gebhart/patrepeval huggingface dataset:
Functionally Biased Agonism of Mu and Kappa Opioid Receptors (2013)

Nearly all opioids approved for human therapeutic use were developed between the early 1900s and the mid 1960’s, mostly on the basis of behavioral experiments performed in vivo. Starting approximately in the 1970s with the discovery of the mu opioid receptor (MOPr) and the endogenous endorphin/enkephalin system, the 40 years up to today have witnessed major advances in the molecular-level understanding of opioid receptor signal transduction pathways, receptor localization and expression, and regulatory systems including phosphorylation and trafficking. It is concluded that the currently marketed opioids have only marginally benefitted from modern biological insight or technology and that further mechanistic optimization toward the goal of separating side effect(s) from analgesia might be possible. The purpose of this chapter is to review the concept of functionally-selective agonists specifically in the context of mu (MOPr) and kappa (KOPr) opioid receptors. If analgesic and non-analgesic responses to opioid agonists are ultimately associated with non-overlapping signal transduction sub-pathways, then this approach may lead to improved analgesic agents.
A Reliable Fusion Methodology for Simultaneous Estimation of Vehicle Sideslip and Yaw Angles (2015)

Vehicle sideslip and yaw angles are critical for many vehicle safety systems. Although much research has been presented to obtain them individually, simultaneous accurate estimation of them, based on affordable sensors for land vehicle applications, is seldom reported. This paper proposes a fusion methodology for integrating a single-frequency double-antenna Global Positioning System (DA-GPS) with other low-cost in-vehicle sensors to achieve reliable estimation of both vehicle sideslip and yaw angles. The proposed methodology adopts a hybrid decentralized filtering architecture. First, a vehicle state estimator (VSE) is developed as a virtual sensor to estimate vehicle state information, mainly according to vehicle dynamics. It is composed of two parallel extended Kalman filters (EKFs). Through the interaction of two EKFs, the VSE can adapt to the variations in tire-road friction and accurately estimate the vehicle roll angle. Then, according to vehicle kinematics, a global federated estimator (GFE) is designed, based on the federated filtering algorithm, to achieve the global fusion of inertial sensors, DA-GPS, and VSE. In particular, an adaptive inference mechanism is proposed and introduced into the GFE to adapt to complex driving situations, such as GPS failure, various driving maneuvers, etc. Finally, the proposed method is evaluated via intensive simulations and experiments. The overall results show that the proposed methodology can provide reliable estimation of two angles under a wide range of driving situations.
Daily Hemodialysis — Will Treatment Each Day Improve the Outcome in Patients with Acute Renal Failure? (2002)

The mortality rate among hospitalized patients with acute renal failure is high and has not changed substantially since dialysis was introduced several decades ago.1 Although it might be argued that patients with acute renal failure are more seriously ill nowadays, attempts to show any substantial improvement in outcome have been disappointing. The mortality rate among patients who require dialysis generally exceeds 50 percent and is especially high among those in intensive care units.1,2 Thus, there is a great deal of interest in developing strategies to reduce the mortality rate.In this issue of the Journal, Schiffl et al.3 report . . .
Supplementary Figure 1 from Development of a Multiplex Quantitative PCR Signature to Predict Progression in Non–Muscle-Invasive Bladder Cancer (2023)

Supplementary Figure 1 from Development of a Multiplex Quantitative PCR Signature to Predict Progression in Non–Muscle-Invasive Bladder Cancer
Microwave ablation with a triaxial antenna: results in ex vivo bovine liver (2005)

We apply a new triaxial antenna for microwave ablation procedures to an ex vivo bovine liver. The antenna consists of a coaxial monopole inserted through a biopsy needle positioned one quarter-wavelength from the antenna base. The insertion needle creates a triaxial structure, which enhances return loss more than 10 dB, maximizing energy transfer to the tissue while minimizing feed cable heating and invasiveness. Numerical electromagnetic and thermal simulations are used to optimize the antenna design and predict heating patterns. Numerical and ex vivo experimental results show that the lesion size depends strongly on ablation time and average input power, but not on peak power. Pulsing algorithms are also explored. We were able to measure a 3.8-cm lesion using 50 W for 7 min, which we believe to be the largest lesion reported thus far using a 17-gauge insertion needle.
Tumor Antigen and Human Chorionic Gonadotropin in CaSki Cells: A New Epidermoid Cervical Cancer Cell Line (1977)

Epidermoid cervical carcinoma cells (CaSki line) have been established in continuous culture. When leukocytes from cervical cancer patients were incubated with CaSki culture fluid concentrates, inhibition of leukocyte migration was observed in more than 70 percent of the patients tested. By contrast, significantly less inhibition was observed with normal donor leukocytes or leukocytes from patients with other types of cancer. These results were consistent with the expression of tumor-associated antigen by CaSki cells. Analysis of the serum from the donor of the cell line at the time of tumor biopsy, and of CaSki culture fluids, demonstrated the presence of the beta subunit of human chorionic gonadotropin.
Response of Swine to Periparturient Vitamin C Supplementation1 (1983)

Two experiments were conducted, involving 68 third-litter sows and 20 first-litter gilts in Exp. 1 and 82 first-litter gilts in Exp. 2. On d 108 of gestation, the dams were moved into individual crates, stratified by parity and breed, and randomly assigned within strata, to one of two treatments: (1) fed a basal 16% protein corn-soybean meal diet, 1.8 and 2.7 kg once daily before farrowing and for the first 7 d of lactation, respectively, and then ad libitum until pigs were weaned at 28 d of age, and (2) fed the basal diet plus 1 g of L-ascorbic acid (vitamin C)/dam daily from d 108 of gestation through d 7 of lactation and on the same feeding schedule as for treatment 1. In Exp. 1, no effect of vitamin C supplementation was observed in sows or gilts on total pigs born/litter, number of live pigs/litter or average live pig weight at birth, 7 or 28 d of age, or on plasma vitamin C concentration of dams at d 108 of gestation or d 7 of lactation or of pigs at birth, 7 or 28 d of age. However, there was a lower (P less than .01) plasma vitamin C concentration of the dams at d 7 of lactation than at d 108 of gestation. Plasma vitamin C concentration also declined (P less than .01) as pigs aged. In Exp. 2, with all gilts, vitamin C supplementation again showed no effect on any of the reproductive traits measured in Exp. 1. It is concluded that daily supplementation of 1 g of vitamin C to either sows or gilts from d 108 of gestation through d 7 of lactation has no beneficial effect on the reproductive or lactation performance of swine.
ACTT: Automotive CAN Tokenization and Translation (2018)

Modern vehicles contain scores of Electrical Control Units (ECUs) that broadcast messages over a Controller Area Network (CAN). Vehicle manufacturers rely on security through obscurity by concealing their unique mapping of CAN messages to vehicle functions which differs for each make, model, year, and even trim. This poses a major obstacle for after-market modifications notably performance tuning and in-vehicle network security measures. We present ACTT: Automotive CAN Tokenization and Translation, a novel, vehicle-agnostic, algorithm that leverages available diagnostic information to parse CAN data into meaningful messages, simultaneously cutting binary messages into tokens, and learning the translation to map these contiguous bits to the value of the vehicle function communicated.
Visual focus of attention in adaptive language acquisition (1992)

In this research on adaptive language acquisition, connectionist systems have been investigated that learn the mapping from a message to a meaningful machine action through interaction with a complex environment. Thus far, the only input to these systems has been the message. However, in many cases, the action also depends on the state of the world, motivating the study of systems with multisensory input. In this work, a task is considered where the machine receives both message and visual input. In particular, the machine action is to focus its attention on one of many blocks of different colors and shapes, in response to a message such as ‘‘Lookattheredsquare.’’ This is done by minimizing a time-varying potential function that correlates the message and visual input. The visual input is factored through color and shape sensoryprimitivenodes in an information-theoreticconnectionistnetwork, allowing generalization between different objects having the same color or shape. The system runs in a conversationalmode where the user can provide clarifying messages and error feedback, until the system responds correctly. During the course of performing its task, a vocabulary of 389 words was acquired from approximately 1300 unconstrained natural language inputs, collected from ten users. The average number of inputs for the machine to respond correctly was only 1.4.
Zinc as an agent for the prevention of biofilm formation by pathogenic bacteria (2013)

The antibiofilm activity of zinc could provide a tool to fight biofilms, and the nonspecific inhibitory effect may well extend to other important human and animal bacterial pathogens.
Platelets, a reliable source for peripheral Alzheimer’s disease biomarkers? (2014)

Peripheral biomarkers play an indispensable role in quick and reliable diagnoses of any kind of disease. With the population ageing, the number of people suffering from age-related diseases is expected to rise dramatically over the coming decades. In particular, all types of cognitive deficits, such as Alzheimer's disease, will increase. Alzheimer's disease is characterised mainly by coexistence of amyloid plaques and neurofibrillary tangles in brain. Reliable identification of such molecular characteristics antemortem, however, is problematic due to restricted availability of appropriate sample material and definitive diagnosis is only possible postmortem. Currently, the best molecular biomarkers available for antemortem diagnosis originate from cerebrospinal fluid. Though, this is not convenient for routine diagnosis because of the required invasive lumbar puncture. As a consequence, there is a growing demand for additional peripheral biomarkers in a more readily accessible sample material. Blood platelets, due to shared biochemical properties with neurons, can constitute an attractive alternative as discussed here. This review summarises potential platelet Alzheimer's disease biomarkers, their role, implication, and alteration in the disease. For easy comparison of their performance, the Hedge effect size was calculated whenever data were available.
Epithelial to mesenchymal transition influences fibroblast phenotype in colorectal cancer by altering miR‐200 levels in extracellular vesicles (2022)

Colorectal cancer (CRC) with a mesenchymal gene expression signature has the greatest propensity for distant metastasis and is characterised by the accumulation of cancer-associated fibroblasts in the stroma. We investigated whether the epithelial to mesenchymal transition status of CRC cells influences fibroblast phenotype, with a focus on the transfer of extracellular vesicles (EVs), as a controlled means of cell-cell communication. Epithelial CRC EVs suppressed TGF-β-driven myofibroblast differentiation, whereas mesenchymal CRC EVs did not. This was driven by miR-200 (miR-200a/b/c, -141), which was enriched in epithelial CRC EVs and transferred to recipient fibroblasts. Ectopic miR-200 expression or ZEB1 knockdown, in fibroblasts, similarly suppressed myofibroblast differentiation. Supporting these findings, there was a strong negative correlation between miR-200 and myofibroblastic markers in a cohort of CRC patients in the TCGA dataset. This was replicated in mice, by co-injecting epithelial or mesenchymal CRC cells with fibroblasts and analysing stromal markers of myofibroblastic phenotype. Fibroblasts from epithelial tumours contained more miR-200 and expressed less ACTA2 and FN1 than those from mesenchymal tumours. As such, these data provide a new mechanism for the development of fibroblast heterogeneity in CRC, through EV-mediated transfer of miRNAs, and provide an explanation as to why CRC tumours with greater metastatic potential are CAF rich.
Importance Caching for Complex Illumination (2012)

Abstract Realistic rendering requires computing the global illumination in the scene, and Monte Carlo integration is the best‐known method for doing that. The key to good performance is to carefully select the costly integration samples, which is usually achieved via importance sampling. Unfortunately, visibility is difficult to factor into the importance distribution, which can greatly increase variance in highly occluded scenes with complex illumination. In this paper, we present importance caching – a novel approach that selects those samples with a distribution that includes visibility, while maintaining efficiency by exploiting illumination smoothness. At a sparse set of locations in the scene, we construct and cache several types of probability distributions with respect to a set of virtual point lights (VPLs), which notably include visibility. Each distribution type is optimized for a specific lighting condition. For every shading point, we then borrow the distributions from nearby cached locations and use them for VPL sampling, avoiding additional bias. A novel multiple importance sampling framework finally combines the many estimators. In highly occluded scenes, where visibility is a major source of variance in the incident radiance, our approach can reduce variance by more than an order of magnitude. Even in such complex scenes we can obtain accurate and low noise previews with full global illumination in a couple of seconds on a single mid‐range CPU.
T1 and magnetization transfer at 7 Tesla in acute ischemic infarct in the rat (1999)

T1 and magnetization transfer at a field strength of 7 Tesla were used to discriminate between water accumulation and protein mobilization in tissue undergoing infarction. Twelve rats subjected to acute stroke via intralumenal suture occlusion of the middle cerebral artery, and 19 controls, were studied. In MRI studies to 6 hr post-ictus, serial data acquisition allowed the measurement of cerebral blood flow (CBF), apparent diffusion coefficient of water (ADCw), equilibrium magnetization (M0) and T1, and equilibrium magnetization and T1 under an off-resonance partial saturation of the macromolecular pool (Msat and T1sat). Using these parameters, the apparent forward transfer rate of magnetization between the free water proton pool and the macromolecular proton pool, kfa, was calculated. Regions of interest (ROIs) were chosen using depressed areas in maps of the ADCw. T1 measurements in bovine serum albumin at 7T were not affected by the mobility of the macromolecular pool (P > 0.2), but magnetization transfer between free water and protein depended strongly on the mobility of the macromolecular pool (P < 0.001). For 6 hr after ictus, kfa uniformly and strongly decreased in the region of the infarct (P < 0.0001). Ratios (ischemic/non-ischemic) of parameters M0, Msat, T1, and T1sat all uniformly and strongly increased in the infarct. The ratio T1/T1sat in the region of infarction showed that a progressive accumulation of free water in the region of interest was the major (>80%) contribution to the decrease in kfa. There also existed a small contribution due to changes at the water-macromolecular interface, possibly due to proteolysis (P = 0.005). Magn Reson Med 41:696–705, 1999. © 1999 Wiley-Liss, Inc.
Superoxide stress identifies neurons at risk in a model of ataxia‐telangiectasia (2001)

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder caused by mutations in the ATM gene. A-T children demonstrate sensitivity to ionizing radiation, predisposition to hematological malignancies, and telangiectasias. However, the hallmark of A-T is fulminant degeneration of cerebellar Purkinje cells accompanied by a progressive ataxia with features of both cerebellar and basal ganglia dysfunction. Although the ATM gene product (ATM) is known to be involved in DNA repair, the mechanisms that link loss of ATM with neurodegeneration remain unknown. Recently, it has been suggested that abnormalities in redox status contribute to the A-T phenotype. To address this question in the nervous system, we measured reactive oxygen species (ROS) in brain regions and specific neuronal populations in ATM−/− mice. We found increased ROS levels in cerebellum and striatum but not cortex of ATM−/− mice compared to ATM+/+ mice. Confocal microscopic examination revealed elevated superoxide levels in cerebellar Purkinje cells and nigral dopaminergic neurons but not cortical neurons, thus mapping increased superoxide levels onto the neuronal populations selectively affected in A-T. These data are the first demonstration of elevated levels of ROS in neurons at risk in any genetic neurodegenerative disorder and, furthermore, suggest that ATM acts as a pro-survival signal in post-mitotic Purkinje cells and dopaminergic neurons by modifying superoxide radical handling in these selectively vulnerable neurons.
A gold(i)-catalysed chemoselective three-component reaction between phenols, α-diazocarbonyl compounds and allenamides (2020)

Gold(i) catalysts are considered to be efficient in promoting sp<sup>2</sup> C-H bond insertion at the para position of unprotected phenols because of the exceptionally chemical reactivity of gold-stabilized carbophilic carbocations. Herein, we present a gold(i)-catalysed three-component reaction between phenols, diazocarbonyl compounds and allenamides, affording the corresponding three-component reaction products with excellent geometric selectivity (E : Z > 20 : 1) in moderate to high yields (up to 90%) under mild conditions. Additionally, a gram-scale transformation and diverse transformations of the resulting product show the high synthetic utility of the present three-component protocol.
Autosomal Genes of Autosomal/X-Linked Duplicated Gene Pairs and Germ-Line Proliferation in Caenorhabditis elegans (2005)

We report molecular genetic studies of three genes involved in early germ-line proliferation in Caenorhabditis elegans that lend unexpected insight into a germ-line/soma functional separation of autosomal/X-linked duplicated gene pairs. In a genetic screen for germ-line proliferation-defective mutants, we identified mutations in rpl-11.1 (L11 protein of the large ribosomal subunit), pab-1 [a poly(A)-binding protein], and glp-3/eft-3 (an elongation factor 1-alpha homolog). All three are members of autosome/X gene pairs. Consistent with a germ-line-restricted function of rpl-11.1 and pab-1, mutations in these genes extend life span and cause gigantism. We further examined the RNAi phenotypes of the three sets of rpl genes (rpl-11, rpl-24, and rpl-25) and found that for the two rpl genes with autosomal/X-linked pairs (rpl-11 and rpl-25), zygotic germ-line function is carried by the autosomal copy. Available RNAi results for highly conserved autosomal/X-linked gene pairs suggest that other duplicated genes may follow a similar trend. The three rpl and the pab-1/2 duplications predate the divergence between C. elegans and C. briggsae, while the eft-3/4 duplication appears to have occurred in the lineage to C. elegans after it diverged from C. briggsae. The duplicated C. briggsae orthologs of the three C. elegans autosomal/X-linked gene pairs also display functional differences between paralogs. We present hypotheses for evolutionary mechanisms that may underlie germ-line/soma subfunctionalization of duplicated genes, taking into account the role of X chromosome silencing in the germ line and analogous mammalian phenomena.
Crescimento e nutrição mineral de Eucalyptus maculata e Eucalyptus urophylla em solução nutritiva com concentração crescente de cobre (2000)

Avaliou-se o efeito de concentrações crescentes de Cu no crescimento, teores e translocação de metais pesados e nutrientes no eucalipto em solução nutritiva. Mudas de Eucalyptus maculata e Eucalyptus urophylla foram crescidas em vasos de 2L contendo solução nutritiva de Clark, adicionando-se 0, 32, 64, 128 e 192 m M de Cu fornecido como CuSO4. Após cinco semanas de exposição aos tratamentos, as plantas exibiram sintomas típicos de toxidez de Cu como manchas aquosas foliares, clorose e necrose internerval, além do escurecimento das raízes e inibição do crescimento mesmo nas menores concentrações do elemento. A concentração crítica de Cu na solução para reduzir em 10% a matéria seca da parte aérea foi de 8,3 miM e 3,3 miM para E. urophylla e E. maculata, respectivamente. O nível crítico de toxidez na matéria seca da parte aérea foi muito baixo, entre 12 e 13 mg Kg-1 para ambas espécies. E. urophylla mostrou-se menos sensível do que E. maculata, sendo isso relacionado à capacidade dessa em restringir a translocação do Cu das raízes para a parte aérea. Além disso, E. urophylla absorveu mais Fe na presença do excesso de Cu. A translocação de Fe das raízes para a parte aérea foi reduzida, independentemente da espécie, de 27% no controle para apenas 12% na concentração de 192 m M Cu, evidenciando a alta interferência do Cu na translocação do Fe, podendo ser uma das causas da fitotoxidez do Cu para o eucalipto. Altas concentrações de Cu não causaram redução na absorção e translocação de P, K, S, Ca e Mg, não representando, portanto, mecanismo de fitotoxidez desse metal pesado para essas espécies.
Membrane‐bound form of fractalkine induces IFN‐γ production by NK cells (2002)

Natural killer (NK) cells participate in both innate and adaptive immunity, in part by their prompt secretion of cytokines including IFN-gamma, a pro-inflammatory cytokine with an important role in Th1 polarization. To assess the involvement of fractalkine in inflammatory processes, we examined the effect of fractalkine on IFN-gamma production by NK cells. Although soluble chemokines, including MCP-1 and RANTES as well as fractalkine, had a negligible effect on IFN-gamma production, immobilized fractalkine markedly induced IFN-gamma production by NK cells in a dose-dependent manner. Pretreatment of NK cells with the phosphatidylinositol 3-kinase (PI 3-K) inhibitor, wortmannin, completely inhibited the production of IFN-gamma induced by fractalkine, and pretreatment with the protein tyrosine kinase inhibitor, herbimycin A, partially suppressed the response, suggesting that augmentation of IFN-gamma production in response to fractalkine treatment of NK cells involves signaling through PI 3-K and protein tyrosine kinases. Furthermore, co-culture of NK cells with fractalkine-transfected 293E cells markedly enhanced IFN-gamma production by NK cells compared with co-culture with control 293E cells. These findings may indicate a paracrine feedback loop system in which endothelial cells may be activated to produce more fractalkine, and also suggest a role for fractalkine expressed on endothelial cells in Th1 polarization through the stimulation of IFN-gamma production by NK cells.