Albany Molecular Research (United States)

Abstract The development and expansion of wind energy is considered a key threat to bat populations in North America and globally. Several approaches to mitigating the impacts of wind energy development on bat populations have been developed, including curtailing wind turbine operation at night during lower wind speeds when bats are thought to be more active. Blanket curtailment approaches have shown substantial promise in reducing bat fatalities at wind energy facilities, but they also reduce the amount of energy extracted from the wind by turbines. A related approach, referred to as smart curtailment, uses bat activity and other variables to predict when bats will be at the greatest risk at a given wind facility. In some contexts, a smart curtailment approach might reduce bat fatalities while also reducing energy loss relative to blanket curtailment. However, it has not been clear how to compare blanket curtailment and smart curtailment approaches in terms of annual energy production at wind facilities. Here, we describe a new approach to simulating the influence of blanket and smart curtailment approaches on energy production at wind energy facilities, and demonstrate the approach using 6 wind energy development areas in the Canadian province of Alberta. We show how stakeholders involved can explore the potential influences of various kinds of bat activity on energy production. We present the results of our Alberta analysis and conclude with some caveats and recommendations for future work on simulating the influences of bat curtailment on energy production at wind energy facilities.

We show for the first time in hardware that in contrast to conventional stochastic gradient descent (SGD), our modified SGD algorithm (TTv2) together with a co-optimized ReRAM material achieves respectable accuracy (98%) on reduced MNIST classification (0 & 1), approaching a floating point (FP) baseline. To extrapolate these insights towards larger DNN training workloads in simulations, we establish an analog switching test sequence and extract key device statistics from 6T1R ReRAM arrays (up to 2k devices) built on a 14nm CMOS baseline. With this, we find that for larger DNN workloads, device and algorithm co-optimization shows dramatic improvements in comparison to standard SGD and baseline ReRAM. The gap to the reference floating-point accuracy across various tested DNNs indicates that further material and algorithmic optimizations are still needed. This work shows a pathway for scalable in-memory deep learning training using ReRAM crossbar arrays.

In this paper, the innovations in device design of the gate-all-around (GAA) nanosheet FET are reviewed. These innovations span enablement of multiple threshold voltages and bottom dielectric isolation in addition to impact of channel geometry on the overall device performance. Current scaling challenges for GAA nanosheet FETs are reviewed and discussed. Finally, an analysis of future innovations required to continue scaling nanosheet FETs and future technologies is discussed.

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 15, No. 8Microdystrophin Therapy Rescues Impaired Na Currents in Cardiac Purkinje Fibers From Dystrophin-Deficient Mdx Mice No AccessLetterRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessLetterRequest AccessFull TextMicrodystrophin Therapy Rescues Impaired Na Currents in Cardiac Purkinje Fibers From Dystrophin-Deficient Mdx Mice Janine Ebner, PhD, Xiufang Pan, PhD, Yongping Yue, BA, Spyridon Sideromenos, MSc, Jessica Marksteiner, MSc, Xaver Koenig, PhD, Karlheinz Hilber, PhD and Dongsheng Duan, PhD Janine EbnerJanine Ebner Department of Neurophysiology & Neuropharmacology, Center for Physiology & Pharmacology, Medical University of Vienna, Vienna, Austria (J.E., S.S., J.M., X.K., K.H.). *J. Ebner and X. Pan contributed equally as first authors. Search for more papers by this author , Xiufang PanXiufang Pan https://orcid.org/0000-0002-2594-5911 Department of Molecular Microbiology & Immunology (X.P., Y.Y., D.D.). *J. Ebner and X. Pan contributed equally as first authors. Search for more papers by this author , Yongping YueYongping Yue https://orcid.org/0000-0002-1640-2106 Department of Molecular Microbiology & Immunology (X.P., Y.Y., D.D.). Search for more papers by this author , Spyridon SideromenosSpyridon Sideromenos Department of Neurophysiology & Neuropharmacology, Center for Physiology & Pharmacology, Medical University of Vienna, Vienna, Austria (J.E., S.S., J.M., X.K., K.H.). Search for more papers by this author , Jessica MarksteinerJessica Marksteiner Department of Neurophysiology & Neuropharmacology, Center for Physiology & Pharmacology, Medical University of Vienna, Vienna, Austria (J.E., S.S., J.M., X.K., K.H.). Search for more papers by this author , Xaver KoenigXaver Koenig https://orcid.org/0000-0002-2423-4966 Department of Neurophysiology & Neuropharmacology, Center for Physiology & Pharmacology, Medical University of Vienna, Vienna, Austria (J.E., S.S., J.M., X.K., K.H.). Search for more papers by this author , Karlheinz HilberKarlheinz Hilber Correspondence to: Karlheinz Hilber, PhD, Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraße 17, 1090 Vienna, Austria. Email E-mail Address: [email protected] https://orcid.org/0000-0002-3033-0874 Department of Neurophysiology & Neuropharmacology, Center for Physiology & Pharmacology, Medical University of Vienna, Vienna, Austria (J.E., S.S., J.M., X.K., K.H.). Search for more papers by this author and Dongsheng DuanDongsheng Duan https://orcid.org/0000-0003-4109-1132 Department of Molecular Microbiology & Immunology (X.P., Y.Y., D.D.). Department of Neurology, Department of Biomedical Sciences, and Department of Biological & Chemical Engineering, The University of Missouri, Columbia, MO (D.D.). Search for more papers by this author Originally published2 Aug 2022https://doi.org/10.1161/CIRCEP.122.011161Circulation: Arrhythmia and Electrophysiology. 2022;15Footnotes*J. Ebner and X. Pan contributed equally as first authors.For Sources of Funding and Disclosures, see page 543.Correspondence to: Karlheinz Hilber, PhD, Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraße 17, 1090 Vienna, Austria. Email karlheinz.[email protected]ac.at

By focusing on food and a pervasive contaminant, this experiment engages student interest and effort while providing essential instruction and experience. As institutions are challenged by existing and emerging budgetary constraints, this experiment offers a determination approach employing commonly available instrumentation, the graphite furnace atomic absorption spectrometer. The module provides a broad range of experiences: it introduces the lyophilizer, offers practice in a multistep novel digestion method, presents the theoretical foundation and practical application of atomic absorption spectroscopy, and provides an opportunity to record, calculate, and report findings. Students whose math skills are in development can complete it successfully because algebraic calculations are used at each stage of the materials’ examination. Finally, when their reports align with extensive international research, the lab offers students assurance of their growing scientific competence.

Abstract Polo Like Kinase 1 (PLK1) is only expressed in dividing cells and plays a critical role in several stages of mitosis. PLK1 is highly expressed in tumors of various origins while its expression is largely absent in normal tissues. PLK1 inhibition selectively kills cancer cells because they are dependent on the mitotic functions of PLK1 overexpression. PLK1 consists of a highly conserved N-terminal catalytic kinase domain and a unique, functionally essential C-terminal Polo Box Domain (PBD). The PBD of each PLK is a phospho-peptide binding motif that determines substrate recognition and sub-cellular localization. PLK1 catalytic inhibitors have advanced to clinical trials but they inhibit other family members PLK2 and PLK3. An alternative approach to developing potent and selective PLK1 inhibitors is to allosterically target the PBD. An iterative strategy called REPLACE involving computational and synthetic approaches was utilized to generate fragment-ligated inhibitory peptides (FLIPs) by rationally replacing amino acid residues in two PLK1 substrate peptides with drug-like small molecule fragments to generate FLIPs. Further application of REPLACE resulted in non-peptidic compounds named abbapolins. Confirmation of engagement of cellular PLK1 by abbapolins was assessed using a cellular thermal shift assay (CETSA), which determines drug binding to target proteins by measuring the shift in a protein's solubility and hence its thermal stability. Abbapolins specifically bound to full-length cellular PLK1 over PLK3 as determined by CETSA in a pattern consistent with in vitro binding affinities to the purified PBD of PLK1 and PLK3. We made an additional unique observation that mitotic PLK1 had a lower thermal stability than non-mitotic PLK1, suggesting that mitotic PLK1 might adopt a different conformation that is less soluble in the CETSA assay. Moreover, we observed that ATP-based inhibitors decreased the thermal stability of mitotic PLK1, whereas PBD inhibitors abbapolins increased the thermal stability of mitotic PLK1 as measured by CETSA. Additional evidence for engagement of cellular PLK1 was obtained through the unique mechanistic observation that abbapolins induced a striking dose dependent reduction in PLK1 protein levels as measured by western blotting and immunofluorescence. The loss of PLK1 was partially due to proteasome mediated degradation because the proteasome inhibitor MG132 partially prevented PLK1 degradation. Moreover, abbapolins caused preferential loss of nuclear PLK1 as determined by cellular fractionation. The therapeutic potential of these compounds was indicated through their antiproliferative activity on a cell line expressing a PLK1 point mutant that is dramatically resistant to ATP competitive PLK1 inhibitors. Future studies will examine in vivo activity of selected abbapolins. Citation Format: Danda Chapagai, Guru Ramamoorthy, Merissa Baxter, Sandra Craig, Elmar Nurmemmedov, McInnes Campbell, Michael Wyatt. Converting high affinity peptides to non-peptidic inhibitors via REPLACE: Novel and new strategies in targeting PLK1 Polo Box Domain (PBD) for anti-cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1241.