The use of genes for performance enhancement: doping or therapy?

Recent biotechnological advances have permitted the manipulation of genetic sequences to treat several diseases in a process called gene therapy. However, the advance of gene therapy has opened the door to the possibility of using genetic manipulation (GM) to enhance athletic performance. In such ‘gene doping’, exogenous genetic sequences are inserted into a specific tissue, altering cellular gene activity or leading to the expression of a protein product. The exogenous genes most likely to be utilized for gene doping include erythropoietin (EPO), vascular endothelial growth factor (VEGF), insulin-like growth factor type 1 (IGF-1), myostatin antagonists, and endorphin. However, many other genes could also be used, such as those involved in glucose metabolic pathways. Because gene doping would be very difficult to detect, it is inherently very attractive for those involved in sports who are prepared to cheat. Moreover, the field of gene therapy is constantly and rapidly progressing, and this is likely to generate many new possibilities for gene doping. Thus, as part of the general fight against all forms of doping, it will be necessary to develop and continually improve means of detecting exogenous gene sequences (or their products) in athletes. Nevertheless, some bioethicists have argued for a liberal approach to gene doping

Analysis of dependence among size, rate and duration in internet flows

In this paper we examine rigorously the evidence for dependence among data size, transfer rate and duration in Internet flows. We emphasize two statistical approaches for studying dependence, including Pearson's correlation coefficient and the extremal dependence analysis method. We apply these methods to large data sets of packet traces from three networks. Our major results show that Pearson's correlation coefficients between size and duration are much smaller than one might expect. We also find that correlation coefficients between size and rate are generally small and can be strongly affected by applying thresholds to size or duration. Based on Transmission Control Protocol connection startup mechanisms, we argue that thresholds on size should be more useful than thresholds on duration in the analysis of correlations. Using extremal dependence analysis, we draw a similar conclusion, finding remarkable independence for extremal values of size and rate.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS268 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Use of altered-specificity binding Oct-4 suggests an absence of pluripotent cell-specific cofactor usage

Oct-4 is a POU domain transcription factor that is critical for maintaining pluripotency and for stem cell renewal. Previous studies suggest that transcription regulation by Oct-4 at particular enhancers requires the input of a postulated E1A-like cofactor that is specific to pluripotent cells. However, such studies have been limited to the use of enhancer elements that bind other POU-protein family members in addition to Oct-4, thus preventing a ‘clean’ assessment of any Oct-4:cofactor relationships. Other attempts to study Oct-4 functionality in a more ‘stand-alone’ situation target Oct-4 transactivation domains to DNA using heterologous binding domains, a methodology which is known to generate artificial data. To circumvent these issues, an altered-specificity binding Oct-4 (Oct-4RR) and accompanying binding site, which binds Oct-4RR only, were generated. This strategy has previously been shown to maintain Oct-1:cofactor interactions that are highly binding-site and protein/binding conformation specific. This system therefore allows a stand-alone study of Oct-4 function in pluripotent versus differentiated cells, without interference from endogenous POU factors and with minimal deviation from bound wild-type protein characteristics. Subsequently, it was demonstrated that Oct-4RR and the highly transactive regions of its N-terminus determined here, and its C-terminus, have the same transactivation profile in pluripotent and differentiated cells, thus providing strong evidence against the existence of such a pluripotent cell-specific Oct-4 cofactor

Theoretical study of the effect of an AlGaAs double heterostructure on metal-semiconductor-metal photodetector performance

The sizing and efficiency of an aircraft is largely determined by the performance of its high-lift system. Subsonic civil transports most often use deployable multi-element airfoils to achieve the maximum-lift requirements for landing, as well as the high lift-to-drag ratios for take-off. However, these systems produce very complex flow fields which are not fully understood by the scientific community. In order to compete in today's market place, aircraft manufacturers will have to design better high-lift systems. Therefore, a more thorough understanding of the flows associated with these systems is desired. Flight and wind-tunnel experiments have been conducted on NASA Langley's B737-100 research aircraft to obtain detailed full-scale flow measurements on a multi-element high-lift system at various flight conditions. As part of this effort, computational aerodynamic tools are being used to provide preliminary flow-field information for instrumentation development, and to provide additional insight during the data analysis and interpretation process. The purpose of this paper is to demonstrate the ability and usefulness of a three-dimensional low-order potentialflow solver, PMARC, by comparing computational results with data obtained from 1/8 scale wind-tunnel tests. Overall, correlation of experimental and computational data reveals that the panel method is able to predict reasonably well the pressures of the aircraft's multi-element wing at several spanwise stations. PMARC's versatility and usefulness is also demonstrated by accurately predicting inviscid threedimensional flow features for several intricate geometrical regions

Non-parabolic hydrodynamic formulations for the simulation of inhomogeneous semiconductor devices

Hydrodynamic models are becoming prevalent design tools for small scale devices and other devices in which high energy effects can dominate transport. Most current hydrodynamic models use a parabolic band approximation to obtain fairly simple conservation equations. Interest in accounting for band structure effects in hydrodynamic device simulation has begun to grow since parabolic models can not fully describe the transport in state of the art devices due to the distribution populating non-parabolic states within the band. This paper presents two different non-parabolic formulations of the hydrodynamic model suitable for the simulation of inhomogeneous semiconductor devices. The first formulation uses the Kane dispersion relationship (hk)(exp 2)/2m = W(1 + alpha(W)). The second formulation makes use of a power law ((hk)(exp 2)/2m = xW(sup y)) for the dispersion relation. Hydrodynamic models which use the first formulation rely on the binomial expansion to obtain moment equations with closed form coefficients. This limits the energy range over which the model is valid. The power law formulation readily produces closed form coefficients similar to those obtained using the parabolic band approximation. However, the fitting parameters (x,y) are only valid over a limited energy range. The physical significance of the band non-parabolicity is discussed as well as the advantages/disadvantages and approximations of the two non-parabolic models. A companion paper describes device simulations based on the three dispersion relationships: parabolic, Kane dispersion, and power low dispersion

Kinematic Orbits and the Structure of the Internal Space for Systems of Five or More Bodies

The internal space for a molecule, atom, or other n-body system can be conveniently parameterised by 3n-9 kinematic angles and three kinematic invariants. For a fixed set of kinematic invariants, the kinematic angles parameterise a subspace, called a kinematic orbit, of the n-body internal space. Building on an earlier analysis of the three- and four-body problems, we derive the form of these kinematic orbits (that is, their topology) for the general n-body problem. The case n=5 is studied in detail, along with the previously studied cases n=3,4.Comment: 38 pages, submitted to J. Phys.

Tomographic inversion for sediment parameters in shallow water

This article discusses inversions for bottom geoacoustic properties using broadband acoustic signals obtained from explosive sources. The experimental data used for the inversions are SUS charge explosions acquired on a vertical hydrophone array during the Shelf Break Primer Experiment conducted south of New England in the Middle Atlantic Bight in August 1996. The SUS signals were analyzed for their time-frequency behavior using wavelets. The group speed dispersion curves were obtained from the wavelet scalogram of the SUS signals. A genetic algorithm (GA) was used for the inversion of sound speeds in the water column and compressional wave speeds in the sediment layers. The variations in the sound speeds in the water column were represented using empirical orthogonal functions (EOFs). A range-independent normal mode routine was used to construct the replica fields corresponding to the parameters. Comparison of group speeds for modes 1 to 9 and for a range of frequencies 8 to 200 Hz was used to arrive at the best parameter fit. An efficient hybrid optimization scheme using the GA and a Levenberg–Marquardt algorithm is presented. Linear perturbation methods were also used to “fine tune” the inversions and to obtain resolution and variance estimates. Analysis was also done to compute the degree of convergence of each of the parameters by explicitly calculating the Hessian matrices numerically. A posteriori estimation of mean and covariance was also done to obtain error estimates. Group speeds for the inverted sound speed fields provide an excellent match to the experimental data. The inverted sediment compressional speed profile compares well with in situ measurements

Thin-film transducers for the detection and imaging of Brillouin oscillations in transmission on cultured cells

Mechanical imaging and characterisation of biological cells has been a subject of interest for the last twenty years. Ultrasonic imaging based on the scanning acoustic microscope (SAM) and mechanical probing have been extensively reported. Large acoustic attenuation at high frequencies and the use of conventional piezo-electric transducers limit the operational frequency of a SAM. This limitation results in lower resolution compared to an optical microscope. Direct mechanical probing in the form of applied stress by contacting probes causes stress to cells and exhibits poor depth resolution. More recently, laser ultrasound has been reported to detect ultrasound in the GHz range via Brillouin oscillations on biological cells. This technique offers a promising new high resolution acoustic cell imaging technique. In this work, we propose, design and apply a thin-film based opto-acoustic transducer for the detection in transmission of Brillouin oscillations on cells. The transducer is used to generate acoustic waves, protect the cells from laser radiation and enhance signal-to-noise ratio (SNR). Experimental traces are presented in water films as well as images of the Brillouin frequency of phantom and fixed 3T3 fibroblast cells