Interactive digital storytelling in the Sarajevo survival tools virtual environment

Virtual museums enable Internet users to explore museum collections online. The question is how to enhance the viewer's experience and learning in such environments. In the Sarajevo Survival Tools virtual museum we introduced a new concept of interactive digital storytelling that will enable the visitors to explore the virtual exhibits - objects from the siege of Sarajevo - guided by a digital story. This way the virtual museum visitors will learn about the context of the displayed objects and be motivated to explore all of them. In this paper we present the virtual environment we developed and our experience with it. The results from three empirical studies we conducted, indicate the positive influence of digital storytelling and sound effects on visitors' perceptual response, resulting in increased motivation and enjoyment, and more effective information conveyance

Functional Crosstalk between Type I and II Interferon through the Regulated Expression of STAT1

Small "priming" quantities of type I interferon enhance cellular responses to type II interferon by maintaining basal levels of STAT1, explaining the observed crosstalk between these two cytokines

Human Cytomegalovirus IE1 Protein Elicits a Type II Interferon-Like Host Cell Response That Depends on Activated STAT1 but Not Interferon-γ

Human cytomegalovirus (hCMV) is a highly prevalent pathogen that, upon primary infection, establishes life-long persistence in all infected individuals. Acute hCMV infections cause a variety of diseases in humans with developmental or acquired immune deficits. In addition, persistent hCMV infection may contribute to various chronic disease conditions even in immunologically normal people. The pathogenesis of hCMV disease has been frequently linked to inflammatory host immune responses triggered by virus-infected cells. Moreover, hCMV infection activates numerous host genes many of which encode pro-inflammatory proteins. However, little is known about the relative contributions of individual viral gene products to these changes in cellular transcription. We systematically analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1) protein, a major transcriptional activator and antagonist of type I interferon (IFN) signaling, on the human transcriptome. Following expression under conditions closely mimicking the situation during productive infection, IE1 elicits a global type II IFN-like host cell response. This response is dominated by the selective up-regulation of immune stimulatory genes normally controlled by IFN-γ and includes the synthesis and secretion of pro-inflammatory chemokines. IE1-mediated induction of IFN-stimulated genes strictly depends on tyrosine-phosphorylated signal transducer and activator of transcription 1 (STAT1) and correlates with the nuclear accumulation and sequence-specific binding of STAT1 to IFN-γ-responsive promoters. However, neither synthesis nor secretion of IFN-γ or other IFNs seems to be required for the IE1-dependent effects on cellular gene expression. Our results demonstrate that a single hCMV protein can trigger a pro-inflammatory host transcriptional response via an unexpected STAT1-dependent but IFN-independent mechanism and identify IE1 as a candidate determinant of hCMV pathogenicity

VIRTUAL MUSEUM APPLICATIONS AND THEIR PUBLIC PERCEPTION IN BOSNIA AND HERZEGOVINA

Bosnia and Herzegovina always has been a place where the East meets the West. Over 1000 years, different cultures, religions and civilizations have left their remains in this small country in Western Balkans. Despite all wars and tragic destructions, today in the heart of Sarajevo one can find mosques, Catholic and Orthodox churches and Jewish synagogues next to each other and people of different nations and religions living together in mutual respect and friendship. Multiethnic spirit of Bosnia and Herzegovina lives through its cultural heritage. Therefore our task is to ensure its presentation and preservation using Information and Communications Technologies (ICT). So far researchers have achieved significant results by creating several virtual museums. In this paper we will present the Museum of Bosnian Traditional Objects, Digital Catalogue of Stecaks and the Virtual Museum of Sarajevo Assassination, giving an overview of the process of creating virtual environments from multiple data sources based on various 3D digitization technologies: some based on traditional 3D modeling, other based on laser scanning or photogrametric techniques

Extrapolation-based approach to optimization with constraints determined by the Robin boundary problem for the Laplace equation

This paper considers the application of extrapolation techniques in finding approximate solutions of some optimization problems with constraints defined by the Robin boundary problem for the Laplace equation. When applied extrapolation techniques produce very accurate solutions of the boundary problems on relatively coarse meshes, but this paper demonstrates that this is not a real restriction when dealing with optimization problems. Producing a solution of continuous problem by polynomial extrapolation based on the low-order discrete problem solutions significantly reduces both computational time and memory. The present paper illustrates this approach using finite-difference and finite-element methods, and finally makes a brief remark about some tacit engineering assumptions regarding numerical solutions of conductive media problems by construction of equivalent resistor networks

B-Raf is required for ERK activation and tumor progression in a mouse model of pancreatic beta-cell carcinogenesis

Activation of the Raf/MEK/ERK pathway, often by gain-of-function mutations of RAS or RAF, is observed in many human cancers. The extracellular signal-regulated kinase (ERK) pathway is required for the proliferation of cancer cell lines harboring activating BRAF or, to a lesser extent, activating RAS mutations. It is still unclear, however, whether the pathway is required in vivo for tumor development, particularly in tumors in which B-Raf is not mutationally activated. During embryonic development, B-Raf is essential for angiogenesis in the placenta. To address the question of whether B-Raf contributed to tumor angiogenesis in vivo we conditionally ablated B-Raf in a model of pancreatic islet carcinoma driven by the functional inactivation of tumor suppressors (RIP1Tag2), which critically depends on angiogenesis for growth. We find that B-Raf is dispensable for the proliferation of tumor cells in culture, but necessary for ERK activation and for the expression of angiogenic factors by tumor cells in vivo and in vitro. In vivo, these defects result in the formation of hollow tumors with decreased vessel density and strongly reduced proliferation. The progression from adenoma to carcinoma is also significantly impaired. Thus, endogenous B-Raf contributes to the development of RIP1Tag2 tumors by supporting the stromal response and tumor progression

p38 MAPK enhances STAT1-dependent transcription independently of Ser-727 phosphorylation

The transcription factor signal transducer and activator of transcription 1 (STAT1) requires phosphorylation at both Tyr-701 and Ser-727 for full activation. IFN-γ induces phosphorylation of both residues, whereas stress signals like UV or lipopolysaccharide stimulate phosphorylation of Ser-727 only. Using p38α mitogen-activated protein kinase (MAPK)-deficient cells, we show that the stress-induced phosphorylation of Ser-727 requires p38α MAPK activity, whereas IFN-γ-stimulated Ser-727 phosphorylation occurs independently of the p38α pathway. Consistently, IFN-γ stimulated expression of the STAT1 target gene IRF1 to a similar extent in both wild-type and p38α-deficient cells. However, stress-induced activation of the p38 MAPK pathway considerably enhanced the IFN-γ-induced expression of both the endogenous IRF1 gene and a reporter driven by the IFN-γ-activated sequence element of the IRF1 promoter. This enhancement occurred independently of increased phosphorylation of Ser-727 by the p38 pathway. Taken together, these results demonstrate an interaction between IFN-γ signaling and the p38 pathway that leads to increased transcriptional activation by STAT1 independently of phosphorylation at Ser-727

Activation of ERα Signaling Differentially Modulates IFN-γ Induced HLA-Class II Expression in Breast Cancer Cells

The coordinate regulation of HLA class II (HLA-II) is controlled by the class II transactivator, CIITA, and is crucial for the development of anti-tumor immunity. HLA-II in breast carcinoma is associated with increased IFN-γ levels, reduced expression of the estrogen receptor (ER) and reduced age at diagnosis. Here, we tested the hypothesis that estradiol (E2) and ERα signaling contribute to the regulation of IFN-γ inducible HLA-II in breast cancer cells. Using a panel of established ER− and ER+ breast cancer cell lines, we showed that E2 attenuated HLA-DR in two ER+ lines (MCF-7 and BT-474), but not in T47D, while it augmented expression in ER− lines, SK-BR-3 and MDA-MB-231. To further study the mechanism(s), we used paired transfectants: ERα+ MC2 (MDA-MB-231 c10A transfected with the wild type ERα gene) and ERα− VC5 (MDA-MB-231 c10A transfected with the empty vector), treated or not with E2 and IFN-γ. HLA-II and CIITA were severely reduced in MC2 compared to VC5 and were further exacerbated by E2 treatment. Reduced expression occurred at the level of the IFN-γ inducible CIITA promoter IV. The anti-estrogen ICI 182,780 and gene silencing with ESR1 siRNA reversed the E2 inhibitory effects, signifying an antagonistic role for activated ERα on CIITA pIV activity. Moreover, STAT1 signaling, necessary for CIITA pIV activation, and selected STAT1 regulated genes were variably downregulated by E2 in transfected and endogenous ERα positive breast cancer cells, whereas STAT1 signaling was noticeably augmented in ERα− breast cancer cells. Collectively, these results imply immune escape mechanisms in ERα+ breast cancer may be facilitated through an ERα suppressive mechanism on IFN-γ signaling