gebhart/patrepeval huggingface dataset:
Differential GLP-1R binding and activation by peptide and non-peptide agonists (2020)

SUMMARY Peptide drugs targeting class B1 GPCRs can treat multiple diseases, however there remains substantial interest in the development of orally delivered non-peptide drugs. Here we reveal unexpected overlap between signalling and regulation of the glucagon-like peptide-1 (GLP-1) receptor by the non-peptide agonist, PF 06882961, and GLP-1 that was not observed for another compound, OWL-833. Both compounds are currently in clinical trials for treatment of type 2 diabetes. High resolution cryo-EM structures reveal the binding sites for PF-06882961 and GLP-1 substantially overlap, whereas OWL-833 adopts a unique binding mode with a more open receptor conformation at the extracellular face. Structural differences involving extensive water-mediated hydrogen bond networks could be correlated to functional data to understand how PF 06882961, but not OWL-833, can closely mimic the pharmacological properties of GLP-1. These findings will facilitate rational structure-based discovery of non-peptide agonists targeting class B GPCRs.
Recent developments in the CONTAIN Project (1994)

CONTAIN is a detailed computer code developed by Sandia National Laboratories under USNRC sponsorship to provide integrated analysis of containment phenomena. CONTAIN provides the knowledgeable analyst with the capability to predict nuclear reaction containment loads, radiological source terms, and associated physical phenomena under accident conditions. The purpose of CONTAIN is to provide the USNRC with predictive containment analysis capabilities, and to serve as a tool which can be used to provide technical information in support of regulatory decisions. CONTAIN represents a balance between the current state of the art in containment phenomenological understanding, simpler parametric models, insight from experimental data, and capabilities to explore phenomenological uncertainties.
Polymorphisms in the GTP cyclohydrolase gene ( GCH1 ) are associated with ratings of capsaicin pain (2008)

Though it is clear that genomic variability plays an integral role in accounting for pain sensitivity, controversy exists over which genes are involved. While recent data suggest a "protective" (i.e., less pain) haplotype in the GTP cyclohydrolase (GCH1) gene, other research has failed to confirm this association. Possibly, the effects of single nucleotide polymorphisms (SNPs) vary depending on the pain task. The current investigation analyzed the association of five previously identified GCH1 SNPs with ratings of pain induced by topical high concentration (10%) capsaicin applied to the skin of 39 healthy human volunteers. Each of the GCH1 polymorphisms was associated with lower pain ratings. When combined, three of the five accounted for a surprisingly high 35% of the inter-individual variance in pain ratings. We conclude that SNPs of the GCH1 gene may profoundly affect the ratings of pain induced by capsaicin.
Design and synthesis of random phase diffusers* (1973)

This paper considers diffusers characterized by random variations of optical path, such as ground-glass-surface diffusers. The theoretical limits on the light distributions realizable with random phase diffusers are derived, and the important parameters controlling these light distributions are identified. Methods for generating controlled random signals that, when converted to optical-path variations, have the correct parameters to synthesize diffusers with any desired, realizable light distribution are described. Some goniophotometric data taken from diffusers synthesized by this method are given in support of the theory. These results represent a basic solution of the random-phase-diffuser synthesis problem.
Quality-aware bandwidth allocation for scalable on-demand streaming in wireless networks (2010)

In this paper, we propose a scalable transport scheme for delivering on-demand video streams over broadband wireless networks in next-generation network/IP multimedia subsystem (NGN/IMS) architecture. The proposed transport scheme makes use of fine-granular-scalability (FGS) encoded videos to accommodate high bandwidth variation of wireless networks. We formulate the bandwidth allocation to FGS-encoded streams as a resource allocation problem and develop a quality-aware bandwidth allocation scheme, called QABA. With QABA, the proposed transport scheme can dynamically adjust the bit rate allocated to different streams to maximize the overall perceptual quality when available network bandwidth varies with time. QABA is theoretically proven to be able to find the optimal bandwidth allocation for all on-demand streams. To validate the effectiveness of QABA, extensive trace-based simulations are performed.
Amplified reflection, phase conjugation, and oscillation in degenerate four-wave mixing (1977)

A number of new optical effects that result from degenerate four-wave mixing in transparent optical media are proposed and analyzed. The applications are relevant to time-reversed (phase-conjugated) propagation as well as to a new mode of parametric oscillation.
The functions of mTOR in ischemic diseases (2011)

Mammalian Target of Rapamycin (mTOR) is a serine/threonine kinase and that forms two multiprotein complexes known as the mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTOR regulates cell growth, proliferation and survival. mTORC1 is composed of the mTOR catalytic subunit and three associated proteins: raptor, mLST8/GβL and PRAS40. mTORC2 contains mTOR, rictor, mLST8/GβL, mSin1, and protor. Here, we discuss mTOR as a promising anti-ischemic agent. It is believed that mTORC2 lies down-stream of Akt and acts as a direct activator of Akt. The different functions of mTOR can be explained by the existence of two distinct mTOR complexes containing unique interacting proteins. The loss of TSC2, which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt. Although mTOR signaling pathways are often activated in human diseases, such as cancer, mTOR signaling pathways are deactivated in ischemic diseases. From Drosophila to humans, mTOR is necessary for Ser473 phosphorylation of Akt, and the regulation of Akt-mTOR signaling pathways may have a potential role in ischemic disease. This review evaluates the potential functions of mTOR in ischemic diseases. A novel mTOR-interacting protein deregulates over-expression in ischemic disease, representing a new mechanism for controlling mTOR signaling pathways and potential therapeutic strategies for ischemic diseases.
CRC handbook of toxicology (1995)

Laboratory Animal Management, J.C. Siglin and G.M. Rutledge Acute, Subchronic, and Chronic Toxicology, C.S. Auletta Dermal Irritation and Sensitization, R.E. Rush, K.L. Bonnette, D.A. Dodds, and T.N. Merriman Toxicology of the Eye, B.J. Dunn Inhalation Toxicology, P.E. Newton Neurotoxicity, G.E. Schulze Preclinical Immunotoxicity Assessment, P.T. Thomas and R.V. House Renal Toxicology: Renal Function Parameters for Adult Fischer-344, Sprague Dawley, and Wistar Rats, W.J. Powers, Jr. Genetic Toxicology, D.L. Putman, R.H.C. San, C.A.H. Bigger, and D. Jacobson-Kram Carcinogenesis, M.J. Derelanko Reproductive Toxicology, D.J. Ecobichon Developmental Toxicology, K.M. MacKenzie and R.M. Hoar Animal Histopathology, J.C. Peckham Animal Clinical Pathology, B.S. Levine Metabolism and Toxicokinetics of Xenobiotics, M.B. Abou-Donia Risk Assessment, M.J. Derelanko Human Clinical Toxicology, J. Dolgin Regulatory Toxicology in the United States: An Overview, M.J. Derelanko Environmental Protection Agency: TSCA, H.C. Fogle U.S. Food and Drug Administration: Pharmaceutical Regulatory Toxicology, W.J. Powers, Jr. Notification of New Substances in the European Community, M.J. Derelanko Appendices: Tables of Toxicological Importance, M.A. Hollinger
Accounting for the dispersion in the x ray properties of early-type galaxies (1990)

The x ray luminosities of early-type galaxies are correlated with their optical (e.g., blue) luminosities (L sub X approx. L sub B exp 1.6), but the x ray luminosities exhibit considerable scatter for a given optical luminosity L sub B. This dispersion in x ray luminosity is much greater than the dispersion of other properties of early-type galaxies (for a given L sub B), such as luminosity scale-length, velocity dispersion, color, and metallicity. Here, researchers consider several possible sources for the dispersion in x ray luminosity. Some of the scatter in x ray luminosity may result from stellar population variations between galaxies with similar L sub B. Since the x ray emitting gas is from accumulated stellar mass loss, the L sub X dispersion may be due to variations in integrated stellar mass loss rates. Another possible cause of the L sub X dispersion may be variations in the amount of cool material in the galaxies; cool gas may act as an energy sink for the hot gas. Infrared emission may be used to trace such cool material, so researchers look for a correlation between the infrared emission and the x ray emission of early-type galaxies at fixed L sub B. Velocity dispersion variations between galaxies of similar L sub B may also contribute to the L sub X dispersion. The most likely a priori source of the dispersion in L sub X is probably the varying amount of ram-pressure stripping in a range of galaxy environments. The hot gaseous halos of early-type galaxies can be stripped in encounters with other galaxies or with ambient cluster gas if the intracluster gas is sufficiently dense. Researchers find that the most likely cause of dispersion in the x ray properties of early type galaxies is probably the ram-pressure stripping of gaseous halos from galaxies. For a sample of 81 early-type galaxies with x ray luminosities or upper limits derived from Einstein Observatory observations (CFT) researchers calculated the cumulative distribution of angular distances between the x ray sample members and bright galaxies from the Revised Shapley - Ames catalog. Collectively, galaxies with low x ray luminosities (for a given L sub B) tend to be in denser environments than galaxies with higher x ray luminosities.
A ratiometric optical imaging probe for intracellular pH based on modulation of europium emission (2008)

A set of three pH-responsive ratiometric Eu(III)complexes has been synthesised incorporating a coordinated azathioxanthone sensitiser and a pH dependent alkylsulfonamide moiety. Emission properties, anion binding affinities, pH response curves and protein binding constants were studied in detail in aqueous media, and solutions containing various concentrations of interfering anions and protein were also examined. The complex, [EuL3] exhibited some interference from protein and endogenous anions, e.g. lactate and hydrogen carbonate, but possessed a protonation constant of 7.2 in human serum solution. A suitable calibration curve was obtained and was used to determine the local pH using a 680/589 nm intensity ratio vs. pH plot. Confocal fluorescence microscopy images revealed fast uptake of the complex and a well distributed localisation within the cell; fast egress also occurred. Ribosomal localisation, with a high concentration within the protein-dense nucleoli was observed, in a similar manner to structurally related complexes bearing the same coordinated sensitising moiety. An IC(50) value of 67 (+/-20) microM was estimated using an MTT assay. Selected emission band ratio versus pH plots allow pH measurement in the range 6 to 8, enabling intracellular pH to be measured by microscopy. A value of 7.4 was estimated for NIH 3T3 cells in the protein rich regions of the nucleolus and ribosomes.
Water sensors with cellular system eliminate tail water drainage in alfalfa irrigation (2011)

Alfalfa is the largest consumer of water among all crops in California. It is generally flood-irrigated, so any system that decreases runoff can improve irrigation efficiency and conserve water. To more accurately manage the water flow at the tail (bottom) end of the field in surface-irrigated alfalfa crops, we developed a system that consists of wetting-front sensors, a cellular communication system and a water advance model. This system detects the wetting front, determines its advance rate and generates a cell-phone alert to the irrigator when the water supply needs to be cut off, so that tail water drainage is minimized. To test its feasibility, we conducted field tests during the 2008 and 2009 alfalfa growing seasons. The field experiments successfully validated the methodology, producing zero tail water drainage.
Routed inter-ALU networks for ILP scalability and performance (2004)

Modern processors rely heavily on broadcast networks to bypass instruction results to dependent instructions in the pipeline. However, as clock rates increase, architectures get wider, and pipelines get deeper, broadcasting becomes more complex, slower, and more difficult to implement. This complexity is compounded by shrinking feature size, as the communication speed decreases relative to transistor switching speeds. We examine the fundamental needs of bypassing networks and propose a method for classifying these inter-ALU networks based on how operands are routed from producers to consumers. We then propose and evaluate at both the circuit and architectural level a fine grain point-to-point routed inter-ALU network (RIAN) that delivers the same or higher instruction throughput as a full bypass network but at higher speeds while using fewer wires.
Modular multi-ported SRAM-based memories (2014)

Multi-ported RAMs are essential for high-performance parallel computation systems. VLIW and vector processors, CGRAs, DSPs, CMPs and other processing systems often rely upon multi-ported memories for parallel access, hence higher performance. Although memories with a large number of read and write ports are important, their high implementation cost means they are used sparingly in designs. As a result, FPGA vendors only provide dual-ported block RAMs to handle the majority of usage patterns. In this paper, a novel and modular approach is proposed to construct multi-ported memories out of basic dual-ported RAM blocks. Like other multi-ported RAM designs, each write port uses a different RAM bank and each read port uses bank replication. The main contribution of this work is an optimization that merges the previous live-value-table (LVT) and XOR approaches into a common design that uses a generalized, simpler structure we call an invalidation-based live-value-table (I-LVT). Like a regular LVT, the I-LVT determines the correct bank to read from, but it differs in how updates to the table are made; the LVT approach requires multiple write ports, often leading to an area-intensive register-based implementation, while the XOR approach uses wider memories to accommodate the XOR-ed data and suffers from lower clock speeds. Two specific I-LVT implementations are proposed and evaluated, binary and one-hot coding. The I-LVT approach is especially suitable for larger multi-ported RAMs because the table is implemented only in SRAM cells. The I-LVT method gives higher performance while occupying less block RAMs than earlier approaches: for several configurations, the suggested method reduces the block RAM usage by over 44% and improves clock speed by over 76%. To assist others, we are releasing our fully parameterized Verilog implementation as an open source hardware library. The library has been extensively tested using ModelSim and Altera's Quartus tools.
Draping technique to isolate lashes and achieve maximum exposure (1998)

A surgical draping technique is presented that decreases surgical time, maximizes surgical site exposure, and decreases the risk of infection. It was also designed to enhance patent comfort.
Acetaminophen-induced acute liver injury in mice (2015)

The induction of acute hepatic damage by acetaminophen (N-acetyl-p-aminophenol [APAP]), also termed paracetamol, is one of the most commonly used experimental models of acute liver injury in mice. The specific values of this model are the highly reproducible, dose-dependent hepatotoxicity of APAP and its outstanding translational importance, because acetaminophen overdose is one of the most frequent reasons for acute liver failure (ALF) in humans. However, preparation of concentrated APAP working solutions, application routes, fasting period and variability due to sex, genetic background or barrier environment represent important considerations to be taken into account before implementing this model. This standard operating procedure (SOP) provides a detailed protocol for APAP preparation and application in mice, aimed at facilitating comparability between research groups as well as minimizing animal numbers and distress. The mouse model of acetaminophen poisoning therefore helps to unravel the pathogenesis of APAP-induced toxicity or subsequent immune responses in order to explore new therapeutic interventions for improving the prognosis of ALF in patients.
Redundancy in Glucose Sensing (2015)

Electrochemical redundancy enhances glucose sensor accuracy and display time compared with each individual sensing element alone. ERS performance compares favorably with 'best-in-class' of non-redundant sensors.
Misexpression of miR482, miR1512, and miR1515 Increases Soybean Nodulation     (2010)

MicroRNAs (miRNAs) are important regulators of plant growth and development. Previously, we identified a group of conserved and novel miRNA families from soybean (Glycine max) roots. Many of these miRNAs are specifically induced during soybean-Bradyrhizobium japonicum interactions. Here, we examined the gene expression levels of six families of novel miRNAs and investigated their functions in nodule development. We used northern-blot analyses to study the tissue specificity and time course of miRNA expression. Transgenic expression of miR482, miR1512, and miR1515 led to significant increases of nodule numbers, while root length, lateral root density, and the number of nodule primordia were not altered in all tested miRNA lines. We also found differential expression of these miRNAs in nonnodulating and supernodulating soybean mutants. The expression levels of 22 predicted target genes regulated by six novel miRNAs were studied by real-time polymerase chain reaction and quantitative real-time polymerase chain reaction. These results suggested that miRNAs play important roles in soybean nodule development.
Fuzzy logic steering controller for a guided vehicle (2002)

This paper presents the development and implementation of a fuzzy logic steering controller for a guided vehicle based on the visual recognition of a white line on the floor. The fuzzy controller is supported by a vision sub-system with a CCD camera. Experimental results obtained with a test platform are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Directive-Based Partitioning and Pipelining for Graphics Processing Units (2017)

The community needs simpler mechanisms to access the performance available in accelerators, such as GPUs, FPGAs, and APUs, due to their increasing use in state-of-the-art supercomputers. Programming models like CUDA, OpenMP, OpenACC and OpenCL can efficiently offload compute-intensive workloads to these devices. By default these models naively offload computation without overlapping it with communication (copying data to or from the device). Achieving performance can require extensive refactoring and hand-tuning to apply optimizations such as pipelining. Further, users must manually partition the dataset whenever its size is larger than device memory, which can be especially difficult when the device memory size is not exposed to the user. We propose a directive-based partitioning and pipelining extension for accelerators appropriate for either OpenMP or OpenACC. Its interface supports overlap of data transfers and kernel computation without explicit user splitting of data. It can map data to a pre-allocated device buffer and automate memory-constrained array indexing and sub-task scheduling. We evaluate a prototype implementation with four different applications. The experimental results show that our approach can reduce memory usage by 52% to 97% while delivering a 1.41× to 1.65× speedup over the naive offload model.
Crystallization of small proteins assisted by green fluorescent protein (2010)

The generation of crystal lattice contacts by proteinaceous tags fused to target proteins is an attractive approach to aid in the crystallization of otherwise intractable proteins. Here, the use of green fluorescent protein (GFP) fusions for this purpose is demonstrated, using ubiquitin and the ubiquitin-binding motif (UBM) of Y-family polymerase ι as examples. The structure of the GFP-ubiquitin fusion protein revealed that the crystal lattice was formed by GFP moieties. Ubiquitin was accommodated in the lattice through interactions with the peripheral loops of GFP. However, in the GFP-UBM fusion crystal UBM formed extensive interactions with GFP and these interactions, together with UBM dimerization, mediated the crystal packing. Interestingly, the tyrosine residues that are involved in mediating crystal contacts in both GFP-ubiquitin and GFP-UBM crystals are arranged in a belt on the surface of the β-barrel structure of GFP. Therefore, it is likely that GFP can assist in the crystallization of small proteins and of protein domains in general.
Use of Tropical Environments in Breeding for Oil Composition of Soybean Genotypes Adapted to Temperate Climates<sup>1</sup> (1983)

The objective of this study was to determine the influence of genotype ✕ environment interaction on selection for fatty acid composition among soybean [ Glycine max (L.) Merr.] lines adapted to the northern United States when grown in tropical environments. Twenty lines of maturity groups I to III were grown in three environments in Iowa and four environments in Puerto Rico. Seeds from two replications in each environment were analyzed for the percentages of palmitic, stearic, oleic, linoleic, and linolenic acids. The line ✕ environment interactions were significant for all fatty acids; however, the phenotypic and rank correlation coefficients for the average performance of lines between Iowa and Puerto Rico were all highly significant. The lines with the lowest average percentage of palmitic, stearic, linoleic, or linolenic acid were the same at both locations. The lines with the highest percentages of the fatty acids in Iowa were ranked within the three highest lines in Puerto Rico. The results indicate that selection for fatty acid composition in tropical environments should be effective for genetic improvement of lines adapted to the northern United States.