gebhart/patrepeval huggingface dataset:
OR23-05 Human Absorption, Metabolism, Excretion, and Absolute Oral Bioavailability of 14C-CRN00808, an Orally Bioavailable, Nonpeptide, Selective, Somatostatin Receptor 2 (sST2) Biased Agonist for the Treatment of Acromegaly (2020)

Abstract Injected depot formulations of somatostatin peptide analogs are routinely used to treat acromegaly and neuroendocrine tumors (NETs). CRN00808, a small molecule nonpeptide selective somatostatin receptor 2 (sst2) agonist, is being evaluated for efficacy and safety in patients with acromegaly. The current Phase 1 study was conducted in two Parts: In Part A, the absorption, metabolism, excretion, and mass balance of a single oral dose of 20 mg [14C]-CRN00808 (3.0 MBq) oral solution was characterized in six healthy male subjects. Plasma, blood, urine, and feces were collected for up to 432 hours, and were analyzed for total radioactivity and CRN00808 concentrations (plasma only). Metabolite profiling was conducted on the plasma, urine, and feces samples. In Part B, the absolute bioavailability of CRN00808 was determined by administering a single oral dose of 20 mg CRN00808 compared with a single micro-tracer intravenous (IV) bolus injection of 50 µg [14C]-CRN00808 (0.0185 MBq) in five healthy male subjects. The IV dose was administered approximately 90 minutes after the oral dose. Plasma samples were collected for up to 144 hours and were analyzed for total radioactivity and CRN00808 concentrations (plasma only). Key data from Part A and Part B will be presented. Available data from Part A of the study show that &gt;90% of radioactivity was recovered within 7 days of dosing. The primary route of excretion was the feces (&gt;90%) with minimal excretion in the urine (&lt;10%). Absorption of total [14C]-CRN00808-derived radioactivity in plasma was rapid (median Tmax=1 hour), and the mean Cmax, AUC0-∞, and t1/2 were determined to be 194 ng-equivalents/mL, 3340 ng-equivalents.hr/mL, and 31 hours, respectively. The pharmacokinetic parameters of unchanged CRN00808 in plasma were similar, suggesting that majority of the circulating drug-derived radioactivity is accounted for by unchanged CRN00808 and there are no abundant circulating metabolites. Treatment emergent adverse events associated with CRN00808 were generally mild and transient, and consistent with those reported with other somatostatin agonists. In conclusion, results from this clinical trial in healthy volunteers confirm that CRN00808 has excellent drug-like properties for chronic once-daily oral treatment of patients with acromegaly.
The design and management of ATM virtual path connection networks (2003)

Modern communication networks can cross connect traffic flows to form logical end-to-end connections between all origin-destination pairs and thus create fully meshed logical networks upon sparse physical networks. Such logical connections are known as virtual path connections (VPCs) and a logical network formed by VPCs is known as a VPC network (VPCN). We present an efficient algorithm called XFG to compute optimal configurations for VPCNs carrying multiservice traffic. We compare the features of the XFG algorithm and the characteristics of standard nonlinear programming solvers. We present a model where a sequence of busy period multiservice traffic is offered to a network. The XFG algorithm is used to compute an optimal VPCN design for each busy period. We compare the grade of service attained by VPCN redesign, dynamic alternative routing (DAR), and a combination of VPCN redesign, call queueing and DAR.
Dual Role of ROS as Signal and Stress Agents: Iron Tips the Balance in favor of Toxic Effects (2016)

Iron is essential for life, while also being potentially harmful. Therefore, its level is strictly monitored and complex pathways have evolved to keep iron safely bound to transport or storage proteins, thereby maintaining homeostasis at the cellular and systemic levels. These sequestration mechanisms ensure that mildly reactive oxygen species like anion superoxide and hydrogen peroxide, which are continuously generated in cells living under aerobic conditions, keep their physiologic role in cell signaling while escaping iron-catalyzed transformation in the highly toxic hydroxyl radical. In this review, we describe the multifaceted systems regulating cellular and body iron homeostasis and discuss how altered iron balance may lead to oxidative damage in some pathophysiological settings.
Resonant behavior of a small aperture backed by a conducting body (1982)

The problem of an electrically small aperture in a conducting screen backed by a conducting body is analyzed. It is found that aperture-body resonances can occur for which the power transmitted through the aperture backed by a conducting body is much larger than that when the body is not present. An example is an electrically small aperture resonated by a capacitor across its midpoint. In the loss-free case, the transmission cross section of a small resonated aperture is <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3\lambda^{2}/4\pi</tex> independent of the size or shape of the aperture. For actual conductors, the transmission cross section will be increasingly reduced by conduction loss as the aperture is made smaller.
Agricultural‐Nitrogen Contributions to Hypoxia in the Gulf of Mexico (1999)

Abstract Nitrate (NO 3 ) is the principal nutrient transported through the Mississippi River basin that is related to hypoxia in the Gulf of Mexico. Agriculture is a major contributor to the N load. Knowledge of the geographic distribution of NO 3 sources and losses within the basin is critical to understanding the problem and identifying potential solutions. This paper defines the geographic distribution, by hydrologic unit, of major agricultural sources and dominant losses of N in the basin. Sources include imported N such as inorganic fertilizer, manure, and atmospheric deposition, and in situ sources such as mineralized N from soil organic matter, N 2 fixed by legumes, and redeposition of locally derived ammonia (NH 3 ). The dominant N losses include crop harvests, losses to the atmosphere through volatilization of manure and inorganic fertilizer, plant senescence, and denitrification of soil NO 3 . National data bases used in the analysis include the State Soils Geographic Database, 1992 Census of Agriculture, and the National Atmospheric Deposition Program/National Trends Network. The hydrologic units with the largest residual N contributions available to streams are located in the Upper Mississippi River and the Ohio River basins. Mineralizable soil N, inorganic N fertilizer, legume fixation, and redeposition of locally derived NH 3 constitute the major sources in this part of the basin, although manure is a minor source. However, these northern hydrologic regions use a greater fraction of the sources to produce crop N than do the southern hydrologic regions. Residual contributions to the Tennessee, Arkansas/Red, and Lower Mississippi hydrologic regions are greatest when analyzed as a percentage of the total sources.
Progressive adult-onset emphysema in transgenic mice expressing human MMP-1 in the lung (2003)

Mice with lung-specific expression of human matrix metalloproteinase-1 (MMP-1) develop emphysematous changes similar to those seen in smoking-induced emphysema in humans. Morphometric analyses of three transgenic lines [homozygous colony (Col) 34, Col 50, and Col 64] with varying temporal expression of MMP-1 were undertaken to determine the validity of this animal as a model of adult-onset emphysema. Line 50 mice, which have early expression of MMP-1 (14 days postconception), exhibited morphometric changes by 5 days of age. In contrast, homozygous line 34 and 64 with delayed expression (birth and 2 wk of age) were normal up until 4 wk of age when progressive changes in their mean linear intercept were first noted. In contrast, heterozygous mice from line 34 with lower transgene expression did not develop emphysema until 1 yr of age. The changes in mean linear intercept coincided with an increase in lung compliance. Emphysema in these mice was associated with decreased immunostaining for type III collagen within the alveolar septa. This study provides evidence that MMP-1 induces progressive adult-onset emphysema by the selective degradation of type III collagen within the alveolar wall.
3- and 4-Substituted 4<i>H</i>-Pyrido[4,3-<i>e</i>]-1,2,4-thiadiazine 1,1-Dioxides as Potassium Channel Openers:  Synthesis, Pharmacological Evaluation, and Structure−Activity Relationships (1996)

4-N-Substituted and -unsubstituted 3-alkyl- and 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides were synthesized and tested vs diazoxide and selected 3-alykl- and 3-(alkylamino)-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxides as potassium channel openers on pancreatic and vascular tissues. Several 4-N-unsubstituted 3-(alkylamino)pyridothiadiazines and some 3-(alkylamino)-7-chlorobenzothiadiazines were found to be more potent than diazoxide for the inhibition of the insulin-releasing process. Moreover, the 3-(alkylamino)pyridothiadiazines appeared to be more selective for the pancreatic than for the vascular tissue. By means of the pharmacological results obtained on pancreatic B-cells, structure--activity relationships were deduced and a pharmacophoric model for the interaction of these drugs with their receptor site associated to the pancreatic K(ATP) channel was proposed. According to their selectivity for the B-cell (endocrine tissue) vs the vascular (smooth muscle tissue) ionic channel, selected 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4,-thiadiazine 1,1-dioxides may serve as pharmacological tools in studying the K(ATP) channels ("pancreatic-like" K(ATP) channels) in other tissues.
Simulative performance analysis of IO-link wireless (2018)

Control applications in factory automation utilizing wireless technologies require well-defined and constant communication performance with respect to cycle time, determinism and availability. These requirements are hard to meet using standard wireless communication technologies in the presence of interferers and challenging fading channels. The recently emerged new standard IO-Link Wireless was tailored to target the required performance characteristics even in densely populated 2.4 GHz ISM band. This work intends to verify by simulative analysis, that the performance indicators meet the target performance. For this purpose, a MATLAB-based simulation framework utilizing IEEE802.11 TGn and interferences with real life active profiles was developed and then used on IO-Link Wireless specification relevant test scenarios.
How Hard Is Deciding Trivial Versus Nontrivial in the Dihedral Coset Problem? (2016)

We study the hardness of the dihedral hidden subgroup problem. It is known that lattice problems reduce to it, and that it reduces to random subset sum with density > 1 and also to quantum sampling subset sum solutions. We examine a decision version of the problem where the question asks whether the hidden subgroup is trivial or order two. The decision problem essentially asks if a given vector is in the span of all coset states. We approach this by first computing an explicit basis for the coset space and the perpendicular space. We then look at the consequences of having efficient unitaries that use this basis. We show that if a unitary maps the basis to the standard basis in any way, then that unitary can be used to solve random subset sum with constant density >1. We also show that if a unitary can exactly decide membership in the coset subspace, then the collision problem for subset sum can be solved for density >1 but approaching 1 as the problem size increases. This strengthens the previous hardness result that implementing the optimal POVM in a specific way is as hard as quantum sampling subset sum solutions.
Synthesis and Biophysical Studies of N2′-Functionalized 2′-Amino-α-L-LNA (2007)

A synthetic route towards a selected set of N-acylated and N-alkylated derivatives of 2'-amino-alpha-L-LNA phosphoramidite building blocks has been developed. Biophysical studies suggest that the 2-oxo-5-azabicyclo[2.2.1]heptane skeleton of 2'-amino-alpha-L-LNA allows precise positioning of intercalators in the core of nucleic acid duplexes.
Every Corporation Owns Its Structure: Corporate Credit Ratings via Graph Neural Networks (2020)

Credit rating is an analysis of the credit risks associated with a corporation, which reflects the level of the riskiness and reliability in investing, and plays a vital role in financial risk. There have emerged many studies that implement machine learning and deep learning techniques which are based on vector space to deal with corporate credit rating. Recently, considering the relations among enterprises such as loan guarantee network, some graph-based models are applied in this field with the advent of graph neural networks. But these existing models build networks between corporations without taking the internal feature interactions into account. In this paper, to overcome such problems, we propose a novel model, Corporate Credit Rating via Graph Neural Networks, CCR-GNN for brevity. We firstly construct individual graphs for each corporation based on self-outer product and then use GNN to model the feature interaction explicitly, which includes both local and global information. Extensive experiments conducted on the Chinese public-listed corporate rating dataset, prove that CCR-GNN outperforms the state-of-the-art methods consistently.
Intrinsic Dimension Estimation Using Packing Numbers (2002)

We propose a new algorithm to estimate the intrinsic dimension of data sets. The method is based on geometric properties of the data and requires neither parametric assumptions on the data generating model nor input parameters to set. The method is compared to a similar, widely-used algorithm from the same family of geometric techniques. Experiments show that our method is more robust in terms of the data generating distribution and more reliable in the presence of noise.
The 6H-SiC structure model: Further refinement from SCXRD data from a terrestrial moissanite (2007)

The crystal structure of a terrestrial 6H-SiC moissanite has been refined in the P63mc S.G. from area detector single crystal X-ray data, down to an R-index on the observed reflections of 0.0205. The cell parameters refined over all the collected reflections are a = 3.0810(2) and c = 15.1248(10) Å. The average Si-C bond lengths are 1.8898 Å, with average bonds along the stacking direction (1.8993 Å) slightly longer than those along the bilayer (1.8862 Å). The interlayer distances, defined as the distances along [0001] between Si-Si layers, which may occur either in cubic (c) or hexagonal (h) configurations, are maximal at the c-h interface (2.5270 Å) and minimal at the h-c interface (2.5165 Å), entailing that the h-bilayer is not equidistant from either c-bilayers. All the tetrahedral angles are identical within the experimental error and close to the ideal value of 109.47°, but those at the c-h interface, where a significant distortion of 0.15° is recorded. Finally, the anisotropic displacement factors are utterly very small, identical among different atoms within the experimental error, and significantly spherical. It thus appears that the 6H-SiC structure is affected by a slight relaxation along the [0001] stacking direction with respect to the ideal cubic structure, and that the relaxation is mainly accomplished at the c-h interface, i.e., at the twin-like boundary, where a bilayer in cubic configuration links a bilayer in antiparallel, hexagonal configuration. As far as we know this is the first crystal structure refinement of a natural 6H-SiC moissanite. Possible implications on the polytype stability in the light of these results are briefly discussed.
SYMPTOMATOLOGICAL CHARACTERISTICS DISTINGUISH BETWEEN FRONTOTEMPORAL DEMENTIA AND VASCULAR DEMENTIA WITH A DOMINANT FRONTAL LOBE SYNDROME (1997)

The findings support our hypothesis.
Serum Chitotriosidase Activity, a Marker of Activated Macrophages, Predicts New Cardiovascular Events Independently of C-Reactive Protein (2007)

Our results suggest that serum chitotriosidase activity predicts the risk of new cardiovascular events in the following 4 years. This new cardiovascular risk marker is independent of CRP and, when combined, the prediction of the risk of new cardiovascular events and the identification of a lower risk group seem to improve.
Prognostic Factor Analysis for Plaque Psoriasis (2005)

Three major prognostic factors were identified. The proposed index may be useful in the design of future clinical trials for psoriasis and in the selection of appropriate therapeutic approaches for individual patients.
Characterizing autism spectrum disorders by key biochemical pathways (2015)

The genetic and phenotypic heterogeneity of autism spectrum disorders (ASD) presents a substantial challenge for diagnosis, classification, research, and treatment. Investigations into the underlying molecular etiology of ASD have often yielded mixed and at times opposing findings. Defining the molecular and biochemical underpinnings of heterogeneity in ASD is crucial to our understanding of the pathophysiological development of the disorder, and has the potential to assist in diagnosis and the rational design of clinical trials. In this review, we propose that genetically diverse forms of ASD may be usefully parsed into entities resulting from converse patterns of growth regulation at the molecular level, which lead to the correlates of general synaptic and neural overgrowth or undergrowth. Abnormal brain growth during development is a characteristic feature that has been observed both in children with autism and in mouse models of autism. We review evidence from syndromic and non-syndromic ASD to suggest that entities currently classified as autism may fundamentally differ by underlying pro- or anti-growth abnormalities in key biochemical pathways, giving rise to either excessive or reduced synaptic connectivity in affected brain regions. We posit that this classification strategy has the potential not only to aid research efforts, but also to ultimately facilitate early diagnosis and direct appropriate therapeutic interventions.
DVB standards development (2009)

The overview of digital video broadcasting (DVB) standards is presented. Particular attention is devoted to standards for terrestrial broadcasting, DVB-T and the newest DVB-T2. The comparison between these standards is derived and the advantages of the DVB-T2 over DVB-T are emphasized.
True Green Laser Diodes at 524 nm with 50 mW Continuous Wave Output Power on<i>c</i>-Plane GaN (2010)

We pushed direct green laser diodes towards longer wavelengths at 524–532 nm based on improvements of epitaxial design and material quality on c-plane GaN substrate. Mounted ridge laser diodes show significant performance improvement in cw operation. For 524 nm laser, wall plug efficiency up to 2.3% at 50 mW optical output power is achieved. In pulse mode operation we demonstrate broad-area test lasers with an emission wavelength of 531.7 nm. Nonpolar and polar substrates are compared with respect to indium content in InGaN quantum wells. The limiting factors for achieving longer wavelengths and better performance of green lasers are discussed from this viewpoint.
Assessment of the effects of pixel loss on image quality in direct digital radiography (2004)

Modern digital radiographic 'flat panel' detectors can exhibit a progressive form of image degradation arising from non-functioning pixels. The effect of these 'dead pixels' on the quantitive image quality measures of modulation transfer function (MTF), noise power spectrum (NPS) and detective quantum efficiency (DQE) is investigated by a simulated degradation of images obtained from an Hologic EPEX system. The effects on the semi-quantitive measures obtained from contrast threshold test objects and resolution gratings are also investigated. Results suggest that the contrast-detail tests often employed in quality assurance measures are not sufficient to reveal the presence of dead pixels until well beyond the recommended replacement point for the flat panel detector. However, measurements of spatial resolution using a line pairs phantom were found to be more sensitive to pixel loss. Measurement of the MTF, NPS and DQE can reveal small changes in image quality with increasing pixel loss, with a distinctive pattern in the trend of the NPS.
25 Years of Proton Pump Inhibitors: A Comprehensive Review (2016)

Proton pump inhibitors (PPIs) were clinically introduced more than 25 years ago and have since proven to be invaluable, safe, and effective agents for the management of a variety of acid-related disorders. Although all members in this class act in a similar fashion, inhibiting active parietal cell acid secretion, there are slight differences among PPIs relating to their pharmacokinetic properties, metabolism, and Food and Drug Administration (FDA)-approved clinical indications. Nevertheless, each is effective in managing gastroesophageal reflux disease and uncomplicated or complicated peptic ulcer disease. Despite their overall efficacy, PPIs do have some limitations related to their short plasma half-lives and requirement for meal-associated dosing, which can lead to breakthrough symptoms in some individuals, especially at night. Longer-acting PPIs and technology to prolong conventional PPI activity have been developed to specifically address these limitations and may improve clinical outcomes.
Analysis of hydrophobicity in the α and β chemokine families and its relevance to dimerization (1994)

The chemokine family of chemotactic cytokines plays a key role in orchestrating the immune response. The family has been divided into 2 subfamilies, alpha and beta, based on the spacing of the first 2 cysteine residues, function, and chromosomal location. Members within each subfamily have 25-70% sequence identity, whereas the amino acid identity between members of the 2 subfamilies ranges from 20 to 40%. A quantitative analysis of the hydrophobic properties of 11 alpha and 9 beta chemokine sequences, based on the coordinates of the prototypic alpha and beta chemokines, interleukin-8 (IL-8), and human macrophage inflammatory protein-1 beta (hMIP-1 beta), respectively, is presented. The monomers of the alpha and beta chemokines have their strongest core hydrophobic cluster at equivalent positions, consistent with their similar tertiary structures. In contrast, the pattern of monomer surface hydrophobicity between the alpha and beta chemokines differs in a manner that is fully consistent with the observed differences in quaternary structure. The most hydrophobic surface clusters on the monomer subunits are located in very different regions of the alpha and beta chemokines and comprise in each case the amino acids that are buried at the interface of their respective dimers. The theoretical analysis of hydrophobicity strongly supports the hypothesis that the distinct dimers observed for IL-8 and hMIP-1 beta are preserved for all the alpha and beta chemokines, respectively. This provides a rational explanation for the lack of receptor crossbinding and reactivity between the alpha and beta chemokine subfamilies.