bluuebunny/crossref_metadata_2025_split huggingface dataset:
USP8 Controls the Trafficking and Sorting of Lysosomal Enzymes
Authors: MacDonald Ewan , Urbé Sylvie , Clague Michael J. 
Published: June 2014

AbstractThe endosomal deubiquitylase USP8 has profound effects on endosomal morphology and organisation. Previous reports have proposed both positive (EGFR, MET) and negative roles in the down‐regulation of receptors (Frizzled, Smoothened). Here we report an additional influence of USP8 on the retromer‐dependent shuttling of ci‐M6PR between the sorting endosome and biosynthetic pathway. Depletion of USP8 leads to a steady state redistribution of ci‐M6PR from the Trans‐Golgi Network (TGN) to endosomal compartments. Consequently we observe a defect in sorting of lysosomal enzymes, evidenced by increased levels of unprocessed Cathepsin D, which is secreted into the medium. The normal distribution of receptor can be restored by expression of siRNA‐resistant USP8 but not by a catalytically inactive mutant or a truncated form, lacking a MIT domain required for endosomal localisation. We suggest that effects of USP8 depletion may reflect the loss of ESCRT‐0 components which associate with retromer components Vps35 and SNX1, whilst failure to efficiently deliver lysosomal enzymes may also contribute to the observed block in receptor tyrosine kinase degradation.
On Nonlinear Dynamics of the STAT5a Signaling Protein
Authors: Nikolova Elena , Jordanov Ivan , Vitanov Nikolay K. 
Published: June 2014

In this paper we model the dynamics of the cross talk between MEK/ERK and JAK/STAT signaling pathways by means of nonlinear ordinary differential equations. The considered system В of four ordinary differential equations is reduced to one ordinary differential equation, representing dynamics of the phosphorylated STAT5a signaling protein. We show that the diffusion together with the corresponding biochemical reactions is likely to play a critical role in governing the dynamical behavior of the considered signaling protein. В By the modified method of simplest equation to the described reaction-diffusion equation we obtain an analytical solution which explains drop and jump propagation of the STAT5a protein concentration.
Risk Based Broken Rail Detection on Railways
Authors: Thurston David F. 
Published: June 2014

There has been a long debate among train control professionals related to broken rail detection; where it is required and how it is achieved. Despite this ongoing discussion, there has been little research in terms of the actual practical application of new technology or risk mitigation approaches since conventional track circuits have been applied to detect broken rails.
This paper first looks at conventional broken rail detection as implemented with various track circuit types, then reviews the current research on alternate means of detection throughout the world.
The paper will then quantify a risk based approach utilizing existing technologies to mitigate the broken rail requirements currently mandated for higher speed rail systems in the United States. Further, the implications for train control systems for both transit and the general system of railroads will be examined.
Engineering Studies on Joint Bar Integrity: Part I — Field Surveys and Observed Failure Modes
Authors: Jeong David Y. , Bruzek Radim , Tajaddini Ali 
Published: June 2014

This paper is the first of a two-part series describing a research project, sponsored by the Federal Railroad Administration (FRA), to study the structural integrity of joint bars. In Part I of this series, observations from field surveys conducted on revenue service track are presented. Automated and visual inspections of rail joints were conducted to identify defective joint bars. Detailed information and measurements were collected at various joint locations.
The survey team consisted of personnel from ENSCO, Inc. and Transportation Technology Center, Inc. (TTCI), working in cooperation with staff from participating railroads. Part II of this series describes the development of finite element analyses of jointed rail, which is being carried out by the Volpe National Transportation Systems Center (Volpe Center).
Assessment of Broken Rail Protection in Audio Frequency Track Circuits
Authors: Schaad Joseph W. 
Published: June 2014

In addition to the vital function of train detection, a track circuit is also expected to provide an indication of a broken rail within its boundaries.
Ability to detect a broken rail in a double rail track circuit is a result of the failsafe design principle, which interrupts the flow of track signal current and drops the track relay in the presence of any credible component failure. The overall result of such an event is identical to that of track occupancy, which causes the associated signals to be set to the most restrictive aspect.
In the case of electrified territory, the ability to detect a broken rail may be compromised by the presence of crossbonds between parallel tracks. These additional connections, which are intended to minimize potential differences in the negative return system, also provide a sneak path for track signal current to flow from transmit to receive ends of the track circuit under broken rail conditions. In most cases involving 2 parallel tracks, application of a simple rule of thumb (described in this paper) regarding crossbond spacing and track circuit length is sufficient to ensure broken rail protection. In situations which are marginal, or where complex track work is involved, a more detailed analysis is necessary. Evaluation of the broken rail protection in such cases requires that the sneak path impedance be calculated and compared to the normal track circuit impedance. A formal method for this impedance calculation, based upon the classical circuit analysis techniques, is presented.
To completely characterize the behavior of the track circuit under broken rail conditions, the operational characteristics of the track circuit must also be considered. In this paper a digital jointless AF track circuit, operating in the 9.5–20.7 kHz range, is used as a basis for this discussion. The operational characteristics of the S-bond, O-bond, as well as the role of overdrive are considered in the context of broken rail (BR) protection.
The mathematical methods described for the simplified examples in this paper can readily be expanded to include any number of parallel tracks.
Ultrasonic Tomography for Rail Flaw Imaging
Authors: Phillips Robert , Lanza di Scalea Francesco , Nucera Claudio , Rizzo Piervincenzo , Al-Nazer Leith 
Published: June 2014

There is a need in the railroad industry to have quantitative information on internal rail flaws, including flaw size and orientation. Such information can lead to knowledge-based decision making on any remedial action, and ultimately increase the safety of train operations by preventing derailments. Current ultrasonic inspection methods leave such sizing determinations to the inspector, and there can be significant variability from one inspector to another depending on experience and other factors. However, this quantitative information can be obtained accurately by 3-D imaging of the rail flaws. It is the goal of this project to develop a portable system that will improve defect classification in rails and ultimately improve public safety.
This paper will present a method for 3-D imaging of internal rail flaws based on Ultrasonic Tomography. The proposed technique combines elements of ultrasonic testing with those of radar and sonar imaging to obtain high-resolution images of the flaws using a stationary array of ultrasonic transducers. The array is operated in a “full matrix capture” scheme that minimizes the number of ultrasonic transmitters, hence simplifying the practical implementation and reducing the inspection time. In this method, a full 3D image of the rail volume identifies the location, size and orientation of the defect. This will help to eliminate human error involved with a typical manual inspection using a single transducer probe inspection. The results of advanced numerical simulations, carried out on a rail profile, will be presented. The simulations show the effectiveness of the technique to image a 5% Head Area Transverse Defect in the railhead. Current efforts are aimed at developing an experimental prototype based on this technology, whose design status is also discussed in this paper.
A Study on a Multiple Film Technique Utilized in Radiographic Examination for Steel Castings With Complicated Geometry
Authors: Ao Zhijun , Li Leon , Wei Zunfa 
Published: June 2014

Castings on transit railcars often have complicated geometry. Varying thicknesses and limited space for shooting are difficult for radiographic testing of such castings. To reach the high-quality requirements of the density, accuracy, contrast, and sharpness of the films, a series of experiment were performed on one casting with complicated geometry to compare different results from different shooting methodologies.
Films with different ISO speeds are suitable for different wall thickness while their detection ranges overlap with each other. By adopting multiple film techniques, radiographic quality is enhanced when inspecting complicated castings geometries. The utilization of lead intensifying screen contributes to improve the image quality of the radiograph, so that the absorption of different sections is equalized and the prescribed quality level and density requirements are met. Latitude of film is improved by selecting appropriate voltage. Source-to-film distance is increased in order to minimize geometric unsharpness and ensure overall uniformity. Lead foil screens are utilized as a filter in front of films to absorb scattered radiation. In addition, back scatter radiation is reduced by placing lead plates behind the cassette. Large focal spot size is adopted. Short time of exposure is preferentially selected for the purpose of reducing the active time of scattered radiation. Moreover, the selection of other associated processing parameters helps to lessen the adverse effects caused by complicated casting geometries.
The results of these experiments show that the quantities of films and inspection cost can be reduced, efficiency of inspection can be improved; missing detection in complicated areas can be effectively avoided; the detection capability is increased and reliability of inspection results is ensured. In conclusion, the multiple film technique is a satisfactory methodology for radiographic testing of steel castings with complicated geometry.
Applying Reliability and Availability Methods to Communication Based Train Control
Authors: Diemunsch Kenneth M. , Muthukrishnan Gopala 
Published: June 2014

Reliability, Availability and Maintainability (RAM) engineering has been applied successfully for decades in many industries such as military electronics for aerospace [1] [2], nuclear power stations [3], and oil field services [4]. Several standards applying to train control have also been produced recently, for instance the IEEE recommended practice on Communication Based Train Control (CBTC) testing [5], the international standard for Reliability Availability Maintainability Safety (RAMS) in railway applications [6] and the European version [7]. Better Reliability and Availability (RA) involves a larger capital investment cost but results in lower maintenance cost and fewer system impacting delays. RAM engineering is used to define the optimal level of reliability and availability to minimize those two costs.
This paper introduces CBTC technology, including typical architectures of the subsystems which need to be modeled for the RA analysis. Basic RAM definitions and methods which can be applied to any system, including train control equipment, are presented. Then, the application of RA methods on CBTC system is discussed in terms of requirements, analysis, testing and methods to choose spare parts quantity.
Advances in Bonded Insulated Rail Joints to Improve Product Performance
Authors: Ciloglu Korhan , Frye Peter C. , Almes Scott , Shue Sidney 
Published: June 2014

Insulated rail joints (IJs) are critical components of railroad track infrastructure. It is essential for IJs to maintain railroad track’s structural continuity while having an important role in track circuit design and implementation. The structural integrity and performance of IJs have been recognized as a key interest area by the railroads as a result of increasing average axle loads and train traffic. While there are many different designs offered by various manufacturers around the globe, the main approach utilized by heavy haul railroads in the US, Canada and many other countries has been to use adhesively bonded insulated joint bars between two rails. This approach offers the benefit of a composite assembly where the continuous bond between rails and bars offer a geometrically uninterrupted transfer of loads between rails and bars. The main components of a bonded IJ are joint bars, insulation material, adhesive, endpost, and bolts or other fasteners. This paper summarizes recent design improvements on these components.
The main focus areas of the research are bar design, bar material selection, insulator and adhesive selection and using a novel endpost design for load transfer between two rails. Track support conditions’ impact on IJ performance has also been considered as a factor influencing IJ performance in track and incorporated in the study. The impact of insulation material selection on IJ performance is discussed. Finite element analysis was used extensively in the study where the analysis results were supported by laboratory and field testing. The results of the study indicate dynamic stresses in bonded IJs can be reduced nearly 40% in joint bars by a combination of design improvements on IJ components. Improved bar material properties are expected to lead to considerably reduced risk of bar fatigue failures in track.
Analysis and Development of Performance-Based Requirements for Railroad Tank Cars
Authors: Kirkpatrick Steven W. , MacNeill Robert A. , Gonzalez Francisco 
Published: June 2014

There has been significant research in recent years to analyze and improve the impact behavior and puncture resistance of railroad tank cars. Ultimately, the results of this work will be used by the Government regulatory agencies in the United States and Canada to establish performance-based testing requirements and to develop methods to evaluate the crashworthiness and structural integrity of different tank car designs.
This paper describes analyses of current impact testing requirements and impact test methodologies using detailed finite element analyses (FEA). The results of these analyses are used to identify characteristics of the test methodologies that are desirable or undesirable for the test requirements in future tank car safety regulations.
Rail Temperature Prediction Model and Heat Slow Order Management
Authors: Bruzek Radim , Biess Larry , Kreisel Leopold , Al-Nazer Leith 
Published: June 2014

Track buckling due to excessive rail temperature may cause derailments with serious consequences. To minimize the risk of derailments, slow orders are typically issued on sections of track in areas where an elevated rail temperature is expected and risk of track buckling is increased. While slow orders are an important preventive safety measure, they are costly as they disrupt timetables and can affect time-sensitive shipments. Optimizing the slow order management process would result in significant cost saving for the railroads.
The Federal Railroad Administration’s (FRA’s) Office of Research and Development has sponsored the development of a model for predicting rail temperatures using real time weather forecast data and predefined track parameters and a web-based system for providing resulting information to operators.
In cooperation with CSX Transportation (CSX) and FRA, ENSCO Inc. conducted a comprehensive model verification study by comparing actual rail temperatures measured by wayside sensors installed at 23 measurement sites located across the CSX network with the rail temperatures predicted by the model based on weather forecast data over the course of spring and summer 2012. In addition to the correlation analysis, detection theory was used to evaluate the model’s ability to correctly identify instances when rail temperatures are elevated above a wide range of thresholds. Detection theory provides a good way of comparing the performance of the model to the performance of the current industry practice of estimating rail temperature based on constant offsets above predicted daily peak ambient air temperatures.
As a next step in order to quantify the impact of implementation of the model on CSX operations, heat slow orders issued by CSX in 2012 on 10 selected subdivisions were compared to theoretical heat slow orders generated by the model.
The paper outlines the analysis approach together with correlation, detection theory and slow order comparison results. The analysis results along with investigation of past heat related track buckle derailments indicate that the railroad would benefit from adopting the rail temperature prediction model along with flexible rail temperature thresholds. The implementation of the model will have a positive impact on safety by allowing for issuing of advance heat slow orders in more accurate, effective and targeted way.
Analysis of the Relationship Between Rail Seat Load Distribution and Rail Seat Deterioration in Concrete Crossties
Authors: Greve Matthew , Dersch Marcus S. , Edwards J. Riley , Barkan Christopher P. L. , Mediavilla Jose , Wilson Brent M. 
Published: June 2014

One of the most common failure modes of concrete crossties in North America is the degradation of the concrete surface at the crosstie rail seat, also known as rail seat deterioration (RSD). Loss of material beneath the rail can lead to wide gauge, rail cant deficiency, and an increased risk of rail rollover. Previous research conducted at the University of Illinois at Urbana-Champaign (UIUC) has identified five primary failure mechanisms: abrasion, crushing, freeze-thaw damage, hydro-abrasive erosion, and hydraulic pressure cracking. The magnitude and distribution of load applied to the rail seat affects four of these five mechanisms; therefore, it is important to understand the characteristics of the rail seat load distribution to effectively address RSD.
As part of a larger study funded by the Federal Railroad Administration (FRA) aimed at improving concrete crossties and fastening systems, researchers at UIUC are attempting to characterize the loading environment at the rail seat using matrix-based tactile surface sensors (MBTSS). This instrumentation technology has been implemented in both laboratory and field experimentation, and has provided valuable insight into the distribution of a single load over consecutive crossties. A review of past research into RSD characteristics and failure mechanisms has been conducted to integrate data from field experimentation with existing knowledge, to further explore the role of the rail seat load distribution on RSD. The knowledge gained from this experimentation will be integrated with associated research conducted at UIUC to form the framework for a mechanistic design approach for concrete crossties and fastening systems.
Improving Resiliency in Communications Systems in Public Transit After Severe Weather Events
Authors: Fitzmaurice Michael 
Published: June 2014

Subway stations and tunnels typically contain many different communications systems used by a transit agency to support the safe movement of passenger trains. When these stations and tunnels are flooded with water from excessive rains or hurricane related storm surges the resulting damage to these systems, devices and associated cabling can render them ineffective or completely inoperable. This in turn leads to costly repairs and replacement programs entailing lengthy service disruptions.
This paper will look at how the repair and replacement of communications systems damaged by the exposure to accumulated rain and salt water from a storm surge can be implemented so as to improve the overall system’s resiliency to future severe weather events.
Secure Communication-Based Train Control: Performance Evaluation of a Design Framework
Authors: Aziminejad Arash , Seckin Mustafa 
Published: June 2014

Railroads are increasingly using Communication-Based Train Control (CBTC) technology to improve service capacity and operating efficiency. CBTC is a mission-critical system under which train monitoring and train control are integrated into a single unified system through data links between vehicles, central processors, and wayside equipment. Radio over fiber technology provides a flexible and efficient solution for the Data Communication System (DCS) which needs to ensure integrity and reliability of message delivery in a transparent manner for the train control functions.
A Security Device (SD) is defined as a network entity located between the railroad administration’s (the customer) trusted wired network and the non-trusted portion of the DCS network including the radio-based segment, which runs on a customized piece of hardware with a secure operating system and provides secure gateway functionality. This paper puts forward a network architecture and SD software platform design which meets the requirements of a typical CBTC system. The IPSEC protocol used by the SD for data protection renders authentication service through X.509 certificates. A network setup is put together as the proof-of-concept for the presented design proposal and performance assessment is conducted through experimental studies.
Metabolic Drug-Drug Interaction Potential of Macrolactin A and 7-
O
-Succinyl Macrolactin A Assessed by Evaluating Cytochrome P450 Inhibition and Induction and UDP-Glucuronosyltransferase Inhibition
In Vitro
Authors: Bae Soo Hyeon , Kwon Min Jo , Park Jung Bae , Kim Doyun , Kim Dong-Hee , Kang Jae-Seon , Kim Chun-Gyu , Oh Euichaul , Bae Soo Kyung 
Published: June 2014

ABSTRACT

Macrolactin A (MA) and 7-
O
-succinyl macrolactin A (SMA), polyene macrolides containing a 24-membered lactone ring, show antibiotic effects superior to those of teicoplanin against vancomycin-resistant enterococci and methicillin-resistant
Staphylococcus aureus
. MA and SMA are currently being evaluated as antitumor agents in preclinical studies in Korea. We evaluated the potential of MA and SMA for the inhibition or induction of human liver cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGTs)
in vitro
to assess their safety as new molecular entities. We demonstrated that MA and SMA are potent competitive inhibitors of CYP2C9, with

K
i

values of 4.06 μM and 10.6 μM, respectively. MA and SMA also weakly inhibited UGT1A1 activity, with

K
i

values of 40.1 μM and 65.3 μM, respectively. However, these macrolactins showed no time-dependent inactivation of the nine CYPs studied. In addition, MA and SMA did not induce CYP1A2, CYP2B6, or CYP3A4/5. On the basis of an
in vitro-in vivo
extrapolation, our data strongly suggested that MA and SMA are unlikely to cause clinically significant drug-drug interactions mediated via inhibition or induction of most of the CYPs involved in drug metabolism
in vivo
, except for the inhibition of CYP2C9 by MA. Similarly, MA and SMA are unlikely to inhibit the activity of UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 enzymes
in vivo
. Although further investigations will be required to clarify the
in vivo
interactions of MA with CYP2C9-targeted drugs, our findings offer a clearer understanding and prediction of drug-drug interactions for the safe use of MA and SMA in clinical practice.