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No capítulo 1, a modelagem HQSAR, a docagem e os estudos de ROCS foram construídos utilizando uma série de 57 inibidores de cruzaína. O melhor modelo HQSAR (q2 = 0,70, r2 = 0,95, r2test = 0,62, q2rand. = 0,09 and r2rand. = 0,26) foi utilizado para predizer a potência de 121 compostos extraídos da literatura (conjunto de dados V1), resultando em um valor de r2 satisfatório de 0,65 para essa validação externa. Uma validação externa adicional foi empregada utilizando uma série de 1223 compostos extraído dos bancos de dados ChEMBL e CDD (conjunto de dados V3); nessa validação externa o valor de AUC (área sob a curva) para a curva ROC foi de 0,70. Os mapas de contribuição, obtidos para o melhor modelo HQSAR 3.4, estão de acordo com as predições do modo de interação e com as bioatividades dos compostos estudados. Nos estudos de ROCS, a forma molecular utilizada como filtro, foi útil na rápida identificação de modificações moleculares promissoras para inibidores de cruzaína. O valor de AUC obtido com a curva ROC foi de 0,72, isso indica que o método foi muito eficiente na distinção entre inibidores ativos e inativos da enzima cruzaína. Em seguida, o melhor modelo HQSAR foi utilizado para predizer os valores de pIC50 para novos compostos. Alguns dos compostos identificados, utilizando esse método, demonstraram valores de potência calculada maior do que a série de treinamento em estudo. No capítulo 2, os efeitos sobre a potência na inibição da enzima cruzaína pela substituição de um grupo nitrila como warhead por outros grupos foi avaliada. Com a síntese de 20 compostos do tipo dipeptidil, avaliou-se a relação estrutura-atividade (SAR), baseado na troca do grupo warhead na porção P1\'. O grupo oxima foi mais potente que o grupo correspondente nitrila em 0,7 unidades logarítmicas. Os compostos do tipo dipeptidil aldeídos e azanitrila obtiveram potências mais elevadas do que o correspondente dipeptidil nitrila em duas de magnitude. Os compostos dipeptidil alfa-beta insaturados foram menos potentes do que o correspondente dipeptidil nitrila. No capítulo 3, estratégias de química medicinal foram empregadas nas sínteses de 23 novos análogos, contendo o esqueleto básico de imidazopiridina. Sete e doze compostos sintetizados exibiram EC50 <= 1µM in vitro contra os parasitos Tripanosoma cruzi (T. cruzi) e brucei (T. brucei), respectivamente. Com os resultados promissores de atividade biológica in vitro, citotoxicidade, estabilidade metabólica, ligação proteica e propriedades farmacocinéticas, o composto 41 foi selecionado como candidato para os estudos de eficácia in vivo. Esse composto foi submetido em um modelo agudo da infecção com T. cruzi em ratos (cepa Tulahuen). Depois de estabelecida a infecção, os ratos foram dosados duas vezes ao dia, durante 5 dias; e monitorados por 6 semanas usando um sistema de imagem in vivo IVIS (do inglês, \"In Vivo Imaging System\"). O composto 41 demonstrou inibição parasitária comparável com o grupo de treinamento dosado com benzonidazol. O composto 41 representa um potencial líder para o desenvolvimento de novos fármacos para o tratamento de tripanossomíases. / In chapter 1, the HQSAR, molecular docking and ROCS were applied to a dataset of 57 cruzain inhibitors. The best HQSAR model (q2 = 0.70, r2 = 0.95, r2test = 0.62, q2rand. = 0.09 and r2rand. = 0.26) was then used to predict the potencies of 121 unknown compounds (the V1 database), giving rise to a satisfactory predictive r2 value of 0.65 (external validation). By employing an extra external dataset comprising 1223 compounds (the V3 database) either retrieved from the ChEMBL or CDD databases, an overall ROC AUC (area under the curve) score well over 0.70 was obtained. The contribution maps obtained with the best HQSAR model (model 3.4) are in agreement with the predicted binding mode and with the biological potencies of the studied compounds. We also screened these compounds using the ROCS method, a Gaussian-shape volume filter able to identify quickly the shapes that match a query molecule. The AUC obtained with the ROC curves (ROC AUC) was 0.72, indicating that the method was very efficient in distinguishing between active and inactive cruzain inhibitors. These set of information guided us to propose novel cruzain inhibitors to be synthesized. Then, the best HQSAR model obtained was used to predict the pIC50 values of these new compounds. Some compounds identified using this method has shown calculated potencies higher than those which have originated them. In chapter 2, the effects on potency of cruzain inhibition of replacing a nitrile group with alternative warheads were explored; with the syntheses of 20 dipeptidyl compounds, we explored the structure activity relationships (SAR) based on exchanging of the warhead portion (P1\'). The oxime was 0.7 units more potent than the corresponding nitrile. Dipeptide aldehydes and azadipeptide nitriles were found to be two orders of magnitude more potent than the corresponding dipeptide nitriles. The vinyl esters and amides were less potent than the corresponding nitrile by between one and two orders of magnitude. In chapter 3, we synthesized 23 new imidazopyridine analogues arising from medicinal chemistry optimization at different sites on the molecule. Seven and twelve compounds exhibited an in vitro EC50 <= 1µM against Trypanosoma cruzi (T. cruzi) and Trypanosoma brucei (T. brucei) parasites, respectively. Based on promising results of in vitro activity (EC50 &lt; 100 nM), cytotoxicity, metabolic stability, protein binding and pharmacokinetics (PK) properties, compound 41 was selected as a candidate for in vivo efficacy studies. This compound was screened in an acute mouse model against T.cruzi (Tulahuen strain). After established infection, mice were dosed twice a day for 5 days, and then monitored for 6 weeks using an in vivo imaging system (IVIS). Compound 41 demonstrated parasite inhibition comparable to the benznidazole treatment group. Compound 41 represents a potential lead for the development of drugs to treat trypanosomiasis.

No capítulo 1, a modelagem HQSAR, a docagem e os estudos de ROCS foram construídos utilizando uma série de 57 inibidores de cruzaína. O melhor modelo HQSAR (q2 = 0,70, r2 = 0,95, r2test = 0,62, q2rand. = 0,09 and r2rand. = 0,26) foi utilizado para predizer a potência de 121 compostos extraídos da literatura (conjunto de dados V1), resultando em um valor de r2 satisfatório de 0,65 para essa validação externa. Uma validação externa adicional foi empregada utilizando uma série de 1223 compostos extraído dos bancos de dados ChEMBL e CDD (conjunto de dados V3); nessa validação externa o valor de AUC (área sob a curva) para a curva ROC foi de 0,70. Os mapas de contribuição, obtidos para o melhor modelo HQSAR 3.4, estão de acordo com as predições do modo de interação e com as bioatividades dos compostos estudados. Nos estudos de ROCS, a forma molecular utilizada como filtro, foi útil na rápida identificação de modificações moleculares promissoras para inibidores de cruzaína. O valor de AUC obtido com a curva ROC foi de 0,72, isso indica que o método foi muito eficiente na distinção entre inibidores ativos e inativos da enzima cruzaína. Em seguida, o melhor modelo HQSAR foi utilizado para predizer os valores de pIC50 para novos compostos. Alguns dos compostos identificados, utilizando esse método, demonstraram valores de potência calculada maior do que a série de treinamento em estudo. No capítulo 2, os efeitos sobre a potência na inibição da enzima cruzaína pela substituição de um grupo nitrila como warhead por outros grupos foi avaliada. Com a síntese de 20 compostos do tipo dipeptidil, avaliou-se a relação estrutura-atividade (SAR), baseado na troca do grupo warhead na porção P1\'. O grupo oxima foi mais potente que o grupo correspondente nitrila em 0,7 unidades logarítmicas. Os compostos do tipo dipeptidil aldeídos e azanitrila obtiveram potências mais elevadas do que o correspondente dipeptidil nitrila em duas de magnitude. Os compostos dipeptidil alfa-beta insaturados foram menos potentes do que o correspondente dipeptidil nitrila. No capítulo 3, estratégias de química medicinal foram empregadas nas sínteses de 23 novos análogos, contendo o esqueleto básico de imidazopiridina. Sete e doze compostos sintetizados exibiram EC50 <= 1µM in vitro contra os parasitos Tripanosoma cruzi (T. cruzi) e brucei (T. brucei), respectivamente. Com os resultados promissores de atividade biológica in vitro, citotoxicidade, estabilidade metabólica, ligação proteica e propriedades farmacocinéticas, o composto 41 foi selecionado como candidato para os estudos de eficácia in vivo. Esse composto foi submetido em um modelo agudo da infecção com T. cruzi em ratos (cepa Tulahuen). Depois de estabelecida a infecção, os ratos foram dosados duas vezes ao dia, durante 5 dias; e monitorados por 6 semanas usando um sistema de imagem in vivo IVIS (do inglês, \"In Vivo Imaging System\"). O composto 41 demonstrou inibição parasitária comparável com o grupo de treinamento dosado com benzonidazol. O composto 41 representa um potencial líder para o desenvolvimento de novos fármacos para o tratamento de tripanossomíases. / In chapter 1, the HQSAR, molecular docking and ROCS were applied to a dataset of 57 cruzain inhibitors. The best HQSAR model (q2 = 0.70, r2 = 0.95, r2test = 0.62, q2rand. = 0.09 and r2rand. = 0.26) was then used to predict the potencies of 121 unknown compounds (the V1 database), giving rise to a satisfactory predictive r2 value of 0.65 (external validation). By employing an extra external dataset comprising 1223 compounds (the V3 database) either retrieved from the ChEMBL or CDD databases, an overall ROC AUC (area under the curve) score well over 0.70 was obtained. The contribution maps obtained with the best HQSAR model (model 3.4) are in agreement with the predicted binding mode and with the biological potencies of the studied compounds. We also screened these compounds using the ROCS method, a Gaussian-shape volume filter able to identify quickly the shapes that match a query molecule. The AUC obtained with the ROC curves (ROC AUC) was 0.72, indicating that the method was very efficient in distinguishing between active and inactive cruzain inhibitors. These set of information guided us to propose novel cruzain inhibitors to be synthesized. Then, the best HQSAR model obtained was used to predict the pIC50 values of these new compounds. Some compounds identified using this method has shown calculated potencies higher than those which have originated them. In chapter 2, the effects on potency of cruzain inhibition of replacing a nitrile group with alternative warheads were explored; with the syntheses of 20 dipeptidyl compounds, we explored the structure activity relationships (SAR) based on exchanging of the warhead portion (P1\'). The oxime was 0.7 units more potent than the corresponding nitrile. Dipeptide aldehydes and azadipeptide nitriles were found to be two orders of magnitude more potent than the corresponding dipeptide nitriles. The vinyl esters and amides were less potent than the corresponding nitrile by between one and two orders of magnitude. In chapter 3, we synthesized 23 new imidazopyridine analogues arising from medicinal chemistry optimization at different sites on the molecule. Seven and twelve compounds exhibited an in vitro EC50 <= 1µM against Trypanosoma cruzi (T. cruzi) and Trypanosoma brucei (T. brucei) parasites, respectively. Based on promising results of in vitro activity (EC50 &lt; 100 nM), cytotoxicity, metabolic stability, protein binding and pharmacokinetics (PK) properties, compound 41 was selected as a candidate for in vivo efficacy studies. This compound was screened in an acute mouse model against T.cruzi (Tulahuen strain). After established infection, mice were dosed twice a day for 5 days, and then monitored for 6 weeks using an in vivo imaging system (IVIS). Compound 41 demonstrated parasite inhibition comparable to the benznidazole treatment group. Compound 41 represents a potential lead for the development of drugs to treat trypanosomiasis.

Shaped charges are explosive devices with a high penetration capability and are used for both civilian and military purposes. In civilian applications shaped charge devices are used in demolition works, oil drilling and mining. In the military applications, shaped charges are used against different kinds of armors, primarily as anti-tank devices. This thesis work involves the modeling and simulation of shaped charge devices, with the focus being on anti-tank warhead design. Both numerical simulation and analytical calculation methods are used to predict shaped charge performance / in the aspects of jet formation, breakup and penetration. The results are compared within themselves and with the data available in the literature. AUTODYN software is used for the numerical simulations. Different solver and modeling alternatives of AUTODYN are evaluated for jet formation and penetration problems. AUTODYN&rsquo / s Euler solver is used to understand how the jet formation is affected by the mesh size and shape and the presence of air as the surrounding medium. Jetting option in the AUTODYN-Euler simulations are used to simulate jet formation as an alternative to simulations performed using AUTODYN&rsquo / s Euler solver. In the jetting option liner elements are modeled as Lagrangian shell elements, rather than Eulerian elements. Analytical codes are written to study the jet formation, breakup and penetration processes. Many alternative formulas that can be used in the analytical calculations are listed and discussed. Parameters of these formulas are varied to investigate their effects on the results. Necessary constants for the analytical formulas are obtained using the results of AUTODYN simulations.

The analysis of penetration of warheads in concrete protective structures is an important part of the study of weapon effects on protective structures. This type of analysis requires that the design load in the form of a warhead is determined, and its characteristic and performance within a protective structure is known. Constitutive equations for concrete subjected to weapon effects have been a major area of interest for a long time, and several material models for concrete behaviour are developed. However, it is not until recent years that it has been possible to use finite element (FE) analyses to simulate the behaviour of concrete targets during projectile penetration with acceptable results. The reason for this is a combination of several factors, e.g. development of suitable material models for concrete, enhancement of numerical methodology and affordable high capacity computer systems. Furthermore, warhead penetration has primary been of interest for the armed forces and military industry, with a large part of the conducted research being classified during considerable time. The theoretical bases for concrete material behaviour and modelling with respect to FE analyses of projectile penetration are treated in the thesis. The development of weapons and fortifications are briefly discussed in the thesis. Warheads may be delivered onto a protective structure by several means, e.g. artillery, missiles or aerial bombing, and two typical warhead types were used within the study. These warhead types were artillery shells and unitary penetration bombs for the use against hardened targets, with penetration data for the later warhead type almost non-existing in the literature. The penetration of warheads in concrete protective structures was therefore studied through a combination of experimental work, empirical penetration modelling and FE analyses to enhance the understanding of the penetration phenomenon. The experimental data was used for evaluation of empirical equations for concrete penetration and FE analyses of concrete penetration, and the use of these methods to predict warhead penetration in protective structures are discussed within the thesis. The use of high performance concrete increased the penetration resistance of concrete targets, and the formation of front and back face craters were prevented with the use of heavily reinforced normal strength concrete (NSC) for the targets. In addition, the penetration depths were reduced in the heavily reinforced NSC. The evaluated existing empirical penetration models did not predict the behaviour of the model scaled hardened buried target penetrators in concrete structures with acceptable accuracy. One of the empirical penetration models was modified to better describe the performance of these penetrators in concrete protective structures. The FE analyses of NSC gave reasonable results for all simulation cases, with the best results obtained for normal impact conditions of the penetrators. / Analyser avseende stridsdelars penetration i skyddskonstruktioner av betong viktigt för studier av vapenverkan mot skyddskonstruktioner. Dessa analyser förutsätter att dimensionerande last i form av stridsdel bestäms, samt att dess karakteristik och verkan mot skyddskonstruktioner är kända. Konstitutiva modeller för betong utsatta för vapenverkan har varit av stort intresse under en lång tid och ett flertal materialmodeller har utvecklats. Det är emellertid först på senare år som det varit möjligt att använda finita element (FE) analyser for att simulera beteendet för betongmål vid projektilpenetration med acceptabla resultat. Anledningen till detta kan tillskrivas kombinationen av ett flertal faktorer, t ex utvecklingen av lämpliga materialmodeller, förbättringar av numerisk metodik och utvecklingen av kostnadseffektiva beräkningsdatorer. Penetration av stridsdelar har dessutom i huvudsak varit av intresse för militären och försvarsindustrin, vilket har resulterat i att en stor del av den bedrivna forskningen har varit hemligstämplad under lång tid. Grunderna avseende betongs materialbeteende och beskrivning av detta med avseende på FE-analyser av projektilpenetration behandlas i denna licentiatuppsats. Den fortifikatoriska utvecklingen och utvecklingen av vapen diskuteras kortfattad i uppsatsen. Ett flertal olika typer av stridsdelar är av intresse avseende verkan mot skyddskonstruktioner, t ex artillerigranater, missiler eller flygbomber. I denna studie beaktades två typiska stridsdelar, artillerigranater och penetrerande bomber. De senare är specifikt konstruerade för användande mot skyddskonstruktioner och företrädesvis mot betongkonstruktioner. Det visade sig dessutom att data avseende penetration i betong för denna typ av penetrerande stridsdelar i stort sett inte var publicerade. Penetration av stridsdelar i betong studerades därför med en kombination av experimentella metoder, empiriska penetrationsmodeller och FE-analyser för att öka förståelsen för problemställningen. De experimentella modellresultaten användes för att utvärdera både de empiriska penetrationsmodellerna och FE-analyserna avseende betongpenetration, med båda metodernas användande diskuterat i uppsatsen. Användandet av högpresterande betong ökade penetrationsmotståndet för betongmålen i jämförelse med standardbetongmålen. Det var även möjligt att förhindra kraterbildningen på fram- och baksidan av de kraftigt armerande standardbetongmålen, detta medförde även en reducerad penetration för projektilerna i målen. De existerande empiriska penetrationsmodellerna kunde inte förutsäga penetrationen av modellprojektilerna i betongmålen med godtagbara resultat. Istället vidareutvecklades en av dessa modeller för att bättre beskriva denna typ av penetrerande stridsdelar i skyddskonstruktioner av betong. Finita elementanalyserna av standardbetongmålen visade sig ge ett rimligt beteende för alla analyserade modeller, med de bästa resultaten erhållna för vinkelrätt anslag för de modellprojektilerna av de penetrerande stridsdelarna. / QC 20111116

At launching the shell body, especially the backplane of the shell body, will be exposed to very high stresses due to acceleration, pressure and increased temperature from the propellant combustion. Defects in the shell body could in worst case for example result in high temperature gas leakage into the warhead and thereby ignite the explosives before exiting the launcher. This kind of explosion results in serious damages and can seriously injure both the gunner and other people in the surroundings. According to earlier study, carbon fibre reinforced epoxy with filament winding manufacturing method was the primary focus. The purpose of this master thesis was to investigate requirements and testing methods on a shell body manufactured in composite that will guarantee the safety of the gunner and surroundings in the launch phase. The pre-study conducted in this project showed that matrix cracks and fibre breakages are most common defects in the shell body that occur during launching affected by burst pressure. Matrix crack is the less dangerous defect among the impact damage types. Discussion with composite manufacturing companies showed that fibre breakage is a very serious type of defect since more breakage of fibres leads to the shell body have reduced stresses and cannot built-up the fully potential burst pressure during launching.   Two requirement specifications were carried out, one for the shell body and another for the detection methods. These were created by own research and ideas according to found information, telephone- and e-mail contact with experts in areas and with personnel at Saab Dynamics AB. Some requirements for the shell body were that it should be fully usable after drop tests from different heights, vibration and transportation tests yield no cyclic damage after a long transport. Furthermore, the shell body should always use a fully isolated driving band to not have hot explosive gases penetrated into critical sections which results in detonation already in the launcher barrel. The most important requirements for the detection methods were to have depth analysis, high reliability and in-field inspection.   Elimination- and decision matrices were made to find which detection methods should be the final selections in order to find the defects in a shell body. The detection methods which did not fulfil the criteria from each separate matrix were eliminated and did not proceed further as a concept. Eliminations were performed in concept generation phase (elimination matrix) and concept selection phase (decision matrix). In final selection phase a couple of methods were chosen that together found as many defects as possible.   By using both acoustic emission and shearography all the critical defects and a wide range of other defects can be detected with very high reliability and resolution at an acceptable cost. These two methods “interact” perfectly with each other. Acoustic emission is the best method to find fibre breakage and matrix cracks, which are the most commonly occurring defects during launching. But shearography does not have a good detectability of fibre breakage and matrix cracks. On the other hand, shearography has good detectability of both planar- and volumetric defects. It is concluded that only two inspection methods, i.e. acoustic emission and shearography are needed to detect all of the possible defects in the grenade shell body. This is more economical solution requiring smaller space and fewer operators compared to one separate NDT method for detecting each type of defect. / Vid utskjutning av granathylsan utsätts framförallt bakplanet, för mycket höga påfrestningar genom acceleration, tryck och förhöjd temperatur från krutförbränningen. Vid en genombränning av granatskalet skulle sprängämnet i verkansdelen kunna tändas redan i eldröret och orsaka en vapensprängning. Den här typen av explosion resulterar i allvarliga skador både för skytten samt folk i dess omgivning.   Med hänsyn till tidigare studier har det varit fokus på kolfiberförstärkt epoxi som är tillverkad av fiberlindning. Syftet var att utreda kravställningar och metoder för provning, som garanterar skyttens och omgivningens säkerhet i utskjutningsfasen av en granat tillverkad av kompositmaterial.   Från förstudien i denna rapport visade sig att matrissprickor och fiberbrott är de vanligaste defekter som uppstår i granathylsan under utskjutningsfasen där den största påverkan är ifrån explosionstrycket. Matrissprickor är de mindre farliga defekter av de som uppstår under intryckning. Diskussion med komposittillverkande företag visade att fiberbrott är en väldigt farlig typ av defekt eftersom fibrerna står för styrkan och brott av fibrer leder till att granathylsan klarar av att utsättas för lägre påfrestningar och kan inte hjälpa till att bygga upp det önskvärda trycket som önskas under utskjutningen.   Två kravspecifikationer utfärdades, en för granathylsan och en annan för detekteringsmetoderna. Dessa två skapades genom egen studie och idéer med hänsyn till hittad information, ifrån telefon- samt email kontakt med experter inom områdena samt med hjälp av personal på Saab Dynamics AB. Några krav som valdes för granathylsan var att den ska vara fullt användbar efter fallskärmsprovning från olika höjder, vibration- och transport tester för att inte få cykliska skador efter en lång transportering samt att alltid ha en fullt isolerad gördel så att inte de heta gaserna från explosivorna tänds redan i eldröret vilket orsakar vapensprängning. Några krav för detekteringsmetoder var att de ska kunna göra mätningar/analyser på djupet, ha hög trovärdighet samt vara portabel.   Eliminering- och beslutsmatriser gjordes för att hitta vilka detekteringsmetoder som skulle bli de slutliga valen i jakten på att finna defekterna i granathylsan. De metoder som inte uppfyllde kriterierna från respektive matris blev eliminerade. Elimineringen utfördes i faserna för konceptgenerering och konceptval. I slutliga valet valdes ett par lämpliga metoder som tillsammans hittar så många defekter som möjligt.   Genom att använda akustisk emission samt shearografi hittades samtliga kritiska defekter plus många andra som inte anses vara kritiska med väldigt hög trovärdighet och upplösning till ett mer acceptabelt pris. Metoderna samverkar väldigt bra med varandra eftersom akustisk emission är bästa metoden att hitta fiberbrott och matrissprickor vilket är vanligt förekommande i utskjutningsfasen. Shearografi har inte samma detekterbarhet på dem två defekterna men de har å andra sidan istället väldigt god detekterbarhet på både volymetriska- och plana defekter.   Slutsatsen är att endast två metoder behövdes för att finna alla defekter vilket blir mer ekonomiskt, tar mindre plats och behöver färre certifierade operatörer jämfört med om man ska ha en detekteringsmetod för att finna respektive defekt.

Modern-day terrorist attacks present a considerable danger for commercial aircrafts. This thesis analyzes potential methods of such attacks with a critical analysis of the most dangerous type: an attack from the outside of the aircraft via a fragmentation missile warhead. Such missiles cause damage to the airframe of the aircraft through fragments created by the explosion. In this thesis, analytical geometry is used to determine the area of the aircraft affected by the fragmentation. The aircraft’s geometry and the fragments’ dispersion are calculated by analytical functions, and the effect of the damage is analyzed. A shooting experiment was also carried out, in which fragments were shot at a reinforced skin panel that was manufactured according to the real design of commercial aircraft. The results of the experiment revealed that only directly hit sections of the structure are damaged. Data obtained by the experiment was then used for the creation and improvement of the model used in the simulation by means of the finite element method. This model is used for the numerical calculation of the damage sustained. Further included in the thesis is an analysis of the change in the load-bearing capacity after such an attack. The relationship between the size of the damage and its effect on the load-bearing capacity of the component as well as the entire structure is defined. First, the effect of component damage is analyzed via the FMEA/FMECA methods. This analysis is then extended using fuzzy logic. Fuzzy logic analysis is based on the determination of the size of the damaged component area and the component’s importance on the structure’s carry loads. Application of the defined approach is described for several parts of an aircraft’s life cycle, including development, operation after the terrorist attack, and assessment of causes after a crash caused by a fragmentation missile warhead.

Modern-day terrorist attacks present a considerable danger for commercial aircrafts. This thesis analyzes potential methods of such attacks with a critical analysis of the most dangerous type: an attack from the outside of the aircraft via a fragmentation missile warhead. Such missiles cause damage to the airframe of the aircraft through fragments created by the explosion. In this thesis, analytical geometry is used to determine the area of the aircraft affected by the fragmentation. The aircraft’s geometry and the fragments’ dispersion are calculated by analytical functions, and the effect of the damage is analyzed. A shooting experiment was also carried out, in which fragments were shot at a reinforced skin panel that was manufactured according to the real design of commercial aircraft. The results of the experiment revealed that only directly hit sections of the structure are damaged. Data obtained by the experiment was then used for the creation and improvement of the model used in the simulation by means of the finite element method. This model is used for the numerical calculation of the damage sustained. Further included in the thesis is an analysis of the change in the load-bearing capacity after such an attack. The relationship between the size of the damage and its effect on the load-bearing capacity of the component as well as the entire structure is defined. First, the effect of component damage is analyzed via the FMEA/FMECA methods. This analysis is then extended using fuzzy logic. Fuzzy logic analysis is based on the determination of the size of the damaged component area and the component’s importance on the structure’s carry loads. Application of the defined approach is described for several parts of an aircraft’s life cycle, including development, operation after the terrorist attack, and assessment of causes after a crash caused by a fragmentation missile warhead.