gebhart/patrepeval huggingface dataset:
Effect of deltorphin on pituitary-adrenal response to insulin-induced hypoglycemia and ovine corticotropin-releasing hormone in healthy man. (1992)

To determine the role of delta-opioid receptors in the modulation of hypothalamic-pituitary-adrenal activity, we studied in normal subjects the effect of the highly selective delta-opioid receptor agonist deltorphin (DT) on the secretion of ACTH, cortisol, and arginine vasopressin in response to insulin-induced hypoglycemia. In an attempt to clarify the site of opiate modulation of ACTH secretion, we also studied in normal subjects the effect of DT on the ACTH response to ovine CRH-41. DT blunted the ACTH, cortisol, and arginine vasopressin responses to insulin-induced hypoglycemia, whereas it had no effect on the ACTH and cortisol responses to CRH. We conclude that DT-induced activation of delta-opioid receptors exerts an inhibitory influence on hypoglycemia-stimulated ACTH secretion. Based on the lack of an effect of DT on the ACTH response to CRH, we postulate that DT may modulate the secretion of ACTH through suprapituitary mechanisms.
Abstract 59: Engineering glypican-3 targeting immunotoxins for the treatment of liver cancer (2017)

Abstract The expression of glypican-3 (GPC3) in hepatocellular carcinoma offers a target with high tissue specificity and cell signaling implications. A human single domain antibody discovered by phage display technology, HN3, was fused to domain II and domain III of Pseudomonas exotoxin A. This protein (HN3-PE38) showed a high level of cytotoxic activity with a IC50 of 0.4 nM on Hep3B cells, but a relatively low maximum tolerated dose of 0.8 mg/kg in mice. In order to produce an immunotoxin with reduced toxicity, a new version was constructed that removed domain II and seven B cell epitopes from the Pseudomonas toxin. This deimmunized immunotoxin (HN3-mPE24) was shown to have a similar IC50 of 0.2 nM on Hep3B cells. To determine if further deimmunization was possible, three new versions have been generated with T cell epitopes or a series of both B and T cell epitopes removed. These include the HN3-T20 immunotoxin which had six T cell epitopes removed, HN3-T19 with 4 B cell, 4 T cell and 2 shared epitopes, and HN3-M11 with 5 B cell, 4 T cell and 2 shared epitopes. A comparative analysis of these immunotoxins was made using in vitro cell proliferation assays using Hep3B. Both the HN3-T20 (IC50 = 0.6 nM) and HN3-T19 (IC50 = 0.8 nM) immunotoxins had similar activity to HN3-mPE24 (IC50 = 0.7 nM) in a side by side comparison. The HN3-M11 variant had poor cytotoxicity and was excluded from in vivo examination. A Hep3B subcutaneous xenograft model was generated in athymic nude mice and was followed by nine rounds of intravenous immunotoxin treatments. The mPE24, T20 and T19 immunotoxins all showed an increase in average survival rate 70 days (mPE24), 76 days (T20) and 72 days (T19) when compared to the 55 days for PE38 and the 41 days for PBS alone. Additionally, the T20 and the T19 showed a maximum tolerated dose that was similar to that of the mPE24 with dosages as high as 10 mg/kg being well tolerated. This data would suggest that the HN3-T19 immunotoxins has potential clinical applications because it represents the most deimmunized immunotoxin to date. Citation Format: Bryan D. Fleming, Brittany Nixon, Ira Pastan, Mitchell Ho. Engineering glypican-3 targeting immunotoxins for the treatment of liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 59. doi:10.1158/1538-7445.AM2017-59
Modeling Electron‐Transfer Degradation of Organic Light‐Emitting Devices (2021)

The operational lifetime of organic light-emitting devices (OLEDs) is governed primarily by the intrinsic degradation of the materials. Therefore, a chemical model capable of predicting the operational stability is highly important. Here, a degradation model for OLEDs that exhibit thermally activated delayed fluorescence (TADF) is constructed and validated. The degradation model involves Langevin recombination of charge carriers on hosts, followed by the generation of a polaron pair through reductive electron transfer from a dopant to a host exciton as the initiation steps. The polarons undergo spontaneous decomposition, which competes with ultrafast recovery of the intact materials through charge recombination. Electrical and spectroscopic investigations provide information about the kinetics of each step in the operation and degradation of the devices, thereby enabling the building of mass balances for the key species in the emitting layers. Numerical solutions enable predictions of temporal decreases of the dopant concentration in various TADF emitting layers. The simulation results are in good agreement with experimental operational stabilities. This research disentangles the chemical processes in intrinsic electron-transfer degradation, and provides a useful foundation for improving the longevity of OLEDs.
A multi-scale integrated analysis identifies KRT8 as a pan-cancer early biomarker (2020)

An early biomarker would transform our ability to screen and treat patients with cancer. The large amount of multi-scale molecular data in public repositories from various cancers provide unprecedented opportunities to find such a biomarker. However, despite identification of numerous molecular biomarkers using these public data, fewer than 1% have proven robust enough to translate into clinical practice. One of the most important factors affecting the successful translation to clinical practice is lack of real-world patient population heterogeneity in the discovery process. Almost all biomarker studies analyze only a single cohort of patients with the same cancer using a single modality. Recent studies in other diseases have demonstrated the advantage of leveraging biological and technical heterogeneity across multiple independent cohorts to identify robust disease biomarkers. Here we analyzed 17149 samples from patients with one of 23 cancers that were profiled using either DNA methylation, bulk and single-cell gene expression, or protein expression in tumor and serum. First, we analyzed DNA methylation profiles of 9855 samples across 23 cancers from The Cancer Genome Atlas (TCGA). We then examined the gene expression profile of the most significantly hypomethylated gene, KRT8, in 6781 samples from 57 independent microarray datasets from NCBI GEO. KRT8 was significantly over-expressed across cancers except colon cancer (summary effect size=1.05; p < 0.0001). Further, single-cell RNAseq analysis of 7447 single cells from lung tumors showed that genes that significantly correlated with KRT8 (p < 0.05) were involved in p53-related pathways. Immunohistochemistry in tumor biopsies from 294 patients with lung cancer showed that high protein expression of KRT8 is a prognostic marker of poor survival (HR = 1.73, p = 0.01). Finally, detectable KRT8 in serum as measured by ELISA distinguished patients with pancreatic cancer from healthy controls with an AUROC=0.94. In summary, our analysis demonstrates that KRT8 is (1) differentially expressed in several cancers across all molecular modalities and (2) may be useful as a biomarker to identify patients that should be further tested for cancer.
Efficient synthesis of azetidine through N‐trityl‐ or N‐dimethoxytritylazetidines starting from 3‐amino‐l‐propanol or 3‐halopropylamine hydrohalides (1993)

Abstract Efficient synthetic routes for the preparation of azetidine starting from commercially available 3‐amino‐l‐propanol or 3‐halopropylamine hydrohalides are reported. First, the appropriate N ‐trityl‐ or N ‐dimethoxy‐trityl protected tosyloxy‐ or halopropylamines were prepared. These precursors were then cyclized into the N ‐trityl‐ or N ‐dimethoxytritylazetidines. The N ‐protecting groups were removed in the presence of perchloric acid giving the hydrogen perchlorate salt of azetidine. The latter compound was transformed into its free base using a strong base under anhydrous conditions. The relatively expensive 4,4′‐dimethoxytrityl chloride and less expensive trityl chloride used in these synthetic procedures were recycled in good yields. Azetidine hydrogenperchlorate can be used to prepare N ‐substituted azetidines without the need to isolate the free azetidine.
Effect of atomizing gas pressure on coating properties in wire arc spraying (1994)

Arc fluctuations due to periodic removal of molten droplets from the wire tips by the atomizing gas stream are characteristic for the wire arc spraying process. Dynamic forces of the atomizing air stream acting on the arc as well as on the droplets lead to different particle sizes which, in turn, determine porosity and oxide content of sprayed coatings. In this study, arc spraying of aluminum coatings is considered with the objective of establishing correlations between atomizing air pressure and coating properties such as porosity and oxide content. Since arc fluctuations may have a strong effect on droplet formation and, therefore, on coating properties, such fluctuations have been recorded by measuring arc voltages synchronized with droplet formation at the wire tips using a laser strobe high speed vision system. Porosity has been measured by optical microscopy combined with computerized image processing. Oxide content has been measured by Auger Electron Spectroscopy. The results revealed that porosity decreases with increasing atomizing gas pressures, while simultaneously the oxide content increases.
Performance of CMR stress/rest automated myocardial perfusion parametric mapping (perfusion map) as compared to manual plotting of the slope curves (2014)

Background Cardiac magnetic resonance (CMR) stress/rest myocardial perfusion is usually assessed in clinical practice by qualitative visual analysis. There might be some added value in analyzing upslope perfusion curves, but those are labor and time consuming. We aimed to evaluate a new inline post processing tool that allows for completely automatic construction of upslope curves with parametric pixelwise construction of perfusion myocardial maps.
Application ofN-methylpyrrolidin-2-one hydrotribromide in organic synthesis (2010)

The review describes the broad applicability of a modern reagent, N-methylpyrrolidin-2-one hydrotribromide (MPHT), in organic synthesis. The methods for its preparation and use in the bromination reactions of different classes of organic compounds (alkenes, alcohols, ketones, etc.), in the oxidation and epoxide ring-opening reactions, in conversions of alkenes to aziridines are considered. Special attention is given to the environmentally friendly character of MPHT.
Cover image, Volume 31 Issue 10 (2018)

The cover image, by Katharina Schregel et al., is based on the Special Issue Research Article Characterization of glioblastoma in an orthotopic mouse model with magnetic resonance elastography, https://doi.org/10.1002/nbm.3840. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 668039.
Physical and Functional Interaction between Wild-Type p53 and mdm2 Proteins (1994)

The mdm2 oncogene, which is often amplified in mammalian tumors, produces a number of transcripts that encode distinct protein forms. Previous studies demonstrating that overexpression of the mdm2 gene can activate its transforming potential, and can inhibit the transcriptional activation function of p53, prompted us to begin to explore possible functional differences among the various mdm2 products. Utilizing a transient transfection assay, we have evaluated four naturally occurring murine mdm2 forms for their ability to inhibit p53-mediated transcriptional activation of reporter genes regulated by p53 response elements. Three of these mdm2 forms were found to physically associate with the wild-type p53 protein and to possess the ability to inhibit its transactivation function. A fourth form failed to exhibit either of these functions. This last mdm2 form lacks the N-terminal protein domain that is present in the other three splice forms examined, pointing to this region as one that is critical for complex formation with the p53 protein. Identifying such differences among mdm2 proteins provides important clues for dissecting their functional domains, and emphasizes that defining the individual properties of these products will be critical in elucidating the overall growth control function of the mdm2 gene.
1043. Intravenous (I.V.) Administration of Manganese Superoxide Dismutase-Plasmid Liposome (MnSOD-PL) Complex Protects Mice from Whole Body Irradiation (2006)

Local administration of MnSOD-PL has been demonstrated to protect normal tissues from irradiation damage including: oral cavity, esophagus, lung, bladder and intestines. To determine whether systemic administration of MnSOD-PL protected the bone marrow from irradiation-induced damage, C57BL/6NHsd female mice were injected intravenously with MnSOD-PL (100 μg plasmid DNA). Groups of the mice were irradiated 24 hours later to 9 Gy, 9.5 Gy or 9.75 Gy whole body irradiation. Following irradiation, the mice were weighed on a daily basis and watched for signs of irradiation- induced hematologic damage. Control mice irradiated to either 9.5 Gy or 9.75 Gy demonstrated a loss of body weight while mice injected with the MnSOD-PL showed no changes in body weight. Mice injected with MnSOD-PL before irradiation demonstrated protection against irradiation with stabilized body weight and increased survival compared to control irradiated mice (p=0.0402 at 9.5 Gy or p = 0.0016 at 9.75 Gy). Therefore, I.V. administration of MnSOD-PL protects mice from bone marrow toxicity of whole body irradiation. Joel S. Greenberger, MD is a co-owner of and holds equity in Automated Cell, Inc., Pittsburgh, PA.
Structural characteristics of industrial lignins in respect to their valorization (2014)

The effect of raw material and pretreatment procedure on the structure and properties of industrial lignins was evaluated by detailed chemical and physical characterization. The application potential of studied lignins was considered based on those. Hydrolysis lignin and steam exploded lignins had clearly distinct characteristics compared to the spent liquor lignins; higher molar mass, significantly higher amount of native aryl ether linkages and thereby low phenol content. The hydrolysis lignin also contained significant amount of carbohydrate and protein residues, which may affect the applicability. For resin applications, the kraft lignins seem most reactive in respect of high phenol content. The high molar mass of hydrolysis lignin and steam exploded lignins could be beneficial for dispersants and composites.
Local inhibition of natural killer cell activity promotes the progressive growth of intraocular tumors. (1997)

AH inhibits NK cell activity in vitro and within the interior of the eye and prevents the rejection of NK-sensitive intraocular tumors.
Motion Prediction Based on Temporal Layering for Layered Video Coding (1998)

In this paper, we proposed a video coding technique which adopts motion estimation and compensation with temporal layering to provide temporal scalability. In this proposed video coding scheme, motion estimation is performed over temporal hierarchy of frames. Various motion estimation intervals of different layers lead to storage of multiple frames as references. These multiple references are stored and managed in a special buffer. The proposed scheme is able to provide a multi-layered bitstream for heterogeneous environments as well as to further reduce the temporal redundancy and thus admit a higher compression ratio than replenishment scheme. I. Introduction Video services are expected to be a significant component of various B-ISDN services. To cover a wide range of services in heterogeneous multicast environments where receivers and networks of different capacities coexist, video coding techniques that can support a variety of bit rates tailored to individual services are needed....
4-2-4 Laminate hotspot identification and joule heating effect assessment via thermoelectrical simulation (2019)

Abstract Laminates or sequential build-up (SBU) laminate comprised of dielectric materials, metal traces, and metal vias not only serve as the mechanical support for the silicon integrated circuits (ICs), but also electrically connect ICs to ball grid array (BGA); by way of an embedded power delivery structure. Electrical current required to power the ICs is carried through spatially distributed metal traces and vias. The non-uniformity in the power distribution may induce hotspots due to parasitic Ohmic heating; especially in regions with high current density. Electrical packaging engineers need effective tools to identify, quantify, and mitigate hot spots in the laminate. Thermoelectrical multiphysical simulation provides a robust platform integrating the electrical, and thermal analyses for the study of joule heating in a complex design. Conventional simulations simplify detailed laminate wiring layout as a single planar with effective orthogonal material properties. Such simplification provides a solution to the inherent simulation challenges encountered with a complex design (i.e. tiny characteristic lengths, high aspect ratios, excessive computational time and resources). However, simplification comes with a price. Information required to optimize the detail trace and via wiring physical design is unavailable in a solution incorporating an effective laminate; laminate joule heating as well as non-uniform trace wiring are left out. The laminate temperature profile is averaged based on effective material properties. Without accurate joule heating evaluation, the hotspots cannot be identified or quantified. Overheating inside the laminate compromises signal speed and integrity, raises reliability concerns, and may even trigger catastrophic damage of dielectric material breakdown. This work introduces an iterative approach integrating the detailed laminate electrical computer aided design (ECAD) and package design to simulate the joule heating with minimum simplification. The iterative loop enables constant update of temperature (thru thermal simulation platform) and power distribution (thru electrical simulation platform) in each trace layer and via. An accurate temperature dependent Joule Heating assessment is achieved upon convergence. The solution captures the dependence on temperature of the material properties and of the Joule heating itself. The package level structure including an IC with a power map is incorporated to simulate in-situ package operating condition. After thorough investigation and analyses of laminate joule heating phenomena under different conditions, a predictive curve for maximum temperature rise percentage has been proposed to guide laminate wiring layout physical design and optimization. A ratio exceeding 4–5% joule heating to IC power is recommended as the check point for simulation to assess laminate overheating issues with detailed trace layout information.
High conductance Ge p-channel heterostructures realized by hybrid epitaxial growth (2004)

Strained Ge p-channel heterostructures have been realized by hybrid-epitaxial growth. Strain-tuning Si0.4Ge0.6 virtual substrates were grown by ultra-high vacuum chemical vapour deposition and active layers were deposited by solid-source molecular beam epitaxy at low temperature. Following ex situ annealing, Hall effect measurements revealed a hole mobility of 1900 cm2 V−1 s−1 at 300 K (27 000 cm2 V−1 s−1 at 10 K), with a density of 1.8 × 1012 cm−2, giving a conductance in excess of current Ge heterostructures. Using a maximum-entropy mobility-spectrum analysis, 1.0 × 1012 cm−2 of these holes were found to have a mobility of 2700 cm2 V−1 s−1 at 300 K.
A SHORT-TERM TREATMENT WITH A COMBINATION OF IL-2/Fc AND MUTANT IL-15/Fc FUSION PROTEINS PROLONGED ISLET GRAFT SURVIVAL IN DIABETIC CYNOMOLGUS MONKEYS (2004)

O332* Aims: Pre-clinical studies in non-human primates are useful to evaluate the safety and efficacy of new approaches for clinical islet transplantation. The NHP model is particularly useful as a means to evaluate the therapeutic efficacy of human therapeutic proteins. Broadly reactive anti-T cell antibodies can lead to potent immunosuppression. Nonetheless, the consequences of such treatment include profound and long-lived T cell depletion and the potential problems that attend homeostatic proliferation in the lymphopenic host. We hypothesize that a strategy that selectively destroys activated cytopathic donor reactive T cells while sparing resting- and immunoregulatory T- cells might by an effective means of producing long-term engraftment and tolerance without disrupting global immunity. Herein, we show a novel means of creating tolerance by combining rapamycin, and IL-2/Fc and mutant antagonist type IL-15/Fc cytolytic fusion proteins (Power mix) for 28 days. Methods: Islet transplants were performed in streptozotocin induced diabetic cynomolgus monkeys. The islets were infused into the portal vein. The sirolimus dose of 1mg/kg (systemically daily) produced blood levels of >10 ng/ml. IL-2- and IL-15-related cytolytic fusion proteins given at 0.5mg/kg but not 0.2mg/kg produced therapeutic levels of the protein in the serum of the cynomolgus monkeys.FigureResults: * Functional Survival = time to FBG>250 for >4days ** C-Peptide = level during period of insulin independence vs. level upon return to insulin dependence Conclusions: These results demonstrate that allogeneic islet transplants can survive for greater then 190 days in monkeys after short-term immunosuppression of RPM, IL-2/Fc-, and mutant IL-15/Fc- cytolytic fusion proteins) for only 28 days.
Modulation, coding, and synchronization for mobile and very small satellite terminals, as part of the updated DVB‐S2 standard (2015)

Summary After 10 years of successful deployment, the second‐generation satellite standard for digital video broadcasting, DVB‐S2, has recently been updated. Very low signal‐to‐noise ratio modes to better support mobile and very small terminal applications are part of the new standard without changing its fundamental structure. This paper provides a high‐level discussion on several of the most important aspects pertaining to the new very low signal‐to‐noise ratio modulation and coding modes of the updated standard. Copyright © 2015 John Wiley &amp; Sons, Ltd.
CYP2J2 and CYP2C8 polymorphisms and coronary heart disease risk: the Atherosclerosis Risk in Communities (ARIC) study (2007)

The G-50T polymorphism in CYP2J2 may be an important risk factor for the development of coronary heart disease events in African-Americans, whereas cigarette smoking may modify the relationship between the I264M and K399R polymorphisms in CYP2C8 and coronary heart disease risk in Caucasians. Confirmation of these findings in an independent population is warranted.