Matrix modification for enhancing the transport properties of the human cartilage endplate to improve disc nutrition.

Poor solute transport through the cartilage endplate (CEP) impairs disc nutrition and could be a key factor that limits the success of intradiscal biologic therapies. Here we demonstrate that treating the CEP with matrix metalloproteinase-8 (MMP-8) reduces the matrix constituents that impede solute uptake and thereby improves nutrient diffusion. Human CEP tissues harvested from four fresh cadaveric lumbar spines (age range: 38-66 years old) were treated with MMP-8. Treatment caused a dose-dependent reduction in sGAG, localized reductions to the amount of collagen, and alterations to collagen structure. These matrix modifications corresponded with 16-24% increases in the uptake of a small solute (376 Da). Interestingly, the effects of MMP-8 treatment depended on the extent of non-enzymatic glycation: treated CEPs with high concentrations of advanced glycation end products (AGEs) exhibited the lowest uptake compared to treated CEPs with low concentrations of AGEs. Moreover, AGE concentrations were donor-specific, and the donor tissues with the highest AGE concentrations appeared to have lower uptake than would be expected based on the initial amounts of collagen and sGAG. Finally, increasing solute uptake in the CEP improved cell viability inside diffusion chambers, which supports the nutritional relevance of enhancing the transport properties of the CEP. Taken together, our results provide new insights and in vitro proof-of-concept for a treatment approach that could improve disc nutrition for biologic therapy: specifically, matrix reduction by MMP-8 can enhance solute uptake and nutrient diffusion through the CEP, and AGE concentration appears to be an important, patient-specific factor that influences the efficacy of this approach

The ROTSE-III Robotic Telescope System

The observation of a prompt optical flash from GRB990123 convincingly demonstrated the value of autonomous robotic telescope systems. Pursuing a program of rapid follow-up observations of gamma-ray bursts, the Robotic Optical Transient Search Experiment (ROTSE) has developed a next-generation instrument, ROTSE-III, that will continue the search for fast optical transients. The entire system was designed as an economical robotic facility to be installed at remote sites throughout the world. There are seven major system components: optics, optical tube assembly, CCD camera, telescope mount, enclosure, environmental sensing & protection and data acquisition. Each is described in turn in the hope that the techniques developed here will be useful in similar contexts elsewhere.Comment: 19 pages, including 4 figures. To be published in PASP in January, 2003. PASP Number IP02-11

Real bad grammar: realistic grammatical description with grammaticality

Sampson (this issue) argues for a concept of “realistic grammatical description” in which the distinction between grammatical and ungrammatical sentences is irrelevant. In this article I also argue for a concept of “realistic grammatical description” but one in which a binary distinction between grammatical and ungrammatical sentences is maintained. In distinguishing between the grammatical and ungrammatical, this kind of grammar differs from that proposed by Sampson, but it does share the important property that invented sentences have no role to play, either as positive or negative evidence

Statewide Survey of Skid Resistances of Pavements [Dec. 1976]

Since 1969, when a research-type, skid-test trailer was acquired, U.S. routes were surveyed in 1970 and 1971, and the interstate and toll road systems were surveyed in 1971. The data were used for research purposes and have been reported. The interstate and toll road systems were surveyed again for research purposes in 1974. Since October 1974, surveys have been performed under a highway safety project grant. All primary and principal secondary roads, involving 4,612 miles (7425 km), were surveyed in 1975. The 1974 and 1975 surveys, data reported herein, represented 25 percent of the mileage of rural, state-maintained roads in Kentucky and 75 percent of all traffic on rural, state-maintained roads. A second skid tester, survey-type, was acquired in April 1976; and survey-testing of major, rural collector roads continued during 1976. About 2 percent of the interstate mileage, about 19 percent of the primary mileage, and about 16 percent of the secondary mileage surveyed may be considered slippery. A small percentage of both state primary (3.7 percent) and state secondary (2.5 percent) roads were classified as very slippery. These pavement sections in particular should be flagged for deslicking. Trends and analysis of accidents on wet pavements from 1969 through 1975 are reported. Description and evaluation of the resurfacing program from the standpoint of deslicking of pavements is also presented. In addition, results of high-accident location testing and evaluation are included

Statewide Survey of Skid Resistances of Pavements (1976)

Statewide survey of skid resistance continued in 1976 with testing of rural, major, collector roads (1985 Functional Classification). This included 5,074 miles (8,166 km) of state secondary roads and 788 miles (1,268 km) of rural secondary roads. About 17 percent of the secondary mileage and about 15 percent of the rural secondary mileage surveyed in 1976 may be considered slippery. A small percentage of both secondary (5.3 percent) and rural secondary (5.8 percent) roads had an average skid number below 26. These sections, in particular, should be flagged for deslicking. Through 1976, 50 percent of the mileage of rural, state-maintained roads in Kentucky were surveyed. These roadways carried 93 percent of all traffic on rural, state-maintained roads

Engineering simulations for cancer systems biology

Computer simulation can be used to inform in vivo and in vitro experimentation, enabling rapid, low-cost hypothesis generation and directing experimental design in order to test those hypotheses. In this way, in silico models become a scientific instrument for investigation, and so should be developed to high standards, be carefully calibrated and their findings presented in such that they may be reproduced. Here, we outline a framework that supports developing simulations as scientific instruments, and we select cancer systems biology as an exemplar domain, with a particular focus on cellular signalling models. We consider the challenges of lack of data, incomplete knowledge and modelling in the context of a rapidly changing knowledge base. Our framework comprises a process to clearly separate scientific and engineering concerns in model and simulation development, and an argumentation approach to documenting models for rigorous way of recording assumptions and knowledge gaps. We propose interactive, dynamic visualisation tools to enable the biological community to interact with cellular signalling models directly for experimental design. There is a mismatch in scale between these cellular models and tissue structures that are affected by tumours, and bridging this gap requires substantial computational resource. We present concurrent programming as a technology to link scales without losing important details through model simplification. We discuss the value of combining this technology, interactive visualisation, argumentation and model separation to support development of multi-scale models that represent biologically plausible cells arranged in biologically plausible structures that model cell behaviour, interactions and response to therapeutic interventions