methylcellulose, polyvinylpyrrolidone, and polyethyleneglycol. The study was split into two parts: a partial least-squares (PLS) model was developed for a pixel-to-pixel quantification of the drug loaded into films. Afterwards, a SPD was developed to study the influence of the polymeric composition of films and the two process conditions related to their preparation (percentage of the drug in the formulations and curing temperature) on the homogeneity of the drug dispersed in the polymeric matrix. Chemical images of each formulation of the SPD were obtained by pixel-to-pixel predictions of the drug using the PLS model of the first part, and macropixel analyses were performed for each image to obtain the y-responses (homogeneity parameter). The design was modeled using PLS regression, allowing only the most relevant factors to remain in the final model. The interpretation of the SPD was enhanced by utilizing the orthogonal PLS algorithm, where the y-orthogonal variations in the design were separated from the y-correlated variation.

Doehlert Design-desirability Function Multi-criteria Optimal Separation Of 17 Phenolic Compounds From Extra-virgin Olive Oil By Capillary Zone Electrophoresis.

In Brazil, the consumption of extra-virgin olive oil (EVOO) is increasing annually, but there are no experimental studies concerning the phenolic compound contents of commercial EVOO. The aim of this work was to optimise the separation of 17 phenolic compounds already detected in EVOO. A Doehlert matrix experimental design was used, evaluating the effects of pH and electrolyte concentration. Resolution, runtime and migration time relative standard deviation values were evaluated. Derringer's desirability function was used to simultaneously optimise all 37 responses. The 17 peaks were separated in 19min using a fused-silica capillary (50μm internal diameter, 72cm of effective length) with an extended light path and 101.3mmolL(-1) of boric acid electrolyte (pH 9.15, 30kV). The method was validated and applied to 15 EVOO samples found in Brazilian supermarkets.

Predictive Value Of Phase I Trials For Safety In Later Trials And Final Approved Dose: Analysis Of 61 Approved Cancer Drugs.

Phase I trials use a small number of patients to define a maximum tolerated dose (MTD) and the safety of new agents. We compared data from phase I and registration trials to determine whether early trials predicted later safety and final dose. We searched the U.S. Food and Drug Administration (FDA) website for drugs approved in nonpediatric cancers (January 1990-October 2012). The recommended phase II dose (R2PD) and toxicities from phase I were compared with doses and safety in later trials. In 62 of 85 (73%) matched trials, the dose from the later trial was within 20% of the RP2D. In a multivariable analysis, phase I trials of targeted agents were less predictive of the final approved dose (OR, 0.2 for adopting ± 20% of the RP2D for targeted vs. other classes; P = 0.025). Of the 530 clinically relevant toxicities in later trials, 70% (n = 374) were described in phase I. A significant relationship (P = 0.0032) between increasing the number of patients in phase I (up to 60) and the ability to describe future clinically relevant toxicities was observed. Among 28,505 patients in later trials, the death rate that was related to drug was 1.41%. In conclusion, dosing based on phase I trials was associated with a low toxicity-related death rate in later trials. The ability to predict relevant toxicities correlates with the number of patients on the initial phase I trial. The final dose approved was within 20% of the RP2D in 73% of assessed trials.

Design And Synthesis Of N-acylated Aza-goniothalamin Derivatives And Evaluation Of Their In Vitro And In Vivo Antitumor Activity.

Herein we describe the synthesis of a focused library of compounds based on the structure of goniothalamin (1) and the evaluation of the potential antitumor activity of the compounds. N-Acylation of aza-goniothalamin (2) restored the in vitro antiproliferative activity of this family of compounds. 1-(E)-But-2-enoyl-6-styryl-5,6-dihydropyridin-2(1H)-one (18) displayed enhanced antiproliferative activity. Both goniothalamin (1) and derivative 18 led to reactive oxygen species generation in PC-3 cells, which was probably a signal for caspase-dependent apoptosis. Treatment with derivative 18 promoted Annexin V/7-aminoactinomycin D double staining, which indicated apoptosis, and also led to G2 /M cell-cycle arrest. In vivo studies in Ehrlich ascitic and solid tumor models confirmed the antitumor activity of goniothalamin (1), without signs of toxicity. However, derivative 18 exhibited an unexpectedly lower in vivo antitumor activity, despite the treatments being administered at the same site of inoculation. Contrary to its in vitro profile, aza-goniothalamin (2) inhibited Ehrlich tumor growth, both on the ascitic and solid forms. Our findings highlight the importance of in vivo studies in the search for new candidates for cancer treatment.

Use Of Experimental Design To Optimize A Triple-potential Waveform To Develop A Method For The Determination Of Streptomycin And Dihydrostreptomycin In Pharmaceutical Veterinary Dosage Forms By Hplc-pad.

An HPLC-PAD method using a gold working electrode and a triple-potential waveform was developed for the simultaneous determination of streptomycin and dihydrostreptomycin in veterinary drugs. Glucose was used as the internal standard, and the triple-potential waveform was optimized using a factorial and a central composite design. The optimum potentials were as follows: amperometric detection, E1=-0.15V; cleaning potential, E2=+0.85V; and reactivation of the electrode surface, E3=-0.65V. For the separation of the aminoglycosides and the internal standard of glucose, a CarboPac™ PA1 anion exchange column was used together with a mobile phase consisting of a 0.070 mol L(-1) sodium hydroxide solution in the isocratic elution mode with a flow rate of 0.8 mL min(-1). The method was validated and applied to the determination of streptomycin and dihydrostreptomycin in veterinary formulations (injection, suspension and ointment) without any previous sample pretreatment, except for the ointments, for which a liquid-liquid extraction was required before HPLC-PAD analysis. The method showed adequate selectivity, with an accuracy of 98-107% and a precision of less than 3.9%.

Efficacy And Safety Of Intravitreal Bevacizumab In Eyes With Neovascular Glaucoma Undergoing Ahmed Glaucoma Valve Implantation: 2-year Follow-up.

To evaluate the efficacy and safety of intravitreal bevacizumab (IVB) in eyes with neovascular glaucoma (NVG) undergoing Ahmed glaucoma valve (AGV) implantation. This was a multicentre, prospective, randomized clinical trial that enrolled 40 patients with uncontrolled neovascular glaucoma that had undergone panretinal photocoagulation and required glaucoma drainage device implantation. Patients were randomized to receive IVB (1.25 mg) or not during Ahmed valve implant surgery. Injections were administered intra-operatively, and 4 and 8 weeks after surgery. After a mean follow-up of 2.25 ± 0.67 years (range 1.5-3 years), both groups showed a significant decrease in IOP (p < 0.05). There was no difference in IOP between groups except at the 18-month interval, when IOP in IVB group was significantly lower (14.57 ± 1.72 mmHg vs. 18.37 ± 1.06 mmHg - p = 0.0002). There was no difference in survival success rates between groups. At 24 months, there was a trend to patients treated with IVB using less antiglaucoma medications than the control group (p = 0.0648). Complete regression of rubeosis iridis was significantly more frequent in the IVB group (80%) than in the control group (25%) (p = 0.0015). Intravitreal bevacizumab may lead to regression of new vessels both in the iris and in the anterior chamber angle in patients with neovascular glaucoma undergoing Ahmed glaucoma valve implantation. There is a trend to slightly lower IOPs and number of medications with IVB use during AGV implantation for neovascular glaucoma.

Long-term Efficacy And Safety Of Tenofovir Disoproxil Fumarate In Hiv-1-infected Adolescents Failing Antiretroviral Therapy: The Final Results Of Study Gs-us-104-0321.

Reports of long-term tenofovir disoproxil fumarate (TDF) treatment in HIV-infected adolescents are limited. We present final results from the open-label (OL) TDF extension following the randomized, placebo (PBO)-controlled, double-blind phase of GS-US-104-0321 (Study 321). HIV-infected 12- to 17-year-olds treated with TDF 300 mg or PBO with an optimized background regimen (OBR) for 24-48 weeks subsequently received OL TDF plus OBR in a single arm study extension. HIV-1 RNA and safety, including bone mineral density (BMD), was assessed in all TDF recipients. Eighty-one subjects received TDF (median duration 96 weeks). No subject died or discontinued OL TDF for safety/tolerability. At week 144, proportions with HIV-1 RNA <50 copies/mL were 30.4% (7 of 23 subjects with baseline HIV-1 RNA >1000 c/mL initially randomized to TDF), 41.7% (5 of 12 subjects with HIV-1 RNA <1000 c/mL who switched PBO to TDF) and 0% (0 of 2 subjects failed randomized PBO plus OBR with HIV-1 RNA >1000 c/mL and switched PBO to TDF). Viral resistance to TDF occurred in 1 subject. At week 144, median decrease in estimated glomerular filtration rate was 38.1 mL/min/1.73 m (n = 25). Increases in median spine (+12.70%, n = 26) and total body less head BMD (+4.32%, n = 26) and height-age adjusted Z-scores (n = 21; +0.457 for spine, +0.152 for total body less head) were observed at week 144. Five of 81 subjects (6%) had persistent >4% BMD decreases from baseline. Some subjects had virologic responses to TDF plus OBR, and TDF resistance was rare. TDF was well tolerated and can be considered for treatment of HIV-infected adolescents.