Browsing by Subject "Characterization"

Now showing 1 - 3 of 3
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    Discovery of novel regulators of aldehyde dehydrogenase isoenzymes
    (2011-05-30) Ivanova, Yvelina Tsvetanova; Hurley, Thomas D., 1961-; Goebl, Mark G.; Srour, Edward F.
    Recent work has shown that specific ALDH isoenzymes can contribute to the underlying pathology of different diseases. Many ALDH isozymes are important in oxidizing reactive aldehydes resulting from lipid peroxidation, and, thus, help maintain cellular homeostasis. Increased expression and activity of ALDH isozymes are found in many human cancers and are often associated with poor prognosis. Therefore, the development of inhibitors of the different ALDH enzymes is of interest as means to treat some of these disease states. Here I describe the results of assays designed to characterize the site of interaction and the mode of inhibition for the unique compounds that function as inhibitors of aldehyde dehydrogenase 2 and determine their respective IC50 values with intent to develop structure-activity relationships for future development.
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    An International Cohort Study of Autosomal Dominant Tubulointerstitial Kidney Disease due to REN Mutations Identifies Distinct Clinical Subtypes
    (Elsevier, 2020-12) Živná, Martina; Kidd, Kendrah; Zaidan, Mohamad; Vyleťal, Petr; Barešová, Veronika; Hodaňová, Kateřina; Sovová, Jana; Hartmannová, Hana; Votruba, Miroslav; Trešlová, Helena; Jedličková, Ivana; Sikora, Jakub; Hůlková, Helena; Robins, Victoria; Hnízda, Aleš; Živný, Jan; Papagregoriou, Gregory; Mesnard, Laurent; Beck, Bodo B.; Wenzel, Andrea; Tory, Kálmán; Häeffner, Karsten; Wolf, Matthias T.F.; Bleyer, Michael E.; Sayer, John A.; Ong, Albert C.M.; Balogh, Lídia; Jakubowska, Anna; Łaszkiewicz, Agnieszka; Clissold, Rhian; Shaw-Smith, Charles; Munshi, Raj; Haws, Robert M.; Izzi, Claudia; Capelli, Irene; Santostefano, Marisa; Graziano, Claudio; Scolari, Francesco; Sussman, Amy; Trachtman, Howard; Decramer, Stephane; Matignon, Marie; Grimbert, Philippe; Shoemaker, Lawrence R.; Stavrou, Christoforos; Abdelwahed, Mayssa; Belghith, Neila; Sinclair, Matthew; Claes, Kathleen; Kopel, Tal; Moe, Sharon; Deltas, Constantinos; Knebelmann, Bertrand; Rampoldi, Luca; Kmoch, Stanislav; Bleyer, Anthony J.; Medicine, School of Medicine
    There have been few clinical or scientific reports of autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN), limiting characterization. To further study this, we formed an international cohort characterizing 111 individuals from 30 families with both clinical and laboratory findings. Sixty-nine individuals had a REN mutation in the signal peptide region (signal group), 27 in the prosegment (prosegment group), and 15 in the mature renin peptide (mature group). Signal group patients were most severely affected, presenting at a mean age of 19.7 years, with the prosegment group presenting at 22.4 years, and the mature group at 37 years. Anemia was present in childhood in 91% in the signal group, 69% prosegment, and none of the mature group. REN signal peptide mutations reduced hydrophobicity of the signal peptide, which is necessary for recognition and translocation across the endoplasmic reticulum, leading to aberrant delivery of preprorenin into the cytoplasm. REN mutations in the prosegment led to deposition of prorenin and renin in the endoplasmic reticulum-Golgi intermediate compartment and decreased prorenin secretion. Mutations in mature renin led to deposition of the mutant prorenin in the endoplasmic reticulum, similar to patients with ADTKD-UMOD, with a rate of progression to end stage kidney disease (63.6 years) that was significantly slower vs. the signal (53.1 years) and prosegment groups (50.8 years) (significant hazard ratio 0.367). Thus, clinical and laboratory studies revealed subtypes of ADTKD-REN that are pathophysiologically, diagnostically, and clinically distinct.
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    SRAM design leveraging material properties of exploratory transistors
    (Elsevier, 2022) Gopinath, Anoop; Cochran, Zachary; Ytterdal, Trond; Rizkalla, Maher; Electrical and Computer Engineering, Purdue School of Engineering and Technology
    While MOSFET miniaturization continues to face increased challenges related to process variations, supply voltage scaling and leakage currents, exploratory devices such as Graphene Nanoribbon Field Effect Transistors (GNRFET), Tunnel Field Effect Transistor (TFET), and Carbon Nanotube Field Effects Transistors (CNFET) could provide solutions for continued device scaling with better power/performance trade-offs. The GaN TFET used in this work is a heterojunction device, where the material properties of Ga and N result in a bandgap of 3.2eV and ultra-low IOFF current. Moreover, the properties of Ga and N result in a steep-switching device with a subthreshold swing of 30mV/decade. The structure of graphene material results in high conductivity of electrons, even at very high operating temperatures, making GNRFETs a high-performance device. However, graphene specific line-edge roughness can degrade performance, and thus process related variations can have a negative impact for GNRFETs. In CNFETs, the mobility and the velocity of the conducting carriers are functions of the carbon nanotube and the gate length. The length and the diameter of the carbon nanotube material adds parasitic capacitance and resistance to the model, contributing to slower speed of the device. In this paper, the impact on power, performance, and static noise margins (SNM) of the traditional single-port 6T-SRAM and modified single-port 8T-SRAMs designed using exploratory devices are analyzed with a set figure of merit (FOM), elucidating the material properties of the devices. The results obtained from this work show that GNRFET-based SRAM have very high performance with a worst-case memory access time of 27.7 ps for a 16x4-bit 4-word array while CNFET-based SRAM bitcell consume the lowest average power during read/write simulations at 3.84 µW, while TFET- based SRAM bitcell show the best overall average and static power consumption at 4.79 µW and 57.8 pW. A comparison of these exploratory devices with FinFET and planar CMOS showed that FinFET-based SRAM bitcell consumed the lowest static power at 39.8 pW and CMOS-based SRAM had the best read, write, and hold SNMs of 201 mV, 438 mV and 413 mV respectively.