gebhart/patrepeval huggingface dataset:
A pharmaceutical approach to achieve synergy in vivo: A fixed ratio formulation of Irinotecan and Floxuridine for treatment of colorectal cancer (2004)

550 Purpose: To define a fixed ratio formulation of irinotecan and floxuridine (CPX-1) for use in the treatment of colorectal cancer. Methods: The cytotoxic effects of irinotecan and floxuridine were examined alone and combined at various fixed ratios in a number of tumor cell lines. These in vitro data were analyzed utilizing the median effect principle (Chou and Talalay, Adv Enzyme Regul, 22: 27-55, 1984). Liposomal formulations were developed for the drug combination with the goal of identifying a single lipid composition capable of encapsulating both drugs in a manner where the rate of drug release from the liposomes following intravenous administration was matched for both agents. The resulting co-encapsulated fixed ratio CPX-1 formulation was then assessed in a number of in vivo tumor models. Results: In vitro results demonstrate that synergistic interactions for irinotecan and floxuridine combinations were dependent on drug-to-drug ratio. In the human colorectal cell lines HCT-116 and HT-29, mole ratios of irinotecan and floxuridine of 1:1, 1:5 and 1:10 produced the largest synergistic effects over the broadest range of effective doses. Exposure of cancer cells to a mole ratio of 10:1 typically resulted in additive or antagonistic interactions. A mole ratio of 1:1 was defined as optimal for a range of tumor cell lines and a liposomal formulation was developed with co-encapsulated irinotecan and floxuridine at this ratio. Evaluations of the co-encapsulated drugs indicated that following i.v. administration the concentrations of each drug in the plasma were comparable over time, thus the drug-to-drug ratio in the plasma was maintained at the optimal 1:1 mole ratio. For HT-29 efficacy studies, delays in tumor growth achieved following treatment with the maximum tolerated dose of the free drug cocktail were significantly less than those achieved with the fixed ratio formulation administered at an 8-fold lower dose. Control tumors grew to 500 mg 28 days after cell inoculation. Using identical drug doses (25 mg/kg of irinotecan and 9.25 mg/kg floxuridine) and treatment schedule (Q7D x 3), HT29 tumors grew to 500 mg by day 30 and 60 following treatment with free irinotecan:floxuridine and CPX-1, respectively. Similar results were seen when evaluating therapy in the HCT-116 xenograft tumor model. Conclusion: Irinotecan and floxuridine acted synergistically in vitro when combined at a molar ratio of 1:1. When evaluated in preclinical models of human solid tumors, a fixed ratio formulation exhibited dramatic improvements in antitumor activity.
Nonlinear optical properties of epitaxial quantum dot lasers on silicon (invited) (2020)

International audience
Petabytes to Science (2019)

A Kavli foundation sponsored workshop on the theme \emph{Petabytes to Science} was held 12$^{th}$ to 14$^{th}$ of February 2019 in Las Vegas. The aim of the this workshop was to discuss important trends and technologies which may support astronomy. We also tackled how to better shape the workforce for the new trends and how we should approach education and public outreach. This document was coauthored during the workshop and edited in the weeks after. It comprises the discussions and highlights many recommendations which came out of the workshop. We shall distill parts of this document and formulate potential white papers for the decadal survey.
Fibroblasts positive for meflin have anti-fibrotic properties in pulmonary fibrosis (2021)

The prognosis of elderly individuals with idiopathic pulmonary fibrosis (IPF) remains poor. Fibroblastic foci, in which aggregates of proliferating fibroblasts and myofibroblasts are involved, are the pathological hallmark lesions in IPF to represent focal areas of active fibrogenesis. Fibroblast heterogeneity in fibrotic lesions hampers the discovery of the pathogenesis of pulmonary fibrosis. Therefore, to determine the pathogenesis of IPF, identification of functional fibroblasts is warranted. The aim of this study was to determine the role of fibroblasts positive for meflin, identified as a potential marker for mesenchymal stromal cells, during the development of pulmonary fibrosis.We characterised meflin-positive cells in a single-cell atlas established by single-cell RNA sequencing (scRNA-seq)-based profiling of 243 472 cells from 32 IPF lungs and 29 normal lung samples. We determined the role of fibroblasts positive for meflin using bleomycin (BLM)-induced pulmonary fibrosis.scRNA-seq combined with <i>in situ</i> RNA hybridisation identified proliferating fibroblasts positive for meflin in fibroblastic foci, not dense fibrosis, of fibrotic lungs in IPF patients. A BLM-induced lung fibrosis model for meflin-deficient mice showed that fibroblasts positive for meflin had anti-fibrotic properties to prevent pulmonary fibrosis. Although transforming growth factor-β-induced fibrogenesis and cell senescence with the senescence-associated secretory phenotype were exacerbated in fibroblasts <i>via</i> the repression or lack of meflin, these were inhibited in meflin-deficient fibroblasts with meflin reconstitution.These findings provide evidence to show the biological importance of meflin expression on fibroblasts and myofibroblasts in the active fibrotic region of pulmonary fibrosis.
Alterations of lymphocyte membranes during HIV‐1 infection via multiple and simultaneous entry strategies (2005)

Human immunodeficiency virus type 1 (HIV-1) must bind to and enter lymphocytes to replicate and cause the acquired immunodeficiency syndrome. The association of viral particles with the lymphocyte plasma membrane may vary according to a multitude of unknown variables, including lymphocyte membrane receptor mobilization, lipid raft aggregation, clathrin, caveolin, endosomes, microendosome-mediated penetration or penetration through a hole in the membrane. The time course of this delivery appears to be short. Fusion of the virion membrane and lymphocyte plasma membrane leads to destabilization of the lymphocyte membrane. Five morphological stages of membrane alteration were observed in the infected lymphocytes: (1) swelling, (2) splitting, (3) fusion, (4) breaking, and (5) thinning of the lipid bilayer. These plasma membrane alterations were not contributed by fixation artifacts, because the dimensions and distance between the subunits of the surface glycoprotein (SU, gp120) and the transmembrane glycoprotein (gp41) of the viral particles adjacent to the infected cells and processed at the same time remained unchanged. Destabilization of lipid raft patches in the lymphocyte plasma membrane by unknown variables may facilitate HIV-1 penetration of lymphocyte, and other cell types. This a combined review of the pertinent literature with our data showing that HIV-1 may take advantage of multiple penetration approaches simultaneously in the same cell type (H9) to overwhelm the infected cells. The ultrastructural details of H9 cultured cells infected in vitro with HIV-1 contribute to our understanding of viral particle association with the plasma membrane of infected cells.
No Superiority of Treatment With Osmotic Controlled-Release Oral Delivery System–Methylphenidate Over Short/Medium-Acting Methylphenidate Preparations in the Rate and Timing of Injuries in Children With Attention-Deficit/Hyperactivity Disorder (2016)

This real-world-naturalistic study in the community demonstrates that, in ADHD pediatric populations, OROS-MPH preparation is not superior to short/medium-acting (4/6-8 hours) MPH preparations regarding the rate and timing of injuries.
Case-matched comparison of ABO-incompatible and ABO-compatible living donor liver transplantation (2015)

The short-term outcomes of ABO-I LDLT were comparable to those of ABO-C LDLT in this study. ABO-I LDLT is an effective and safe transplant option with the potential to expand the pool of live donors.
ChemInform Abstract: A NEW CLASS OF NITROSOUREAS. I. SYNTHESIS AND ANTITUMOR ACTIVITY OF 1‐(2‐CHLOROETHYL)‐3,3‐DISUBSTITUTED‐1‐NITROSOUREAS HAVING A HYDROXYL GROUP AT THE β‐POSITION OF THE SUBSTITUENTS (1982)

Abstract Die N‐Nitrosoharnstoffe (IV) werden aus den Aminen (I) durch Umsetzung mit dem Isocyanat (II) zu (III) und anschließende Nitrosierung hergestellt und auf ihre Antitumor‐Aktivität geprüft.
Anomalous modulation of spin torque-induced ferromagnetic resonance caused by direct currents in permalloy/platinum bilayer thin films (2017)

We systematically investigated the spin-torque ferromagnetic resonance (ST-FMR) in permalloy/Pt bilayer thin films under bias direct currents. According to the conventional ST-FMR theory, the half widths of the resonant peaks in the spectra can be modulated by bias currents, which give a reliable value of the spin injection efficiency of the spin Hall effect. On the other hand, the symmetric components of the spectra show an unexpected strong bias current dependence, while the asymmetric components are free from the modulation. These findings suggest that some contributions are missing in the ST-FMR analysis of the ferromagnetic/nonmagnetic metal bilayer thin films.
Deep Learning for Anomaly Detection: Challenges, Methods, and Opportunities (2021)

In this tutorial we aim to present a comprehensive survey of the advances in deep learning techniques specifically designed for anomaly detection (deep anomaly detection for short). Deep learning has gained tremendous success in transforming many data mining and machine learning tasks, but popular deep learning techniques are inapplicable to anomaly detection due to some unique characteristics of anomalies, e.g., rarity, heterogeneity, boundless nature, and prohibitively high cost of collecting large-scale anomaly data. Through this tutorial, audiences would gain a systematic overview of this area, learn the key intuitions, objective functions, underlying assumptions, advantages and disadvantages of different categories of state-of-the-art deep anomaly detection methods, and recognize its broad real-world applicability in diverse domains. We also discuss what challenges the current deep anomaly detection methods can address and envision this area from multiple different perspectives. Any audience who may be interested in deep learning, anomaly/outlier/novelty detection, out-of-distribution detection, representation learning with limited labeled data, and self-supervised representation learning would find it very helpful in attending this tutorial. Researchers and practitioners in finance, cybersecurity, healthcare would also find the tutorial helpful in practice.
Global tool interference detection in five-axis machining of sculptured surfaces (2002)

This paper presents a new method for the detection and elimination of global interference in five-axis machining of sculptured surfaces. Projecting points on the surface to the axis of cutter, the minimum distance from surface to cutter axis can be directly calculated by an iterative algorithm; the amount of interference is subsequently determined. A corrective method for generating an interferential-free cutter location is then proposed. The implementation has proved that the proposed method has a high efficiency and precision.
Opposing actions of angiopoietin-2 on Tie2 signaling and FOXO1 activation (2016)

Angiopoietin-2 (ANG2) regulates blood vessel remodeling in many pathological conditions through differential effects on Tie2 signaling. While ANG2 competes with ANG1 to inhibit Tie2, it can paradoxically also promote Tie2 phosphorylation (p-Tie2). A related paradox is that both inactivation and overactivation of Tie2 can result in vascular remodeling. Here, we reconciled these opposing actions of ANG2 by manipulating conditions that govern its actions in the vasculature. ANG2 drove vascular remodeling during Mycoplasma pulmonis infection by acting as a Tie2 antagonist, which led to p-Tie2 suppression, forkhead box O1 (FOXO1) activation, increased ANG2 expression, and vessel leakiness. These changes were exaggerated by anti-Tie2 antibody, inhibition of PI3K signaling, or ANG2 overexpression and were reduced by anti-ANG2 antibody or exogenous ANG1. In contrast, under pathogen-free conditions, ANG2 drove vascular remodeling by acting as an agonist, promoting high p-Tie2, low FOXO1 activation, and no leakage. Tie1 activation was strong under pathogen-free conditions, but infection or TNF-α led to Tie1 inactivation by ectodomain cleavage and promoted the Tie2 antagonist action of ANG2. Together, these data indicate that ANG2 activation of Tie2 supports stable enlargement of normal nonleaky vessels, but reduction of Tie1 in inflammation leads to ANG2 antagonism of Tie2 and initiates a positive feedback loop wherein FOXO1-driven ANG2 expression promotes vascular remodeling and leakage.
Search for gravitational wave radiation associated with the pulsating tail of the SGR1806−20hyperflare of 27 December 2004 using LIGO (2007)

We have searched for gravitational waves (GWs) associated with the SGR $1806\ensuremath{-}20$ hyperflare of 27 December 2004. This event, originating from a Galactic neutron star, displayed exceptional energetics. Recent investigations of the x-ray light curve's pulsating tail revealed the presence of quasiperiodic oscillations (QPOs) in the 30--2000 Hz frequency range, most of which coincides with the bandwidth of the LIGO detectors. These QPOs, with well-characterized frequencies, can plausibly be attributed to seismic modes of the neutron star which could emit GWs. Our search targeted potential quasimonochromatic GWs lasting for tens of seconds and emitted at the QPO frequencies. We have observed no candidate signals above a predetermined threshold, and our lowest upper limit was set by the 92.5 Hz QPO observed in the interval from 150 s to 260 s after the start of the flare. This bound corresponds to a (90% confidence) root-sum-squared amplitude ${\mathrm{h}}_{\mathrm{rss}\mathrm{\text{\ensuremath{-}}}\mathrm{det}﻿}^{90%}=4.5\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}22}\text{ }\text{ }\mathrm{\text{strain}}\text{ }\text{ }{\mathrm{Hz}}^{\ensuremath{-}1/2}$ on the GW waveform strength in the detectable polarization state reaching our Hanford (WA) 4 km detector. We illustrate the astrophysical significance of the result via an estimated characteristic energy in GW emission that we would expect to be able to detect. The above result corresponds to $7.7\ifmmode\times\else\texttimes\fi{}{10}^{46}\text{ }\text{ }\mathrm{erg}$ ($=4.3\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}8}\text{ }\text{ }{\mathrm{M}}_{\ensuremath{\bigodot}}{\mathrm{c}}^{2}$), which is of the same order as the total (isotropic) energy emitted in the electromagnetic spectrum. This result provides a means to probe the energy reservoir of the source with the best upper limit on the GW waveform strength published and represents the first broadband asteroseismology measurement using a GW detector.
Synthesis of Internally Fluorescence-Quenched Sugar Nucleotides (2004)

The synthesis of intramolecularly quenched UDP-Gal analogues bearing a fluorescence emitter attached to the galactose moiety and a quencher on the uracil portion is described. The rate of transfer using several galactosyltransferases was examined. Our results demonstrate that galactose-modified, sugar-nucleotide-modified and double modified UDP-Gal analogues are recognized as weak substrates by three of the galactosyltransferases.
A compact omnidirectional stereo camera for autonomous driving (2020)

Compact and low-cost devices are needed for autonomous driving to image and measure distances to objects 360-degree around. We have been developing an omnidirectional stereo camera exploiting two hyperbolic mirrors and a single set of a lens and sensor, which makes this camera cost efficient. This paper presents a new calibration method for this camera. Based on the original calibration method by Mei and Rives, we improve the calibration accuracy by considering higherorder radial distortion, detailed tangential distortion, an image sensor tilt, and a lens-mirror offset. Our method is applied to our prototype and reduces the root mean square of the calibration accuracy by 1.2 times and 2.2 times for the upper- and lower-view images, respectively. The distance error is less than 8% up to objects 14 meters apart, which is improved more than seven times compared to the original method, although the error is still larger than the target value of 5%. We consider that the remaining calibration error is due to distortion of the glass cylinder and a degraded optical resolution. As future work, we plan to make further improvements in the calibration and optical resolution of the prototype. In addition, a rectification method for cylindrically expanded images needs to be developed.
Dispersion polymerization of styrene in supercritical carbon dioxide utilizing random copolymers containing a fluorinated acrylate for preparing micron-size polystyrene particles (2000)

The dispersion polymerization of styrene in supercritical CO2 utilizing CO2-philic random copolymers was investigated. The resulting high yield of polystyrene particles in the micron-size range was formed using various random copolymers as stabilizers. The particle diameter was shown to be dependent on the composition of the stabilizer, and the weight percent of the stabilizer added to the system. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1146–1153, 2000
Lateral Control Of Tractor-semitrailer Vehicles In Automated Highway Systems (1996)

In this paper, linear quadratic optimal control with and without frequency shaping is utilized to design a steering controller for tractor- semitrailer vehicles in Automated Highway Systems (AHS). To enhance driving safety, the authors propose to use independent braking forces in the trailer as another control input. The combined steering and braking controller is designed by utilizing Input/Output linearization and backstepping design techniques.
ChemInform Abstract: Two Tandem Sequential Reactions Catalyzed by [Au], N‐Heterocyclic Carbenes (NHC) and Organic Bases. (2011)

Abstract Depending on the base used, either chalcon derivatives (III) or alkenyl benzoic esters (IV) are formed by the title reaction of benzaldehydes with alkyne (II).
<title>Visual mining business service using pixel bar charts</title> (2004)

Basic bar charts have been commonly available, but they only show highly aggregated data. Finding the valuable information hidden in the data is essential to the success of business. We describe a new visualization technique called pixel bar charts, which are derived from regular bar charts. The basic idea of a pixel bar chart is to present all data values directly instead of aggregating them into a few data values. Pixel bar charts provide data distribution and exceptions besides aggregated data. The approach is to represent each data item (e.g. a business transaction) by a single pixel in the bar chart. The attribute of each data item is encoded into the pixel color and can be accessed and drilled down to the detail information as needed. Different color mappings are used to represent multiple attributes. This technique has been prototyped in three business service applications-Business Operation Analysis, Sales Analysis, and Service Level Agreement Analysis at Hewlett Packard Laboratories. Our applications show the wide applicability and usefulness of this new idea.
Supplementary Data 5 from Discovery of JNJ-63576253, a Next-Generation Androgen Receptor Antagonist Active Against Wild-Type and Clinically Relevant Ligand Binding Domain Mutations in Metastatic Castration-Resistant Prostate Cancer (2023)

&lt;p&gt;93-cell line proliferation assay was performed and data analyzed by OncoLead&lt;/p&gt;
Functional Characterization of Six SLCO1B1 (OATP1B1) Variants Observed in Finnish Individuals with a Psychotic Disorder (2023)

Variants in the <i>SLCO1B1</i> (solute carrier organic anion transporter family member 1B1) gene encoding the OATP1B1 (organic anion transporting polypeptide 1B1) protein are associated with altered transporter function that can predispose patients to adverse drug effects with statin treatment. We explored the effect of six rare <i>SLCO1B1</i> single nucleotide variants (SNVs) occurring in Finnish individuals with a psychotic disorder on expression and functionality of the OATP1B1 protein. The SUPER-Finland study has performed exome sequencing on 9381 individuals with at least one psychotic episode during their lifetime. <i>SLCO1B1</i> SNVs were annotated with PHRED-scaled combined annotation-dependent (CADD) scores and the Ensembl variant effect predictor. In vitro functionality studies were conducted for the SNVs with a PHRED-scaled CADD score of >10 and predicted to be missense. To estimate possible changes in transport activity caused by the variants, transport of 2',7'-dichlorofluorescein (DCF) in OATP1B1-expressing HEK293 cells was measured. According to the findings, additional tests with rosuvastatin and estrone sulfate were conducted. The amount of OATP1B1 in crude membrane fractions was quantified using a liquid chromatography tandem mass spectrometry-based quantitative targeted absolute proteomics analysis. Six rare missense variants of <i>SLCO1B1</i> were identified in the study population, located in transmembrane helix 3: c.317T>C (p.106I>T), intracellular loop 2: c.629G>T (p.210G>V), c.633A>G (p.211I>M), c.639T>A (p.213N>L), transmembrane helix 6: 820A>G (p.274I>V), and the C-terminal end: 2005A>C (p.669N>H). Of these variants, <i>SLCO1B1</i> c.629G>T (p.210G>V) resulted in the loss of in vitro function, abolishing the uptake of DCF, estrone sulfate, and rosuvastatin and reducing the membrane protein expression to 31% of reference OATP1B1. Of the six rare missense variants, <i>SLCO1B1</i> c.629G>T (p.210G>V) causes a loss of function of OATP1B1 transport in vitro and severely decreases membrane protein abundance. Carriers of <i>SLCO1B1</i> c.629G>T might be susceptible to altered pharmacokinetics of OATP1B1 substrate drugs and might have increased likelihood of adverse drug effects such as statin-associated musculoskeletal symptoms.
Zn–Cu Alloy Nanofoams as Efficient Catalysts for the Reduction of CO2 to Syngas Mixtures with a Potential‐Independent H2/CO Ratio (2019)

Alloying strategies are commonly used to design electrocatalysts that take on properties of their constituent elements. Herein, such a strategy is used to develop Zn-Cu alloyed electrodes with unique hierarchical porosity and tunable selectivity for CO<sub>2</sub> versus H<sup>+</sup> reduction. By varying the Zn/Cu ratio, tailored syngas mixtures are obtained without the production of other gaseous products, which is attributed to preferential CO- and H<sub>2</sub> -forming pathways on the alloys. The syngas ratios are also significantly less sensitive to the applied potential in the alloys relative to pure metal equivalents; an essential quality when coupling electrocatalysis with renewable power sources that have fluctuating intensity. As such, industrially relevant syngas ratios are achieved at large currents (-60 mA) for extensive operating times (>9 h), demonstrating the potential of this strategy for fossil-free fuel production.
ChemInform Abstract: Orthogonal Cu‐ and Pd‐Based Catalyst Systems for the O‐ and N‐Arylation of Aminophenols. (2010)

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.