We present a novel distributed Gauss–Newton method for the non-linear state estimation (SE) model based on a probabilistic inference method called belief propagation (BP). The main novelty of our work comes from applying BP sequentially over a sequence of linear approximations of the SE model, akin to what is done by the Gauss–Newton method. The resulting iterative Gauss–Newton belief propagation (GN-BP) algorithm can be interpreted as a distributed Gauss–Newton method with the same accuracy as the centralized SE, however, introducing a number of advantages of the BP framework. The paper provides extensive numerical study of the GN-BP algorithm, provides details on its convergence behavior, and gives a number of useful insights for its implementation.

Breast cancer intra-tumor heterogeneity contributes to chemotherapy resistance and decreased patient survival, yet no reliable in vitro models exist to study this phenomenon. To address this need we developed an in vitro 3D organoid culture system using primary human breast cancer tissue. A major difficulty in the development of such models is to identify robust in vitro conditions that preserve the breast cancer phenotypes observed in situ. To address this challenge we used quantitative immunofluorescence imaging to compare the cellular phenotypes in the starting tumor tissue with those observed in the tumor organoids cultured in 3D. We utilized a clustering algorithm and utility function to quantitatively assess whether tumor organoids generated in vitro faithfully recapitulated intra- and inter-tumor heterogeneity of the tumor tissue in situ. This approach generated a normalized score that reflects tissue-organoid similarity. To test the sensitivity of our method to overall changes in tissue phenotype we focused on three distinct breast cancer subtypes distinguished by expression of estrogen receptor (ER), progesterone receptor (PR) and amplification of ERBB2/HER2 (HER2). Using our approach, we successfully recapitulated the tumor phenotypes present in ER+, ER+/HER2+ and triple negative breast cancer. We discovered that EGF preserves the TNBC phenotype, whereas AREG is required for recapitulating the phenotype of ER+ and ER+/HER2+ breast cancers. Additionally, our data demonstrate that HER1 ligands drive inter- and intra-tumor heterogeneity. To investigate how intra-tumor heterogeneity contributes to therapy responses we treated organoids with standard agents used clinically to treat each of the distinct subtypes. For all tumor subtypes we observed differential vulnerabilities between patients to drug treatments. Importantly, our analysis identified divergent cellular phenotypes that have various sensitivities to chemotherapies. Taken together, our methodology provides an unprecedented view of intra-tumor heterogeneity and allows for the investigation of chemo-resistance mechanisms. Further, this approach will provide a powerful tool, which will enhance the identification of novel therapies and facilitate personalized medicine. Citation Format: Sowder ME, Ludwik KA, Pasic L, Brenin DR, Stricker TP, Macara IG, Lannigan DA. Breast cancer organoid cultures preserve intra-tumor heterogeneity and reveal intrinsically resistant phenotypes to standard chemotherapies [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-06-05.

Social capital is used in interdisciplinary research as an analytical tool for explaining how culture, trust, and cooperation between people may be put into a function of general good, economic development and society in general. The objective of this paper consists of identification and analysis of status in the field of groups and networks, trust and solidarity, collective action and cooperation, information and communication, social cohesion and inclusion, and empowerment and political action, as key dimensions of social capital, and all in the context of overview of its significance in socio-economic development of Bosnia and Herzegovina. For the purpose of implementation of the named aim, a secondary and primary research has been conducted (by surveying 100 members of the top management teams in Bosnian and Herzegovinian SMEs). The research results show a relatively unsatisfactory status in the area of observed dimensions of social capital in Bosnia and Herzegovina, and the decision makers and creators of socio-economic policies should put in a more significant effort in the area of development of social capital which has a significant potential in the context of incitement of socio-economic development.