gebhart/patrepeval huggingface dataset:
The Design and Evaluation of Heparin‐Binding Foldamers (2005)

Kontrolle über den Blutverlust: Die Wechselwirkung der Arylamidoligomere 1, deren Synthese hier vorgestellt wird, mit Heparin inhibiert die Fähigkeit von Heparin, Antithrombin zu aktivieren. Diese Arylamidoligomere sind die ersten Beispiele für niedermolekulare Antagonisten, die die antikoagulierende Wirkung von Heparin inhibieren.
Antibody engineering to generate SKY59, a long-acting anti-C5 recycling antibody (2018)

Modulating the complement system is a promising strategy in drug discovery for disorders with uncontrolled complement activation. Although some of these disorders can be effectively treated with an antibody that inhibits complement C5, the high plasma concentration of C5 requires a huge dosage and frequent intravenous administration. Moreover, a conventional anti-C5 antibody can cause C5 to accumulate in plasma by reducing C5 clearance when C5 forms an immune complex (IC) with the antibody, which can be salvaged from endosomal vesicles by neonatal Fc receptor (FcRn)-mediated recycling. In order to neutralize the increased C5, an even higher dosage of the antibody would be required. This antigen accumulation can be suppressed by giving the antibody a pH-dependent C5-binding property so that C5 is released from the antibody in the acidic endosome and then trafficked to the lysosome for degradation, while the C5-free antibody returns back to plasma. We recently demonstrated that a pH-dependent C5-binding antibody, SKY59, exhibited long-lasting neutralization of C5 in cynomolgus monkeys, showing potential for subcutaneous delivery or less frequent administration. Here we report the details of the antibody engineering involved in generating SKY59, from humanizing a rabbit antibody to improving the C5-binding property. Moreover, because the pH-dependent C5-binding antibodies that we first generated still accumulated C5, we hypothesized that the surface charges of the ICs partially contributed to a slow uptake rate of the C5-antibody ICs. This idea motivated us to engineer the surface charges of the antibody. Our surface-charge engineered antibody consequently exhibited a high capacity to sweep C5 and suppressed the C5 accumulation in vivo by accelerating the cycle of sweeping: uptake of ICs into cells, release of C5 from the antibody in endosomes, and salvage of the antigen-free antibody. Thus, our engineered anti-C5 antibody, SKY59, is expected to provide significant benefits for patients with complement-mediated disorders.
NMR Assessment of Therapeutic Peptides and Proteins: Correlations That Reveal Interactions and Motions (2019)

NMR measurements of rotational and translational diffusion are used to characterize the solution behavior of a wide variety of therapeutic proteins and peptides. The timescales of motions sampled in these experiments reveal complicated intrinsic solution behavior such as flexibility, that is central to function, as well as self-interactions, stress-induced conformational changes and other critical attributes that can be discovery and development liabilities. Trends from proton transverse relaxation (R<sub>2</sub> ) and hydrodynamic radius (R<sub>h</sub> ) are correlated and used to identify and differentiate intermolecular from intramolecular interactions. In this study, peptide behavior is consistent with complicated multimer self-assembly, while multi-domain protein behavior is dominated by intramolecular interactions. These observations are supplemented by simulations that include effects from slow transient interactions and rapid internal motions. R<sub>2</sub> -R<sub>h</sub> correlations provide a means to profile protein motions as well as interactions. The approach is completely general and can be applied to therapeutic and target protein characterization.
Abstract 11040: Poloxamer 188 Protects Endothelial Cells From Hypoxia/Reoxygenation Injury - Implications for Cardio- and Neuroprotection After Cardiac Arrest (2015)

Introduction: Cardiac arrest is a leading cause of death. Even with the best CPR, many patients die or suffer severe cardio-cerebral damage. Reintroduction of blood flow at the start of CPR after systemic ischemia may cause additional injury to organs such as the heart and brain beyond that caused by the ischemia itself. Determining the mechanism of action of a compound administered during CPR on the cellular dysfunction caused by ischemia/reperfusion could improve CPR practices in the future. Hypothesis: Poloxamer 188 (P188), with its unique hydro-/lipophilic chemical properties, protects coronary and cerebral endothelial cells against hypoxia/reoxygenation (H/R) injury. Methods: Endothelial cells (human coronary artery [HCAECs] and rat brain [RBECs]) underwent 2 hrs hypoxia (1% O2) then 2 hrs reoxygenation ± P188. Endpoints were markers of cellular injury (lactate dehydrogenase [LDH] release, mitochondrial dehydrogenase activity), proliferation, and nitric oxide (NO) release. Statistics: Student t-test followed by SNK post hoc comparisons, *p&lt;0.05 vs control, † vs normoxia. Results: In HCAECs, H/R caused significant LDH release compared to cells in normoxic conditions (†0.774±0.084 vs 0.562±0.141 abs/mg protein; n=5). P188 significantly decreased LDH release in both hypoxic and normoxic conditions (*0.215±0.024 vs *0.273±0.02). P188 also significantly attenuated decreased mitochondrial dehydrogenase activity caused by H/R (*0.379±0.015 vs 0.468±0.035 abs/mg protein). NO measurement by DAF-2DA fluorescence showed higher levels in cells treated with P188 upon reoxygenation than controls (*164,944±6,716 vs 139,942±2,511 RFUs). In proliferation assays of HCAECs and RBECs, there was significantly lower proliferation following H/R than during normoxia (HCAECs: 16,030±716 vs †7,500±465; RBECs: 13,563±1,251 vs †7,323±297 cells/well). This decrease was dose-dependently attenuated by P188 when compared to control (HCAECs: 1μM, *8,523±495; 1mM, *8,827±375. RBECs: 1μM, *7,782±274; 1mM, *8,930±177). Conclusions: HCAECs and RBECs were protected by P188 against H/R, and P188 also increased NO release in HCAECs. P188 protection of cardiomyocytes and neurons may be mediated by the preservation of NO release from the endothelium.
Von Willebrand factor promoter targets the expression of amyloid β protein precursor to brain vascular endothelial cells of transgenic mice (2003)

Dysfunction of brain vascular endothelial cells may be associated with the pathogenesis of several diseases including cerebral amyloid angiopathy, hemorrhagic stroke and Alzheimer disease. New model systems are necessary to examine the contribution of brain endothelial cells in these disorders. The Von Willebrand factor gene promoter fragment that spans sequences -487 to +247 targets the expression of LacZ marker gene in transgenic mice specifically to brain vascular endothelial cells. Transgenic mice have been prepared that express human amyloid beta protein precursor protein (AbetaPP) isoforms 695 and 751 (wild-type and Dutch variant mutations) under the regulation of this VWF promoter sequence. These AbetaPP transgenes are specifically expressed in brain vascular endothelial cells. The VWF promoter is a valuable tool for targeting gene expression to brain vascular endothelial cells to provide a model to directly examine endothelial cell placement of genes and their contribution to cerebral vascular disease.
2‐D chromatography applied to the study of block copolymers synthesized by nitroxide‐mediated controlled free‐radical seeded emulsion polymerization (2010)

2-D chromatography with gradient polymer elution chromatography in the first dimension was used to characterize a series of block copolymers prepared by nitroxide-mediated controlled free-radical seeded emulsion polymerization. The data provide a detailed picture of the different populations generated during the successive stages of the reaction. In particular, deviations from ideal conditions, such as an exothermic temperature spike, are obvious from the 2-D chromatogram, and its interpretation provides unique insight into the reaction mechanisms. Finally, atomic force microscopy images obtained on films cast from copolymer solutions evidence the relationship between polymer microstructure and film morphology.
UWTOR-M-a conceptual design study of a modular stellarator power reactor (1981)

A preliminary design of a 5500 MW <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> modular stellarator power reactor, UWTOR-M, is presented. Discrete twisted coils are used in an l = 3 configuration with maintainability as a prime consideration. The natural steliarator divertor is used for impurity control in conjunction with innovative high performance divertor targets. A unique blanket design is proposed which minimizes the overall tritium inventory in the reactor. Finally, a scheme for maintaining the first wall/blanket and other reactor components is discussed.
Compact high brightness and high power diode laser source for materials processing (2001)

A compact, reliable semiconductor laser source for materials processing, medical and pumping applications is described. This industrial laser source relies on a combination of technologies that have matured in recent years. In particular, effective means of stacking and imaging monolithic semiconductor laser arrays (bars), together with advances in the design and manufacture of the bars, have enabled the production of robust sources at market-competitive costs. Semiconductor lasers are presently the only lasers known combining an efficiency of about 50% with compact size and high reliability. Currently the maximum demonstrated output power of a 10-mm wide semiconductor laser bar exceeds the 260 W level when assembled on an actively cooled heat sink. (The rated power is in the range of 50 to 80 W with a projected lifetime of 10.000 hours) Power levels in the kW range can be reached by stacking such devices. The requirements on the stacking technique and the optical assembly to achieve high brightness are discussed. An example of the optical setup, used in materials processing, will be shown. Spot sizes as low as 0.06 mm × 1.2 mm (FWHM) at a numerical aperture of 0.3 and output power of 500 W is achieved. This results in a power density of more than 600 kW/cm2. For increase of power wavelength coupling is used.
Low-Level Endogenous PSMA Expression in Nonprostatic Tumor Xenografts Is Sufficient for In Vivo Tumor Targeting and Imaging (2017)

Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and within the neovasculature of other solid tumors. The nonprostatic expression of PSMA has been reported exclusively within the neovasculature endothelial cells of nonprostatic cancers; however, there are few reports on PSMA expression in epithelial cells. Herein, we describe PSMA expression in nonprostatic epithelial cells and characterize the potential of PSMA-binding agents to noninvasively detect that expression. <b>Methods:</b> PSMA expression data were extracted from publicly available genomic databases. Genomic data were experimentally validated for PSMA expression-by quantitative reverse transcription polymerase chain reaction, flow cytometry, and Western blotting-in several nonprostatic cell lines and xenografts of melanoma and small cell lung cancer (SCLC) origin. The feasibility of PSMA detection in those tumor models was further established using PSMA-based nuclear and optical imaging agents and by biodistribution, blocking, and ex vivo molecular characterization studies. <b>Results:</b> We discovered that a small percentage of nonprostatic cancer cell lines and tumors express PSMA. Importantly, PSMA expression was sufficiently high to image established melanoma and SCLC xenografts using PSMA-based nuclear and optical imaging agents. <b>Conclusion:</b> These results indicate that PSMA expression in nonprostatic tumors may not be limited to the endothelium but may also include solid tumor tissue of nonprostatic cancers including melanoma and SCLC. Our observations indicate broader applicability of PSMA-targeted imaging and therapeutics.
Electrochemical detection of fulleronium and highly reduced fulleride (C605-) ions in solution (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrochemical detection of fulleronium and highly reduced fulleride (C605-) ions in solutionDominique Dubois, Karl M. Kadish, Scott Flanagan, and Lon J. WilsonCite this: J. Am. Chem. Soc. 1991, 113, 20, 7773–7774Publication Date (Print):September 1, 1991Publication History Published online1 May 2002Published inissue 1 September 1991https://doi.org/10.1021/ja00020a056RIGHTS & PERMISSIONSArticle Views552Altmetric-Citations219LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (281 KB) Get e-Alerts Get e-Alerts
Respiratory Deficiency Enhances the Sensitivity Candida to Photodynamic Treatment (2008)

DOI: 10.1111/j.1751-1097.2007.00280.x In the most recent issue of Photochemistry and Photobiology, 2008, 84(5), 1141–1148, an error in Figure 2 was published. The corrected Figure 2 is shown:
Influence of proinflammatory cytokines on Actinobacillus actinomycetemcomitans specific IgG responses (2005)

The cytokines IL-1alpha, IL-1beta, IFN-gamma, IL-12, and PGE(2) were all necessary for optimal production of human anti-A. actinomycetemcomitans and the need for proinflammatory cytokines including the T helper 1 (Th1) cytokines is consistent with a response with a significant IgG2 component.
Insight into the Cellular Uptake Mechanism of a Secondary Amphipathic Cell-Penetrating Peptide for siRNA Delivery (2010)

Delivery of siRNA remains a major limitation to their clinical application, and several technologies have been proposed to improve their cellular uptake. We recently described a peptide-based nanoparticle system for efficient delivery of siRNA into primary cell lines: CADY. CADY is a secondary amphipathic peptide that forms stable complexes with siRNA and improves their cellular uptake independently of the endosomal pathway. In the present work, we have combined molecular modeling, spectroscopy, and membrane interaction approaches in order to gain further insight into CADY/siRNA particle mechanism of interaction with biological membrane. We demonstrate that CADY forms stable complexes with siRNA and binds phospholipids tightly, mainly through electrostatic interactions. Binding to siRNA or phospholipids triggers a conformational transition of CADY from an unfolded state to an alpha-helical structure, thereby stabilizing CADY/siRNA complexes and improving their interactions with cell membranes. Therefore, we propose that CADY cellular membrane interaction is driven by its structural polymorphism which enables stabilization of both electrostatic and hydrophobic contacts with surface membrane proteoglycan and phospholipids.
Peripheral Nerve Stimulation (PNS) Analysis of MRI Head Gradient Coils with Human Body Models (2022)

Abstract The main objective of this chapter is to provide a comprehensive and intuitive introduction to MRI gradient coil related PNS modeling with human body models. We will present the fundamental concepts and analytical processes behind gradient coil-induced peripheral nerve stimulation (PNS) modeling and also show some new results of our work. We first describe the process of performing electromagnetic simulation of a gradient coil, the neurodynamic simulation of nerves, and the gradient coil design. Then, we present improvements of two existing human body models by adding more nerve trajectories in the head and upper body to reduce the discrepancies between the simulated and measured results for PNS thresholds in head gradient coils. Further, we apply the modified human body models to analyze three folded and non-folded gradient coils and reveal the relationship between the eddy current flow in the human body and the gradient coil wire pattern and its impact on the PNS. We also show the connection between concomitant fields and PNS and assess the accuracy of PNS calculations in human body models with simplified tissue properties. Finally, we give our thoughts on the future direction of this work.
Time series data analysis using fractional calculus concepts and fractal analysis (2009)

A study is conducted on time series data analysis relating the concept of the fractional calculus to fractals and to the fractal dimension. A new definition of the fractal dimension is provided based on a property of the fractional derivative. Using fractional Gaussian noise and fractional Brownian motion, simulations show the information content of a time series can be easily manipulated by the fractional derivative method and generated in real time.
Quantitative pattern analysis of the N‐terminally processed isoforms of platelet factor‐4 in serum (2013)

This study is the first report on the levels of N-terminally processed PF4 isoforms in serum. Also, this study shows the usefulness of SRM in determining concentrations of protein isoform variants, which can be often overlooked in immunoassay analysis.
Data from Blockade of Myeloid-Derived Suppressor Cell Expansion with All-<i>Trans</i> Retinoic Acid Increases the Efficacy of Antiangiogenic Therapy (2023)

&lt;div&gt;Abstract&lt;p&gt;Intrinsic and adaptive resistance hampers the success of antiangiogenic therapies (AAT), especially in breast cancer where this treatment modality has proven largely ineffective. Therefore, novel strategies to improve the efficacy of AAT are warranted. Solid tumors such as breast cancer are characterized by a high infiltration of myeloid-derived suppressor cells (MDSC), which are key drivers of resistance to AAT. Therefore, we hypothesized that all-&lt;i&gt;trans&lt;/i&gt; retinoic acid (ATRA), which induces differentiation of MDSC into mature cells, could improve the therapeutic effect of AAT. ATRA increased the efficacy of anti–VEGFR2 antibodies alone and in combination with chemotherapy in preclinical breast cancer models. ATRA reverted the anti–VEGFR2-induced accumulation of intratumoral MDSC, alleviated hypoxia, and counteracted the disorganization of tumor microvessels. Mechanistic studies indicate that ATRA treatment blocked the AAT-induced expansion of MDSC secreting high levels of vessel-destabilizing S100A8. Thus, concomitant treatment with ATRA holds the potential to improve AAT in breast cancer and possibly other tumor types.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Significance:&lt;/b&gt; Increasing the therapeutic efficiency of antiangiogenic drugs by reducing resistance-conferring myeloid-derived suppressor cells might improve breast cancer treatment.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Graphical Abstract:&lt;/b&gt; &lt;a href="http://cancerres.aacrjournals.org/content/canres/78/12/3220/F1.large.jpg" target="_blank"&gt;http://cancerres.aacrjournals.org/content/canres/78/12/3220/F1.large.jpg&lt;/a&gt;. &lt;i&gt;Cancer Res; 78(12); 3220–32. ©2018 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Study on Heavy Metal Accumulation of Plantsin Gejiu Tin Mining Area (2014)

Based on determination of heavy metal contents in soils and plants, understanding pollution of heavy metal in soils and plants, as well as the heavy metal accumulation in plants, in order to provide scientific basis for phytoremediation of heavy metals in mining areas. The determination and analysis on the concent of Zn, Cu, Pb, Cd, Mn was made in Niuba and southern mining area in Gejiu City. The result showed that the soil pollution from Cd is the most serious while the pollution from Zn was relative to minimum in Niuba abandoned mining area. In southern mining area, Pb in soil pollution was the most serious while Cu was relative to minimum Analysis on correlation between the heavy metal content in plants and soils was made based on the 5 plant samples (Pyracantha fortuneana, Zea mays, Acroptilon repens, Equisetum ramosissimum and Cucurbita moschata) collected from Niuba reclamation area and 5 plant samples (Corylus yunnanensis, Alnus nepalensis, Pyracantha fortuneana,Cupressus torulosa,Acacia dealbata) from recovery area of southern mining area. The results show that Pyracantha fortuneana has a better correlation with soil than other plants, Cucurbita moschata and soil have poor correlation, Corylus yunnanensis has better correlation with soil compared to other plants, Acacia dealbata has poor correlation with soil.
A general framework for MIMO receivers with low-resolution quantization (2017)

The capacity of a discrete-time, multi-input multi-output (MIMO) channel with output quantization is investigated for different receiver architectures. A general framework for low-resolution quantization is proposed in which the antenna outputs are processed by analog combiners and sign quantizers are used for analog-to-digital conversion. The configuration of the analog combiners is chosen as a function of the channel realization so that the transmission rate can be maximized over the set of available configurations. To exemplify the proposed approach, four analog receiver architectures are considered: (a) sign quantization of the antenna outputs, (b) single antenna selection, (c) multiple antenna selection, and (d) linear processing of the antenna outputs. In each scenario, capacity is investigated as a function of the transmit power, the number of transmit/receive antennas and sign quantizers. In particular, it is shown that architecture (a) is sufficient to approach the optimal high signal-to-noise ratio (SNR) performance for a MIMO receiver in which the number of receive antennas is larger than the number of sign quantizers. Numerical evaluations of the average performance are presented for the case in which the channel gains are i.i.d. Gaussian distributed.