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Journal articles on the topic 'AT901'

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Published: 4 June 2021
Last updated: 14 February 2022

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1

Theissen, Nikolas Alexander, Monica Katherine Gonzalez, Asier Barrios, and Andreas Archenti. "Quasi-Static Compliance Calibration of Serial Articulated Industrial Manipulators." International Journal of Automation Technology 15, no. 5 (September 5, 2021): 590–98. http://dx.doi.org/10.20965/ijat.2021.p0590.

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This article presents a procedure for the quasi-static compliance calibration of serial articulated industrial manipulators. Quasi-static compliance refers to the apparent stiffness displayed by manipulators at low-velocity movements, i.e., from 50 to 250 mm/s. The novelty of the quasi-static compliance calibration procedure lies in the measurement phase, in which the quasi-static deflections of the manipulator’s end effector are measured under movement along a circular trajectory. The quasi-static stiffness might be a more applicable model parameter, i.e., representing the actual manipulator more accurately, for manipulators at low-velocity movements. This indicates that the quasi-static robot model may yield more accurate estimates for the trajectory optimization compared with static stiffness in the implementation phase. This study compares the static and apparent quasi-static compliance. The static deflections were measured at discretized static configurations along circular trajectories, whereas the quasi-static deflections were measured under circular motion along the same trajectories. Loads of different magnitudes were induced using the Loaded Double Ball Bar. The static and quasi-static displacements were measured using a linear variable differential transformer embedded in the Loaded Double Ball Bar and a Leica AT901 laser tracker. These measurement procedures are implemented in a case study on a large serial articulated industrial manipulator in five different positions of its workspace. This study shows that the measured quasi-static deflections are bigger than the measured static deflections. This, in turn, indicates a significant difference between the static and apparent quasi-static compliance. Finally, the implementation of the model parameters to improve the accuracy of robots and the challenges in realizing cost-efficient compliance calibration are discussed.
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2

Peng, You-Wel, and Dominic Man-Kit lam. "Organization and development of horizontal cells in the goldfish retina, I: The use of monoclonal antibody AT101." Visual Neuroscience 6, no. 4 (April 1991): 357–70. http://dx.doi.org/10.1017/s0952523800006581.

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AbstractWe have produced and characterized a monoclonal antibody, AT101, which selectively labels both viable and formaldehyde-fixed horizontal cell axon terminals, but not their somas or axons, of the goldfish (Carassius auratus) retina. The antigen recognized by AT101 appears to be a cell surface glycoprotein with a molecular weight of about 35,000 Daltons, and is present exclusively or predominantly in nervous tissues of all vertebrate species examined. We have used AT101 as a probe to analyze immunocytochemically the organization of horizontal cell axon terminals (HCATs) in the adult goldfish retina, and the emergence and maturation of these terminals during retinal development. Because of continued growth at the retinal margin in adult goldfish, there is a peripheral-to-central gradient in the age of cells, with the most mature in the center and the youngest in the periphery. In the center and near periphery of the adult retina, HCATs have a fusiform morphology and form a dense network in the middle and proximal part of the inner nuclear layer. In the far peripheral retina, the axon terminals appear round or ellipsoid. The retina closest to the retinal margin is devoid of AT101 staining, indicating that either HCATs are absent or the antigen recognized by AT101 is not present on HCATs at this stage. A similar sequence of changes in staining pattern is seen during development. Although AT101 staining can first be demonstrated in the larval retina at 1 month after hatching, it appears mostly as punctate structures. At a later stage, there are round or ellipsoid structures that resemble in morphology and location (in the inner nuclear layer) those found in the far peripheral adult retina. Double-labeling experiments with AT101 and antiserum against tubulin also indicate that AT101 labels the HCATs when they first appear during development. These data suggest that the emergence and maturation of HCAT is a late event in retinal development.
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Caylioglu, Deniz, Rieke Johanna Meyer, Dana Hellmold, Carolin Kubelt, Michael Synowitz, and Janka Held-Feindt. "Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche." International Journal of Molecular Sciences 22, no. 7 (March 30, 2021): 3606. http://dx.doi.org/10.3390/ijms22073606.

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Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences.
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Prada, Carlos E., Januario E. Castro, Dayong Zhai, Shinichi Kitada, John C. Reed, and Thomas J. Kipps. "R-(−)-Gossypol (AT101) Binds to Bcl-2 Family Proteins and Induces Apoptosis in CLL." Blood 106, no. 11 (November 16, 2005): 2978. http://dx.doi.org/10.1182/blood.v106.11.2978.2978.

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Abstract Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of monoclonal B cells in the blood, secondary lymphoid tissues, and marrow. The leukemia cells primarily are arrested in the G0/G1 phase of the cell cycle and appear resistant to programmed cell death. Several anti-apoptotic proteins are over expressed in CLL and this correlates with resistance to treatment, disease progression and overall poor prognosis. Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L), Bcl-2, and Mcl-1, are overexpressed in many cancers including CLL and contribute to tumour initiation, progression and resistance to therapy. Mcl-1 is of particular interest because this molecule appears to be regulated by Nurse-like Cells and other stromal cells that promote survival of CLL cells in vitro and very likely also in vivo. These proteins enhance the resistance of CLL cells to spontaneous and/or drug-induced apoptosis primarily by interacting with, and antagonizing the activity of mitochondria membrane pro-apoptotic proteins such as Bax and Bak. The protein-protein interaction of Bcl-2 family members is critical for their activity, and these interactions are governed by binding to the BH3 domain. Racemic gossypol is found in cotton seeds and has been studied as a cytotoxic agent in cancer cell lines and in clinical studies in patients with a large variety of cancers. The antitumor activity of racemic gossypol appears to reside principally in the R-(−)-enantiomer (AT101), with reduced activity observed for the S-(+)-enantiomer. AT101 is an antagonist of the BH3-binding groove of the Bcl-2 family of proteins that can inhibit the interactions of these proteins with pro-apoptotic molecules. We examined whether AT101 could induce apoptosis in Chronic Lymphocytic Leukemia (CLL) and its ability to bind in vitro anti-apoptotic molecules from the Bcl-2 family. Using a Fluorescence Polarization Assay (FPA) we studied the competitive binding affinity of AT101 to Bcl-2 family member proteins. We observed that both, racemic gossypol and AT101 had comparable affinity for Bck-2, Bcl-B, Bfl-1 with EC50=0.6 to 10 μM range. AT101 had a stronger binding affinity to Bcl-X(L) (EC50=0.998 μM vs. 3.084 μM for racemic gossypol), and to Mcl-1 (EC50= 0.52μM vs. 1.07μM for racemic gossypol). CLL cells were incubated with AT101 for 48 hrs at different concentrations. We observed that leukemia cells were induced to undergo apoptosis in a time and dose dependent manner and that this effect was independent of ZAP-70 expression or IgVH gene mutational status (IC50= 2μM). Cells undergoing apoptosis showed PARP-1 cleavage and upregulation of pro-apoptotic molecules such as Bid, p53, as well as downregulation of Mcl-1. These results indicate that AT101 has stronger pan-specific binding affinity for Bcl-2 family proteins than racemic gossypol, in particular to Mcl-1 and Bcl-X(L), and that this compound induces apoptosis in CLL B cells independently of ZAP-70 expression or IgVH gene mutational status. Because of these encouraging results a clinical trial using AT101 in CLL patients with high-risk features is currently open at our institution.
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5

Ibrahim, N. B., Ftema W. Aldbea, and Mustaffa Hj Abdullah. "Effects of Annealing Temperature on Structure and Magnetic Properties ofTbxY3−xFe5O12(x=0.2and 0.4) Thin Films." Journal of Nanomaterials 2012 (2012): 1–5. http://dx.doi.org/10.1155/2012/154192.

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Terbium-substituted yttrium iron garnet (TbxY3−xFe5O12(x=0.2and 0.4)) thin films have been successfully prepared by a sol-gel method followed by spin-coating process. The annealing of the films was performed at different temperatures like 700, 800, and900°Cand found that the films annealed at900°Cturned out to be crystallized into a pure garnet phase. All of the films were bearing grains of nanometer in size. Increasing the annealing temperature gave extra energy to the grains causing to be agglomerates. The lattice contraction occurred as the grain’s sizes were decreased due to the decrease of Fe2+formation. The magnetic measurements show that all of the films are soft magnetic materials with low saturation magnetization values. The hysteresis loops of the films which were annealed at900°Cwere found angular in shape similar to the single crystal-like YIG film.
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Dvořáček, Filip. "LABORATORY TESTING OF LEICA AT401 LASER TRACKER." Acta Polytechnica 56, no. 2 (April 30, 2016): 88. http://dx.doi.org/10.14311/ap.2016.56.0088.

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<p>This paper describes laboratory tests on a Leica AT401laser tracker. As the newer Leica AT402 model also uses the same firmware package, most of the results should also be valid for this device. First, we present the instrument’s firmware errors and the software used for testing. The ASME B89.4.19-2006 standard for testing laser trackers is briefly presented. The warm-up effect of the instrument is inspected with respect to both angle measurement and distance measurement. The absolute distance meter (ADM) is compared with a laboratory interferometer on a 30-meter long rail and also on a bench with automated movement of the carriage of the reflector. A time series of measurements for determining the additive constant is evaluated. A simple test of the stability of the distance measurement in field conditions is introduced. Most of the tests were carried out at the Research Institute of Geodesy, Topography and Cartography (RIGTC) and at the Faculty of Civil Engineering (FCE) of the Czech Technical University in Prague (CTU).</p>
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7

Dvořáček, Filip. "System Software Testing of Laser Tracker Leica AT401." Geoinformatics FCE CTU 13 (December 21, 2014): 49–57. http://dx.doi.org/10.14311/gi.13.6.

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The article introduces a group of instruments called laser trackers and specificallyfocuses on one of them - Leica AT401. At the Research Institute of Geodesy, To-pography and Cartography the instrument has been tested both in laboratory andoutdoor conditions. Several significant errors in the instrument’s system softwarehave been found, mostly due to the creation of user-programmed controlling appli-cation called ATControl. The errors are related to a selection, a computation andan evaluation procedure of the refractive index of air. Finally, notes of the newmeasurement modes of Leica AT40x are given and a range of distance measure-ment is discussed.
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Mallick, David J., and Alan Eastman. "AT101 [(-)-Gossypol] Selectively Inhibits MCL1 and Sensitizes Carcinoma to BH3 Mimetics by Inducing and Stabilizing NOXA." Cancers 12, no. 8 (August 15, 2020): 2298. http://dx.doi.org/10.3390/cancers12082298.

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Anti-apoptotic BCL2 proteins are important targets for cancer therapy as cancers depend on their activity for survival. Direct inhibitors of MCL1 have entered clinical trials, although their efficacy may be limited by toxicity. An alternative approach may be to induce the pro-apoptotic protein NOXA which selectively inhibits MCL1 in cells. Many compounds originally proposed as inhibitors of the BCL2 family were subsequently found to induce the pro-apoptotic protein NOXA through the unfolded protein response. In the present study, we compared various putative BH3 mimetics across a panel of carcinoma cell lines and measured expression of NOXA protein and mRNA, as well as the kinetics of NOXA induction. We found that AT101 [(-)-gossypol] induces high levels of NOXA in carcinoma cell lines yet cells survive. When combined with an appropriate BCL2 or BCL-XL inhibitor, NOXA-dependent sensitization occurs. NOXA protein continues to accumulate for many hours after AT101 is removed, providing a window for administering these combinations. As MCL1 promotes drug resistance and overall survival, we propose that NOXA induction is an alternative therapeutic strategy to target MCL1 and either kill cancer cells that are dependent on MCL1 or sensitize cancer cells to other BCL2 inhibitors.
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Flak, Dorota K., Vivian Adamski, Grzegorz Nowaczyk, Kosma Szutkowski, Michael Synowitz, Stefan Jurga, and Janka Held-Feindt. "AT101-Loaded Cubosomes as an Alternative for Improved Glioblastoma Therapy." International Journal of Nanomedicine Volume 15 (October 2020): 7415–31. http://dx.doi.org/10.2147/ijn.s265061.

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10

Dvořáček, Filip. "ATControl Software for Leica AT40x Laser Trackers." Geoinformatics FCE CTU 14, no. 2 (December 8, 2015): 9–20. http://dx.doi.org/10.14311/gi.14.2.2.

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The paper describes a software called ATControl which is based on the Matworks Matlab high-level programming language. This software is under constant development by the author in order to collect geospatial data by measuring with the absolute laser tracker Leica AT40x (AT401, AT402). Commercially available software solutions are shortly reviewed and the reasons for developing the new controlling application are discussed. Advantages of ATControl concerning metrological traceability of measured distances are stated. Key functional features of software are introduced.
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Dvořáček, Filip. "Precision Tests of Geodetic Centring Equipment." Geoinformatics FCE CTU 15, no. 2 (December 8, 2016): 5–14. http://dx.doi.org/10.14311/gi.15.2.1.

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The paper introduces testing procedures of several different geodetic centring devices performed mostly at the laboratory of the Research Institute of Geodesy, Topography and Cartography. Functional construction characteristics of a spherically mounted retroreflector Leica RRR 1.5’’, rotatable carriers Sokkia AP41 and Leica GZR3 and 12 different geodetic tribraches were examined. Further, a centring displacement instrument developed at the Czech Technical University in Prague, Faculty of Civil Engineering, Department of Special Geodesy, is evaluated in both laboratory and field conditions. For all tests, laser tracker Leica AT401 with a 5 μm standard uncertainty of absolute distance measurement, was employed.
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Doudican, Nicole A., Shireen Vali, Shweta Kapoor, Anay Talawdekar, Taher Abbasi, Gautam Sethi, and Amitabha Mazumder. "Rational Design of a Therapeutic Program for Multiple Myeloma Using a Strategy of Drug Repurposing and Combination Therapy." Blood 120, no. 21 (November 16, 2012): 5022. http://dx.doi.org/10.1182/blood.v120.21.5022.5022.

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Abstract Abstract 5022 Background: The extremely long development time and low success rate for new drug development programs has translated into limited clinical options in the treatment of cancer. The challenge is further compounded by drug resistance seen in clinical settings for approved standard of care therapeutic options like chemotherapy and targeted drugs like Bortezomib in Multiple Myeloma (MM). This has accelerated the need for initiatives and strategies which promote innovation but drastically reduce drug development failures through prediction of clinical outcomes. We present here a methodology and rationally designed therapeutic program for MM. This program has novel first-in-class mechanism of action and has been developed using a strategy of re-purposing and combinations based on National Center for Advanced Translational Sciences (NCATS) library of industry-provided drugs. Methods: The therapy design and development was completed using validated proprietary technology from Cellworks which enables simulation of cancer disease physiology computationally for predicting clinical outcomes. The comprehensive integrated representation of signaling and metabolic networks across all disease phenotypes and functional proteomics abstraction facilitated a large number of predictive studies in weeks with quantitative transparency into the network. The predictive cancer technology was customized to four MM profiles: OPM2, RPM1, SKMM2 and U266. Ten of the molecularly targeted drugs from the NCATS library were digitally screened alone and in combinations of two across the four MM profiles at four concentrations (C, C/2, C/4, and C/8). Based on screening of over six thousand predictive studies, three designed therapeutics hits were intelligently shortlisted based on synergistic impact on viability and proliferation. Results: The focused therapeutic candidate hit was selected based on synergy using viability endpoints and apoptosis markers such as caspase 3, PARP1 at sub-therapeutic doses. The proposed therapeutic regimen is a sub-therapeutic combination of AT101 and AVE0847. AT101 is a BCL2 inhibitor and AVE0847 is a PPAR alpha and gamma agonist agent. The concentration of each drug used in the designed therapy was close to IC30. The predictive results showed a synergistic increase in apoptotic markers caspase 3 and PARP1 cleaved form. This hit candidate is being pre-clinically validated experimentally across four MM profiles and results will be presented. Conclusion: The design of first in class mechanism of action based therapeutic strategies of drug rescue/repurposing has been used to identify AT101 and AVE0847 as a promising drug combination for use in MM which predicatively results in a synergistic increase in apoptosis. These results are currently being validated in vitro. The inherent multi target mechanism of action predicted by this combination could potentially eliminate the drug resistance challenges of single target therapeutics. Disclosures: No relevant conflicts of interest to declare.
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Kaza, Niroop, Latika Kohli, Christopher D. Graham, Barbara J. Klocke, Steven L. Carroll, and Kevin A. Roth. "BNIP3 Regulates AT101 [(-)-Gossypol] Induced Death in Malignant Peripheral Nerve Sheath Tumor Cells." PLoS ONE 9, no. 5 (May 13, 2014): e96733. http://dx.doi.org/10.1371/journal.pone.0096733.

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Xin, Xin, Guo Dong Wang, Ju Liang Xiao, and Gang Wang. "The Research of Robot Handheld Intelligent Terminal System Base on ARM9." Applied Mechanics and Materials 220-223 (November 2012): 1217–20. http://dx.doi.org/10.4028/www.scientific.net/amm.220-223.1217.

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Traditional developments of intelligent terminal system could control only one robot and most were based on WinCE platform, which have poor versatility and expansibility. The robot hand intelligent terminal system proposed by this paper was an embedded equipment based on AT91 series chip. It had good human-machine interface with Linux system and Qt4 as software support. It adopted touch-screen technology and I2C keyboard as input device. It had two kinds of programming method, manual teaching-programming and off-line programming. The test shows that its volume is small and its weight is light to easy to operate robot handily.
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Dvořáček, Filip. "SURVEY OF SELECTED PROCEDURES FOR THE INDIRECT DETERMINATION OF THE GROUP REFRACTIVE INDEX OF AIR." Acta Polytechnica 58, no. 1 (February 28, 2018): 9. http://dx.doi.org/10.14311/ap.2018.58.0009.

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The main aim of the research was to evaluate numeric procedures of the indirect determination of the group refractive index of air and to choose the suitable ones for requirements of ordinary and high accuracy distance measurement in geodesy and length metrology. For this purpose, 10 existing computation methods were derived from various authors’ original publications and all were analysed for wide intervals of wavelengths and atmospheric parameters. The determination of the phase and the group refractive indices are essential parts in the evaluation of the first velocity corrections of laser interferometers and electronic distance meters. The validity of modern procedures was tested with respect to updated CIPM-2007 equations of the density of air. The refraction model of Leica AT401 laser tracker was analysed.
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Kaza, Niroop, Latika Kohli, Christopher D. Graham, Barbara J. Klocke, Steven L. Carroll, and Kevin A. Roth. "Correction: BNIP3 Regulates AT101 [(-)-Gossypol] Induced Death in Malignant Peripheral Nerve Sheath Tumor Cells." PLOS ONE 10, no. 8 (August 27, 2015): e0137153. http://dx.doi.org/10.1371/journal.pone.0137153.

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Doudican, Nicole A., Shireen Vali, Shweta Kapoor, Anay Talawdekar, Zeba Sultana, Aftab Alam, Taher Abbasi, and Amitabha Mazumder. "Predictive Simulation Based Design and Validation Of Repurposed Novel Therapeutics With Multi-Target Mechanisms For Multiple Myeloma." Blood 122, no. 21 (November 15, 2013): 3859. http://dx.doi.org/10.1182/blood.v122.21.3859.3859.

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Abstract Introduction Development of resistance to single agent therapy is a significant clinical obstacle in the treatment of multiple myeloma (MM). Genetic mutations and the bone marrow micro-environment are major determinants of MM resistance mechanisms. Given the complexity of MM, the need for combinatorial therapeutic regimens targeting multiple biological mechanisms of action is pressing. Repurposing has the advantage of using drugs with known clinical history. Methodology We used a predictive simulation-based approach that models MM disease physiology in plasma cells by integrating and aggregating signaling and metabolic networks across all disease phenotypes. We tested the efficacy of over 50 repurposed molecularly targeted agents both individually and in combination across simulation avatars of the MM cell lines OPM2 and U266. OPM2 harbors mutations in KRAS, CDKN2A/2C, PTEN, RASSF1A and P53, whereas U266’s mutational components include BRAF, CDKN2A, P53, P73, RASSF1A and RB1. These cell lines were used as models because they possess mutations in genes classically known to be involved in myeloma. The predicted activity of novel combinations of existing drug agents was validated in vitro using standard molecular assays. MTT and flow cytometry were used to assess cellular proliferation. Western blotting was used to monitor the combinatorial effects on apoptotic and cellular signaling pathways. Synergy was analyzed using isobologram plots and the Bliss independence model. Results Through simulation modeling, we identified two novel therapeutic regimens for MM using repurposed drugs: (1) AT101 (Bcl2 antagonist) and tesaglitazar (PPAR α/γ agonist) and (2) Ursolic acid (UA, inhibitor of NFκβ) and SP600125 (pan-JNK inhibitor). Simulation predictions showed that combining the IC30 concentrations with respect to viability of AT101 and tesaglitazar reduced proliferation by 40% and viability by 50%. Similarly simulation predictions showed that the combination of the IC30 concentrations of UA and SP600125 reduced proliferation by 50% and viability by 40%. Corroborating our predictive simulation assays, 10 µM tesaglitazar and 2 µM AT101 caused minimal growth inhibition as single agents in OPM2 and U266 MM cell lines. Growth inhibition in these cell lines is synergistically enhanced when the drugs are used in combination, reducing cellular viability by 88% and 77% in OPM2 and U266 cells, respectively. Similarly, proliferation was reduced by 34% with 7.5 μM UA and 25% with 10 μM SP600125 in OPM2 cells. When used in combination, cellular proliferation was synergistically reduced by 64%. In addition, isobologram analysis predicted synergy of lowered doses of the drugs in combination. Both combinations synergistically inhibited proliferation and induced apoptosis as evidenced by an increase in the percentage sub-G1 phase cells and cleavage of caspase 3 and poly ADP ribose polymerase (PARP). Conclusions These results highlight and validate the use of our predictive simulation approach to design therapeutic regimens with novel biological mechanisms using drugs with known chemistries. This allows for design of personalized treatments for patients using their tumor genomic signature beyond the “one-gene, one-drug” paradigm. The reuse of existing drugs with clinical data facilitates a rapid translational path into clinic and avoids the uncertainties associated with new chemistry. The corroboration of these results with patient derived cell lines will be pursued and discussed. Disclosures: No relevant conflicts of interest to declare.
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El-Badawy, Ayman A., and Mohamed A. Bakr. "Quadcopter Aggressive Maneuvers along Singular Configurations: An Energy-Quaternion Based Approach." Journal of Control Science and Engineering 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/7324540.

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Automatic aggressive maneuvers with quadcopters are regarded as a highly challenging control problem. The aim is to tackle the singularities that exist in a vertical looping maneuver. Modeling singularities are resolved by writing the equations-of-motion of the quadcopter in quaternion form. Physical singularities due to underactuation are resolved by using an energy-based control. Energy-based control is utilized to overcome the uncontrollability of the quadcopter at physical singular configurations, for instance, when commanding the quadcopter to gain altitude while pitched at90∘. Three looping strategies (circular, clothoidal, and newly developed constant thrust) are implemented on a nonlinear model of the quadcopter. The three looping strategies are discussed along with their advantages and limitations.
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Liu, Zhigang, Xiaodong Li, Yonghua Leng, Jingbao Lian, Shaohong Liu, Zhimeng Xiu, Di Huo, Ji-Guang Li, and Xudong Sun. "Homogeneous Precipitation Synthesis and Magnetic Properties of Cobalt Ferrite Nanoparticles." Journal of Nanomaterials 2008 (2008): 1–4. http://dx.doi.org/10.1155/2008/921654.

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Magnetic nanoparticles (NPs) of cobalt ferrite have been synthesized via a homogeneous precipitation route using hexamethylenetetramine (HMT) as the precipitant. The particle size, crystal structure, and magnetic properties of the synthesized particles were investigated by X-ray diffraction, transmission electron microscopy, and vibrating sample magnetometer. The NPs are of cubic inverse spinel structure and nearly spherical shape. With the increase of oxidation time from 30 to 180 minutes in the reaction solution at90∘C, the average particle size increases from ~30 nm to ~45 nm. The as-synthesized NPs ~30 nm in size show higherMs(61.5 emu/g) and moderate Hc (945 Oe) andMr/Ms(0.45) value compared with the materials synthesized by coprecipitation method using NaOH as precipitate at high pH value.
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Adamski, Vivian, Annika Hempelmann, Charlotte Flüh, Ralph Lucius, Michael Synowitz, Kirsten Hattermann, and Janka Held-Feindt. "Dormant glioblastoma cells acquire stem cell characteristics and are differentially affected by Temozolomide and AT101 treatment." Oncotarget 8, no. 64 (November 18, 2017): 108064–78. http://dx.doi.org/10.18632/oncotarget.22514.

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Collin, E., and R. Duclos. "ATS01 - Évaluation de la formation médicale continue du médecin de la douleur : les critères d’une formation validante." Douleurs : Evaluation - Diagnostic - Traitement 7 (November 2006): 52. http://dx.doi.org/10.1016/s1624-5687(06)77815-5.

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Mehner, Moiken, Carolin Kubelt, Vivian Adamski, Christina Schmitt, Michael Synowitz, and Janka Held-Feindt. "Combined treatment of AT101 and demethoxycurcumin yields an enhanced anti-proliferative effect in human primary glioblastoma cells." Journal of Cancer Research and Clinical Oncology 146, no. 1 (December 16, 2019): 117–26. http://dx.doi.org/10.1007/s00432-019-03107-7.

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Wei, Xi, Wei Duan, Ying Li, Sheng Zhang, Xiaojie Xin, Lei Sun, Ming Gao, Qing Li, and Dong Wang. "AT101 exerts a synergetic efficacy in gastric cancer patients with 5-FU based treatment through promoting apoptosis and autophagy." Oncotarget 7, no. 23 (April 30, 2016): 34430–41. http://dx.doi.org/10.18632/oncotarget.9119.

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Hu, Wenbin, Fang Wang, Jingsheng Tang, Xinyu Liu, Zhu Yuan, Chunlai Nie, and Yuquan Wei. "Proapoptotic Protein Smac Mediates Apoptosis in Cisplatin-resistant Ovarian Cancer Cells When Treated with the Anti-tumor Agent AT101." Journal of Biological Chemistry 287, no. 1 (November 3, 2011): 68–80. http://dx.doi.org/10.1074/jbc.m111.271205.

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Zhou, Minghua, Jun Zhang, Bei Cheng, and Huogen Yu. "Enhancement of Visible-Light Photocatalytic Activity of Mesoporous Au-TiO2Nanocomposites by Surface Plasmon Resonance." International Journal of Photoenergy 2012 (2012): 1–10. http://dx.doi.org/10.1155/2012/532843.

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Mesoporous Au-TiO2nanocomposite plasmonic photocatalyst with visible-light photoactivity was prepared by a simple spray hydrolytic method using photoreduction technique at90∘C. The prepared samples were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and N2adsorption-desorption isotherms. The formation of hydroxyl radicals (•OH) on the surface of visible-light illuminated Au-TiO2nanocomposites was detected by the luminescence technique using terephthalic acid as probe molecules. The photocatalytic activity was evaluated by photocatalytic decolorization of Rhodamine-B (RhB) aqueous solution under visible-light irradiation (λ > 420 nm). The results revealed that the TiO2could be crystallizedviaspray hydrolysis method, and the photoreduction technique was facilitated to prepare Au nanoparticles in the mesoporous TiO2at90∘C. The light absorption, the formation rate of hydroxyl radicals, and photocatalytic decolorization of Rhodamine-B aqueous solution were significantly enhanced by those embedded Au nanoparticles in the Au-TiO2nanocomposites. The prepared Au-TiO2nanocomposites exhibit a highly visible-light photocatalytic activity for photocatalytic degradation of RhB in water, and their photocatalytic activity is higher than that of the pristine TiO2nanoparticles due to the surface plasmon resonance.
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Soares, João Vitor Camargo, Jânia Lília da Silva Bentes, and Luadir Gasparotto. "Reação de genótipos de Capsicum spp. à podridão do colo (Sclerotium rolfsii)." Summa Phytopathologica 43, no. 1 (March 2017): 58–59. http://dx.doi.org/10.1590/0100-5405/2182.

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RESUMO Espécies do gênero Capsicum nativas da Amazônia são desconhecidas cientificamente e são potenciais fontes de genes de resistência aos problemas fitossanitários. A podridão do colo causada pelo fungo Sclerotium rolfsii Sacc. é uma das doenças mais comuns em cultivos pimentão no Amazonas, causando a perda plantas em campo e em cultivo protegido. O Objetivo deste trabalho foi avaliar a resistência de 18 genótios de Capsicum nativos da Amazônia à podridão do colo. Os experimentos foram conduzidos em casa de vegetação, em delineamento inteiramente casualizado, com três repetições. As inoculações foram realizadas por meio da deposição de três discos de meio de cultura contendo a colônia do patógeno em contato com o colo da planta aos 35 dias após a semeadura. A severidade foi avaliada de acordo com uma escala descritiva do progresso dos sintomas da doença. Foi calculada a área abaixo da curva de progresso da doença (AACPD) e as médias dos dados foram comparados entre si pelo teste de Tukey (P≤0.05). Os genótipos MA03, BC16, LA02, TBT01, MA18, MA34, MA43, BC01, ATN01, IRB02, ATN02, ATN04, CDJ01, MA35 e MA37 comportaram-se como resistentes e apresentam potencial para futuros estudos de melhoramento genético de pimentas e pimentões para obtenção de cultivares resistentes à podridão do colo.
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De Paula Ramos, Sérgio. "What can we learn from psychoanalysis and prospective studies about chemically dependent patients?" International Journal of Psychoanalysis 85, no. 2 (April 2004): 467–87. http://dx.doi.org/10.1516/d7uk-ulmk-at01-mycq.

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Adamski, Vivian, Christina Schmitt, Florian Ceynowa, Rainer Adelung, Ralph Lucius, Michael Synowitz, Kirsten Hattermann, and Janka Held-Feindt. "Effects of sequentially applied single and combined temozolomide, hydroxychloroquine and AT101 treatment in a long-term stimulation glioblastoma in vitro model." Journal of Cancer Research and Clinical Oncology 144, no. 8 (June 1, 2018): 1475–85. http://dx.doi.org/10.1007/s00432-018-2680-y.

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Zhang, Leisi, Yong Zhou, Kai Chen, Pengcheng Shi, Yin Li, Manman Deng, Zhiwu Jiang, Xiangmeng Wang, Peng Li, and Bing Xu. "The pan-Bcl2 Inhibitor AT101 Activates the Intrinsic Apoptotic Pathway and Causes DNA Damage in Acute Myeloid Leukemia Stem-Like Cells." Targeted Oncology 12, no. 5 (July 14, 2017): 677–87. http://dx.doi.org/10.1007/s11523-017-0509-2.

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30

Paulus, Aneel, Pooja Advani, Betsy R. Laplant, Sharoon Akhtar, Taimur Sher, Candido E. Rivera, James M. Foran, et al. "Phase I/II Clinical Trial of Lenalidomide in Combination with AT101 for the Treatment of Relapsed B-Cell Chronic Lymphocytic Leukemia (B-CLL)." Blood 126, no. 23 (December 3, 2015): 5299. http://dx.doi.org/10.1182/blood.v126.23.5299.5299.

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Abstract Background: Lenalidomide (Len) is clinically active in CLL patients (pts). Robust anti-leukemic immune response from Len is truncated by dysfunctional immune system in CLL and anti-apoptotic bcl-2 protein. We hypothesized that therapeutic downregulation of Bcl-2 may help enhance the killing potential of immune effector cells that are activated by Len. AT-101 is a novel, orally active BH3-mimetic that binds to antiapoptotic Bcl-2 family proteins (Bcl-2, Mcl-1 and Bcl-xL) and induces CLL cell death ex vivo (Masood et al British Journal of Haematology 2012). Encouraging efficacy and safety results of AT-101 alone or in combination with rituximab in CLL have been reported in Phase I/II studies. We have previously demonstrated that bcl-2 downregulation in CLL cells enhanced the killing potential of Len-activated immune cells. Conversely, pretreatment of CLL cells with Len enhanced AT-101 cytotoxicity in an immune cell independent manner (Masood et al British Journal of Haematology 2012). These preclinical findings formed the basis of a phase I/II clinical trial testing the combination of AT-101 and lenalidomide in relapsed B-CLL patients. Methods: The phase I portion of this study (NCT 01003769) utilizes a standard cohort of three design to determine the maximum tolerated dose (MTD) of the combination regimen. The MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients. Following the MTD determination, the phase 2 portion will assess the efficacy of this combination using a one-stage design with an interim analysis. Key inclusion criteria include adult CLL pts with relapsed disease who have received 1-4 prior lines of treatment (Rx) (phase I) or 1-2 lines of Rx (phase II), last dose > 4 weeks from enrollment, ECOG performance status 0-2, good renal/liver function, acceptable blood counts. Patients with known hypersensitivity to thalidomide/Len or prior use of gossypol/AT-101 were excluded. Cycle 1 Rx includes Len alone and cycles 2-12 includes Len and AT-101. Starting doses of Len and AT-101 are 5mg oral daily on days 1-21 and 40 mg oral twice daily (b.i.d) on days 1-3 of a 28-day cycle. Planned dose escalation is shown in Table 1. Three pts will be treated at each dose level and observed during the first cycle of the combination Rx. Dose limiting toxicity is defined as grade 4 anemia unrelated to disease, thrombocytopenia-grade 4 or grade 3 with bleeding/requiring platelets, ANC <500 for >14 days, febrile neutropenia , Grade 3/4 non-hematologic toxicity. Dose from Phase II will be based on MTD from phase I. Peripheral blood and bone marrow will be collected and analyzed for immune cellular microenvironment and effect of Len and AT-101 on molecular targets. Optional lymph node biopsy will be done at baseline and if tumor-flare reaction occurs. This study is expected to accrue a maximum of 26 pts in phase I and 34 pts in phase II, overall maximum sample size of 60 pts. Five pts in phase I have been accrued to date. Table 1 (* starting dose level) Table 1. (* starting dose level) Disclosures No relevant conflicts of interest to declare.
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Wehtje, G., and T. L. Grey. "Response of New Cultivars to Early Postemergence Chlorimuron Applications1." Peanut Science 31, no. 2 (July 1, 2004): 119–23. http://dx.doi.org/10.3146/pnut.31.2.0011.

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Abstract Field studies were conducted in Alabama and Georgia in 2002 and 2003 to determine whether the peanut cultivar that replaced the cultivar Florunner can tolerate earlier applications of the herbicide chlorimuron than what is registered. The application timing restriction of chlorimuron on peanut had been established in the late 1980s with Florunner. In a factorial treatment arrangement, the cultivars AT201, Georgia Green, Viragard, C99R, and Florunner were treated with chlorimuron at 8.75 g ai/ha at 5, 7, 9, or 11 wk after planting. Only the later two application timings are covered by the current registration. Across all 4 yr-location replications, yield was influenced by the main effect of peanut cultivar. C99R was consistently the highest yielding cultivar. Chlorimuron had no effect on yield, regardless of application timing when compared to the nontreated entries in three of the four repetitions (i.e. Plains 2002, Plains 2003, and Headland 2002). Cultivar-based chlorimuron tolerance differences were detected only at Headland in 2003. For this location, chlorimuron applied at 5 wk after planting reduced yield across all cultivars, while application at 7, 9, and 11 WAP had no effect on yield. Results indicate that chlorimuron possesses a yield-reducing risk only when the crop has been stressed by other factors. Assuming that the crop has been stressed, the potential of yield reduction can be avoided only by observing the currently registered application timing. No clear indication was obtained that one cultivar was more tolerant to chlorimuron than another cultivar.
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Dhanasekaran, D. "Influence of growth regulating chemicals on growth and flowering in Jasmine (Jasminum sambac.Ait.)." Journal of Horticultural Sciences 13, no. 2 (December 31, 2018): 221–26. http://dx.doi.org/10.24154/jhs.2018.v13i02.016.

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Jasmine is an important commercial flower crop in Tamil Nadu. The crop has a main floweringseason during March to October and an off-season from November to February. During thisoff-season, flowering is very poor or there is no flowering in many growing areas. In recentyears, growth regulators are valuable in floriculture for manipulating growth and flowering ofmany crops and hence and attempt has been made to induce flowering during off season usinggrowth regulators in Jasmine in the Floriculture unit of the Department of Horticulture, Facultyof Agriculture, Annamalai University, Tamil Nadu during November, 2016 to February, 2017.The treatment comprises of three concentrations of each of two growth promoting substancesviz., NAA and GA3 and two growth retardants (Cycocel and Maleic Hydrazide). The experimentwas laid out in randomized block design with three replications. Among the various treatments,application of NAA @ 75 ppm (T6) recorded the highest plant height (130.6 cm and 178.5 cm at90 and 180 DAP respectively), number of primary shoots (21.68 and 35.68 at 90 and 180 DAPrespectively), number of nodes (9.86 and 15.89 cm at 90 and 180 DAP respectively) and numberof leaves (1250.0 and 2689.5 at 90 and 180 DAP respectively). Earliness in flowering (26.38DAP) and maximum duration of flowering (171.00 days) was noticed in (GA3@ 150 ppm T3).From the above studies, it is inferred that application of GA3 @ 150 ppm could be recommendedfor enhanced growth and higher flower yield in Jasminum sambac.
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33

Paudel, Bishnu Hari, and S. Kumar. "EFFECT OF WATER AND SALINE LOAD ON URINARY OUTPUT IN HEALTHY UNDERGRADUATE MEDICAL STUDENTS." Journal of Nepal Medical Association 42, no. 145 (January 1, 2003): 23–26. http://dx.doi.org/10.31729/jnma.712.

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ABSTRACTWater and electrolyte balance is a vital homeostatic function. Their excretion depends on various factors –state of hydration, plasma osmolarity etc. There are rare reports on effect of hypertonic solution on urinaryoutput. Therefore, the study aimed at investigating the effect of water or saline (especially the hypertonic)load on urinary output (UO) in healthy undergraduate male medical students (17-20 years). They (n=20)were randomised into 4 equal groups: control, water, normal and hypertonic saline (1.8%). The study wasa part of undergraduate practical conducted under controlled conditions in the Physiology Department,BPKIHS. The day before the experiment, all of them were given same instructions. Next day, the experimentalgroups drank water/saline solution 12 ml/kg. Then the UO was measured ½-hourly. A non-parametric –Friedman test was used for intra- and inter-group differences in UO and specific gravity. The data arepresented as median (range). In water group the 60-min UO was significantly higher than the 30-min UO[178.5 (24-415) vs. 22.5 (21-81) ml, p<0.05]. This group also had significantly higher UO than the control at90-min [84 (20-250) vs. 19 (18-23) ml, p<0.05)]. The UO of normal-saline group was significantly higherthan that of control at 90-min [40 (22-250) vs. 19 (18-23) ml, p<0.05]. There was no significant difference inspecific gravity. The water and normal saline loads were adequate to elicit physiological response, thehypertonic solution was not strong enough to show significant physiological response suggesting need ofsaline load to be more than twice of the plasma osmolarity.Key Words: homeostasis, water-electrolyte balance, salt load, water load.
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34

Sonpavde, G., V. B. Matveev, J. M. Burke, J. R. Caton, M. T. Fleming, P. A. Karlov, J. Holmlund, B. A. Wood, M. Brookes, and L. H. Leopold. "A randomized, double-blind phase II trial of docetaxel plus prednisone (DP) combined with either AT101 or placebo for the first-line therapy of metastatic castration-resistant prostate cancer (CRPC)." Journal of Clinical Oncology 29, no. 7_suppl (March 1, 2011): 125. http://dx.doi.org/10.1200/jco.2011.29.7_suppl.125.

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125 Background: AT-101 (A), a small molecule oral inhibitor of the Bcl-2 protein family has broad preclinical activity including synergy with docetaxel (D). AT-101 has demonstrated activity alone and in combination with D in D-refractory patients with metastatic CRPC. Methods: A randomized, double-blind, placebo-controlled phase II trial was conducted to compare the combination of DP with either A or placebo in chemo-naive men with progressive metastatic CRPC. A key requirement was progression (bone scan, RECIST or rising PSA ≥ 2 ng/mL) despite androgen deprivation. Stratification factors were pain and performance status. Patients received DP (75mg/m2 day 1; 5mg PO b.i.d.) Q 21 days (1 cycle) with either A (40 mg b.i.d.) or placebo PO on days 1–3. Radiological assessments were performed every 3 cycles. Primary endpoint was overall survival (OS) and 221 patients were planned for 110 events (80% power, HR 0.67, 1-sided alpha 0.1). Results: 221 patients were randomized to ADP or placebo-DP and baseline factors were balanced. Efficacy outcomes (OS, PFS, PSA declines, disease control) were not significantly different ( Table ). In a subgroup of patients with poor-risk CRPC (n=34), efficacy endpoints appeared to favor ADP with a median OS of 19 months vs.14 months for placebo-DP. Grade 3/4 AEs that occurred with higher incidence in the ADP arm compared to placebo-DP included cardiac AEs (5% vs. 2%), lymphopenia (23% vs. 16%), neutropenia (47% vs. 40%), ileus (2% vs. 0%) and pulmonary embolism (6% vs. 2%). Conclusions: The combination of AT-101 with DP in men with chemonaive metastatic CRPC was well tolerated but did not extend OS compared to placebo-DP. There was a potential benefit in a subset of high-risk patients. [Table: see text] [Table: see text]
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35

Kumar, Shaji, Michael Kline, Terry Kimlinger, Michael Timm, Jessica Haug, Philip R. Greipp, Dajun Yang, and S. Vincent Rajkumar. "AT-101, a Small Molecule Inhibitor of Bcl-2 Family Proteins, Has Significant In Vitro Activity in Multiple Myeloma." Blood 106, no. 11 (November 16, 2005): 1581. http://dx.doi.org/10.1182/blood.v106.11.1581.1581.

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Abstract Background: Multiple myeloma (MM) is a plasma cell proliferative disorder that results in considerable morbidity and mortality. As it is incurable with the current therapeutic approaches, more effective therapies based on better understanding of the pathobiology of the disease are needed. In MM, malignant plasma cells are characterized by low proliferative and apoptotic rates compared to other malignancies. Studies have shown elevated expression of anti-apoptotic proteins of the Bcl-2 family in MM cells, which appear to correlate with resistance to therapy with certain drugs. Hence, accelerating the apoptotic process by targeting the Bcl-2 family of proteins appears to be an attractive strategy for the treatment of MM. AT-101 is an orally bioavailable derivative of gossypol in cancer clinical trials, and is being developed by Ascenta Therapeutics. AT-101 behaves as a small molecule inhibitor of Bcl-2 and Bcl-XL, binding to the BH3-binding pocket of these proteins and inhibiting their ability to suppress the activity of pro-apoptotic proteins, resulting in apoptosis. Methods and Results: AT-101 was cytotoxic to several different myeloma cell lines with a median effect observed at around 5μM concentration using an MTT cell proliferation assay. Additionally, at similar doses AT-101 induced cytotoxicity in myeloma cell lines resistant to conventional agents such as Melphalan (LR50), Doxorubicin (Dox40) and Dexamethasone (MM1.R), indicating non-overlapping mechanisms. To evaluate the ability of the drug to induce cell death in the tumor microenvironment, MM cells were co-cultured with marrow stromal cells or in the presence of VEGF or IL-6, two cytokines known to be important for myeloma growth and survival. AT-101 was cytotoxic to myeloma cells under these conditions as well with a median effect at concentrations of 5–10μM. AT-101 was able to induce apoptosis in myeloma cells in a dose- and time dependent fashion, as demonstrated by flow cytometry using Annexin/PI staining as well as cell cycle studies. AT-101 also resulted in cytotoxicity of freshly isolated primary patient myeloma cells, inducing apoptosis in a dose dependent manner. We also studied the effect of AT-101 on levels of different pro- and anti-apoptotic proteins using flow cytometry on permeabilized cells. A time-dependent increase in the level of BAX was observed following treatment with AT-101 without any associated change in levels of Bcl-xL or Bcl-2. Further studies evaluating the combination of AT101 with other active myeloma agents as well as a detailed evaluation of its mechanisms in myeloma are ongoing. Conclusion: AT-101 has significant activity in vitro in the setting of myeloma as demonstrated by its effect on myeloma cell lines and primary patient cells. More importantly, it has activity against cell lines resistant to conventional anti-myeloma agents. In addition, Phase I studies with this agent are currently ongoing in patients with solid tumors. The results from these studies form the rationale for early phase clinical trials in MM, either alone or in combination with other active therapies.
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36

Song, Shumei, Qiongrong Chen, Yuan Li, Guang Lei, Ailing Scott, Longfei Huo, Cordelia Y. Li, et al. "Targeting cancer stem cells with a pan-BCL-2 inhibitor in preclinical and clinical settings in patients with gastroesophageal carcinoma." Gut, January 24, 2021, gutjnl—2020–321175. http://dx.doi.org/10.1136/gutjnl-2020-321175.

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ObjectiveGastro-oesophageal cancers (GEC) are resistant to therapy and lead to poor prognosis. The cancer stem cells (CSCs) and antiapoptotic pathways often confer therapy resistance. We sought to elucidate the antitumour action of a BCL-2 inhibitor, AT101 in GEC in vitro, in vivo and in a clinical trial.MethodsExtensive preclinical studies in vitro and in vivo were carried out to establish the mechanism action of AT101 on targeting CSCs and antiapoptotic proteins. A pilot clinical trial in patients with GEC was completed with AT-101 added to standard chemoradiation.ResultsOverexpression of BCL-2 and MCL-1 was noted in gastric cancer tissues (GC). AT-101 induced apoptosis, reduced proliferation and tumour sphere formation in MCL-1/BCL-2 high GC cells. Interestingly, AT101 dramatically downregulated genes (YAP-1/Sox9) that control CSCs in GEC cell lines regardless of BCL-2/MCL-1 expression. Addition of docetaxel to AT-101 amplified its antiproliferation and induced apoptosis effects. In vivo studies confirmed the combination of AT101 and docetaxel demonstrated stronger antitumour activity accompanied with significant decrease of CSCs biomarkers (YAP1/SOX9). In a pilot clinical trial, 13 patients with oesophageal cancer (EC) received AT101 orally concurrently with chemoradiation. We observed dramatic clinical complete responses and encouraging overall survival in these patients. Clinical specimen analyses revealed that AT-101 dramatically reduced the expression of CSCs genes in treated EC specimens indicating antitumour activity of AT101 relies more on its anti-CSCs activity.ConclusionsOur preclinical and clinical data suggest that AT-101 overcomes resistance by targeting CSCs pathways suggesting a novel mechanism of action of AT101 in patients with GEC.
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Kaza, Niroop, Steven L. Carroll, and Kevin A. Roth. "BNIP3 regulates AT101 induced cytotoxicity in MPNST cells." FASEB Journal 27, S1 (April 2013). http://dx.doi.org/10.1096/fasebj.27.1_supplement.380.3.

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38

Holm Hansen, Anders Cai, Ivan Glaucio Paulino-Lima, Kosuke Fujishima, Lynn Justine Rothschild, and Peter Ruhdal Jensen. "Draft Genome Sequence of Hymenobacter sp. Strain AT01-02, Isolated from a Surface Soil Sample in the Atacama Desert, Chile." Genome Announcements 4, no. 1 (February 11, 2016). http://dx.doi.org/10.1128/genomea.01701-15.

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Here, we report the 5.09-Mb draft genome sequence of Hymenobacter sp. strain AT01-02, which was isolated from a surface soil sample in the Atacama Desert, Chile. The isolate is extremely resistant to UV-C radiation and is able to accumulate high intracellular levels of Mn/Fe.
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Mullis, Megan M., Rachel E. Weisend, and Brandi Kiel Reese. "Draft Genome Sequences of Idiomarina abyssalis Strain KJE, Marinobacter salarius Strain NP2017, and Marinobacter salarius Strain AT3901, Isolated from Deep-Sea Sediment near the Western Flank of the Mid-Atlantic Ridge." Microbiology Resource Announcements 10, no. 3 (January 21, 2021). http://dx.doi.org/10.1128/mra.01295-20.

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We report the draft genomes of environmental cultures collected from shallow sediment from the western flank of the Mid-Atlantic Ridge. The isolates were most closely related to Idiomarina abyssalis strain KJE (100% complete), Marinobacter salarius strain NP2017 (97.6% complete), and Marinobacter salarius strain AT3901 (98.4% complete). Isolates identified as an Idiomarina species possess complete nitrite oxidation and reduction pathways, and isolates identified as a Marinobacter species possess complete dissimilatory nitrate reduction pathways.
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40

"American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias." American Journal of Respiratory and Critical Care Medicine 165, no. 2 (January 15, 2002): 277–304. http://dx.doi.org/10.1164/ajrccm.165.2.ats01.

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41

Graham, Christopher, Niroop Kaza, Barbara Klocke, and Kevin Roth. "AT101 Down‐regulates CXLC12 mRNA and Secreted Protein in Malignant Peripheral Nerve Sheath Tumor cells." FASEB Journal 29, S1 (April 2015). http://dx.doi.org/10.1096/fasebj.29.1_supplement.149.2.

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42

Gopal, Keshav, Qutuba Karwi, Seyed Amirhossein Tabatabaei Dakhili, Riccardo Perfetti, Ravichandran Ramasamy, John R. Ussher, and Gary D. Lopaschuk. "Abstract 15649: Pharmacological Inhibition of Aldose Reductase by AT001 Prevents Abnormal Cardiac Energy Metabolism and Improves Heart Function in an Animal Model of Diabetic Cardiomyopathy." Circulation 142, Suppl_3 (November 17, 2020). http://dx.doi.org/10.1161/circ.142.suppl_3.15649.

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Introduction: Diabetic Cardiomyopathy (DCM) is a major cause of death in people with type 2 diabetes (T2D). Alterations in cardiac energy metabolism including increased fatty acid oxidation rates and reduced glucose oxidation rates are key contributing factors to the development of DCM. Studies have shown that Aldose Reductase (AR), an enzyme activated under hyperglycemic conditions, can modulate myocardial glucose and fatty acid oxidation, and promotes cardiac dysfunction. Hypothesis: Pharmacological inhibition of AR using a next-generation inhibitor AT-001, can mitigate DCM in mice by modulating cardiac energy metabolism and improving cardiac efficiency. Methods: Male human AR overexpressing (hAR-Tg) and C57BL/6J (Control) mice were subjected to experimental T2D (high-fat diet [60% kcal from lard] for 10-wk with a single intraperitoneal streptozotocin injection of 75 mg/kg) and treated for the last 3-wk with AT-001 (40mg/kg/day) or vehicle via oral gavage. Cardiac energy metabolism and in vivo cardiac function were assessed via isolated working heart perfusions and ultrasound echocardiography, respectively. Results: AT-001 treatment significantly improved cardiac energetics in a murine model of DCM (hAR-Tg mice with T2D). Particularly, AT-001-treated mice exhibited decreased cardiac fatty acid oxidation rates compared to the vehicle-treated mice (342 ± 53 vs 964 ± 130 nmol/min/g dry wt.). Concurrently, there was a significant decrease in cardiac oxygen consumption in the AT-001-treated compared to the vehicle-treated mice (41 ± 12 vs 60 ± 11 μmol/min/g dry wt.), suggesting increased cardiac efficiency. Furthermore, treatment with AT-001 prevented cardiac structural and functional abnormalities present in DCM, including diastolic dysfunction as reflected by an increase in the tissue Doppler E’/A’ ratio and decrease in E/E’ ratio. Moreover, AT-001 treatment prevented cardiac hypertrophy as reflected by a decrease in LV mass in AT-001-treated mice. Conclusions: AR inhibition with AT-001 prevents cardiac structural and functional abnormalities in a mouse model of DCM, and normalizes cardiac energetics by shifting cardiac metabolism towards a non-diabetic metabolic state.
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