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3. Prolonged voluntary wheel running reveals unique adaptations in mdx mice treated with microdystrophin constructs ± the nNOS-binding site

Author

Hamm, S. E., primary, Yuan, C., additional, McQueen, L. F., additional, Wallace, M. A., additional, Zhang, H., additional, Arora, A., additional, Garafalo, A. M., additional, McMillan, R. P., additional, Lawlor, M. W., additional, Prom, M. J., additional, Ott, E. M., additional, Yan, J., additional, Addington, A. K., additional, Morris, C. A., additional, Gonzalez, J. P., additional, and Grange, R. W., additional

Published
2023
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4. Prolonged voluntary wheel running reveals unique adaptations in mdx mice treated with microdystrophin constructs +/- the nNOS-binding site

Author

Hamm, S. E., Yuan, C., McQueen, L. F., Wallace, M. A., Zhang, H., Arora, A., Garafalo, A. M., McMillan, R. P., Lawlor, M. W., Prom, M. J., Ott, E. M., Yan, J., Addington, A. K., Morris, C. A., Gonzalez, J. P., Grange, R. W., Hamm, S. E., Yuan, C., McQueen, L. F., Wallace, M. A., Zhang, H., Arora, A., Garafalo, A. M., McMillan, R. P., Lawlor, M. W., Prom, M. J., Ott, E. M., Yan, J., Addington, A. K., Morris, C. A., Gonzalez, J. P., and Grange, R. W.

Abstract

We tested the effects of prolonged voluntary wheel running on the muscle function of mdx mice treated with one of two different microdystrophin constructs. At 7 weeks of age mdx mice were injected with a single dose of AAV9-CK8-microdystrophin with (gene therapy 1, GT1) or without (gene therapy 2, GT2) the nNOS-binding domain and were assigned to one of four gene therapy treated groups: mdxRGT1 (run, GT1), mdxGT1 (no run, GT1), or mdxRGT2 (run,GT2), mdxGT2 (no run, GT2). There were two mdx untreated groups injected with excipient: mdxR (run, no gene therapy) and mdx (no run, no gene therapy). A third no treatment group, Wildtype (WT) received no injection and did not run. mdxRGT1, mdxRGT2 and mdxR performed voluntary wheel running for 52 weeks; WT and remaining mdx groups were cage active. Robust expression of microdystrophin occurred in diaphragm, quadriceps, and heart muscles of all treated mice. Dystrophic muscle pathology was high in diaphragms of non-treated mdx and mdxR mice and improved in all treated groups. Endurance capacity was rescued by both voluntary wheel running and gene therapy alone, but their combination was most beneficial. All treated groups increased in vivo plantarflexor torque over both mdx and mdxR mice. mdx and mdxR mice displayed ∼3-fold lower diaphragm force and power compared to WT values. Treated groups demonstrated partial improvements in diaphragm force and power, with mdxRGT2 mice experiencing the greatest improvement at ∼60% of WT values. Evaluation of oxidative red quadriceps fibers revealed the greatest improvements in mitochondrial respiration in mdxRGT1 mice, reaching WT levels. Interestingly, mdxGT2 mice displayed diaphragm mitochondrial respiration values similar to WT but mdxRGT2 animals showed relative decreases compared to the no run group. Collectively, these data demonstrate that either microdystrophin construct combined with voluntary wheel running increased in vivo maximal muscle strength, power, and endurance. However

Published
2023

5. Millisecond Annealing for Semiconductor Device Applications

Author

Timans, P. J., Xing, G., Cibere, J., Hamm, S., McCoy, S., Hull, Robert, Series editor, Jagadish, Chennupati, Series editor, Osgood, Richard M., Series editor, Parisi, Jürgen, Series editor, Wang, Zhiming M., Series editor, Skorupa, Wolfgang, editor, and Schmidt, Heidemarie, editor

Published
2014
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8. Improving Markets and Marketing

Author

Mishev, P., Mihaylova, M., Young, N., Hughes, D., Hamm, S., Dinar, Ariel, editor, Zilberman, David, editor, Schmitz, Andrew, editor, Moulton, Kirby, editor, Buckwell, Allan, editor, and Davidova, Sofia, editor

Published
1994
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26. Rectifying organic junctions of molecular assemblies based on perylene ion salts.

Author

Hamm, S. and Wachtel, H.

Subjects
*SOLID state chemistry, *DIFFUSION, *PERYLENE, *IONS, *ELECTRON paramagnetic resonance
Abstract

Using a solid-state diffusion technique, conducting perylene radical ion salt films have been prepared with alkali ions (Na+ and K+) and antimony hexachloride (SbCl6-) as counter ions. The successful preparation of separate radical anion salt films and cation salt films, respectively, is proved by in situ absorption spectroscopy, conductivity measurements, and electron spin resonance. In contrast to comparatively weakly doped inorganic semiconductors, the ion salts have a high concentration of charge carriers of roughly one charge per molecular unit entailing correlation of the carriers. The sandwich structures consisting of both the cation salt layer and the anion salt layer, form an electrical junction comparable to the PIN-junctions (p-doped, intrinsic, n-doped) known from inorganic diodes. The rectifying ratio amounts up to 105:1 at ±0.5 V and the breakdown voltage in the reverse sense is -20 V at 300 K. © 1995 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Published
1995
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37. Delta(2)-oxazolines-1,3 and N-acylaziridines as potential proinsecticides of carboxylic acids. V. Direct thin-layer chromatography monitoring of the metabolism in locust tissues

Author

Beaufour, M., Cherton, J.C, Carlin-Sinclair, A, Hamm, S, Synthèse, interactions et réactivité en chimie organique et bioorganique (SIRCOB), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Insecticides, [SDV]Life Sciences [q-bio], Aziridines, Carboxylic Acids, Animals, Chromatography, Thin Layer, Grasshoppers, Oxazoles
Abstract

International audience; Modern thin-layer chromatography (TLC) was used for the evaluation of delta2-oxazolines-1,3 I and N-acylaziridine VII structures, as potential proinsecticides of carboxylic acids III. Thus the unmasking2 of the active principles III from delta2-oxazolines-1,3 Ia-c and N-acylaziridine VIIc was monitored by spotting aliquots directly onto RP-18 TLC plates, without any sample pretreatment during in vitro assays performed in concentrated locust tissues. To achieve a good separation of carboxylate IIIa from endogenous components of the tissues, a short preliminary development with methanol or ion-pairing was necessary. From UV-TLC chromatograms (densitograms) it appeared that in a phosphate buffer at pH 7.4, the oxazoline Ia with a C2 substituent devoid of alpha-ramification or alpha,beta-insaturation hydrolysed slowly into the corresponding beta-hydroxylamide VIa and intermediate aminoester Va. Significantly, locust mesenteron (or fat body) efficiently triggered the unmasking of IIIa, a transformation which corresponds to the expected proinsecticide behavior of Ia. Conducting TLC monitoring in the same locust tissues also revealed that the oxazolines Ib and Ic with an alpha-ramification and an alpha,beta-insaturation, respectively, cannot be considered as proinsecticides of the corresponding carboxylic acids IIIb and IIIc. In contrast, the N-acylaziridine VIIc appeared as a convenient proinsecticide structure for masking the carboxylic acid IIIc.

Published
2001
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38. Potential proinsecticides of fluorinated carboxylic acids and β-ethanolamines: IV. Evaluation of the Δ2-oxazoline-1,3 structure by 19F NMR monitoring of the in vitro metabolism in locust tissues

Author

Cherton, J.-C, Hamm, S, Hallé, J.-C, Menguy, L, Beaufour, M., Synthèse, interactions et réactivité en chimie organique et bioorganique (SIRCOB), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience; The enzymatic effect of locust tissues upon hydrolysis of the fluorinated Δ2-oxazoline-1,3 Ia was elucidated using 19F[1H] NMR monitoring.In a phosphate buffer at pH=7.4 (mean physiological pH of locust tissues), the substrate Ia hydrolyses slowly into the corresponding fluorinated hydroxylamide VIa.If diluted, locust haemolymph (12.5% in phosphate buffer) catalyses slightly this hydrolytic pathway, it overall triggers the unmasking of carboxylate IIIa, corresponding to the expected proinsecticide behaviour of Ia. This behaviour is spectacularly almost the unique reaction observed during in vitro assays in concentrated fat body and mesenteron. Inasmuch as β-hydroxylamide VIa is not hydrolysed into carboxylate IIIa during such conditions, it must be concluded that carboxylate formation exclusively results from hydration and hydrolysis of substrate Ia via the aminoester Va. The formation of this intermediate aminoester is demonstrated by complementary assays. The enzymes supposed to intervene are of the α-chymotrypsine type for the first step (hydration) and of the esterase type for subsequent hydrolysis of intermediate aminoester Va.Thus, this work constitutes the first example of a Δ2-oxazoline-1,3 structure exploited for elaborating proinsecticides of carboxylates III and/or β-ethanolamines II based on enzymatic activation in insects.

Published
2001
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43. Extended Point Defects in Crystalline Materials: Ge and Si

Author

Cowern, N. E. B., primary, Simdyankin, S., additional, Ahn, C., additional, Bennett, N. S., additional, Goss, J. P., additional, Hartmann, J.-M., additional, Pakfar, A., additional, Hamm, S., additional, Valentin, J., additional, Napolitani, E., additional, De Salvador, D., additional, Bruno, E., additional, and Mirabella, S., additional

Published
2013
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