gebhart/patrepeval huggingface dataset:
The role of <i>α</i><sub>2</sub>‐adrenoceptor antagonism in the anti‐cataleptic properties of the atypical neuroleptic agent, clozapine, in the rat (1998)

1. The mechanism underlying the anticataleptic properties of the atypical neuroleptic agent, clozapine, has been investigated in the rat. 2.The close structural analogues of clozapine, loxapine (0.1 mg kg(-1) s.c.) and iso-clozapine (1 and 3 mg kg(-1) s.c.) induced catalepsy in rats. In contrast, clozapine and the regio-isomer of loxapine, iso-loxapine (up to 10 mg kg(-1) s.c.) did not produce catalepsy, but at a dose of 1 mg kg(-1) significantly inhibited catalepsy induced by loxapine (0.3 mg kg(-1) s.c.). 3. Radioligand binding assays showed that cataleptogenic potential was most clearly predicted by the D2/5-HT1A, D2/5-HT1B/1D and D2/alpha2-receptor affinity (KD) ratios: i.e. 30-100-fold higher ratios were calculated for loxapine and iso-clozapine, whereas the ratios were less than 1 for clozapine and iso-loxapine. The ratios of affinities for D2 to 5-HT2A, 5-HT2C or D1 did not reflect the grouping of cataleptic and non-cataleptic compounds. 4. Co-treatment with the alpha2-adrenoceptor antagonists, yohimbine (1-10 mg kg(-1) s.c.), RX 821002 (1-10 mg kg(-1) s.c.) and MK-912 (0.3 and 1 mg kg(-1) s.c.) dose-dependently inhibited the cataleptic response to loxapine (0.3 mg kg(-1)). Yohimbine (1-10 mg kg(-1) s.c.) also dose-dependently inhibited the cateleptic response to haloperidol (0.3 mg kg(-1) s.c.). The alpha2-adrenoceptor antagonists had no effect per se. 5. Neither yohimbine (10 mg kg(-1)) nor RX821002 (3 mg kg(-1)) altered the cataleptic response to the D1 receptor antagonist, SCH 23390 (1 mg kg(-1) s.c.), while, like clozapine, both compounds abolished the response to the 5-HT2A receptor antagonist, MDL 100,151 (3 mg kg(-1) s.c.). 6. The present data strongly implicate alpha2-adrenoceptor blockade in the anticataleptic properties of clozapine and suggest that its lack of extrapyramidal side effects in the clinic may also be a consequence of this property.
Aluminum Hydroxide Adjuvants Activate Caspase-1 and Induce IL-1β and IL-18 Release (2007)

Aluminum hydroxide (Alum) is the only adjuvant approved for routine use in humans, although the basis for its adjuvanticity remains poorly understood. In this study, we show that Alum activates caspase-1 and induce secretion of mature IL-1beta and IL-18. Human PBMC or dendritic cells stimulated with pure TLR4 and TLR2 agonists released only traces of IL-1beta or IL-18, despite the fact that the IL-1beta mRNA was readily induced by both TLR agonists. In contrast, cells costimulated with TLR agonists plus Alum released large amount of IL-1beta and IL-18. Alum-induced IL-1beta and IL-18 production was not due to enhancement of TLR signaling but rather reflected caspase-1 activation and in mouse dendritic cells occurred in a MyD88-independent fashion. Secretion of other proinflammatory cytokines such as IL-8 was not affected by Alum treatments. However, TLR-induced production of IL-10 was increased and that of IFN-gamma-inducible protein decreased by Alum cotreatment. Considering the immunostimulatory activities of these cytokines and the ability of IL-1beta to act as adjuvant, our results suggest a mechanism for the adjuvanticity of Alum.
Prevention of the Angiographic Progression of Coronary and Vein-Graft Atherosclerosis by Gemfibrozil After Coronary Bypass Surgery in Men With Low Levels of HDL Cholesterol (1997)

Gemfibrozil therapy retarded the progression of coronary atherosclerosis and the formation of bypass-graft lesions after coronary bypass surgery in men with low HDL cholesterol as their main lipid abnormality.
Efficient computer simulation of distortion in electronic circuits (1973)

A general-purpose electronic-circuit simulation program is employed to efficiently compute second- and third-order distortion due to weak nonlinearities in bipolar junction transistor (BJT) circuits of arbitrary complexity. The method is based on the Volterra-series representation of the electronic circuit and is valid at all frequencies. The transistors are represented by a simple modified Ebers-Moll model, and the adjoint-network concept is employed to efficiently compute the contribution of each nonlinearity in the circuit to the distortion at the output. The method is illustrated with a practical electronic-circuit example.
Design and Activity of Specific Hypoxia-Inducible Factor-2α (HIF-2α) Inhibitors for the Treatment of Clear Cell Renal Cell Carcinoma: Discovery of Clinical Candidate (<i>S</i>)-3-((2,2-Difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1<i>H</i>-inden-4-yl)oxy)-5-fluorobenzonitrile (PT2385) (2018)

HIF-2α, a member of the HIF family of transcription factors, is a key oncogenic driver in cancers such as clear cell renal cell carcinoma (ccRCC). A signature feature of these cancers is the overaccumulation of HIF-2α protein, often by inactivation of the E3 ligase VHL (von Hippel-Lindau). Herein we disclose our structure based drug design (SBDD) approach that culminated in the identification of PT2385, the first HIF-2α antagonist to enter clinical trials. Highlights include the use of a putative n → π*<sub>Ar</sub> interaction to guide early analog design, the conformational restriction of an essential hydroxyl moiety, and the remarkable impact of fluorination near the hydroxyl group. Evaluation of select compounds from two structural classes in a sequence of PK/PD, efficacy, PK, and metabolite profiling identified 10i (PT2385, luciferase EC<sub>50</sub> = 27 nM) as the clinical candidate. Finally, a retrospective crystallographic analysis describes the structural perturbations necessary for efficient antagonism.
Discovery of the First Selective Inhibitor of Excitatory Amino Acid Transporter Subtype 1 (2009)

The discovery of the first class of subtype-selective inhibitors of the human excitatory amino acid transporter subtype 1 (EAAT1) and its rat orthologue GLAST is reported. An opening structure-activity relationship of 25 analogues is presented that addresses the influence of substitutions at the 4- and 7-positions of the parental skeleton 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile. The most potent analogue 1o displays high nanomolar inhibitory activity at EAAT1 and a >400-fold selectivity over EAAT2 and EAAT3, making it a highly valuable pharmacological tool.
Stochastic search using the natural gradient (2009)

To optimize unknown 'fitness' functions, we present Natural Evolution Strategies, a novel algorithm that constitutes a principled alternative to standard stochastic search methods. It maintains a multinormal distribution on the set of solution candidates. The Natural Gradient is used to update the distribution's parameters in the direction of higher expected fitness, by efficiently calculating the inverse of the exact Fisher information matrix whereas previous methods had to use approximations. Other novel aspects of our method include optimal fitness baselines and importance mixing, a procedure adjusting batches with minimal numbers of fitness evaluations. The algorithm yields competitive results on a number of benchmarks.
How many relevances in information retrieval? (1998)

The aim of an information retrieval system is to find relevant documents, thus relevance is a (if not ‘the’) central concept of information retrieval. Notwithstanding its importance, and the huge amount of research on this topic in the past, relevance is not yet a well understood concept, also because of inconsistently used terminology. In this paper, I try to clarify this issue, classifying the various kinds of relevance. I show that: (i) there are many kinds of relevance, not just one; (ii) these kinds can be classified in a formally defined four dimensional space, and (iii) such classification helps us to understand the nature of relevance and relevance judgement. Finally, the consequences of this classification on the design and evaluation of information retrieval systems are analysed.
Integrating Hospital Information Systems. The challenges and advantages of (re-)starting now. (1993)

With the new technologies available today, more complex and useful Hospital Information Systems (HIS) can be designed and implemented. These new technologies have allowed that information from different sources and nature such as documents, images and signals be integrated within a single environment. Open standards, reliable networks, powerful hardware and software and lower prices are among the issues that make all this possible. One of the main issues is what to do with old systems that do not adhere to this new HIS concept. At the Heart Institute (InCor), a decision was made towards starting developing a new system called I3S. This paper gives a brief description of that system.
Mechanism of the Augmentative Effect of High Polyethylene Glycol (PEG) Concentrations on the Thyroid Stimulating Activity in TSAb-IgG Using a Porcine Thyroid Cell Assay (1999)

We previously demonstrated that high polyethylene glycol (PEG) concentrations (5% PEG) significantly augmented cAMP production in response to TSAb-IgG using the porcine thyroid cell (PTC) assay. The mechanism of the stimulatory effect of 5% PEG on cAMP production was examined by a two-step incubation with PTC. TSAb-IgG was preincubated with or without addition of 5% PEG in the PTC assay for 2.5 hr (1st incubation) and separated PTC was re-incubated with fresh Hank's buffer for 5 hr (2nd incubation). cAMP production in the 1st incubation medium by co-incubation of TSAb-IgG and 5% PEG for 2.5 hr was significantly increased (3.3-fold) compared to that without 5% PEG. When the cAMP content in PTC and the incubation medium were compared in the same volume of incubation medium after co-incubation of TSAb-IgG and 5% PEG for 2.5 hr, cAMP contents in PTC were about 7-fold higher than that in the incubation medium, and this ratio did not change in the incubation medium of TSAb-IgG without 5% PEG. Similar increases in cAMP contents in PTC (6.6-fold) compared to the incubation medium were also observed with bTSH, although there was no augmentative effect of 5% PEG on cAMP production by bTSH in either the incubation medium or PTC. When PTC, which had been preincubated with normal-IgG and 5% PEG in the 1st incubation, was re-incubated with TSAb-IgG in the 2nd incubation medium, cAMP production by TSAb-IgG was not stimulated by 5% PEG. The augmentative effect of 5% PEG on cAMP production by TSAb-IgG was observed whenever 5% PEG and TSAb-IgG were co-incubated in either the 1st or 2nd incubation. However, no stimulatory effect of 5% PEG on bTSH was observed. These results suggested the stimulatory effect of 5% PEG on TSAb-IgG-stimulated cAMP production may be due to the increase of binding or incorporation of TSAb-IgG into the membranes of PTC compared to TSH.
ChemInform Abstract: Catalytic Asymmetric C—H Activation of Alkanes and Tetrahydrofuran. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Contribution of collagen and mineral to the elastic-plastic properties of bone (1975)

Tension testing of wet bovine haversian cortical bone demonstrated marked plastic behavior. Progressive surface decalcification of this bone with dilute hydrochloric acid resulted in progressive decreases in the tension yield point and the ultimate stress with no change in the yield strain or ultimate strain unless decalcification was complete. The slope of the plastic region remained identical throughout decalcification. These findings are consistent with an elastic-perfectly plastic model for the mineral phase of bone tissue in which the mineral contributes the major portion of the tension yield strength. The slope or stiffness of the plastic region of the stress-strain curve is a function only of the properties of collagen, which itself plays a minor role in the tension yield strength of bone.
Scalable High-Performance Image Registration Framework by Unsupervised Deep Feature Representations Learning (2015)

Feature selection is a critical step in deformable image registration. In particular, selecting the most discriminative features that accurately and concisely describe complex morphological patterns in image patches improves correspondence detection, which in turn improves image registration accuracy. Furthermore, since more and more imaging modalities are being invented to better identify morphological changes in medical imaging data, the development of deformable image registration method that scales well to new image modalities or new image applications with little to no human intervention would have a significant impact on the medical image analysis community. To address these concerns, a learning-based image registration framework is proposed that uses deep learning to discover compact and highly discriminative features upon observed imaging data. Specifically, the proposed feature selection method uses a convolutional stacked autoencoder to identify intrinsic deep feature representations in image patches. Since deep learning is an unsupervised learning method, no ground truth label knowledge is required. This makes the proposed feature selection method more flexible to new imaging modalities since feature representations can be directly learned from the observed imaging data in a very short amount of time. Using the LONI and ADNI imaging datasets, image registration performance was compared to two existing state-of-the-art deformable image registration methods that use handcrafted features. To demonstrate the scalability of the proposed image registration framework, image registration experiments were conducted on 7.0-T brain MR images. In all experiments, the results showed that the new image registration framework consistently demonstrated more accurate registration results when compared to state of the art.
Pancreatic Polypeptide Reduces Appetite and Food Intake in Humans (2003)

Pancreatic polypeptide (PP) is a gut hormone released from the pancreas in response to ingestion of food. Plasma PP has been shown to be reduced in conditions associated with increased food intake and elevated in anorexia nervosa. In addition peripheral administration of PP has been shown to decrease food intake in rodents. These findings suggest that PP may act as a circulating factor that regulates food intake. Therefore we investigated the effect of intravenous infusion of PP (10 pmol/kg/min) on appetite and food intake in a randomised double-blind placebo-controlled crossover study in ten healthy volunteers. Infusion of PP reduced appetite and decreased the energy intake at a buffet lunch two hours post-infusion by 21.8 +/- 5.7% (P < 0.01). More importantly the inhibition of food intake was sustained, such that energy intake, as assessed by food diaries, was significantly reduced both the evening of the study and the following morning. Overall PP infusion reduced cumulative 24-hour energy intake by 25.3 +/- 5.8%. In conclusion our data demonstrates that PP causes a sustained decrease in both appetite and food intake.
A Highly Active and Air-Stable Ruthenium Complex for Olefin Metathesis This work was supported by the Fonds der Chemischen Industrie. (2002)

A bulky binol-based ligand is the key structural feature of the ruthenium complex 1, which displays an unprecedented metathesis activity combined with high stability. For a range of dienes, ring-closing metathesis reactions catalyzed by 1 lead to near quantitative yields of cycloalkenes after a few minutes.
Interactive Bayesian optimization : learning user preferences for graphics and animation (2011)

Bayesian optimization with Gaussian processes has become increasingly popular in the machine learning community. It is efficient and can be used when very little is known about the objective function, making it useful for optimizing expensive black box functions. We examine the case of using Bayesian optimization when the objective function requires feedback from a human. We call this class of problems \emph{interactive} Bayesian optimization. Here, we assume a parameterized model, and a user whose task is to find an acceptable set of parameters according to some perceptual value function that cannot easily be articulated. This requires special attention to the qualities that make this a unique problem, and so, we introduce three novel extensions: the application of Bayesian optimization to "preference galleries", where human feedback is in the form of preferences over a set of instances; a particle-filter method for learning the distribution of model hyperparameters over heterogeneous users and tasks; and a bandit-based method of using a portfolio of utility functions to select sample points. Using a variety of test functions, we validate our extensions empirically on both low- and high-dimensional objective functions. We also present graphics and animation applications that use interactive Bayesian optimization techniques to help artists find parameters on difficult problems. We show that even with minimal domain knowledge, an interface using interactive Bayesian optimization is much more efficient and effective than traditional "parameter twiddling" techniques on the same problem.
A simple scalable space-frequency coding scheme for MIMO-OFDM (2005)

Several space-time and space-frequency coding schemes have been proposed in the literature for MIMO-OFDM. We present a linear space-frequency coding scheme based on permutation matrices; it is scalable with the number of antennas and spatial-multiplexing (SM) rate, and is easy to implement. Furthermore, the design allows for low cost power amplifier (PA) design. For SM rate 1, our space-frequency coding scheme is backwards compatible with legacy receivers using only 1 receive antenna. These features of our codes, named permuted space frequency codes, enable seamless deployment of multiple antenna OFDM transceivers in existing wireless networks with legacy single antenna transceivers.
Oxidative Stress and HPV Carcinogenesis (2013)

Extensive experimental work has conclusively demonstrated that infection with certain types of human papillomaviruses, the so-called high-risk human papillomavirus (HR-HPV), represent a most powerful human carcinogen. However, neoplastic growth is a rare and inappropriate outcome in the natural history of HPV, and a number of other events have to concur in order to induce the viral infection into the (very rare) neoplastic transformation. From this perspective, a number of putative viral, host, and environmental co-factors have been proposed as potential candidates. Among them oxidative stress (OS) is an interesting candidate, yet comparatively underexplored. OS is a constant threat to aerobic organisms being generated during mitochondrial oxidative phosphorylation, as well as during inflammation, infections, ionizing irradiation, UV exposure, mechanical and chemical stresses. Epithelial tissues, the elective target for HPV infection, are heavily exposed to all named sources of OS. Two different types of cooperative mechanisms are presumed to occur between OS and HPV: I) The OS genotoxic activity and the HPV-induced genomic instability concur independently to the generation of the molecular damage necessary for the emergence of neoplastic clones. This first mode is merely a particular form of co-carcinogenesis; and II) OS specifically interacts with one or more molecular stages of neoplastic initiation and/or progression induced by the HPV infection. This manuscript was designed to summarize available data on this latter hypothesis. Experimental data and indirect evidences on promoting the activity of OS in viral infection and viral integration will be reviewed. The anti-apoptotic and pro-angiogenetic role of NO (nitric oxide) and iNOS (inducible nitric oxide synthase) will be discussed together with the OS/HPV cooperation in inducing cancer metabolism adaptation. Unexplored/underexplored aspects of the OS interplay with the HPV-driven carcinogenesis will be highlighted. The aim of this paper is to stimulate new areas of study and innovative approaches.
Sugar-Installed Block Copolymer Micelles:  Their Preparation and Specific Interaction with Lectin Molecules (2001)

Several types of sugar-installed poly(ethylene glycol)/poly(dl-lactide) (sugar-PEG/PLA) block copolymers were synthesized. The synthesized block copolymer forms a core−shell type polymeric micelle in aqueous media possessing sugar molecules on its surface. Specific recognition of lectin proteins with the sugar molecules on the micelle surface was observed. Both the galactose- and lactose-installed micelles specifically interacted with RCA-1; on the other hand the mannose-installed micelle interacted specifically with Con A. With a lectin-immobilized affinity column, the cluster effect of the sugar molecule on the micelle surface was clearly observed.
Towards a new concept of lignin condensation in kraft pulping. Initial results (2004)

In kraft pulping, a comparatively large amount of lignin remains in the fibres after the cook. Based on various analytical techniques for lignin, such as thioacidolysis, GPC and NMR, it is suggested that lignin condensation reactions take place during the cook. The reaction seems, however, not to involve ionic intermediates as has been suggested previously but rather a one-electron mechanism with elemental sulphur as the initiator. Support for such a reaction has been found through kraft cooks in the presence of an added phenol, 2,6-xylenol, as well as through NMR analysis of kraft lignin. It was found that the added phenol is incorporated in the pulp lignin with linkages indicative of radical coupling. Furthermore, kraft lignin was found to contain substantial amounts of chemically linked fatty acids. By complementary analyses of sulphur and polysulphide in an industrial black liquor, the presence of these compounds throughout a kraft cook was demonstrated.
HiLighter: automatically building robust signatures of performance behavior for small- and large-scale systems (2008)

Previous work showed that statistical analysis techniques could successfully be used to construct compact signatures of distinct operational problems in Internet server systems. Because signatures are amenable to well-known similarity search techniques, they can be used as a way to index past problems and identify particular operational problems as new or recurrent. In this paper we use a different statistical technique for constructing signatures (logistic regression with L1 regularization) that improves on previous work in two ways. First, our new approach works for cases where the number of features is an order of magnitude larger than the number of samples and also scales to problems with over 50,000 samples. Second, we get encouraging results regarding the stability of the models and the signatures by cross-validating the accuracy of the models from one section of the data center on another section. We validate our approach on data from an Internet service testbed and also from a production enterprise system comprising hundreds of servers in several data centers. 1