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Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at five separate time points to characterize growth and development of the tumor. After 25 days, the final tumor volumes of

Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at five separate time points to characterize growth and development of the tumor. After 25 days, the final tumor volumes of the mice varied from 12 mm3 to 62 mm3, even though mice were inoculated from the same tumor cell line under carefully controlled conditions. We generated hypotheses to explore large variances in final tumor size and tested them with our simple reaction-diffusion model in both a 3-dimensional (3D) finite difference method and a 2-dimensional (2D) level set method. The parameters obtained from a best-fit procedure, designed to yield simulated tumors as close as possible to the observed ones, vary by an order of magnitude between the three mice analyzed in detail. These differences may reflect morphological and biological variability in tumor growth, as well as errors in the mathematical model, perhaps from an oversimplification of the tumor dynamics or nonidentifiability of parameters. Our results generate parameters that match other experimental in vitro and in vivo measurements. Additionally, we calculate wave speed, which matches with other rat and human measurements.

ContributorsRutter, Erica (Author) / Stepien, Tracy (Author) / Anderies, Barrett (Author) / Plasencia, Jonathan (Author) / Woolf, Eric C. (Author) / Scheck, Adrienne C. (Author) / Turner, Gregory H. (Author) / Liu, Qingwei (Author) / Frakes, David (Author) / Kodibagkar, Vikram (Author) / Kuang, Yang (Author) / Preul, Mark C. (Author) / Kostelich, Eric (Author) / College of Liberal Arts and Sciences (Contributor)
Created2017-05-31
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Description

Novel hydride chemistries are employed to deposit light-emitting Ge1-y Snyalloys with y ≤ 0.1 by Ultra-High Vacuum Chemical Vapor Deposition (UHV-CVD) on Ge-buffered Si wafers. The properties of the resultant materials are systematically compared with similar alloys grown directly on Si wafers. The fundamental difference between the two systems is a fivefold

Novel hydride chemistries are employed to deposit light-emitting Ge1-y Snyalloys with y ≤ 0.1 by Ultra-High Vacuum Chemical Vapor Deposition (UHV-CVD) on Ge-buffered Si wafers. The properties of the resultant materials are systematically compared with similar alloys grown directly on Si wafers. The fundamental difference between the two systems is a fivefold (and higher) decrease in lattice mismatch between film and virtual substrate, allowing direct integration of bulk-like crystals with planar surfaces and relatively low dislocation densities. For y ≤ 0.06, the CVD precursors used were digermane Ge2H6 and deuterated stannane SnD4. For y ≥ 0.06, the Ge precursor was changed to trigermane Ge3H8, whose higher reactivity enabled the fabrication of supersaturated samples with the target film parameters. In all cases, the Ge wafers were produced using tetragermane Ge4H10 as the Ge source. The photoluminescence intensity from Ge1-y Sny /Ge films is expected to increase relative to Ge1-y Sny /Si due to the less defected interface with the virtual substrate. However, while Ge1-y Sny /Si films are largely relaxed, a significant amount of compressive strain may be present in the Ge1-y Sny /Ge case. This compressive strain can reduce the emission intensity by increasing the separation between the direct and indirect edges. In this context, it is shown here that the proposed CVD approach to Ge1-y Sny /Ge makes it possible to approach film thicknesses of about 1  μm, for which the strain is mostly relaxed and the photoluminescence intensity increases by one order of magnitude relative to Ge1-y Sny /Si films. The observed strain relaxation is shown to be consistent with predictions from strain-relaxation models first developed for the Si1-x Gex /Si system. The defect structure and atomic distributions in the films are studied in detail using advanced electron-microscopy techniques, including aberration corrected STEM imaging and EELS mapping of the average diamond–cubic lattice.

ContributorsSenaratne, Charutha Lasitha (Author) / Gallagher, J. D. (Author) / Jiang, Liying (Author) / Aoki, Toshihiro (Author) / Smith, David (Author) / Menéndez, Jose (Author) / Kouvetakis, John (Author) / Department of Chemistry and Biochemistry (Contributor)
Created2014-10-07
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Description

The emission properties of GeSn heterostructure pin diodes have been investigated. The devices contain thick (400–600 nm) Ge1-y Sny i-layers spanning a broad compositional range below and above the crossover Sn concentration yc where the Ge1-y Sny alloy becomes a direct-gap material. These results are made possible by an optimized device

The emission properties of GeSn heterostructure pin diodes have been investigated. The devices contain thick (400–600 nm) Ge1-y Sny i-layers spanning a broad compositional range below and above the crossover Sn concentration yc where the Ge1-y Sny alloy becomes a direct-gap material. These results are made possible by an optimized device architecture containing a single defected interface thereby mitigating the deleterious effects of mismatch-induced defects. The observed emission intensities as a function of composition show the contributions from two separate trends: an increase in direct gap emission as the Sn concentration is increased, as expected from the reduction and eventual reversal of the separation between the direct and indirect edges, and a parallel increase in non-radiative recombination when the mismatch strains between the structure components is partially relaxed by the generation of misfit dislocations. An estimation of recombination times based on the observed electroluminescence intensities is found to be strongly correlated with the reverse-bias dark current measured in the same devices.

ContributorsGallagher, J. D. (Author) / Senaratne, Charutha Lasitha (Author) / Sims, Patrick (Author) / Aoki, Toshihiro (Author) / Menéndez, Jose (Author) / Kouvetakis, John (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-03-02
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Description

The development of non-volatile logic through direct coupling of spontaneous ferroelectric polarization with semiconductor charge carriers is nontrivial, with many issues, including epitaxial ferroelectric growth, demonstration of ferroelectric switching and measurable semiconductor modulation. Here we report a true ferroelectric field effect—carrier density modulation in an underlying Ge(001) substrate by switching

The development of non-volatile logic through direct coupling of spontaneous ferroelectric polarization with semiconductor charge carriers is nontrivial, with many issues, including epitaxial ferroelectric growth, demonstration of ferroelectric switching and measurable semiconductor modulation. Here we report a true ferroelectric field effect—carrier density modulation in an underlying Ge(001) substrate by switching of the ferroelectric polarization in epitaxial c-axis-oriented BaTiO3 grown by molecular beam epitaxy. Using the density functional theory, we demonstrate that switching of BaTiO3 polarization results in a large electric potential change in Ge. Aberration-corrected electron microscopy confirms BaTiO3 tetragonality and the absence of any low-permittivity interlayer at the interface with Ge. The non-volatile, switchable nature of the single-domain out-of-plane ferroelectric polarization of BaTiO3 is confirmed using piezoelectric force microscopy. The effect of the polarization switching on the conductivity of the underlying Ge is measured using microwave impedance microscopy, clearly demonstrating a ferroelectric field effect.

ContributorsPonath, Patrick (Author) / Fredrickson, Kurt (Author) / Posadas, Agham B. (Author) / Ren, Yuan (Author) / Wu, Xiaoyu (Author) / Vasudevan, Rama K. (Author) / Okatan, M. Baris (Author) / Jesse, S. (Author) / Aoki, Toshihiro (Author) / McCartney, Martha (Author) / Smith, David (Author) / Kalinin, Sergei V. (Author) / Lai, Keji (Author) / Demkov, Alexander A. (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-01-01
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Description

The compositional dependence of the lowest direct and indirect band gaps in Ge1-ySny alloys has been determined from room-temperature photoluminescence measurements. This technique is particularly attractive for a comparison of the two transitions because distinct features in the spectra can be associated with the direct and indirect gaps. However, detailed

The compositional dependence of the lowest direct and indirect band gaps in Ge1-ySny alloys has been determined from room-temperature photoluminescence measurements. This technique is particularly attractive for a comparison of the two transitions because distinct features in the spectra can be associated with the direct and indirect gaps. However, detailed modeling of these room temperature spectra is required to extract the band gap values with the high accuracy required to determine the Sn concentration yc at which the alloy becomes a direct gap semiconductor. For the direct gap, this is accomplished using a microscopic model that allows the determination of direct gap energies with meV accuracy. For the indirect gap, it is shown that current theoretical models are inadequate to describe the emission properties of systems with close indirect and direct transitions. Accordingly, an ad hoc procedure is used to extract the indirect gap energies from the data. For y < 0.1 the resulting direct gap compositional dependence is given by ΔE0 = −(3.57 ± 0.06)y (in eV). For the indirect gap, the corresponding expression is ΔEind = −(1.64 ± 0.10)y (in eV). If a quadratic function of composition is used to express the two transition energies over the entire compositional range 0 ≤ y ≤ 1, the quadratic (bowing) coefficients are found to be b0 = 2.46 ± 0.06 eV (for E0) and bind = 1.03 ± 0.11 eV (for Eind). These results imply a crossover concentration yc = $0.073 [+0.007 over -0.006], much lower than early theoretical predictions based on the virtual crystal approximation, but in better agreement with predictions based on large atomic supercells.

ContributorsJiang, L. (Author) / Gallagher, J. D. (Author) / Senaratne, Charutha Lasitha (Author) / Aoki, Toshihiro (Author) / Mathews, J. (Author) / Kouvetakis, John (Author) / Menéndez, Jose (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-11-01
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Description

Background: The Nike + Fuelband is a commercially available, wrist-worn accelerometer used to track physical activity energy expenditure (PAEE) during exercise. However, validation studies assessing the accuracy of this device for estimating PAEE are lacking. Therefore, this study examined the validity and reliability of the Nike + Fuelband for estimating PAEE during physical activity in

Background: The Nike + Fuelband is a commercially available, wrist-worn accelerometer used to track physical activity energy expenditure (PAEE) during exercise. However, validation studies assessing the accuracy of this device for estimating PAEE are lacking. Therefore, this study examined the validity and reliability of the Nike + Fuelband for estimating PAEE during physical activity in young adults. Secondarily, we compared PAEE estimation of the Nike + Fuelband with the previously validated SenseWear Armband (SWA).

Methods: Twenty-four participants (n = 24) completed two, 60-min semi-structured routines consisting of sedentary/light-intensity, moderate-intensity, and vigorous-intensity physical activity. Participants wore a Nike + Fuelband and SWA, while oxygen uptake was measured continuously with an Oxycon Mobile (OM) metabolic measurement system (criterion).

Results: The Nike + Fuelband (ICC = 0.77) and SWA (ICC = 0.61) both demonstrated moderate to good validity. PAEE estimates provided by the Nike + Fuelband (246 ± 67 kcal) and SWA (238 ± 57 kcal) were not statistically different than OM (243 ± 67 kcal). Both devices also displayed similar mean absolute percent errors for PAEE estimates (Nike + Fuelband = 16 ± 13 %; SWA = 18 ± 18 %). Test-retest reliability for PAEE indicated good stability for Nike + Fuelband (ICC = 0.96) and SWA (ICC = 0.90).

Conclusion: The Nike + Fuelband provided valid and reliable estimates of PAEE, that are similar to the previously validated SWA, during a routine that included approximately equal amounts of sedentary/light-, moderate- and vigorous-intensity physical activity.

ContributorsTucker, Wesley (Author) / Bhammar, Dharini M. (Author) / Sawyer, Brandon J. (Author) / Buman, Matthew (Author) / Gaesser, Glenn (Author) / College of Health Solutions (Contributor)
Created2015-06-30
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Description

Background: Little research has explored who responds better to an automated vs. human advisor for health behaviors in general, and for physical activity (PA) promotion in particular. The purpose of this study was to explore baseline factors (i.e., demographics, motivation, interpersonal style, and external resources) that moderate intervention efficacy delivered by

Background: Little research has explored who responds better to an automated vs. human advisor for health behaviors in general, and for physical activity (PA) promotion in particular. The purpose of this study was to explore baseline factors (i.e., demographics, motivation, interpersonal style, and external resources) that moderate intervention efficacy delivered by either a human or automated advisor.

Methods: Data were from the CHAT Trial, a 12-month randomized controlled trial to increase PA among underactive older adults (full trial N = 218) via a human advisor or automated interactive voice response advisor. Trial results indicated significant increases in PA in both interventions by 12 months that were maintained at 18-months. Regression was used to explore moderation of the two interventions.

Results: Results indicated amotivation (i.e., lack of intent in PA) moderated 12-month PA (d = 0.55, p < 0.01) and private self-consciousness (i.e., tendency to attune to one’s own inner thoughts and emotions) moderated 18-month PA (d = 0.34, p < 0.05) but a variety of other factors (e.g., demographics) did not (p > 0.12).

Conclusions: Results provide preliminary evidence for generating hypotheses about pathways for supporting later clinical decision-making with regard to the use of either human- vs. computer-delivered interventions for PA promotion.

ContributorsHekler, Eric (Author) / Buman, Matthew (Author) / Otten, Jennifer (Author) / Castro, Cynthia (Author) / Grieco, Lauren (Author) / Marcus, Bess (Author) / Friedman, Robert H. (Author) / Napolitano, Melissa A. (Author) / King, Abby C. (Author) / College of Health Solutions (Contributor)
Created2013-09-22
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Description

The Ni/NiO core/shell structure is one of the most efficient co-catalysts for solar water splitting when coupled with suitable semiconducting oxides. It has been shown that pretreated Ni/NiO core/shell structures are more active than pure Ni metal, pure NiO or mixed dispersion of Ni metal and NiO nanoparticles. However, Ni/NiO

The Ni/NiO core/shell structure is one of the most efficient co-catalysts for solar water splitting when coupled with suitable semiconducting oxides. It has been shown that pretreated Ni/NiO core/shell structures are more active than pure Ni metal, pure NiO or mixed dispersion of Ni metal and NiO nanoparticles. However, Ni/NiO core/shell structures on TiO2 are only able to generate H2 but not O2 in aqueous water. The nature of the hydrogen evolution reaction in these systems was investigated by correlating photochemical H2 production with atomic resolution structure determined with aberration corrected electron microscopy. It was found that the core/shell structure plays an important role for H2 generation but the system undergoes deactivation due to a loss of metallic Ni. During the H2 evolution reaction, the metal core initially formed partial voids which grew and eventually all the Ni diffused out of the core-shell into solution leaving an inactive hollow NiO void structure. The H2 evolution was generated by a photochemical reaction involving photocorrosion of Ni metal.

ContributorsCrozier, Peter (Author) / Zhang, Liuxian (Author) / Aoki, Toshihiro (Author) / Liu, Qianlang (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015
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Description

Introduction: The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC) is a nutritionally complete, commercially available 4∶1 (fat∶ carbohydrate+protein) ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis

Introduction: The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC) is a nutritionally complete, commercially available 4∶1 (fat∶ carbohydrate+protein) ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas.

Methods: We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD) or KC. The mice received 2×4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging.

Results: Animals fed KC had elevated levels of β-hydroxybutyrate (p = 0.0173) and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001). Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days.

Conclusions: KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.

ContributorsAbdelwahab, Mohammed G. (Author) / Fenton, Kathryn E. (Author) / Preul, Mark C. (Author) / Rho, Jong M. (Author) / Lynch, Andrew (Author) / Stafford, Phillip (Author) / Scheck, Adrienne C. (Author) / Biodesign Institute (Contributor)
Created2012-05-01
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Description

Background: The successful treatment of malignant gliomas remains a challenge despite the current standard of care, which consists of surgery, radiation and temozolomide. Advances in the survival of brain cancer patients require the design of new therapeutic approaches that take advantage of common phenotypes such as the altered metabolism found in

Background: The successful treatment of malignant gliomas remains a challenge despite the current standard of care, which consists of surgery, radiation and temozolomide. Advances in the survival of brain cancer patients require the design of new therapeutic approaches that take advantage of common phenotypes such as the altered metabolism found in cancer cells. It has therefore been postulated that the high-fat, low-carbohydrate, adequate protein ketogenic diet (KD) may be useful in the treatment of brain tumors. We have demonstrated that the KD enhances survival and potentiates standard therapy in a mouse model of malignant glioma, yet the mechanisms are not fully understood.

Methods: To explore the effects of the KD on various aspects of tumor growth and progression, we used the immunocompetent, syngeneic GL261-Luc2 mouse model of malignant glioma.

Results: Tumors from animals maintained on KD showed reduced expression of the hypoxia marker carbonic anhydrase 9, hypoxia inducible factor 1-alpha, and decreased activation of nuclear factor kappa B. Additionally, tumors from animals maintained on KD had reduced tumor microvasculature and decreased expression of vascular endothelial growth factor receptor 2, matrix metalloproteinase-2 and vimentin. Peritumoral edema was significantly reduced in animals fed the KD and protein analyses showed altered expression of zona occludens-1 and aquaporin-4.

Conclusions: The KD directly or indirectly alters the expression of several proteins involved in malignant progression and may be a useful tool for the treatment of gliomas.

ContributorsWoolf, Eric (Author) / Curley, Kara L. (Author) / Liu, Qingwei (Author) / Turner, Gregory H. (Author) / Charlton, Julie A. (Author) / Preul, Mark C. (Author) / Scheck, Adrienne C. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-06-17