Single step production of nanoporous electrospun poly(ε-caprolactone) fibres

Nanoporous polymer fibres are currently attracting increasing interest due to their unique characteristics. Increased specific surface area, improved mechanical properties and improved cellular growth are amongst the advantages that set porous fibres as ideal candidates in applications like catalysis, separation and tissue engineering. This work explores the single step production of porous poly(ε-caprolactone) (PCL) fibres through combinative electrospinning and Non-solvent Induced Phase Separation (NIPS) technique. Theoretical models, based on three different contact models (Hertzian, DMT, JKR), correlating the fibrous network specific surface area to material properties (density, surface tension, Young s modulus, Poisson s ratio) and network physical properties (density) and geometrical characteristics (fibre radius, fibre aspect ratio, network thickness) were developed in order to calculate the surface area increase caused by pore induction. Experimental results proved that a specific surface area increase of up to 56% could be achieved, compared to networks composed of smooth surfaced fibres. The good solvent effect on electrospun fibre surface morphology and size was examined through experimental investigation of four different good solvent (chloroform, dichloromethane, tetrahydrofuran and formic acid) based solutions at various good/poor solvent ratios. Chloroform was proven to be the most suitable solvent for good /poor solvent ratios varying from 75-90% v/v, whereas alternative mechanisms leading to different fibre morphologies were identified, interpreted and discussed. Evaporation rate of the good solvent was identified as the key parameter of the process. Second order polynomial equations, derived from the experimental data, correlating the feed solution physical parameters (viscosity, conductivity, surface tension) to the fibre average diameter produced were developed and validated. Response surface methodology was implemented for the design and conduction of electrospinning experiments on a 12.5 % w/v Chloroform/DMSO solution 90/10 % v/v in order to determine the individual process parameters (spinning distance, applied voltage, solution flow rate) effect in fibre surface morphology and size. The increase in any of these parameters results in increase of both the fibre size and the tendency for pore generation, whereas applied voltage was the parameter with the strongest effect. Findings from this thesis expand the knowledge about both phenomena occurring during the production process and end product properties, and can be used for the production of controlled morphology and size porous poly(ε-caprolactone) (PCL) fibres

Development of liposomal Carnosine for dermatological and cosmeceutical use

Η Καρνοσίνη είναι ένα διπεπτίδιο ((β-alanyl- L-histidine) με μοναδικές αντιοξειδωτικές και αντιγηραντικές ιδιότητες , που υπάρχει ενδογενώς στο ανθρώπινο σώμα και παίζει σημαντικό ρόλο σε αρκετές φυσιολογικές διαδικασίες που εξασφαλίζουν την ομοιόσταση. Τα τελευταία χρόνια χρησιμοποιήθηκε σε αρκετά καλλυντικά προϊόντα για να ενισχύσει την αντιγηραντική και επουλωτική δράση τους. Παρ’ όλα αυτά η δια δερμική διείσδυση της καρνοσίνης είναι χαμηλή και οι έρευνες επικεντρώνονται στην ανακάλυψη τρόπων να ξεπεραστεί ο φραγμός της κεράτινης στοιβάδας του δέρματος . Τα λιποσώματα είναι μια βιώσιμη και καλά μελετημένη λύση για την μεταφορά φαρμάκων διαμέσου του δέρματος. Διαφορετικοί τύποι λιποσωμάτων έχουν χρησιμοποιηθεί για να αυξήσουν την δια δερμική διαπερατότητα των δραστικών συστατικών Τρείς τύποι λιποσωμάτων που περιείχαν Καρνοσίνη (2,5% w/w ) αναπτύχθηκαν με την τροποποιημένη μέθοδο θέρμανσης (Modified Heating Method ,MHM) και πραγματοποιήθηκε εκτίμηση των φυσικοχημικών τους χαρακτηριστικών και της σταθερότητας τους σε μια περίοδο 2 μηνών. Η σταθερότητα τους αξιολογήθηκε σε δύο σενάρια αποθήκευσης των λιποσωμάτων . Σε αποθήκευση σε θερμοκρασία περιβάλλοντος και σε συντήρηση τους σε κατάλληλο φαρμακευτικό ψυγείο . Συγκεκριμένα παρασκευάσθηκαν ένα συμβατικό λιπόσωμα , ένα τρανσφερόσωμα με Tween 80 και ένα λιπόσωμα με κεραμίδια. Τα λιποσώματα αυτά ενσωματώθηκαν σε ουδέτερη γέλη ώστε το τελικό προϊόν να περιέχει 0,5 % Καρνοσίνη. Χρησιμοποιήθηκαν δυο τύποι ουδέτερης γέλης, μια με υαλουρονικό οξύ σε περιεκτικότητα 0,1% και μια χωρίς υαλουρονικό οξύ . Στις συνέχεια έγινε έλεγχος της διατήρησης των φυσικοχημικών ιδιοτήτων των λιποσωμάτων εντός του τελικού προϊόντος. Οι τρείς τύποι λιποσωμάτων που παρασκευάστηκαν με την τροποποιημένη μέθοδο θέρμανσης , παρουσίασαν αποδεκτά φυσικοχημικά χαρακτηριστικά , συνεπή με την ύπαρξη μεγάλων πολυστιβαδικών σωματιδίων ( MLV s) ή μεγάλων μονοστιβαδικών σωματιδίων ( ULVs ) στο σύστημα διασποράς , με μέγεθος που κυμαίνεται από 300- 500 nm. To Z-δυναμικό βρέθηκε να κυμαίνεται από -40 mV μέχρι -50mV το οποίο σχετίζεται με καλή σταθερότητα των νάνο -κολλοειδούς συστήματος. Ο δείκτης διασποράς (polydispersity index ) ήταν ενδεικτικός καλής ομοιογένειας μεγέθους . Πιο συγκεκριμένα την ημέρα της παρασκευής των λιποσωμάτων το PDI ήταν 0.295 S. D +/- 0.023 για τα συμβατικά λιποσώματα, ,0.293 S. D +/- 0.015 για τα τρανσφεροσώματα και 0.267 S. D +/- 0.027 για τα λιποσώματα με τα κεραμίδια. Ο βαθμός ενκαψυλίωσης της Καρνοσίνης εντός του λιποσώματος ( encapsulation efficiency ,EE%) ήταν 62,67% για τα συμβατικά λιποσώματα ,66,33% για τα τρανσφεροσώματα και 28,33% για τα λιποσώματα με κεραμίδια. Τα δείγματα που συντηρήθηκαν στο ψυγείο έδειξαν καλύτερη σταθερότητα σε όλες τις μετρήσιμές παραμέτρους καθόλη την διάρκεια του πειράματος , καθώς στα δείγματα που συντηρήθηκαν σε θερμοκρασία περιβάλλοντος ανέπτυξαν μικροβιακή επιμόλυνση που επηρέασε σημαντικά τις τιμές pH , το χρώμα και την οσμή τους . Η διάμετρος των σωματιδίων , ο δείκτης διασποράς και ο βαθμός ενκαψυλίωσης της καρνοσίνης δεν επηρεάστηκαν σημαντικά από τις συνθήκες συντήρησης. Η ενσωμάτωση των συμβατικών λιποσωμάτων στην ουδέτερη γέλη δεν επηρέασε σημαντικά το μέγεθος των σωματιδίων όταν αυτό συγκρίθηκε με το αρχικό τους μέγεθος (341.14 S. D +/- 4.7) αλλά υπήρχε σημαντική αύξηση του δείκτη διασποράς (0.642 S. D +/- 0.012). Τα τρανσφεροσώματα και τα λιποσώματα με κεραμίδια έδειξαν σημαντική πτώση στο μέγεθος τους όταν ενσωματώθηκαν στην γέλη (258.6 S. D +/- 6.3 vs 432.76 S. D +/- 16.03 and 394.10 S. D +/- 10.2 vs 558.37 S. D +/- 22.26 αντίστοιχα) και αρκετά μεγάλη αύξηση στον δείκτη διασποράς (0.581 S. D +/- 0.009 vs 0.280 S. D +/- 0.016 and 0.919 S. D +/- 0.140 vs 0.263 S. D +/- 0.039). Η προσθήκη του υαλουρονικού οξέος δεν επηρέασε τις φυσικοχημικές ιδιότητες των λιποσωμάτων στο τελικό προϊόνCarnosine is a dipeptide (β-alanyl- L-histidine) with unique antioxidant and antiaging properties, that exists endogenously in the human body and plays a key role in several physiological aspects of homeostasis. Recently it has been used in several cosmeceutical products to enhance their antiaging and wound healing effect. However, skin penetration of carnosine is rather poor, and research is focusing on finding ways to overcome stratum corneum barrier. Liposomes are a viable and well-studied solution for drug delivery through the skin. Different types of liposomes have been utilized to increase skin penetration of active ingredients. Three types of carnosine loaded liposomes (2.5% w/w) were developed with Modified Heating Method (MHM) and evaluated in terms of physicochemical stability in a period of 2 months in two different storage scenarios, room temperature and refrigerator. Specifically, a conventional liposome, an ultradeformable liposome (transferosome)with Tween 80 and a ceramide containing liposome (ceramidosome) were studied and then formulated in a neutral gel for dermatological use with the final formula containing 0.5% of liposomal carnosine w/w. Two types of neutral gel were prepared, one containing 0.1% hyaluronic acid and one without. Final formulations of gel were tested to evaluate if liposomes retained their unique properties in the final product All three types of liposomes prepared with this method exhibit acceptable physicochemical properties consistent with the characteristics of multilamellar vesicles (MLVs) or Large unilamellar vesicles (LUVs) in the range of 300 to 500nm. Z-potential was found in the range of -40mV up to -50mV that correlates to good stability of nanocolloidal system. Polydispersity index showed that all liposomes were homogenous since at day one was found to be 0.295 S. D +/- 0.023 for the conventional liposome, 0.293 S. D +/- 0.015 for the transferosomes and 0.267 S. D +/- 0.027 for the ceramidosomes. Conventional liposomes and transferosomes have been found to have the highest encapsulation efficiency (EE%) at 62.67% and 66.33% respectively, with ceramidosomes having 28.33% carnosine encapsulation. Liposomes that were stored in the refrigerator performed better in terms of stability over time retaining their initial measurements, whereas liposomes stored in room temperature developed microbial growth that affected their pH, their color and resulted in the formation of aggregates that were easily dissolved after mild agitation of the container. Hydrodynamic diameter, dispersity, and EE% were not significantly affected from the storage conditions. When incorporated in the neutral gel only conventional liposomes retained size measurements near to those of pre formulation (341.14 S. D +/- 4.7) but PDI showed a significant rise (0.642 S. D +/- 0.012) when compared to the original liposome. Transferosomes and ceramidosomes exhibit a drop on their size (258.6 S. D +/- 6.3 vs 432.76 S. D +/- 16.03 and 394.10 S. D +/- 10.2 vs 558.37 S. D +/- 22.26 respectively) and significant rise in PDI (0.581 S. D +/- 0.009 vs 0.280 S. D +/- 0.016 and 0.919 S. D +/- 0.140 vs 0.263 S. D +/- 0.039). The addition of hyaluronic acid in the neutral gel did not seem to further affect the physicochemical properties of the liposomes in the final formulation

Porous electrospun polycaprolactone (PCL) fibres by phase separation

The effect of different binary solvent systems on the size and surface morphology of electrospun poly(ε-caprolactone) (PCL) fibres was investigated in this study. Chloroform (CF), dichloromethane (DCM), tetrahydrofuran (THF) and formic acid (FA) were used in mixtures with dimethyl sulfoxide (DMSO) in order to generate pores on the fibre surface, through a non-solvent induced phase separation mechanism. The production of porous, bead free fibres with an average diameter ranging from 1470 to 2270 nm was achieved using 12.5% w/v PCL in CF/DMSO solution with good/poor solvent ratios varying from 75-90% v/v at the applied voltage of 15 kV, a spinning distance of 20 cm, and the feed flow rate of 1 ml/h. DCM and THF were proven to be less suitable good solvents for the process due to the formation of a solid skin on the jet surface, caused by the limited diffusivity of the polymer molecules from the jet surface to the liquid core and its subsequent collapse. FA was found to be unsuitable due to its similar evaporation rate to DMSO. The pore formation was favoured at high good/poor solvent ratios, whereas, the production of fibres with ribbon cross sections or fibres with beads was more pronounced at low good/poor solvent ratios. Data fitting was used for the development of a second order polynomial equation, correlating the produced fibre average diameter to the solution parameters (conductivity, surface tension, and viscosity), for the given polymer and solvent systems, under the specific experimental conditions used in this study. The ternary mixture compositions that lead to the formation of porous fibres were mapped on a ternary graph

Porous electrospun polycaprolactone fibres: Effect of process parameters

The effect of electrospinning process parameters (solution flow rate, applied voltage, spinning distance) on the size and surface morphology of porous electrospun poly(ε-caprolactone) was investigated in this study. Response surface methodology was implemented for the design and conduction of electrospinning experiments. The feed solution was a 12.5% w/v poly(ε-caprolactone) (PCL) solution in a binary solvent mixture of 90%v/v chloroform/ dimethyl sulfoxide. Spinning distance of 10-25 cm, applied voltage of 10-25 kV and feed flow rate of 0.5-5 ml/h were the range of limiting values of the independent variables used for the development of a central composite design. Second order polynomial equations, correlating electrospinning process parameters to relative pore coverage and fibre average diameter were developed and validated. An increase in any of the electrospinning process parameters favoured pore formation and fibre diameter increase. Under the experimental conditions investigated, the relative pore surface coverage was 15.8-31.9% and the average fibre diameter was in the range of 1.6-3.3 μm. Applied voltage was proven to be the parameter with the strongest impact on both, fibre diameter and surface morphology

Translating Natural Language to SQL using Deep Learning

Οι βάσεις δεδομένων περιέχουν τεράστια ποσότητα δεδομένων, τα οποία χρησιμοποιούνται για την υποστήριξη ενός μεγάλου εύρους δραστηριοτήτων από επιχειρηματικές δραστηριότητες, επιστημονικά πειράματα μέχρι δραστηριότητες της καθημερινότητας μας. Παρά όλα αυτά παραμένουν μη προσβάσιμες για έναν χρήστη χωρίς γνώση Γλώσσας Δομημένων Ερωτημάτων (SQL). Οι διεπαφές φυσικής γλώσσας για βάσεις δεδομένων καταρίπτουν αυτά τα εμπόδια και τελευταία βρίσκονται σε άνοδο. Στα πλαίσια αυτής της πτυχιακής εργασίας, θα ξεκινήσουμε παρουσιάζοντας το πρόβλημα NL2SQL (μετάφραση φυσικής γλώσσας σε γλώσσα δομημένων ερωτημάτων), τα πιο σημαντικά του σημεία και την ανατομία ενός συστήματος NL2SQL. Θα συγκρίνουμε κάποια συστήματα και θα δούμε πως το καθένα από αυτά έχει επιλέξει να αντιμετωπίσει το πρόβλημα. Στο κύριο μέρος της εργασίας, θα εστιάσουμε στο SQLNet, ένα σύστημα το οποίο χρησιμοποιεί τεχνικές βαθιάς μάθησης για να αντιμετωπίσει το πρόβλημα NL2SQL. Επίσης, θα δοκιμάσουμε τη δική μας υλοποίηση του συστήματος, θα προσπαθήσουμε να εφαρμόσουμε κάποιες βελτιώσεις και θα ελέγξουμε πόσο καλά λειτουργεί σε διάφορες περιπτώσεις.Databases contain a vast amount of data, used to support a range of operations, from business operations, scientific experiments to activities in our everyday lives. However they are still inaccessible for non-technical users, without knowledge of Structured Query Language (SQL). Natural language interfaces to databases lift these obstacles for such users and they have recently bloomed. In this thesis, we will start by presenting the NL2SQL problem (translating Natural Language to Structured Query Language), its most important aspects and the anatomy of a NL2SQL system. We will compare some systems and see how each one of them chooses to tackle the problem. In the main part of this work, we will focus on the SQLNet system which uses deep learning methods to tackle the NL2SQL problem. We will also test our own implementation of the system, investigate possible improvements and test how well it works on various cases

ScienceBenchmark: A Complex Real-World Benchmark for Evaluating Natural Language to SQL Systems

Natural Language to SQL systems (NL-to-SQL) have recently shown a significant increase in accuracy for natural language to SQL query translation. This improvement is due to the emergence of transformer-based language models, and the popularity of the Spider benchmark - the de-facto standard for evaluating NL-to-SQL systems. The top NL-to-SQL systems reach accuracies of up to 85\%. However, Spider mainly contains simple databases with few tables, columns, and entries, which does not reflect a realistic setting. Moreover, complex real-world databases with domain-specific content have little to no training data available in the form of NL/SQL-pairs leading to poor performance of existing NL-to-SQL systems. In this paper, we introduce ScienceBenchmark, a new complex NL-to-SQL benchmark for three real-world, highly domain-specific databases. For this new benchmark, SQL experts and domain experts created high-quality NL/SQL-pairs for each domain. To garner more data, we extended the small amount of human-generated data with synthetic data generated using GPT-3. We show that our benchmark is highly challenging, as the top performing systems on Spider achieve a very low performance on our benchmark. Thus, the challenge is many-fold: creating NL-to-SQL systems for highly complex domains with a small amount of hand-made training data augmented with synthetic data. To our knowledge, ScienceBenchmark is the first NL-to-SQL benchmark designed with complex real-world scientific databases, containing challenging training and test data carefully validated by domain experts.Comment: 12 pages, 2 figures, 5 table

Assessing the increase in specific surface area for electrospun fibrous network due to pore induction

The effect of pore induction on increasing electrospun fibrous network specific surface area was investigated in this study. Theoretical models based on the available surface area of the fibrous network and exclusion of the surface area lost due to fibre-to-fibre contacts, were developed. The models for calculation of the excluded area are based on Hertzian, Derjaguin-Muller-Toporov (DMT) and Johnson-Kendall-Roberts (JKR) contact models. Overall, the theoretical models correlated the network specific surface area to the material properties including density, surface tension, Young’s modulus, Poisson’s ratio as well as network physical properties such as density and geometrical characteristics including fibre radius, fibre aspect ratio and network thickness. Pore induction proved to increase the network specific surface area up to 52%, compared to the maximum surface area that could be achieved by non-porous fibre network with the same physical properties and geometrical characteristics. The model based on Johnson-Kendall-Roberts contact model describes accurately the fibre-to-fibre contact area under the experimental conditions used for pore generation. The experimental results and the theoretical model based on Johnson-Kendall-Roberts contact model show that the increase in network surface area due to pore induction can reach to up to 58%

A Compilation of Europe-Wide Databases from Published Measurements of PCBs, Dioxins and Furans

Chemical risk assessment always entails an evaluation of expected environmental concentrations of substances; these concentrations may be predicted using mathematical models or may be chosen on the basis of experimental observations and monitoring activities. The work discusses the usefulness and limitations in building compilations of published monitoring data by describing a feasibility study on polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), for which observed concentration data were retrieved from scientific journal articles published between 2000 and 2009. These chemicals are typical POPs and are of constantly high concern for their potential adverse effects on human health and ecosystems. PCBs were mainly used by the power industry in electrical transformers, capacitors, hydraulic equipment, and as lubricants. PCDD/Fs are formed as unintentional by-products of chemical manufacturing and incineration processes, as well as natural processes such as volcanic eruptions, and biomass burning. Emissions from incineration of industrial wastes such as metal reclamation and domestic heating (especially in central Europe) are considered as current sources of PCDD/Fs to the environment. A database of published observed concentrations of PCBs and PCDD/Fs in air, soil sediments and water was built as described in details in the report. As continental scale assessment is aimed more at the evaluation of the regional distribution of contamination, we excluded from the database those measurements taken close to known PCB or PCCD/F pollution sources of exceptional entity such as waste incinerators or contaminated sites. After presenting and interpreting the results of the literature search, we critically examine the completeness and usability of this information, and the usefulness of data compilations in the framework of chemical risk assessment.JRC.H.5-Rural, water and ecosystem resource

Effective Hamiltonians with Relativistic Corrections I: The Foldy--Wouthuysen transformation versus the direct Pauli reduction

Two different methods of obtaining ``effective $2\times 2$ Hamiltonians'' which include relativistic corrections to nonrelativistic calculations are discussed, the standard Foldy--Wouthuysen transformation and what we call the ``direct Pauli reduction''. We wish to investigate under which circumstances the two approaches yield the same result. Using a generic interaction with harmonic time dependence we show that differences in the corresponding effective S--matrices do arise beyond first--order perturbation theory. We attribute them to the fact that the use of the direct reduction effective Hamiltonian involves the additional approximation of neglecting contributions from the negative--energy intermediate states, an approximation which is unnecessary in the Foldy--Wouthuysen case as there the $4\times 4$ Hamiltonian does not connect positive-- and negative--energy states. We conclude that at least in the cases where the relativistic Hamiltonian is known, using the direct Pauli reduction effective Hamiltonian introduces spurious relativistic effects and therefore the Foldy--Wouthuysen reduction should be preferred.Comment: TRIUMF preprint TRI-PP-93-1