Plasma-assisted ALD of LiPO(N) for solid state batteries

All solid state 3D batteries are pursued for their increased safety and high power capabilities. At present conformai coating of the solid electrolyte remains one of the key hurdles for the implementation of such devices. In the present work we investigate atomic layer deposition (ALD) as means of conformai deposition of lithium phosphate (Li3PO4) and nitrogen doped lithium phosphates (LiPON). These processes are characterized here to obtain the highest possible Li-ion conductivity. Li3PO4 is shown to yield a conductivity of 10-10 S/cm. On the other hand, an optimized LiPON process gave rise to a Li-ion conductivity of 510-7 S/cm. In addition, good conformality of the LiPON process was shown on high aspect ratio pillars. Furthermore, a solid state battery device was fabricated comprising a Li4Ti5O12 cathode, a 70 nm thick ALD LiPON solid electrolyte and a metallic lithium anode. The fabricated device is based on the thinnest solid electrolyte used so far as well as on the first ALD deposited solid electrolyte.</p

Collaboration: A Youth Development Initiative of the Faribault Youth Service Center.

Prepared in partnership with the Faribault Youth Service Center by the Community Assistantship Program (CAP) administered by the Center for Urban and Regional Affairs, University of Minnesota

Metabolic reprogramming of mammary epithelial cells during TGF-beta-induced epithelial-to-mesenchymal transition

The cytokine transforming growth factor-beta (TGF-beta) can induce normal breast epithelial cells to take on a mesenchymal phenotype, termed epithelial-to-mesenchymal transition (EMT). While the transcriptional and proteomic changes during TGF-beta-induced EMT have been described, the metabolic rewiring that occurs in epithelial cells undergoing EMT is not well understood. Here, we quantitively analyzed the TGF-beta-induced metabolic reprogramming during EMT of non-transformed NMuMG mouse mammary gland epithelial cells using nuclear magnetic resonance (NMR) spectroscopy. We found that TGF-beta elevates glycolytic and tricarboxylic acid (TCA)-cycle activity and increases glutaminolysis. Additionally, TGF-beta affects the hexosamine pathway, arginine-proline metabolism, the cellular redox state, and strongly affects choline metabolism during EMT. TGF-beta was found to induce phosphocholine production. A kinase inhibitor RSM-93A that inhibits choline kinase alpha (CHK alpha) mitigated TGF-beta-induced changes associated with EMT, i.e., increased filamentous (F)-actin stress fiber formation and N-Cadherin mesenchymal marker expression.Cancer Signaling networks and Molecular Therapeutic

Simulations of the effects of tin composition gradients on the superconducting properties of Nb3Sn conductors

In powder-in-tube (PIT) Nb3Sn composites, the A15 phase forms between a central tin-rich core and a coaxial Nb tube, thus causing the tin content and superconducting properties to vary with radius across the A15 layer. Since this geometry is also ideal for magnetic characterization of the superconducting properties with the field parallel to the tube axis, a system of concentric shells with varying tin content was used to simulate the superconducting properties, the overall severity of the Sn composition gradient being defined by an index N. Using well-known scaling relationships and property trends developed in an earlier experimental study, the critical current density for each shell was calculated, and from this the magnetic moment of each shell was found. By summing these moments, experimentally measured properties such as pinning-force curves and Kramer plots could be simulated. We found that different tin profiles have only a minor effect on the shape of Kramer plots, but a pronounced effect on the irreversibility fields defined by the extrapolation of Kramer plots. In fact, these extrapolated values H_K are very close to a weighted average of the superconducting properties across the layer for all N. The difference between H_K and the upper critical field commonly seen in experiments is a direct consequence of the different ways measurements probe the simulated Sn gradients. Sn gradients were found to be significantly deleterious to the critical current density Jc, since reductions to both the elementary pinning force and the flux pinning scaling field H_K compound the reduction in Jc. The simulations show that significant gains in Jc of Nb3Sn strands might be realized by circumventing strong compositional gradients of tin.Comment: 10 pages, 8 figures, 2 tables, submitted to J. Appl. Phy

Nonhuman primate adenoviruses of the human adenovirus B species are potent and broadly acting oncolytic vector candidates

The use of human adenoviruses (hAds) as oncolytic agents has demonstrated considerable potential. However, their efficacy in clinical studies is generally moderate and often varies between patients. This may, in part, be attributable to variable pre-existing neutralizing immunity in patients, which can impact the antitumor efficacy and lead to response heterogeneity. Our aim was to isolate new Ads for the development of oncolytic vectors with low prevalence of neutralizing immunity in the human population. To this end, we isolated a collection of new nonhuman primate (nhp) Ads from stool samples of four great ape species held captive. We elected 12 isolates comprising the broadest genetic variability for further characterization. For three new nhpAds, all classified as the human adenovirus B (HAdV-B) species, no neutralizing activity could be detected when exposed to a preparation of immunoglobulins isolated from a pool of >1,000 donors as a surrogate of population immunity. In addition, the nhpAds of the HAdV-B species showed enhanced oncolytic potency compared to nhpAds of the HAdV-C species as well as to human adenovirus type 5 (HAdV-C5) in vitro when tested in a panel of 29 human cancer cell lines. Next-generation sequencing of the viral genomes revealed higher sequence similarity between hAds and nhpAds of HAdV-B compared to HAdV-C, which might underlie the differences in oncolytic ability. As a proof-of-concept, the Rb-binding domain of the E1A protein of the gorilla-derived HAdV-B nhpAd-lumc007 was deleted, thereby creating a new oncolytic derivative, which demonstrated increased oncolytic potential compared to HAdV-C5. Collectively, our data demonstrate that nhpAds of the HAdV-B species can serve as an alternative for the development of potent oncolytic Ad vectors with limited pre-existing neutralizing immunity in humans.Therapeutic cell differentiatio

Redefining the role of FOXO in cancer

The highly conserved Forkhead Box O (FOXO) family of transcription factors are key regulators of cellular homeostasis, proliferation, apoptosis and lifespan. FOXO transcription factors function downstream of PI3K-PKB signaling as putative tumor suppressors by repressing cell proliferation as well as stimulating apoptosis and anoikis. Conversely, FOXOs can support tumorigenesis by maintaining cellular homeostasis, stimulating metastasis and regulating therapy resistance. In line with these conflicting properties, using FOXO levels or activity as prognostic markers for cancer patient disease progression yields contradictory results. Clearly FOXOs are involved in various aspects of cancer but it remains unclear if they function as tumor suppressors or supporters. Studies dedicated to clarifying the role of FOXO in cancer therefore are essential but lacking. In this thesis we aim to address if FOXOs are tumor suppressors or tumor supporters. We do so by characterizing conditional FOXO loss, over-expression and hyper-activation in a robust orthotopic transplantation model for mouse invasive lobular carcinoma (mILC). This system allows us to determine how different levels of FOXO expression and activity affects both tumor growth and metastasis. Our studies support that FOXO3 hyper-activation suppresses tumorigenesis but unveils that FOXO loss is more detrimental to tumor growth and the metastatic capacity of mILC. We show that FOXOs support tumorigenesis by regulating cell migration, providing anoikis resistance and maintaining cellular redox homeostasis and bioenergetics. Additionally, we find that FOXOs are key regulators of the PI3K-PKB signaling feedback loop that retains PI3K-PKB activity in cancer. Based on our results we conclude that instead of being tumor suppressors FOXOs are essential for tumorigenesis albeit FOXO activity needs to be carefully tuned for tumor growth and metastasis formation. Disruption of this balance can now be pursued as a promising strategy for cancer therapy