jimnoneill/paper-to-field-training huggingface dataset:
First Human Dosing Experience with TRV130, a Biased Ligand at the Mu Opioid Receptor (P02.013)

OBJECTIVE: To evaluate the safety, tolerability, PK and PD of TRV130. BACKGROUND: TRV130 is a novel highly selective G-protein biased ligand of the mu opioid receptor; it stimulates canonical G protein coupling while simultaneously blocking s-arrestin-mediated signaling. In animals, TRV130 is a potent, efficacious analgesic with improved GI and respiratory side effects compared to morphine. DESIGN/METHODS: A 3-part clinical study was conducted to evaluate the tolerability, PK and PD of TRV130 in healthy male subjects. The study was conducted under GCP principles. RESULTS: In Part A eight cohorts of 8 subjects were enrolled. In each cohort, placebo (n=2) or TRV130 (n=6) was administered as a one-hour infusion. The TRV130 starting dose was selected based on the preclinical toxicology studies with subsequent doses determined by tolerability. TRV130 had a half-life of approximately 2 hours and produced a dose-related pupil constriction. TRV130 4 mg produced significant, near-maximal pupil constriction with no nausea or vomiting. In Part B, the PK of TRV130 was evaluated in 4 phenotypic CYP2D6 poor metabolizers (PMs). In PMs, TRV130 had similar maximal plasma concentrations and an approximately 50% reduction in clearance as non-PMs at the same dose. This suggests that tolerability will be similar in PMs and non-PMs, although PMs may require less frequent dosing. In Part C, the tolerability of bolus administration was studied. Six subjects received TRV130 1.5 mg administered over 30, 15, 5 and 1 minute on successive study days. TRV130 was well-tolerated at all rates. The effect of the 1.5 mg dose on pupil diameter was in line with the expected effect given the plasma concentrations observed. CONCLUSIONS: TRV130 is a novel mu opioid receptor G-biased ligand which exhibited excellent PK, PD and tolerability. Additional studies are planned to continue development of TRV130 for post-operative analgesia and to explore the feasibility of developing a transdermal formulation. Supported by: Trevena, Inc. Disclosure: Dr. Soergel has received personal compensation for activities with Trevena, Inc. as an employee. Dr. Subach has received personal compensation for activities with Trevena, Inc. as an employee. Dr. Violin has received personal compensation for activities with Trevena, Inc. as an employee. Dr. Yamashita has received personal compensation for activities with Trevena, Inc. as an employee. Dr. Gowen has received personal compensation for activities with Trevena, Inc., and GlaxoSmithKline, Inc. Dr. Gowen holds stock and/or stock options in Human Genome Sciences. Dr. Lark has reeived personal compensation as an employee of Trevena, Inc. Dr. Lark holds stock and/or stock options in Johnson & Johnson.

Topic: Receptor Mechanisms and Signaling
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Law and practice of financial appeal bodies (ESAs’ Board of Appeal, SRB Appeal Panel): A view from the inside

This paper offers some lessons drawn from the first years of experience of both the joint Board of Appeal (BoA) of the European Supervisory Authorities and the Appeal Panel (AP) of the Single Resolution Board.The paper outlines their institutional design and the main substantive and procedural issues that have arisen in the cases so far decided by both bodies. It offers a view “from the inside”, which shows not only the certainties of appeal bodies, but also their many challenges. The paper also discusses design strengths and weaknesses of the current EU adjudicatory system of public law disputes in the Banking Union and the Capital Markets Union, bearing in mind the importance of independent review, and the Vaassen criteria for “courts”. The paper concludes by offering preliminary stocktaking and reflections on a possible way forward to enhance the complementary (and supporting) role of financial appeal bodies to the EU courts.

Topic: European and International Law Studies
Subfield: Political Science and International Relations
Field: Social Sciences
Domain: Social Sciences
The Relationship between Marketing and Green Services with the Tourism Industry

Green or environmental marketing includes activities that are designed to create and facilitate exchanges to satisfy human needs, in such a way that satisfying these needs and desires with minimal harmful and destructive effects on the environment. This type of tourism with different names; Flexible tourism, responsible tourism, beneficial tourism or alternative tourism are known. Therefore, the main goal of this research is to investigate the effect of green marketing on attracting tourists in hotels in the east of Gilan province. Based on the goals, this research is of the type of applied research and is based on data collection and research design in a descriptive-survey method, and since we are looking to find the relationship between the variables of the research, this research is also of the correlation type. In the current research of the statistical community, all the tourists of the hotels in the east of Gilan province, of which there are 100,000 people, of which 390 people were selected by simple random sampling using Morgan's table. A questionnaire was used to collect data. We have used the regression model to check the false assumptions, and the results indicate that the green price has a positive and significant effect on the attraction of tourists in the hotels in the east of Mazandaran province. Green services have a positive and significant effect on attracting tourists in hotels in the east of Gilan province. Green promotion has a positive and meaningful effect on attracting tourists in hotels in the east of Gilan province. Also, the green place has a positive and significant effect on attracting tourists in hotels in the east of Gilan province.

Topic: Environmental Sustainability in Business
Subfield: Marketing
Field: Business, Management and Accounting
Domain: Social Sciences
Long-term results of surgically-assisted maxillary protraction

Objective: The long-term treatment results of surgically-assisted facemask therapy were assessed by a comparison of the immediate protraction effects with those seen at five years review. Materials and methods: Nine patients treated with a corticotomy-assisted maxillary protraction protocol were recalled five years following protraction. Cephalometric films taken before treatment (TO), immediately after maxillary protraction (T1) and five years after treatment (T2) were compared. Results: The short-term results of surgically-assisted facemask therapy showed significant skeletal and soft tissue changes. After five years, the profile and dental relationships were well maintained and a cephalometric analysis revealed a stable vertical increase but only partially maintained soft tissue changes with loss of sagittal advancement. There was significant upper incisor proclination providing dental camouflage. Conclusion: Patients who are treated with corticotomy-assisted maxillary advancement should be very carefully selected. Assessment criteria include a low mandibular plane angle Class Ill patients who have severe maxillary retrognathism unable to be treated by conventional orthopaedic correction alone; patients who have almost completed growth and missed the chance of earlier orthopaedic correction, as well as patients who are not willing to accept bimaxillary orthognothic surgery, may be successfully treated.

Topic: Orthodontics and Dentofacial Orthopedics
Subfield: Orthodontics
Field: Dentistry
Domain: Health Sciences
GROUNDING OF THE DIRECTIONS FOR IMPROVEMENT OF ORGANIZATIONAL AND ECONOMIC LOGISTIC ACTIVITIES SUPPORT OF A TRADE ENTERPRISE

Introduction. The article deals with theoretical aspects of the problem under study. It identifies the main elements and proposes a system of indicators for assessing the organizational and economic logistics activities support of a trade enterprise. The research presents the sequence of determination of directions and tools for improvement of the organizational and economic logistics activities support of a trade enterprise. Purpose. The article aims to study the methodological principles of problem diagnostics and to determine the directions of improvement of the organizational and economic logistics activities support of a trade enterprise. Method (methodology) The methods of system and structural analysis, method of causative analysis, method synthesis and the relational method have been used in this research. On the basis of these methods the directions of the improvement of the organizational and economic logistics activities support of a trade enterprise are proposed. Results. In the conducted research the problem zones of organizational and economic support according to the main elements have been determined. The grouping of measures and tools for improvement of organizational and economic support of logistic activity while taking into account the criteria of operational efficiency has been done. The degree of coverage of the problem areas has been defined. The positive changes in logistics activities of the trade enterprise have been determined.

Topic: Economic and Business Development Strategies
Subfield: Economics and Econometrics
Field: Economics, Econometrics and Finance
Domain: Social Sciences
Multiagent Intelligent System of Convergent Sensor Data Processing for the Smart&amp;Safe Road

The results of monitoring and analyzing traffic accidents, fixed by an intelligent monitoring system with photoradar complexes, are considered. The system works with a network of distributed photoradar vehicle detectors for road accidents, video surveillance cameras, vehicle information and communication systems, built-in car navigation equipment and mobile communication equipment. A multiagent approach developed to address the tasks of sensor data collecting and processing. The system functionality is implemented by several agents that perform data collecting, cleaning, clustering, comparing time series, retrieving data for visualization, preparing charts and reports, performing spatial and intellectual analysis, etc. Convergent approach is the convergence of cloud, fog and mobile data processing technologies. The diagnostic system is necessary for remote maintenance of photoradar equipment. The structure of the neural network is adapted to the diagnosing problems and forecasting. The tasks of intellectual analysis and forecasting traffic accidents are solved. The hybrid fuzzy neural network is synthesized. Because of the comparison of time series of traffic accidents and time series of meteorological factors, the presence of factors to become determinants for an abnormal change in the traffic situation in controlled areas is established.

Topic: Economic and Technological Systems Analysis
Subfield: Management of Technology and Innovation
Field: Business, Management and Accounting
Domain: Social Sciences
<i>Sarbanes-Oxley</i> and the Search for Accountable Corporate Governance

AbstractThe following sestions are included:‘PURPOSE’ AND THE ASSESSMENT OF CORPORATE GOVERNANCE REFORMUNCOVERING THE HISTORICAL PURPOSE OF CORPORATE GOVERNANCEThe Modern Corporate Form as HybridInventing the Corporate FormCLARIFYING THE STANDARDThe Stakeholder ModelThe Fiduciary ModelThe Accountability ModelASSESSING ACCOUNTABLE GOVERNANCE: A FRAMEWORKASSESSING SARBANES-OXLEYThe Performative ProvisionsThe Regulatory ProvisionsManagerial Provisions and the Absence of Fourth Order ProvisionsCONCLUSION

Topic: Corporate Finance and Governance
Subfield: Accounting
Field: Business, Management and Accounting
Domain: Social Sciences
Diesel and biodiesel exhaust particle effects on rat alveolar macrophages with in vitro exposure

Combustion emissions from diesel engines emit particulate matter which deposits within the lungs. Alveolar macrophages (AM) encounter the particles and attempt to engulf the particles. Emissions particles from diesel combustion engines have been found to contain diverse biologically active components including metals and polyaromatic hydrocarbons which cause adverse health effects. However little is known about AM response to particles from the incorporation of biodiesel. The objective of this study was to examine the toxicity in Wistar Kyoto rat AM of biodiesel blend (B20) and low sulfur petroleum diesel (PDEP) exhaust particles. Particles were independently suspended in media at a range of 1–500µg/mL. Results indicated B20 and PDEP initiated a dose dependent increase of inflammatory signals from AM after exposure. After 24hr exposure to B20 and PDEP gene expression of cyclooxygenase-2 (COX-2) and macrophage inflammatory protein 2 (MIP-2) increased. B20 exposure resulted in elevated prostaglandin E2 (PGE2) release at lower particle concentrations compared to PDEP. B20 and PDEP demonstrated similar affinity for sequesteration of PGE2 at high concentrations, suggesting detection is not imparied. Our data suggests PGE2 release from AM is dependent on the chemical composition of the particles. Particle analysis including measurments of metals and ions indicate B20 contains more of select metals than PDEP. Other particle components generally reduced by 20% with 20% incoporation of biodiesel into original diesel. This study shows AM exposure to B20 results in increased production of PGE2in vitro relative to diesel.

Topic: Energy and Environment Impacts
Subfield: Pollution
Field: Environmental Science
Domain: Physical Sciences
Integration, Part III. Sierra geophysics - User interface, standards, portability are the keys

The Sierra 2DI software package is reviewed. The package is an interactive 2-D seismic interpretation system that allows the picking of seismic events on a computer monitor. Seismic section and well log data are integrated for fast, efficacious interpretation and data manipulation. 2DI also produces quick, accurate, presentation-quality maps. These maps include contours; composites that reflect isochron structures, amplitude, depth; and time maps that include cultural features, well locations and lease boundaries.

Topic: Geological Modeling and Analysis
Subfield: Geochemistry and Petrology
Field: Earth and Planetary Sciences
Domain: Physical Sciences
The Groma and the Gladius: Roman Surveyors in the Later Republic

&lt;p&gt;Boundaries have been a concern for all settled peoples in all times and places. The Romans were no exception to this rule. Literary documents from the second century B.C. right through to the end of the Western Empire in the fifth century A.D. show a continuous preoccupation with the delineation of boundaries and the ownership or control of land. As part of this preoccupation, the Romans developed a complex legal framework for coping with property ownership. To accompany this legal framework, they developed a sophisticated system of boundary marking and land surveying known as centuriation. A great deal of scholarly attention has been expended on understanding both the system of centuriation and the legal framework governing Roman land use. Far less attention has been paid to the social development of the agrimensores or land surveyors who actually carried out the operation of centuriation and dealt with the problems of property disputes in the Imperial period. This thesis will focus on the social identity of the Roman land surveyors with a particular emphasis on understanding their origins in the surveying institutions of the later Republic. To accomplish this study, the thesis will be broken down into three broad chapters, each chapter containing two or three subsections. The first chapter will examine the social identity and evolution of the finitor, who has traditionally been considered the surveyor of the Roman Republic. The second chapter will examine the identity of the agrimensores or mensores in the particular context of the Roman army in an effort to distinguish them from the metatores, three names which have been considered to refer to the same or a similar occupation. The third chapter will examine the mensor in the context of the Roman Republic and trace the social forces that shaped their identity as specialists in land law and surveying.&lt;/p&gt;

Topic: Classical Studies and Legal History
Subfield: History
Field: Arts and Humanities
Domain: Social Sciences
Screening of a point charge by an anisotropic medium: Anamorphoses in the method of images

We extend the classical dielectric image problem for an external point charge interacting with a semi-infinite medium to the case of an anisotropic dielectric. We show that the exterior potential is a solution to an unconventional image problem. By contrast the interior potential is not a solution to any simple image system; instead it can be obtained through an anamorphic transformation of an image solution. We calculate the volume bound charge density that is induced within the anisotropic dielectric and distinguishes it from an isotropic medium where the volume density vanishes. This solution provides a very simple and physically relevant example in which the physics of the surface and volume bound charge densities in a polarized dielectric can be analyzed.

Topic: Electromagnetic Scattering and Analysis
Subfield: Atomic and Molecular Physics, and Optics
Field: Physics and Astronomy
Domain: Physical Sciences
The metabolic and neuroinflammatory changes induced by consuming a cafeteria diet are age-dependent

The 3- and 18-month-old rats responded differently to a cafeteria diet. Insulin and leptin levels are elevated in young animals fed a cafeteria diet, whereas aged animals are prone to neuroinflammation (indicated by an increase in interleukin-1β levels). A combination of hypercaloric diet and senescence have detrimental effects on the inflammatory response in the brain, which may predispose to neurological diseases.

Topic: Regulation of Appetite and Obesity
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Two New Species and a New Variety in the Genus Arachnophroctonus (Hymenoptera: Psammocharidae) With Photomicrographs of the Genitalia and Subgenital Plate for the Genus and for Several Other Species

Arachnophroctonus is used here as characterized by Evans (1951) in his monograph, except that I accord it generic rank, while Evans considers it to be a subgenus of Anoplius. In this sense the genus includes those species previously included in Psdmmochares (Pompilus) which have stout, backward directed bristles on the pygidium of the female, amd which have all the claws cleft in the male. Evans states that an invarible character in separating this genus is that the basal vein is either insterstitial or the transverse median meets the media slightly before the basal. Evans did an excellent job in removing the confusion existing in this group and the writer agrees with him fully in his presentation of the genus, except in a few minor cases. Two new species and a new variety, however, were discovered in my study of this family and the descriptions follow. Photomicrographs of the male genitalia and subgenital plates of all the species are presented, as welI as Anoplius depressipes Banks (figs. 5, 10), A. fulgidus (Cr.) (figs. 20, 27), (which were not available when the paper (Dreisbach, 1950) on that genus was published) and also Anopliodes parsoni Banks (figs. 21, 22). In comparing the drawings in Evans' paper with the photomicrographs, certain differences are noticeable. In the case of Anopliodes parsoni the errors which arise in making drawings (in spite of great care) are very evident. The parapenial lobes seem to be almost as long as aedeagus in the photo and somewhat heavier than in drawing, while thie parameres have almost parallel sides whereas the drawing shows them becoming narrower from base to tip. Also, the drawings of the subgenital plates of A. americanus and A. apiculatus groups do not quite agree with the photos.

Topic: Plant and animal studies
Subfield: Ecology, Evolution, Behavior and Systematics
Field: Agricultural and Biological Sciences
Domain: Life Sciences
Wool wagons on Hopwood's Ferry crossing the Murray River at Echuca, Victoria

Hopwood's floating pontoon bridge at Echuca with his ferry. The nearest vessel is Hopwood's pontoon bridge and the second vessel is Hopwoods pontoon bridge. The ferry ran from Echuca, Victoria to Moama, New South Wales.

Topic: Maritime and Coastal Archaeology
Subfield: Archeology
Field: Arts and Humanities
Domain: Social Sciences
Calix[6]tren and copper(II): A third generation of funnel complexes on the way to redox calix-zymes

Mono-copper enzymes play an important role in biology and their functionality is based on Cu(II)/Cu(I) redox processes. Modeling a mono-nuclear site remains a challenge for a better understanding of its intrinsic reactivity. The first member of a third generation of calixarene-based mono-copper “funnel” complexes is described. The ligand is a calix[6]arene capped by a tren unit, hence presenting a N 4 coordination site confined in a cavity. Its Cu(II) complexes were characterized by electronic and EPR spectroscopies. The x-ray structure of one of them shows a five-coordinated metal ion in a slightly distorted trigonal bipyramidal geometry thanks to its coordination to a guest ligand L (ethanol). The latter sits in the heart of the hydrophobic calixarene cone that mimics the active site chamber and the hydrophobic access channel of enzymes. Competitive binding experiments showed a preference order dimethylformamide &gt; ethanol &gt; MeCN for L binding at the single exchangeable metal site. Cyclic voltammetry studies showed irreversible redox processes in CH 2 Cl 2 when L is an oxygen donor caused by the redox-driven ejection of the guest at the Cu(I) level. In the presence of MeCN, a pseudoreversible process was obtained, owing to a fast equilibrium between a fourand a five-coordinate Cu(I) species. Finally, a redox-driven ligand interchange of dimethylformamide for MeCN at the Cu(I) state allowed the trapping of the thermodynamically less stable Cu(II)-MeCN adduct. Hence, this work represents an important step toward the elaboration of a functional supramolecular model for redox mono-copper enzymes, named redox calix-zymes.

Topic: Metal-Catalyzed Oxygenation Mechanisms
Subfield: Inorganic Chemistry
Field: Chemistry
Domain: Physical Sciences
Efficacy of <i>Sophora japonica</i> L. Pill in Subjective Memory Complaints in Healthy Adults: a protocol of randomized, double-blind, placebo-controlled, parallel-group, clinical trial

This study will provide evidence on the efficacy and safety of <i>S. japonica</i> extract for improving cognitive function in adults with subjective memory complaints. If proven effective, this supplement could offer a new approach for supporting cognitive health in aging populations. The comprehensive assessment of cognitive, mood, and quality of life outcomes will allow thorough evaluation of its potential benefits.

Topic: Neurological Disease Mechanisms and Treatments
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences