gebhart/patrepeval huggingface dataset:
Abstract 977: 3D-models of patient-derived colon tumors for the identification of genetic factors important in the regulation of cancer stem cells (2015)

Abstract Colon cancer is a heterogeneous tumour entity. Growing evidence supports a subpopulation of cancer stem cells (CSCs) as both the drivers of tumour growth and the source of relapse following treatment. Elucidation of the cellular heterogeneity within a tumour would therefore facilitate better characterization of patient subtypes and lead to more personalized and effective treatments. Here, as part of the OncoTrack* consortium, we report the use of a Matrigel-based 3D in vitro model for the identification of genetic factors important in the regulation of CSCs. The identity and frequency of CSCs within each patient-derived culture model was determined by separating cells using fluorescence assisted cell sorting (FACS) based on expression of previously defined markers of colon CSCs (ALDH+ CD44+ CD166+). Isolated subpopulations of cells are functionally tested for CSC properties in vitro (limiting dilution serial passage and population dynamics analysis) and in vivo (limiting dilution serial xenotransplantation). These studies reveal ALDH+ colon cancer cells to be highly enriched for CSCs and demonstrate large levels of variation in CSC frequency between patients. To identify genes and pathways that could be used to specifically target CSC function, ALDH+ tumour cell subpopulations were subjected to genome-wide analyses using next-generation sequencing for detailed characterization at the level of the transcriptome and methylome. To date, genes important in the regulation of normal stem cells and CSCs, such as BMI1, EPHB2 and the WNT signalling pathway, were found to be highly expressed in CSCs. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) mediated gene technology was used to knock out genes of interest and their role in regulating CSC function was confirmed using established functional assays. These studies provide insight into the relationship between variable tumour composition and the variable response of tumours to treatment. Ultimately, these studies will facilitate the more accurate classification and personalized treatment of colon tumours. *The research leading to these results has received funding from the European Union's Seventh Framework Program (FP7/2007-2013) for the Innovative Medicine Initiative under grant agreement n°115234. Citation Format: Joseph L. Regan, Dirk Schumacher, Stephanie Staudte, Karsten Boehnke, Ulrich Keilholz, Johannes Haybaeck, Hans Lehrach, David Henderson, Reinhold Schaefer, Christian R. Regenbrecht, Dominik Mumberg, Martin Lange. 3D-models of patient-derived colon tumors for the identification of genetic factors important in the regulation of cancer stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 977. doi:10.1158/1538-7445.AM2015-977
4564 Nilotinib alters microRNAs that regulate specific autophagy and ubiquitination genes in the cerebrospinal fluid of Parkinson’s patients (2020)

OBJECTIVES/GOALS: Our preclinical data demonstrate that the principal effects of nilotinib, a multi-tyrosine kinase inhibitor, in models of neurodegeneration is clearance of misfolded proteins via autophagy. Here we aimed to evaluate the effects of nilotinib on microRNAs in the cerebrospinal fluid of Parkinson’s disease patients. METHODS/STUDY POPULATION: Cerebrospinal fluid (CSF) was collected as part of an open label phase I (NCT02281474) (n = 12, 300 mg nilotinib taken orally once daily for 6 months), and a phase II randomized, double-blind, placebo-controlled study (NCT02954978) (n = 75, randomized 1:1:1 into placebo, 150 mg or 300 mg nilotinib taken orally once daily for 12 months). RNA was isolated from CSF and Indexed sequencing libraries were prepared from total RNA plus miRNA. Next generation whole-genome sequencing (single-end 1x75 bp, 25 million raw reads per sample) was performed to identify miRNAs significantly differentially expressed (fold-change ≥ 2, Benjamini-Hochberg FDR p-value ≤ 0.05 or Empirical Bayes FDR ≤ 0.05) with treatment compared to baseline. RESULTS/ANTICIPATED RESULTS: Next generation whole-genome sequencing of microRNAs in the CSF demonstrated that nilotinib significantly increases microRNAs that specifically regulate expression of autophagy and ubiquitination genes in individuals with Parkinson’s disease. In the open label phase I, samples, 28 microRNAs found to regulate autophagy and ubiquitination genes, were significantly altered with treatment (Benjamini-Hochberg FDR p-value ≤ 0.05). In the phase II randomized, double-blind, placebo-controlled study samples, we verified several of those 28 candidate microRNAs had been significantly deferentially expressed with treatment (Empirical Bayes FDR p-value ≤ 0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Our data provide robust evidence that nilotinib’s effects on misfolded protein clearance is via autophagy and CSF miRNA sequencing is a valid biomarker of nilotinib’s effects in a definitive phase III study to investigate nilotinib in Parkinson’s and other neurodegenerative diseases. CONFLICT OF INTEREST DESCRIPTION: Charbel Moussa is listed as an inventor on several Georgetown University patents for the use of tyrosine kinase inhibitors as a treatment for neurodegenerative diseases
5G Internet of radio light services for supermarkets (2017)

In this paper we present a 5G Internet Radio-Light (IoRL) architecture for supermarkets that can be readily deployed because it utilizes unlicensed visible light and millimeter wave part of the spectrum and which is used to provide shoppers with accurate location, interaction, access to Internet and Cloud based services such as high resolution video on a Tablet PC. The paper describes the supermarket use cases, the user and functional requirements and the IoRL architecture.
Multiobjective Optimization of Bespoke Gradient-Index Lenses: A Powerful Tool for Overcoming the Limitations of Transformation Optics (2022)

Gradient-index (GRIN) lenses have paved the way for electromagnetic wave tailoring due to their spatially varying permittivities, which enable continuous manipulation of the wave as it passes through the lens volume. However, traditional GRIN design methodologies, such as transformation optics or geometrical optics, often generate lens profiles that are limited to single-band performance. Here, we propose a multiobjective optimization strategy customized for designing dual-band GRIN lenses. Utilizing this powerful inverse-design tool, in conjunction with an advanced manufacturing technique, a GRIN lens with compact size and nonintuitive permittivity distribution is designed, fabricated, and characterized. The lens is capable of realizing two unique gain enhancement objectives at the L and C bands simultaneously, where different feeding sources are employed at the two bands.
Endogenous TOM20 Proximity Labelling: A Swiss-Knife for the Study of Mitochondrial Proteins in Human Cells (2023)

Biotin-based proximity labeling approaches, such as BioID, have demonstrated their use for the study of mitochondria proteomes in living cells. The use of genetically engineered BioID cell lines enables the detailed characterization of poorly characterized processes such as mitochondrial co-translational import. In this process, translation is coupled to the translocation of the mitochon-drial proteins, alleviating the energy cost typically associated with the post-translational import relying on chaperone systems. However, the mechanisms are still unclear with only few actors identified but none that have been described in mammals yet. We thus profiled the TOM20 prox-isome using BioID, assuming that some of identified proteins could be molecular actors of the co-translational import in human cells. The obtained results showed a high enrichment of RNA bind-ing proteins close to the TOM complex. However, for the few selected candidates, we could not demonstrate a role in the mitochondrial co-translational import process. Nonetheless, we were able to demonstrate additional uses of our BioID cell line. Indeed, the experimental approach used in this study is thus proposed for the identification of mitochondrial co-translational import effec-tors and for the monitoring of protein entry inside mitochondria with a potential application in the prediction of mitochondrial protein half-life.
An All-Optical Silicon Nano-Transistor (2004)

Abstract : We provide Silicon with optoelectronic capabilities using highly confined photonic structures. The photonic structures enhance the free carrier injection effect on the Silicon index of refraction, by orders of magnitude. We present experimental demonstration of fast all-optical switching on a silicon photonic integrated device by employing a strong light-confinement structure to enhance sensitivity to small changes in the refractive index. By use of a control light pulse with energy as low as 40 pJ, the optical transmission of the structure is modulated by more than 97% with a time response of 450 ps. We also demonstrate a 20-micrometer-long tunable optical resonator integrated on a silicon-on-insulator waveguide. The microresonator consists of a planar Fabry-Perot microcavity defined by deep Si/SiO2 Bragg reflectors with a high finesse of 11.2. The device is electrically driven and shows a modulation depth as high as 53% for a power consumption of only 20 mW. The results could enable an all-optical CMOS compatible chip, where all of the devices would be monolithically grown on-chip.
Kinetics of high concentration arsenic deactivation at moderate to low temperatures (1992)

This work investigates the kinetics of arsenic deactivation at temperatures from 500 to 800[degrees]C and for concentrations between 1 x 10[sup 20] and 1 x 10[sup 21]/cm[sup 3]. Using profiles created by repeated laser melt annealing, the authors determine mobility as a function of both active and inactive dopant concentration and then characterize the dynamics of carrier deactivation. Retrograde resistivity versus concentration was observed at high doses, which is explained by a mobility reduction due to the inactive arsenic and by retrograde electrical activity of the dopant itself.
Hommage à Yves Laporte (2013)

Yves Laporte est né à Toulouse le 21 décembre 1920. Durant la seconde guerre mondiale, il a été membre de la Résistance française et après sa démobilisation de la 1ère Armée Française, il se voit décerner en 1945 la Médaille de la Résistance et la Croix de guerre. Sur les conseils d'Alfred Fessard, alors titulaire de la chaire de Neurophysiologie au Collège de France, il part pour deux ans aux états-Unis où, grâce à un soutien des relations culturelles puis comme boursier de la Fondation Roc...
A Novel Type V CRISPR System with Potential for Genome Editing in the Liver (2021)

Abstract RNA guided CRISPR genome editing systems can make specific changes to the genomes of mammalian cells and have the potential to treat a range of diseases including those that can be addressed by editing hepatocytes. Attempts to edit the liver in vivo have relied almost exclusively on the Cas9 nucleases derived from the bacteria S treptococcus pyogenes or Staphylococcus aureus to which humans are commonly exposed. Pre-existing immunity to both these proteins has been reported in humans which raises concerns about their in vivo application. In silico analysis of a large metagenomics database followed by testing in mammalian cells in culture identified MG29-1, a novel CRISPR system which is a member of the Type V family but exhibits only 41 % amino acid identity to Francisella tularensis Cas12a/cpf1. MG29-1 is a 1280 amino acid RNA programmable nuclease that utilizes a single guide RNA comprised of a 22 nucleotide (nt) constant region and a 20 to 25 nt spacer, recognizes the PAM KTTN (predicted frequency 1 in 16 bp) and generates staggered cuts. MG29-1 was derived from a sample taken from a hydrothermal vent and it is therefore unlikely that humans will have developed pre-existing immunity to this protein. A screen for sgRNA targeting serum albumin in the mouse liver cell line Hepa1-6 identified 6 guides that generated more than 80% INDELS. The MG29-1 system was optimized for in vivo delivery by screening chemical modifications to the guide that improve stability in mammalian cell lysates while retaining or improving editing activity. Two lead guide chemistries were evaluated in mice using MG29-1 mRNA and sgRNA packaged in lipid nanoparticles (LNP). Three days after a single IV administration on-target editing was evaluated in the liver by Sanger sequencing. The sgRNA that was the most stable in the in vitro assay generated INDELS that ranged from 20 to 25% while a sgRNA with lower in vitro stability failed to generate detectable INDELs. The short sgRNA and small protein size compared to spCas9 makes MG29-1 an attractive alternative to spCas9 for in vivo editing applications. Evaluation of the potential of MG29-1 to perform gene knockouts and gene additions via non-homologous end joining is ongoing. Disclosures No relevant conflicts of interest to declare.
Endothelin-1 Enhances Nitric Oxide–Induced Cytotoxicity in Vascular Smooth Muscle (1995)

Prolonged incubation with 1 nmol/L interleukin-1 induced high levels of nitric oxide release and cytotoxicity in vascular smooth muscle cells. NG-Monomethyl-L-arginine, an inhibitor of nitric oxide synthesis, inhibited interleukin-1-induced cytotoxicity at a concentration of 3 mmol/L. Furthermore, prolonged incubation with 0.1 mmol/L sodium nitroprusside, a nitric oxide donor, also induced cytotoxicity. On the other hand, endothelin-1 at concentrations from 10(-10) to 10(-7) mol/L induced a concentration-dependent enhancement of cytotoxicity induced by interleukin-1. However, endothelin-1 did not affect interleukin-1-induced nitric oxide production. Coculture study of vascular smooth muscle cells and endothelial cells without direct cell contact revealed that incubation for 72 hours with interleukin-1 induced high levels of nitric oxide release from cocultured vascular smooth muscle cells to the same degree as release from vascular smooth muscle cells alone. However, interleukin-1-induced cytotoxicity was more enhanced in cocultured vascular smooth muscle cells than in vascular smooth muscle cells alone. Furthermore, coincubation with 20 nmol/L BQ-485, an antagonist of one type of endothelin receptor (ETA), prevented the enhancement of interleukin-1-induced cytotoxicity in cocultured vascular smooth muscle cells. These findings suggest that endothelin-1 secreted from endothelial cells may enhance nitric oxide-induced cytotoxicity by means of the ETA receptor in vascular smooth muscle cells.
Mechanisms of Organocatalytic Amidation and Trans-Esterification of Aromatic Esters As a Model for the Depolymerization of Poly(ethylene) Terephthalate (2012)

We describe investigations with B3LYP density functional theory to probe mechanisms for the organocatalyzed depolymerization of poly(ethylene) terephthalate (PET) into ester and amide products. These investigations utilize model systems involving the trans-esterification and amidation of methylbenzoate (MB) with ethylene glycol (EG), ethylenediamine (EDA), and ethanolamine (EA) organocatalyzed by 1,5,7-triazabicyclododecene (TBD) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Mechanisms for reactions in which TBD acts as the lone catalyst have been compared with pathways in which TBD and DBU catalyze these processes with an additional molecule of the amine or alcohol acting as a cocatalyst. Calculations suggest that the combination of an organocatalyst with a molecule of an alcohol or amine cocatalyst is slightly more activating than a lone catalyst. Our results predict that nucleophilic attack is the rate-determining step in reactions involving EDA and EG and that TBD is a better catalyst than DBU in the amidation of MB with EDA; in addition, both organocatalysts activate alcohols more than amines during nucleophilic attack. Amidation and trans-esterification possess similar barriers for reactions involving EA; but the amide, which is the thermodynamic product, is preferentially formed instead of the ester.
From membrane‐in‐the‐middle to mirror‐in‐the‐middle with a high‐reflectivity sub‐wavelength grating (2014)

A “membrane‐in‐the‐middle” optomechanical system is demonstrated using a silicon nitride membrane patterned as a subwavelength grating. The grating has a reflectivity of over 99.8 %, effectively creating two sub‐cavities, with free spectral ranges of 6 GHz, optically coupled via photon tunneling. Measurements of the transmission and reflection spectra show an avoided crossing where the two sub‐cavities simultaneously come into resonance, with a frequency splitting of 54 MHz. Expressions for the lineshapes of the symmetric and antisymmetric modes at the avoided crossing are derived, and the grating reflection, transmission, absorption, and scattering are inferred through comparison with the experimental data.
Femtocell interference analysis based on the development of system-level LTE simulator (2012)

Abstract Although femtocell can confer various benefits to both operators and users, many technical issues, such as interference coordination, network synchronization, self-configuration, and self-optimization must be considered to effectively deploy femtocells in real environments. In this article, we develop a system-level simulator in order to evaluate performance of long-term evolution (LTE)-femtocell systems. The simulator consists of five functional modules which realize packet scheduling and call admission control functionalities and model various wireless channel effects, real and non-real time traffics, and user mobility. These modules are managed by operational modules that follow event-driven programming. In addition, the simulator adopts a graphical user interface (GUI) that facilitates configuration, management, and observation of simulations in real time. Based on the simulator, we analyze effects of signal interference between macro- and femtocells under four scenarios. From the results, we confirm that the developed LTE-femtocell simulator can effectively support performance evaluation and analysis on various femtocell deployment scenarios.
Improvement in impact strength of modified cardanol‐bonded cellulose thermoplastic resin by using olefin resins (2013)

ABSTRACT Impact strength of a modified cardanol‐bonded cellulose thermoplastic resin was greatly improved by using a small amount of olefin resins. As we showed, this thermoplastic resin (3‐pentadecylphenoxy acetic acid (PAA)‐bonded cellulose diacetate (CDA): PAA‐bonded CDA) exhibited high practical properties such as bending strength, heat resistance, and water resistance. However, its impact strength was insufficient for use in durable products. We improved the impact strength of PAA‐bonded CDA by adding hydrophobic olefin resins, such as polyethylene or polypropylene, while maintaining good bending strength and breaking strain. Furthermore, the application of olefin resins also increased water resistance and fluidity. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131 , 39829.
In vitro and In vivo Radiosensitization of Glioblastoma Cells by the Poly (ADP-Ribose) Polymerase Inhibitor E7016 (2009)

These results indicate that E7016 can enhance tumor cell radiosensitivity in vitro and in vivo through the inhibition of DNA repair. Moreover, enhanced growth delay with the addition of E7016 to temozolomide and radiotherapy in a glioma mouse model suggests a potential role for this drug in the treatment of glioblastoma multiforme.
A Fully Integrated Micro‐Magnetometer/Microspacecraft for Multipoint Measurements: the Free‐Flyer Magnetometer (2013)

In the decades since the advent of in situ plasma measurements on board spacecraft, the instrumentation has grown bigger, heavier, and more complex as our understanding of space plasmas improves and our appetite for more information increases...There has thus been a recent interest in the miniaturization of both spacecraft and the instrument payload... This paper describes the results and status of an ongoing design study to understand the problems and trade space of fully integrating an instrument into a micro-spacecraft.
Increased production using excimer lasers through enhanced beam utilization factors (1998)

Excimer lasers are the third major classification of industrial laser in use today (the first being CO<SUB>2</SUB> lasers and the second being solid state lasers, such as YAG). Excimer lasers are used with far field mask image projection techniques, and as such are potentially inefficient due to UV photons being lost at the mask. Cost effective materials processing requires that the maximum amount of available UV photons are efficiently utilized. This paper outlines some of the latest excimer laser beam delivery techniques currently used for high volume micromachining and via drilling production applications. UV solid state lasers are increasing in average power and beam quality but are still limited to a few watts of average power. New mask illumination techniques can improve production throughputs by factors of 2X to &gt;10X over conventional excimer mask projection processing. This paper discusses methods currently available applying the high average power of 50 to 100 watts available with increasing cost effectiveness.
Identification of a Novel Genetic Locus for Familial Cardiac Myxomas and Carney Complex (1998)

The ultimate identification and analysis of the Carney complex disease gene at this human chromosome 17q2 locus will facilitate diagnosis and treatment of cardiac myxomas and will foster new concepts in regulation of cardiac cell growth and differentiation.
Modified radius directed equaliser for high order QAM (2015)

The RDE for M-ary QAM equalisation is modified using a low-complexity probabilistic update algorithm. Performance is investigated in simulation and experiment for 8 GBd DP-64QAM and DP-256QAM. DP-64QAM improved by 3.2 dB Q <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> -factor for a dynamic channel with high OSNR.
Merkel Cell Polyomavirus Large T Antigen Disrupts Lysosome Clustering by Translocating Human Vam6p from the Cytoplasm to the Nucleus (2011)

Merkel cell polyomavirus (MCV) has been recently described as the cause for most human Merkel cell carcinomas. MCV is similar to simian virus 40 (SV40) and encodes a nuclear large T (LT) oncoprotein that is usually mutated to eliminate viral replication among tumor-derived MCV. We identified the hVam6p cytoplasmic protein involved in lysosomal processing as a novel interactor with MCV LT but not SV40 LT. hVam6p binds through its clathrin heavy chain homology domain to a unique region of MCV LT adjacent to the retinoblastoma binding site. MCV LT translocates hVam6p to the nucleus, sequestering it from involvement in lysosomal trafficking. A naturally occurring, tumor-derived mutant LT (MCV350) lacking a nuclear localization signal binds hVam6p but fails to inhibit hVam6p-induced lysosomal clustering. MCV has evolved a novel mechanism to target hVam6p that may contribute to viral uncoating or egress through lysosomal processing during virus replication.