Targeting tumor multicellular aggregation through IGPR-1 inhibits colon cancer growth and improves chemotherapy

Adhesion to extracellular matrix (ECM) is crucially important for survival of normal epithelial cells as detachment from ECM triggers specific apoptosis known as anoikis. As tumor cells lose the requirement for anchorage to ECM, they rely on cell-cell adhesion 'multicellular aggregation' for survival. Multicellular aggregation of tumor cells also significantly determines the sensitivity of tumor cells to the cytotoxic effects of chemotherapeutics. In this report, we demonstrate that expression of immunoglobulin containing and proline-rich receptor-1 (IGPR-1) is upregulated in human primary colon cancer. Our study demonstrates that IGPR-1 promotes tumor multicellular aggregation, and interfering with its adhesive function inhibits multicellular aggregation and, increases cell death. IGPR-1 supports colon carcinoma tumor xenograft growth in mouse, and inhibiting its activity by shRNA or blocking antibody inhibits tumor growth. More importantly, IGPR-1 regulates sensitivity of tumor cells to the chemotherapeutic agent, doxorubicin/adriamycin by a mechanism that involves doxorubicin-induced AKT activation and phosphorylation of IGPR-1 at Ser220. Our findings offer novel insight into IGPR-1's role in colorectal tumor growth, tumor chemosensitivity, and as a possible novel anti-cancer target.Grant support from: R01 CA175382/CA/NCI NIH HHS/United States, R21 CA191970/CA/NCI NIH HHS/United States, and R21 CA193958/CA/NCI NIH HHS/United State

Towards measurable resilience: A novel framework tool for the assessment of resilience levels in slums

This paper investigates the need for a generic technique to be applied in the assessment of resilience-related projects in slums – particularly for localised infrastructure at a community level – and proposes a novel framework tool for this purpose. The paper outlines the development of the framework tool, as well as its pilot testing on the Kenya Slum Upgrading Programme in Kibera, Nairobi. The evaluation demonstrates an improvement in asset base, capacities and external resources for the community post intervention. The lack of land tenure was identified to be a key weakness and factor which impacted resilience of the local residents

Fast Monte Carlo simulations and singularities in the probability distributions of non-equilibrium systems

A numerical technique is introduced that reduces exponentially the time required for Monte Carlo simulations of non-equilibrium systems. Results for the quasi-stationary probability distribution in two model systems are compared with the asymptotically exact theory in the limit of extremely small noise intensity. Singularities of the non-equilibrium distributions are revealed by the simulations.Comment: 4 pages, 4 figure

Development of the fast neutron imaging telescope

We report on the development of a next generation neutron telescope, with imaging and energy measurement capabilities, sensitive to neutrons in the 2-20 MeV energy range. The Fast Neutron Imaging Telescope (FNIT) was initially conceived to study solar neutrons as a candidate instrument for the Inner Heliosphere Sentinels (IHS) program under formulation at NASA. This detector is now being adapted to locate Special Nuclear Material (SNM) for homeland security purposes by detecting fission neutrons and reconstructing the image of their source. In either case, the detection principle is based on multiple elastic neutron-proton scatterings in organic scintillator. By reconstructing the scattering coordinates and measuring the recoil proton energy, the direction and energy of each neutron can be determined and discrete neutron sources identified. We describe the performance of the FNIT prototype, report on the current status of R&D efforts and present the results of recent laboratory measurements

Theory of Systematic Computational Error in Free Energy Differences

Systematic inaccuracy is inherent in any computational estimate of a non-linear average, due to the availability of only a finite number of data values, N. Free energy differences (DF) between two states or systems are critically important examples of such averages in physical, chemical and biological settings. Previous work has demonstrated, empirically, that the ``finite-sampling error'' can be very large -- many times kT -- in DF estimates for simple molecular systems. Here, we present a theoretical description of the inaccuracy, including the exact solution of a sample problem, the precise asymptotic behavior in terms of 1/N for large N, the identification of universal law, and numerical illustrations. The theory relies on corrections to the central and other limit theorems, and thus a role is played by stable (Levy) probability distributions.Comment: 5 pages, 4 figure

Webifying the computerized execution of Clinical Practice Guidelines

The means through which Clinical Practice Guidelines are dissemi-nated and become accessible are a crucial factor in their later adoption by health care professionals. Making these guidelines available in Clinical Decision Sup-port Systems renders their application more personal and thus acceptable at the moment of care. Web technologies may play an important role in increasing the reach and dissemination of guidelines, but this promise remains largely unful-filled. There is a need for a guideline computer model that can accommodate a wide variety of medical knowledge along with a platform for its execution that can be easily used in mobile devices. This work presents the CompGuide frame-work, a web-based and service-oriented platform for the execution of Computer-Interpretable Guidelines. Its architecture comprises different modules whose in-teraction enables the interpretation of clinical tasks and the verification of clinical constraints and temporal restrictions of guidelines represented in OWL. It allows remote guideline execution with data centralization, more suitable for a work en-vironment where physicians are mobile and not bound to a machine. The solution presented in this paper encompasses a computer-interpretable guideline model, a web-based framework for guideline execution and an Application Programming Interface for the development of other guideline execution systems.This work is part-funded by ERDF - European Regional Development Fund through the COMPETE Programme (operational programme for competitiveness) and by National Funds through the FCT – Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) within project FCOMP-01-0124-FEDER-028980 (PTDC/EEI-SII/1386/2012). The work of Tiago Oliveira is supported by doctoral grant by FCT (SFRH/BD/85291/2012)

Three very young HgMn stars in the Orion OB1 Association

We report the detection of three mercury-manganese stars in the Orion OB1 association. HD 37886 and BD-0 984 are in the approximately 1.7 million year old Orion OB1b. HD 37492 is in the approximately 4.6 million year old Orion OB1c. Orion OB1b is now the youngest cluster with known HgMn star members. This places an observational upper limit on the time scale needed to produce the chemical peculiarities seen in mercury-manganese stars, which should help in the search for the cause or causes of the peculiar abundances in HgMn and other chemically peculiar upper main sequence stars.Comment: 8 pages including 1 figure. To appear in Astrophysical Journal Letter