gebhart/patrepeval huggingface dataset:
Abstract 491: NLG919, a novel indoleamine-2,3-dioxygenase (IDO)-pathway inhibitor drug candidate for cancer therapy. (2013)

Abstract The IDO pathway mediates immunosuppressive effects through the metabolization of tryptophan (Trp) to kynurenine (Kyn), triggering downstream signaling through GCN2, mTOR and AHR that can affect differentiation and proliferation of T cells. Expression of the IDO1 gene by tumor cells or host APCs can inhibit tumor-specific effector CD8+ T cells and enhance the suppressor activity of Tregs, and high expression of IDO correlates with worse clinical prognosis in patients with a variety of malignancies. Therefore, targeting the IDO pathway via inhibition of the IDO enzyme or blocking its downstream signaling effects is a prime target for small-molecule immunomodulatory drugs in cancer. Here we describe the pharmacological and biological properties of NLG919, a novel small-molecule IDO-pathway inhibitor. NLG919 potently inhibits this pathway in vitro and in cell based assays (Ki=7 nM; EC50 =75 nM). It is orally bioavailable (F&gt;70%); and has a favorable pharmacokinetic and toxicity profile. In mice, a single oral administration of NLG919 reduces the concentration of plasma and tissue Kyn by ∼ 50%. Using IDO-expressing human monocyte-derived DCs in allogeneic MLR reactions, NLG919 potently blocked IDO-induced T cell suppression and restored robust T cell responses with an ED50=80 nM. Similarly, using IDO-expressing mouse DCs from tumor-draining lymph nodes, NLG919 abrogated IDO-induced suppression of antigen-specific T cells (OT-I) in vitro, with ED50=120 nM. In vivo, in mice bearing large established B16F10 tumors, administration of NLG919 markedly enhanced the anti-tumor responses of naïve, resting pmel-1 cells to vaccination with cognate hgp100 peptide plus CpG-1826 in IFA. In this stringent established-tumor model, NLG919 plus pmel 1/vaccine produced a dramatic collapse of tumor size within 4 days of vaccination (∼95% reduction in tumor volume compared to control animals receiving pmel-1/vaccine alone without NLG919). In conclusion, NLG919 is a potent IDO pathway inhibitor with desirable pharmacological properties, suitable for the treatment of immunosuppression associated with cancer. Citation Format: Mario R. Mautino, Firoz A. Jaipuri, Jesse Waldo, Sanjeev Kumar, James Adams, Clarissa Van Allen, Agnieszka Marcinowicz-Flick, David Munn, Nicholas Vahanian, Charles J. Link. NLG919, a novel indoleamine-2,3-dioxygenase (IDO)-pathway inhibitor drug candidate for cancer therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 491. doi:10.1158/1538-7445.AM2013-491
A Study of Poly(hydroxyalkanoate)s by Quantitative <sup>31</sup>P NMR Spectroscopy:  Molecular Weight and Chain Cleavage (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunication to the...Communication to the EditorNEXTA Study of Poly(hydroxyalkanoate)s by Quantitative 31P NMR Spectroscopy: Molecular Weight and Chain CleavageA. Spyros, D. S. Argyropoulos, and R. H. MarchessaultView Author Information Department of Chemistry and Pulp and Paper Research Centre, McGill University, 3420 University Street, Montreal, Quebec H3A 2A7, Canada Cite this: Macromolecules 1997, 30, 2, 327–329Publication Date (Web):January 27, 1997Publication History Received7 February 1996Revised12 August 1996Published online27 January 1997Published inissue 1 January 1997https://pubs.acs.org/doi/10.1021/ma9601979https://doi.org/10.1021/ma9601979rapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views1104Altmetric-Citations50LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Biopolymers,Gel permeation chromatography,Nuclear magnetic resonance spectroscopy,Plastics,Polymers Get e-Alerts
<title>Multiscale image contrast amplification (MUSICA)</title> (1994)

This article presents a novel approach to the problem of detail contrast enhancement, based on multiresolution representation of the original image. The image is decomposed into a weighted sum of smooth, localized, 2D basis functions at multiple scales. Each transform coefficient represents the amount of local detail at some specific scale and at a specific position in the image. Detail contrast is enhanced by non-linear amplification of the transform coefficients. An inverse transform is then applied to the modified coefficients. This yields a uniformly contrast- enhanced image without artefacts. The MUSICA-algorithm is being applied routinely to computed radiography images of chest, skull, spine, shoulder, pelvis, extremities, and abdomen examinations, with excellent acceptance. It is useful for a wide range of applications in the medical, graphical, and industrial area.
Designing multicore ECU architecture in vehicle networks using AUTOSAR (2011)

The number of electronic control units (ECUs) in modern vehicles has continuously increased in last few decades. In addition, advanced functionalities antilock braking systems, adaptive cruise control and climate control put higher computational demand on ECUs, which further increases the design complexity of automotive control systems. Multicore processors having multiple processing units are integrated on a single chip, have emerged to be the main computing controllers not only for high-end servers but also for embedded control systems. Using multicore processors, more centralized architecture designs can be adopted for automotive control systems. The recent initiative on AUTOmotive Open System ARchitecture (AUTOSAR) has established several standards for automotive software and hardware designs, which include guidelines for designing centralized architecture with multicore ECUs for automotive control systems. With AUTOSAR, it is expected that computational control tasks of different functions can share one ECU or run on any ECU connected with in-vehicle network like CAN and FlexRay. Also, In this paper, we describe some key analytical components that together characterize the hierarchical bus structures composed of FlexRay, CANbus and LINbus. Our analysis shows that the practical constraints imposed by standards such as AUTOSAR can lead to higher levels of schedulable resource utilization. This reduces both the overall component count and cost, while facilitating easy enhancements.
Insulin Action in Brain Regulates Systemic Metabolism and Brain Function (2014)

Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases.
Synthesis and Characterization of n‐Type Materials for Non‐Doped Organic Red‐Light‐Emitting Diodes (2005)

Abstract Two compounds, 2,3‐dicyano‐5,6‐di(4′‐diphenylamino‐biphenyl‐4‐yl)pyrazine (CAPP) and 6,7‐dicyano‐2,3‐di(4′‐diphenylamino‐biphenyl‐4‐yl)quinoxaline (CAPQ), capable of intramolecular charge transfer, have been designed and synthesized in high yield by a convenient procedure. The compounds have been fully characterized spectroscopically. They have a high thermal stability and show bright light emission both in non‐polar solvents and in the solid state. Moreover, they exhibit excellent reversible oxidation and reduction waves. The higher energy level of the highest occupied molecular orbital (–5.3 eV) and the triphenylamine group are advantageous for hole‐injection/transport. In addition, the high electron affinities of 3.4 eV and the observed reversible reductive process suggest that these compounds enhance electron injection and have potential for use in electron transport. Three types of non‐doped red‐light‐emitting diodes have been studied using CAPP and CAPQ as the electron‐transporting and host‐light‐emitting layers, respectively. The devices exhibit red electroluminescence (EL), and constant Commission Internationale de l'Eclairage coordinates have been observed on increasing the current density. Pure red EL of CAPP, with a maximum brightness of 536 cd m –2 and an external quantum efficiency of 0.7 % in ambient air, was achieved.
Inhibitory Effects of Citrus hassaku Extract and Its Flavanone Glycosides on Melanogenesis (2009)

The 50% ethanolic extract (CH-ext) obtained from the unripe fruit of Citrus hassaku exhibited significant tyrosinase inhibitory activity. The CH-ext showed antioxidant activity, such as superoxide dismutase (SOD)-like activity and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity. Activity-guided fractionation of the CH-ext indicated that flavanone glycoside-rich fractions showed potent tyrosinase inhibitory activity. Further examination revealed that the tyrosinase inhibitory activity and antioxidant activity of the CH-ext were attributable to naringin and neohesperidin, respectively. The CH-ext showed inhibition of melanogenesis without any effects on cell proliferation in cultured murine B16 melanoma cells after glucosamine exposure. The topical application of the CH-ext to the dorsal skin of brownish guinea pigs showed in vivo preventive effects against UVB-induced pigmentation.
A Review of Bayesian Networks and Structure Learning (2012)

This article reviews the topic of Bayesian networks. A Bayesian network  is a factorisation of a probability distribution along a directed acyclic graph. The relation between graphical d-separation and independence is described. A short article by Arthur Cayley (1853) [7] is discussed, which laid ideas later used in Bayesian networks: factorisation, the noisy `or' gate, applications of algebraic geometry to Bayesian networks. The ideas behind Pearl's intervention calculus when the DAG represents a causal dependence structure; the relation between the work of Cayley and Pearl is commented on. Most of the discussion is about structure learning, outlining the two main approaches; search and score versus constraint based. Constraint based algorithms often rely on the assumption of faithfulness, that the data to which the algorithm is applied is generated from distributions satisfying a faithfulness assumption where graphical d- separation and independence are equivalent. The article presents some considerations for constraint based algorithms based on recent data analysis, indicating a variety of situations where the faithfulness assumption does not hold.
High abundance of Serine/Threonine-rich regions predicted to be hyper-O-glycosylated in the secretory proteins coded by eight fungal genomes (2012)

About one fourth of secretory fungal proteins were predicted to have at least one hyper-O-glycosylated region, which consists of 45 amino acids on average and displays at least one O-glycosylated Ser or Thr every four residues. These putative highly O-glycosylated regions can be found anywhere along the proteins but have a slight tendency to be at either one of the two ends.
Fluorosulfonyl-Substituted Xanthines as Selective Irreversible Antagonists for the A<sub>1</sub>-Adenosine Receptor (2000)

FSCPX (1) has been reported to be a potent, selective, and irreversible antagonist for the A(1)-adenosine receptor (AR). To obtain an irreversible A(1)AR antagonist with potentially better stability and to further elucidate the effects of linker structure on the pharmacological characteristics, several new analogues were targeted in which the labile ester linkage of 1 was replaced by more stable functionalities. In particular, alkyl and amide linkers between the xanthine pharmacophore and the reactive 4-fluorosulfonylphenyl group were explored. The data showed that the chemical composition of the linker affects the affinity and apparent irreversible binding to the A(1)AR. Overall, compound 23b appeared to have the most advantageous characteristics as a potential irreversible ligand for the A(1)AR. These include relatively high affinity for the A(1)AR as compared to the A(2A)AR, concentration-dependent and selective apparent irreversible binding to the A(1)AR, and ease of removal of unbound ligand from biological membranes. These properties indicate that 23b has the potential to be a useful tool for further study of the structure and function of the A(1)AR.
Cost-effective capacity provisioning in wide area networks with Shoofly (2021)

In this work we propose Shoofly, a network design tool that minimizes hardware costs of provisioning long-haul capacity by optically bypassing network hops where conversion of signals from optical to electrical domain is unnecessary and uneconomical. Shoofly leverages optical signal quality and traffic demand telemetry from a large commercial cloud provider to identify optical bypasses in the cloud WAN that reduce the hardware cost of long-haul capacity by 40%. A key challenge is that optical bypasses cause signals to travel longer distances on fiber before re-generation, potentially reducing link capacities and resilience to optical link failures. Despite these challenges, Shoofly provisions bypass-enabled topologies that meet 8X the present-day demands using existing network hardware. Even under aggressive stochastic and deterministic link failure scenarios, these topologies save 32% of the cost of long-haul capacity.
Radiometal-Labeled Somatostatin Analogs for Applications in Cancer Imaging and Therapy (2007)

The use of radiolabeled peptides for the diagnosis and therapy of cancer has increased greatly over the last few decades. Skillfully crafted peptide systems, which have high affinity for receptors that are overexpressed in human tumors, offer the potential to improve the characterization, grading, and eventual therapy of human cancer. Robust peptide systems can be labeled with radioactive atoms for imaging purposes using single-photon emission computed tomography and positron emission tomography technologies, or can be labeled with therapeutic nuclides for the efficient killing of tumor cells. This method-based review discusses one such class of receptor-targeted peptides and their radiolabeling with radioactive metals. The somatostatin receptor is upregulated in many types of cancer, and when labeled with a radiometal atom via a bifunctional chelate, can be employed as an agent for the imaging and radiotherapy of cancer. This review will discuss the methods used in the synthesis of the somatostatin peptides, conjugation with bifunctional chelators, and radiolabeling with metal radionuclides. Methods will also be presented for the in vitro and in vivo evaluation of the compounds produced.
Mechanism of cyclics formation in the cationic copolymerization of tetrahydrofuran with ethylene oxide in the presence of diols (1999)

Cationic copolymerization of ethylene oxide (EO) with tetrahydrofuran (THF) in the presence of diols leads to the formation of hydroxytelechelic copolymers. The process combines the features of an activated monomer mechanism (secondary oxonium ions as active species) with those of an active chain end mechanism (tertiary oxonium ions as active species). Due to the participation of tertiary oxonium ions, back-biting leads to the formation of cyclic oligomers. The effect of reaction conditions on the content of the cyclic fraction was studied, the individual cyclic oligomers were identified, and the results are interpreted in terms of a reaction mechanism.
An open-source solution for advanced imaging flow cytometry data analysis using machine learning (2016)

Imaging flow cytometry (IFC) enables the high throughput collection of morphological and spatial information from hundreds of thousands of single cells. This high content, information rich image data can in theory resolve important biological differences among complex, often heterogeneous biological samples. However, data analysis is often performed in a highly manual and subjective manner using very limited image analysis techniques in combination with conventional flow cytometry gating strategies. This approach is not scalable to the hundreds of available image-based features per cell and thus makes use of only a fraction of the spatial and morphometric information. As a result, the quality, reproducibility and rigour of results are limited by the skill, experience and ingenuity of the data analyst. Here, we describe a pipeline using open-source software that leverages the rich information in digital imagery using machine learning algorithms. Compensated and corrected raw image files (.rif) data files from an imaging flow cytometer (the proprietary .cif file format) are imported into the open-source software CellProfiler, where an image processing pipeline identifies cells and subcellular compartments allowing hundreds of morphological features to be measured. This high-dimensional data can then be analysed using cutting-edge machine learning and clustering approaches using "user-friendly" platforms such as CellProfiler Analyst. Researchers can train an automated cell classifier to recognize different cell types, cell cycle phases, drug treatment/control conditions, etc., using supervised machine learning. This workflow should enable the scientific community to leverage the full analytical power of IFC-derived data sets. It will help to reveal otherwise unappreciated populations of cells based on features that may be hidden to the human eye that include subtle measured differences in label free detection channels such as bright-field and dark-field imagery.
Hole inflation and tapering of stock photonic crystal fibres (2005)

We report controlled hole expansion in photonic crystal fibres (PCFs) by heating the fibre while the holes were pressurised. This was done by post-processing an existing fibre, not during fibre fabrication. Small holes in an endlessly single-mode (ESM) PCF were inflated to become large holes. The large-hole PCF was then tapered to produce a "cobweb" PCF with a small highly-nonlinear core, interfaced to the ESM PCF at both ends by gradual transitions. The loss was less than 0.4 dB in the complete structure, which was used to demonstrate supercontinuum generation when pumped with a fs Ti:sapphire laser.
Oxysterols, but Not Cholesterol, Inhibit Human Immunodeficiency Virus Replication <i>in Vitro</i> (1998)

Oxysterols, oxygenated derivatives of cholesterol selected for their cytostatic activity and their inhibitory effect on cholesterol synthesis, have been investigated for their anti-human immunodeficiency virus (HIV) activity in vitro. The three oxysterols tested, 7 beta-hydroxycholesterol (7 beta-OHC), 25-hydroxycholesterol (25-OHC) and 7 beta, 25-dihydroxycholesterol (7,25-OHC), inhibit viral replication at micromolar concentrations. The selectivity indexes for 7 beta-OHC and 25-OHC are quite modest (2 to 8) but reproducible; the dihydroxycholesterol 7,25-OHC exhibited antiviral properties at concentrations 13- to 25-fold lower than the highest concentration tested at which no toxicity was measurable. Oxysterols are naturally occurring compounds, and we speculate on their physiological relevance in HIV-infected individuals.
On the Detectability of Scan Chain Internal Faults An Industrial Case Study (2008)

Scan chains contain approximately 50% of the logic transistors in large industrial designs. Yet, faults in the scan cells are not directly targeted by scan tests and assumed detected by flush tests. Reported results of targeting the scan cell internal faults using checking sequences show such tests to be about 4.5 times longer than scan stuck-at test sets and require a sequential test generator, even for full scan circuits. We present the first step in developing an alternative test methodology for scan cell internal faults. Fault detection capability of existing tests (flush tests, stuck-at tests and transition delay fault tests) are quantified. Existing tests are shown to have similar coverage as checking sequences. A new flush test, viz. half-speed flush test, is defined. This new test is shown to add 2.3% and 8.8% to the stuck-at and stuck-on fault coverage, respectively.
MreB, the cell shape‐determining bacterial actin homologue, co‐ordinates cell wall morphogenesis in <i>Caulobacter crescentus</i> (2004)

The bacterial actin homologue, MreB, is required for the maintenance of a rod-shaped cell and has been shown to form spirals that traverse along the longitudinal axis of Bacillus subtilis and Escherichia coli cells. The depletion of MreB in Caulobacter crescentus resulted in lemon-shaped cells that possessed defects in the integrity of the cell wall. MreB localization appeared as bands or spirals that encircled the cell along its entire length and switched to a mid-cell location at a time that coincided with the initiation of cell division. The formation of smaller MreB spirals or bands at the mid-cell was dependent on the presence on the cytokinetic protein, FtsZ. Penicillin-binding protein 2 (PBP2) also formed band-like structures perpendicular to the cell periphery that resembled, and depended upon, MreB localization. PBP2 co-immunoprecipitated with several other penicillin-binding proteins, suggesting that these proteins are in association in Caulobacter cells. We hypothesize that MreB filaments function as a cytoskeleton that serves as an organizer or tracking device for the PBP2-peptidoglycan biosynthesis complex.
Donor site pain from the ilium. A complication of lumbar spine fusion (1989)

Chronic pain at the donor site was reported by 25% of 290 patients who had undergone anterior lumbar spine fusion for low back pain. Donor site pain has characteristic clinical features, may be severely disabling and is stubbornly resistant to treatment. The highest prevalence was in patients who had a tricortical full thickness graft taken through a separate incision overlying the iliac crest. Patients with a clinically unsatisfactory result from the spine fusion also had a significantly higher prevalence of donor site pain.