A mass action model of a fibroblast growth factor signaling pathway and its simplification

We consider a kinetic law of mass action model for Fibroblast Growth Factor (FGF) signaling, focusing on the induction of the RAS-MAP kinase pathway via GRB2 binding. Our biologically simple model suffers a combinatorial explosion in the number of differential equations required to simulate the system. In addition to numerically solving the full model, we show that it can be accurately simplified. This requires combining matched asymptotics, the quasi-steady state hypothesis, and the fact subsets of the equations decouple asymptotically. Both the full and simplified models reproduce the qualitative dynamics observed experimentally and in previous stochastic models. The simplified model also elucidates both the qualitative features of GRB2 binding and the complex relationship between SHP2 levels, the rate SHP2 induces dephosphorylation and levels of bound GRB2. In addition to providing insight into the important and redundant features of FGF signaling, such work further highlights the usefulness of numerous simplification techniques in the study of mass action models of signal transduction, as also illustrated recently by Borisov and co-workers (Borisov et al. in Biophys. J. 89, 951–66, 2005, Biosystems 83, 152–66, 2006; Kiyatkin et al. in J. Biol. Chem. 281, 19925–9938, 2006). These developments will facilitate the construction of tractable models of FGF signaling, incorporating further biological realism, such as spatial effects or realistic binding stoichiometries, despite a more severe combinatorial explosion associated with the latter

Analysis of UV protection requirements and testing of candidate attenuators for the Haloe optical instrument

Results of calculations are presented which simulate photolytic processes occurring in HALOE gas calibration cells exposed to extra-terrestrial solar ultraviolet photons. These calculations indicate that significant photolysis takes place in two of the sapphire-enclosed cells over the exposure periods of the proposed mission. A subsequent laboratory investigation is also described in which a high-voltage discharge hydrogen light source is used in conjunction with a vacuum ultraviolet spectrograph. The UV emission from this lamp was used to expose two candidate UV attenuators (ZnSe and coated Ge) to ascertain their suitability as UV filters while maintaining original infrared optical properties. Both materials were found to be effectively opaque to vacuum UV radiaton and suffered no adverse effects regarding their infrared transmissivity

Relay-Assisted User Scheduling in Wireless Networks with Hybrid-ARQ

This paper studies the problem of relay-assisted user scheduling for downlink wireless transmission. The base station or access point employs hybrid automatic-repeat-request (HARQ) with the assistance of a set of fixed relays to serve a set of mobile users. By minimizing a cost function of the queue lengths at the base station and the number of retransmissions of the head-of-line packet for each user, the base station can schedule an appropriate user in each time slot and an appropriate transmitter to serve it. It is shown that a priority-index policy is optimal for a linear cost function with packets arriving according to a Poisson process and for an increasing convex cost function where packets must be drained from the queues at the base station.Comment: 14 pages, 5 figures, submitted to the IEEE Transactions on Vehicular Technology in October 2008, revised in March 2009 and May 200

Supporting Special-Purpose Health Care Models via Web Interfaces

The potential of the Web, via both the Internet and intranets, to facilitate development of clinical information systems has been evident for some time. Most Web-based clinical workstations interfaces, however, provide merely a loose collection of access channels. There are numerous examples of systems for access to either patient data or clinical guidelines, but only isolated cases where clinical decision support is presented integrally with the process of patient care, in particular, in the form of active alerts and reminders based on patient data. Moreover, pressures in the health industry are increasing the need for doctors to practice in accordance with ¿best practice¿ guidelines and often to operate under novel health-care arrangements. We present the Care Plan On-Line (CPOL) system, which provides intranet-based support for the SA HealthPlus Coordinated Care model for chronic disease management. We describe the interface design rationale of CPOL and its implementation framework, which is flexible and broadly applicable to support new health care models over intranets or the Internet

Characterization of the receptor binding sites of human leukemia inhibitory factor and creation of antagonists

Residues in human leukemia inhibitory factor (hLIF) crucial for binding to both the human LIF receptor (R) and gp130 were identified by analysis of alanine scanning mutants of hLIF in assays for both receptor binding and bioactivity. The region of hLIF most important for binding to the hLIF-R is composed of residues from the amino terminus of the D-helix, carboxyl terminus of the B-helix, and C-D loop. This site forms a distinct surface at the end of the four-helix bundle in the tertiary structure of the closely related murine LIF. The two residues of hLIF that contribute the majority of free energy for hLIF-R binding, Phe-156 and Lys-159 are surrounded by other residues which have only a moderate impact. This arrangement of a few key residues surrounded by less important ones is analogous to the functional binding epitope of human growth hormone for its receptor. A second region of hLIF that includes residues from the carboxyl terminus of the D-helix and A-B loop also had a weak influence on hLIF-R binding. Residues in hLIF from both the A- and C-helices are involved in binding the gp130 co-receptor. Abolition of the gp130 binding site in hLIF created antagonists of LIF action

Upward Three-Dimensional Grid Drawings of Graphs

A \emph{three-dimensional grid drawing} of a graph is a placement of the vertices at distinct points with integer coordinates, such that the straight line segments representing the edges do not cross. Our aim is to produce three-dimensional grid drawings with small bounding box volume. We prove that every $n$-vertex graph with bounded degeneracy has a three-dimensional grid drawing with $O(n^{3/2})$ volume. This is the broadest class of graphs admiting such drawings. A three-dimensional grid drawing of a directed graph is \emph{upward} if every arc points up in the z-direction. We prove that every directed acyclic graph has an upward three-dimensional grid drawing with $(n^3)$ volume, which is tight for the complete dag. The previous best upper bound was $O(n^4)$. Our main result is that every $c$-colourable directed acyclic graph ($c$ constant) has an upward three-dimensional grid drawing with $O(n^2)$ volume. This result matches the bound in the undirected case, and improves the best known bound from $O(n^3)$ for many classes of directed acyclic graphs, including planar, series parallel, and outerplanar

On Recognizing Transparent Objects in Domestic Environments Using Fusion of Multiple Sensor Modalities

Current object recognition methods fail on object sets that include both diffuse, reflective and transparent materials, although they are very common in domestic scenarios. We show that a combination of cues from multiple sensor modalities, including specular reflectance and unavailable depth information, allows us to capture a larger subset of household objects by extending a state of the art object recognition method. This leads to a significant increase in robustness of recognition over a larger set of commonly used objects.Comment: 12 page

SLoMo: automated site localization of modifications from ETD/ECD mass spectra

Recently, software has become available to automate localization of phosphorylation sites from CID data and to assign associated confidence scores. We present an algorithm, SLoMo (Site Localization of Modifications), which extends this capability to ETD/ECD mass spectra. Furthermore, SLoMo caters for both high and low resolution data and allows for site-localization of any UniMod post-translational modification. SLoMo accepts input data from a variety of formats (e.g., Sequest, OMSSA). We validate SLoMo with high and low resolution ETD, ECD, and CID data

User's guide for the Solar Backscattered Ultraviolet (SBUV) and the Total Ozone Mapping Spectrometer (TOMS) RUT-S and RUT-T data sets: October 31, 1978 to November 1, 1980

Raw data from the Solar Backscattered Ultrviolet/Total Ozone Mapping Spectrometer (SBUV/TOMS) Nimbus 7 operation are available on computer tape. These data are contained on two separate sets of RUTs (Raw Units Tapes) for SBUV and TOMS, labelled RUT-S and RUT-T respectively. The RUT-S and RUT-T tapes contain uncalibrated radiance and irradiance data, housekeeping data, wavelength and electronic calibration data, instrument field-of-view location and solar ephemeris information. These tapes also contain colocated cloud, terrain pressure and snow/ice thickness data, each derived from an independent source. The "RUT User's Guide" describes the SBUV and TOMS experiments, the instrument calibration and performance, operating schedules, and data coverage, and provides an assessment of RUT-S and -T data quality. It also provides detailed information on the data available on the computer tapes

Dating Methods and Techniques at the John Hallowes Site (44WM6): A Seventeenth-Century Example

The John Hallowes site (44WM6) in Westmoreland County, Virginia, was excavated between July 1968 and August 1969. No report of the excavations was completed at that time, although an article summarizing the findings was published in Historical Archaeology in 1971, dating the site’s occupation to the period from the 1680s to 1716. From 2010 to 2012, a systematic reanalysis of the site, features, history, and artifacts was conducted by archaeologists at the University of Tennessee, Knoxville. Benefiting from nearly 40 years of advances in Chesapeake archaeology, the reanalysis has challenged accepted dates for the site’s occupation, which is now placed at 1647–1681. In this article, we will discuss the multiple lines of evidence in support of the newly interpreted date range