gebhart/patrepeval huggingface dataset:
Soluble Guanylate Cyclase Stimulators and Activators (2018)

When Furchgott, Murad, and Ignarro were honored with the Nobel prize for the identification of nitric oxide (NO) in 1998, the therapeutic implications of this discovery could not be fully anticipated. This was due to the fact that available therapeutics like NO donors did not allow a constant and long-lasting cyclic guanylyl monophosphate (cGMP) stimulation and had a narrow therapeutic window. Now, 20 years later, the stimulator of soluble guanylate cyclase (sGC), riociguat, is on the market and is the only drug approved for the treatment of two forms of pulmonary hypertension (PAH/CTEPH), and a variety of other sGC stimulators and sGC activators are in preclinical and clinical development for additional indications. The discovery of sGC stimulators and sGC activators is a milestone in the field of NO/sGC/cGMP pharmacology. The sGC stimulators and sGC activators bind directly to reduced, heme-containing and oxidized, heme-free sGC, respectively, which results in an increase in cGMP production. The action of sGC stimulators at the heme-containing enzyme is independent of NO but is enhanced in the presence of NO whereas the sGC activators interact with the heme-free form of sGC. These highly innovative pharmacological principles of sGC stimulation and activation seem to have a very broad therapeutic potential. Therefore, in both academia and industry, intensive research and development efforts have been undertaken to fully exploit the therapeutic benefit of these new compound classes. Here we summarize the discovery of sGC stimulators and sGC activators and the current developments in both compound classes, including the mode of action, the chemical structures, and the genesis of the terminology and nomenclature. In addition, preclinical studies exploring multiple aspects of their in vitro, ex vivo, and in vivo pharmacology are reviewed, providing an overview of multiple potential applications. Finally, the clinical developments, investigating the treatment potential of these compounds in various diseases like heart failure, diabetic kidney disease, fibrotic diseases, and hypertension, are reported. In summary, sGC stimulators and sGC activators have a unique mode of action with a broad treatment potential in cardiovascular diseases and beyond.
Techniques and Applications of Wearable Augmented Reality Audio (2003)

The concept of augmented reality audio characterizes techniques where real sound environment is extended with virtual auditory environments and communications scenarios. This article introduces a framework for Wearable Augmented Reality Audio (WARA) based on a speci c headset con guration and a real-time audio software system. We will review relevant literature and aim at identifying most potential application scenarios for WARA. Listening test results with a prototype system will be presented. AES 114TH CONVENTION, AMSTERDAM, THE NETHERLANDS, 2003 MARCH 22–25 1
CloudLSTM: A Recurrent Neural Model for Spatiotemporal Point-cloud Stream Forecasting (2021)

This paper introduces CloudLSTM, a new branch of recurrent neural models tailored to forecasting over data streams generated by geospatial point-cloud sources. We design a Dynamic Point-cloud Convolution (DConv) operator as the core component of CloudLSTMs, which performs convolution directly over point-clouds and extracts local spatial features from sets of neighboring points that surround different elements of the input. This operator maintains the permutation invariance of sequence-to-sequence learning frameworks, while representing neighboring correlations at each time step -- an important aspect in spatiotemporal predictive learning. The DConv operator resolves the grid-structural data requirements of existing spatiotemporal forecasting models and can be easily plugged into traditional LSTM architectures with sequence-to-sequence learning and attention mechanisms. We apply our proposed architecture to two representative, practical use cases that involve point-cloud streams, i.e. mobile service traffic forecasting and air quality indicator forecasting. Our results, obtained with real-world datasets collected in diverse scenarios for each use case, show that CloudLSTM delivers accurate long-term predictions, outperforming a variety of competitor neural network models.
Evolution, substrate specificity and subfamily classification of glycoside hydrolase family 5 (GH5) (2012)

Overall, the subfamily division of GH5 provides an actively curated resource for large-scale protein sequence annotation for glycogenomics; the subfamily assignments are openly accessible via the Carbohydrate-Active Enzyme database at http://www.cazy.org/GH5.html.
Effects of exercise on muscle transverse relaxation determined by MR imaging and in vivo relaxometry (2000)

The purpose of this study was to determine the effects of intense exercise on the proton transverse (T(2)) relaxation of human skeletal muscle. The flexor digitorium profundus muscles of 12 male subjects were studied by using magnetic resonance imaging (MRI; 6 echoes, 18-ms echo time) and in vivo magnetic resonance relaxometry (1,000 echoes, 1.2-ms echo time), before and after an intense handgrip exercise. MRI of resting muscle produced a single T(2) value of 32 ms that increased by 19% (P < 0.05) with exercise. In vivo relaxometry showed at least three T(2) components (>5 ms) for all subjects with mean values of 21, 40, and 137 ms and respective magnitudes of 34, 49, and 14% of the total magnetic resonance signal. These component magnitudes changed with exercise by -44% (P < 0.05), +52% (P < 0.05), and +23% (P < 0.05), respectively. These results demonstrate that intense exercise has a profound effect on the multicomponent T(2) relaxation of muscle. Changes in the magnitudes of all the T(2) components synergistically increase MRI T(2), but changes in the two shortest T(2) components predominate.
Pathogenic Mycoplasmas: Cultivation and Vertebrate Pathogenicity of a New Spiroplasma (1977)

A spiroplasma recovered from allantoic fluids of chick embryos infected with the tick-derived suckling mouse cataract agent was grown in continuous passage on a new artificial culture medium. The cultured organisms induced typical ocular and other disease symptoms in susceptible animals, and were reisolated from involved host tissues. Although spiroplasmas have been previously recognized as plant and insect pathogens, this is the first spiroplasma shown to multiply at 37 degrees C and to be pathogenic for vertebrates.
Structural Effects on the Biodegradation of Aliphatic Polyesters (1997)

In advance of a discussion on structural effects on biodegradation, aliphatic polyesters as biodegradable structural materials were classified into four types regarding chemical structure, that is poly(ω-hydroxy acid), poly(β-hydroxyalkanoate), poly(ω-hydroxyalkanoate) and poly(alkylene dicarboxylate), and reviewed on synthesis route, thermal and physical properties, and biodegradability. The biodegradation mechanism of these aliphatic polyesters were discussed on the major mode of hydrolysis reaction in regard whether it was enzyme-catalyzed or not, and the substrate specificities of enzymes, such as lipases or PHA depolymerases, were discussed on the hydrolysis of the aliphatic polyesters in respect of primary structure. Moreover, the biodegradation behaviors were exceedingly influenced by solid-state morphology in addition to primary structure. The rate of enzymatic degradation of polycaprolactone fibers drawn with various draw ratios was dependent on draw ratios, suggesting that crystallinity and orientation of them affected biodegradability by lipase. In the study of enzymatic degradation of films made from butylene succinate – ethylene succinate copolymer, the dependence of degradation rate on polymeric compositions was ascribed to the degree of crystallinity rather than the primary structure. These studies revealed that the degree of crystallinity was the major rate-determining factor of biodegradation of solid polymers. © 1997 John Wiley & Sons, Ltd.
A Bayesian Formulation of Exploratory Data Analysis and Goodness‐of‐fit Testing* (2003)

Summary Exploratory data analysis (EDA) and Bayesian inference (or, more generally, complex statistical modeling)—which are generally considered as unrelated statistical paradigms—can be particularly effective in combination. In this paper, we present a Bayesian framework for EDA based on posterior predictive checks. We explain how posterior predictive simulations can be used to create reference distributions for EDA graphs, and how this approach resolves some theoretical problems in Bayesian data analysis. We show how the generalization of Bayesian inference to include replicated data y rep and replicated parameters θ rep follows a long tradition of generalizations in Bayesian theory. On the theoretical level, we present a predictive Bayesian formulation of goodness‐of‐fit testing, distinguishing between p ‐values (posterior probabilities that specified antisymmetric discrepancy measures will exceed 0) and u ‐values (data summaries with uniform sampling distributions). We explain that p ‐values, unlike u ‐values, are Bayesian probability statements in that they condition on observed data. Having reviewed the general theoretical framework, we discuss the implications for statistical graphics and exploratory data analysis, with the goal being to unify exploratory data analysis with more formal statistical methods based on probability models. We interpret various graphical displays as posterior predictive checks and discuss how Bayesian inference can be used to determine reference distributions. The goal of this work is not to downgrade descriptive statistics, or to suggest they be replaced by Bayesian modeling, but rather to suggest how exploratory data analysis fits into the probability‐modeling paradigm. We conclude with a discussion of the implications for practical Bayesian inference. In particular, we anticipate that Bayesian software can be generalized to draw simulations of replicated data and parameters from their posterior predictive distribution, and these can in turn be used to calibrate EDA graphs.
A novel B–H⇀Ru agostic bond. Crystal structure of [RuCl{7,8-µ-S(CH<sub>2</sub>CH<sub>2</sub>)S-C<sub>2</sub>B<sub>9</sub>H<sub>10</sub>}(PPh<sub>3</sub>)<sub>2</sub>]·Me<sub>2</sub>CO (1992)

The complex [RuCl{7,8-µ-S(CH2CH2)S-C2B9H10}(PPh3)2]·Me2CO 1 contains octahedral ruthenium(II), the sixth coordination site being occupied by an agostic B–H⇀Ru in the first example of B(3)–H⇀Ru coordination in the solid state; solution NMR studies show the presence of B(3)–Ru–H bonding.
IRAK-2 Participates in Multiple Toll-like Receptor Signaling Pathways to NFκB via Activation of TRAF6 Ubiquitination (2007)

Toll-like receptor (TLR) signaling is known to involve interleukin-1 receptor-associated kinases (IRAKs), however the particular role of IRAK-2 has remained unclear. Further, although IRAK-1 was originally thought to be central for the TLR-NFkappaB signaling axis, recent data have shown that it is dispensable for NFkappaB activation for some TLRs and demonstrated an alternative role for it in interferon regulatory factor activation. Here we show that IRAK-2 is critical for the TLR-mediated NFkappaB activation pathway. The poxviral TLR antagonist A52 inhibited NFkappaB activation by TLR2, -3, -4, -5, -7, and -9 ligands, via its interaction with IRAK-2, while not affecting interferon regulatory factor activation. Knockdown of IRAK-2 expression by small interfering RNA suppressed TLR3, TLR4, and TLR8 signaling to NFkappaB in human cell lines, and importantly, TLR4-mediated chemokine production in primary human cells. IRAK-2 usage by different TLRs was distinct, because it acted downstream of the TLR adaptors MyD88 and Mal but upstream of TRIF. Expression of IRAK-2, but not IRAK-1, led to TRAF6 ubiquitination, an event critical for NFkappaB activation. Further, IRAK-2 loss-of-function mutants, which could not activate NFkappaB, were incapable of promoting TRAF6 ubiquitination. Thus we propose that IRAK-2 plays a more central role than IRAK-1 in TLR signaling to NFkappaB.
Engineering Response to Global Climate Change: Planning a Research and Development Agenda (1997)

The Fifth Revolution, R.G. Watts Introduction The Nature of the Problem The Greenhouse Effect and Climate Change Detecting Climate Change Has the Time Come to Respond? About This Book Appendix: A Brief History of the Greenhouse Problem References Emissions and Budgets of Radiatively Important Atmospheric Constituents, D. Wuebbles, J. Edmonds, J. Dignon, W. Emanuel, D. Fisher, R. Gammon, R. Hangebrauck, R. Harris, M.A.K. Khalil, J. Spence, and T.M. Thompson Introduction Budgets of Radiatively Important Constituents Reducing the Uncertainties in Greenhouse Gas Budgets Stabilizing the Atmosphere References Energy Demand Reduction, A. Rosenfeld, B. Atkinson, L. Price, B. Ciliano, J.I. Mills, K. Friedman, E. Flynn, M. Hopkins, H. Shaw, J. Wilson, F. Wood, R. Reck, and E. Larson Introduction Eight Major Recent Studies of Demand Reduction Potential U.S. Sectoral Analysis Achievable Savings and Remaining Barriers Examples of Successes Proposed Research Development and Demonstration International Issues Summary References Energy Supply, M. Hoffert, S.D. Potter, J. Delene, P.E. Glaser, M. Golay, H.M. Hubbard, M. Kadiramangalam, A. Perry, M. Steinberg, and C.-J. Winter Introduction Energy and Global Change Energy Supply and Wealth Toward a Nonfossil Fuel Civilization References Water Resources, W.H. McAnally, P.H. Burgi, D. Calkins, R.H. French, J.P. Holland, B. Hsieh, B. Miller, J. Thomas, W.D. Martin, and J.R. Tuttle Introduction Problem Overview Impacts to the Hydrometeorological Cycle Water Resources Impacts Issues Research and Development References Sea Level Rise and Coastal Hazards: An Assessment of Impacts and Coastal Engineering Research Needs, A. Mehta, R. Dean, H. Kunz, V. Law, S.-C. Lee, and Z. Tarapore Synopsis Introduction Sea Level Change Impacts of Relative Mean Sea Level Rise Impacts of Changes in Episodic Events Predictive Constraints Research Needs Elements of Management Responses Goal and Recommended Tasks Concluding Comments References Agriculture and Biological Systems, N. Scott, G. Arkin, J. DeShazer, G. Evans, G. Hoffman, J. Jones, and J. Walker Introduction Climatic Factors of Importance to Agriculture Potential Adaptations by Agriculture Engineering Issues Related to the Impacts of Climate Changes on Agriculture Reduction of Agriculture's Contribution to Atmospheric Change Research Goals and Objectives References Geoengineering Climate, B.P. Flannery, H. Kheshgi, G. Marland, M.C. MacCraken, H. Komiyama, W. Broecker, H. Ishatani, N. Rosenberg, M. Steinberg, T. Wigley, and M. Morantine Introduction The Potential for Climate Modification Goals and Criteria Options for Sequestering Carbon Options for Geoengineering the Climate System Future Research Actions References The Engineering Response to Global Environmental Change, R.G. Watts Introduction Energy, Time, and Information The Social Context of Engineering Opportunities, Challenges, and Possibilities A Research and Development Agenda No Regrets Opportunities Challenges Possibilities References Appendix: Author List and Affiliations Index
The Recording of Standing Buildings (1990)

This contribution to the debate begun in VA 20, written from the perspective of the Royal Commission on the Historical Monuments of England, suggests that neither the wholly archaeological nor the wholly selective record is appropriate in every case, and that the approach adopted should more usually lie between the two.
Hybrid TLB Coalescing (2017)

To mitigate excessive TLB misses in large memory applications, techniques such as large pages, variable length segments, and HW coalescing, increase the coverage of limited hardware translation entries by exploiting the contiguous memory allocation. However, recent studies show that in non-uniform memory systems, using large pages often leads to performance degradation, or allocating large chunks of memory becomes more difficult due to memory fragmentation. Although each of the prior techniques favors its own best chunk size, diverse contiguity of memory allocation in real systems cannot always provide the optimal chunk of each technique. Under such fragmented and diverse memory allocations, this paper proposes a novel HW-SW hybrid translation architecture, which can adapt to different memory mappings efficiently. In the proposed hybrid coalescing technique, the operating system encodes memory contiguity information in a subset of page table entries, called anchor entries. During address translation through TLBs, an anchor entry provides translation for contiguous pages following the anchor entry. As a smaller number of anchor entries can cover a large portion of virtual address space, the efficiency of TLB can be significantly improved. The most important benefit of hybrid coalescing is its ability to change the coverage of the anchor entry dynamically, reflecting the current allocation contiguity status. By using the contiguity information directly set by the operating system, the technique can provide scalable translation coverage improvements with minor hardware changes, while allowing the flexibility of memory allocation. Our experimental results show that across diverse allocation scenarios with different distributions of contiguous memory chunks, the proposed scheme can effectively reap the potential translation coverage improvement from the existing contiguity.
Differential sensitivity of AKR murine leukemia and normal bone marrow cells to hyperthermia. (1983)

To determine if there is a differential effect of hyperthermia on AKR murine leukemia and AKR normal bone marrow cells incubated in vitro, the fractional survival of leukemic and of normal cells with proliferative potential as a function of heating exposure was estimated by evaluating spleen colony formation. Normal bone marrow colony-forming units were assayed in lethally irradiated (750 centigrays) mice; leukemic colony-forming units were assayed in nonirradiated mice. Electron micrographic studies of leukemic cells treated with 41.8 degrees hyperthermia found that structural damage to the cell, i.e., changes in the Golgi apparatus, was associated with the lack of ability to form colonies. AKR leukemia cells were more sensitive than normal cells to hyperthermic killing at 41.8 degrees and at 42.5 degrees. This differential was found whether cells of each type were heated separately or when mixed together. This model system demonstrates an inherently greater sensitivity of neoplastic cells, as compared to normal syngeneic stem cells, to thermal killing. This finding may have relevance to autologous bone marrow transplantation in humans.
Actions of Neurotensin: A Review of the Electrophysiological Studiesa (1992)

Three effects of NT were observed on midbrain DA cells. The modulatory effect of NT, that is, the attenuation of DA-induced inhibition, has been most extensively examined. Studies indicate that this effect of NT was not simply due to a nonspecific excitation. NT selectively attenuated DA-induced inhibition without affecting either GABA-induced inhibition or glutamate-induced excitation of the same cells, and the attenuation of DA-induced inhibition could be observed at the doses at which the basal activity of DA cells was not changed by NT. The attenuation of DA-induced inhibition by NT is also unlikely to result from the formation of a DA-NT complex, since neuromedin N, which competes with NT for the same receptor but does not bind to DA, mimicked the effects, and neurotensin(1-11), which forms a complex with DA but is inactive in competing for NT receptors, did not. The similarities between the effects of NT and those of 8-bromo-cAMP and forskolin suggest that intracellular cAMP and protein kinase A may be involved. This suggestion was supported by the findings that IBMX (an inhibitor of phosphodiesterases) potentiated the effect of NT; and SQ22536 (an inhibitor of adenylate cyclase) and H8 (an inhibitor of protein kinase A) antagonized it. Phorbal-12,13-dibutyrate (an activator of protein kinase C) did not mimic the effect of neurotensin, and H7 (an inhibitor of protein kinase C) did not reduce the effect, suggesting that protein kinase C is unlikely to be involved in the modulatory effect of neurotensin. Experiments in vitro indicated that the excitatory effect of NT on DA cells occurred at higher concentrations (> 10 nM) than those needed for producing the modulatory effect. Its persistence during DA receptor blockade by sulpiride suggests that this effect was not entirely mediated by an attenuation of the inhibition induced by endogenously released DA. At even higher concentrations (> 100 nM), a sudden cessation of cell activity preceded by an increase in firing rate was observed. Whether this effect of NT was due to depolarization inactivation or a toxic effect of the peptide at high concentrations remains to be determined. In most other areas studied, the excitatory effect of NT was most commonly observed. In many areas, this excitatory effect was apparently a direct postsynaptic effect of NT. However, different mechanisms may be involved (see Table 1). For example, in some areas NT acted through a decrease in membrane conductance, while in others no change or an increase in the membrane conductance was observed.(ABSTRACT TRUNCATED AT 400 WORDS)
Fluorine‐Free Anti‐Smudge Polyurethane Coatings (2015)

Conventionally, low-surface-tension fluorinated reagents are incorporated into anti-smudge (oil- and water-repellent) coatings for oil repellency. However, fluorinated compounds are expensive and an environmental concern because of their high stability and bioaccumulation. These factors limit their widespread application. We report herein the development of fluorine-free anti-smudge polyurethane coatings that are clear at thicknesses up to tens of micrometers and are able to sustain extensive surface damage. We demonstrate that these coatings can be applied readily onto a diverse range of substrates.
Clinical utility and validity of minoxidil response testing in androgenetic alopecia (2014)

Clinical response to 5% topical minoxidil for the treatment of androgenetic alopecia (AGA) is typically observed after 3-6 months. Approximately 40% of patients will regrow hair. Given the prolonged treatment time required to elicit a response, a diagnostic test for ruling out nonresponders would have significant clinical utility. Two studies have previously reported that sulfotransferase enzyme activity in plucked hair follicles predicts a patient's response to topical minoxidil therapy. The aim of this study was to assess the clinical utility and validity of minoxidil response testing. In this communication, the present authors conducted an analysis of completed and ongoing studies of minoxidil response testing. The analysis confirmed the clinical utility of a sulfotransferase enzyme test in successfully ruling out 95.9% of nonresponders to topical minoxidil for the treatment of AGA.