Identification of osteopontin-dependent signaling pathways in a mouse model of human breast cancer

<p>Abstract</p> <p>Background</p> <p>Osteopontin (OPN) is a secreted phosphoprotein which functions as a cell attachment protein and cytokine that signals through two cell adhesion molecules, α_vβ₃-integrin and CD44, to regulate cancer growth and metastasis. However, the signaling pathways associated with OPN have not been extensively characterized. In an in vivo xenograft model of MDA-MB-231 human breast cancer, we have previously demonstrated that ablation of circulating OPN with an RNA aptamer blocks interaction with its cell surface receptors to significantly inhibit adhesion, migration and invasion in vitro and local progression and distant metastases.</p> <p>Findings</p> <p>In this study, we performed microarray analysis to compare the transcriptomes of primary tumor in the presence and absence of aptamer ablation of OPN. The results were corroborated with RT-PCR and Western blot analysis. Our results demonstrate that ablation of OPN cell surface receptor binding is associated with significant alteration in gene and protein expression critical in apoptosis, vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), interleukin-10 (IL-10), granulocyte-macrophage colony stimulating factor (GM-CSF) and proliferation signaling pathways. Many of these proteins have not been previously associated with OPN.</p> <p>Conclusion</p> <p>We conclude that secreted OPN regulates multiple signaling pathways critical for local tumor progression.</p

Manual of Water Quality Models for Virginia Estuaries

It is not the purpose of this manual to make a nonmodeler able to develop a model by reading through it, since no manual of this nature can accomplish such a task. This manual is intended to increase the planner or manager\u27s options by acquainting him with various types of models and informing him of the availability of currently working models. This manual contains the following: 1. A scheme indicating the types of water quality models which could be constructed, i.e. an overview of choices in models. 2. A brief description of each type of models developed under the Cooperative State ~gencies program. 3. A list of empirical formulas or values for the rate constants used in the models. 4. A directory of water quality models which have been applied to Virginia estuaries

Innate Pathways of Immune Activation in Transplantation

Studies of the immune mechanisms of allograft rejection have predominantly focused on the adaptive immune system that includes T cells and B cells. Recent investigations into the innate immune system, which recognizes foreign antigens through more evolutionarily primitive pathways, have demonstrated a critical role of the innate immune system in the regulation of the adaptive immune system. Innate immunity has been extensively studied in its role as the host's first-line defense against microbial pathogens; however, it is becoming increasingly recognized for its ability to also recognize host-derived molecules that result from tissue damage. The capacity of endogenous damage signals acting through the innate immune system to lower immune thresholds and promote immune recognition and rejection of transplant grafts is only beginning to be appreciated. An improved understanding of these pathways may reveal novel therapeutic targets to decrease graft alloreactivity and increase graft longevity

Diagnosis, Management, and Pathogenetic Studies in Medullary Thyroid Carcinoma Syndrome

A retrospective study of 224 patients with medullary thyroid carcinoma (MTC) diagnosed between 1963 and 1988 was performed to 1) establish the diagnosis of MTC in early childhood, 2) establish the role of prophylactic regional lymphadenectomy in patients with MTC, 3) study the effect of chemotherapy on MTC patients with metastatic disease, 4) study the effect of somatostatin analog 201-995 (Sandoz Pharmaceuticals) on the frequency of diarrhea in MTC, and 5) locate the common region(s) of gene deletion on chromosome 1 and examine the loss of heterozygosity on chromosome 10 in tumors. Our data indicated that a progressive rise of serum calcitonin in early childhood (rather than the expected fall with age seen in normal subjects) is diagnostic of MTC. No differences in clinical course or prognosis were observed between patients with MTC localized to the thyroid who had prophylactic neck node dissection and those who did not. Conventional chemotherapy had no significant benefit in the treatment of patients with metastatic disease. The somatostatin analog was found to be an effeciive drug in the treatment of diarrhea associated with MTC. Allelic losses were frequently found in MTCs and pheochromocytomas, and the loss of DNA sequences in these tumors appeared to involve the distal third of the short arm of chromosome 1, with a common breakpoint at 1p32

Prevalence of Tidal Interactions among Local Seyfert Galaxies: The Control Experiment

We test whether there is a relation between the observed tidal interactions and Seyfert activity by imaging in HI twenty inactive galaxies at the same spatial resolution and detection threshold as the Seyfert sample. This control sample of inactive galaxies were closely matched in Hubble type, range in size and inclination, and have roughly comparable galaxy optical luminosity to the Seyfert galaxies. We find that only ~15% of the galaxies in our control sample are disturbed in HI, whereas the remaining ~85% show no disturbances whatsoever in HI. Even at a spatial resolution of ~10 kpc, none of the latter galaxies show appreciable HI disturbances reminiscent of tidal features. In a companion paper (Kuo et al. 2008), we report results from the first systematic imaging survey of Seyfert galaxies in atomic hydrogen (HI) gas. We find that only ~28% of the eighteen Seyfert galaxies in that sample are visibly disturbed in optical starlight. By contrast, ~94% of the same Seyfert galaxies are disturbed spatially and usually also kinematically in HI gas on galactic scales of >~20 kpc. In at least ~67% and up to perhaps ~94% of cases, the observed disturbances can be traced to tidal interactions with neighboring galaxies detected also in HI. The dramatic contrast between the observed prevalence of HI disturbances in the Seyfert and control samples implicates tidal interactions in initiating events that lead to luminous Seyfert activity in a large fraction of local disk galaxies.Comment: 38 pages, 27 figures, Accepted for publication in ApJ. Changes from previous version: The title of the previous version of this paper appeared in Astroph was incorrect. It has been replaced with the correct on

Evaluation of Cancer Stem Cell Migration Using Compartmentalizing Microfluidic Devices and Live Cell Imaging

In the last 40 years, the United States invested over 200 billion dollars on cancer research, resulting in only a 5% decrease in death rate. A major obstacle for improving patient outcomes is the poor understanding of mechanisms underlying cellular migration associated with aggressive cancer cell invasion, metastasis and therapeutic resistance1. Glioblastoma Multiforme (GBM), the most prevalent primary malignant adult brain tumor2, exemplifies this difficulty. Despite standard surgery, radiation and chemotherapies, patient median survival is only fifteen months, due to aggressive GBM infiltration into adjacent brain and rapid cancer recurrence2. The interactions of aberrant cell migratory mechanisms and the tumor microenvironment likely differentiate cancer from normal cells3. Therefore, improving therapeutic approaches for GBM require a better understanding of cancer cell migration mechanisms. Recent work suggests that a small subpopulation of cells within GBM, the brain tumor stem cell (BTSC), may be responsible for therapeutic resistance and recurrence. Mechanisms underlying BTSC migratory capacity are only starting to be characterized1,4

Solar Dynamics Observatory Launch and Commissioning

The Solar Dynamics Observatory (SDO) was launched on February 11, 2010. Over the next three months, the spacecraft was raised from its launch orbit into its final geosynchronous orbit and its systems and instruments were tested and calibrated in preparation for its desired ten year science mission studying the Sun. A great deal of activity during this time involved the spacecraft attitude control system (ACS); testing control modes, calibrating sensors and actuators, and using the ACS to help commission the spacecraft instruments and to control the propulsion system as the spacecraft was maneuvered into its final orbit. This paper will discuss the chronology of the SDO launch and commissioning, showing the ACS analysis work performed to diagnose propellant slosh transient and attitude oscillation anomalies that were seen during commissioning, and to determine how to overcome them. The simulations and tests devised to demonstrate correct operation of all onboard ACS modes and the activities in support of instrument calibration will be discussed and the final maneuver plan performed to bring SDO on station will be shown. In addition to detailing these commissioning and anomaly resolution activities, the unique set of tests performed to characterize SDO's on-orbit jitter performance will be discussed

On a Jansen leg with multiple gait patterns for reconfigurable walking platforms

Legged robots are able to move across irregular terrains and those based on 1-degree-of-freedom planar linkages can be energy efficient, but are often constrained by a limited range of gaits which can limit their locomotion capabilities considerably. This article reports the design of a novel reconfigurable Theo Jansen linkage that produces a wide variety of gait cycles, opening new possibilities for innovative applications. The suggested mechanism switches from a pin-jointed Grübler kinematic chain to a 5-degree-of-freedom mechanism with slider joints during the reconfiguration process. It is shown that such reconfigurable linkage significantly extend the capabilities of the original design, while maintaining its mechanical simplicity during normal operation, to not only produce different useful gait patterns but also to realize behaviors beyond locomotion. Experiments with an implemented prototype are presented, and their results validate the proposed approach

Attitude Control System Design for the Solar Dynamics Observatory

The Solar Dynamics Observatory mission, part of the Living With a Star program, will place a geosynchronous satellite in orbit to observe the Sun and relay data to a dedicated ground station at all times. SDO remains Sun- pointing throughout most of its mission for the instruments to take measurements of the Sun. The SDO attitude control system is a single-fault tolerant design. Its fully redundant attitude sensor complement includes 16 coarse Sun sensors, a digital Sun sensor, 3 two-axis inertial reference units, 2 star trackers, and 4 guide telescopes. Attitude actuation is performed using 4 reaction wheels and 8 thrusters, and a single main engine nominally provides velocity-change thrust. The attitude control software has five nominal control modes-3 wheel-based modes and 2 thruster-based modes. A wheel-based Safehold running in the attitude control electronics box improves the robustness of the system as a whole. All six modes are designed on the same basic proportional-integral-derivative attitude error structure, with more robust modes setting their integral gains to zero. The paper details the mode designs and their uses