Gordon M. Turner

Subpicosecond carrier dynamics in low-temperature grown GaAs as measured by time-resolved terahertz spectroscopy

The transient photoconductivity in a 1 μm layer of low temperature grown GaAs (LT-GaAs) on a GaAs substrate was measured using time-resolved terahertz spectroscopy. When photoexcitation occurs at 400 nm we find a time-dependent mobility that increases from 400±100 to 1100±100 cm2 V−1 s−1 with a time constant of 2 ps. Photoexcitation at 800 nm produces a time-independent mobility of 3000±500 cm2 V−1 s−1. We determine the carrier lifetime in LT-GaAs to be 1.1 ± 0.1 ps.

Estrogen-related Receptor γ Is a Key Regulator of Muscle Mitochondrial Activity and Oxidative Capacity

Estrogen-related receptor γ (ERRγ) regulates the perinatal switch to oxidative metabolism in the myocardium. We wanted to understand the significance of induction of ERRγ expression in skeletal muscle by exercise. Muscle-specific VP16ERRγ transgenic mice demonstrated an increase in exercise capacity, mitochondrial enzyme activity, and enlarged mitochondria despite lower muscle weights. Furthermore, peak oxidative capacity was higher in the transgenics as compared with control littermates. In contrast, mice lacking one copy of ERRγ exhibited decreased exercise capacity and muscle mitochondrial function. Interestingly, we observed that increased ERRγ in muscle generates a gene expression profile that closely overlays that of red oxidative fiber-type muscle. We further demonstrated that a small molecule agonist of ERRβ/γ can increase mitochondrial function in mouse myotubes. Our data indicate that ERRγ plays an important role in causing a shift toward slow twitch muscle type and, concomitantly, a greater capacity for endurance exercise. Thus, the activation of this nuclear receptor provides a potential node for therapeutic intervention for diseases such as obesity, which is associated with reduced oxidative metabolism and a lower type I fiber content in skeletal muscle.

Coherent terahertz emission from ferromagnetic films excited by femtosecond laser pulses

It is shown that the laser induced ultrafast demagnetization of ferromagnetic films results in the emission of a terahertz electromagnetic pulse. This emission has been detected from Ni films using free-space electro-optic sampling. The radiated electric field E(t) is explained by Maxwell equations (radiation from a time dependent magnetic dipole), and is expected to be proportional to the second time derivative of the magnetization d2M/dt2, as measured in the far field. This technique opens appealing perspectives in the context of measuring and understanding the ultrafast spin dynamics as well as the interaction of electrons (both charge and spin) with electromagnetic fields.

Complete-angle projection diffuse optical tomography by use of early photons

We present the first, to our knowledge, experimental images of complex-shaped phantoms embedded in diffuse media by use of optical tomography. Imaging is based on a complete-angle projection tomographic technique that utilizes transmitted early photons. Results are contrasted with measurements obtained at later gates as well as pseudocontinuous-wave data. The scanning system developed employs noncontact illumination and detection technologies that allow for high spatial sampling of transmitted photons. Combining this system with complete-angle illumination is found to be an important strategy toward improved imaging performance, resulting in a better-posed inversion problem. The appropriateness of reconstruction algorithms similar to those employed in x-ray computed tomography are showcased, and suggestions for model improvements are provided.

Planar fluorescence imaging using normalized data

Fluorescence imaging of tissues has gained significant attention in recent years due to the emergence of appropriate reporter technologies that enable noninvasive sensing of molecular function in vivo. Two major approaches have been used so far for fluorescence molecular imaging, i.e., epi-illumination (reflectance) imaging and fluorescence molecular tomography. Transillumination is an alternative approach that has been employed for imaging tissues in the past and could be similarly beneficial for fluorescence molecular imaging. We investigate data normalization schemes in reflectance and transillumination mode and experimentally demonstrate that normalized transillumination offers significant advantages over planar reflectance imaging and over nonnormalized methods. Our observations, based on phantoms and on postmortem and in vivo mouse measurements display image quality improvement, superior depth sensitivity, and improved imaging accuracy over the nonnormalized methods examined. Normalized planar imaging retains implementation simplicity and could be used to improve on standard fluorescence reflectance imaging and as a simplified alternative to the more integrated and accurate tomographic methods.

Time-resolved imaging of optical coefficients through murine chest cavities

As small animal optical imaging and tomography are gaining popularity for interrogating functional and molecular events in vivo, it becomes increasingly necessary to gain knowledge of the optical properties of the species investigated to better understand and describe photon propagation through their tissues. To achieve characterization of the spatial variation of average optical properties through murine chest cavities, time- and spatially resolved measurements of femto-second laser pulse transmission are performed through mice using a high-speed gated image intensifier. Application of time-resolved diffusion theory for finite slab geometry is first confirmed on phantoms and then applied to in vivo measurements for spatially resolving and quantifying mouse optical properties. Photon transmission images through mouse chest cavities are further obtained at different time gates to visualize the spatial variation observed and confirm the optical coefficient patterns calculated.

Validation of in vivo fluorochrome concentrations measured using fluorescence molecular tomography

Fluorescence molecular tomography (FMT) has emerged as a means of quantitatively imaging fluorescent molecular probes in three dimensions in living systems. To assess the accuracy of FMT in vivo, translucent plastic tubes containing a turbid solution with a known concentration of Cy 5.5 fluorescent dye are constructed and implanted subcutaneously in nude mice, simulating the presence of a tumor accumulating a fluorescent molecular reporter. Comparisons between measurements of fluorescent tubes made before and after implantation demonstrate that the accuracy of FMT reported for homogeneous phantoms extends to the in vivo situation. The sensitivity of FMT to background fluorescence is tested by imaging fluorescent tubes in mice injected with Cy 5.5-labeled Annexin V. For small tube fluorochrome concentrations, the presence of background fluorescence results in increases in the reconstructed concentration. This phenomenon is counteracted by applying a simple subtraction correction to the measured fluorescence data. The effects of varying tumor photon absorption are simulated by imaging fluorescent tubes with varying ink concentrations, and are found to be minor. These findings demonstrate the in vivo quantitative accuracy of fluorescence tomography, and encourage further development of this imaging modality as well as application of FMT in molecular imaging studies using fluorescent reporters.

Small-molecule WNK inhibition regulates cardiovascular and renal function

The With-No-Lysine (K) (WNK) kinases play a critical role in blood pressure regulation and body fluid and electrolyte homeostasis. Herein, we introduce the first orally bioavailable pan-WNK-kinase inhibitor, WNK463, that exploits unique structural features of the WNK kinases for both affinity and kinase selectivity. In rodent models of hypertension, WNK463 affects blood pressure and body fluid and electro-lyte homeostasis, consistent with WNK-kinase-associated physiology and pathophysiology.

Electrical Impedance as a Novel Biomarker of Myotube Atrophy and Hypertrophy

Measuring myotube thickness is a physiological and unbiased approach for screening therapeutic compounds that prevent skeletal muscle atrophy or induce hypertrophy. However, an accurate cell thickness estimate is often quite challenging because of the extreme heterogeneity of the myotube cellular population and therefore the lack of a regular distribution of perturbed myotubes. Here the authors present a novel method to evaluate changes in myotube thickness via measuring cellular electrical impedance. They demonstrate that both qualitative and quantitative changes in electrical impedance as a function of cellular adhesion in real time correlate well with variation in myotube thickness caused by atrophy or hypertrophy agents. Conversely, pharmacologically blocking myotube hypertrophy prevents changes in electrical impedance. Thus, impedance can be used as a reliable and sensitive biomarker for myotube atrophy or hypertrophy. Application of this technique to drug screening might be beneficial in finding novel treatments preventing muscle atrophy and other diseases associated with any morphological change in cell shape.

Inversion with early photons.

Optical tomography using early photons can improve resolution and reduce the ill-posed nature of the inversion problem. In this work we use 360 degrees projection experimental data to investigate the inversion performance of three commonly used numerical inversion methods: the random algebraic reconstruction technique (rART), singular value decomposition (SVD), and the conjugate-gradient-type method LSQR. Results are contrasted to each other and the effects of different photon propagation models are also investigated. We find that all methods perform adequately given appropriate regularization parameters, and that an experimentally measured photon weight function yields superior results over two approximate weights that have been previously used.