Theoretical and implementation aspects in the mechanization of the metatheory of programming languages

Interactive theorem provers are tools designed for the certification of formal proofs developed by means of man-machine collaboration. Formal proofs obtained in this way cover a large variety of logical theories, ranging from the branches of mainstream mathematics, to the field of software verification. The border between these two worlds is marked by results in theoretical computer science and proofs related to the metatheory of programming languages. This last field, which is an obvious application of interactive theorem proving, poses nonetheless a serious challenge to the users of such tools, due both to the particularly structured way in which these proofs are constructed, and to difficulties related to the management of notions typical of programming languages like variable binding. This thesis is composed of two parts, discussing our experience in the development of the Matita interactive theorem prover and its use in the mechanization of the metatheory of programming languages. More specifically, part I covers: - the results of our effort in providing a better framework for the development of tactics for Matita, in order to make their implementation and debugging easier, also resulting in a much clearer code; - a discussion of the implementation of two tactics, providing infrastructure for the unification of constructor forms and the inversion of inductive predicates; we point out interactions between induction and inversion and provide an advancement over the state of the art. In the second part of the thesis, we focus on aspects related to the formalization of programming languages. We describe two works of ours: - a discussion of basic issues we encountered in our formalizations of part 1A of the Poplmark challenge, where we apply the extended inversion principles we implemented for Matita; - a formalization of an algebraic logical framework, posing more complex challenges, including multiple binding and a form of hereditary substitution; this work adopts, for the encoding of binding, an extension of Masahiko Sato's canonical locally named representation we designed during our visit to the Laboratory for Foundations of Computer Science at the University of Edinburgh, under the supervision of Randy Pollack.

Glutamate iontophoresis induces long-term potentiation in the absence of evoked presynaptic activity

$\rm\underline{L}$ong-$\rm\underline{t}$erm $\rm\underline{p}$otentiation (LTP) is a candidate cellular mechanism underlying mammalian learning and memory. Protocols that induce LTP typically involve afferent stimulation. The experiments described in this dissertation tested the hypothesis that LTP induction does not require presynaptic activity. The significance of this hypothesis is underscored by results suggesting that LTP expression may involve activity-dependent presynaptic changes. An induction protocol using glutamate iontophoresis was developed that reliably induces LTP in hippocampal slices without afferent stimulation (ionto-LTP). Ionto-LTP is induced when excitatory postsynaptic potentials are completely blocked with adenosine and $\rm\underline{t}$etrodo$\rm\underline{t}$o$\rm\underline{x}$in (TTX). These results suggest constraints on the involvement of presynaptic mechanisms and putative retrograde messengers in LTP induction and expression; namely, these processes must function without many forms of activity-dependent presynaptic processes.^ In testing the role of pre-and postsynaptic mechanisms in LTP expression whole-cell recordings were used to examine the frequency and amplitude of $\rm\underline{s}$pontaneous $\rm\underline{e}$xcitatory $\rm\underline{p}$o$\rm\underline{s}$ynaptic $\rm\underline{c}$urrents (sEPSCs) in CA1 pyramidal neurons. sEPSCs where comprised of an equal mixture of TTX insensitive miniature EPSCs and sEPSCs that appeared to result from spontaneous action potentials (i.e., TTX sensitive EPSCs). The detection of all sEPSCs was virtually eliminated by CNQX, suggesting that sEPSCs were glutamate mediated synaptic events. Changes in the amplitude and frequency sEPSCs were examined during the expression of ionto-LTP to obtain new information about the cellular location of mechanisms involved in synaptic plasticity. The findings of this dissertation show that ionto-LTP expression results from increased sEPSC amplitude in the absence of lasting increases in sEPSC frequency. Potentiation of sEPSC amplitude without changes in sEPSC frequency has been previously interpreted to be due to postsynaptic mechanisms. Although this interpretation is supported by findings from peripheral synapses, its application to the central nervous system is unclear. Therefore, alternative mechanisms are also considered in this dissertation. Models based on increased release probability for action potential dependent transmitter release appear insufficient to explain our results. The most straightforward interpretation of the results in this dissertation is that LTP induced by glutamate iontophoresis on dendrites of CA1 pyramidal neurons is mediated by postsynaptic mechanisms. ^

Fine-scale population structure analysis of seven local Swiss sheep breeds using genome-wide SNP data

As part of the global sheep Hapmap project, 24 individuals from each of seven indigenous Swiss sheep breeds (Bundner Oberländer sheep (BOS), Engadine Red sheep (ERS), Swiss Black-Brown Mountain sheep (SBS), Swiss Mirror sheep (SMS), Swiss White Alpine (SWA) sheep, Valais Blacknose sheep (VBS) and Valais Red sheep (VRS)), were genotyped using Illumina’s Ovine SNP50 BeadChip. In total, 167 animals were subjected to a detailed analysis for genetic diversity using 45 193 informative single nucleotide polymorphisms. The results of the phylogenetic analyses supported the known proximity between populations such as VBS and VRS or SMS and SWA. Average genomic relatedness within a breed was found to be 12 percent (BOS), 5 percent (ERS), 9 percent (SBS), 10 percent (SMS), 9 percent (SWA), 12 percent (VBS) and 20 percent (VRS). Furthermore, genomic relationships between breeds were found for single individuals from SWA and SMS, VRS and VBS as well as VRS and BOS. In addition, seven out of 40 indicated parent–offspring pairs could not be confirmed. These results were further supported by results from the genome-wide population cluster analysis. This study provides a better understanding of fine-scale population structures within and between Swiss sheep breeds. This relevant information will help to increase the conservation activities of the local Swiss sheep breeds.

Tab. 1: Rb-Sr data on metasediments in the Shackleton Range

Summary: The stratigraphy of the Shackleton Range established by Stephenson (1966) and Clarkson (1972) was revised by results of the German Expedition GEISHA 1987/88. The "Turnpike Bluff Group" does not form a stratigraphic unit. The stratigraphic correlation of its formations is still a matter of discussion. The following four formations are presumed to belong to different units: The Stephenson Bastion Formation and Wyeth Heights Formation are probably of Late Precambrian age. The Late Precambrian Watts Needle Formation, which lies unconformably on the Read Group, is an independant unit which has to be separated from the "Turnpike Bluff Group". The Mount Wegener Formation has been thrusted over the Watts Needle Formation. Early Cambrian fossils (Oldhamia sp., Epiphyton sp., Botomaella (?) sp. and echinoderms) were found in the Mt. Wegener Formation in the Read Mountains. The Middle Cambrian trilobite shales on Mount Provender, which form the Haskard Highlands Formation, are possibly in faulted contact with the basement complex (Pioneers and Stratton Groups). They are overlain by the Blaiklock Glacier Group, for which an Ordovician age is indicated by trilobite tracks and trails, low inclination of the paleomagnetic field and the similarity to the basal units of the Table Mountain Quartzite in South Africa. The Watts Needle Formation represents epicontinental shelf sediments, the Mount Wegener Formation was deposited in a (continental) back-arc environment, and the Blaiklock Glacier Group is a typical molasse sediment of the Ross Orogen.

XRF data, magnetic susceptibility, greyscale values and revised depths of sediments from ODP Leg 154 sites

The distinctly cyclic sediments recovered during ODP Leg 154 played an important role in constructing the astronomical time scale and associated astro(bio)chronology for the Miocene, and in deciphering ocean-climate history. The accuracy of the timescale critically depends on the reliability of the shipboard splice used for the tuning and on the tuning itself. New high-resolution colour- and magnetic susceptibility core scanning data supplemented with limited XRF-data allow improvement of the stratigraphy. The revised composite record results in an improved astronomical age model for ODP Site 926 between 5 and 14.4 Ma. The new age model is confirmed by results of complex amplitude demodulation of the precession and obliquity related cycle patterns. Different values for tidal dissipation are applied to improve the fit between the sedimentary cycle patterns and the astronomical solution. Due to the improved stratigraphy and tuning, supported by the results of amplitude demodulation, the revised time scale yields more reliable age estimates for planktic foraminiferal and calcareous nannofossil events. The results of this study highlight the importance of stratigraphy for timescale construction.

El bienestar social durante el peronismo clásico. La expansión de los servicios de salud hacia las áreas rurales de los municipios de la provincia de Mendoza (1946-1955)

Con la llegada del peronismo al gobierno se produjeron reformas en relación a la organización y funcionamiento del sistema de salud pública. Pero más allá de sus éxitos o fracasos, el cuidado y la preservación de la salud de la población, incluyendo la de las zonas más apartadas y atrasadas del interior del país, fue una de las metas principales del gobierno de Juan Domingo Perón. A partir de esto, nuestro objetivo central es estudiar las políticas sanitarias en los municipios de la provincia de Mendoza durante el período 1946-1955, atendiendo a dos aspectos: el primero de ellos, relacionado con el rol del gobierno nacional y provincial en la ejecución de esta política pública, y el segundo, con los resultados, logros y efectos de la misma en los departamentos mendocinos. Este estudio empírico, en el cual se cotejan programas con resultados, permitirá conocer entonces el real cumplimiento de los objetivos establecidos por el peronismo.

El bienestar social durante el peronismo clásico. La expansión de los servicios de salud hacia las áreas rurales de los municipios de la provincia de Mendoza (1946-1955)

Con la llegada del peronismo al gobierno se produjeron reformas en relación a la organización y funcionamiento del sistema de salud pública. Pero más allá de sus éxitos o fracasos, el cuidado y la preservación de la salud de la población, incluyendo la de las zonas más apartadas y atrasadas del interior del país, fue una de las metas principales del gobierno de Juan Domingo Perón. A partir de esto, nuestro objetivo central es estudiar las políticas sanitarias en los municipios de la provincia de Mendoza durante el período 1946-1955, atendiendo a dos aspectos: el primero de ellos, relacionado con el rol del gobierno nacional y provincial en la ejecución de esta política pública, y el segundo, con los resultados, logros y efectos de la misma en los departamentos mendocinos. Este estudio empírico, en el cual se cotejan programas con resultados, permitirá conocer entonces el real cumplimiento de los objetivos establecidos por el peronismo.

El bienestar social durante el peronismo clásico. La expansión de los servicios de salud hacia las áreas rurales de los municipios de la provincia de Mendoza (1946-1955)

Con la llegada del peronismo al gobierno se produjeron reformas en relación a la organización y funcionamiento del sistema de salud pública. Pero más allá de sus éxitos o fracasos, el cuidado y la preservación de la salud de la población, incluyendo la de las zonas más apartadas y atrasadas del interior del país, fue una de las metas principales del gobierno de Juan Domingo Perón. A partir de esto, nuestro objetivo central es estudiar las políticas sanitarias en los municipios de la provincia de Mendoza durante el período 1946-1955, atendiendo a dos aspectos: el primero de ellos, relacionado con el rol del gobierno nacional y provincial en la ejecución de esta política pública, y el segundo, con los resultados, logros y efectos de la misma en los departamentos mendocinos. Este estudio empírico, en el cual se cotejan programas con resultados, permitirá conocer entonces el real cumplimiento de los objetivos establecidos por el peronismo.

Sea surface temperature reconstruction of sediment profile W8709A-8

Assessment of changes in surface ocean conditions, in particular, sea-surface temperature (SST), is essential to understand long-term changes in climate especially in regions where continental climate is strongly influenced by oceanographic processes. To evaluate changes in SST in the northeast Pacific, we have analyzed long-chain alkenones of prymnesiophyte origin at 38 depths in a piston and associated trigger core collected beneath the contemporary core of the California Current System at 42°N, ~270 km off the coast of Oregon/California. The samples span 30,000 years of deposition at this location. Unsaturation patterns (UK'37) in the alkenone series display a statistically significant difference (p <<0.001) between interglacial (0.44 ± 0.02, n = 11) and glacial (0.29 ± 0.04, n = 20) intervals of the cores. Detailed examination of other compositional features of the C37, C38, C39 alkenone series and a related C36 alkenoate series measured downcore suggests the published UK'37 - temperature calibration (UK'37 = 0.034 * T + 0.039 ) , defined for cultures of a strain of Emiliania huxleyi isolated from the subarctic Pacific, provides best estimates of winter SST at our study site. This inference is purely statistical and does not imply, however, that the phytoplankton source of these biomarkers is most productive in winter or at the ocean surface. The temperature record for UK'37 implies (1) an ~4°C shift occurred in winter SST from ~7.5 ± 1.1°C at the last glacial maximum to ~11.7 ± 0.7°C in the present interglacial period, and (2) this warming trend was confined to the time frame 14-10 Ka within the glacial to interglacial transition period. These conclusions are corroborated entirely by results from an independent SST transformation of radiolarian species assemblage data obtained from the same core materials.

Physical oceanography and current measurements in the Filchner Depression (Weddell Sea, Antarctica) during Ernest Shackleton cruise ES060

Cold and dense ice shelf water (ISW) emerging from the Filchner-Ronne Ice Shelf cavity in the southwestern Weddell Sea flows northward through the Filchner Depression to eventually descend the continental slope and contribute to the formation of bottom water. New ship-born observations of hydrography and currents from Filchner Depression in January 2013 suggest that the northward flow of ISW takes place in a middepth jet along the eastern flank of the depression, thus questioning the traditional view with outflow along the western flank. This interpretation of the data is supported by results from a regional numerical model, which shows that ISW flowing northward along the eastern coast of Berkner Island turns eastward and crosses the depression to its eastern side upon reaching the Filchner ice front. The ice front represents a sudden change in the thickness of the water column and thus a potential vorticity barrier. Transport estimates of northward ISW flux based on observations ranges from 0.2 to 1.0 Sv.

Plasma kinetics issues in an ESA study for a plasma laboratory in space

A study supported by the European Space Agency (ESA), in the context of its General Studies Programme, performed an investigation of the possible use of space for studies in pure and applied plasma physics, in areas not traditionally covered by ‘space plasma physics’. A set of experiments have been identified that can potentially provide access to new phenomena and to allow advances in several fields of plasma science. These experiments concern phenomena on a spatial scale (101–104 m) intermediate between what is achievable on the ground and the usual solar system plasma observations. Detailed feasibility studies have been performed for three experiments: active magnetic experiments, largescale discharges and long tether–plasma interactions. The perspectives opened by these experiments are discussed for magnetic reconnection, instabilities, MHD turbulence, atomic excited states kinetics, weakly ionized plasmas,plasma diagnostics, artificial auroras and atmospheric studies. The discussion is also supported by results of numerical simulations and estimates.

Interaction between like-charged colloidal spheres in electrolyte solutions

How colloidal particles interact with each other is one of the key issues that determines our ability to interpret experimental results for phase transitions in colloidal dispersions and our ability to apply colloid science to various industrial processes. The long-accepted theories for answering this question have been challenged by results from recent experiments. Herein we show from Monte-Carlo simulations that there is a short-range attractive force between identical macroions in electrolyte solutions containing divalent counterions. Complementing some recent and related results by others, we present strong evidence of attraction between a pair of spherical macroions in the presence of added salt ions for the conditions where the interacting macroion pair is not affected by any other macroions that may be in the solution. This attractive force follows from the internal-energy contribution of counterion mediation. Contrary to conventional expectations, for charged macroions in an electrolyte solution, the entropic force is repulsive at most solution conditions because of localization of small ions in the vicinity of macroions. Both Derjaguin–Landau–Verwey–Overbeek theory and Sogami–Ise theory fail to describe the attractive interactions found in our simulations; the former predicts only repulsive interaction and the latter predicts a long-range attraction that is too weak and occurs at macroion separations that are too large. Our simulations provide fundamental “data” toward an improved theory for the potential of mean force as required for optimum design of new materials including those containing nanoparticles.

Heat flow and heat conductivity coefficient measured in bottom sediments collected in Cruise 13 of R/V Akademik Sergey Vavilov in the Pechora Sea

In Cruise 13 of R/V Akademik Sergey Vavilov in the Pechora Sea, six heat flow varied from 50 to 75 mW/m**2. Deep heat flow in the Pechora Sea was calculated equal to 45 mW/m**2, which is confirmed by results of geological and geophysical studies and corresponds to Middle Baikal age of the basement. A model of structure of the lithosphere in the Pechora Sea is suggested. Total thickness of the lithosphere in the basin (190 km) determined from geothermal data agrees well with that in transition zones from the continent to the ocean. According to estimates of deep heat flow in the region obtained, thickness of the mantle (160 km), of the basaltic (15 km), and of the granitic (15 km) layers of the lithosphere were also evaluated. Temperature values at boundaries of the sedimentary layers were calculated over a geological and geophysical profile crossing the Pechora Sea basin. Temperatures obtained agree with the temperature interval of hydrocarbon generation and correspond to Permian-Triassic sedimentary sequences, which are the most productive ones in the Pechora Sea region from the point of view of oil and gas potential.

The effect of lignin and inorganic species in biomass on pyrolysis oil yields, quality and stability

This paper investigates four reference fuels and three low lignin Lolium Festuca grasses which were subjected to pyrolysis to produce pyrolysis oils. The oils were analysed to determine their quality and stability, enabling the identification of feedstock traits which affect oil stability. Two washed feedstocks were also subjected to pyrolysis to investigate whether washing can enhance pyrolysis oil quality. It was found that the mineral matter had the dominate effect on pyrolysis in compared to lignin content, in terms of pyrolysis yields for organics, char and gases. However the higher molecular weight compounds present in the pyrolysis oil are due to the lignin derived compounds as determined by results of GPC and liquid-GC/MS. The light organic fraction also increased in yield, but reduced in water content as metals increased at the expense of the lignin content. It was found that the fresh oil and aged oil had different compound intensities/concentrations, which is due to a large number of reactions occurring when the oil is aged day by day. These findings agree with previous reports which suggest that a large amount of re-polymerisation occurs as levoglucosan yields increase during the aging progress, while hydroxyacetaldehyde decrease. In summary the paper reports a window for producing a more stable pyrolysis oil by the use of energy crops, and also show that washing of biomass can improve oil quality and stability for high ash feedstocks, but less so for the energy crops.

Engineering liposomal systems to develop solubility enhancing technology

This research primarily focused on identifying the formulation parameters which control the efficacy of liposomes as delivery systems to enhance the delivery of poorly soluble drugs. Preliminary studies focused on the drug loading of ibuprofen within vesicle systems. Initially both liposomal and niosomal formulations were screened for their drug-loading capacity: liposomal systems were shown to offer significantly higher ibuprofen loading and thereafter lipid based systems were further investigated. Given the key role cholesterol is known to play within the stability of bilayer vesicles. the optimum cholesterol content in terms of drug loading and release of poorly soluble drugs was then investigated. From these studies a concentration of 11 total molar % of cholesterol was used as a benchmark for all further formulations. Investigating the effect of liposomc composition on several low solubility drugs, drug loading was shown to be enhanced by adopting longer chain length lipids. cationic lipids and. decreasing drug molecular weight. Drug release was increased by using cationic lipids and lower molecular weight of drug; conversely, a reduction was noted when employing longer chain lipids thus supporting the rational of longer chain lipids producing more stable liposomes, a theory also supported by results obtained via Langmuir studies· although it was revealed that stability is also dependent on geometric features associated with the lipid chain moiety. Interestingly, reduction in drug loading appeared to be induced when symmetrical phospholipids were substituted for lipids constituting asymmetrical alkyl chain groups thus further highlighting the importance of lipid geometry. Combining a symmetrical lipid with an asymmetrical derivative enhanced encapsulation of a hydrophobic drug while reducing that of another suggesting the importance of drug characteristics. Phosphatidylcholine liposornes could successfully be prepared (and visualised using transmission electron microscopy) from fatty alcohols therefore offering an alternative liposomal stabiliser to cholesterol. Results obtained revealed that liposomes containing tetradecanol within their formulation shares similar vesicle size, drug encapsulation, surface charge. and toxicity profiles as liposomes formulated with cholesterol, however the tetradecanol preparation appeared to release considerably more drug during stability studies. Langmuir monolayer studies revealed that the condensing influence by tetradecanol is less than compared with cholesterol suggesting that this reduced intercalation by the former could explain why the tetradecanol formulation released more drug compared with cholesterol formulations. Environmental scanning electron microscopy (ESEM) was used to analyse the morphology and stability of liposomes. These investigations indicated that the presence of drugs within the liposomal bilayer were able to enhance the stability of the bilayers against collapse under reduced hydration conditions. In addition the presence of charged lipids within the formulation under reduced hydration conditions compared with its neutral counterpart. However the applicability of using ESEM as a new method to investigate liposome stability appears less valid than first hoped since the results are often open to varied interpretation and do not provide a robust set of data to support conclusions in some cases.