The age-related decline in intestinal lipid uptake is associated with a reduced abundance of fatty acid-binding protein

Aging is associated with changes in the absorptive capacity of the small intestine. We tested the hypotheses that (i) aging is associated with a decline in lipid absorption, and that (ii) this decreased lipid absorption is due to a decline in the abundance of mRNA and/or the enterocyte cytosolic intestinal FA-binding protein (I-FABP), the liver FA-binding protein (L-FABP), and the ileal lipid-binding protein (ILBP). In vitro uptake studies were performed on Fischer 344 rats at ages 1, 9, and 24 mon. Northern blotting (L-FABP, ILBP) and immunohistochemistry (I-FABP, ILBP) were performed. Aging was associated with decreased animal weights, but the surface area of the intestine was not significantly altered with age. The rates of ileal uptake of 16∶0, 18∶0, 18∶1, and 18∶2 were reduced by greater than 50% with aging when expressed on the basis of mucosal weight. This decline was not associated with reduced expression of mRNA for L-FABP or ILBP but was associated with a 50% decrease in the abundance of I-FABP and a 40% decrease in the abundance of ILBP. Thus, the decrease with aging in the ileal uptake of some FA when rates were expressed on the basis of mucosal weight was associated with a reduced abundance of I-FABP and ILBP.     

Brain-computer interface design for asynchronous control applications: improvements to the LF-ASD asynchronous brain switch

The low-frequency asynchronous switch design (LF-ASD) was introduced as a direct brain-computer interface (BCI) technology for asynchronous control applications. The LF-ASD operates as an asynchronous brain switch (ABS) which is activated only when a user intends control and maintains an inactive state output when the user is not meaning to control the device (i.e., they may be idle, thinking about a problem, or performing some other action). Results from LF-ASD evaluations have shown promise, although the reported error rates are too high for most practical applications. This paper presents the evaluation of four new LF-ASD designs with data collected from individuals with high-level spinal cord injuries and able-bodied subjects. These new designs incorporated electroencephalographic energy normalization and feature space dimensionality reduction. The error characteristics of the new ABS designs were significantly better than the LF-ASD design with true positive rate increases of approximately 33% for false positive rates in the range of 1%-2%. The results demonstrate that the dimensionality of the LF-ASD feature space can be reduced without performance degradation. The results also confirm previous findings that spinal cord-injured subjects can operate ABS designs to the same ability as able-bodied subjects.     

A unified modeling and solution framework for combinatorial optimization problems

Combinatorial optimization problems are often too complex to be solved within reasonable time limits by exact methods, in spite of the theoretical guarantee that such methods will ultimately obtain an optimal solution. Instead, heuristic methods, which do not offer a convergence guarantee, but which have greater flexibility to take advantage of special properties of the search space, are commonly a preferred alternative. The standard procedure is to craft a heuristic method to suit the particular characteristics of the problem at hand, exploiting to the extent possible the structure available. Such tailored methods, however, typically have limited usefulness in other problems domains.An alternative to this problem specific solution approach is a more general methodology that recasts a given problem into a common modeling format, permitting solutions to be derived by a common, rather than tailor-made, heuristic method. Because such general purpose heuristic approaches forego the opportunity to capitalize on domain-specific knowledge, they are characteristically unable to provide the effectiveness or efficiency of special purpose approaches. Indeed, they are typically regarded to have little value except for dealing with small or simple problems.This paper reports on recent work that calls this commonly held view into question. We describe how a particular unified modeling framework, coupled with latest advances in heuristic search methods, makes it possible to solve problems from a wide range of important model classes.Correspondence to: Gary A. Kochenberger.This research was supported in part by ONR grants N000140010598 and N000140310621.     

Quantitative 13C NMR analysis of sequence distributions in poly(ethylene-co-1-hexene)

Different 13C NMR methods of determining triad distributions in two poly(ethylene-co-1-hexene) copolymers are examined using high signal-to-noise ratio 13C NMR spectra of the copolymers dissolved in deuterated 1,2,4-trichlorobenzene at 398 K. This examination includes a comparison of three integration techniques. The experimental impact of decoupler sidebands and significantly nonequal 13C NOE values are examined. A least-squares regression analysis technique for solving for triad mole fractions is tested and appears to be more reliable than two published algebraic expressions (and other expressions examined in the work reported here). The resultant triad mole fractions are compared to sequence distribution parameters expected by Bernoullian and first-order Markovian statistical models. On the basis of 13C NMR-determined average reactivity ratios, the copolymer designated sample B (5.3 mol % 1-hexene) appears to be a Bernoullian copolymer resulting from a single-site catalytic system. The copolymer designated sample S (3.6 mol % 1-hexene overall) is better described as a mixture of polyethylene and a Bernoullian copolymer with 6.4 mol % 1-hexene content, and thus appears to result from a multisite catalytic system.     

Computer simulations of time-dependent suppression of EOF by polymer coatings

We use molecular dynamics simulations in order to investigate the time evolution of the effect of adsorbed polymer coatings on the electro-osmotic flow (EOF) in a capillary. Weakly adsorbed coatings show no time-dependent performance, but they do not strongly reduce the EOF. On the other hand, strongly adsorbed coatings made of longer polymer chains are often quenched in non-equilibrium conformations that can strongly reduce the EOF over extremely long periods of time. For intermediate adsorption strengths, we observe that the EOF increases as a function of time due to the relaxation of the coating layer. The concentration of polymers in solution and the length of the polymer chains also affect the time-dependence of the EOF. These results show that the quality of electrophoretic separations can depend on the waiting time between the formation of the coating and the beginning of the separation. We conclude by suggesting experimental tests of our predictions.     

Chromosomal instability and its relationship to other end points of genomic instability

Chromosomal destabilization is one end point of the more general phenomenon of genomic instability. We previously established that chromosomal instability can manifest in clones derived from single progenitor cells several generations after X-irradiation. To understand the potential relationship between chromosomal destabilization and the other end points of genomic instability, we generated a series of chromosomally stable and unstable clones by exposure to X-rays. All clones were derived from the human-hamster hybrid line GM10115, which contains a single copy of human chromosome 4 in a background of 20-24 hamster chromosomes. These clones were then subjected to a series of assays to determine whether chromosomal instability is associated with a general "mutator phenotype" and whether it modulates other end points of genomic instability. Thus, we analyzed clones for sister chromatid exchange, delayed reproductive cell death, delayed mutation, mismatch repair, and delayed gene amplification. Statistical analyses performed on each group of chromosomally stable and unstable clones indicated that, although individual clones within each group were significantly different from unirradiated clones for many of the end points, there was no significant correlation between chromosomal instability and sister chromatid exchange, delayed mutation, and mismatch repair. Delayed gene amplification was found to be marginally correlated to chromosomal instability (P < 0.1), and delayed reproductive cell death (the persistent reduction in plating efficiency after irradiation) was found to be significantly correlated (P < 0.05). These correlations may be explained by chromosomal destabilization, which can mediate gene amplification and can result in cellular lethality. These data implicate multiple molecular and genetic pathways leading to different manifestations of genomic instability in GM10115 cells surviving exposure to DNA-damaging agents.     

Vortex dynamics at the superfluid λ-transition

A vortex-ring theory of the superfluid⁴He -transition is extended to include the dynamics of the transition. The response of the vortices to an oscillating superflow is found by solving the Fokker-Planck equation. This allows a calculation of the superfluid relaxation time, which is in agreement with Landau-Khalatnikov theory and with dynamic scaling. At high frequencies the transition becomes broadened, with both the superfluid density and the dissipation remaining finite at and above T. Comparison is made to earlier theories that use high-temperature expansions and renormalization-group expansions. Applications to other subjects such as mutual friction, high-T_c superconductors, and rapidly quenched systems are briefly discussed.     

CLUSTEREASY: A program for lattice simulations of scalar fields in an expanding universe on parallel computing clusters

We describe an MPI C++ program that we have written and made available for calculating the evolution of interacting scalar fields in an expanding universe on parallel clusters. The program is a parallel programming extension of the simulation program LATTICEEASY. The ability to run these simulations on parallel clusters, however, greatly extends the range of scales and times that can be simulated. The program is particularly useful for the study of reheating and thermalization after inflation. The program and its full documentation are available on the Web at http://www.science.smith.edu/departments/Physics/fstaff/gfelder/latticeeasy/. In this paper we provide a brief overview of what the program does and what it is useful for.

Program summary

Program title: CLUSTEREASYCatalogue identifier: AEBJ_v1_0Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEBJ_v1_0.htmlProgram obtainable from: CPC Program Library, Queen's University, Belfast, N. IrelandLicensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.htmlNo. of lines in distributed program, including test data, etc.: 7469No. of bytes in distributed program, including test data, etc.: 613 334Distribution format: tar.gzProgramming language: C++/MPIComputer: Cluster. Must have the library FFTW installedOperating system: AnyRAM: Typically 4 MB to 1 GB per processorClassification: 1.9External routines: A single-precision version of the FFTW library (http://www.fftw.org/) must be available on the target machine.Nature of problem: After inflation the universe consisted of interacting fields in a high energy, nonthermal state [1]. The evolution of these fields cannot be described with standard approximation techniques such as linearization, kinetic theory, or Hartree expansion, and must thus be simulated numerically. Fortunately, the fields rapidly acquire large occupation numbers over a range of frequencies, so their evolution can be accurately modeled with classical field theory [2]. The specific fields and interactions relevant at these high energies are not known, so different models must be tested phenomenologically. In many cases, e.g., those involving symmetry breaking, the wide range of physical time and length scales in the problem requires parallel computing.Solution method: CLUSTEREASY solves the equations of motion for interacting scalar fields in an expanding universe. The user describes a particular theory by entering the field potential and its derivatives in a model file and the program then uses a staggered leapfrog method to evolve the field equations and Friedmann equation for the fields and the expansion of the universe. Different processors compute the evolution on subgrids defined by block decomposition, and the processors exchange edge data after each time step to allow for calculation of spatial derivatives.Restrictions: In its current form CLUSTEREASY only includes scalar fields and does not include metric perturbations. For 2D and 3D simulations the cluster must already have the (free) libraries FFTW installed.Additional comments: CLUSTEREASY is the parallel form of the program LATTICEEASY (AEAW_v1_0), Comp. Phys. Comm. 178 (2008) 929.Note: The default installation type for FFTW is double-precision so care must be taken to specify single-precision when running the “configure” file associated with the FFTW software package installation.Running time: The running time can range from minutes to weeks.References:[1] A.D. Linde, Particle Physics and Inflationary Cosmology, Harwood, Chur, Switzerland, 1990.[2] S. Khlebnikov, I. Tkachev, Phys. Rev. Lett. 77 (1996) 219, hep-ph/9603378.     

Doxorubicin eluting beads—2: methods for evaluating drug elution and in-vitro:in-vivo correlation

DC Bead™ is a sulfonate-modified, PVA-based microspherical embolisation agent approved for the treatment of hypervascular tumours and arterio-venous malformations. The beads have previously been shown to actively sequester oppositely charged drugs, such as doxorubicin hydrochloride (dox) by an ion-exchange mechanism. In order to characterise the release kinetics and predict the in vivo behaviour of drug eluting beads (DEB), two elution methods were utilised. The first, an application of the USP dissolution method Type II - Apparatus, enables study of the complete elution of loaded DC Bead in less than 4 h, allowing relatively rapid comparison to be made between different products and formulations. Release data obtained using this method were fitted to first order kinetics (R ² > 0.998) and the elution constants shown to increase with the total surface area of the beads exposed to the elution medium. Diffusion coefficients were calculated adopting the Fickian diffusion model, which predicted slow elution rates under physiological conditions. The second method involved the use of a T-Apparatus where the drug experiences an element of diffusion through a static environment. This method was developed to resemble the in vivo situation in embolisation procedures more closely. Slow release of dox from DC Bead with half-lives over 1,500 h were predicted for all size ranges using a slow release model. A strong linear relationship was found between the release data from T-Apparatus and pharmacokinetic data obtained from patients treated with DC Bead loaded with dox in transarterial chemoembolisation (TACE) procedures. These data indicated a Level A in vitro–in vivo correlation (IVIVC) for the first 24 h post embolisation. Both systems developed were automated and good reproducibility was obtained for all samples, demonstrating the usefulness of these elution techniques for product development and comparative testing.