Relativistic Binaries in Globular Clusters

Galactic globular clusters are old, dense star systems typically containing 10\super{4}--10\super{7} stars. As an old population of stars, globular clusters contain many collapsed and degenerate objects. As a dense population of stars, globular clusters are the scene of many interesting close dynamical interactions between stars. These dynamical interactions can alter the evolution of individual stars and can produce tight binary systems containing one or two compact objects. In this review, we discuss theoretical models of globular cluster evolution and binary evolution, techniques for simulating this evolution that leads to relativistic binaries, and current and possible future observational evidence for this population. Our discussion of globular cluster evolution will focus on the processes that boost the production of hard binary systems and the subsequent interaction of these binaries that can alter the properties of both bodies and can lead to exotic objects. Direct {\it N}-body integrations and Fokker--Planck simulations of the evolution of globular clusters that incorporate tidal interactions and lead to predictions of relativistic binary populations are also discussed. We discuss the current observational evidence for cataclysmic variables, millisecond pulsars, and low-mass X-ray binaries as well as possible future detection of relativistic binaries with gravitational radiation.Comment: 88 pages, 13 figures. Submitted update of Living Reviews articl

Mechanisms of Matrix-Induced Chemoresistance of Breast Cancer Cells—Deciphering Novel Potential Targets for a Cell Sensitization

Tumor cell binding to microenvironment components such as collagen type 1 (COL1) attenuates the sensitivity to cytotoxic drugs like cisplatin (CDDP) or mitoxantrone (MX), referred to as cell adhesion mediated drug resistance (CAM-DR). CAM-DR is considered as the onset for resistance mutations, but underlying mechanisms remain elusive. To evaluate CAM-DR as target for sensitization strategies, we analyzed signaling pathways in human estrogen-positive MCF-7 and triple-negative MDA-MB-231 breast cancer cells by western blot, proteome profiler array and TOP-flash assay in presence of COL1. β1-Integrins, known to bind COL1, appear as key for mediating COL1-related resistance in both cell lines that primarily follows FAK/PI3K/AKT pathway in MCF-7, and MAPK pathway in MDA-MB-231 cells. Notably, pCREB is highly elevated in both cell lines. Consequently, blocking these pathways sensitizes the cells evidently to CDDP and MX treatment. Wnt signaling is not relevant in this context. A β1-integrin knockdown of MCF-7 cells (MCF-7-β1-kd) reveals a signaling shift from FAK/PI3K/AKT to MAPK pathway, thus CREB emerges as a promising primary target for sensitization in MDA-MB-231, and secondary target in MCF-7 cells. Concluding, we provide evidence for importance of CAM-DR in breast cancer cells and identify intracellular signaling pathways as targets to sensitize cells for cytotoxicity treatment regimes

A long-term field study on the adoption of smartphones by children in Panama

Computing technology is currently adopted in emerging countries. Especially mobile phones and smart phones become widely used - with a much higher penetration than traditional computers. In our work we investigate how computing technologies and particularly mobile devices can support education. While previous work focused on controlled experiments, in this paper we present the results of a 20 weeks long study of mobile phone usage in an emerging region. Our aim was not only to investigate how the phones are used for education but also to learn how they are adopted by children in daily life. By logging screenshots, we used an unsupervised approach that allowed to unobtrusively observe usage patterns without the presence of researchers. Instead of offering tailored teaching applications, we used general-purpose applications to support teaching and found that the phone itself was an empowering technology similar to pen and paper. Based on a detailed analysis of actual use in a natural setting, we derived a set of typical use cases for mobile phones in education and describe how they change learning. From in-depth interviews with a teacher, selected guardians and pupils we show that introducing mobiles phones has great potential for supporting education in emerging regions

A long-term field study on the adoption of smartphones by children in Panama

Computing technology is currently adopted in emerging countries. Especially mobile phones and smart phones become widely used - with a much higher penetration than traditional computers. In our work we investigate how computing technologies and particularly mobile devices can support education. While previous work focused on controlled experiments, in this paper we present the results of a 20 weeks long study of mobile phone usage in an emerging region. Our aim was not only to investigate how the phones are used for education but also to learn how they are adopted by children in daily life. By logging screenshots, we used an unsupervised approach that allowed to unobtrusively observe usage patterns without the presence of researchers. Instead of offering tailored teaching applications, we used general-purpose applications to support teaching and found that the phone itself was an empowering technology similar to pen and paper. Based on a detailed analysis of actual use in a natural setting, we derived a set of typical use cases for mobile phones in education and describe how they change learning. From in-depth interviews with a teacher, selected guardians and pupils we show that introducing mobiles phones has great potential for supporting education in emerging regions.Computing technology is currently adopted in emerging countries. Especially mobile phones and smart phones become widely used - with a much higher penetration than traditional computers. In our work we investigate how computing technologies and particularly mobile devices can support education. While previous work focused on controlled experiments, in this paper we present the results of a 20 weeks long study of mobile phone usage in an emerging region. Our aim was not only to investigate how the phones are used for education but also to learn how they are adopted by children in daily life. By logging screenshots, we used an unsupervised approach that allowed to unobtrusively observe usage patterns without the presence of researchers. Instead of offering tailored teaching applications, we used general-purpose applications to support teaching and found that the phone itself was an empowering technology similar to pen and paper. Based on a detailed analysis of actual use in a natural setting, we derived a set of typical use cases for mobile phones in education and describe how they change learning. From in-depth interviews with a teacher, selected guardians and pupils we show that introducing mobiles phones has great potential for supporting education in emerging regions.SIGCHI ACM Special Interest Group on Computer-Human Interactio

Synergistic activity of bortezomib and HDACis in preclinical models of B-cell precursor acute lymphoblastic leukemia via modulation of p53, PI3K/AKT and NF-κB

PURPOSE: Relapse of disease and subsequent resistance to established therapies remains a major challenge in the treatment of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). New therapeutic options, such as proteasome and histone deacetylase inhibitors (HDACis) with a toxicity profile differing from that of conventional cytotoxic agents are needed for these extensively pre-treated patients. EXPERIMENTAL DESIGN: Anti-proliferative and pro-apoptotic effects of combined HDACi/proteasome inhibitor treatments were analyzed using BCP-ALL monocultures, cocultures with primary mesenchymal stroma cells from ALL-patients and xenograft mouse models. The underlying molecular mechanisms associated with combined treatment were determined by gene expression profiling and protein validation. RESULTS: We identified the proteasome inhibitor bortezomib (BTZ) as a promising combination partner for HDACis due to the substantial synergistic antileukemic activity in BCP-ALL cells after concomitant application. This effect was maintained or even increased in the presence of chemotherapeutic agents. The synergistic effect of combined HDACi/BTZ treatment was associated with the regulation of genes involved in cell cycle, JUN/MAPK-, PI3K/AKT-, p53-, ubiquitin-proteasome and NF-{kappa}B pathways. We observed an activation of NF-{kappa}B after BTZ treatment and the induction of apoptosis-related NF-{kappa}B target genes such as TNF{alpha}Rs after concomitant treatment, indicating a possible involvement of NF-{kappa}B as pro-apoptotic mediator. In this context, significantly lower NF-{kappa}B subunits gene expression was detected in leukemia cells from patients, who developed a relapse during frontline chemotherapy, compared to those who relapsed after cessation of frontline therapy. CONCLUSION: These results provide a rationale for the integration of HDACi/BTZ combinations into current childhood BCP-ALL treatment protocols