While the poisonous effects of botulinum neurotoxin (BoNT) have been recognized since antiquity, the overall actions and mechanisms of effects of BoNT have been elucidated primarily over the past several decades. The general utility of BoNT is described in the paper, but the focus is mainly on the approaches towards negating the toxic effects of BoNT, and on the projection of an engineered BoNT molecule serving as a Trojan Horse to deliver a therapeutic load for treatment of a host of medical disorders. The BoNT molecule is configured with a binding domain, a zinc-dependent protease with specificity primarily for vesicular proteins, and a translocation domain for delivery of the metalloprotease into the cytoplasm. The anti-toxin approaches for BoNT include the use of vaccines, antibodies, block of BoNT binding or translocation, inhibition of metalloprotease activity, impeded translocation of the protease/catalytic domain, and inhibition of the downstream Src signaling pathway. Projections of BoNT as a therapeutic include its targeting to non-cholinergic nerves, also targeting to non-neuronal cells for treatment of hypersecretory disorders (e.g., cystic fibrosis), and treatment of hormonal disorders (e.g., acromegaly). Still in the exploratory phase, there is the expectation of major advances in BoNT neuroprotective strategies and burgeoning utility of engineered BoNTs as therapeutics.

This dissertation focuses on the forensic validation of computer evidence. It is a burgeoning field, by necessity, and there have been significant advances in the detection and gathering of evidence related to electronic crimes. What makes the computer forensics field similar to other forensic fields is that considerable emphasis is placed on the validity of the digital evidence. It is not just the methods used to collect the evidence that is a concern. What is also a problem is that perpetrators of digital crimes may be engaged in what is called anti-forensics. Digital forensic evidence techniques are deliberately thwarted and corrupted by those under investigation. In traditional forensics the link between evidence and perpetrator's actions is often straightforward: a fingerprint on an object indicates that someone has touched the object. Anti-forensic activity would be the equivalent of having the ability to change the nature of the fingerprint before, or during the investigation, thus making the forensic evidence collected invalid or less reliable. This thesis reviews the existing security models and digital forensics, paying particular attention to anti-forensic activity that affects the validity of data collected in the form of digital evidence. This thesis will build on the current models in this field and suggest a tentative first step model to manage and detect possibility of anti-forensic activity. The model is concerned with stopping anti-forensic activity, and thus is not a forensic model in the normal sense, it is what will be called a “meta-forensic” model. A meta-forensic approach is an approach intended to stop attempts to invalidate digital forensic evidence. This thesis proposes a formal procedure and guides forensic examiners to look at evidence in a meta-forensic way.

Intellectual Property (IP) based Integrated Circuit (IC) design is an established approach for the design of a complex System-on-Chip (SoC). Porting the preparatory designs to third-party without enough security margin exposes an attacker to perform reverse engineering (RE) on the designs and hence counterfeiting, IP theft etc., are common now-a-days. Design obfuscation can reduce RE attempt by an attacker. In this work, we propose a key based obfuscation and anonymization method for a behavioral IP. Given a behavioral VHDL description, the assignment and conditional statements are modified by incorporating random boolean operations with unique random key bits. The obfuscated VHDL is then anonymized by random identifiers. The resultant behavioral model can be simulated correctly upon application of original key sequence. Simulation results with nine datapath intensive benchmarks with three different lengths of test sequences show that the simulation overhead is negligible (only a few seconds). We evaluate the probability of reverse engineering the obfuscated design and show that it is extremely low.

Derivados de alumínio e gálio trivalentes com os sideróforos desferrioxamina (dfo) e desferrioxamina-cafeína (dfcaf) foram preparados e caracterizados em solução através de espectrometria de massas, voltametria cíclica, espectroscopia vibracional na região do infravermelho e ressonância magnética nuclear de próton. Confirmações adicionais da formação de MeL (Me = Al3+, Ga3+; L = dfo ou dfcaf) foram obtidas através de equilíbrios competitivos com as sondas fluorimétricas 8-hidroquinolina e desferrioxamina fluorescente. Observou-se que os complexos MeL são estáveis em solução, e que os derivados de alumínio são mais estáveis do que os de gálio. Também através da interação com o complexo calceína-ferro, observou-se que MeL se formaram em solução. Estudos de docking preliminares mostram que dfcaf pode ter o mesmo mecanismo de entrada em Escherichia coli que outros antibióticos transportadores de ferro. O efeito \"cavalo de Tróia\" consiste no carregamento seletivo de íons tóxicos através do sistema de absorção de ferro dos microrganismos mediado por sideróforos. A atividade biológica dos complexos MeL foi estudada através da inibição do crescimento de Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus e Candida albican. Em geral, dfcaf é mais ativo do que dfo, possivelmente devido à sua maior lipofilicidade. Os complexos MeL foram em geral mais ativos do que os metais ou ligantes separadamente, possivelmente pela absorção dos íons tóxicos facilitada pelos sideróforos, demonstrando o efeito \"cavalo de Tróia\". A bactéria Gram-positiva S. aureus apresentou maior resistência do que as Gram-negativas, e interessantemente o fungo C. albicans foi sensível a esses tratamentos. Esses resultados mostram a possibilidade de usar tais metalofármacos como tratamento para infecções microbianas. / Trivalent aluminum gallium derivatives with siderophores desferrioxamine (dfo) and desferrioxamine-caffeine (dfcaf) were prepared and characterized in solution using mass spectroscopy, cyclic voltammetry, vibrational spectroscopy and 1H nuclear magnetic resonance. Further confirmation of the formation of MeL (Me = Al3+, Ga3+, L = dfo or dfcaf) was obtained through competitive equilibria with the fluorimetric probes 8-quinoline and fluorescent desferrioxamine. It was observed that MeL complexes are stable in solution, and that aluminum derivatives are more stable than gallium. Also through interaction with calcein-iron complex, it was observed that MeL formed in solution. Preliminary docking studies show that complexes derived from dfcaf may have the same internalization mechanism in Escherichia coli as other iron-carrier antibiotics. The \"Trojan horse effect\" is the selective loading of toxic ions through the iron uptake system of microorganisms mediated by siderophores. The biological activity of MeL complexes was studied by growth inhibition of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. In general, dfcaf is more active than dfo possibly due to its increased lipophilicity. MeL complexes were generally more active than the metals or ligands separately, possibly by absorption of toxic ions facilitated by siderophores, demonstrating the \"Trojan horse effect\". The Gram-positive bacterium S. aureus showed greater resistance than Gram-negative bacteria , and interestingly the fungus C. albicans was sensitive to these treatments. These results show the possibility of using such metallodrugs as a treatment for microbial infections.

Derivados de alumínio e gálio trivalentes com os sideróforos desferrioxamina (dfo) e desferrioxamina-cafeína (dfcaf) foram preparados e caracterizados em solução através de espectrometria de massas, voltametria cíclica, espectroscopia vibracional na região do infravermelho e ressonância magnética nuclear de próton. Confirmações adicionais da formação de MeL (Me = Al3+, Ga3+; L = dfo ou dfcaf) foram obtidas através de equilíbrios competitivos com as sondas fluorimétricas 8-hidroquinolina e desferrioxamina fluorescente. Observou-se que os complexos MeL são estáveis em solução, e que os derivados de alumínio são mais estáveis do que os de gálio. Também através da interação com o complexo calceína-ferro, observou-se que MeL se formaram em solução. Estudos de docking preliminares mostram que dfcaf pode ter o mesmo mecanismo de entrada em Escherichia coli que outros antibióticos transportadores de ferro. O efeito \"cavalo de Tróia\" consiste no carregamento seletivo de íons tóxicos através do sistema de absorção de ferro dos microrganismos mediado por sideróforos. A atividade biológica dos complexos MeL foi estudada através da inibição do crescimento de Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus e Candida albican. Em geral, dfcaf é mais ativo do que dfo, possivelmente devido à sua maior lipofilicidade. Os complexos MeL foram em geral mais ativos do que os metais ou ligantes separadamente, possivelmente pela absorção dos íons tóxicos facilitada pelos sideróforos, demonstrando o efeito \"cavalo de Tróia\". A bactéria Gram-positiva S. aureus apresentou maior resistência do que as Gram-negativas, e interessantemente o fungo C. albicans foi sensível a esses tratamentos. Esses resultados mostram a possibilidade de usar tais metalofármacos como tratamento para infecções microbianas. / Trivalent aluminum gallium derivatives with siderophores desferrioxamine (dfo) and desferrioxamine-caffeine (dfcaf) were prepared and characterized in solution using mass spectroscopy, cyclic voltammetry, vibrational spectroscopy and 1H nuclear magnetic resonance. Further confirmation of the formation of MeL (Me = Al3+, Ga3+, L = dfo or dfcaf) was obtained through competitive equilibria with the fluorimetric probes 8-quinoline and fluorescent desferrioxamine. It was observed that MeL complexes are stable in solution, and that aluminum derivatives are more stable than gallium. Also through interaction with calcein-iron complex, it was observed that MeL formed in solution. Preliminary docking studies show that complexes derived from dfcaf may have the same internalization mechanism in Escherichia coli as other iron-carrier antibiotics. The \"Trojan horse effect\" is the selective loading of toxic ions through the iron uptake system of microorganisms mediated by siderophores. The biological activity of MeL complexes was studied by growth inhibition of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. In general, dfcaf is more active than dfo possibly due to its increased lipophilicity. MeL complexes were generally more active than the metals or ligands separately, possibly by absorption of toxic ions facilitated by siderophores, demonstrating the \"Trojan horse effect\". The Gram-positive bacterium S. aureus showed greater resistance than Gram-negative bacteria , and interestingly the fungus C. albicans was sensitive to these treatments. These results show the possibility of using such metallodrugs as a treatment for microbial infections.

Silver nanoparticles (AgNPs) containing consumer products have increasingly emerged in the market because of their potential antibacterial property, which might result in increased human exposure and environmental contamination. AgNPs are toxic to mammalian and other cells but the determinants of this toxicity remain to be fully characterised and the potential impact of DNA repair systems has been poorly explored. This study, therefore, examined to what extent the size and shape of synthesised AgNPs determined AgNP toxicity in DNA repair proficient and deficient (8-oxoguanine DNAglycosylase; WT and OGG1-/-, respectively) mouse embryonic fibroblasts (MEFs) as well as a well-known human cell line used in the toxicity testing, HepG2 cells. Citrate-stabilised spherical- and triangular-shaped AgNPs (S-AgNPs andT-AgNPs, respectively) were synthesised chemically from AgNO3 using combinations of NaBH4 and sodium citrate as a reducing and stabilising agent, respectively, and purified by dialysis. Three different sized S-AgNPs were prepared with diameters of 7.6 ± 1.2, 14.3 ± 4.2, and 52.5 ± 17.9 nm as measured using transmission electron microscope (TEM), and their zeta potentials were -36.1±2.7, -39.5±2.7 and -36.7±4.1 mV, respectively. T-AgNPs had an edge length and thickness of 71.4 ± 11.1 nm and 5.7 ± 0.8 nm, respectively. The size and zeta potential of the purified AgNPs were constant in distilled water for at least 6 months. The uptake of both S- and T-AgNPs by cells resulted in a time and dose-dependent increase in the number of cellular AgNPs and the amount of Ag+ released intracellularly. These increases were associated with a decrease in cell viability (as measured using the MTT assay) and cell survival (the clonogenic assay), and an induction in ROS generation (the DCF assay) and DNA damage(the alkaline Comet assay) for all three cell lines. AgNPs were observed in cells using TEM, suggesting the uptake of AgNPs via an endocytosis pathway. Results suggested that an increase in cellular AgNP level and intracellular released Ag+ content were associated with a time and dose-dependent toxicity. Interestingly, cellular AgNP level and intracellular released Ag+ content might play an important role in size-dependent AgNP toxicity, in which exposure to the smaller S-AgNP sizes (7nm and 14nm) resulted in higher levels of both cellular AgNPs and Ag+ released intracellularly, and then to increased toxicity when compared with the larger S-AgNP size (50nm). Moreover, different shaped AgNPs might induce toxicity by different mechanisms: ROS-mediated toxicity might be induced by both 70nm T-AgNPs and 50nm S-AgNPs and 70nm T-AgNPs might also induce cell membrane damage. AgNP-induced toxicity was different in different cell lines with HepG2 cells being more sensitive to AgNPs particularly using the clonogenic assay, and this toxicity was associated with higher DNA damage observed in HepG2 cells after 24 h. OGG1-/- MEFs were more sensitive to intracellular released Ag+, leading to higher ROS formation and DNA damage in OGG1-/- MEFs than that observed in WT MEFs. In summary, this study strongly suggests that AgNPs induce toxicity via a Trojan-horse type mechanism, and not only Ag+ released intracellularly but also cellular AgNPs take part in this toxicity, and will eventually result in the biological responses of the cells.

In the continuously evolving field of malware investigation, a Trojan horse, which appears as innocent software from the user's perspective, represents a significant threat and challenge for antivirus solutions because of their deceptive nature and the various malicious functionalities they provide. This study will compare the effectiveness of three free antiviruses for Linux systems (DrWeb, ClamAV, ESET NOD32) against a dataset of 1919 Trojan malware samples. The evaluation will assess their detection capabilities, resource usage, and the core functionalities they offer. The results revealed a trade-off between these three aspects: DrWeb achieved the highest detection rate (93.43%) but consumed the most resources and provided the most comprehensive functionalities. While ClamAV balanced detection and resource usage with less functionality, ESET NOD32 prioritised low resource usage but showcased a lower detection rate than the other engines (80.93%). Interestingly, the results showed that the category of Trojan horse malware and the file format analysed can affect the detection capabilities of the evaluated antiviruses. This suggests that there is no “silver bullet” for Linux systems against Trojans, and further research in this area is needed to assess the detection capabilities of antivirus engines thoroughly and propose advanced detection methods for robust protection against Trojans on Linux systems.

A Astrofísica Nuclear é a chave para explicar, entre outras coisas, a produção de energia nas estrelas, a evolução estelar e a síntese de elementos químicos e seus isótopos no Universo. Nesses casos, as reações nucleares formam a estrutura principal, cujas seções de choque e taxas de reação precisam ser determinadas com bastante precisão em laboratório. Devido às condições extremas encontradas nas estrelas, o entendimento dos processos nucleares que ocorrem em seus interiores se tornaram um grande desafio para os físicos nucleares teóricos e experimentais. Nos últimos 40 anos, os físicos vem medindo as taxas dessas reações, porém, as incertezas nesses valores são altas em razão das dificuldades experimentais encontradas nas medidas de seção de choque de processos que ocorrem em energias extremamente baixas (região do pico de Gamow). Desta forma, apenas em alguns casos é possível medir diretamente a seção de choque e o comportamento em baixas energias é geralmente extrapolado da região de energias mais altas. Para evitar o procedimento da extrapolação, alguns métodos indiretos estão sendo 5 usados com sucesso nos últimos anos. Em particular, o método do Cavalo de Tróia permite obter o fator astrofísico S(E) de reações nucleares envolvendo partículas carregadas a baixas energias sem necessidade de extrapolação e sem o efeito da blindagem eletrônica. As reações 10B(p,a)7Be e 11B(p,a)8Be são as principais responsáveis pela queima do boro em estrelas do grupo F e G da sequência principal. As respectivas seções de choque já foram obtidas em experimentos diretos anteriores, porém, os dados não chegam na região do pico de Gamow e o comportamento do fator astrofísico é extrapolado de energias mais altas. Neste trabalho, obteve-se o fator astrofísico S(E) das reações 10B(p,a)7Be e 11B(p,a)8Be através do método indireto do Cavalo de Tróia (THM) aplicado às reações de três corpos 2H(10B,a7Be)n e 2H(11B,a8Be)n sem necessidade de extrapolação. O fator astrofísico obtido por meio do THM para a reação 10B(p,a)7Be é duas vezes menor na região do pico de Gamow comparado com estudos diretos anteriores. Para a reação 11B(p,a)8Be foram estudados separadamente os canais a0 e a1 e o fator astrofísico obtido por meio do THM está de acordo com os estudos diretos anteriores. / Nuclear Astrophysics is the key to explain, among other things, the production of energy in stars, stellar evolution and the synthesis of chemical elements and isotopes in the Universe. In such cases, nuclear reactions are the main structure, where cross sections and reaction rates must be determined with reasonable accuracy in the laboratory. Because the extreme conditions found in stars, the understanding of nuclear processes that occur in their interiors have become a big challenge for theoretical and experimental nuclear physicists. In the last 40 years, physicists are getting the rates of these reactions but the uncertainty in these values are high due to difficulties found in the experimental cross section measurements at very low energies (Gamow peak region). Thus, only in some cases it is possible to measure directly the cross section and the behavior at low energies is usually extrapolated from the region of higher energy. To avoid the procedure of extrapolation, some indirect methods are being used successfully in recent years. In particular, the Trojan Horse Method gives the Astrophysics 7 S(E) factor of nuclear reactions involving charged particles at low energies without extrapolation and without electron screening effects. The reactions 10B(p,a)7Be and 11B(p,a)8Be are the main responsible for the burning process of boron inside F and G main sequence stars. The cross sections of these reactions have been obtained in previous direct experiments, but the data did not reach the Gamow peak and the behavior of the S(E) factor is then extrapolated from higher energies. In this work, we extract the S(E) factor for the reactions 10B(p,a)7Be and 11B(p,a)8Be through the indirect Trojan Horse Method (THM) applied to the three body reactions 2H(10B,a7Be)n e 2H(11B,a8Be)n without extrapolation. The astrophysical S(E)-factor for the 10B(p,a)7Be reaction was extracted by means of the THM and it is a factor 2 less in the Gamow peak if compared with previous direct studies. For the 11B(p,a)8Be reaction both a0 e a1 channels were studied by means of the THM and the astrophysical S(E)-factor extracted is in good agreement with direct previous studies.

Le XXIe siècle voit la consécration des technologies numériques comme la fin du Moyen Âge a vu celle de l’imprimerie. L’ère numérique ignore désormais toutes les frontières. Elle permet l’accès à la culture et à la connaissance, favorise les échanges entre les personnes. Elle rend possible la constitution d’une économie en ligne et rapproche le citoyen de son administration. Les technologies numériques sont porteuses d’innovation et de croissance, en même temps qu’elles peuvent aider ou accélérer le développement des pays émergents. Mais un certain pessimisme vient tempérer cette approche idéaliste. Tous les progrès génèrent aussi de nouvelles fragilités et vulnérabilités propices aux menaces ou aux risques, car ils aiguisent l’imagination des criminels. La cybercriminalité est désormais une réalité. Elle est d’autant plus dangereuse qu’elle pénètre au sein des familles, là où la délinquance ordinaire n’avait pas accès jusqu’à présent. Dès lors, cette nouvelle forme de criminalité laisse apparaître comme une évidence, l'adaptation du système judiciaire. En effet, face à ces atteintes, il existe bel et bien des lois qui sont d'ores et déjà appliquées à l’Internet. Mais sont-elles réellement efficaces ? Dans le même sens, la coopération interétatique est-elle également suffisante pour lutter efficacement contre la cybercriminalité ? Ainsi, il importe de se demander si dans notre société moderne, le cadre normatif et la coopération institutionnelle tant européenne qu'internationale, sont suffisants et efficaces pour sanctionner les infractions cybercriminelles ? / The twenty-first century sees the consecration of digital technologies just as the end of the Middle-Ages saw the creation of printing.Henceforth, the digital era has no limits. It gives access to culture and knowledge, encourages the exchanges between people.It allows the constitution of an economy online and brings citizens closer to their adminitration. Digital technologies generate innovation and growth, and can help or accelerate the development of the emergent countries as well. But a certain pessimism moderates this idealistic approach.All these advances also generate new fragilities and vulnerabilities propicious to threats or risks, as they stimulate the criminals' imagination.Now , cybercriminality has become reality.It is all the more dangerous as it penetrates within families , where ordinary delinquency didn't exist until now. From now on, this new kind of criminality made it obvious that the judicial system had to be adapted. Indeed , faced with these violations , there are of course laws that are applied here and now to the Internet.But , are they really efficient? In the same way, is the intersate cooperation also sufficient to fight against cybercriminality? So , it is important to wonder whether , in our modern society , the legislative framework and the institutional cooperation , both european and international , are sufficient and efficient to penalize the cybercriminal offences.

A Astrofísica Nuclear é a chave para explicar, entre outras coisas, a produção de energia nas estrelas, a evolução estelar e a síntese de elementos químicos e seus isótopos no Universo. Nesses casos, as reações nucleares formam a estrutura principal, cujas seções de choque e taxas de reação precisam ser determinadas com bastante precisão em laboratório. Devido às condições extremas encontradas nas estrelas, o entendimento dos processos nucleares que ocorrem em seus interiores se tornaram um grande desafio para os físicos nucleares teóricos e experimentais. Nos últimos 40 anos, os físicos vem medindo as taxas dessas reações, porém, as incertezas nesses valores são altas em razão das dificuldades experimentais encontradas nas medidas de seção de choque de processos que ocorrem em energias extremamente baixas (região do pico de Gamow). Desta forma, apenas em alguns casos é possível medir diretamente a seção de choque e o comportamento em baixas energias é geralmente extrapolado da região de energias mais altas. Para evitar o procedimento da extrapolação, alguns métodos indiretos estão sendo 5 usados com sucesso nos últimos anos. Em particular, o método do Cavalo de Tróia permite obter o fator astrofísico S(E) de reações nucleares envolvendo partículas carregadas a baixas energias sem necessidade de extrapolação e sem o efeito da blindagem eletrônica. As reações 10B(p,a)7Be e 11B(p,a)8Be são as principais responsáveis pela queima do boro em estrelas do grupo F e G da sequência principal. As respectivas seções de choque já foram obtidas em experimentos diretos anteriores, porém, os dados não chegam na região do pico de Gamow e o comportamento do fator astrofísico é extrapolado de energias mais altas. Neste trabalho, obteve-se o fator astrofísico S(E) das reações 10B(p,a)7Be e 11B(p,a)8Be através do método indireto do Cavalo de Tróia (THM) aplicado às reações de três corpos 2H(10B,a7Be)n e 2H(11B,a8Be)n sem necessidade de extrapolação. O fator astrofísico obtido por meio do THM para a reação 10B(p,a)7Be é duas vezes menor na região do pico de Gamow comparado com estudos diretos anteriores. Para a reação 11B(p,a)8Be foram estudados separadamente os canais a0 e a1 e o fator astrofísico obtido por meio do THM está de acordo com os estudos diretos anteriores. / Nuclear Astrophysics is the key to explain, among other things, the production of energy in stars, stellar evolution and the synthesis of chemical elements and isotopes in the Universe. In such cases, nuclear reactions are the main structure, where cross sections and reaction rates must be determined with reasonable accuracy in the laboratory. Because the extreme conditions found in stars, the understanding of nuclear processes that occur in their interiors have become a big challenge for theoretical and experimental nuclear physicists. In the last 40 years, physicists are getting the rates of these reactions but the uncertainty in these values are high due to difficulties found in the experimental cross section measurements at very low energies (Gamow peak region). Thus, only in some cases it is possible to measure directly the cross section and the behavior at low energies is usually extrapolated from the region of higher energy. To avoid the procedure of extrapolation, some indirect methods are being used successfully in recent years. In particular, the Trojan Horse Method gives the Astrophysics 7 S(E) factor of nuclear reactions involving charged particles at low energies without extrapolation and without electron screening effects. The reactions 10B(p,a)7Be and 11B(p,a)8Be are the main responsible for the burning process of boron inside F and G main sequence stars. The cross sections of these reactions have been obtained in previous direct experiments, but the data did not reach the Gamow peak and the behavior of the S(E) factor is then extrapolated from higher energies. In this work, we extract the S(E) factor for the reactions 10B(p,a)7Be and 11B(p,a)8Be through the indirect Trojan Horse Method (THM) applied to the three body reactions 2H(10B,a7Be)n e 2H(11B,a8Be)n without extrapolation. The astrophysical S(E)-factor for the 10B(p,a)7Be reaction was extracted by means of the THM and it is a factor 2 less in the Gamow peak if compared with previous direct studies. For the 11B(p,a)8Be reaction both a0 e a1 channels were studied by means of the THM and the astrophysical S(E)-factor extracted is in good agreement with direct previous studies.