bluuebunny/crossref_metadata_2025_split huggingface dataset:
Passenger Vehicle Characterization, Modeling, Validation, and Sensitivity Analysis
Authors: Klopp Adam , Schultz Jack , Tajaddini Ali 
Published: June 2018

As part of the vehicle qualification process, the Federal Railroad Administration (FRA) currently requires in its track and passenger equipment safety standards that a validated vehicle model be used to demonstrate safe dynamic vehicle response to allowable track geometry variations. Transportation Technology Center, Inc. (TTCI) was contracted by FRA to characterize, model, and analyze a high speed passenger vehicle in order to provide guidance related to the vehicle qualification process. The overall objective of the project was to evaluate methods required to demonstrate the validity of a vehicle dynamics model project and investigate how different input parameters affect the accuracy of the model. The project consisted of four main tasks: (1) characterize a high speed passenger vehicle; (2) develop a mathematical model of the vehicle using measured parameters; (3) validate the mathematical model using on-track tests; and (4) conduct a sensitivity analysis of the vehicle model to determine the critical parameters.
FRA tasked TTCI with applying the testing and modeling methodology to FRA’s DOTX 216 geometry car. Specific parameters were identified that needed to be measured in order to develop a dynamic vehicle model of the car. A characterization test regime was outlined and performed to determine the necessary mass, stiffness, and damping characteristics, and the measured parameter values were used to create a mathematical model of the vehicle using TTCI’s NUCARS®* dynamic modeling software. A series of on-track validation tests were performed on different tracks at the Transportation Technology Center (TTC) using the DOTX 216 car to facilitate model validation efforts. The model was then used to simulate the on-track testing regime conducted at TTC. Model validation was evaluated using displacement, acceleration, and wheel/rail force measurements. Results from the simulations and test data were compared using multiple methods to demonstrate the validation of the DOTX 216 model. TTCI also conducted a parameter sensitivity analysis using the validated model to assess its sensitivity to changes in different parameter values and to identify the most critical parameters for simulating passenger vehicles. The testing, modeling, and model validation methodology described in this work provide a practical example of developing a validated vehicle model for use in the vehicle qualification process.
Analysis of Wheel Impact Load Detector (WILD) System Implementation on Metro-North Railroad
Authors: Stewart Monique , Flynn Edward , Pouryousef Hamed , Singh Som P. , Prabhakaran Anand 
Published: June 2018

The Federal Railroad Administration (FRA) has partnered with Metro-North Railroad (MNR), Long Island Rail Road (LIRR) and New York & Atlantic Railway (NYA) to promote operations safety through implementation of wayside detection systems and technologies. Under this partnership, opportunities were identified to enhance safety operations through the analysis of existing and planned wheel impact load detector (WILD) installations and operational procedures, including recommendations for future wayside detection systems implementations on these networks.
Currently, MNR has a four-detector system operating near the Grand Central Terminal, since 2010. This paper includes an analysis of this WILD system and its impact on rolling stock maintenance. The analysis shows that the WILD system has gradually reduced the annual average number of high impact load wheels from 0.32/car in 2010 to 0.27/car in 2015.
Review of data from the detectors on four tracks at the WILD site shows that train operations below a certain speed has a significant effect on the detection rate and should be a major consideration in selecting a location for WILD installation.
The data show that the highest number of high impact wheels is detected in the month of November, potentially due to leaves on the rails during fall season.
Our analysis shows that the currently used trigger threshold of dynamic ratio (DR)≥3 at MNR provides well-reasoned balance between the available fleet, maintenance demand and the maintenance shop capacity. At this threshold setting, the number of wheels detected per million wheel passages is quite small indicating a well maintained fleet.
Proper Testing of DC High Speed Circuit-Breakers and Protection Relays in a Railway Environment
Authors: D’Hooghe Wim 
Published: June 2018

DC High Speed circuit-breakers (DC-HSCB’s) and Protective Relays (PR’s) are present in all sorts of rail infrastructure. National or urban railways, tramways or metro’s, they all rely on this equipment to protect them from disastrous situations. The circuit-breakers can be installed either on board of the trains or on the trackside, in traction power substations. Protection Relays are, in most cases, part of the fixed installation. Needless to say that the DC-HSCB and PR are critical parts of the rail infrastructure. In the best case a faulty unit can cause the trains to stand still, in the worst case it can blow up parts of the infrastructure and cause casualties.
The life-cycle of circuit-breakers is long, some of the units still in operation are more than 50 years old. The first digital protective relays were introduced in the eighties. Proper testing of DC-HSCB and PR is a hot topic these days as a result of a number of incidents on various LRT and tramway systems (STEVO Electric, 2015). This paper describes some issues with testing and how to resolve them.
Solving Various Train Approach Speeds to Highway Crossings Using Innovative Technologies
Authors: Hofbauer John 
Published: June 2018

The use of using cleaner energy (zero emissions) transportation has become a key focus in the North America even within rail transportation. Within in North America the migration from Diesel to Electric Locomotives, utilizing overhead catenary systems with voltages in the 25kV range for passenger trains has become the standard. In addition, “Shared-Use Rail Corridors” have become more prevalent in North America (USA and Canada), the use of Constant Warning Time Devices (CWTD) based on a change of inductance in the rail are less reliable within Electrified railroads.
With shared use track, it is understood that a difference exists between freight and passenger train speeds, resulting in the need for other methods to detect and determine the correct approach times become a priority. Implementing Computer-Based Train Control (CBTC) systems or Positive Train Control (PTC) technology can mitigate the problem if they communicate / request highway crossing activation. But in locations where PTC is not being installed or in Canada where it is not required, other methods need to be explored. This paper will review and analyze the following:
1. Review the existing systems being deployed;
2. Evaluate the deployed systems effectiveness;
3. Test and record data using various innovative technologies including: Axle counters determining speed of approaching train, acceleration (+ / −);
4. Conclusion for the integrating new axle counter technologies and existing track circuits.
EU-funded initiatives for real world evidence: descriptive analysis of their characteristics and relevance for regulatory decision-making
Authors: Plueschke Kelly , McGettigan Patricia , Pacurariu Alexandra , Kurz Xavier , Cave Alison 
Published: June 2018

IntroductionA review of European Union (EU)-funded initiatives linked to ‘Real World Evidence’ (RWE) was performed to determine whether their outputs could be used for the generation of real-world data able to support the European Medicines Agency (EMA)’s regulatory decision-making on medicines.MethodThe initiatives were identified from publicly available websites. Their topics were categorised into five areas: ‘Data source’, ‘Methodology’, ‘Governance model’, ‘Analytical model’ and ‘Infrastructure’. To assess their immediate relevance for medicines evaluation, their therapeutic areas were compared with the products recommended for EU approval in 2016 and those included in the EMA pharmaceutical business pipeline.ResultsOf 171 originally identified EU-funded initiatives, 65 were selected based on their primary and secondary objectives (35 ‘Data source’ initiatives, 15 ‘Methodology’, 10 ‘Governance model’, 17 ‘Analytical model’ and 25 ‘Infrastructure’). These 65 initiatives received over 734 million Euros of public funding. At the time of evaluation, the published outputs of the 40 completed initiatives did not always match their original objectives. Overall, public information was limited, data access was not explicit and their sustainability was unclear. The topics matched 8 of 14 therapeutic areas of the products recommended for approval in 2016 and 8 of 15 therapeutic areas in the 2017–2019 pharmaceutical business pipeline. Haematology, gastroenterology or cardiovascular systems were poorly represented.ConclusionsThis landscape of EU-funded initiatives linked to RWE which started before 31 December 2016 highlighted that the immediate utilisation of their outputs to support regulatory decision-making is limited, often due to insufficient available information and to discrepancies between outputs and objectives. Furthermore, the restricted sustainability of the initiatives impacts on their downstream utility. Multiple projects focussing on the same therapeutic areas increase the likelihood of duplication of both efforts and resources. These issues contribute to gaps in generating RWE for medicines and diminish returns on the public funds invested.
S1P Stimulates Proliferation by Upregulating CTGF Expression through S1PR2-Mediated YAP Activation
Authors: Cheng Jung-Chien , Wang Evan Y. , Yi Yuyin , Thakur Avinash , Tsai Shu-Huei , Hoodless Pamela A. 
Published: June 2018

Abstract
Dysregulation of the Hippo pathway in the liver results in overgrowth and eventually tumorigenesis. To date, several upstream mechanisms have been identified that affect the Hippo pathway, which ultimately regulate YAP, the major downstream effector of the pathway. However, upstream regulators of the Hippo pathway in the liver remain poorly defined. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that has been shown to stimulate hepatocellular carcinoma (HCC) cell proliferation, but whether the Hippo pathway is involved in S1P-stimulated HCC cell proliferation remains to be determined. Here it is demonstrated that S1P activates YAP and that the S1P receptor 2 (S1PR2/S1P2) mediates S1P-induced YAP activation in both human and mouse HCC cells. S1P promotes YAP-mediated upregulation of cysteine-rich protein 61 and connective tissue growth factor (CTGF), and stimulates HCC cell proliferation. By using siRNA-mediated knockdown approaches, only CTGF was required for S1P-stimulated cell proliferation. Of note, S1P activates YAP in a MST1/2-independent manner suggesting that the canonical Hippo kinase is not required for S1P-mediated proliferation in liver. The upregulation of CTGF and S1P2 were also observed in liver-specific YAP overexpression transgenic mouse hepatocytes. Moreover, YAP regulated liver differentiation–dependent gene expression by influencing the chromatin binding of HNF4α based on ChIP-seq analysis. Finally, results using gain- and loss-of-function approaches demonstrate that HNF4α negatively regulated S1P-induced CTGF expression.
Implications: These findings reveal a role for S1P in stimulating HCC cell proliferation by upregulating CTGF expression through S1P2-mediated YAP activation. Mol Cancer Res; 16(10); 1543–55. ©2018 AACR.
Daxx Functions Are p53-Independent In Vivo
Authors: Wasylishen Amanda R. , Estrella Jeannelyn S. , Pant Vinod , Chau Gilda P. , Lozano Guillermina 
Published: June 2018

Abstract
Mutations in the death domain–associated protein (DAXX) have been recently identified in a substantial proportion of human pancreatic neuroendocrine tumors (PanNETs). Remarkably, however, little is known about the physiologic role(s) of DAXX despite in vitro studies suggesting potential functions. Most prominently, and supported by tumor sequencing data, DAXX functions in concert with alpha thalassemia/mental retardation X-linked (ATRX) as a histone chaperone complex for the H3.3 variant. Studies have also identified potential roles in apoptosis, transcription, and negative regulation of the p53 tumor suppressor pathway. Herein, a mouse modeling approach was used to specifically address the latter and no significant genetic interaction between Daxx and the p53 pathway was determined. The embryonic lethal phenotype of Daxx loss is not p53-dependent. In addition, Daxx heterozygosity does not sensitize mice to a sublethal dose of ionizing radiation or alter the survival or tumor phenotype of Mdm2 transgenic mice. However, the data support a tumor suppressor role for DAXX as low-dose ionizing radiation produced a higher proportion of carcinomas in Daxx heterozygous mice than wild-type controls.
Implications: While DAXX has important in vivo functions, they are independent of an inhibitory role on the p53 tumor suppressor pathway. Mol Cancer Res; 16(10); 1523–9. ©2018 AACR.
Aspects of Methamphetamine Abuse in Adolescents and Young Adults in a Thuringian County
Authors: Dhein Stefan , Schmelmer Katrin , Guenther Julika , Salameh Aida 
Published: June 2018

<b><i>Background/Objective:</i></b> Drug abuse is an increasing problem among young adults in European countries. We wanted to assess the prevalence of methamphetamine and cannabis use in young people and to ask for their socioeconomic, parental and emotional background. <b><i>Methods:</i></b> All pupils (<i>n</i> = 1,087) in the final class of 3 school types (­general school [in Germany: Hauptschule/Regelschule mit Hauptschulabschluss] class 9, regular school [in Germany: Regelschule] class 10, high school [in Germany: Gymnasium] class 10) and the first 2 classes of the vocational school (in Germany: Berufsschule) in the entire rural district of Altenburger Land, a Thuringian county in Germany with a total of 92,344 inhabitants were asked to fill out a 2-page questionnaire. In all, 920 questionnaires could be finally evaluated (mean age: 16.6 ± 0.07 years; mode value: 16; maximum range: 13–29). <b><i>Results:</i></b> In the entire group, 5.81% (33 females, 20 males) reported the use of methamphetamine, while 42.8% stated that they have used it only once, the remaining 57.2% specified that they have used it on a more regular basis, mostly once a month, but 14.2% had used it almost daily. With regard to the socioeconomic background, 55% of the parents of the methamphetamine users were employees and 10% of the parents were in a leading position. This was not different from the non-user group (<i>p</i> = 0.193). Unemployment of the parents was found in 6.5% of the methamphetamine users and in 4.7% of the non-users. Overall, 67.92% had a basic knowledge of the side effects of this drug. In 55.32% of the methamphetamine users, the parents lived alone, were divorced or widowed, while this was only 33.1% in the non-user group. Of all the methamphetamine users, 69% had friends who also consumed the drug, which may give a hint on the impact of a peer group. In the entire group, 29.84% were smokers (female group: 28.47%; male group 31.25%) and 25.5% consumed cannabis. Ecstasy was used by a total of 4.05% and cocaine by 1.53%. No participant mentioned that they have used opiates. <b><i>Conclusion:</i></b> Among pupils aged about 16 years nearly 6% reported to have consumed methamphetamine. This group has a middle socioeconomic background. Two factors were strongly associated with methamphetamine usage: a family with only a single parent and friends who were used to taking methamphetamine. The self-perception of users was generally considered to be a disadvantage as compared to the other factors.
Inactivation of the E3 Ubiquitin Ligase IDOL Attenuates Diet-Induced Obesity and Metabolic Dysfunction in Mice
Authors: van Loon Nienke M. , Ottenhoff Roelof , Kooijman Sander , Moeton Martina , Scheij Saskia , Roscam Abbing Reinout L.P. , Gijbels Marion J.J. , Levels Johannes H.M. , Sorrentino Vincenzo , Berbée Jimmy F.P. , Rensen Patrick C.N. , Zelcer Noam 
Published: June 2018

Objective—
The E3 ubiquitin ligase IDOL (inducible degrader of the LDLR [LDL (low-density lipoprotein) receptor]) is a post-transcriptional regulator of LDLR abundance. Model systems and human genetics support a role for IDOL in regulating circulating LDL levels. Whether IDOL plays a broader metabolic role and affects development of metabolic syndrome-associated comorbidities is unknown.

Approach and Results—

We studied WT (wild type) and
Idol
(−/−)
(Idol-KO) mice in 2 models: physiological aging and diet-induced obesity. In both models, deletion of
Idol
protected mice from metabolic dysfunction. On a Western-type diet,
Idol
loss resulted in decreased circulating levels of cholesterol, triglycerides, glucose, and insulin. This was accompanied by protection from weight gain in short- and long-term dietary challenges, which could be attributed to reduced hepatosteatosis and fat mass in Idol-KO mice. Although feeding and intestinal fat uptake were unchanged in Idol-KO mice, their brown adipose tissue was protected from lipid accumulation and had elevated expression of UCP1 (uncoupling protein 1) and TH (tyrosine hydroxylase). Indirect calorimetry indicated a marked increase in locomotion and suggested a trend toward increased cumulative energy expenditure and fat oxidation. An increase in in vivo clearance of reconstituted lipoprotein particles in Idol-KO mice may sustain this energetic demand. In the BXD mouse genetic reference population, hepatic
Idol
expression correlates with multiple metabolic parameters, thus providing support for findings in the Idol-KO mice.

Conclusions—
Our study uncovers an unrecognized role for Idol in regulation of whole body metabolism in physiological aging and on a Western-type diet. These findings support Idol inhibition as a therapeutic strategy to target multiple metabolic syndrome-associated comorbidities.
T Cells Prevent Hemorrhagic Transformation in Ischemic Stroke by P-Selectin Binding
Authors: Salas-Perdomo Angélica , Miró-Mur Francesc , Urra Xabier , Justicia Carles , Gallizioli Mattia , Zhao Yashu , Brait Vanessa H. , Laredo Carlos , Tudela Raúl , Hidalgo Andrés , Chamorro Ángel , Planas Anna M. 
Published: June 2018

Objective—
Hemorrhagic transformation is a serious complication of ischemic stroke after recanalization therapies. This study aims to identify mechanisms underlying hemorrhagic transformation after cerebral ischemia/reperfusion.

Approach and Results—

We used wild-type mice and Selplg
−/−
and Fut7
−/−
mice defective in P-selectin binding and lymphopenic Rag2
−/−
mice. We induced 30-minute or 45-minute ischemia by intraluminal occlusion of the middle cerebral artery and assessed hemorrhagic transformation at 48 hours with a hemorrhage grading score, histological means, brain hemoglobin content, or magnetic resonance imaging. We depleted platelets and adoptively transferred T cells of the different genotypes to lymphopenic mice. Interactions of T cells with platelets in blood were studied by flow cytometry and image stream technology. We show that platelet depletion increased the bleeding risk only after large infarcts. Lymphopenia predisposed to hemorrhagic transformation after severe stroke, and adoptive transfer of T cells prevented hemorrhagic transformation in lymphopenic mice. CD4
+
memory T cells were the subset of T cells binding P-selectin and platelets through functional P-selectin glycoprotein ligand-1. Mice defective in P-selectin binding had a higher hemorrhagic score than wild-type mice. Adoptive transfer of T cells defective in P-selectin binding into lymphopenic mice did not prevent hemorrhagic transformation.

Conclusions—
The study identifies lymphopenia as a previously unrecognized risk factor for secondary hemorrhagic transformation in mice after severe ischemic stroke. T cells prevent hemorrhagic transformation by their capacity to bind platelets through P-selectin. The results highlight the role of T cells in bridging immunity and hemostasis in ischemic stroke.
The EU in the Central Mediterranean: Impact and Implications of the Comprehensive Approach
Authors: Dura Sophie 
Published: June 2018

Abstract
The implications of the comprehensive approach to the EU refugee crisis are becoming apparent in the current actions of different players in the central Mediterranean, where a Common Security and Defence Policy (CSDP) military operation is present alongside Frontex’s joint operation Triton. Both cooperate closely with Libyan border authorities and the European Migrant Smuggling Centre of Europol. But this not only poses humanitarian problems as to how the EU should cooperate on these matters with Libyan officials, it also leads to a confusing meddling of different EU actors from distinct policy areas in matters of crucial importance to the Union. Against this background, the article delineates the competences and powers of the different actors. Another issue is the role of the European Parliament in the situation: it has little influence in the CSDP but strong links to the agencies. In this context the article will discuss the influence of the cooperation on parliamentary accountability.
Review of the Japanese Microtendipes (Diptera: Chironomidae: Chironominae), with description of a new species
Authors: TANG HONGQU , NIITSUMA HIROMI 
Published: June 2018

Japanese species of Microtendipes are reviewed. Eleven names proposed in this genus, including Russian M. sakhalinensis Zorina, 2001, are synonymized with M. umbrosus Freeman, 1955, for which male and female adults, pupa and larva are redescribed based on specimens collected from Japan. Two species, M. shoukomaki Sasa, 1989 and M. famiefeus Sasa, 1996, are validated based on the re-examination of type specimens and are redescribed based on specimens newly collected from Japan. Descriptions of the larva of M. shoukomaki and the female adult, pupa and larva of M. famiefeus are given here for the first time. Microtendipes chloris (Meigen, 1818) sensu Sasa is redescribed as a new species, M. parachloris Niitsuma & Tang sp. nov., based on the male adult. Additionally, synonymic notes of Polypedilum (Cerobregma) yamasinense (Tokunaga, 1940) comb. nov. and P. (Polypedilum) tsukubaense (Sasa, 1979), transferred from Microtendipes, are given. Polypedilum kamotertium Sasa, 1989 and M. iriocedeus Sasa & Suzuki, 2000 are synonymized with the above two species, respectively, based on each original description. The distribution of M. umbrosus extends from Africa to the Russian Far East and East Asia (Japan, China), and Australia and Thailand (with new distributions reported here). Although no African type material is examined here, the morphological features of those populations are consistent with Freeman’s concept.