The North First Street revitalization project /

"Fall 1993."

Towards Automation in Digital Investigations : Seeking Efficiency in Digital Forensics in Mobile and Cloud Environments

Cybercrime and related malicious activity in our increasingly digital world has become more prevalent and sophisticated, evading traditional security mechanisms. Digital forensics has been proposed to help investigate, understand and eventually mitigate such attacks. The practice of digital forensics, however, is still fraught with various challenges. Some of the most prominent of these challenges include the increasing amounts of data and the diversity of digital evidence sources appearing in digital investigations. Mobile devices and cloud infrastructures are an interesting specimen, as they inherently exhibit these challenging circumstances and are becoming more prevalent in digital investigations today. Additionally they embody further characteristics such as large volumes of data from multiple sources, dynamic sharing of resources, limited individual device capabilities and the presence of sensitive data. These combined set of circumstances make digital investigations in mobile and cloud environments particularly challenging. This is not aided by the fact that digital forensics today still involves manual, time consuming tasks within the processes of identifying evidence, performing evidence acquisition and correlating multiple diverse sources of evidence in the analysis phase. Furthermore, industry standard tools developed are largely evidence-oriented, have limited support for evidence integration and only automate certain precursory tasks, such as indexing and text searching. In this study, efficiency, in the form of reducing the time and human labour effort expended, is sought after in digital investigations in highly networked environments through the automation of certain activities in the digital forensic process. To this end requirements are outlined and an architecture designed for an automated system that performs digital forensics in highly networked mobile and cloud environments. Part of the remote evidence acquisition activity of this architecture is built and tested on several mobile devices in terms of speed and reliability. A method for integrating multiple diverse evidence sources in an automated manner, supporting correlation and automated reasoning is developed and tested. Finally the proposed architecture is reviewed and enhancements proposed in order to further automate the architecture by introducing decentralization particularly within the storage and processing functionality. This decentralization also improves machine to machine communication supporting several digital investigation processes enabled by the architecture through harnessing the properties of various peer-to-peer overlays. Remote evidence acquisition helps to improve the efficiency (time and effort involved) in digital investigations by removing the need for proximity to the evidence. Experiments show that a single TCP connection client-server paradigm does not offer the required scalability and reliability for remote evidence acquisition and that a multi-TCP connection paradigm is required. The automated integration, correlation and reasoning on multiple diverse evidence sources demonstrated in the experiments improves speed and reduces the human effort needed in the analysis phase by removing the need for time-consuming manual correlation. Finally, informed by published scientific literature, the proposed enhancements for further decentralizing the Live Evidence Information Aggregator (LEIA) architecture offer a platform for increased machine-to-machine communication thereby enabling automation and reducing the need for manual human intervention.

Effekter av Internet of Things : Scenariobaserad studie som beskriver inledande effekter av Internet of Things i en verksamhet

Med begreppet "Internet of Things" menas att ett objekt ur den riktiga världen blir en del av internet. Tunabyggen i Borlänge planerar att implementera ett sådant informationssystem som med hjälp av sensorer och en ständig internetuppkoppling håller uppsikt över temperatur och luftfuktighet i utvalda lokaler. Det är ett enkelt system som till synes inte har så stora effekter på den nuvarande verksamheten. De ekonomiska effekterna går ofta att räkna på i förhand men effekterna på personal, miljö och rutiner kan glömmas bort. Vi har därför med detta examensarbete undersökt vilka inledande effekter som kan tänkas uppkomma efter implementering av ett nytt informationssystem med "Internet of Things" funktionalitet i en verksamhet. Detta sker inom kategorierna ekonomi, arbetsmiljö, miljöpåverkan och systemförvaltning. För att kunna besvara detta har vi gjort en fallstudie baserad på en scenariometodik som består av fyra faser. Fas 1, där vi fick vårt Case och skapade en förståelse för scenariofältet. Fas 2, där vi identifierade nyckelfaktorer. Detta har gjorts genom en litteraturstudie samt intervju med berörd personal på Tunabyggen. Fas 3, där analysen av dessa nyckelfaktorer skedde genom nulägesanalys och framtidsanalys av nyckelfaktorer. Fas 4, där vi genererade scenarier av de analyserade nyckelfaktorerna. Det har sedan gjorts en SWOT-analys för att belysa styrkor, svagheter, möjligheter och hot. Resultatet visar tydliga tecken på att det kommer att bli många effekter för Tunabyggen efter implementering av det nya informationssystemet som yttrar sig i alla kategorier. Slutsatsen är att vid implementation av ett informationssystem som detta är effekterna många. Detta är något som vi anser bör beaktas av alla verksamheter som har tankar på att införskaffa ett nytt informationssystem. De bör inte bara utvärdera informationssystem rent ekonomiskt utan borde ta i beaktning att det finns ett antal andra faktorer som har en avgörande roll om implementation av informationssystem ska bli lyckad.

Proposta de implementação de uma metodologia SMED numa metalomecânica

O presente trabalho é o resultado de um projecto experimental que teve como principal objetivo a redução dos tempos de setup, através da implementação da metodologia Single Minute Exchange of Die (SMED) em equipamentos de eletroerosão (EDM) por fio e penetração. Para garantir o sucesso da implementação, após uma revisão bibliográfica centrada no tema SMED, estabelece-se uma metodologia, numa lógica de melhoria contínua análoga a um ciclo PDCA. A metodologia estabelecida envolve as seguintes fases: caracterização da situação inicial, observação, recolha de dados, análise dos dados e implementação SMED. A caracterização da situação inicial visa qualificar a situação encontrada e identificar a zona de atuação - equipamentos em estudo. A observação do processo produtivo é suportada pela ferramenta fluxograma do processo, por sua vez, a recolha de dados visa a avaliação inicial e nessa perspectiva recorre-se à abordagem OEE. Na fase de análise dos dados são introduzidas as ferramentas de análise VSM e diagrama de causa e efeito que auxiliam a identificação de um conjunto de acções de melhoria, a realizar previamente à fase de implementação SMED, culminando assim uma fase PRÉ-SMED. Reunidas as condições ideais iniciou-se a implementação efectiva da metodologia SMED obtendo-se reduções do tempo total de setup superiores a 60%. O presente estudo permite concluir que podem surgir diferenças significativas em diversas aplicações SMED, enfatizando a importância de uma fase PRÉ-SMED de modo a potenciar os resultados alcançados com uma implementação SMED.

Modelo gerador de questões no reforço da aprendizagem das radiações e conteúdos de física moderna no ensino secundário

Os avanços e a disseminação do uso das Tecnologias de Informação e Comunicação (TIC) descortinam novas perspetivas para a educação com suporte em ambientes digitais de aprendizagem usados via internet (Fiolhais & Trindade, 2003). A plataforma usada no Projeto Matemática Ensino (PmatE) da Universidade de Aveiro (UA) é uma das ferramentas informáticas que suporta esses ambientes através da avaliação baseada no Modelo Gerador de Questões (MGQ), possibilitando a obtenção da imagem do progresso feito pelos alunos (Vieira, Carvalho & Oliveira, 2004). Reconhecendo a importância didática desta ferramenta, já demonstrada noutras investigações (por exemplo, Carvalho, 2011; Pais de Aquino, 2013; Peixoto, 2009), o presente estudo tem como objetivo geral desenvolver material didático digital de Física, no contexto do programa moçambicano de Física da 12ª classe, para alunos e professores sobre radiações e conteúdos da Física Moderna. Pretendeu-se, ainda, propor estratégias de trabalho com recurso às TIC para a melhoria da qualidade das aprendizagens nesta disciplina. O estudo assentou nas três seguintes questões de investigação: (a) Como conceber instrumentos de avaliação das aprendizagens baseadas no modelo gerador de questões para o estudo das radiações e conteúdos da Física Moderna, no contexto do programa moçambicano de Física da 12ª classe? (b) Que potencialidades e constrangimentos apresentam esses instrumentos quando implementados com alunos e professores? (c) De que forma o conhecimento construído pode ser mobilizado para outros temas da Física e para o ensino das ciências em geral? O estudo seguiu uma metodologia de Estudos de Desenvolvimento, de natureza mista, que compreendeu as fases da Análise, Design, Desenvolvimento e Avaliação, seguindo como paradigma um estudo de cariz exploratório, com uma vertente de estudo de caso. Assim, na Análise, foi discutido o contexto da educação em Moçambique e a problemática da abordagem das radiações e conteúdos de Física Moderna no ensino secundário no quadro desafiante que se coloca atualmente à educação científica. No Design foram avaliadas as abordagens dasTIC no ensino e aprendizagem da Física e das ciências em geral e construída a árvore de objetivos nos conteúdos referidos na fase anterior. Na fase do Desenvolvimento foram construídos os instrumentos de recolha de dados, elaborados os protótipos de MGQ e sua posterior programação, validação e testagem em formato impresso no estudo exploratório. Na Avaliação, foi conduzido o estudo principal com a aplicação dos modelos no formato digital e feita sua avaliação, o que incluiu a administração de inquéritos por questionário a alunos e professores. Os resultados indicam que na conceção de MGQ, a definição dos objetivos de aprendizagem em termos comportamentais é fundamental na formulação de questões e na análise dos resultados da avaliação com o objetivo de reajustar as estratégias didáticas. Apontam também que a plataforma do PmatE que suporta os MGQ, embora possua constrangimentos devido a sua dependência da internet e limitações de ordem didática, contribui positivamente na aprendizagem e na identificação das dificuldades e principais erros dos alunos, por um lado. Por outro, estimula através da avaliação os processos de assimilação e acomodação do conhecimento. O estudo recomenda a necessidade de mudanças nas práticas de ensino e de aprendizagem para que seja possível a utilização de conteúdos digitais como complemento à abordagem didática de conteúdos.

Analysis of acute-phase proteins, AHSG, C3, CLI, HP and SAA, reveals distinctive expression patterns associated with breast, colorectal and lung cancer

Early detection, clinical management and disease recurrence monitoring are critical areas in cancer treatment in which specific biomarker panels are likely to be very important in each of these key areas. We have previously demonstrated that levels of alpha-2-heremans-schmid-glycoprotein (AHSG), complement component C3 (C3), clusterin (CLI), haptoglobin (HP) and serum amyloid A (SAA) are significantly altered in serum from patients with squamous cell carcinoma of the lung. Here, we report the abundance levels for these proteins in serum samples from patients with advanced breast cancer, colorectal cancer (CRC) and lung cancer compared to healthy controls (age and gender matched) using commercially available enzyme-linked immunosorbent assay kits. Logistic regression (LR) models were fitted to the resulting data, and the classification ability of the proteins was evaluated using receiver-operating characteristic curve and leave-one-out cross-validation (LOOCV). The most accurate individual candidate biomarkers were C3 for breast cancer [area under the curve (AUC) = 0.89, LOOCV = 73%], CLI for CRC (AUC = 0.98, LOOCV = 90%), HP for small cell lung carcinoma (AUC = 0.97, LOOCV = 88%), C3 for lung adenocarcinoma (AUC = 0.94, LOOCV = 89%) and HP for squamous cell carcinoma of the lung (AUC = 0.94, LOOCV = 87%). The best dual combination of biomarkers using LR analysis were found to be AHSG + C3 (AUC = 0.91, LOOCV = 83%) for breast cancer, CLI + HP (AUC = 0.98, LOOCV = 92%) for CRC, C3 + SAA (AUC = 0.97, LOOCV = 91%) for small cell lung carcinoma and HP + SAA for both adenocarcinoma (AUC = 0.98, LOOCV = 96%) and squamous cell carcinoma of the lung (AUC = 0.98, LOOCV = 84%). The high AUC values reported here indicated that these candidate biomarkers have the potential to discriminate accurately between control and cancer groups both individually and in combination with other proteins. Copyright © 2011 UICC.

First-cycle rash and survival in patients with advanced non-small-cell lung cancer receiving cetuximab in combination with first-line chemotherapy : a subgroup analysis of data from the FLEX phase 3 study

Background: The randomised phase 3 First-Line Erbitux in Lung Cancer (FLEX) study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival compared with chemotherapy alone in the first-line treatment of advanced non-small-cell lung cancer (NSCLC). The main cetuximab-related side-effect was acne-like rash. Here, we assessed the association of this acne-like rash with clinical benefit. Methods: We did a subgroup analysis of patients in the FLEX study, which enrolled patients with advanced NSCLC whose tumours expressed epidermal growth factor receptor. Our landmark analysis assessed if the development of acne-like rash in the first 21 days of treatment (first-cycle rash) was associated with clinical outcome, on the basis of patients in the intention-to-treat population alive on day 21. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. Findings: 518 patients in the chemotherapy plus cetuximab group-290 of whom had first-cycle rash-and 540 patients in the chemotherapy alone group were alive on day 21. Patients in the chemotherapy plus cetuximab group with first-cycle rash had significantly prolonged overall survival compared with patients in the same treatment group without first-cycle rash (median 15·0 months [95% CI 12·8-16·4] vs 8·8 months [7·6-11·1]; hazard ratio [HR] 0·631 [0·515-0·774]; p<0·0001). Corresponding significant associations were also noted for progression-free survival (median 5·4 months [5·2-5·7] vs 4·3 months [4·1-5·3]; HR 0·741 [0·607-0·905]; p=0·0031) and response (rate 44·8% [39·0-50·8] vs 32·0% [26·0-38·5]; odds ratio 1·703 [1·186-2·448]; p=0·0039). Overall survival for patients without first-cycle rash was similar to that of patients that received chemotherapy alone (median 8·8 months [7·6-11·1] vs 10·3 months [9·6-11·3]; HR 1·085 [0·910-1·293]; p=0·36). The significant overall survival benefit for patients with first-cycle rash versus without was seen in all histology subgroups: adenocarcinoma (median 16·9 months, [14·1-20·6] vs 9·3 months [7·7-13·2]; HR 0·614 [0·453-0·832]; p=0·0015), squamous-cell carcinoma (median 13·2 months [10·6-16·0] vs 8·1 months [6·7-12·6]; HR 0·659 [0·472-0·921]; p=0·014), and carcinomas of other histology (median 12·6 months [9·2-16·4] vs 6·9 months [5·2-11·0]; HR 0·616 [0·392-0·966]; p=0·033). Interpretation: First-cycle rash was associated with a better outcome in patients with advanced NSCLC who received cisplatin and vinorelbine plus cetuximab as a first-line treatment. First-cycle rash might be a surrogate clinical marker that could be used to tailor cetuximab treatment for advanced NSCLC to those patients who would be most likely to derive a significant benefit. Funding: Merck KGaA. © 2011 Elsevier Ltd.

Molecular biomarkers in non-small-cell lung cancer : a retrospective analysis of data from the phase 3 FLEX study

Background: Findings from the phase 3 FLEX study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival, compared with cisplatin and vinorelbine alone, in the first-line treatment of EGFR-expressing, advanced non-small-cell lung cancer (NSCLC). We investigated whether candidate biomarkers were predictive for the efficacy of chemotherapy plus cetuximab in this setting. Methods: Genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissue of patients enrolled in the FLEX study was screened for KRAS codon 12 and 13 and EGFR kinase domain mutations with PCR-based assays. In FFPE tissue sections, EGFR copy number was assessed by dual-colour fluorescence in-situ hybridisation and PTEN expression by immunohistochemistry. Treatment outcome was investigated according to biomarker status in all available samples from patients in the intention-to-treat population. The primary endpoint in the FLEX study was overall survival. The FLEX study, which is ongoing but not recruiting participants, is registered with ClinicalTrials.gov, number NCT00148798. Findings: KRAS mutations were detected in 75 of 395 (19%) tumours and activating EGFR mutations in 64 of 436 (15%). EGFR copy number was scored as increased in 102 of 279 (37%) tumours and PTEN expression as negative in 107 of 303 (35%). Comparisons of treatment outcome between the two groups (chemotherapy plus cetuximab vs chemotherapy alone) according to biomarker status provided no indication that these biomarkers were of predictive value. Activating EGFR mutations were identified as indicators of good prognosis, with patients in both treatment groups whose tumours carried such mutations having improved survival compared with those whose tumours did not (chemotherapy plus cetuximab: median 17·5 months [95% CI 11·7-23·4] vs 8·5 months [7·1-10·8], hazard ratio [HR] 0·52 [0·32-0·84], p=0·0063; chemotherapy alone: 23·8 months [15·2-not reached] vs 10·0 months [8·7-11·0], HR 0·35 [0·21-0·59], p<0·0001). Expression of PTEN seemed to be a potential indicator of good prognosis, with patients whose tumours expressed PTEN having improved survival compared with those whose tumours did not, although this finding was not significant (chemotherapy plus cetuximab: median 11·4 months [8·6-13·6] vs 6·8 months [5·9-12·7], HR 0·80 [0·55-1·16], p=0·24; chemotherapy alone: 11·0 months [9·2-12·6] vs 9·3 months [7·6-11·9], HR 0·77 [0·54-1·10], p=0·16). Interpretation: The efficacy of chemotherapy plus cetuximab in the first-line treatment of advanced NSCLC seems to be independent of each of the biomarkers assessed. Funding: Merck KGaA. © 2011 Elsevier Ltd.

EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer : analysis of data from the phase 3 FLEX study

Background: Findings from the phase 3 First-Line ErbituX in lung cancer (FLEX) study showed that the addition of cetuximab to first-line chemotherapy significantly improved overall survival compared with chemotherapy alone (hazard ratio [HR] 0·871, 95% CI 0·762-0·996; p=0·044) in patients with advanced non-small-cell lung cancer (NSCLC). To define patients benefiting most from cetuximab, we studied the association of tumour EGFR expression level with clinical outcome in FLEX study patients. Methods: We used prospectively collected tumour EGFR expression data to generate an immunohistochemistry score for FLEX study patients on a continuous scale of 0-300. We used response data to select an outcome-based discriminatory threshold immunohistochemistry score for EGFR expression of 200. Treatment outcome was analysed in patients with low (immunohistochemistry score <200) and high (≥200) tumour EGFR expression. The primary endpoint in the FLEX study was overall survival. We analysed patients from the FLEX intention-to-treat (ITT) population. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. Findings: Tumour EGFR immunohistochemistry data were available for 1121 of 1125 (99·6%) patients from the FLEX study ITT population. High EGFR expression was scored for 345 (31%) evaluable patients and low for 776 (69%) patients. For patients in the high EGFR expression group, overall survival was longer in the chemotherapy plus cetuximab group than in the chemotherapy alone group (median 12·0 months [95% CI 10·2-15·2] vs 9·6 months [7·6-10·6]; HR 0·73, 0·58-0·93; p=0·011), with no meaningful increase in side-effects. We recorded no corresponding survival benefit for patients in the low EGFR expression group (median 9·8 months [8·9-12·2] vs 10·3 months [9·2-11·5]; HR 0·99, 0·84-1·16; p=0·88). A treatment interaction test assessing the difference in the HRs for overall survival between the EGFR expression groups suggested a predictive value for EGFR expression (p=0·044). Interpretation: High EGFR expression is a tumour biomarker that can predict survival benefit from the addition of cetuximab to first-line chemotherapy in patients with advanced NSCLC. Assessment of EGFR expression could offer a personalised treatment approach in this setting. Funding: Merck KGaA. © 2012 Elsevier Ltd.

Molecular network analysis using reverse phase protein microarrays for patient tailored therapy.

The practice of medicine has always aimed at individualized treatment of disease. The relationship between patient and physician has always been a personal one, and the physician's choice of treatment has been intended to be the best fit for the patient's needs. The necessary pooling/grouping of disease families and their assignment to a number of drugs or treatment methods has, consequently, led to an increase in the number of effective therapies. However, given the heterogeneity of most human diseases, and cancer specifically, it is currently impossible for the treating clinician to effectively predict a patient's response and outcome based on current technologies, much less the idiosyncratic resistances and adverse effects associated with the limited therapeutic options.

An investigation of goethite-seeded Al(OH)3 precipitation using in situ X-ray diffraction and Rietveld-based quantitative phase analysis

An in situ X-ray diffraction investigation of goethite-seeded Al(OH)3 precipitation from synthetic Bayer liquor at 343 K has been performed. The presence of iron oxides and oxyhydroxides in the Bayer process has implications for alumina reversion, which causes significant process losses through unwanted gibbsite precipitation, and is also relevant for the nucleation and growth of scale on mild steel process equipment. The gibbsite, bayerite and nordstrandite polymorphs of Al(OH)3 precipitated from the liquor; gibbsite appeared to precipitate first, with subsequent formation of bayerite and nordstrandite. A Rietveld-based approach to quantitative phase analysis was implemented for the determination of absolute phase abundances as a function of time, from which kinetic information for the formation of the Al(OH)3 phases was determined.

Use of reverse phase protein microarrays and reference standard development for molecular network analysis of metastatic ovarian carcinoma

Cancer can be defined as a deregulation or hyperactivity in the ongoing network of intracellular and extracellular signaling events. Reverse phase protein microarray technology may offer a new opportunity to measure and profile these signaling pathways, providing data on post-translational phosphorylation events not obtainable by gene microarray analysis. Treatment of ovarian epithelial carcinoma almost always takes place in a metastatic setting since unfortunately the disease is often not detected until later stages. Thus, in addition to elucidation of the molecular network within a tumor specimen, critical questions are to what extent do signaling changes occur upon metastasis and are there common pathway elements that arise in the metastatic microenvironment. For individualized combinatorial therapy, ideal therapeutic selection based on proteomic mapping of phosphorylation end points may require evaluation of the patient's metastatic tissue. Extending these findings to the bedside will require the development of optimized protocols and reference standards. We have developed a reference standard based on a mixture of phosphorylated peptides to begin to address this challenge.