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Impatto della stimolazione tetanica del ventral subiculum sui neuroni dopaminergici dell’area ventrale tegmentale
Get PDFThe hippocampus (HPC) is recognized as an important structure in learning and memory, including the integration of relevant informations to modulate the behavior. Tetanic burst stimulation of the HPC has been shown to generate adaptive synaptic changes, like long term potentiation (LTP), outside the HPC. Using in vivo extracellular recording techniques in anesthetized rats, we have investigated how the firing of dopaminergic neurons is affected by the delta frequency stimulation of the ventral subiculum of hippocampus (vSUB). This work shows that the delta burst stimulation in vSUB induce a LTP in Bed nucleus of the stria terminalis (BNST) neurons that projecting to the ventral tegmental area (VTA). Also, this LTP
is blocked when we administrated the AP5 (a NMDA receptors antagonist) on the BNST neurons before tetanus.
In addition, this work shows that 24 hours after the induction of a tetanic stimulation in vSUB, there is an increase of the activity (firing rate, bursting activity) of DA neurons. We also demonstrated that an intra‐BNST infusion of AP5 prior the vSUB tetanus blocks the
effect of delta burst stimulation on VTA dopamine neurons bursting parameters.
These results contribute to clarify important points concerning the regulation of VTA DA neurons activity by the vSUB, probably through a balance of excitatory and inhibitory inputs from the BNST
Studies On Monolithic Active Pixel Sensors and Detector Performance for the Inner Tracking System Upgrade of ALICE
Get PDFALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector
at the CERN LHC designed to study the physics of strongly interacting matter, and in particular the properties of the Quark-Gluon Plasma (QGP), using Pb-Pb collisions
at unprecedented energy densities. During the first three years of operation, it has demonstrated very good capabilities for measurements at high energy Pb-Pb collisions.
But there are certain measurements like high precision measurements of rare probes over a wide range of momenta, which would require high statistics and are not satisfactory
or even possible with the current experimental setup. These measurements would help to achieve the long term physics goals of ALICE and would go a long way forward
in understanding and characterizing the Quark Gluon Plasma (QGP). To enhance its physics capabilities, ALICE has formulated an upgrade of its detectors, motivated by
an upgrade of the LHC during the LHC Long Shutdown 2 (2018-2020).
The LHC upgrade features which primarily motivated the ALICE upgrade programme are, in particular, Pb-Pb collisions with a high interaction rate of up to 50 kHz
corresponding to an instantaneous luminosity, L = 6 × 1027cm−2s−1 and, the installation of a narrower beam pipe. Accordingly, ALICE would require detector upgrades
to cope with the upgrade scenario. These upgrades should help to improve tracking and vertexing capabilities, radiation hardness and allow readout of all interactions to
accumulate enough statistics for the upgrade physics programme. The objective is to accumulate 10 nb−1 of Pb–Pb collisions, recording about 1011 interactions.
Within this upgrade strategy, the Inner Tracking System (ITS) upgrade forms an important cornerstone, providing improved vertexing and readout capabilities. The
new ITS will have a barrel geometry consisting of seven layers of Monolithic Active Pixel Sensors (MAPS) with high granularity which would cater to the material budget,
readout and radiation hardness requirements for the upgrade. The geometry is optimized
for high efficiency, both in standalone tracking and ITS-TPC combined tracking. TowerJazz 0.18 μm technology is selected for designing the pixels for ITS upgrade.
This technology provides attractive features like the option to implement a deep pwell
allowing the implementation of a full CMOS process in the pixel. The ongoing research and development on these pixels investigates different design strategies and
would converge towards the final design of the detector by the end of 2014. Several prototypes have been designed to investigate and validate the different design strategies
and the different components of the pixel detector using this technology.
The work presented in this thesis can be categorized in two parts. The first part concerns the results of characterization of some of the pixel prototype circuits developed for the ITS upgrade, in particular MIMOSA32, MIMOSA32Ter and Explorer-1. The second part discusses the detector performance studies of the upgraded ITS.
MIMOSA32 and MIMOSA32Ter were one of the first prototypes designed with the TowerJazz technology in the upgrade programme. The motivation was to validate
the technology. This thesis includes the results of tests and characterization of pixel structures of these prototypes and qualifies the technology in terms of charge collection and radiation tolerance and the usage of the deep p-well structure. This provides a
starting point for future prototypes where the deep p-well could be implemented in a
full CMOS process, thus allowing in-pixel sophisticated signal processing circuits.
The Explorer prototypes are developed at CERN with the main motivation towards developing a detector with low power density, lower than the maximum permissible limits
for the upgrade programme. This would provide a margin to reduce the material budget of the detection layers, improving the detector performance. The Explorer prototypes
are designed to study the ratio of the collected charge to the input capacitance (Q/C), in particular, its dependence on the size of the collection diode and its distance
to the adjacent p-well of the input transistors. The Explorer prototypes allows the application
of a back-bias voltage which has an effect on the signal collection properties.
In a pixel detector, improvement of the Q/C ratio enhances the signal amplitude
at the collection node of the pixel circuit which is connected to the analog frontend.
This would help in optimizing the analog frontend to improve the signal to noise ratio of the detector, which has a direct consequence in minimizing the power consumption
of the detector. This thesis includes the test and characterization of Explorer-1 prototype circuits
with different starting materials. The results show that Q/C improves with higher back bias voltage and increased spacing between the collection electrode and the adjacent
p-well.
With these results, the future prototypes of Explorer could concentrate on Optimizing the size of the input transistors to study its effects on the Random Telegraph
Signal noise. In parallel, optimization of the signal processing circuits would also be carried out in other prototypes.
The second part of the thesis studies the performance of a baseline configuration of the upgraded detector in terms of impact parameter resolution, momentum resolution
and tracking efficiency both in standalone tracking mode and ITS-TPC combined tracking. The performance is compared with the current ITS to study the improvements
in the upgraded ITS. The performance is affected by the radial position and material budget of the layers and the detector intrinsic resolution. The detector specifications
in this regard are still evolving specially for the Outer Barrel (the outermost four layers). The studies show the effects of variation of the specifications in terms
of material budget and intrinsic resolution on the detector performance. This would help to finalize the detector specifications for an optimized detector performance. The
thesis also concludes that a reduction in the beam pipe radius (lower than the baseline upgrade scenario) would not affect detector performance but may facilitate the installation of the Inner Barrel. Redundancy studies show that the presence of a dead layer can degrade the detector performance significantly. This defines a key requirement of
easy and rapid accessibility to the detector in the design of the upgraded ITS. The ITS upgrade timeline foresees the finalization of the final pixel architecture in
late 2014. Mass production of the final circuit is planned for 2015. The construction of the detector modules, tests, assembling and pre-commissioning will be carried out
throughout 2016-2017 followed by the installation of the detector in the ALICE cavern
in 2018
Acquisition systems and decoding algorithms of peripheral neural signals for prosthetic applications
Get PDFDuring the years, neuroprosthetic applications have obtained a great deal of attention by
the international research, especially in the bioengineering field, thanks to the huge investments
on several proposed projects funded by the political institutions which consider the treatment of this particular disease of fundamental importance for the global community.
The aim of these projects is to find a possible solution to restore the functionalities lost by a patient subjected to an upper limb amputation trying to develop, according to physiological considerations, a communication link between the brain in which the significant signals are
generated and a motor prosthesis device able to perform the desired action. Moreover, the designed system must be able to give back to the brain a sensory feedback about the surrounding world in terms of pressure or temperature acquired by tactile biosensors placed at the surface of the cybernetic hand. It in fact allows to execute involuntarymovements when for example the armcomes in contact with hot objects.
The development of such a closed-loop architecture involves the need to address some critical issues which depend on the chosen approach. Several solutions have been proposed
by the researches of the field, each one differing with respect to where the neural signals are acquired, either at the central nervous systemor at the peripheral one,most of themfollowing the former even that the latter is always considered by the amputees amore natural way
to handle the artificial limb. This research work is based on the use of intrafascicular electrodes directly implanted in the residual peripheral nerves of the stump which represents a good compromise choice in terms of invasiveness and selectivity extracting electroneurographic
(ENG) signals from which it is possible to identify the significant activity of a quite limited number of neuronal cells. In the perspective of the hardware implementation of
the resulting solution which can work autonomously without any intervention by the amputee in an adaptive way according to the current characteristics of the processed signal and by using batteries as power source allowing portability, it is necessary to fulfill the tight
constraints imposed by the application under consideration involved in each of the various phases which compose the considered closed-loop system.
Regarding to the recording phase, the implementation must be able to remove the unwanted interferences mainly due to the electro-stimulations of themuscles placed near the
electrodes featured by an order of magnitude much greater in comparison to that of the signals of interest amplifying the frequency components belonging to the significant bandwidth, and to convert them with a high resolution in order to obtain good performance at the next processing phases. To this aim, a recording module for peripheral neural signals will be presented, based on the use of a sigma-delta architecture which is composed by
two main parts: an analog front-end stage for neural signal acquisition, pre-filtering and sigma-delta modulation and a digital unit for sigma-delta decimation and system configuration.
Hardware/software cosimulations exploiting the Xilinx System Generator tool in Matlab Simulink environment and then transistor-level simulations confirmed that the system
is capable of recording neural signals in the order of magnitude of tens of μV rejecting the huge low-frequency noise due to electromyographic interferences.
The same architecture has been then exploited to implement a prototype of an 8-channel implantable electronic bi-directional interface between the peripheral nervous system and the neuro-controlled hand prosthesis. The solution includes a custom designed Integrated Circuit (0.35μm CMOS technology), responsible of the signal pre-filtering and sigma-delta modulation for each channel and the neural stimuli generation (in the opposite path) based
on the directives sent by a digital control systemmapped on a low-cost Xilinx FPGA Spartan-3E 1600 development board which also involves the multi-channel sigma-delta decimation
with a high-order band-pass filter as first stage in order to totally remove the unwanted interferences.
In this way, the analog chip can be implanted near the electrodes thanks to its limited size avoiding to add a huge noise to theweak neural signals due to longwires connections and to cause heat-related infections, shifting the complexity to the digital part which can be hosted on a separated device in the stump of the amputeewithout using complex laboratory instrumentations. The system has been successfully tested from the electrical point
of view and with in-vivo experiments exposing good results in terms of output resolution and noise rejection even in case of critical conditions.
The various output channels at the Nyquist sampling frequency coming from the acquisition system must be processed in order to decode the intentions of movements of the amputee, applying the correspondent electro-mechanical stimulation in input to the cybernetic hand in order to perform the desired motor action. Different decoding approaches have been presented in the past, the majority of them were conceived starting from the relative
implementation and performance evaluation of their off-line version. At the end of the research, it is necessary to develop these solutions on embedded systems performing an online processing of the peripheral neural signals. However, it is often possible only by using
complex hardware platforms clocked at very high operating frequencies which are not be compliant with the low-power requirements needed to allow portability for the prosthetic
device.
At present, in fact, the important aspect of the real-time implementation of sophisticated signal processing algorithms on embedded systems has been often overlooked, notwithstanding the impact that limited resources of the former may have on the efficiency/effectiveness
of any given algorithm. In this research work it has been addressed the optimization of a state-of-the-art algorithmfor PNS signals decoding that is a step forward for its real-time, full implementation onto a floating-point Digital Signal Processor (DSP). Beyond low-level
optimizations, different solutions have been proposed at an high level in order to find the best trade-off in terms of effectiveness/efficiency. A latency model, obtained through cycle accurate profiling of the different code sections, has been drawn in order to perform a fair
performance assessment. The proposed optimized real-time algorithmachieves up to 96% of correct classification on real PNS signals acquired through tf-LIFE electrodes on animals, and performs as the best off-line algorithmfor spike clustering on a synthetic cortical dataset
characterized by a reasonable dissimilarity between the spikemorphologies of different neurons.
When the real-time requirements are joined to the fulfilment of area and power minimization
for implantable/portable applications, such as for the target neuroprosthetic devices, only custom VLSI implementations can be adopted. In this case, every part of the algorithmshould be carefully tuned. To this aim, the first preprocessing stage of the decoding algorithmbased on the use of aWavelet Denoising solution able to remove also the in-band noise sources has been deeply analysed in order to obtain an optimal hardware implementation.
In particular, the usually overlooked part related to threshold estimation has been evaluated in terms of required hardware resources and functionality, exploiting the commercial Xilinx System Generator tool for the design of the architecture and the co-simulation. The
analysis has revealed how the widely used Median Absolute Deviation (MAD) could lead o hardware implementations highly inefficient compared to other dispersion estimators
demonstrating better scalability, relatively to the specific application.
Finally, two different hardware implementations of the reference decoding algorithm have been presented highlighting pros and cons of each one of them. Firstly, a novel approach based on high-level dataflow description and automatic hardware generation is presented
and evaluated on the on-line template-matching spike sorting algorithmwhich represents the most complex processing stage. It starts from the identification of the single kernels with the greater computational complexity and using their dataflow description to generate the HDL implementation of a coarse-grained reconfigurable global kernel characterized by theminimumresources in order to reduce the area and the energy dissipation for
the fulfilment of the low-power requirements imposed by the application. Results in the best case have revealed a 71%of area saving compared tomore traditional solutions,without any accuracy penalty. With respect to single kernels execution, better latency performance are achievable stillminimizing the number of adopted resources.
The performance in terms of latency can also be improved by tuning the implemented parallelismin the light of a defined number of channels and real-time constraints, by using
more than one reconfigurable global kernel in order that they can be exploited to perform the same or different kernels at the same time in a parallel way, due to the fact that each one can execute the relative processing only in a sequential way. For this reason, a second FPGA-based prototype has been proposed based on the use of aMulti-Processor System-on-Chip (MPSoC) embedded architecture. This prototype is capable of respecting the real-time
constraints posed by the application when clocked at less than 50 MHz, in comparison to 300 MHz of the previous DSP implementation. Considering that the application workload
is extremely data dependent and unpredictable due to the sparsity of the neural signals, the architecture has to be dimensioned taking into account critical worst-case operating conditions in order to always ensure the correct functionality. To compensate the resulting overprovisioning
of the system architecture, a software-controllable power management based on the use of clock gating techniques has been integrated in order tominimize the dynamic
power consumption of the resulting solution.
Summarizing, this research work can be considered a sort of proof-of-concept for the proposed techniques considering all the design issues which characterize each stage of the
closed-loop system in the perspective of a portable low-power real-time hardware implementation of the neuro-controlled prosthetic device
La tutela dell’apparenza nella disciplina della rappresentanza
Get PDFThe topic of apparent representation suggests the coexistence of principles in the juridical order, which are antithetical at first sight, on the purpose of jurisprudence, which lie in the border line between the activities of interpretation and creation of juridical norms and in the delicate equilibrium between freedom to negotiate and resposibility.
The interpretation doubts regard mainly the issues of generality or exceptionality. The difficulties that arise in answering such question are due to the sacrality of the general principles which constitute the Italian system of private law.
On one hand, there are fundamental rules to natural law according to which nobody can be bounded if not as a consequence of an act of its own will. On the other hand, there is the principle of entrusting according to which a given circumstance becomes not binding if it is not known to a given party or if it is opposed by a given appearance.
Understanding how the balance between such opposing directives has been addressed by the legislator becomes even harder in the discipline of representation, where no reference to rules of appearance can be found.
This uncertainty suggests to pause and reflect on the meaning of private autonomy, especially where we wish to remind the teachings of who warned against risks and dangers linked to the private initiative, recommending a careful and wise exercise of the autonomy.
To describe the risks and dangers coming from the negligence and inertia of the party affected by the commitment to its own negotiating declaration, it has been made reference to the notion of <<selfresponsibility>>. Selfresposibility is called upon by many as the juridic foundation of the principle of appearance and it allows to shed light on the interpretation of the correct reconstruction of the applicative assumptions of the discipline.
The investigation proposed in this work moves in the direction of explaining a criterion to link the negotiating activity put into being by the apparent representative, the juridical sphere of the apparent represented and the nature of the entrusting held by the third contractor, to clarify in which way the legislator intended to regulate the conflict of interest between the third contractor and the apparent represented
Il negozio di accertamento, limite all'autonomia privata
Get PDFThis thesis aims to verify the eligibility and limits of the figure of the conventional assessment, which finds widespread use in judicial practice, but unlike the German B.G.B., it is not explicitly covered in the Italian Civil Code.
In the first part I have tried to identify the boundaries between the legal transaction of assessment and the typical assumptions governed by the legislature that in this case might have a confirmatory function.
The research was then directed to verify whether it is permissible an atypical legal transaction of assessment or if the private autonomy has some limits. The legal transaction of assessment is, in fact, oriented towards the past, the parties by agreement or unilaterally turn back to a fact or a previous legal situation subjectively uncertain, in order to clarify the meaning.
The first limit that the parties meet is a temporal limit. It cannot be changed a fact as it has happened in reality: the parties assess a fact, but this fact must correspond to reality, otherwise the fact is not assessed, but it is changed. If, however, the parties turn back to a previous contract now concluded, there is assessment in the hypothesis of authentic interpretation: the parties clarify , verify the previous legal relationship and, in this hypothesis, unlike the previous one did, they don’t meet the limit of truth, because they experience a legal situation and not a fact.
The most important implications of the legal transaction of assessment is found in the process when one party, failing commitment, sue the other party: the defendant may assert the legal transaction of assessment and be exempt from the burden of proving the fact or the underlying relationship and it will be up to the other party the burden of proving the contrary.
In the Italian legal order, the basis of this operation can be inferred from the combined provisions of Articles 1321, 1322 , 2648 of the Italian Civil Code. In fact, by the article 1321 we know that the contract can not only be, but also regulate, the capital legal relationship. To the broad meaning of the regulation it can be linked, therefore, also the effect to assess a pre-existing situation. While the admissibility of an atypical figure comes from the article 1322, it is crucial to determine whether the cause is worthy of protection, worthiness that can be found in the need for certainty. The parties when assessing a fact or a pre-existing situation look to the past, they assume that the fact or the relationship is just as they assessed. The logical reasoning underlying it is that of abductive inference. In other words , from the effects , meaning from the fact assessed, it goes back to the cause, that is the pre-existing fact. The legal transaction of assessment, operates as a conventional presumption and its foundation is found in the article 2698 of the Civil Code, that allows the parties to invert conventionally the burden of proof even with the limitations of the rights available. The parties, therefore, are not precluded from sue, but the party that don’t respect the agreement shall bear the reversal of the burden of proof even if restricted to the assessed fact
Host Defence Peptides (HDPs): investigating the structure-to-function relationship through bio-physical techniques
Get PDFDuring last decades, more and more microorganisms resistant to conventional
antibiotics were isolated while few new antimicrobial drugs were developed. The urgent need
for novel efficient antibiotics led a great attention on cationic host defense peptides (HDP)
since their discovery in 1980s. The role of these molecules in the defense of organism against
pathogens attack, together with their high selectivity for bacterial cells over the eukaryotic
ones, made them attractive candidates for the development of a new class of antimicrobial
drugs. At present, a vast range of both natural and synthetic HDPs sequences are reported in
the literature but they still present remarkable limitations to an effective applicability in vivo,
such as the high sensitivity to proteases and strong activity reduction in the presence of
physiological electrolytes concentration. A lot of effort have been put into improving their
pharmacokinetics in order to develop new antimicrobial drugs based on their sequences.
The present Ph.D. work is focused on the elucidation of the structure-to-function
relationships of three different peptides, chosen as representative of different HDP categories.
Esculentin-1b(1-18) is the ‘classic’ natural antimicrobial peptide (AMP), Plasticin-L1, is an
immunomodulatory peptide devoid of direct bactericidal activity, and a group of four
synthetic peptide analogues based on a semi-synthetic dendrimeric and lipidated peptide
called SB056. The latter, in particular, represent an innovative class of peptides, whose
structural features, three-dimensional folding and mode of action are absolutely peculiar and
almost completely unknown before this project started.
The interesting and multidisciplinary field of HDPs is presented in the first chapter.
The origins, the structural features and the modes of action proposed for these compounds in
the literature are briefly summarized. A brief excursus on the limits of their applicability in
the clinical practice and the strategies adopted to overcome this issue is also included. In the
second chapter, all the materials, the methods and experimental protocols are described, going
from typical biological assays to biophysical methods.. The main technique used to elucidate
the three-dimensional structure of the peptides, the nuclear magnetic resonance (NMR), is
described in more detail. The computational tools used in concert with the NMR data are also
described.
The chapters 3, 4 and 5 are devoted to the results and discussion of the studies
performed on the three aforementioned peptides. Esculentin-1b(1-18) is the 18-mer Nterminal
fragment of the peptide esculentin-1b, which was isolated from the granular skin
secretions of the European frog Pelophylax lessonae/ridibundus. It is presented in the Chapter
3. The next chapter is dedicated to the studies performed on Plasticin-L1, a 25 amino acid residue peptide isolated from the skin secretions of the South-American Santa Fe frog
Leptodactylus laticeps (Leptodactylidae). In Chapter 5 the extensive and challenging work on
the four SB056 analogs is reported. Among various scientific collaborations, it has to be
emphasized that part of the study on the SB056 peptides was performed in the prof. A.S.
Ulrich’s labs at the Karlsruhe Institute of Technology, Germany, where I personally spent a 6
months stage.
Finally, in the last chapter, which is devoted to the main conclusions, a general
overview of the results is given, highlighting the advance gained in the field of the HDPs and
presenting possible outlooks for further peptides improvemen
Design, synthesis and characterization of new iron and aluminium chelating agents
Get PDFChelation therapy is widely used for metal-unbalance related diseases, namely those due to disorders on metal metabolism, such as beta-thalassemia, hemochromatosis
(Fe), and neurodegenerative diseases (Cu, Fe, Zn and Al). The study of metal chelators for clinical applications, either as chelating therapeutics able to target specific metal ions in the body, or as metal-carriers for therapeutic or imaging purposes, is a topical
research area which faces up to urgent medical problems. Metal-chelating drugs are used in many ways for the prevention, diagnosis and treatment of cancer, since cancer
cells, like normal cells, require essential metal ions such as iron, copper and zinc for growth and proliferation. Chelators can target the metabolic pathways of cancer cells
through the control of proteins involved in the regulation of these metals and also of other molecules involved in cell cycle control, angiogenesis and metastatic
suppression. The thermodynamic aspects regarding the complexation of metal ions of medical interest are of primary importance for a correct understanding of the role of metals in human diseases in order to rationalize the design of new molecules for diagnostic and therapeutic purposes. A typical case is the treatment of metal overload
diseases where the highest thermodynamic stability and largest selectivity of the
complexes are crucial factors in the ligand design.
This thesis is focused on the development and study of new compounds which, as a result of their strong interaction with specific metal ions, can be potentially used as
pharmaceutical drugs for diagnosis or therapy. The work was performed with a multidisciplinary approach regarding mostly chemistry, but including also biochemistry
and biology. The work presented in this thesis is devoted to reach the following aims:
Design and synthesis of new multivalent ligands in order to enhance the efficiency and selectivity of both metal-interaction and biomolecular recognition of available ligands (or metal complexes), as well as the
targeting for drug delivery; Assessment of the most important physical and chemical properties of
metal related compounds, namely metal-chelating efficacy and selectivity (thermodynamic and kinetic) with respect to other biometals or biological molecules, mostly in solution but also in silico;
Bioevoluation, in vitro and in vivo, for the most promising compounds. This thesis is divided in two chapters. Chapter I is dedicated to a description of Chelation Therapy for treating metal intoxication in humans. The importance of
chelating agents in neurodegenerative diseases like Alzheimer disease, is introduced. The main aspects of Fe, Al, and Cu metabolism in humans are presented. The papers I,
II, III and IV relative to this chapter has been appended.
Chapter II describes the synthesis of the new studied ligands, and the experimental methods and techniques that were used for the investigation of the ligands and of
their complexes with a number of metal ions. Important features of the used techniques are briefly described including basic principles, advantages and limitations.
The papers V, VI, and VII explain in detail the developed work. The main conclusions of this work are:
A new family of hydroxypyrone ligands (L4, L5, L6, L7, L8, and L9) has been synthesized and fully characterized. These ligands are easy and cheap to produce;
Complex formation equilibria showed good efficiency and selectivity for iron and aluminium. With Fe3+ various protonated 2:3 Fe:L species have been detected (with exception for L7). Experimental data give evidence of
a strong chelating ability for L8 and, in order of decreasing ability, for ligands L5 > L4 > L9 = L6 > L7. Al3+ also forms 2:3 Al:L complexes with the
ligands L4, L5, L6, and L9. The ligand with a shorter linker, L8, forms the most stable complexes of stoichiometry 2:2 (Al:L). Also Al3+ forms with L8
the strongest complexes, and in order of decreasing stabilities with the ligands L6 > L5 > L4 > L9 > L7.
Studies in mice confirmed the high in vivo metal scavenging ability of the tetradentate ligands (L4, L5, L6, L8, and L9) in comparison with the corresponding bidentate (L7). The excellent chelating properties recommend further toxicological and pharmacological research on these
new promising ligands
Inkjet printing: technique and applications for organic electronic devices
Get PDFSince the discovery of the polyacetylene conductivity in 1977 by Shirakawa,MacDiarmid and Heeger, Organic Electronics has been growing and establishing for a new generation of electronic devices. On one hand, the unique properties of polymeric semiconductors and conductors,
such as flexibility and transparency, allow the fabrication of low-cost devices over large area: the most common are the Organic Light Emitting Diodes (OLEDs) and the organic
photovoltaic cells. On the other hand, much effort has been made to investigate new technologies and processes for the realization of high-performance organic transistors and
sensors. Among them, Inkjet Printing is a promising technique which exploits all the advantages
of organic materials, such as low-cost and solution processability, and allows the large-scale automated fabrication of large area devices. This thesis describes the work carried outwith a piezoelectric drop-on-demand inkjet printer, theDimatixMaterials Printer 2831. The first chapter gives an overview on Organic and Printed
Electronics state-of-art, also describing the physical principles of conductivity in organic molecules. The second chapter is totally focused on the inkjet printing technique: after a brief description of the printer employed, a detailed description of the printing process, from the ink formulation to the drop deposition and drying phenomena, is presented. Moreover the materials employed are described together with the printing parameters set for achieving the best deposition condition. Chapter 3 is devoted to tactile sensing, which is the main application
of the Organic Field-Effect Transistors (OFETs) in this work within the ROBOSKIN project. After an overview of inorganic tactile sensors and of the fundamentals of strain sensing in OFETs, the fabrication steps are described followed by the detailed electromechanical
characterization of the various strain sensors realized. Finally, the fourth chapter describes other applications of inkjet printing developed in this work: organic diodes and photodiodes within the HYMEC project, patterned electrodes for the detection of cells electrical activity,
both in vivo and in vitro, and a RFID tag antenna
Engineering geological characterization of volcanic rocks of ethiopian and sardinian highlands to be used as construction materials
Get PDFThis thesis presents the results of the study conducted on the “Geoengineering characterization
of volcanic rocks from Ethiopian and Sardinian highlands to be used as construction
materials”. Though, the two project areas are geographically far apart, both are partly
covered with volcanic rocks mainly consisting of basic and subordinate felsic rocks.
The research was conducted in two countries; part I, the Ethiopian Project area located on the
northwestern central Highlands of the Amhara regional state. It is characterized by rugged
topography being situated on the western margin of the Main Ethiopian Rift, while, Part II, the
Sardinian Project area, is located in the northwestern central part of the Island stretched from
Abbasanta-Borore on the Altopiano di Abbasanta.
The major objectives of the study in both project areas include; a) engineering geological
characterization of the volcanic rocks of Sardinian (Abbasanta-Borore area) and Ethiopian
highland (Tarmaber formation) to be used as construction materials b)assessing the volcanic
rocks for their suitability to be used as building stone and coarse aggregates/construction
materials with regard to the various time honoured standards and specifications like American
Society for Testing and Materials(ASTM), British Standards(BS), American Association of
State Highway and Transportation Officials (AASHTO), Ente Nazionale Italiano di
Unificazione (UNIEN) c) presenting a conceptual framework which puts forward a vision for
future crushed aggregate characterization of the Tarmaber formation, d)evaluation and
comparison of the physical and mechanical properties of the Sardinian highland Plio-
Quaternary basalt with that of Ethiopian Tarmaber formation(basalt).
The field work in the Ethiopian study area was accomplished in two phases, the first field work
was conducted during the months of February and July, 2011 and the second was in February
and September, 2012, while the Sardinian project field work was carried out during May and
June, 2012. In all these field work periods geological traverses, field documentations and
adequate samples were collected for the various laboratory tests in both project areas.
Laboratory testing of chemical, physical and mechanical properties were carried out to
characterize the volcanic rocks from both study areas to ascertain the suitability of the rocks
as construction materials.
iv
Geologically, the Ethiopian study area is part of the Miocene Shield volcanic terrain that
covered the western and north western central plateaux of Ethiopia forming a conspicuous
land feature in East Africa. The studied area is specifically covered with the Tarmaber
formation (Megezez subdivision) consisting of aphyric basalt, phyric basalt, trachybasalt,
ignimbrite/rhyolite, tuff and minor trachyte.
Thorough literature review has been conducted on volcanic rocks as construction materials
and from the compiled information a laboratory testing program was envisaged and conducted
on the samples collected from the studied areas. Selection of the tests was based upon the tests’
precision, efficiency, and predictive capabilities and relevancy for the specific geographic
location and geologic formation. In the laboratory testing phase of this project, the proposed
tests were used to evaluate the full range of the project area crushed aggregate resources.
Moreover, a conceptual laboratory test flow diagram is developed for future aggregate
characterization of the Ethiopian project area. Furthermore, a geological map is prepared
outlining the various lithotypes which could help to predict the geo-engineering properties of
the rocks by identifying the rock types.
The Ethiopian project area is the major source and future potential of crushed coarse
aggregates by both private and public sectors. This study has identified recent advances in the
understanding and testing of crushed aggregates to be produced from the Tarmaber formation
(Megezez subdivision).
The geo-engineering properties depend on the mineral composition, texture and overall fabrics
of the rock. Each of the rock type crushed aggregate demonstrates rather well defined ranges
of geo-engineering properties and mineralogical characteristics. The laboratory work included
Uniaxial Compressive Strength, Abrasion resistance, Ultrasonic pulse velocity, Bulk density,
Water absorption, Specific gravity, Porosity, Petrographic examination, Aggregate Impact
Value (AIV), Aggregate Crushing Value (ACV), Los Angeles Abrasion Value (LAAV), Sodium
Sulphate Soundness Value (SSSV), X-ray Diffraction(XRD) and Alkali-Silica Reactivity(ASR),
Water soluble Sulphate and Chloride tests.
The physical and mechanical properties like Water absorption, Flakiness and Elongation
indices, and Specific gravity, strength and durability parameters have been determined and
examined critically with reference to suitability and stability, taking into consideration the
various specifications and time honoured standards. Hence, based on the geo-engineering and
petrographic properties, optimal end uses of the different rock types have also been discussed
even though the current study is mainly geared towards crushed aggregate sources for cement
and asphalt concrete mix.
The field and laboratory works were compiled and compared together to reveal the
engineering performance of the basaltic rocks in terms of crushed coarse aggregates
suitability. The basaltic rocks show a variety of textural and mineralogical characteristics,
which may affect their physical and mechanical properties as well as their use as construction
materials. The Uniaxial compressive strength of the basaltic rock ranges from 130MPa to
350MPa, Ultrasonic pulse velocity from 4000m/s to7000m/s, Open porosity from 0.95% to
3.08%, Bulk density from 2.8g/cm3 to 3.03g/cm3, Point load index from 4.83 to15.29MPa,
Water absorption from 0.33% to 1.08%, Dynamic Elastic Modulus from 64GPa to 120GPa,
Abrasion Resistance(Capon wheel) from 15.5mm to 25.2mm, Specific gravity from 2.51 to
3.00, SSSV from 1% to 10%, ACV from 15% to 30%, AIV from 20% to 36%, TPFV from 110kN
to 200kN, Los Angeles Abrasion Value from 12% to 30%, Flakiness index from 15% to 37%,
and Elongation index from 15% to 38%. The Alkali-Silica Reactivity test was carried out using
‘Mielenz quick chemical’ test (ASTM C289) and few basaltic flow layers were found to be
potentially Alkali-Silica Reactive. The petrographic examination and XRD analysis also
confirmed the presence of reactive quartz and harmful zeolite group minerals.
In this study, the different rock types has been investigated as sources of individual rock type
crushed aggregate for specific end use rather than aggregates comprised of various rock types.
In this respect, the aphyric basalts are found to be the most suitable crushed aggregate source
for ordinary Portland cement and asphalt concrete, sub base and base course. The porphyritic
basalt and glassy rhyolite should be used in unbound pavements only. The minor amounts of
zeolite bearing uppermost layer of phyric columnar basalt also should be avoided from
concrete making for safe stability of structures due to risk of potential Alkali silica reactivity.
Geochemically the Tarmaber formation represents alkaline-subalkaline bimodal mafic-felsic
volcanic series. The mafic volcanic suite is more abundant and characterized by alkaline
basalts and minor silica undersaturated rocks (basanites) and the felsic suite is relatively less
abundant and represented by strongly welded ignimbrite/rhyolite, tuff and minor lava flows of
trachyte. Furthermore, the mafic suite is characterized by sodic affinity on conventional K2O
versus Na2O diagram. The Fe2O3 content is high for all the samples (11.53-15.79%) and high
Na2O + K2O content (~4.04-6.2%) is typical of alkaline basalts of Tarmaber formation. The
MgO is low (3.45-7%), while 0.3-1.3%P2O5 and 2.8-4.5%TiO2 are relatively high. Loss On
Ignition (LOI) varies between 0.5% and 1.5% indicating the unaltered nature of the sampled
rocks.
The geo-engineering properties of the Tarmaber formation (the basalts and
pyroclastics/ignimbrite) indicated that the pyroclastics (ignimbrite) are found to be good
building materials with regard to their high uniaxial compressive strength, abrasion resistance
and weathering index. However, their relatively higher water absorption and porosity limit
them not to be used in public walkways, horizontal pavements, public car parks and flooring in
supermarkets in an open environment as intensive use while some flow layers of the basalts are
mainly suitable for production of coarse aggregates for cement concrete mix.
The Sardinian project area is part of the Plio-Quaternary volcanic rocks that covered the north
western central plateaux of the island forming flat topped land feature. The studied area is
specifically covered with the ‘Basalti di Plateau” consisting of porphyritic basalt, vesicular
basalt, andesitic basalt and trachybasalt. The physical and mechanical tests conducted on
these rocks proved the high potential of the studied rocks to be used in the construction
industry. The Uniaxial compressive strength ranges from 35 to 177MPa, Ultrasonic P-wave
velocity from 4143m/s to 6066m/s, Water absorption from 1.51 to 3.11%, Porosity from 0.64 to
10.33%, Specific gravity from 2.26 to 2.71, Bulk density from 2.2 to 2.69g/cm3, Abrasion
Resistance(Capon wheel) from 19.4 to 23.6mm, Point Load index from 1.98 to 7.05MPa, ACV
from 19 to 46%, LAAV from 17 to 33%, Dynamic Young’s Modulus from 33GPa to 92GPa to
mention a few test results. Furthermore, Alkali Silica Reactivity test, X-ray diffraction analysis
and detail petrographic studies were conducted on the collected Sardinian samples. According
to the Alkali Silica Reactivity test, a sample is found to be deleterious (highly reactive) and
later XRD analysis and petrographic study also confirmed the Alkali Silica Reactivity test
result.
The Sardinian samples have shown acceptable abrasion resistance values and uniform
physical and mechanical properties which guarantee to be used as dimension stone/cut stone.
The Abbasanta-Borore Plio-Quaternary basalt resource is huge; however, some clays in some
samples were indicated by the XRD analysis and these clays might have deleterious effect when
using these basalts as aggregate; therefore, the clay fraction should be determined with
quantitative XRD analysis for curiosity, otherwise, almost all the conducted aggregate tests
indicated relatively good quality aggregate resource except the vesicular basalt. The vesicular
basalt showed poor aggregate test values, like LAAV and Water absorption, ACV and
Uncompacted bulk density. However, for its aesthetic value, the vesicular basalt could be used
for indoor and sheltered cladding purposes as the case may be.
One of the purposes of this research was to compare some of the engineering properties of
basaltic rocks to determine whether there are similarities and differences between each of the
different source countries, Ethiopia and Sardinia. This is particularly interesting given the
distance between the two countries and the different processes that have occurred since the
formation of these basaltic rocks. The Ethiopian volcanic successions lack rocks of
intermediate composition (bulk rock chemistry: SiO2, 52-63%), defining strong silica gap as
observed in other volcanic areas, suggesting the bimodal volcanism nature of the Ethiopian
volcanic suite in non subduction tectonic setting and implying anorogenic magmatism
probably connected to plume/hot spot source.
Geochemically, the Sardinian Plio-Quaternary volcanic rocks lack significant ultrabasic
compositions (i.e., bulk rock silica SiO2 composition <45% are rare, Lustrino et al., 2007)
while the Ethiopian Tarmaber formation bulk rock silica composition reaches as low as 42%
and not greater than 51% while the Sardinian rocks reaches as high as 63% (andesitic).
Intermediate rocks are totally absent in the Ethiopian Tarmaber formation. The physical and
mechanical properties of the Tarmaber basalt are found to be higher than the Sardinian Plio-
Quaternary basalts. Although grouped under the engineering term “basaltic”, there are
distinct differences within the specific types present in each of the countries considered in this
study, i.e. mainly basaltic andesite in Sardinia and basalt in Ethiopia.
Evaluation of the physical and mechanical data indicates that the Ethiopian basalts are
typically of higher density and resistance to static crushing than the Sardinian Plio-Quaternary
basalt. The difference in engineering properties of aggregates from Sardinia on one hand and
Ethiopia on the other hand is explained partly by the chemical composition of the material, but
also by geological age, geological history and climate.
In both countries the geological history of the basalts might have influenced the aggregate
properties. Furthermore and more importantly, regional conditions (such as hydrothermal
activity) might have influenced the rock properties and alteration products. The physical and
mechanical properties of the Ethiopian basalts have shown better compliance with the various
specifications than the Sardinian basaltic samples especially the aggregate test results.
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Comparison of the results is revealing that different physical and mechanical trends are
observed from rocks that are similar in basic mineralogical composition. This suggests that the
relationships between physical and mechanical properties are often specific to rock type and
occurrence.
Aggregate quarrying provides necessary raw materials for infrastructure and civil
development; however, mining and/or quarrying operations have a non-zero environmental
impact. By the very nature of the requirements for the final products, dimension stone and
aggregate quarrying is a clean industry from a polluting point of view. Natural aggregates and
dimension stone are used in its natural state, and do not require concentration and extraction
from an ore; it is these latter two processes that result in significant environmental impacts.
However, the visual impacts are often significant, given that many deposits are situated in
topographically high areas. The environmental impacts of dimension stone and aggregate
quarrying are mainly of temporary duration, and can be effectively managed via revegetation,
landscaping, rock shading, if appropriate planning and consideration is followed from the
exploration stage through to quarry closure. Hence, quarrying and post-quarrying activities
should always target the mitigation of potential environmental and/or social impacts
Characterization of the mechanism of action of new HIV-1 reverse transcriptase-associated ribonuclease H inhibitors
Get PDFHIV-1 the Reverse Transcriptase (RT), the most renowned retroviral specific enzyme, was the first anti-HIV target to be exploited, as. HIV-1 RT combines two functions essential for viral replication: DNA polymerase, synthesis DNA either in a RNA dependent (RDDP) or DNA dependent (DDDP) manner, and Ribonuclease H (RNase H) . The RNase H activity catalyzes highly specific hydrolytic events on the RNA strand of the RNA/DNA replication intermediate, critical to the synthesis of integration-competent double-stranded proviral DNA. Because of its essential role, RNase H is a promising target for drug development. However, despite years of efforts, no RNase H inhibitor (RHI) has yet reached clinical approval.
In this work we pursued the identification and characterization of new promising RHIs targeting either the RNase H active site itself (RNase H active site chelating agents) or both RNase H and RDDP activities (allosteric dual inhibitors).
The first approach faced the challenging nature of the RNase H active site region, the morphology of wich is, more open than that of the relatively similar,HIV-1 integrase (IN). This hampers the identification of a druggable pocket. We initially used Foamy Virus RT as a tool, to perform NMR and docking analyses on the interaction between FV RT RNase H domain and a previously identified diketo acid (DKA) derivative, inhibitor RDS1643. The amino acid residues of the FV RNase H active site region (T641, I647, Y672 and W703) were established to be important for the interaction with the inhibitor and analogous residues were successfully identified in the HIV-1 RNase H domain using structural overlays. Further docking and site directed mutagenesis studies were performed using six couples of ester/acid DKA, derived from RDS1643, showing for the first time, a broad interaction between RHIs and conserved residues in the HIV-1 RNase H active site region (R448, N474, Q475, Y501 and R557). Moreover, ester and acid derivatives exhibited a different binding orientation, that reflected a different specificity for RNase H versus IN. Among the synthesised derivatives one, RDS1759, showed to be an RNase H selective active site inhibitor characterized also, for the first time,in cell-based assays.
The second approach focused on the determination of the mechanism of action of a new isatine-derived RNase H/RDDP dual inhibitor, RMNC6. Docking analysis and site directed mutagenesis results suported the hypothesis of a two-sites mode of action, with an independent role for two pockets,to be further characterized for a rational optimization of the scaffold