bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll‐like receptors 2 and 4 exert opposite effects on the contractile response induced by serotonin in mouse colon: role of serotonin receptors
Authors: Forcén R. , Latorre E. , Pardo J. , Alcalde A. I. , Murillo M. D. , Grasa L. 
Published: June 2016

New Findings
What is the central question of this study?
The action of Toll‐like receptors (TLRs) 2 and 4 on the motor response to serotonin in mouse colon has not previously been reported.

What is the main finding and its importance?
Toll‐like receptors 2 and 4 modulate the serotonin‐induced contractile response in mouse colon by modifying the expression of serotonin (5‐HT) receptors. Alterations in 5‐HT2A and 5‐HT2C receptors explain the increase of the response to serotonin in TLR2−/− mice. Alterations in 5‐HT2C and 5‐HT4 receptors explain the suppression of the response to serotonin in TLR4−/− mice.

The microbiota, through Toll‐like receptors (TLRs), may regulate gastrointestinal motility by activating neuroendocrine mechanisms. We evaluated the influence of TLR2 and TLR4 in spontaneous contractions and in the serotonin (5‐HT)‐induced motor response in mouse colon, and assessed the 5‐HT receptors involved. Muscle contractility studies to evaluate the intestinal spontaneous motility and the response to 5‐HT were performed in the colon from wild‐type (WT), TLR2−/−, TLR4−/− and TLR2/4 double knockout (DKO) mice. The 5‐HT receptor mRNA expression was determined by real‐time PCR. The amplitude and frequency of the spontaneous contractions of the colon were smaller in TLR4−/− and TLR2/4 DKO mice with respect to WT mice. In WT, TLR2−/− and TLR2/4 DKO mice, 100 μm 5‐HT evoked a contractile response. The contractile response induced by 5‐HT was significantly higher in TLR2−/− than in WT mice. In TLR4−/− mice, 5‐HT did not evoke any contractile response. The mRNA expression of 5‐HT2A was increased in TLR2−/− and TLR2/4 DKO mice. The 5‐HT2C and 5‐HT4 mRNA expressions were increased in TLR4−/− and TLR2/4 DKO mice. The 5‐HT2C mRNA expression was diminished in TLR2−/− mice. The 5‐HT3 mRNA expression was increased in TLR2−/−, TLR4−/− and TLR2/4 DKO mice. The 5‐HT7 mRNA expression was diminished in TLR2/4 DKO mice. In WT, TLR2−/− and TLR2/4 DKO mice, 5‐HT2, 5‐HT3, 5‐HT4 and 5‐HT7 receptor antagonists reduced or blocked the contractile response evoked by 5‐HT. We postulate that TLR2 and TLR4 modulate the serotonin contractile motor response in mouse colon in an opposing manner by modifying the expression of several serotonin receptors.
Rail Integrity Experience on the Washington Metro System
Authors: Frison Benjamin , Jeong David Y. 
Published: June 2016

The Washington Metropolitan Area Transit Authority (WMATA) provides passenger rail service to the nation’s capital. Although the rail system carries only passenger trains, the rail integrity issues that WMATA must manage are similar to those that freight railroads also face. These issues include occurrences of broken rail from internal rail head defects, detection of such defects, and repair of the rail to restore service. Another example is the development of damage on the running surface of the rail, called rolling contact fatigue (RCF). Such surface damage is known to adversely affect the detection of internal rail head defects beneath RCF conditions. While WMATA’s rail integrity issues may be similar to those that freight railroads also encounter, the management of such issues are different, which are also discussed in this paper.
This paper describes the recent experience of broken rails on the WMATA rail system. In addition, results from engineering fracture mechanics analyses are presented to help understand how operational, environmental, design, and maintenance factors influence rail failure.
On Railroad Tank Car Puncture Performance: Part II — Estimating Metrics
Authors: Jeong David Y. , Carolan Michael E. , Perlman Benjamin 
Published: June 2016

This paper is the second in a two-part series on the puncture performance of railroad tank cars carrying hazardous materials in the event of an accident. Various metrics are often mentioned in the open literature to characterize the structural performance of tank cars under accident loading conditions. One of the consequences in terms of structural damage to the tank during accidents is puncture. This two-part series of papers focuses on four metrics to quantify the performance of tank cars against the threat of puncture: (1) speed, (2) force, (3) energy, and (4) conditional probability of release.
In Part I, generalized tank car impact scenarios were illustrated. Particular focus is given to the generalized shell impact scenario because performance-based requirements for shell puncture resistance are being considered by the regulatory agencies in United States and Canada. Definitions for the four performance metrics were given. Physical and mathematical relationships among these metrics were outlined. Strengths and limitations of these performance metrics were discussed.
In this paper (Part II), the multi-disciplinary approach to develop engineering tools to estimate the performance metrics is described. The complementary connection between testing and modeling is emphasized. Puncture performance metrics, which were estimated from other sources, are compared for different tank car designs. These comparisons are presented to interpret the metrics from a probabilistic point of view. In addition, sensitivity of the metrics to the operational and design factors is examined qualitatively.
NYCT Solid State Interlocking (SSI) Safety Certification
Authors: Georgiadis Sofia K. , Parrella William , Hacken George 
Published: June 2016

The New York City Transit (NYCT) Signal Modernization Program has been ongoing since the mid-1990s. The current phase of modernization involves the procurement of Solid State Interlocking (SSI) systems that are designed to replace relay-based interlockings. SSI procurement has necessitated significant adjustments to NYCT’s system deployment processes, most notably in the areas of design, implementation, test, maintenance, and safety certification. NYCT has successfully met the challenge of applying the updated deployment processes to multiple, concurrent system procurements.
The most fundamental change to the NYCT procurement approach required a shift from the traditional design-build model of acquisition for relay-based systems to a software-based development lifecycle for SSIs. The relay-based Interlocking systems’ design-build model has traditionally involved the realization of complex relay logic with well-known hardware components such as relays, trip-stops, signals and switch machines. The SSI systems’ software model however requires additional consideration of software and hardware development phases, such as designated in the V-lifecycle.
V-model phases include requirement, design, implementation, and test. For SSI systems, NYCT adopted a “double” V-Life cycle approach, one V for the supplier’s SSI hardware and software (executive) platform, and one V for the SSI application (site-specific field) logic. At NYCT, the first V is dedicated to the suppliers’ executive platform. Hardware and software comprising the supplier platform are verified to meet safety and performance requirements. Safety analyses such as Fault Tree Analysis, Failure Modes and Effects Analysis, Timing Analysis, and Hazard Analysis are generated by SSI suppliers. System Safety Concepts, e.g., Numerical Assurance, Checked Redundancy, Intrinsic Fail-Safety are also assessed. NYCT’s second V is dedicated to the application software, i.e., the site-specific relay-based logic, which is implemented as Boolean logic within the SSI. For the Booleans, the process of traditional circuit checking is supplemented by Model Checking, wherein NYCT General Safety Properties are used to verify the site-specific logic. Model Checking provides assurance that safety properties are met throughout the entire interlocking design, for every system state, and does not rely on a manual review process. This paper will focus on the benefits NYCT has realized as a result of adopting Model Checking as a requirement for safety certification, along with an overview of the NYCT SSI safety certification process.
Multi-Tiered Cognitive Radio Network for Positive Train Control Operations
Authors: Bandara K. R. Damindra S. , Melaragno Anthony P. , Wijesekara Duminda , Costa Paulo 
Published: June 2016

Positive Train Controller (PTC) is a communication based system designed to enforce PTC safety objectives for trains such as train-to-train collisions, train derailments, and ensure railroad worker safety. Existing PTC designs consider risks due to operational environment such as location of other trains, switches, and speed limits.
We propose to enhance PTC by using a multi-tiered cognitive radio network that considers multiple risks such as those due to bandwidth congestion, packet length limitations, propagation losses, detectable exploitation of Software Defined Radio vulnerabilities, and protocol vulnerabilities. Radios operating at PTC nodes (such as train, WIU and Base station) is equipped with a cognitive layer, which communicates with other nodes to create a cognitive radio network. The proposed network as a whole strives to provide spectrum management and security for the radio communication system, which can enhance the PTC functionality.
Each cognitive radio in our proposed network consists of multiple tiers. The upper tier consists of a master cognitive engine that holistically evaluates the operational risks of the network and acts to mitigate them using the lower tiers. The lower tier (immediate slave tier to the master) consists of sub cognitive engines for cryptographic operations and spectrum management. The traditional PTC protocol is implemented at a lower tier module that interface with the master Cognitive Engine (CE). The master-slave communications within one radio is implemented using middleware.
The proposed cognitive radio network can be modeled as a cyber-physical system by incorporating train movement dynamics, radio transmission characteristics and cryptographical computations, thereby constituting a distributed system of communicating hybrid automatons. This design enables us to verify safety and the security of the system using formal methods, which constitutes our ongoing work. We also discuss potential issues such as FRA mandated safety cases that needs to be addressed if the proposed features are to be added to the PTC systems.
Tank Car Top Fittings Protection: Evaluation of Derailment Failure Risks — A Conceptual Study
Authors: Di Bacco Barbara , Kirney Christopher , Prabhakaran Anand , Booth Graydon F. , Gantoi Florentina M. , Wen Rou 
Published: June 2016

Top fittings devices on tank cars are subject to damage and failure under derailment conditions, potentially leading to the release of hazardous lading. This paper describes the conceptual development of an objective methodology for evaluating the risk of fittings protection failure and the potential reduction in that risk when mitigating strategies such as improved fittings protective structure are deployed. The methodology captures several key elements that affect fittings survival, including: the speed of derailment initiation, the impact velocity/force spectrum experienced by the fittings protective structure during the event, the strength/structural capacity of the protective structure, and the rigidity of the ground surface.
Detailed finite element modeling efforts were employed to capture derailment dynamics and corresponding impact velocity spectra, as well as the strength of multiple protective designs. Future work, including validation, is planned to extend the concept into a detailed methodology.
Online 3D EPID‐based dose verification: Proof of concept
Authors: Spreeuw Hanno , Rozendaal Roel , Olaciregui‐Ruiz Igor , González Patrick , Mans Anton , Mijnheer Ben , van Herk Marcel 
Published: June 2016

Purpose:Delivery errors during radiotherapy may lead to medical harm and reduced life expectancy for patients. Such serious incidents can be avoided by performing dose verification online, i.e., while the patient is being irradiated, creating the possibility of halting the linac in case of a large overdosage or underdosage. The offline EPID‐based 3D in vivo dosimetry system clinically employed at our institute is in principle suited for online treatment verification, provided the system is able to complete 3D dose reconstruction and verification within 420 ms, the present acquisition time of a single EPID frame. It is the aim of this study to show that our EPID‐based dosimetry system can be made fast enough to achieve online 3D in vivo dose verification.Methods:The current dose verification system was sped up in two ways. First, a new software package was developed to perform all computations that are not dependent on portal image acquisition separately, thus removing the need for doing these calculations in real time. Second, the 3D dose reconstruction algorithm was sped up via a new, multithreaded implementation. Dose verification was implemented by comparing planned with reconstructed 3D dose distributions delivered to two regions in a patient: the target volume and the nontarget volume receiving at least 10 cGy. In both volumes, the mean dose is compared, while in the nontarget volume, the near‐maximum dose (D2) is compared as well. The real‐time dosimetry system was tested by irradiating an anthropomorphic phantom with three VMAT plans: a 6 MV head‐and‐neck treatment plan, a 10 MV rectum treatment plan, and a 10 MV prostate treatment plan. In all plans, two types of serious delivery errors were introduced. The functionality of automatically halting the linac was also implemented and tested.Results:The precomputation time per treatment was ∼180 s/treatment arc, depending on gantry angle resolution. The complete processing of a single portal frame, including dose verification, took 266 ± 11 ms on a dual octocore Intel Xeon E5‐2630 CPU running at 2.40 GHz. The introduced delivery errors were detected after 5–10 s irradiation time.Conclusions:A prototype online 3D dose verification tool using portal imaging has been developed and successfully tested for two different kinds of gross delivery errors. Thus, online 3D dose verification has been technologically achieved.
The arithmetic of reducing relative and absolute inequalities in health: a theoretical analysis illustrated with European mortality data
Authors: Mackenbach Johan P , Martikainen Pekka , Menvielle Gwenn , de Gelder Rianne 
Published: June 2016

BackgroundReducing inequalities in health is a great challenge for public health, but how relative and absolute inequalities in mortality respond to changes in mortality by socioeconomic group is not well understood.MethodsWe derived arithmetically what combinations of changes and starting levels of mortality by socioeconomic group produce narrowing, and what combinations produce widening of relative and absolute inequalities in mortality. We then determined empirically how often these scenarios actually occur with data on inequalities in cause-specific mortality in five European countries spanning four decades (1970–2010).ResultsChanges in the rate ratio depend exclusively on the ratio of relative mortality change between socioeconomic groups, whereas changes in the rate difference depend on whether the ratio of relative mortality change between socioeconomic groups is larger or smaller than the rate ratio. This implies that, in case of declining mortality and faster relative mortality decline in higher socioeconomic groups, the rate difference will increase until the rate ratio becomes equal to the ratio of relative mortality decline, but will then start to decline. In the most common scenario in our data set (starting rate ratio above 1.00 and faster relative mortality decline in higher than lower socioeconomic groups), the rate ratio indeed always goes up but the rate difference goes down in about half of all cases, sometimes after a period of growth.ConclusionsA narrowing of absolute inequalities occurs under a wider range of conditions than a narrowing of relative inequalities in mortality.
CSR
Authors: Shalev Noam , Harpaz Eran , Porat Hagar , Keidar Idit , Weinsberg Yaron 
Published: June 2016

One of the adverse effects of shrinking transistor sizes is that processors have become increasingly prone to hardware faults. At the same time, the number of cores per die rises. Consequently, core failures can no longer be ruled out, and future operating systems for many-core machines will have to incorporate fault tolerance mechanisms.
We present CSR, a strategy for recovery from unexpected permanent processor faults in commodity operating systems. Our approach overcomes surprise removal of faulty cores, and also tolerates cascading core failures. When a core fails in user mode, CSR terminates the process executing on that core and migrates the remaining processes in its run-queue to other cores. We further show how hardware transactional memory may be used to overcome failures in critical kernel code. Our solution is scalable, incurs low overhead, and is designed to integrate into modern operating systems. We have implemented it in the Linux kernel, using Haswell's Transactional Synchronization Extension, and tested it on a real system.
M3
Authors: Asmussen Nils , Völp Marcus , Nöthen Benedikt , Härtig Hermann , Fettweis Gerhard 
Published: June 2016

In the last decade, the number of available cores increased and heterogeneity grew. In this work, we ask the question whether the design of the current operating systems (OSes) is still appropriate if these trends continue and lead to abundantly available but heterogeneous cores, or whether it forces a fundamental rethinking of how systems are designed. We argue that: 1. hiding heterogeneity behind a common hardware interface unifies, to a large extent, the control and coordination of cores and accelerators in the OS, 2. isolating at the network-on-chip rather than with processor features (like privileged mode, memory management unit, ...), allows running untrusted code on arbitrary cores, and 3. providing OS services via protocols over the network-on-chip, instead of via system calls, makes them accessible to arbitrary types of cores as well.
In summary, this turns accelerators into first-class citizens and enables a single and convenient programming environment for all cores without the need to trust any application.
In this paper, we introduce network-on-chip-level isolation, present the design of our microkernel-based OS, M3, and the common hardware interface, and evaluate the performance of our prototype in comparison to Linux. A bit surprising, without using accelerators, M3 outperforms Linux in some application-level benchmarks by more than a factor of five.
Activation of Peroxisome Proliferator–Activated Receptor-δ as Novel Therapeutic Strategy to Prevent In-Stent Restenosis and Stent Thrombosis
Authors: Hytönen Jarkko , Leppänen Olli , Braesen Jan Hinrich , Schunck Wolf-Hagen , Mueller Dominik , Jung Friedrich , Mrowietz Christoph , Jastroch Martin , von Bergwelt-Baildon Michael , Kappert Kai , Heuser Arnd , Drenckhahn Jörg-Detlef , Pieske Burkert , Thierfelder Ludwig , Ylä-Herttuala Seppo , Blaschke Florian 
Published: June 2016

Objective—
Drug-eluting coronary stents reduce restenosis rate and late lumen loss compared with bare-metal stents; however, drug-eluting coronary stents may delay vascular healing and increase late stent thrombosis. The peroxisome proliferator–activated receptor-delta (PPARδ) exhibits actions that could favorably influence outcomes after drug-eluting coronary stents placement.

Approach and Results—
Here, we report that PPARδ ligand–coated stents strongly reduce the development of neointima and luminal narrowing in a rabbit model of experimental atherosclerosis. Inhibition of inflammatory gene expression and vascular smooth muscle cell (VSMC) proliferation and migration, prevention of thrombocyte activation and aggregation, and proproliferative effects on endothelial cells were identified as key mechanisms for the prevention of restenosis. Using normal and PPARδ-depleted VSMCs, we show that the observed effects of PPARδ ligand GW0742 on VSMCs and thrombocytes are PPARδ receptor dependent. PPARδ ligand treatment induces expression of pyruvate dehydrogenase kinase isozyme 4 and downregulates the glucose transporter 1 in VSMCs, thus impairing the ability of VSMCs to provide the increased energy demands required for growth factor–stimulated proliferation and migration.

Conclusions—
In contrast to commonly used drugs for stent coating, PPARδ ligands not only inhibit inflammatory response and proliferation of VSMCs but also prevent thrombocyte activation and support vessel re-endothelialization. Thus, pharmacological PPARδ activation could be a promising novel strategy to improve drug-eluting coronary stents outcomes.
Physically Plausible Methods for Projecting Changes in Great Lakes Water Levels under Climate Change Scenarios
Authors: Lofgren Brent M. , Rouhana Jonathan 
Published: June 2016

Abstract
A method for projecting the water levels of the Laurentian Great Lakes under scenarios of human-caused climate change, used almost to the exclusion of other methods in the past, relies very heavily on the large basin runoff model (LBRM) as a component for determining the water budget for the lake system. This model uses near-surface air temperature as a primary predictor of evapotranspiration (ET); as in previous published work, it is shown here that the model’s very high sensitivity to temperature causes it to overestimate ET in a way that is greatly at variance with the fundamental principle of conservation of energy at the land surface. The traditional formulation is characterized here as being equivalent to having several suns in the virtual sky created by LBRM. More physically based methods show, relative to the traditional method, often astoundingly less potential ET and less ET, more runoff from the land and net basin supply for the lake basins, and higher lake water levels in the future. Using various methods of estimating the statistical significance, it is found that, at minimum, these discrepancies in results are significant at the 99.998% level. The lesson for the larger climate impact community is to use caution about whether an impact is forced directly by air temperature itself or is significantly forced by season or latitude independently of temperature. The results here apply only to the water levels of the Great Lakes and the hydrology of its basin and do not affect larger questions of climate change.