A Fine-grained Data Set and Analysis of Tangling in Bug Fixing Commits

Context: Tangled commits are changes to software that address multiple concerns at once. For researchers interested in bugs, tangled commits mean that they actually study not only bugs, but also other concerns irrelevant for the study of bugs. Objective: We want to improve our understanding of the prevalence of tangling and the types of changes that are tangled within bug fixing commits. Methods: We use a crowd sourcing approach for manual labeling to validate which changes contribute to bug fixes for each line in bug fixing commits. Each line is labeled by four participants. If at least three participants agree on the same label, we have consensus. Results: We estimate that between 17% and 32% of all changes in bug fixing commits modify the source code to fix the underlying problem. However, when we only consider changes to the production code files this ratio increases to 66% to 87%. We find that about 11% of lines are hard to label leading to active disagreements between participants. Due to confirmed tangling and the uncertainty in our data, we estimate that 3% to 47% of data is noisy without manual untangling, depending on the use case. Conclusion: Tangled commits have a high prevalence in bug fixes and can lead to a large amount of noise in the data. Prior research indicates that this noise may alter results. As researchers, we should be skeptics and assume that unvalidated data is likely very noisy, until proven otherwise.Comment: Status: Accepted at Empirical Software Engineerin

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

“Listening to the Terrorists” - On the Role of Religion behind Islamist Terrorism : A qualitative Analysis of the Radicalization Processes of Islamist Terrorists

Understanding the motives behind Islamist terrorist attacks is not only relevant for the field of politics but preoccupies research within academia. One of the most debated is certainly the role of religion. This thesis addresses this gap by asking the question, what role does religion play in the radicalization processes of Islamist terrorists attacking western targets? It combines an emotional approach to religion, with religiosity as defined by religious practices in everyday life and by the self-perception of individuals themselves. It further argues that when religion is perceived as emotionally meaningful, this results in spiritual selective incentives, individuals perceive as worth engaging in terrorism. Using process tracing and structured focused comparison, it conducts an analysis of the radicalisation processes of three individuals, within a comparative case study design, using autobiographies, court documents, previous case studies and news articles. The results show that the individuals perceived their emotions in a religious context and support is found for the hypothesis that justification for violence emerges out of religious motives. The Thesis concludes that religion does have explanatory power as an independent variable, but causal relationships are complex. This leaves room for further research which focuses more on religion as an independent variable

“Listening to the Terrorists” - On the Role of Religion behind Islamist Terrorism : A qualitative Analysis of the Radicalization Processes of Islamist Terrorists

Understanding the motives behind Islamist terrorist attacks is not only relevant for the field of politics but preoccupies research within academia. One of the most debated is certainly the role of religion. This thesis addresses this gap by asking the question, what role does religion play in the radicalization processes of Islamist terrorists attacking western targets? It combines an emotional approach to religion, with religiosity as defined by religious practices in everyday life and by the self-perception of individuals themselves. It further argues that when religion is perceived as emotionally meaningful, this results in spiritual selective incentives, individuals perceive as worth engaging in terrorism. Using process tracing and structured focused comparison, it conducts an analysis of the radicalisation processes of three individuals, within a comparative case study design, using autobiographies, court documents, previous case studies and news articles. The results show that the individuals perceived their emotions in a religious context and support is found for the hypothesis that justification for violence emerges out of religious motives. The Thesis concludes that religion does have explanatory power as an independent variable, but causal relationships are complex. This leaves room for further research which focuses more on religion as an independent variable

Formation of Porphyrin Isomers from Porphobilinogen by Various Hemolysates of Red Cells from Bovine and Human Subjects with Erythropoietic (Uro-) Porphyria

Peer Reviewe

Acquired Resistance to Antibody-Drug Conjugates

Antibody-drug conjugates (ADCs) combine the tumor selectivity of antibodies with the potency of cytotoxic small molecules thereby constituting antibody-mediated chemotherapy. As this inherently limits the adverse effects of the chemotherapeutic, such approaches are heavily pursued by pharma and biotech companies and have resulted in four FDA (Food and Drug Administration)-approved ADCs. However, as with other cancer therapies, durable responses are limited by the fact that under cell stress exerted by these drugs, tumors can acquire mechanisms of escape. Resistance can develop against the antibody component of ADCs by down-regulation/mutation of the targeted cell surface antigen or against payload toxicity by up-regulation of drug efflux transporters. Unique resistance mechanisms specific for the mode of action of ADCs have also emerged, like altered internalization or cell surface recycling of the targeted tumor antigen, changes in the intracellular routing or processing of ADCs, and impaired release of the toxic payload into the cytosol. These evasive changes are tailored to the specific nature and interplay of the three ADC constituents: the antibody, the linker, and the payload. Hence, they do not necessarily endow broad resistance to ADC therapy. This review summarizes preclinical and clinical findings that shed light on the mechanisms of acquired resistance to ADC therapies