gebhart/patrepeval huggingface dataset:
Abstract 257: Targeting AML through apoptosis activation using Bcl-2/Mcl-1 or Bcl-2/Hdm2 inhibitor combination therapies (2019)

Acute myeloid leukemia (AML) is an aggressive and heterogeneous hematologic malignancy, characterized by uncontrolled proliferation and impaired differentiation of myeloid cells. With the exception of certain subtypes, the average long-term survival rate remains low, thus underlining the need to further improve the outcome of AML patients. Since AML is one of the least mutated cancer types, the majority of AML patients may not carry targetable genetic alterations. However, the anti-apoptotic proteins of the Bcl-2 family, such as Bcl-2 and Mcl-1, are often overexpressed in AML, allowing deregulated survival; hence pro-apoptosis priming with small molecule inhibitors of Bcl-2 and Mcl-1 may provide a broader therapeutic benefit across the disease. In addition, a majority of AML patients carry wild-type p53, providing therapeutic opportunity for Hdm2 inhibitors to stabilize p53 and lead to expression of pro-apoptotic molecules (e.g., PUMA & BAX). Therefore, targeting the combined apoptosis mechanisms by inhibiting different anti-apoptotic Bcl-2 family of proteins and activating p53 concomitantly may synergistically enhance apoptotic cell death of AML tumor cells.We tested the combination of Bcl-2 inhibitors (BCL201/S55746 or venetoclax) with either MIK665/S64315, a novel and selective inhibitor of Mcl-1 or HDM201, a selective small molecule inhibitor of p53:Hdm2 interaction, in a series of in vitro and in vivo studies in AML. In vitro, strong combination synergy was observed with a remarkable induction of cell death for both combinations. In vivo, the combination of Bcl-2 inhibitors with MIK665/S64315 or HDM201 lead to complete and durable antitumor responses in a variety of p53wt AML patient-derived xenograft models of heterogeneous genetic profiles. Notably, lowering the dose of HDM201 by 4 fold from its most efficacious dose, resulted in a high degree of tumor regressions while mitigating the toxicity effects on platelets. Taken together, these data demonstrate that a combination of Bcl-2 inhibitor (BCL201/S55746 or venetoclax) with MIK665/S64315 or HDM201 provide therapeutic benefit over the monotherapy, and support a rationale for testing these apoptosis enhancing combination approaches in AML patients.Citation Format: Youzhen Wang, Shumei Qui, Sneha Sanghavi, Iain Mulford, Gaëlle Lysiak, Maïa Chanrion, Prakash Mistry, Ulrike Pfaar, Marie Schoumacher, Audrey Claperon, Laurence Kraus-Berthier, Sébastien Banquet, Alix Derreal, Claire Fabre, Heiko Maacke, Frédéric Colland, Olivier Geneste, Erick Morris, Ensar Halilovic. Targeting AML through apoptosis activation using Bcl-2/Mcl-1 or Bcl-2/Hdm2 inhibitor combination therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 257.
Supplemental Table 1 from Prospective Evaluation of Doxorubicin Cardiotoxicity in Patients with Advanced Soft-tissue Sarcoma Treated in the ANNOUNCE Phase III Randomized Trial (2023)

&lt;p&gt;Cardiac treatment-emergent adverse events in the two trial groups&lt;/p&gt;
Initiation of Radical Chain Reactions of Thiol Compounds and Alkenes without any Added Initiator: Thiol‐Catalyzed cis/trans Isomerization of Methyl Oleate (2012)

Abstract A kinetic study of the dodecanethiol‐catalyzed cis/trans isomerization of methyl oleate ( cis ‐ 2 ) without added initiator was performed by focusing on the initiation of the radical chain reaction. The reaction orders of the rate of isomerization were 2 and 0.5 for 1 and cis ‐ 2 , respectively, and an overall kinetic isotope effect k H / k D of 2.8 was found. The initiation was shown to be a complex reaction. The electron‐donor/‐acceptor (EDA) complex of dodecanethiol ( 1 ) and cis ‐ 2 formed in a pre‐equilibrium reacts with thiol 1 to give a stearyl and a sulfuranyl radical through molecule‐assisted homolysis (MAH) of the sulfur–hydrogen bond. Fragmentation of the latter gives the thiyl radical, which catalyzes the cis/trans isomerization. A computational study of the EDA complex, MAH reaction, and the sulfuranyl radical calculated that the activation energy of the isomerization was in good agreement with the experimental result of E A =82 kJ M −1 . Overall, the results may explain that the thermal generation of thiyl radicals without any initiator is responsible for many well‐known thermally initiated addition reactions of thiol compounds to alkenes and their respective polymerizations and for the low shelf‐life stability of cis ‐unsaturated thiol compounds and of mixtures of alkenes and thiol compounds.
Far-field approximation for a point-excited anisotropic plate (2013)

An analytic approximation is derived for the far-field response of a generally anisotropic plate subject to a time-harmonic point force acting normal to the plate. This approximation quantifies the directivity of the flexural wave field that propagates away from the force, which is expected to be useful in the design and testing of anisotropic plates. Derivation of the approximation begins with a two-dimensional Fourier transform of the flexural equation of motion. Inversion to the spatial domain is accomplished by contour integration over the radial component of wave number followed by an application of the method of stationary phase to integration over the circumferential component of wave number. The resulting approximation resembles that of an isotropic plate but involves wave numbers, wave amplitudes, and phases that depend on propagation angle. Numerical results for a plate comprised of bonded layers of a graphite-epoxy material illustrate the accuracy of the method compared to a numerical simulation based on discrete Fourier analysis. Three configurations are analyzed in which the relative angles of the layers are varied. In all cases, the agreement is quite good when the distance between force and observation point is greater than a few wavelengths.
Metabotropic Glutamate Receptor Type 4 Is Involved in Autoinhibitory Cascade for Glucagon Secretion by α-Cells of Islet of Langerhans (2004)

In islets of Langerhans, L-glutamate is stored in glucagon-containing secretory granules of alpha-cells and cosecreted with glucagon under low-glucose conditions. The L-glutamate triggers secretion of gamma-aminobutyric acid (GABA) from beta-cells, which in turn inhibits glucagon secretion from alpha-cells through the GABAA receptor. In the present study, we tested the working hypothesis that L-glutamate functions as an autocrine/paracrine modulator and inhibits glucagon secretion through a glutamate receptor(s) on alpha-cells. The addition of L-glutamate at 1 mmol/l; (R,S)-phosphonophenylglycine (PPG) and (S)-3,4-dicarboxyphenylglycine (DCPG), specific agonists for class III metabotropic glutamate receptor (mGluR), at 100 micromol/l; and (1S,3R,4S)-1-aminocyclopentane-1,3,4-tricarboxylic acid (ACPT-I) at 50 micromol/l inhibited the low-glucose-evoked glucagon secretion by 87, 81, 73, and 87%, respectively. This inhibition was dose dependent and was blocked by (R,S)-cyclopropyl-4-phosphonophenylglycine (CPPG), a specific antagonist of class III mGluR. Agonists of other glutamate receptors, including kainate and quisqualate, had little effectiveness. RT-PCR and immunological analyses indicated that mGluR4, a class III mGluR, was expressed and localized with alpha- and F cells, whereas no evidence for expression of other mGluRs, including mGluR8, was obtained. L-Glutamate, PPG, and ACPT-I decreased the cAMP content in isolated islets, which was blocked by CPPG. Dibutylyl-cAMP, a nonhydrolyzable cAMP analog, caused the recovery of secretion of glucagon. Pertussis toxin, which uncouples adenylate cyclase and inhibitory G-protein, caused the recovery of both the cAMP content and secretion of glucagon. These results indicate that alpha- and F cells express functional mGluR4, and its stimulation inhibits secretion of glucagon through an inhibitory cAMP cascade. Thus, L-glutamate may directly interact with alpha-cells and inhibit glucagon secretion.
Endothelium and growth factors in vascular remodeling of hypertension. (1991)

The pioneering work of Furchgott, Moncada, and Vane has clearly established that the endothelium plays a critical role in the regulation of vascular tone. The endothelium produces several potent vasoactive substances, including vasodilators such as endothelium-derived relaxing factor and prostacyclin as well as vasoconstrictors such as angiotensin II and endothelin. These vasoactive substances not only have short-term effects on vascular tone but also appear to induce long-term effects on vascular structure. This process of vascular remodeling involves cell growth or regression and extracellular matrix expansion or contraction. As the interface between the bloodstream and the vessel wall, the endothelium plays a pivotal role in sensing and transducing the stimulus that induces vascular remodeling as well as producing the mediators that alter cell growth and the composition of the extracellular matrix. The endothelium maintains homeostasis within the vasculature by a balance between vasodilators and vasoconstrictors or growth inhibitors and growth promoters. Endothelial cell dysfunction may alter the delicate balance of mediators necessary to maintain homeostasis. Indeed, endothelial cell dysfunction is a common pathogenetic defect in animal models of hypertension as well as in hypertensive humans. Further understanding of the cellular and molecular mechanisms of vascular remodeling induced by endothelial cell-derived mediators may have important implications in the pathogenesis and treatment of hypertension.
Narrow-beam divergence 1.3-μm multiple-quantum-well laser diodes with monolithically integrated tapered thickness waveguide (1997)

This paper describes the optimum design, fabrication, and performance of a 1.3-/spl mu/m multiple-quantum-well (MQW) laser diode monolithically integrated with a tapered thickness spot-size transformer. The dependence of the lasing characteristics on the thickness distribution of the core layer and on the current injection profile of the device were analyzed. This integrated laser with its optimized structure performed at a low threshold current of 22.2 mA, even at 85/spl deg/C. The integrated spot-size transformer effectively reduced the lateral and vertical far-field FWHM's to 8/spl deg/ and 9/spl deg/, respectively. A very long lifetime of over 1/spl times/10/sup 5/ h was estimated at 85/spl deg/C and 8 mW under CW operation.
Alkali modified P25 with enhanced CO2 adsorption for CO2 photoreduction (2020)

To improve the CO<sub>2</sub> adsorption on the photocatalyst, which is an essential step for CO<sub>2</sub> photoreduction, solid solutions were fabricated using a facile calcination treatment at 900 °C. Using various alkalis, namely NaOH, Na<sub>2</sub>CO<sub>3</sub>, KOH, K<sub>2</sub>CO<sub>3</sub>, the resulted samples presented a much higher CO<sub>2</sub> adsorption capacity, which was measured with the pulse injection of CO<sub>2</sub> on the temperature programmed desorption workstation, compared to the pristine Evonik P25. As a result, all of the fabricated solid solutions produced higer yield of CO under UV light irradiation due to the increased basicity of the solid solutions even though they possessed only the rutile polymorph of TiO<sub>2</sub>. The highest CO<sub>2</sub> adsorption capacity under UV irradiation was observed in the sample treated with NaOH, which contained the highest amount of isolated hydroxyls, as shown in the FTIR studies.
Low-loss tunable capacitors fabricated directly on gold bottom electrodes (2006)

At microwave frequencies, conductor losses due to the bottom electrode resistance severely limit the performance of metal-insulator-metal capacitors that employ tunable dielectric thin films. Here we demonstrate that a novel tunable dielectric, bismuth zinc niobate (BZN), can be integrated directly with low-resistivity Au bottom electrodes. The favorable crystallization kinetics allowed for a low thermal budget process compatible with Au electrodes. BZN thin films on Au bottom electrodes showed low dielectric loss tangents of ∼0.0005 and high dielectric tunabilities of ∼50%. The Au/BZN interface was abrupt and free of reaction phases. At high frequencies (&amp;gt;1MHz) the total Au/BZN capacitor device loss was reduced compared to capacitors with Pt bottom electrodes. The low device losses of Au/BZN capacitors revealed a device geometry-dependent loss mechanism that contributed significantly to the device loss at high frequencies.
COMPARATIVE ANALYSIS OF DIFFERENT BRANDS OF DICLOFENAC SODIUM (2014)

Objective: The aim of this study to analyze the different brands of diclofenac sodium. Diclofenac is a widely used analgesic, classified as Non steroidal anti inflammatory drug. In different clinical conditions such as acute or chronic pain and inflammation especially as in surgery, back pain, dysmenorrhea, renal and biliary colic as well as in postoperative and post-traumatic conditions, diclofenac sodium has been an effective analgesic agent. No one of the NSAID non-steroidal anti-inflammatory agents is suitable drug for all patients requiring such therapy. Therefore it is important to choose best brand because different brands available in markeet. Method: In our present study different brands of Diclofenac Sodium are evaluated for weight variation, hardness and friability. Results: The results showed that all parameters (weight-variation, thickness, hardness, friability of different brands of Diclofenac Sodium, are in accordance with the BP/USP limits. Conclusion: We conclude that all drugs are in accordance with USP/BP therefore we can choose from any one of them for therapeutic purpose.
Single-mode optical fibers using Pade approximants (1998)

We propose a new, fast, and accurate numerical technique for analyzing single-mode optical fibers with arbitrary (transverse) refractive index profile. The method is based upon a Pade (rational) approximation of the spectral domain Green's function of the fiber, obtained by solving a hierarchy of static problems. The sought eigenfrequency and modal field are accordingly estimated by computing, respectively, the dominant pole and the related residual of the rational approximant. Numerical simulations and comparison with known analytical results indicate that the proposed method is highly accurate, reliable, and computationally affordable.
Wedge Shock and Nozzle Exhaust Plume Interaction in a Supersonic Jet Flow (2014)

Fundamental research for sonic boom reduction is needed to quantify the interaction of shock waves generated from the aircraft wing or tail surfaces with the nozzle exhaust plume. Aft body shock waves that interact with the exhaust plume contribute to the near-field pressure signature of a vehicle. The plume and shock interaction was studied using computational fluid dynamics and compared with experimental data from a coaxial convergent-divergent nozzle flow in an open jet facility. A simple diamond-shaped wedge was used to generate the shock in the outer flow to study its impact on the inner jet flow. Results show that the compression from the wedge deflects the nozzle plume and shocks form on the opposite plume boundary. The sonic boom pressure signature of the nozzle exhaust plume was modified by the presence of the wedge. Both the experimental results and computational predictions show changes in plume deflection.
Structural insight into glucose dehydrogenase from the thermoacidophilic archaeonThermoplasma volcanium (2014)

Glucose dehydrogenase from the thermoacidophilic archaeon Thermoplasma volcanium (tvGlcDH) is highly active towards D-glucose and D-galactose, but does not utilize aldopentoses such as D-xylose as substrates. In the present study, the crystal structures of substrate/cofactor-free tvGlcDH and of a tvGlcDH T277F mutant in a binary complex with NADP and in a ternary complex with D-glucose and nicotinic acid adenine dinucleotide phosphate, an NADP analogue, were determined at resolutions of 2.6, 2.25 and 2.33 Å, respectively. The overall structure of each monomer showed notable similarity to that of the enzyme from Sulfolobus solfataricus (ssGlcDH-1), which accepts a broad range of C5 and C6 sugars as substrates. However, the amino-acid residues of tvGlcDH involved in substrate binding markedly differed from those of ssGlcDH-1. Structural comparison revealed that a decreased number of interactions between the C3-hydroxyl group of the sugar and the enzyme are likely to be responsible for the lack of reactivity of tvGlcDH towards D-xylose.
Differences in the amount and structure of extractable skin and seed tannins amongst red grape varieties (2008)

Background and Aims: Red wine is a very rich source of flavanols, consisting of catechins and oligomeric and polymeric proanthocyanidins (PAs). The aim of this study was to investigate the composition of the fraction of flavanols, which is extractable from the grape into the wine. Methods and Results: Using HPLC-DAD-MS analysis carried out before and after thioacidolysis of wine-like extracts obtained from skins and seeds, the flavanol composition of 20 samples derived from Cabernet Sauvignon, Carmenere, Marzemino, Merlot, Pinot Noir, Syrah and Teroldego was determined. Conclusions: It was confirmed that grape extracts are mainly rich in monomers and small oligomers (mean degree of polymerization <8). Grape seed extracts contained three monomers (catechin, epicatechin and epicatechin gallate) and procyanidin oligomers. Grape skin extracts contained four monomers (catechin, epicatechin, gallocatechin and epigallocatechin), procyanidins and prodelphinidins oligomers. Upper and extension units of PAs were constituted mainly of epicatechin units, with the co-presence of catechin and epicatechin gallate in the seed PAs, and of gallocatechin in the case of skin PAs. The terminal units of the grape PAs were a mixture of five compounds, the same found also as monomers. Catechin gallate, gallocatechin gallate and epigallocatechin gallate, which are found in other flavanol-rich, plant-derived foods and beverages, were not present in grape extracts. Significance of the Study: The grape variety determines both the amount and the structure of wine flavanols, leading to differences in the composition, which are likely to play an important role in the nutritional and sensorial properties of the wines.
Low threshold Be implanted (GaAl)As laser on semi-insulating substrate (1980)

Be implanted stripe geometry double heterostructure lasers have been fabricated on a semi-insulating GaAs substrate, with threshold currents as low as 15 mA for a cavity length of 100 μm. The laser has been monolithically integrated with a metal-semiconductor field-effect transistor.
Supplementary Figure S2. HuR binds and stabilizes PARG mRNA from Posttranscriptional Regulation of <i>PARG</i> mRNA by HuR Facilitates DNA Repair and Resistance to PARP Inhibitors (2023)

&lt;p&gt;HuR directly binds and regulates poly-ADP ribose glycohydrolase mRNA expression particularly under PARPi stress, but doesn't affect expression of other PAR polymerases or hydrolyzing enzymes.&lt;/p&gt;
Photoacoustic Tomography Shows the Branching Pattern of Anterolateral Thigh Perforators In Vivo (2018)

Diagnostic, IV.
<title>Nonlinear approach to the 3-D reconstruction of microscopic objects</title> (1991)

The 3-D reconstruction of light microscopic objects has been extensively investigated in the past, but fundamental problems remain. The real object under observation does not normally have high transparency, and light transmission will be attenuated introducing nonlinearities in the imaging process. A nonlinear approach to this problem has been developed. In this nonlinear approach the authors regard the 3-dimensional spatially resolved light absorption coefficient as the object information of interest. A nonlinear equation system modeling the imaging process is proposed.
Effects of strained layer near SiO2–Si interface on electrical characteristics of ultrathin gate oxides (2000)

Ultrathin gate oxides formed by different process technologies are investigated in detail. The following important evidence is found: the discrepant result on the two time-dependent dielectric breakdown (TDDB) lifetime measurements, the constant-current stress, and the constant-voltage stress. The discrepancy is due mainly to the difference in the oxide leakage characteristics. Apparent changes in the activation energy and the defect generation rate during the TDDB testing are also experimentally observed for the two oxides formed by different process technologies. From the analysis based on the x-ray photoelectron spectroscopy by means of the oxide etch by dilute HF and the Fourier-transform infrared attenuated total reflection method, we consider that the above phenomena are induced by the difference in the built-in compressive strain of the Si–O network near the SiO2 and Si interface.
The sprint of COACH (2002)

COACH, a computer assisted wheelchair for handicapped people, is designed to assist its user to move in an every day environment, equipped with an embedded computer and data sensors. We tried to avoid the solutions that were too 'high-tech' in order to produce a representative prototype. For this reason the regular POIRIER electric wheelchair is used. The computer used is a simple PC, and the proximity sensors implemented are standard infrared and ultrasonic sensors.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Pathogenic T helper type 17 cells contribute to type 1 diabetes independently of interleukin-22 (2015)

We have shown that pathogenic T helper type 17 (Th17) cells differentiated from naive CD4(+) T cells of BDC2·5 T cell receptor transgenic non-obese diabetic (NOD) mice by interleukin (IL)-23 plus IL-6 produce IL-17, IL-22 and induce type 1 diabetes (T1D). Neutralizing interferon (IFN)-γ during the polarization process leads to a significant increase in IL-22 production by these Th17 cells. We also isolated IL-22-producing Th17 cells from the pancreas of wild-type diabetic NOD mice. IL-27 also blocked IL-22 production from diabetogenic Th17 cells. To determine the functional role of IL-22 produced by pathogenic Th17 cells in T1D we neutralized IL-22 in vivo by using anti-IL-22 monoclonal antibody. We found that blocking IL-22 did not alter significantly adoptive transfer of disease by pathogenic Th17 cells. Therefore, IL-22 is not required for T1D pathogenesis. The IL-22Rα receptor for IL-22 however, increased in the pancreas of NOD mice during disease progression and based upon our and other studies we suggest that IL-22 may have a regenerative and protective role in the pancreatic islets.
Investigation of spontaneously adsorbed globular protein films using high-frequency bulk acoustic wave resonators (2010)

In this paper we use micromachined, high-frequency, quartz bulk acoustic wave resonators to systematically study the physical and viscoelastic properties of spontaneously adsorbed globular protein films with molecular weights (MW) spanning two orders of magnitude. Specifically, changes in the frequency and the β-factor of the micromachined resonator array were studied as a function of concentration for three proteins, namely Human Serum albumin (HSA), Immunoglobulin G (IgG) and Human Fibrinogen (Fib) at the fundamental and third resonance modes. The results obtained were interpreted using equivalent electrical impedance models for the multilayer stack on the QCM surface. Discrete changes in the protein adsorption rate constant and the viscoelastic behavior was observed for all the three protein films. The spherical core-shell protein model is used to provide a simple explanation of the results. The work presented is a systematic and quantitative evaluation of the density, thickness, viscosity, and elastic modulus of the globular protein films, which was possible, due the use of the micromachined high frequency bulk acoustic wave resonators.