gebhart/patrepeval huggingface dataset:
Cell Surface Structures Influence Lung Clearance Rate of Systemically Infused Mesenchymal Stromal Cells (2012)

Abstract The promising clinical effects of mesenchymal stromal/stem cells (MSCs) rely especially on paracrine and nonimmunogenic mechanisms. Delivery routes are essential for the efficacy of cell therapy and systemic delivery by infusion is the obvious goal for many forms of MSC therapy. Lung adhesion of MSCs might, however, be a major obstacle yet to overcome. Current knowledge does not allow us to make sound conclusions whether MSC lung entrapment is harmful or beneficial, and thus we wanted to explore MSC lung adhesion in greater detail. We found a striking difference in the lung clearance rate of systemically infused MSCs derived from two different clinical sources, namely bone marrow (BM-MSCs) and umbilical cord blood (UCB-MSCs). The BM-MSCs and UCB-MSCs used in this study differed in cell size, but our results also indicated other mechanisms behind the lung adherence. A detailed analysis of the cell surface profiles revealed differences in the expression of relevant adhesion molecules. The UCB-MSCs had higher expression levels of α4 integrin (CD49d, VLA-4), α6 integrin (CD49f, VLA-6), and the hepatocyte growth factor receptor (c-Met) and a higher general fucosylation level. Strikingly, the level of CD49d and CD49f expression could be functionally linked with the lung clearance rate. Additionally, we saw a possible link between MSC lung adherence and higher fibronectin expression and we show that the expression of fibronectin increases with MSC culture confluence. Future studies should aim at developing methods of transiently modifying the cell surface structures in order to improve the delivery of therapeutic cells.
THE VVV TEMPLATES PROJECT TOWARDS AUTOMATED CLASSIFICATION OF VVV LIGHT CURVES (2011)

Americanae nace como un proyecto conjunto que surge dentro de la Red Europea de Información y Documentación sobre América Latina (REDIAL), y que ha afrontado la Biblioteca de la Agencia Española de Cooperación Internacional para el Desarrollo (AECID). Esta nueva biblioteca virtual hace más accesibles los libros digitales de tema americanista a los investigadores y usuarios interesados de cualquier parte del mundo.
Expérimentation et modélisation du comportement au feu des matériaux : de l’échelle du laboratoire au cas réel (2020)

International audience
VU6007477, a Novel M1 PAM Based on a Pyrrolo[2,3-b]pyridine Carboxamide Core Devoid of Cholinergic Adverse Events (2018)

Herein, we report the chemical optimization of a new series of M<sub>1</sub> positive allosteric modulators (PAMs) based on a novel pyrrolo[2,3-<i>b</i>]pyridine core, developed via scaffold hopping and iterative parallel synthesis. The vast majority of analogs in this series proved to display robust cholinergic seizure activity. However, by removal of the secondary hydroxyl group, VU6007477 resulted with good rat M<sub>1</sub> PAM potency (EC<sub>50</sub> = 230 nM, 93% ACh max), minimal M<sub>1</sub> agonist activity (agonist EC<sub>50</sub> > 10 μM), good CNS penetration (rat brain/plasma <i>K</i> <sub>p</sub> = 0.28, <i>K</i> <sub>p,uu</sub> = 0.32; mouse <i>K</i> <sub>p</sub> = 0.16, <i>K</i> <sub>p,uu</sub> = 0.18), and no cholinergic adverse events (AEs, e.g., seizures). This work demonstrates that within a chemical series prone to robust M<sub>1</sub> ago-PAM activity, SAR can result, which affords pure M<sub>1</sub> PAMs, devoid of cholinergic toxicity/seizure liability.
In Vitro Evaluation of Optionally Retrievable and Permanent IVC Filters (2007)

Optionally retrievable IVC filters are efficient. Clot size, IVC filter type, and position significantly influence capture rate. Deliberate selection of the most efficient IVC filter and concentric positioning are important to ensure optimal results.
DuraSeal Spinal Sealant as an Adjunct to Sutured Dural Repair in the Spine (2009)

Wright, Neill M. M.D.; Kim, Kee Duk M.D.; Cosgrove, Rees M.D.; Tew, John M. M.D.; Kaiser, Michael G. M.D.; McCormick, Paul C. M.D.; Chestnut, Randall; Ellenbogen, Richard G. M.D.; Van Loveren, Harry R. M.D.; Vale, Fernando L. M.D.; Shaffrey, Mark E. M.D.; Chen, Thomas C. M.D., Ph.D.; Wang, Michael Y. M.D.; Mayberg, Marc R. M.D.; Sharan, Ashwini D. M.D.; Gerszten, Peter C. M.D., M.P.H.; Welch, William C. M.D.; Graham, R. Scott M.D.; Brown, Frederick D. M.D.; Fessler, Richard G. M.D.; Deutsch, Harel M.D.; Shah, Mitesh V. M.D.; McCutcheon, Ian E. M.D.; Karahalios, Dean G. M.D.; Long, Donlin M. M.D.; Hopkins, L. Nelson M.D.; Jallo, Jack M.D., Ph.D.; Delashaw, Johnny B. M.D.; Ondra, Stephen L. M.D.; Gross, Robert E. M.D., Ph.D.
A short feasibility study of a cognitive TV black space system (2011)

This paper evaluates the feasibility of overlaying a secondary system on a digital TV (DTV) system. We denote this type of approach TV black space (in contrast to TV white space). In this type of operation the secondary transmitter transmits on the same spectrum resources as the DTV system. Particularly, we consider the case where the secondary transmitter is collocated with the DTV transmitter and uses the same antennas. The fraction of the total transmitted power that is used for the secondary signal is set low enough so that the DTV receivers are always able to decode the DTV signals. The black space receivers decode the TV signal component and cancel it from the total received signal which results in an improved SINR of the secondary signal in the residual. Numerical evaluations show that this type of overlay in the DTV spectrum is feasible only when the secondary system is satisfied with relatively low SINR values of around 5 to 10 dB. A critical parameter when determining the secondary signal SINR after DTV signal cancellation is the SINR requirements by the primary system: DVB-T systems typically require SINR values above 20 dB and then overlay becomes less feasible since the fraction of power left for the secondary signal becomes very low. Additionally, realistic levels of TX EVM noise (around 6% to 8%) at the transmitter causes low achievable SINR values for the secondary signal even after DTV signal cancellation at the receiver side.
Direct injection supersonic cluster beam source for FT-ICR studies of clusters (1990)

A miniaturized pulsed supersonic beam source has been developed using laser vaporization of a computer-controlled target disk, producing intense beams of cluster ions with excellent repeatability and control. Due to its small size and narrow pulse width, the entire source is adequately pumped by a single 170 ℓ /s turbopump. The resultant vacuum quality permits this source to be attached to a Fourier transform ion cyclotron resonance apparatus (FT-ICR) such that the supersonic cluster ion beam is directly injected. The result is a powerful but simple FT-ICR instrument of wide applicability. The new source is suited as well for a variety of other uses such as molecular beam epitaxy.
Data from Mutant p53 (G199V) Gains Antiapoptotic Function through Signal Transducer and Activator of Transcription 3 in Anaplastic Thyroid Cancer Cells (2023)

&lt;div&gt;Abstract&lt;p&gt;In the present study, we identified a missense mutation (G199V) in KAT-18 cell line established from primary cultures of anaplastic thyroid cancer (ATC). Notably, knockdown of this mutant (mt) p53 reduced cell viability and exerted antitumor activity equivalent to high doses of several chemotherapeutic agents. We showed that p53 knockdown had an antitumor effect via the induction of apoptosis. We further examined the underlying mechanism by which mt p53 (G199V) gains antiapoptotic function in KAT-18 cells. Microarray analysis revealed that p53 knockdown modified the expression of numerous apoptosis-related genes. Importantly, p53 knockdown led to downregulation of signal transducer and activator of transcription-3 (&lt;i&gt;STAT3&lt;/i&gt;) gene expression. We further observed that p53 knockdown induced the downregulation of STAT3 protein. We also observed that a STAT3 inhibitor augmented the reduction of cell viability induced by p53 knockdown, whereas interleukin-6 treatment alleviated this effect. In addition, overexpression of STAT3 protected ATC cells against cell death induced by p53 knockdown. Taken together, these data show that mt p53 (G199V) gains antiapoptotic function mediated by STAT3 in ATC cells. Inhibition of the function of mt p53 (G199V) could be a novel and useful therapeutic strategy for decreasing the extent and severity of toxicity due to chemotherapeutic agents. (Mol Cancer Res 2009;7(10):1645–54)&lt;/p&gt;&lt;/div&gt;
P-Ink: Intelligent Color (2007)

This paper, presents some of the recent research on photonic ink dubbed P-Ink, a hybrid material of a metallopolymer gel and a colloidal photonic crystal that enables intelligent color, namely color from the interaction of light with a periodic microstructure rather than color from the absorption or emission of light by a chromophore or fluorophore. In this context, structural color refers to the color of optically Bragg diffracted light from a three-dimensional photonic crystal, a periodic dielectric whose lattice dimensions are in the light scale. The intelligence in the color stems from the tunable lattice dimensions and refractive index contrast of the photonic crystal, which enables the full gamut of colors to be obtained from a single material. P-Ink therefore has the potential to revolutionize full color display technologies because most color displays use the standard tri-chromatic color mixing of television screens to produce different colors, whereas P-Ink changes the color of the screen through control over the intrinsic color in each pixel.
Lanthanide(III) Methylsquarates:  Synthesis and X-ray Structures (2001)

Reaction of 3-methyl-4-hydroxycyclobut-3-ene-1,2-dione (methylsquarate) with LaCl3·7H2O and M(NO3)3·xH2O (M = Eu, Gd, and Tb) in alcoholic solutions afforded the polymeric complexes {La[μ3-(CH3C4O3)][(H2O)6][Cl2]·H2O}n (1), {Eu[μ-(CH3C4O3)3][(H2O)2]}n (3), {Gd[μ-(CH3C4O3)2][(H2O)4][NO3]·H2O}n (4), and {Tb[μ-(CH3C4O3)2][(H2O)4][NO3]·H2O}n (5), respectively and with La(NO3)3·6H2O, the monomer La(CH3C4O3)3(H2O)6·H2O (2). Complex 1 crystallizes in the orthorhombic space group Pca21, with a = 13.239(2) Å, b = 7.836(1) Å, c = 14.209(2) Å, and Z = 4. The lanthanum atom is nine-coordinate adopting a monocapped square antiprismatic geometry, being bonded to three μ3-bridging methylsquarate and six pendant aqua ligands and forming cationic polymer sheets which are intercalated by chloride ions and water of crystallization. Complex 3 is a 3-dimensional neutral network polymer in which the methylsquarate ligands are μ-1,3-bridging and the europium atoms adopt a bicapped trigonal prismatic geometry. 3 crystallizes in the orthorhombic space group Pbna with a = 8.713(1) Å, b = 13.115(1) Å, c = 15.253(1) Å, and Z = 4. The gadolinium and terbium complexes, 4 and 5, are isomorphous cationic sheet polymers with the methylsquarate ligand again adopting a μ-1,3-bridging role and with the metal having square antiprismatic geometry. Adjacent sheets are arranged so as to form channels within which the nitrate anions and water molecules are located. Complex 4 crystallizes in the monoclinic space group P21/c, with a = 14.543(2) Å, b = 8.396(1) Å, c = 15.251(2) Å, β = 109.37(1)°, and Z = 4. The monomer 2 crystallizes in the space group P21/c with a = 10.438(2) Å, b = 14.813(2) Å, c = 15.151(2) Å, β = 108.21(1)°, and Z = 4. The lanthanum atom is nine-coordinate adopting a monocapped square antiprismatic geometry with each metal atom being coordinated to three methylsquarate and six aqua ligands. In all of the polymeric species there is a pattern of delocalization which extends to include adjacent metal centers.
In situ cross-linking of androgen receptors to nuclear acceptor sites of rat prostate with formaldehyde. (1985)

Androgen receptors were attached covalently in situ to their nuclear acceptor sites with the contact site cross-linker, formaldehyde. Chromatin, prepared from sonicated nuclei of rat prostate, was labeled by isotope exchange with [3H]dihydrotestosterone and found to contain 19,000 +/- 900 (mean +/- S.E.) salt-extractable androgen receptors/nucleus which sedimented in the 3-4 S region of 7.6-76% (v/v) glycerol gradients and at a density of approximately 1.28-1.35 g/ml in CsCl gradients. After incubation of the chromatin with 0.5% (w/v) formaldehyde for 1 h at 4 degrees C, there was a 90% reduction in the concentration of free androgen receptors and an increase in the density of the androgen binding sites recovered from CsCl gradients. Extensive digestion of the cross-linked chromatin with micrococcal nuclease liberated 18% of the androgen receptors as 3-4 S entities and caused an overall decrease in the density of the receptor-acceptor complexes. Ribonuclease digestions had no effect on the androgen receptors cross-linked to chromatin. Mild digestion of the cross-linked preparations with trypsin, alone or in combination with micrococcal nuclease, resulted in the release of 74% and 97% of the androgen receptors, respectively. Together, these findings imply that two classes of receptor-acceptor complexes are present in prostatic chromatin--one, containing about 20% of the androgen receptors in which the receptors are in direct contact with DNA but not with proteins and the other, containing most of the androgen receptors in which the receptors are adjacent to acceptor proteins but not to DNA.
PD-1 blockade in mismatch repair deficient non-colorectal gastrointestinal cancers. (2016)

195 Background: Mismatch repair (MMR) deficient tumors harbor hundreds to thousands of mutations that may produce neoantigens that can be recognized and targeted by T cells. We have shown that MMR deficiency can serve as a predictive biomarker for selection of tumors across tumor histologies that may respond to programmed death-1 (PD-1) blockade. MMR deficiency is present in 15% of colorectal (CRC) however is also detected in 2-20% of gastric, small bowel, and hepatobiliary cancers. Methods: We conducted a phase II study to evaluate anti-PD-1, pembrolizumab, in patients with previously-treated, progressive, advanced cancer. Twenty-one patients with MMR deficient tumors were enrolled onto the non-CRC cohort with an additional 50 patient expansion underway. The pembrolizumab dose is 10mg/kg intravenously every 2 weeks. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) will be reported in at least the first 17 patients with non-CRC gastrointestinal (GI) cancers. Results: As of September 18, 2015, 17 patients with non-CRC GI cancers have been enrolled on the protocol with additional patients identified. The diseases represented are ampullary (N=4), pancreas (N=4), biliary (N=3), small bowel (N=3), and gastric (N=3) cancers. For the 10 evaluable patients at the time of abstract admission, ORR is 50 % (N=5/10), disease control rate is 70% (N=7/10), OS is 21 months and the median duration of response (range 5.5-17+ months) and PFS have not been reached. The median follow up duration is 7.6 months. Conclusions: PD-1 blockade shows promising activity in mismatch repair deficient GI cancers. Clinical trial information: NCT01876511.
Ruthenium complex dyes and photovoltaic cells utilizing them as photosensitizers (1994)

Patent number: 93-EP2221-9404497 Reference LPI-PATENT-1994-001Search for this record at the European Patent Office Record created on 2006-02-21, modified on 2016-08-08
Chromatin Regulator CHD1 Remodels the Immunosuppressive Tumor Microenvironment in PTEN-Deficient Prostate Cancer (2020)

Genetic inactivation of <i>PTEN</i> is common in prostate cancer and correlates with poorer prognosis. We previously identified <i>CHD1</i> as an essential gene in PTEN-deficient cancer cells. Here, we sought definitive <i>in vivo</i> genetic evidence for, and mechanistic understanding of, the essential role of CHD1 in PTEN-deficient prostate cancer. In <i>Pten</i> and <i>Pten</i>/<i>Smad4</i> genetically engineered mouse models, prostate-specific deletion of <i>Chd1</i> resulted in markedly delayed tumor progression and prolonged survival. <i>Chd1</i> deletion was associated with profound tumor microenvironment (TME) remodeling characterized by reduced myeloid-derived suppressor cells (MDSC) and increased CD8<sup>+</sup> T cells. Further analysis identified IL6 as a key transcriptional target of CHD1, which plays a major role in recruitment of immunosuppressive MDSCs. Given the prominent role of MDSCs in suppressing responsiveness to immune checkpoint inhibitors (ICI), our genetic and tumor biological findings support combined testing of anti-IL6 and ICI therapies, specifically in PTEN-deficient prostate cancer. SIGNIFICANCE: We demonstrate a critical role of CHD1 in MDSC recruitment and discover CHD1/IL6 as a major regulator of the immunosuppressive TME of PTEN-deficient prostate cancer. Pharmacologic inhibition of IL6 in combination with immune checkpoint blockade elicits robust antitumor responses in prostate cancer.<i>This article is highlighted in the In This Issue feature, p. 1241</i>.
Abstract 4306: Bioconjugation of near infrared dyes by PEGylation improves pharmacokinetics and allows for better labeling and imaging of human gastrointestinal cancers (2014)

Abstract NIR dyes are becoming increasingly popular due to their good tissue penetration, low tissue autofluorescence and resistance to hemoglobin quenching. However, they are still limited by lower hydrophilicity and poor chemical and photo-stability in-vivo. We aimed to try to improve these properties by covalent modification of these dyes by addition of polyethylene glycol (PEG) chains. We studied 2 commercially-available NIR dyes, DyLight 650 and 750, to evaluate how PEGylation affects the pharmacokinetics, biodistribution and imaging. PEGylated and non-PEGylated DyLight 650 and 750 dyes were conjugated to a chimeric anti-CEA antibody and were injected intravenously into nude mice. Serum samples were collected at various time points to determine serum concentrations and clearance kinetics. Biodistribution was determined by tissue sonication and analyzing tissue concentration profiles over time. PEGylated dyes had significantly higher serum concentrations than non-PEGylated dyes with p=0.005 for the 650 dyes and p&amp;lt;0.001 for the 750 dyes. PEGylated dyes had significantly lower liver concentrations (p=0.03 for the 650 dyes; p=0.002 for the 750 dyes) and higher renal concentrations (p=0.003 for the 650 dyes and p&amp;lt;0.001 for the 750 dyes) compared to non-PEGylated dyes. Human pancreatic tumors subcutaneously implanted into nude mice were labeled with antibody-dye conjugates and serially imaged. Labeling with PEGylated dyes resulted in significantly brighter tumors compared to the non-PEGylated dyes (p&amp;lt;0.001 for the 650 dyes; p=0.01 for 750 dyes). In a liver metastasis model of colon cancer, PEGylated dyes showed bright labeling of metastatic tissue with good contrast between normal and malignant tissue. PEGylation of the NIR dyes DyLight 650 and 750 significantly changes their pharmacokinetics and biodistribution, allowing higher serum concentrations, longer half-life, brighter tissue labeling and decreased accumulation in lymphoid organs. This allows for high fidelity imaging of metastatic disease to any lymphoid or hemoglobin dense organ such as the liver. Citation Format: Ali A. Maawy, Yukihiko Hiroshima, George A. Luiken, Yong Zhang, Robert M. Hoffman, Michael Bouvet. Bioconjugation of near infrared dyes by PEGylation improves pharmacokinetics and allows for better labeling and imaging of human gastrointestinal cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4306. doi:10.1158/1538-7445.AM2014-4306
Towards Sustainable Funding Models for the European Open Science Cloud (2022)

This progress report presents the main findings to date of the Financial Sustainability Task Force. The Task Force has scoped and defined the EOSC Exchange and Data Federation in the context of financial sustainability, identified barriers and boundary conditions, and performed initial development of financial scenarios for the EOSC Core, Exchange and Data Federation which address the period from 2027 onwards, after current EC Framework Programme seed funding for EOSC runs out.
Rounding algorithms for IEEE multipliers (2003)

Several technology independent rounding algorithms for multiplying normalized numbers are presented. The first is a simple rounding algorithm suitable for software simulation or moderate performance hardware multipliers. The next two algorithms are parallel addition schemes suitable for high-performance VLSI multipliers. One of them eliminates the carry produced by the lower-order bits from the critical path. Several methods for computing the sticky bit are also presented. Included is a new fast and efficient technique for computing the sticky bit directly from the carry-save form without undergoing the expense of a carry-propagate addition.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Identifying Performance Regression Conditions for Testing & Evaluation of Autonomous Systems (2021)

This paper addresses the problem of identifying whether/how a black-box autonomous system has regressed in performance when compared to previous versions. The approach analyzes performance datasets (typically gathered through simulation-based testing) and automatically extracts test parameter clusters of predicted performance regression. First, surrogate modeling with quantile random forests is used to predict regions of performance regression with high confidence. The predicted regression landscape is then clustered in both the output space and input space to produce groupings of test conditions ranked by performance regression severity. This approach is analyzed using randomized test functions as well as through a case study to detect performance regression in autonomous surface vessel software.
α3β1 Integrin-Targeting Polymersomal Docetaxel as an Advanced Nanotherapeutic for Nonsmall Cell Lung Cancer Treatment (2020)

Docetaxel (DTX) widely used for treating nonsmall cell lung cancer (NSCLC) patients is associated with dose-limiting side effects, especially neurotoxicity and myelosuppression. Here, we have developed cyclic cNGQGEQc peptide-directed polymersomal docetaxel (cNGQ-PS-DTX) as a targeted and multifunctional formulation for NSCLC. cNGQ-PS-DTX carrying 8.1 wt % DTX had a size of 93 nm, neutral surface charge, high stability, and glutathione-triggered DTX release behavior. Cytotoxicity studies demonstrated a clearly better antitumor activity of cNGQ-PS-DTX in α<sub>3</sub>β<sub>1</sub> integrin overexpressing A549 human lung cancer cells than free DTX and nontargeted PS-DTX. cNGQ-PS-DTX showed a remarkably high tolerability (over 8 times better than free DTX) and slow elimination in mice. Importantly, cNGQ-PS-DTX exhibited greatly improved tumor accumulation and higher suppression of subcutaneous and orthotopic A549 xenografts as compared to PS-DTX and free DTX controls. α<sub>3</sub>β<sub>1</sub> integrin-targeting polymersomal docetaxel emerges as an advanced nanotherapeutic for NSCLC treatment.