gebhart/patrepeval huggingface dataset:
Abstract B05: Inhibition of ER/Stat3 signaling pathways drive the evolution of ER+ metastatic breast cancer through the generation of ER-independent OXPHOShi self-renewing cells (2016)

Abstract A better understanding of the molecular features of the metastatic switch might reveal new cancer cell liabilities to develop novel therapeutics for metastatic cancer patients. Here we demonstrated that the generation of dormant and tumor-initiating cells takes place in the tumor microenvironment through a metabolic reprogramming in luminal (ER+) breast cancer. The expression of the surface markers interleukin 6 receptor (IL6R) and CD44 identify distinct tumor initiating and dormant cells. We demonstrated that IL6Rlo/CD44hi cells originate in hypoxic niches and self-renew following re-oxygenation via estrogen receptor alpha (ER)-dependent up-regulation of oxidative phosphorylation (OXPHOS). Conversely, IL6Rhi/Stat3hi cells are dormant populations arising in an environment defined by recurrent episodes of hypoxia/normoxia. These cells were characterized by decreased OXPHOS and ER activities. Reducing Stat3 expression resulted in cells resistant to hypoxia/re-oxygenation-mediated dormancy. Molecularly, Stat3lo cells had reduced ER signaling, high OXPHOS and increased metastatic capacity. Thus we propose that inhibition of ER/Stat3 signaling pathways drive the evolution of ER+ metastatic breast cancer through the generation of ER-independent-OXPHOShi self-renewing cancer cells. Citation Format: Pasquale Sansone, Marjan Berishaj, Qing Chang, Antonio Strillacci, Ferdinando Giacco, Jacqueline Bromberg. Inhibition of ER/Stat3 signaling pathways drive the evolution of ER+ metastatic breast cancer through the generation of ER-independent OXPHOShi self-renewing cells. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B05.
Role of Vitronectin-Rich Protein Corona on Tumor-Specific siRNA Delivery and Transfection with Lipid Nanoparticles (2021)

<b>Aim:</b> To evaluate the role of vitronectin-enriched protein corona on systemic delivery of siRNA-encapsulated cationic lipid nanoparticles (LNPs) to αvβ3 integrin expressing solid tumors. <b>Materials & methods:</b> 1,2-Dioleoyl-3-trimethylammonium-propane LNPs were formulated, protein corona formed in nude mice serum and its impact on drug delivery were analyzed. <b>Results:</b> 1,2-Dioleoyl-3-trimethylammonium-propane-containing LNP led to enhanced recruitment of vitronectin and showed preferential transfection to αvβ3-expressed cells relative to controls. Upon systemic administration in mice, the LNPs accumulated in the αvβ3-expressing endothelial lining of the tumor blood vessels before reaching tumor cells. <b>Conclusion:</b> These results present an optimized LNP that selectively recruits endogenous proteins <i>in situ</i> to its corona which may lead to enhanced delivery and transfection in tissues of interest.
Analysis Of Heart Beat Dynamics Through Singularity Spectrum (2011)

The analysis to detect arrhythmias and life-threatening conditions are highly essential in today world and this analysis can be accomplished by advanced non-linear processing methods for accurate analysis of the complex signals of heartbeat dynamics. In this perspective, recent developments in the field of multiscale information content have lead to the Microcanonical Multiscale Formalism (MMF). We show that such framework provides several signal analysis techniques that are especially adapted to the study of heartbeat dynamics. In this paper, we just show first hand results of whether the considered heartbeat dynamics signals have the multiscale properties by computing local preticability exponents (LPEs) and the Unpredictable Points Manifold (UPM), and thereby computing the singularity spectrum.
An Engineered Spider Silk Protein Forms Microspheres (2008)

Fibrils or spheres? Spider silk proteins belong to the class of natively unfolded proteins. Depending on the experimental conditions, these proteins form nanofibrils or microspheres following two distinct aggregation pathways. A detailed model describes the assembly mechanism of spider silk proteins into microspheres. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z800683_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
MOCVD Growth of Transparent Conducting Cd2SnO4 Thin Films (2004)

The first preparation of transparent conducting Cd 2 SnO 4 thin films by a simple MOCVD process is described. As‐deposited films using Cd(hfa) 2 (TMEDA) (Figure), at 365 °C are found to be highly crystalline with a relatively wide range of grain size of 100–300 nm. XRD indicates a cubic spinel Cd 2 SnO 4 crystal structure and the possible presence of a small amount of CdO. The films exhibit conductivities of 2170 S/cm and a bandgap of 3.3 eV, rivaling those of commercial tin‐doped indium oxide.
Valorisation of technical lignin in rigid polyurethane foam: a critical evaluation on trends, guidelines and future perspectives (2021)

Lignin is an inexpensive raw material that can be utilised in polymer industry. This review critically appraises the recent progress and provides framework for future developments in lignin valorisation into rigid polyurethane foam.
Oncometabolites d- and l-2-Hydroxyglutarate Inhibit the AlkB Family DNA Repair Enzymes under Physiological Conditions (2017)

Cancer-associated mutations often lead to perturbed cellular energy metabolism and accumulation of potentially harmful oncometabolites. One example is the chiral molecule 2-hydroxyglutarate (2HG); its two stereoisomers (d- and l-2HG) have been found at abnormally high concentrations in tumors featuring anomalous metabolic pathways. 2HG has been demonstrated to competitively inhibit several α-ketoglutarate (αKG)- and non-heme iron-dependent dioxygenases, including some of the AlkB family DNA repair enzymes, such as ALKBH2 and ALKBH3. However, previous studies have only provided the IC<sub>50</sub> values of d-2HG on the enzymes, and the results have not been correlated to physiologically relevant concentrations of 2HG and αKG in cancer cells. In this work, we performed detailed kinetic analyses of DNA repair reactions catalyzed by ALKBH2, ALKBH3, and the bacterial AlkB in the presence of d- and l-2HG in both double- and single-stranded DNA contexts. We determined the kinetic parameters of inhibition, including k<sub>cat</sub>, K<sub>M</sub>, and K<sub>i</sub>. We also correlated the relative concentrations of 2HG and αKG previously measured in tumor cells with the inhibitory effect of 2HG on the AlkB family enzymes. Both d- and l-2HG significantly inhibited the human DNA repair enzymes ALKBH2 and ALKBH3 at pathologically relevant concentrations (73-88% for d-2HG and 31-58% for l-2HG inhibition). This work provides a new perspective that the elevation of the d- or l-2HG concentration in cancer cells may contribute to an increased mutation rate by inhibiting the DNA repair performed by the AlkB family enzymes and thus exacerbate the genesis and progression of tumors.
Dual Sofosbuvir/Daclatasvir Therapy in Adolescent Patients With Chronic Hepatitis C Infection (2018)

SOF/DCV combined therapy could be a safe and effective treatment in adolescent patients 12 to 17 years old with chronic HCV genotype 4 infection. (See Video, Supplemental Digital Content, http://links.lww.com/MPG/B348).
3-Aza-Cope Rearrangement of Quaternary N-Allyl Enammonium Salts. Stereospecific 1,3 Allyl Migration from Nitrogen to Carbon on a Tricyclic Template (2000)

N-Allyl enamines can undergo a [3,3] sigmatropic rearrangement known as a 3-aza-Cope (or amino-Claisen) reaction. We explored a 3-aza-Cope reaction involving 1,3 allylic migration from nitrogen to carbon in N-allyl enammonium quaternary salts, exemplified by benzo[a]quinolizine 8 and pyrrolo[2,1-a]isoquinoline 13, with an interest in stereochemistry and mechanism. Salts 8 and 13 were accessed, respectively, through stereospecific allylation of hydroxy amines 4 and 11a/11b to give 7 and 12a/12b, which were dehydrated with trifluoroacetic acid. Allylic migration in these tricyclic tetrahydroisoquinolines occurred with high stereospecificity, with the major products 9 (from 8) and 15a (from 13) apparently deriving from a concerted suprafacial [3,3] rearrangement. The rearrangement of 8 to 9 was facile at 23 degrees C (t(1/2) = ca. 5 h) and was >98% stereospecific, whereas the rearrangement of 13 to 15a/15b required heating between 50 and 100 degrees C, with ca. 90-95% stereospecificity (t(1/2) = ca. 0.3 h at 100 degrees C). A deuterium-labeling experiment with 21 ((2)H-13) confirmed that allylic inversion accompanies the 1,3 migration en route to major isomer 22a ((2)H-15a), supporting the predominance of a concerted [3, 3] sigmatropic mechanism. However, the 5-10% loss of stereospecificity in the rearrangements of the pyrroloisoquinolines 13 and 21, reflected by formation of minor isomers 15b and 22b, respectively, indicates a minor nonconcerted reaction pathway.
Theseus' Paradox:: History, Authenticity and Identity (2019)

In the Life of Theseus, Plutarch observes: ship on which Theseus sailed with the youths and returned in safety, the thirty-oared galley, was preserved by the Athenians down to the time of Demetrius Phalereus. They took away the old timbers from time to time, and put new and sound ones in their places, so that the vessel became a standing illustration for the philosophers in the mooted question of growth, some declaring that it remained the same, others that it was not the same vessel.” (Plutarch, Perrin, 1914, V 1,49). Thereafter, the paradox sparked discussion regarding an object's authenticity and identity. For Barthes (1974), the paradox presents form-permanence as a Structural argument. Walter Benjamin (1969) disagreed noting that [t]he presence of the original is the prerequisite to the concept of authenticity.” When original producers are not available we can evaluate the relationship of contemporary design with historic modes of production through Material Culture. By privileging knowledge of what the spatial product is and how it was produced, the essay examines the role of History in addressing spatial authenticity. The essay uses Theseus' Paradox as a theoretical framework to evaluate authenticity and identity. Architectural objects either continue or discontinue the aesthetic language of their context; as designers cite History to generate designs claiming contextual site sensitivity, it is important to evaluate the validity of this approach. Specifically, Theseus' Ship is deconstructed using the philosophical arguments of atomism and essentialism. Atomism, a Positivist tool, determines elementary physical characteristics of a society's spatial practice. Essentialism (Aristotle) focuses on the nature of the spatial product: what it has been, it is, and could be. Designers can use Theseus' Paradox as a comparative framework to evaluate to what degree their proposal continues authentic modes of production rooted in historic spatial traditions and identity-based placemaking.
Role of intermediate state in the excited state dynamics of highly efficient TADF molecules (2016)

We hereby report the results of our direct investigation into the excited-state dynamics of thermally activated delayed fluorescence (TADF) molecules in solution using pump-probe transient absorption spectroscopy (TAS). We found that the charge-transfer (CT) state commonly stated for TADF molecules encompasses two forms: localized and delocalized CT states. A highly efficient TADF molecule, 4CzIPN [Uoyama et al., Nature, 492, 234-238 (2012)], showed both the localized and delocalized CT states, while an inefficient TADF molecule, 2CzPN, exhibited only a localized CT state. By analyzing the time profile of triplet species observed in TAS, we propose that the reverse intersystem crossing (RISC) of 4CzIPN occurs via a mutual interaction in multiple energy levels of localized neutral and CT states, and delocalized CT states.
Low-energy run of Fermilab Electron cooler's beam generation system (2010)

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Plasticity Underlying Multipotent Tumor Stem Cells (2009)

Aggressive cancer cells manifest stem-cell-like qualities that allow them to self-renew and to derive a heterogeneous tumor. Ultimately, this multipotent phenotype facilitates metastasis and resistance to therapy. Cancer cells likely acquire and maintain multipotent phenotypes by aberrantly expressing embryonic factors, such as Nodal and Notch, which maintain pluripotency in normal embryonic stem cell types. Recent studies have shown that Nodal, an embryonic morphogen belonging to the transforming growth factor-beta (TGF-β) superfamily, is aberrantly expressed in melanoma and breast carcinoma cells. Moreover, Nodal facilitates breast cancer and melanoma tumorigenesis. During development, Nodal is regulated by the spatial and temporal expression of inhibitors such as Lefty. In aggressive cancer cells, this balance of regulatory mediators is disrupted, leading to unchecked Nodal expression. By exposing aggressive cancer cells to embryonic microenvironments, inclusive of Lefty, Nodal expression is decreased and tumorigenesis is suppressed. Embryonic stem cell-derived factors, such as Lefty, may provide therapeutic modalities that may be used to specifically differentiate and eradicate aggressive cancers.
Solution-phase dielectric characterization of the 4-amino-4′-dicyanovinylazobenzene nonlinear-optical chromophore (1990)

The dielectric constants of solutions of 4-amino-4′-dicyanovinylazobenzene chromophore (DCV) at a wide range of concentrations in dioxane were measured. The chromophore dipole moment was determined to be 9.4 D in dioxane and in methyl trimethylacetate. Somewhat smaller values for the dipole moment were obtained when the chromophore was dissolved in chloroform or when it was covalently attached to a polymethacrylate backbone. No significant nonlinearity was observed in plots of dielectric constant versus concentration, even at concentrations approaching the solubility limit. Theoretical modeling indicates that such nonlinearity would have been observed if appreciable aggregation had occurred. It is predicted that dipole-dipole aggregation should not diminish the electric-field-induced alignment achievable in macroscopically homogeneous DCV-containing materials.
Abstract 4140: Discovery and characterization of novel highly potent A2A adenosine receptor antagonists for cancerimmunotherapy (2019)

Introduction: Extracellular adenosine produced at high concentrations within the tumor micro-environment (TME) and suppresses immune function via inhibition of immune cell activation. Targeting adenosine receptors has emerged as a novel method to activate anti-tumor immunity. In particular, A2A adenosine receptor (A2AR), one of the G-protein-coupled-receptors, exhibits immunosuppressive functions. Herein, we suggest novel A2AR antagonist lead compounds as a highly potent antagonist of A2AR for immunotherapy.Materials and Methods: Novel A2AR antagonist lead compounds were designed using CADD and synthesized as the active biologic inhibitory compound. The protein preparation and molecular docking were performed using Glide (Schrödinger). A radioligand binding assay was performed to evaluate the affinities of A2AR Antagonists for the human adenosine A2AR. The potencie of A2AR antagonists were determined by cAMP assay in HEK293-hA2AR cells and cAMP-mediated pCREB assay in human CD8+ T cells from whole blood. In vivo CT26 and MC38 syngeneic tumor models were used to assess the therapeutic effect of A2AR antagonists.Results: A2AR antagonist lead compounds showed strong binding affinities toward human A2AR. They also potently inhibited the NECA-mediated production of intracellular cAMP in HEK293 cells expressing human A2AR. Elevated intracellular cAMP following A2AR activation results in the phosphorylation of CREB (cAMP response element-binding protein). A2AR antagonist lead compounds treatment inhibited pCREB in NECA-stimulated HEK293-hA2AR and human CD8+ T cells. A2AR antagonist lead compounds inhibited tumor growth of mouse syngeneic tumor models as a single agent and combination with anti-PD-L1. In combination with anti-PD-L1, A2AR antagonist lead compounds had remarkable antitumor activities in multiple mouse tumor models, including restoration of immune responses in models that incompletely responded to anti-PD-L1 monotherapy.Conclusion: These results showed the potencies of A2AR antagonist lead compounds with high capability of A2AR inhibition. Blockade of the adenosine signaling pathway may be vital for enhancing anti-tumor responses in solid tumors that show an incomplete response to anti-PD-L1 therapy. A2AR antagonist lead compounds demonstrate a novel approach to anti-cancer immunotherapy.Citation Format: Kyungik Lee, Seungah Jun, EunYoung Byun, Hosun Lee, Yongtaek Lee, MiJin Moon, Yu-Yon Kim, Hyun Jeong Kang, YoungGil Ahn, YoungHoon Kim, Kwee Hyun Suh. Discovery and characterization of novel highly potent A2A adenosine receptor antagonists for cancerimmunotherapy [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 4140.
PRO-2000 exhibits SARS-CoV-2 antiviral activity by interfering with spike-heparin binding (2023)

Here, we report on the anti-SARS-CoV-2 activity of PRO-2000, a sulfonated polyanionic compound. In Vero cells infected with the Wuhan, alpha, beta, delta or omicron variant, PRO-2000 displayed EC<sub>50</sub> values of 1.1 μM, 2.4 μM, 1.3 μM, 2.1 μM and 0.11 μM, respectively, and an average selectivity index (i.e. ratio of cytotoxic versus antiviral concentration) of 172. Its anti-SARS-CoV-2 activity was confirmed by virus yield assays in Vero cells, Caco2 cells and A549 cells overexpressing ACE2 and TMPRSS2 (A549-AT). Using pseudoviruses bearing the SARS-CoV-2 spike (S), PRO-2000 was shown to block the S-mediated pseudovirus entry in Vero cells and A549-AT cells, with EC<sub>50</sub> values of 0.091 μM and 1.6 μM, respectively. This entry process is initiated by interaction of the S glycoprotein with angiotensin-converting enzyme 2 (ACE2) and heparan sulfate proteoglycans. Surface Plasmon Resonance (SPR) studies showed that PRO-2000 binds to the receptor-binding domain (RBD) of S with a K<sub>D</sub> of 1.6 nM. Similar K<sub>D</sub> values (range: 1.2 nM-2.1 nM) were obtained with the RBDs of the alpha, beta, delta and omicron variants. In an SPR neutralization assay, PRO-2000 had no effect on the interaction between the RBD and ACE2. Instead, PRO-2000 was proven to inhibit binding of the RBD to a heparin-coated sensor chip, yielding an IC<sub>50</sub> of 1.1 nM. To conclude, PRO-2000 has the potential to inhibit a broad range of SARS-CoV-2 variants by blocking the heparin-binding site on the S protein.
Amorphous Silica Nanoparticles Promote Monocyte Adhesion to Human Endothelial Cells: Size‐Dependent Effect (2012)

There is evidence that nanoparticles can induce endothelial dysfunction. Here, the effect of monodisperse amorphous silica nanoparticles (SiO(2)-NPs) of different diameters on endothelial cells function is examined. Human endothelial cell line (EA.hy926) or primary human pulmonary artery endothelial cells (hPAEC) are seeded in inserts introduced or not above triple cell co-cultures (pneumocytes, macrophages, and mast cells). Endothelial cells are incubated with SiO(2)-NPs at non-cytotoxic concentrations for 12 h. A significant increase (up to 2-fold) in human monocytes adhesion to endothelial cells is observed for 18 and 54 nm particles. Exposure to SiO(2)-NPs induces protein expression of adhesion molecules (ICAM-1 and VCAM-1) as well as significant up-regulation in mRNA expression of ICAM-1 in both endothelial cell types. Experiments performed with fluorescent-labelled monodisperse amorphous SiO(2)-NPs of similar size evidence nanoparticle uptake into the cytoplasm of endothelial cells. It is concluded that exposure of human endothelial cells to amorphous silica nanoparticles enhances their adhesive properties. This process is modified by the size of the nanoparticle and the presence of other co-cultured cells.
Zeroth-Order Optimization on Subsets of Symmetric Matrices With Application to MPC Tuning (2021)

This article provides a zeroth-order optimization framework for nonsmooth and possibly nonconvex cost functions with matrix parameters that are real and symmetric. We provide complexity bounds on the number of iterations required to ensure a given accuracy level for both the convex and nonconvex cases. The derived complexity bounds for the convex case are less conservative than available bounds in the literature since we exploit the symmetric structure of the underlying matrix space. Moreover, the nonconvex complexity bounds are novel for the class of optimization problems that we consider. The utility of the framework is evident in the suite of applications that use symmetric matrices as tuning parameters. Of primary interest here is the challenge of tuning the gain matrices in model predictive controllers, as this is a challenge known to be inhibiting the industrial implementation of these architectures. To demonstrate the framework, we consider the problem of MIMO diesel air-path control and implement the framework iteratively “in-the-loop” to reduce tracking error on the output channels. Both simulations and experimental results are included to illustrate the effectiveness of the proposed framework over different engine drive cycles.
ChemInform Abstract: Synthesis of Enantiomerically Pure Amino Acids Containing 2,5‐Disubstituted THF Rings in the Molecular Backbone. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
High-precision fringe tracking invariant to systematic model errors (2001)

We present a new approach to processing of interferometric data, which dramatically improves operation on the smallest fraction of the fringe (approximately 1/1,000 of a wavelength and beyond). In particular, this approach, dubbed the variation-invariant subspace tracking approach (VISTA), makes it possible to operate a Michelson interferometer in a highly stable mode in which the estimation of optical path delay becomes invariant (insensitive) to a large class of systematic model errors. This previously unknown invariance property of interferometry follows from the fundamental odd-even symmetry of the channeled spectrum and its derivatives. VISTA offers a powerful algorithmic alternative for alleviating technological challenges in the design of high-precision long-baseline spaceborne interferometers.
Edema by T2-weighted imaging in salvaged myocardium is extracellular, not intracellular (2011)

T2-weighted MRI can image myocardial edema in salvaged, non-infarcted myocardium. However, it is unclear whether this edema is mostly intra-, extracellular, or balanced.