gebhart/patrepeval huggingface dataset:
Abstract 1622: Block-Removed Immunoglobulin Technology (BRITE) to enhance rituximab effector function by counteracting CA125/MUC16-mediated immunosuppression (2021)

Abstract Rituximab is a CD20-targeting antibody that is the standard-of-care for patients with Non-Hodgkin Lymphoma (NHL) cases. Rituximab's mechanism of action includes complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) - herein referred to as Humoral Immuno-Oncology (HIO) mechanism. Recent clinical evidence suggest that high serum levels of the tumor-produced MUC16/CA125 protein has a negative impact on the effectiveness of rituximab clinical activity on up to 40% of follicular lymphoma patients. In this study we demonstrate that CA125 binds to rituximab and reduces its tumor cell killing activity. Moreover, we describe the generation of a rituximab variant, named NAV-006, using a proprietary technology called Block-Removed Immunoglobulin Technology (BRITE) that employs randomized amino substitution and high-throughput screening to identify HIO-refractory rituximab variants. Here, we demonstrate that NAV-006 is more refractory to the immunosuppressive effects mediated by CA125 as shown by its reduced CA125 interaction and increased HIO activity. These data warrants further investigation of NAV-006 as a next generation anti-CD20 antibody that could improve upon the efficacy of the parent rituximab in NHL patients with high levels of CA125. Citation Format: Luigi Grasso, J. Bradford Kline, Nicholas C. Nicolaides. Block-Removed Immunoglobulin Technology (BRITE) to enhance rituximab effector function by counteracting CA125/MUC16-mediated immunosuppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1622.
4th Industrial Revolution Driven by AI Service Platform (2018)

우리는 헐리우드 SF 영화들을 통해서 미래의 기술 및 사회를 엿보고, 시간이 흘러 그것이 현재가 되어 있는 것을 목격한다. 마이너리티 리포트, 이글 아이, 아바타 등은 모든 객체가 연결되고, 분석되고, 예측되며, 제어 가능한 미래상을 그리고 있으며, 가상현실과 물리현실이 혼합되어 운용되는 미래사회를 그려내고 있다. 사물인터넷 기반의 초연결성, 인공지능 기반의 초지능, 그리고 물리객체와 가상객체가 동기화된 혼합현실은 4차 산업혁명의 핵심 키워드들이다. 초연결성, 초지능, 혼합현실은 플랫폼 기술을 통해서 다양한 서비스로 현실화 될 것이며, 기존 산업의 고도화, 산업 간 융합, 신산업 창출의 기회를 제공할 것이다. 본 논문에서는 사물인터넷 환경에서의 인공지능 서비스 플랫폼 기술이 무엇인지를 분석하고, 인공지능 서비스 플랫폼의 기술적 역량과 이러한 기술적 역량이 가져올 산업적, 경제적, 사회적 변화상에 대한 분석 결과를 기술한다.
Intranephron Distribution of Insulin Binding in Wistar Kyoto and Spontaneously Hypertensive Rats (1989)

In male 8-week-old hypertensive rats (SHR), a significant decrease in specific [125I]insulin binding capacity per both unit tubule length and milligram protein was observed in the terminal proximal tubule (S3) compared with normotensive rats (WKY).
A tryptophan hydroxylase inhibitor produced by a streptomycete: 2,5-Dihydro-L-phenylalanine. (1977)

Een calibratie techniek wordt besproken om de nauwkeurigheid te verbeteren met een 2D gemoduleerd verstrooings array. Er wordt uitgelegd hoe een niet-uniforme karakteristiek in amplitude en phase gecorrigeerd kan worden met een aparte meting met een vlakke golf belichting van het array in een Compacte Antenne Test Range. Een vergelijking wordt gepresenteerd van een near-field meting van een hoorn antenne voor en na zo'n calibratie This paper presents a calibration technique for improving the accuracy of the near-field measurement with a 2D modulated scattering array. It is explained how the non-uniform characteristics in amplitude and in phase of a 2D array can be corrected by using a separate assessment of the array with a plane wave illumination (CATR). A comparison of a near-field measurement of a pyramidal horn is shown before and after such calibration.
Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer (2010)

Chemotherapy resistance is a major obstacle in cancer treatment, yet the mechanisms of response to specific therapies have been largely unexplored in vivo. Employing genetic, genomic, and imaging approaches, we examined the dynamics of response to a mainstay chemotherapeutic, cisplatin, in multiple mouse models of human non-small-cell lung cancer (NSCLC). We show that lung tumors initially respond to cisplatin by sensing DNA damage, undergoing cell cycle arrest, and inducing apoptosis-leading to a significant reduction in tumor burden. Importantly, we demonstrate that this response does not depend on the tumor suppressor p53 or its transcriptional target, p21. Prolonged cisplatin treatment promotes the emergence of resistant tumors with enhanced repair capacity that are cross-resistant to platinum analogs, exhibit advanced histopathology, and possess an increased frequency of genomic alterations. Cisplatin-resistant tumors express elevated levels of multiple DNA damage repair and cell cycle arrest-related genes, including p53-inducible protein with a death domain (Pidd). We demonstrate a novel role for PIDD as a regulator of chemotherapy response in human lung tumor cells.
Abstract 4534: Cyclooxygenase inhibitors as delivery vehicles for histone deacetylase inhibitors (2015)

Abstract Reversible acetylation state of histones determines the existence of the chromatin in either the euchromatin state or the heterochromatin state, which in turn control the accessibility of transcription factors to promoter regions of genes on the chromatin. This reversible acetylation state is regulated by two enzymes: histone deacetylases (HDAC) and histone acetyl transferases (HAT). Imbalance in the expression of these enzymes is associated with many diseases, with equilibrium tilted towards HDAC in tumors. Reversal of the HDAC enzymes to their basal expression level, by small molecule inhibition, has been shown to significantly reduce the growth of tumors and/or completely eliminate them. Currently, there are three (3) FDA approved HDAC inhibitors in the market: vorinostat, FK228 and belinostat (all approved by the FDA for treatment of cutaneous T-cell lymphoma). Although highly effective, these compounds suffer drawbacks such as lack of activity against solid tumors, off-target toxicities, short half-life, and lack of HDAC isoform selectivity. To address some of these challenges, we chose to incorporate a targeting moiety to the head group in the classical vorinostat pharmacophoric model (comprising head group, linker and zinc binding group (ZBG)). We envisaged that selective toxicity towards tumors (hence, reduction in off-target toxicities), may be achieved if the HDAC inhibitor is selectively delivered to tumor cells expressing cyclooxygenase 2 (COX-2) enzyme. COX-2, which catalyzes the conversion of arachidonic acid to prostaglandins, is ubiquitously expressed in a wide range of cancer types and has been exploited to selectively image cancer cells in the past. To achieve this, we designed and synthesized series of hydroxamic acid-based compounds having either celecoxib or indomethacin (COX-2 inhibitors) as the targeting moiety. In addition to these compounds, we made compounds having “biaryl group” as ZBG. Compounds based on this ZBG have been reported to selectively inhibit HDAC isoforms 1&amp;2, both culprits in a wide range of cancer types. Consistent with the reported HDAC isoform selectivity, our “biaryl” ZBG compounds potently and selectively inhibited HDACs 1&amp; 2. Also, our hydroxamic acid-based compounds were better than vorinostat in cell-free assay and showed potent activity in MCF-7, A549 and HCT-116 cancer cell lines. Effort is underway to evaluate the in vivo activity of our lead compounds in animal models. Citation Format: Idris Olawale Raji, Emily Janeira, Fatima Yadudu, Fathi Shaghayegh, James Kornacki, Milan Mrksich, Adegboyega Oyelere. Cyclooxygenase inhibitors as delivery vehicles for histone deacetylase inhibitors. [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 4534. doi:10.1158/1538-7445.AM2015-4534
Drug screening at single-organoid resolution via bioprinting and interferometry (2021)

Abstract High-throughput drug screening is an established approach to investigate tumor biology and identify therapeutic leads. Traditional platforms for high-throughput screening use two-dimensional cultures of immortalized cell lines which do not accurately reflect the biology of human tumors. More clinically relevant model systems, such as three-dimensional tumor organoids, can be difficult to screen and scale. For example, manually seeded organoids coupled to destructive endpoint assays allow for the characterization of response to treatment, but do not capture the transitory changes and intra-sample heterogeneity underlying clinically observed resistance to therapy. We therefore developed a pipeline to generate bioprinted tumor organoids linked to label-free, real-time imaging via high-speed live cell interferometry (HSLCI) and machine learning-based quantitation of individual organoids. Bioprinting cells gives rise to 3D organoid structures that preserve tumor histology and gene expression. HSLCI imaging in tandem with machine learning-based image segmentation and organoid classification tools enables accurate, label-free parallel mass measurements for thousands of bioprinted organoids. We demonstrate that our method quantitatively identifies individual organoids as insensitive, transiently sensitive, or persistently sensitive to specific treatments. This opens new avenues for rapid, actionable therapeutic selection using automated tumor organoid screening.
Mapping Spiking Neural Networks to Neuromorphic Hardware (2019)

Neuromorphic hardware implements biological neurons and synapses to execute a spiking neural network (SNN)-based machine learning. We present SpiNeMap, a design methodology to map SNNs to crossbar-based neuromorphic hardware, minimizing spike latency and energy consumption. SpiNeMap operates in two steps: SpiNeCluster and SpiNePlacer. SpiNeCluster is a heuristic-based clustering technique to partition an SNN into clusters of synapses, where intracluster local synapses are mapped within crossbars of the hardware and intercluster global synapses are mapped to the shared interconnect. SpiNeCluster minimizes the number of spikes on global synapses, which reduces spike congestion and improves application performance. SpiNePlacer then finds the best placement of local and global synapses on the hardware using a metaheuristic-based approach to minimize energy consumption and spike latency. We evaluate SpiNeMap using synthetic and realistic SNNs on a state-of-the-art neuromorphic hardware. We show that SpiNeMap reduces average energy consumption by 45% and spike latency by 21%, compared to the best-performing SNN mapping technique.
The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC) (2020)

The advancement of new therapies, including targeted therapies and immunotherapies, has improved the survival of non-small-cell lung cancer (NSCLC) patients in the last decade. Some NSCLC patients still do not benefit from therapies or encounter progressive disease during the course of treatment because they have intrinsic resistance, acquired resistance, or lack a targetable driver mutation. More investigations on the molecular biology of NSCLC are needed to find useful biomarkers for current therapies and to develop novel therapeutic strategies. Src is a non-receptor tyrosine kinase protein that interacts with cell surface growth factor receptors and the intracellular signaling pathway to maintain cell survival tumorigenesis in NSCLC. The Yes-associated protein (YAP) is one of the main effectors of the Hippo pathway and has been identified as a promoter of drug resistance, cancer progression, and metastasis in NSCLC. Here, we review studies that have investigated the activation of YAP as mediated by Src kinases and demonstrate that Src regulates YAP through three main mechanisms: (1) direct phosphorylation; (2) the activation of pathways repressing Hippo kinases; and (3) Hippo-independent mechanisms. Further work should focus on the efficacy of Src inhibitors in inhibiting YAP activity in NSCLC. In addition, future efforts toward developing potentially reasonable combinations of therapy targeting the Src-YAP axis using other therapies, including targeted therapies and/or immunotherapies, are warranted.
Real‐time motion correction for high‐resolution larynx imaging (2011)

Motion--both rigid-body and nonrigid--is the main limitation to in vivo, high-resolution larynx imaging. In this work, a new real-time motion compensation algorithm is introduced. Navigator data are processed in real time to compute the displacement information, and projections are corrected using phase modulation in k-space. Upon automatic feedback, the system immediately reacquires the data most heavily corrupted by nonrigid motion, i.e., the data whose corresponding projections could not be properly corrected. This algorithm overcomes the shortcomings of the so-called diminishing variance algorithm by combining it with navigator-based rigid-body motion correction. Because rigid-body motion correction is performed first, continual bulk motion no longer impedes nor prevents the convergence of the algorithm. Phantom experiments show that the algorithm properly corrects for translations and reacquires data corrupted by nonrigid motion. Larynx imaging was performed on healthy volunteers, and substantial reduction of motion artifacts caused by bulk shift, swallowing, and coughing was achieved.
RNA INTERFERENCE AS ANTIVIRAL THERAPY: DREAM OR REALITY? (2013)

Soon aft er discovery of RNA interference (RNAi), its potential as eff ective antiviral therapy was recognized. Since then RNAi has been variously exploited for antiviral purposes which could eff ectively block viral replication in vitro. For invivo use, however, delivery issue, toxicity, RNAi suppression and viral escape are still major hurdles. Here, we providean overview of the RNAi strategy and review the approaches that have been developed to surpass the obstacles and to achieve targeted gene silencing for antiviral and other therapies. (Resume d'auteur)
Additive solution deposition of multi-layered semiconducting polymer films for design of sophisticated device architectures (2018)

Mutually soluble semiconducting polymer films are sequentially deposited from solution to form multiple layers with minimal mixing.
Catalysis in Water Remediation (2008)

Abstract The sections in this article are Introduction Oxidation Processes Wet Air Oxidation ( WAO ) Conventional Wet Air Oxidation Supercritical Water Oxidation Catalytic Wet Air Oxidation ( CWAO ) Fenton Processes Conventional Fenton Processes Photo‐Assisted Fenton Processes Applications of Fenton Processes Photocatalysis Other Oxidation Processes Reduction Processes Hydrodechlorination/Hydrodehalogenation Hydrodechlorination by Zero‐Valent Metals Hydrodechlorination with Supported Metal Catalysts Hydrodenitration Conclusions
Liposomal mr contrast agents (1994)

AbstractLiposomes are spheres composed of relatively non-toxic and biodegradable lipids which are useful for entrapping a variety of drugs, decreasing drug toxicity and targeting. For a number of years we have evaluated the use of liposomes as MR contrast agents. We have prepared and tested contrast agents entrapped within the internal aqueous space of liposomes as well as liposomes incorporating lipophilic contrast agents in the lipid bilayer. When chelates such as Gd-DTPA are entrapped within the internal aqueous space of lipid vesicles, delivery is primarily to the Kupffer cells and clearance is slow. Manganese ions entrapped within lipid vesicles cause more enhancement per micromole of paramagnetic ion than gadolinium. Lipophilic derivatives of manganese EDTA chelates when incorporated into liposomes confer the greatest hepatic enhancement per micromole of metal ion and have favorable clearance kinetics. An apparently hepatocyte specific liposomal MR contrast agent has been prepared based upon a lipophilic derivative of manganese EDTA, which enhances the liver and increases liver/tumor contrast to noise more than most other contrast agents per micromole of metal ion. The agent has very high relaxivity, Rl over 30 and R2 over 40 per micromole of manganese. Cardiac imaging shows pronounced blood pool enhancement with potential for myocardial perfusion imaging. Membrane bound lipophilic paramagnetic chelates hold promise as improved liposomal contrast agents for MR.
Oscillatory Optical Response of an Amorphous Two-Dimensional Array of Gold Nanoparticles (2012)

The optical response of metallic nanoparticle arrays is dominated by localized surface plasmon excitations and is the sum of individual particle contributions modified by interparticle coupling that depends on specific array geometry. We demonstrate a so far unexplored distinct oscillatory behavior of the plasmon peak position, full width at half maximum, and extinction efficiency in large area amorphous arrays of Au nanodisks, which depend on the minimum particle center-to-center distance in the array. Amorphous arrays exhibit short-range order and are completely random at long distances. In our theoretical analysis we introduce a film of dipoles approach, within the framework of the coupled dipole approximation, which describes the array as an average particle surrounded by a continuum of dipoles with surface densities determined by the pair correlation function of the array.
Detection of Spatial-Specific Phytochrome Responses Using Targeted Expression of Biliverdin Reductase in Arabidopsis (2008)

To regulate levels of holophytochrome in a spatial-specific manner and investigate the major sites of action of phytochromes during seedling development, we constructed transgenic Arabidopsis (Arabidopsis thaliana) plant lines expressing plastid-targeted mammalian biliverdin IXalpha reductase (pBVR) under regulatory control of CAB3 and MERI5 promoters. Comparative photobiological and phenotypic analyses indicated that spatial-specific expression of pBVR led to the disruption of distinct subsets of phytochrome-regulated responses for different promoters. pBVR expression in photosynthetic tissues (CAB3::pBVR lines) had intermediate effects on chlorophyll accumulation, carotenoid production, anthocyanin synthesis, and leaf development responses in white-light conditions. CAB3::pBVR expression, however, resulted in distinctive phenotypes in far-red (FR) conditions. A number of FR high irradiance responses were disrupted in CAB::pBVR lines, including FR-dependent inhibition of hypocotyl elongation and stimulation of anthocyanin accumulation. By contrast, preferential expression of pBVR in the shoot apical meristem in MERI5::pBVR lines resulted in a phytochrome-deficient, leaf development phenotype under short-day growth conditions. These results implicate leaf-localized phytochrome A as having a unique role in regulating FR-mediated hypocotyl elongation and meristem- and/or leaf primordia-localized phytochromes as having a novel role in phytochrome-dependent responses. Taken together, these studies demonstrate the efficacy of selectively inactivating distinct phytochrome-mediated responses by regulated expression of BVR in transgenic plants, a novel means to investigate the sites of phytochrome photoperception and to regulate specifically light-mediated plant growth and development.
Smart Drilling Fluids Formulations for Sensitive Shale Formations Using Surfactants and Nanoparticles (2023)

Abstract The demand for oil and gas is continuing to rise with a growing population and worldwide industrialization. Surfactants are considered excellent additives for drilling formulations because of their unique properties and chemical structure. The surface-modified nanoparticles in the drilling fluids (DFs) help to improve the rheological and filtration properties of water-sensitive shale formations. The water-sensitive shale formations in the wellbore often result in swelling after interacting with water-based DFs. The swelling of shale formation impacts the rheological and filtration properties of DFs. The aim of this study is to formulate DFs with cationic surfactants and surface-modified nanoparticles to minimize shale swelling and improve the rheological and filtration properties. Various drilling fluid formulations were prepared with bentonite as a basic constituent of DFs while Gemini surfactant and graphene nanoparticles were added with concentrations of 0.5%. The rheological and filtration properties were determined at room temperature. The shale inhibition tests were performed to analyze the swelling inhibition properties of DFs. The surface-modified nanoparticles along with the cationic surfactant make a stable dispersion of DFs. The presence of nanoparticles in the DFs enhances the rheological and filtration properties. The filtrate loss has been significantly reduced by incorporating graphene nanoparticles and Gemini surfactant-modified graphene nanoparticles. The rheological properties such as plastic viscosity, yield stress, and gel strengths have been improved by the combined addition of surfactant-modified nanoparticles. The reduction of filtrate loss was due to the clogging effect of small passages in the filter cake while long alkyl chains of surfactant molecules spread over the filter cake making a hydrophobic film that minimizes the contact of water with the filter cake. Moreover, the swelling inhibition test such as the linear swelling test showed that the presence of nanoparticles and cationic surfactants significantly enhanced the shale swelling inhibition and reduced the percentage of swelling compared to the DI water. The cationic surfactant interacts with the negatively charged clay particles through electrostatic forces and surfactant along alkyl chains wraps around the clay particles which leads to the minimum swelling of shale formations. This study reveals that the formulations based on surface-modified nanoparticles and surfactants in water-based DFs can inhibit shale swelling and improves the borehole stability for water-sensitive shale formations.
Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions. (2019)

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P &lt; 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P &lt; 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.