Documents published in 2017 : Scipedia

Fast vector quantization using a Bat algorithm for image compression
C. Karri, U. Jena

Collection of Engineering Science and Technology, an International Journal (2017).

Abstract
Linde–Buzo–Gray (LBG), a traditional method of vector quantization (VQ) generates a local optimal codebook which results in lower PSNR value. The performance of vector quantization (VQ) depends on the appropriate codebook, so researchers proposed optimization techniques for global codebook generation. Particle swarm optimization (PSO) and Firefly algorithm (FA) generate an efficient codebook, but undergoes instability in convergence when particle velocity is high and non-availability of brighter fireflies in the search space respectively. In this paper, we propose a new algorithm called BA-LBG which uses Bat Algorithm on initial solution of LBG. It produces an efficient codebook with less computational time and results very good PSNR due to its automatic zooming feature using adjustable pulse emission rate and loudness of bats. From the results, we observed that BA-LBG has high PSNR compared to LBG, PSO-LBG, Quantum PSO-LBG, HBMO-LBG and FA-LBG, and its average convergence speed is 1.841 times faster than HBMO-LBG and FA-LBG but no significance difference with PSO.
Abstract
Linde–Buzo–Gray (LBG), a traditional method of vector quantization (VQ) generates a local optimal codebook which results in lower PSNR value. The performance of vector [...]
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Impact of chemical reaction on Cu, Al2 O3 and SWCNTs–nanofluid flow under slip conditions
R. Kandasamy, R. Mohamad, M. Ismoen

Collection of Engineering Science and Technology, an International Journal (2017).

Abstract
Single walled carbon nanotube, alumina and copper nanoparticles on convective mass transfer in the presence of base fluid (water) over a horizontal plate are investigated numerically. The governing partial differential equations with auxiliary conditions are reduced into the system of coupled ordinary differential equations via similarity transformation and it has been solved numerically using fourth or fifth order Runge–Kutta–Fehlberg method with shooting technique. The results display that the diffusion boundary layer thickness of the water based Cu and SWCNTs is stronger than Al2 O3 –water with increase of chemical reaction.
Abstract
Single walled carbon nanotube, alumina and copper nanoparticles on convective mass transfer in the presence of base fluid (water) over a horizontal plate are investigated [...]
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Comparison of reliability techniques of parametric and non-parametric method
C. Kalaiselvan, L. Rao

Collection of Engineering Science and Technology, an International Journal (2017).

Abstract
Reliability of a product or system is the probability that the product performs adequately its intended function for the stated period of time under stated operating conditions. It is function of time. The most widely used nano ceramic capacitor C0G and X7R is used in this reliability study to generate the Time-to failure (TTF) data. The time to failure data are identified by Accelerated Life Test (ALT) and Highly Accelerated Life Testing (HALT). The test is conducted at high stress level to generate more failure rate within the short interval of time. The reliability method used to convert accelerated to actual condition is Parametric method and Non-Parametric method. In this paper, comparative study has been done for Parametric and Non-Parametric methods to identify the failure data. The Weibull distribution is identified for parametric method, Kaplan–Meier and Simple Actuarial Method are identified for non-parametric method. The time taken to identify the mean time to failure (MTTF) in accelerating condition is the same for parametric and non-parametric method with relative deviation.
Abstract
Reliability of a product or system is the probability that the product performs adequately its intended function for the stated period of time under stated operating conditions. [...]
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Parametric simulation and experimental analysis of earth air heat exchanger with solar air heating duct
S. Jakhar, R. Misra, M. Soni, N. Gakkhar

Collection of Engineering Science and Technology, an International Journal (2017).

Abstract
Earth air heat exchanger (EAHE) systems are insufficient to meet the thermal comfort requirements in winter conditions. The low heating potential of such systems can be improved by integrating the system with solar air heating duct (SAHD). The aim of this paper is to present a model to estimate the heating potential for EAHE system with and without SAHD. The model is generated using TRNSYS 17 simulation tool and validated against experimental investigation on an experimental set-up in Ajmer, India. The experiment was done during the winter season, where the system was evaluated for different inlet flow velocities, length and depth of buried pipe. From the experimentation, it was observed that the depth of 3.7 m is sufficient for pipe burial and the 34 m length of pipe is sufficient to get optimum EAHE outlet temperature. It is also observed that increase in flow velocity results in drop in EAHE outlet temperature, while room temperature is found to increase for higher velocities (5 m/s). The COP of the system also increased up to 6.304 when assisted with solar air heating duct. The results obtained from the experiment data are in good agreement with simulated results within the variation of up to 7.9%.
Abstract
Earth air heat exchanger (EAHE) systems are insufficient to meet the thermal comfort requirements in winter conditions. The low heating potential of such systems can be improved [...]
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An improved energy aware distributed unequal clustering protocol for heterogeneous wireless sensor networks
V. Gupta, R. Pandey

Collection of Engineering Science and Technology, an International Journal (2017).

Abstract
In this paper, an improved version of the energy aware distributed unequal clustering protocol (EADUC) is projected. The EADUC protocol is commonly used for solving energy hole problem in multi-hop wireless sensor networks. In the EADUC, location of base station and residual energy are given importance as clustering parameters. Based on these parameters, different competition radii are assigned to nodes. Herein, a new approach has been proposed to improve the working of EADUC, by electing cluster heads considering number of nodes in the neighborhood in addition to the above two parameters. The inclusion of the neighborhood information for computation of the competition radii provides better balancing of energy in comparison with the existing approach. Furthermore, for the selection of next hop node, the relay metric is defined directly in terms of energy expense instead of only the distance information used in the EADUC and the data transmission phase has been extended in every round by performing the data collection number of times through use of major slots and mini-slots. The methodology used is of retaining the same clusters for a few rounds and is effective in reducing the clustering overhead. The performance of the proposed protocol has been evaluated under three different scenarios and compared with existing protocols through simulations. The results show that the proposed scheme outperforms the existing protocols in terms of network lifetime in all the scenarios.
Abstract
In this paper, an improved version of the energy aware distributed unequal clustering protocol (EADUC) is projected. The EADUC protocol is commonly used for solving energy [...]
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Multiple-valued logic design based on the multiple-peak BiCMOS-NDR circuits
K. Gan, J. Lu, W. Yeh, Y. Chen, Y. Chen

Collection of Engineering Science and Technology, an International Journal (2017).

Abstract
Three different multiple-valued logic (MVL) designs using the multiple-peak negative-differential-resistance (NDR) circuits are investigated. The basic NDR element, which is made of several Si-based metal-oxide-semiconductor field-effect-transistor (MOS) and SiGe-based heterojunction-bipolar-transistor (HBT) devices, can be implemented by using a standard BiCMOS process. These MVL circuits are designed based on the triggering-pulse control, saw-tooth input signal, and peak-control methods, respectively. However, there are some transient states existing between the multiple stable levels for the first two methods. These states might affect the circuit function in practical application. As a result, our proposed peak-control method for the MVL design can be used to overcome these transient states.
Abstract
Three different multiple-valued logic (MVL) designs using the multiple-peak negative-differential-resistance (NDR) circuits are investigated. The basic NDR element, which [...]
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Numerical study on flow separation in 90° pipe bend under high Reynolds number by k-ε modelling
P. Dutta, S. Saha, N. Nandi, N. Pal

Collection of Engineering Science and Technology, an International Journal (2017).

Abstract
The present paper makes an effort to find the flow separation characteristics under high Reynolds number in pipe bends. Single phase turbulent flow through pipe bends is investigated using k-ε turbulence model. After the validation of present model against existing experimental results, a detailed study has been performed to study the influence of Reynolds number on flow separation and reattachment. The separation region and the velocity field of the primary and the secondary flows in different sections have been illustrated. Numerical results show that flow separation can be clearly visualized for bend with low curvature ratio. Distributions of the velocity vector show the secondary motion clearly induced by the movement of fluid from inner to outer wall of the bend leading to flow separation. This paper provides numerical results to understand the flow characteristics of fluid flow in 90° bend pipe.
Abstract
The present paper makes an effort to find the flow separation characteristics under high Reynolds number in pipe bends. Single phase turbulent flow through pipe bends is investigated [...]
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Application of grey fuzzy logic for the optimization of CNC milling parameters for Al–4.5%Cu–TiC MMCs with multi-performance characteristics
B. Das, S. Roy, R. Rai, S. Saha

Collection of Engineering Science and Technology, an International Journal (2017).

Abstract
With the major application of MMCs, it is thus necessary to develop an appropriate technology for their efficient machining. Milling is the most common and versatile technology among different machining processes, characterized by an extensive range of metal cutting capacity that places it in a central role in the manufacturing industries. In the present study an attempt has been made to find out the most optimal level of process parameters for CNC milling of Al–4.5%Cu–TiC metal matrix composites using grey-fuzzy algorithm. Taguchis L25 orthogonal array design is used for performing CNC milling operation on the composite plates. The Grey fuzzy optimization of CNC milling parameters consist of three different output characteristics, such as, cutting force Fc, surface roughness Ra and surface roughness Rz. It was found that a cutting speed of 600 rpm, feed of 40 mm/min and a depth of cut of 0.30 mm is the optimal combination of CNC milling parameters that has produced a high value of grey fuzzy reasoning grade of 0.8191 which is close to the reference value. ANOVA analysis is carried out and it is found that among three different process parameters, the cutting speed played a major role on the determination of GFRG.
Abstract
With the major application of MMCs, it is thus necessary to develop an appropriate technology for their efficient machining. Milling is the most common and versatile technology [...]
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Test case minimization approach using fault detection and combinatorial optimization techniques for configuration-aware structural testing
B. Ahmed

Collection of Engineering Science and Technology, an International Journal (2017).

Abstract
This paper presents a technique to minimize the number of test cases in configuration-aware structural testing. Combinatorial optimization is used first to generate an optimized test suite by sampling the input configuration. Second, for further optimization, the generated test suite is filtered based on an adaptive mechanism by using a mutation testing technique. The initialized test suite is optimized using cuckoo search (CS) along with combinatorial approach, and mutation testing is used to seed different faults to the software-under-test, as well as to filter the test cases based on the detected faults. To measure the effectiveness of the technique, an empirical study is conducted on a software system. The technique proves its effectiveness through the conducted case study. The paper also shows the application of combinatorial optimization and CS to the software testing.
Abstract
This paper presents a technique to minimize the number of test cases in configuration-aware structural testing. Combinatorial optimization is used first to generate an optimized [...]
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Optimizing real power loss and voltage stability limit of a large transmission network using firefly algorithm
P. Balachennaiah, M. Suryakalavathi, P. Nagendra

Collection of Engineering Science and Technology, an International Journal (2017).

Abstract
This paper proposes a Firefly algorithm based technique to optimize the control variables for simultaneous optimization of real power loss and voltage stability limit of the transmission system. Mathematically, this issue can be formulated as nonlinear equality and inequality constrained optimization problem with an objective function integrating both real power loss and voltage stability limit. Transformers taps, unified power flow controller and its parameters have been included as control variables in the problem formulation. The effectiveness of the proposed algorithm has been tested on New England 39-bus system. Simulation results obtained with the proposed algorithm are compared with the real coded genetic algorithm for single objective of real power loss minimization and multi-objective of real power loss minimization and voltage stability limit maximization. Also, a classical optimization method known as interior point successive linear programming technique is considered here to compare the results of firefly algorithm for single objective of real power loss minimization. Simulation results confirm the potentiality of the proposed algorithm in solving optimization problems.
Abstract
This paper proposes a Firefly algorithm based technique to optimize the control variables for simultaneous optimization of real power loss and voltage stability limit of the [...]
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Analysis of enhancement in available power transfer capacity by STATCOM integrated SMES by numerical simulation studies
S. Ananthavel, S. Padmanaban, S. Shanmugham, F. Blaabjerg, A. Ertas, V. Fedak

Collection of Engineering Science and Technology, an International Journal (2017).

Abstract
Power system researches are mainly focused in enhancing the available power capacities of the existing transmission lines. But still, no prominent solutions have been made due to several factors that affect the transmission lines which include the length, aging of the cables and losses on generation, transmission and distribution etc. This paper exploited the integration of static synchronous compensator (STATCOM) and superconducting magnetic energy storage (SMES) which is then connected to existing power transmission line for enhancing the available power transfer capacity (ATC). STATCOM is power electronic voltage source converter (VSC) which is connected to the transmission system for shunt reactive power and harmonics compensation. SMES is a renowned clean energy storage technology. Feasibility of the proposed power system can control the real as well as reactive power flow independently between the transmission lines and STATCOM-(SMES) units. Complete proposed power system is implemented in numerical simulation software (Matlab/Simulink) and its performance is validated based on obtained investigation results.
Abstract
Power system researches are mainly focused in enhancing the available power capacities of the existing transmission lines. But still, no prominent solutions have been made [...]
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Mechanical strength development of mortars containing volcanic scoria-based binders with different fineness
A. al-Swaidani, S. Aliyan, N. Adarnaly

Collection of Engineering Science and Technology, an International Journal (2017).

Abstract
The benefits of using natural pozzolan as cement replacement are often associated with shortcomings such as the need to moist-curing for longer time and a reduction of strength at early ages. The objective of the study is to investigate the influence of binder fineness on the mechanical strength development of scoria-based binder mortars. In the study, mortar specimens have been produced with four types of binder: one plain Portland cement (control) and three scoria-based binders with three replacement levels: 25%, 30% and 35%, respectively. All scoria-based binders have been inter-ground into four different Blaine fineness: 2400, 3200, 4200 and 5100 cm2 /g. The development of the compressive and flexural tensile strength of all mortar specimens with curing time has been investigated. The effects of the Blaine fineness of the scoria-based blended cement on the compressive and flexural strengths of mortar have been evaluated at curing ages of 2, 7, 28 and 90 days, respectively. Particle size distribution measured by a laser diffractometer has been considered in the study. Test results revealed that there is a decrease in strength with increasing amounts of scoria. In addition, there was found an increase in strength with increasing the Blaine fineness values. No direct relationship between Blaine and particle size distribution was observed. Effects of Blaine fineness on some physical properties of blended cements such as water demand, setting times and soundness have also been investigated. Further, an estimation equation for strength development incorporating the effects of fineness measured either by Blaine or by particle size distribution has been derived by the authors.
Abstract
The benefits of using natural pozzolan as cement replacement are often associated with shortcomings such as the need to moist-curing for longer time and a reduction of strength [...]
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Comparison of different pressure waveforms for heat transfer performance of oscillating flow in a circular cylinder
M. Abdulhameed, D. Vieru, S. Shafie

Collection of Engineering Science and Technology, an International Journal (2017).

Abstract
In the present investigation, an oscillating motion of unsteady Burgers fluid in a circular cylinder was modeled with different pressure waveforms. Three different waveforms are considered: the case of a trapezoidal, triangular and sinusoidal waveform. Analytical solutions of velocity and temperature distribution are obtained for an oscillating laminar flow, which can be used to analyze the effects of flow type on the heat transfer performance. The limiting cases have been considered to examine the heat transfer performance of four different non-Newtonian fluids. Results show that the heat transfer of the oscillating flow depends on the fluid material parameter, Prandtl number, amplitude oscillating waveform and radial coordinate. The trapezoidal and sinusoidal waveforms of oscillating motion can result in a higher heat transfer performance.
Abstract
In the present investigation, an oscillating motion of unsteady Burgers fluid in a circular cylinder was modeled with different pressure waveforms. Three different waveforms [...]
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Flower pollination algorithm to solve combined economic and emission dispatch problems
A. Abdelaziz, E. Ali, S. Elazim

Collection of Engineering Science and Technology, an International Journal (2017).

Abstract
Economic Load Dispatch (ELD) is the process of allocating the required load between the available generation units such that the cost of operation is minimized. The ELD problem is formulated as a nonlinear constrained optimization problem with both equality and inequality constraints. The dual-objective Combined Economic Emission Dispatch (CEED) problem is considering the environmental impacts that accumulated from emission of gaseous pollutants of fossil-fuelled power plants. In this paper, an implementation of Flower Pollination Algorithm (FPA) to solve ELD and CEED problems in power systems is discussed. Results obtained by the proposed FPA are compared with other optimization algorithms for various power systems. The results introduced in this paper show that the proposed FPA outlasts other techniques even for large scale power system considering valve point effect in terms of total cost and computational time.
Abstract
Economic Load Dispatch (ELD) is the process of allocating the required load between the available generation units such that the cost of operation is minimized. The ELD problem [...]
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Facing Challenges Together
Z. Zhong, R. Reddy

Collection of Engineering (2017).
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The Shandong Shidao Bay 200 MWe High-Temperature Gas-Cooled Reactor Pebble-Bed Module (HTR-PM) Demonstration Power Plant: An Engineering and Technological Innovation
Z. Zhang, Y. Dong, F. Li, Z. Zhang, H. Wang, X. Huang, H. Li, B. Liu, X. Wu, H. Wang, X. Diao, H. Zhang, J. Wang

Collection of Engineering (2017).

Abstract
After the first concrete was poured on December 9, 2012 at the Shidao Bay site in Rongcheng, Shandong Province, China, the construction of the reactor building for the worlds first high-temperature gas-cooled reactor pebble-bed module (HTR-PM) demonstration power plant was completed in June, 2015. Installation of the main equipment then began, and the power plant is currently progressing well toward connecting to the grid at the end of 2017. The thermal power of a single HTR-PM reactor module is 250 MWth, the helium temperatures at the reactor core inlet/outlet are 250/750 °C, and a steam of 13.25 MPa/567 °C is produced at the steam generator outlet. Two HTR-PM reactor modules are connected to a steam turbine to form a 210 MWe nuclear power plant. Due to Chinas industrial capability, we were able to overcome great difficulties, manufacture first-of-a-kind equipment, and realize series major technological innovations. We have achieved successful results in many aspects, including planning and implementing R&D, establishing an industrial partnership, manufacturing equipment, fuel production, licensing, site preparation, and balancing safety and economics, these obtained experiences may also be referenced by the global nuclear community.
Abstract
After the first concrete was poured on December 9, 2012 at the Shidao Bay site in Rongcheng, Shandong Province, China, the construction of the reactor building for the worlds [...]
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Chinas Urban Infrastructure Challenges
Y. Pan

Collection of Engineering (2017).
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Health in an Aging World: What Should We Do?
Y. Wen

Collection of Engineering (2017).
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Sustainable Management of Water Resources
Y. Qian

Collection of Engineering (2017).
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Design and R&D Progress of China Lead-Based Reactor for ADS Research Facility
Y. Wu

Collection of Engineering (2017).

Abstract
In 2011, the Chinese Academy of Sciences launched an engineering project to develop an accelerator-driven subcritical system (ADS) for nuclear waste transmutation. The China Lead-based Reactor (CLEAR), proposed by the Institute of Nuclear Energy Safety Technology, was selected as the reference reactor for ADS development, as well as for the technology development of the Generation IV lead-cooled fast reactor. The conceptual design of CLEAR-I with 10 MW thermal power has been completed. KYLIN series lead-bismuth eutectic experimental loops have been constructed to investigate the technologies of the coolant, key components, structural materials, fuel assembly, operation, and control. In order to validate and test the key components and integrated operating technology of the lead-based reactor, the lead alloy-cooled non-nuclear reactor CLEAR-S, the lead-based zero-power nuclear reactor CLEAR-0, and the lead-based virtual reactor CLEAR-V are under realization.
Abstract
In 2011, the Chinese Academy of Sciences launched an engineering project to develop an accelerator-driven subcritical system (ADS) for nuclear waste transmutation. The China [...]
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The Progress and Grand Challenge of Urbanization in China
X. Kuangdi

Collection of Engineering (2017).
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HPR1000: Advanced Pressurized Water Reactor with Active and Passive Safety
J. Xing, D. Song, Y. Wu

Collection of Engineering (2017).

Abstract
HPR1000 is an advanced nuclear power plant (NPP) with the significant feature of an active and passive safety design philosophy, developed by the China National Nuclear Corporation. On one hand, it is an evolutionary design based on proven technology of the existing pressurized water reactor NPP, on the other hand, it incorporates advanced design features including a 177-fuel-assembly core loaded with CF3 fuel assemblies, active and passive safety systems, comprehensive severe accident prevention and mitigation measures, enhanced protection against external events, and improved emergency response capability. Extensive verification experiments and tests have been performed for critical innovative improvements on passive systems, the reactor core, and the main equipment. The design of HPR1000 fulfills the international utility requirements for advanced light water reactors and the latest nuclear safety requirements, and addresses the safety issues relevant to the Fukushima accident. Along with its outstanding safety and economy, HPR1000 provides an excellent and practicable solution for both domestic and international nuclear power markets.
Abstract
HPR1000 is an advanced nuclear power plant (NPP) with the significant feature of an active and passive safety design philosophy, developed by the China National Nuclear Corporation. [...]
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Responding to Global Changes as a Community of Common Destiny
X. Du

Collection of Engineering (2017).
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Fitting on the Earth: Challenges of Carbon and Nitrogen Cycle to Preserve the Habitability of the Planet
R. Socolow

Collection of Engineering (2017).
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Informatics: The Frontier of Innovation in Health and Healthcare
M. Coye

Collection of Engineering (2017).
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Human-Centered Mobility: A New Approach to Designing and Improving Our Urban Transport Infrastructure
D. Mitchell, S. Claris, D. Edge

Collection of Engineering (2017).
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In-Vessel Melt Retention of Pressurized Water Reactors: Historical Review and Future Research Needs
W. Ma, Y. Yuan, B. Sehgal

Collection of Engineering (2017).

Abstract
A historical review of in-vessel melt retention (IVR) is given, which is a severe accident mitigation measure extensively applied in Generation III pressurized water reactors (PWRs). The idea of IVR actually originated from the back-fitting of the Generation II reactor Loviisa VVER-440 in order to cope with the core-melt risk. It was then employed in the new deigns such as Westinghouse AP1000, the Korean APR1400 as well as Chinese advanced PWR designs HPR1000 and CAP1400. The most influential phenomena on the IVR strategy are in-vessel core melt evolution, the heat fluxes imposed on the vessel by the molten core, and the external cooling of the reactor pressure vessel (RPV). For in-vessel melt evolution, past focus has only been placed on the melt pool convection in the lower plenum of the RPV, however, through our review and analysis, we believe that other in-vessel phenomena, including core degradation and relocation, debris formation, and coolability and melt pool formation, may all contribute to the final state of the melt pool and its thermal loads on the lower head. By looking into previous research on relevant topics, we aim to identify the missing pieces in the picture. Based on the state of the art, we conclude by proposing future research needs.
Abstract
A historical review of in-vessel melt retention (IVR) is given, which is a severe accident mitigation measure extensively applied in Generation III pressurized water reactors [...]
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Climate Intervention: Possible Impacts on Global Security and Resilience
M. McNutt

Collection of Engineering (2017).
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Insecurity by Design: Todays IoT Device Security Problem
M. O’Neill

Collection of Engineering (2017).
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A Triumph of Science−and Engineering
L. Davis

Collection of Engineering (2017).
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Can Engineers Lead Again?
K. Clarke

Collection of Engineering (2017).
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The Power of an Idea: The International Impacts of the Grand Challenges for Engineering
C. Jr., D. Dowling, J. Zhou

Collection of Engineering (2017).
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A Bright Future for Sustainable Development: Ushered in by Innovation
J. Chen

Collection of Engineering (2017).
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The Future of Nuclear Energy Relies on Integrated Reactor Development Processes
H. Machenaud

Collection of Engineering (2017).
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The Beginnings of Wisdom: Challenges in Engineering Education
H. Atkinson

Collection of Engineering (2017).
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The Traveling Wave Reactor: Design and Development
J. Gilleland, R. Petroski, K. Weaver

Collection of Engineering (2017).

Abstract
The traveling wave reactor (TWR) is a once-through reactor that uses in situ breeding to greatly reduce the need for enrichment and reprocessing. Breeding converts incoming subcritical reload fuel into new critical fuel, allowing a breed-burn wave to propagate. The concept works on the basis that breed-burn waves and the fuel move relative to one another. Thus either the fuel or the waves may move relative to the stationary observer. The most practical embodiments of the TWR involve moving the fuel while keeping the nuclear reactions in one place−sometimes referred to as the standing wave reactor (SWR). TWRs can operate with uranium reload fuels including totally depleted uranium, natural uranium, and low-enriched fuel (e.g., 5.5% 235 U and below), which ordinarily would not be critical in a fast spectrum. Spent light water reactor (LWR) fuel may also serve as TWR reload fuel. In each of these cases, very efficient fuel usage and significant reduction of waste volumes are achieved without the need for reprocessing. The ultimate advantages of the TWR are realized when the reload fuel is depleted uranium, where after the startup period, no enrichment facilities are needed to sustain the first reactor and a chain of successor reactors. TerraPowers conceptual and engineering design and associated technology development activities have been underway since late 2006, with over 50 institutions working in a highly coordinated effort to place the first unit in operation by 2026. This paper summarizes the TWR technology: its development program, its progress, and an analysis of its social and economic benefits.
Abstract
The traveling wave reactor (TWR) is a once-through reactor that uses in situ breeding to greatly reduce the need for enrichment and reprocessing. Breeding converts incoming [...]
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A New Look at Building Facades as Infrastructure
D. Sung

Collection of Engineering (2017).

Abstract
Like the hard surfaces of streets and sidewalks in an urban environment, the vertical and horizontal surface area on the outside of urban buildings contributes to the constant heating of large cities around the world. However, little is done to design this surface to benefit the public sphere. Instead, the facade of a building performs either as a component that focuses only on the quality of comfort for interior occupants, while ignoring effects on the exterior of the building, or as an identifiable aesthetic for the buildings owners. This essay proposes the rethinking of the building facade as a steward of outdoor pedestrian welfare, and the conception of public health as an added function of the building envelope−a concept that may fall into the jurisdiction of public works. If the huge total surface area of a citys buildings is thought of as part of the citys infrastructure, then its public contribution may not only make outdoor areas comfortable, clean, and enjoyable, but also help to alleviate the bigger problem of rising temperatures in cities.
Abstract
Like the hard surfaces of streets and sidewalks in an urban environment, the vertical and horizontal surface area on the outside of urban buildings contributes to the constant [...]
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The Greatest Global Grand Challenge: Preparing Our Next Generations to Solve the Challenges of Tomorrow: International First and the National Academies Partnership
D. Kamen

Collection of Engineering (2017).
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Application of Biomaterials in Cardiac Repair and Regeneration
Z. Cui, B. Yang, R. Li

Collection of Engineering (2017).

Abstract
Cardiovascular disease is a leading cause of death throughout the world. The demand for new therapeutic interventions is increasing. Although pharmacological and surgical interventions dramatically improve the quality of life of cardiovascular disease patients, cheaper and less invasive approaches are always preferable. Biomaterials, both natural and synthetic, exhibit great potential in cardiac repair and regeneration, either as a carrier for drug delivery or as an extracellular matrix substitute scaffold. In this review, we discuss the current treatment options for several cardiovascular diseases, as well as types of biomaterials that have been investigated as potential therapeutic interventions for said diseases. We especially highlight investigations into the possible use of conductive polymers for correcting ischemic heart disease-induced conduction abnormalities, and the generation of biological pacemakers to improve the conduction pathway in heart block.
Abstract
Cardiovascular disease is a leading cause of death throughout the world. The demand for new therapeutic interventions is increasing. Although pharmacological and surgical [...]
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Tumor Molecular Imaging with Nanoparticles
Z. Cheng, X. Yan, X. Sun, B. Shen, S. Gambhir

Collection of Engineering (2017).

Abstract
Molecular imaging (MI) can provide not only structural images using traditional imaging techniques but also functional and molecular information using many newly emerging imaging techniques. Over the past decade, the utilization of nanotechnology in MI has exhibited many significant advantages and provided new opportunities for the imaging of living subjects. It is expected that multimodality nanoparticles (NPs) can lead to precise assessment of tumor biology and the tumor microenvironment. This review addresses topics related to engineered NPs and summarizes the recent applications of these nanoconstructs in cancer optical imaging, ultrasound, photoacoustic imaging, magnetic resonance imaging (MRI), and radionuclide imaging. Key challenges involved in the translation of NPs to the clinic are discussed.
Abstract
Molecular imaging (MI) can provide not only structural images using traditional imaging techniques but also functional and molecular information using many newly emerging [...]
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Good Morning Engineers: A Wake up Call
C. Holliday

Collection of Engineering (2017).
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Marine Renewable Energy Seascape
A. Borthwick

Collection of Engineering (2017).

Abstract
Energy production based on fossil fuel reserves is largely responsible for carbon emissions, and hence global warming. The planet needs concerted action to reduce fossil fuel usage and to implement carbon mitigation measures. Ocean energy has huge potential, but there are major interdisciplinary problems to be overcome regarding technology, cost reduction, investment, environmental impact, governance, and so forth. This article briefly reviews ocean energy production from offshore wind, tidal stream, ocean current, tidal range, wave, thermal, salinity gradients, and biomass sources. Future areas of research and development are outlined that could make exploitation of the marine renewable energy (MRE) seascape a viable proposition, these areas include energy storage, advanced materials, robotics, and informatics. The article concludes with a sustainability perspective on the MRE seascape encompassing ethics, legislation, the regulatory environment, governance and consenting, economic, social, and environmental constraints. A new generation of engineers is needed with the ingenuity and spirit of adventure to meet the global challenge posed by MRE.
Abstract
Energy production based on fossil fuel reserves is largely responsible for carbon emissions, and hence global warming. The planet needs concerted action to reduce fossil fuel [...]
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Tackling Global Grand Challenges in Our Cities
A. Chan

Collection of Engineering (2017).
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The Status of the US High-Temperature Gas Reactors
A. Kadak

Collection of Engineering (2017).

Abstract
In 2005, the US passed the Energy Policy Act of 2005 mandating the construction and operation of a high-temperature gas reactor (HTGR) by 2021. This law was passed after a multiyear study by national experts on what future nuclear technologies should be developed. As a result of the Act, the US Congress chose to develop the so-called Next-Generation Nuclear Plant, which was to be an HTGR designed to produce process heat for hydrogen production. Despite high hopes and expectations, the current status is that high temperature reactors have been relegated to completing research programs on advanced fuels, graphite and materials with no plans to build a demonstration plant as required by the US Congress in 2005. There are many reasons behind this diminution of HTGR development, including but not limited to insufficient government funding requirements for research, unrealistically high temperature requirements for the reactor, the delay in the need for a “hydrogen” economy, competition from light water small modular light water reactors, little utility interest in new technologies, very low natural gas prices in the US, and a challenging licensing process in the US for non-water reactors.
Abstract
In 2005, the US passed the Energy Policy Act of 2005 mandating the construction and operation of a high-temperature gas reactor (HTGR) by 2021. This law was passed after a [...]
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The Lead Fast Reactor: An Opportunity for the Future?
A. Alemberti

Collection of Engineering (2017).
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Oral Anticoagulants and Renal Impairment: The Convoluting Dilemma
V. Serebruany

Collection of EBioMedicine (2017).
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Deciphering “B-others”: Novel fusion genes driving B-cell acute lymphoblastic leukemia
S. Izraeli

Collection of EBioMedicine (2017).
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Identification of Immune Activation Profiles That May Predict Morbidity During Antiretroviral Therapy Treated HIV Infection
N. Funderburg

Collection of EBioMedicine (2017).
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The right and wrong of DOKing the nuclear receptor
I. Astsaturov

Collection of EBioMedicine (2017).
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Multifunctional Fanconi proteins, inflammation and the Fanconi phenotype
G. Bagby

Collection of EBioMedicine (2017).
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Huntingtons Disease: The Most Curable Incurable Brain Disorder?
E. Wild

Collection of EBioMedicine (2017).
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The Eyes Have it! Protective Role of Prolactin in the Retina
D. Grattan

Collection of EBioMedicine (2017).
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The Power of an Idea: The International Impacts of the Grand Challenges for Engineering
C. Jr., D. Dowling, J. Zhou

Collection of EBioMedicine (2017).
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Implications of Genetic and Epigenetic Alterations of CDKN2A (p16 ) in Cancer
R. Zhao, B. Choi, M. Lee, A. Bode, Z. Dong

Collection of EBioMedicine (2017).

Abstract
Aberrant gene silencing is highly associated with altered cell cycle regulation during carcinogenesis. In particular, silencing of the CDKN2A tumor suppressor gene, which encodes the p16INK4a protein, has a causal link with several different types of cancers. The p16INK4a protein plays an executional role in cell cycle and senescence through the regulation of the cyclin-dependent kinase (CDK) 4/6 and cyclin D complexes. Several genetic and epigenetic aberrations of CDKN2A lead to enhanced tumorigenesis and metastasis with recurrence of cancer and poor prognosis. In these cases, the restoration of genetic and epigenetic reactivation of CDKN2A is a practical approach for the prevention and therapy of cancer. This review highlights the genetic status of CDKN2A as a prognostic and predictive biomarker in various cancers.
Abstract
Aberrant gene silencing is highly associated with altered cell cycle regulation during carcinogenesis. In particular, silencing of the CDKN2A tumor suppressor gene, which [...]
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Gap Junctions Contribute to Ictal/Interictal Genesis in Human Hypothalamic Hamartomas
J. Wu, M. Gao, S. Rice, C. Tsang, J. Beggs, D. Turner, G. Li, B. Yang, K. Xia, F. Gao, S. Qiu, Q. Liu, J. Kerrigan

Collection of EBioMedicine (2017).

Abstract
Human hypothalamic hamartoma (HH) is a rare subcortical lesion associated with treatment-resistant epilepsy. Cellular mechanisms responsible for epileptogenesis are unknown. We hypothesized that neuronal gap junctions contribute to epileptogenesis through synchronous activity within the neuron networks in HH tissue. We studied surgically resected HH tissue with Western-blot analysis, immunohistochemistry, electron microscopy, biocytin microinjection of recorded HH neurons, and microelectrode patch clamp recordings with and without pharmacological blockade of gap junctions. Normal human hypothalamus tissue was used as a control. Western blots showed increased expression of both connexin-36 (Cx36) and connexin-43 (Cx43) in HH tissue compared with normal human mammillary body tissue. Immunohistochemistry demonstrated that Cx36 and Cx43 are expressed in HH tissue, but Cx36 was mainly expressed within neuron clusters while Cx43 was mainly expressed outside of neuron clusters. Gap-junction profiles were observed between small HH neurons with electron microscopy. Biocytin injection into single recorded small HH neurons showed labeling of adjacent neurons, which was not observed in the presence of a neuronal gap-junction blocker, mefloquine. Microelectrode field recordings from freshly resected HH slices demonstrated spontaneous ictal/interictal-like discharges in most slices. Bath-application of gap-junction blockers significantly reduced ictal/interictal-like discharges in a concentration-dependent manner, while not affecting the action-potential firing of small gamma-aminobutyric acid (GABA) neurons observed with whole-cell patch-clamp recordings from the same patients HH tissue. These results suggest that neuronal gap junctions between small GABAergic HH neurons participate in the genesis of epileptic-like discharges. Blockade of gap junctions may be a new therapeutic strategy for controlling seizure activity in HH patients.
Abstract
Human hypothalamic hamartoma (HH) is a rare subcortical lesion associated with treatment-resistant epilepsy. Cellular mechanisms responsible for epileptogenesis are unknown. [...]
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Corrigendum to “Syk and ye shall find” [EBioMedicine 2 (11) (2015) 190-1591]
B. Wolozin, T. Ikezu

Collection of EBioMedicine (2017).
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Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations
. Wei, H. Guo, M. Ma, R. Markham, X. Yu

Collection of EBioMedicine (2017).

Abstract
Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome MxB restriction without compromise of viral fitness has been undefined. Here, we have discovered that naturally occurring capsid (CA) variants can render HIV-1 resistant to the activity of MxB without losing viral infectivity or the ability to escape from interferon induction. Moreover, these MxB resistant HIV-1 variants do not lose MxB recognition. Surprisingly, MxB resistant CA variants are most commonly found in the Clade C HIV-1 that is the most rapidly expanding Clade throughout the world. Accumulation of MxB resistant mutations is also observed during HIV-1 spreading in human populations. These findings support a potential role for MxB as a selective force during HIV-1 transmission and evolution.
Abstract
Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome [...]
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The Effect of Latency Reversal Agents on Primary CD8 + T Cells: Implications for Shock and Kill Strategies for Human Immunodeficiency Virus Eradication
V. Walker-Sperling, C. Pohlmeyer, P. Tarwater, J. Blankson

Collection of EBioMedicine (2017).

Abstract
Shock and kill strategies involving the use of small molecules to induce viral transcription in resting CD4 + T cells (shock) followed by immune mediated clearance of the reactivated cells (kill), have been proposed as a method of eliminating latently infected CD4 + T cells. The combination of the histone deacetylase (HDAC) inhibitor romidepsin and protein kinase C (PKC) agonist bryostatin-1 is very effective at reversing latency in vitro. However, we found that primary HIV-1 specific CD8 + T cells were not able to eliminate autologous resting CD4 + T cells that had been reactivated with these drugs. We tested the hypothesis that the drugs affected primary CD8 + T cell function and found that both agents had inhibitory effects on the suppressive capacity of HIV-specific CD8 + T cells from patients who control viral replication without antiretroviral therapy (elite suppressors/controllers). The inhibitory effect was additive and multi-factorial in nature. These inhibitory effects were not seen with prostratin, another PKC agonist, either alone or in combination with JQ1, a bromodomain-containing protein 4 inhibitor. Our results suggest that because of their adverse effects on primary CD8 + T cells, some LRAs may cause immune-suppression and therefore should be used with caution in shock and kill strategies.
Abstract
Shock and kill strategies involving the use of small molecules to induce viral transcription in resting CD4 + T cells (shock) followed by immune mediated clearance of the [...]
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LEDGIN-mediated Inhibition of Integrase–LEDGF/p75 Interaction Reduces Reactivation of Residual Latent HIV
L. Vranckx, J. Demeulemeester, S. Saleh, A. Boll, G. Vansant, R. Schrijvers, C. Weydert, E. Battivelli, E. Verdin, A. Cereseto, F. Christ, R. Gijsbers, Z. Debyser

Collection of EBioMedicine (2017).

Abstract
Persistence of latent, replication-competent Human Immunodeficiency Virus type 1 (HIV-1) provirus is the main impediment towards a cure for HIV/AIDS (Acquired Immune Deficiency Syndrome). Therefore, different therapeutic strategies to eliminate the viral reservoirs are currently being explored. We here propose a novel strategy to reduce the replicating HIV reservoir during primary HIV infection by means of drug-induced retargeting of HIV integration. A novel class of integration inhibitors, referred to as LEDGINs, inhibit the interaction between HIV integrase and the LEDGF/p75 host cofactor, the main determinant of lentiviral integration site selection. We show for the first time that LEDGF/p75 depletion hampers HIV-1 reactivation in cell culture. Next we demonstrate that LEDGINs relocate and retarget HIV integration resulting in a HIV reservoir that is refractory to reactivation by different latency-reversing agents. Taken together, these results support the potential of integrase inhibitors that modulate integration site targeting to reduce the likeliness of viral rebound.
Abstract
Persistence of latent, replication-competent Human Immunodeficiency Virus type 1 (HIV-1) provirus is the main impediment towards a cure for HIV/AIDS (Acquired Immune Deficiency [...]
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What Lies Beneath: Antibody Dependent Natural Killer Cell Activation by Antibodies to Internal Influenza Virus Proteins
H. Vanderven, F. Ana-Sosa-Batiz, S. Jegaskanda, S. Rockman, K. Laurie, I. Barr, W. Chen, B. Wines, P. Hogarth, T. Lambe, S. Gilbert, M. Parsons, S. Kent

Collection of EBioMedicine (2017).

Abstract
The conserved internal influenza proteins nucleoprotein (NP) and matrix 1 (M1) are well characterised for T cell immunity, but whether they also elicit functional antibodies capable of activating natural killer (NK) cells has not been explored. We studied NP and M1-specific ADCC activity using biochemical, NK cell activation and killing assays with plasma from healthy and influenza-infected subjects. Healthy adults had antibodies to M1 and NP capable of binding dimeric FcγRIIIa and activating NK cells. Natural symptomatic and experimental influenza infections resulted in a rise in antibody dependent NK cell activation post-infection to the hemagglutinin of the infecting strain, but changes in NK cell activation to M1 and NP were variable. Although antibody dependent killing of target cells infected with vaccinia viruses expressing internal influenza proteins was not detected, opsonising antibodies to NP and M1 likely contribute to an antiviral microenvironment by stimulating innate immune cells to secrete cytokines early in infection. We conclude that effector cell activating antibodies to conserved internal influenza proteins are common in healthy and influenza-infected adults. Given the significance of such antibodies in animal models of heterologous influenza infection, the definition of their importance and mechanism of action in human immunity to influenza is essential.
Abstract
The conserved internal influenza proteins nucleoprotein (NP) and matrix 1 (M1) are well characterised for T cell immunity, but whether they also elicit functional antibodies [...]
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Catecholamines Facilitate Fuel Expenditure and Protect Against Obesity via a Novel Network of the Gut-Brain Axis in Transcription Factor Skn-1 -deficient Mice
S. Ushiama, Y. Ishimaru, M. Narukawa, M. Yoshioka, C. Kozuka, N. Watanabe, M. Tsunoda, N. Osakabe, T. Asakura, H. Masuzaki, K. Abe

Collection of EBioMedicine (2017).

Abstract
Taste signals and nutrient stimuli sensed by the gastrointestinal tract are transmitted to the brain to regulate feeding behavior and energy homeostasis. This system is referred to as the gut-brain axis. Here we show that both brush cells and type II taste cells are eliminated in the gastrointestinal tract of transcription factor Skn-1 knockout (KO) mice. Despite unaltered food intake, Skn-1 KO mice have reduced body weight with lower body fat due to increased energy expenditure. In this model, 24-h urinary excretion of catecholamines was significantly elevated, accompanied by increased fatty acid β-oxidation and fuel dissipation in skeletal muscle and impaired insulin secretion driven by glucose. These results suggest the existence of brain-mediated energy homeostatic pathways originating from brush cells and type II taste cells in the gastrointestinal tract and ending in peripheral tissues, including the adrenal glands. The discovery of food-derived factors that regulate these cells may open new avenues the treatment of obesity and diabetes. Taste signals and nutrient stimuli sensed by the gastrointestinal tract are transmitted to the brain to regulate feeding behavior and energy homeostasis along the gut-brain axis. We propose the concept that taste-receiving cells in the oral cavity and/or food-borne chemicals-receiving brush cells in the gut are involved in regulation of the body weight and adiposity via the brain. The discovery of food-derived factors that regulate these cells may open new avenues for the treatment of obesity and diabetes.
Abstract
Taste signals and nutrient stimuli sensed by the gastrointestinal tract are transmitted to the brain to regulate feeding behavior and energy homeostasis. This system is referred [...]
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Low Circulating Amino Acids and Protein Quality: An Interesting Piece in the Puzzle of Early Childhood Stunting
R. Uauy, D. Suri, S. Ghosh, A. Kurpad, I. Rosenberg

Collection of EBioMedicine (2017).
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A Class of Diacylglycerol Acyltransferase 1 Inhibitors Identified by a Combination of Phenotypic High-throughput Screening, Genomics, and Genetics
K. Tschapalda, Y. Zhang, L. Liu, K. Golovnina, T. Schlemper, T. Eichmann, M. Lal-Nag, U. Sreenivasan, J. McLenithan, S. Ziegler, C. Sztalryd, A. Lass, D. Auld, B. Oliver, H. Waldmann, Z. Li, M. Shen, M. Boxer, M. Beller

Collection of EBioMedicine (2017).

Abstract
Excess lipid storage is an epidemic problem in human populations. Thus, the identification of small molecules to treat or prevent lipid storage-related metabolic complications is of great interest. Here we screened > 320.000 compounds for their ability to prevent a cellular lipid accumulation phenotype. We used fly cells because the multifarious tools available for this organism should facilitate unraveling the mechanism-of-action of active small molecules. Of the several hundred lipid storage inhibitors identified in the primary screen we concentrated on three structurally diverse and potent compound classes active in cells of multiple species (including human) and negligible cytotoxicity. Together with Drosophila in vivo epistasis experiments, RNA-Seq expression profiles suggested that the target of one of the small molecules was diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in the production of triacylglycerols and prominent human drug target. We confirmed this prediction by biochemical and enzymatic activity tests.
Abstract
Excess lipid storage is an epidemic problem in human populations. Thus, the identification of small molecules to treat or prevent lipid storage-related metabolic complications [...]
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A Nexus Consisting of Beta-Catenin and Stat3 Attenuates BRAF Inhibitor Efficacy and Mediates Acquired Resistance to Vemurafenib
T. Sinnberg, E. Makino, M. Krueger, A. Velic, B. Macek, U. Rothbauer, N. Groll, O. Pötz, S. Czemmel, H. Niessner, F. Meier, K. Ikenberg, C. Garbe, B. Schittek

Collection of EBioMedicine (2017).

Abstract
Acquired resistance to second generation BRAF inhibitors (BRAFis), like vemurafenib is limiting the benefits of long term targeted therapy for patients with malignant melanomas that harbor BRAF V600 mutations. Since many resistance mechanisms have been described, most of them causing a hyperactivation of the MAPK- or PI3K/AKT signaling pathways, one potential strategy to overcome BRAFi resistance in melanoma cells would be to target important common signaling nodes. Known factors that cause secondary resistance include the overexpression of receptor tyrosine kinases (RTKs), alternative splicing of BRAF or the occurrence of novel mutations in MEK1 or NRAS. In this study we show that β-catenin is stabilized and translocated to the nucleus in approximately half of the melanomas that were analyzed and which developed secondary resistance towards BRAFi. We further demonstrate that β-catenin is involved in the mediation of resistance towards vemurafenib in vitro and in vivo . Unexpectedly, β-catenin acts mainly independent of the TCF/LEF dependent canonical Wnt-signaling pathway in resistance development, which partly explains previous contradictory results about the role of β-catenin in melanoma progression and therapy resistance. We further demonstrate that β-catenin interacts with Stat3 after chronic vemurafenib treatment and both together cooperate in the acquisition and maintenance of resistance towards BRAFi.
Abstract
Acquired resistance to second generation BRAF inhibitors (BRAFis), like vemurafenib is limiting the benefits of long term targeted therapy for patients with malignant melanomas [...]
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Diagnostic Performance of Bronchoalveolar Lavage Fluid CD4/CD8 Ratio for Sarcoidosis: A Meta-analysis
Y. Shen, C. Pang, Y. Wu, D. Li, C. Wan, Z. Liao, T. Yang, L. Chen, F. Wen

Collection of EBioMedicine (2017).

Abstract
The usefulness of bronchoalveolar lavage fluid (BALF) CD4/CD8 ratio for diagnosing sarcoidosis has been reported in many studies with variable results. Therefore, we performed a meta-analysis to estimate the overall diagnostic accuracy of BALF CD4/CD8 ratio based on the bulk of published evidence. Studies published prior to June 2015 and indexed in PubMed, OVID, Web of Science, Scopus and other databases were evaluated for inclusion. Data on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were pooled from included studies. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Deekss funnel plot was used to detect publication bias. Sixteen publications with 1885 subjects met our inclusion criteria and were included in this meta-analysis. Summary estimates of the diagnostic performance of the BALF CD4/CD8 ratio were as follows: sensitivity, 0.70 (95%CI 0.64–0.75), specificity, 0.83 (95%CI 0.78–0.86), PLR, 4.04 (95%CI 3.13–5.20), NLR, 0.36 (95%CI 0.30–0.44), and DOR, 11.17 (95%CI 7.31–17.07). The area under the SROC curve was 0.84 (95%CI 0.81–0.87). There was no evidence of publication bias. Measuring the BALF CD4/CD8 ratio may assist in the diagnosis of sarcoidosis when interpreted in parallel with other diagnostic factors.
Abstract
The usefulness of bronchoalveolar lavage fluid (BALF) CD4/CD8 ratio for diagnosing sarcoidosis has been reported in many studies with variable results. Therefore, we performed [...]
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Ethnicity matters: A Systematic Review and Meta-Analysis of the Non-Linear Relationship Between Alcohol Consumption and Prevalence and Incidence of Hepatic Steatosis
M. Roerecke, R. Nanau, J. Rehm, M. Neuman

Collection of EBioMedicine (2017).

Abstract
Fatty liver (hepatic steatosis) is one of the most common diseases globally, with increasing prevalence. The role of alcohol consumption in the development of hepatic steatosis has not been systematically examined. We searched Medline, Embase, and ProQuest Dissertations & Theses Global for original data on the relationship between alcohol consumption and hepatic steatosis measured by non-invasive imagery, excluding studies conducted in participants < 18 years, or subgroups related to viral and drug-induced liver disease. We identified 18 articles reporting adjusted data (Japan = 11, other high-income countries = 7). Random-effect categorical meta-analyses (< 20 g/day pure alcohol consumption vs non-drinkers) and dose-response meta-analyses for the whole range of alcohol consumption were conducted. In total, 99, 370 participants and 25, 662 cases of hepatic steatosis were included. In Japan, low alcohol consumption was consistently associated with substantially reduced incidence and prevalence of hepatic steatosis compared to non-drinkers (RR for < 20 g pure alcohol/day = 0.75, 95% CI: 0.71–0.79, I2 = 0%). No overall association was found in other countries (RR = 1.05, 95% CI: 0.86–1.30, I2 = 84%). Dose-response analyses in Japan (up to 80 g/day) showed an inverse relationship in men and a J-shape in women. Alcohol consumption showed a complex association with hepatic steatosis with substantial differences by ethnicity and sex. Low alcohol consumption was beneficial in Japan with good epidemiological evidence, whereas there was no association in other countries. However, heterogeneity was large in countries other than Japan. More and higher quality research in diverse ethnic populations is needed to further clarify this relationship.
Abstract
Fatty liver (hepatic steatosis) is one of the most common diseases globally, with increasing prevalence. The role of alcohol consumption in the development of hepatic steatosis [...]
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One of the immune activation profiles observed in HIV-1-infected adults with suppressed viremia is linked to metabolic syndrome: The ACTIVIH study
C. Psomas, M. Younas, C. Reynes, R. Cezar, P. Portalès, E. Tuaillon, A. Guigues, C. Merle, N. Atoui, C. Fernandez, V. Moing, C. Barbuat, G. Marin, N. Nagot, A. Sotto, J. Eliaou, R. Sabatier, J. Reynes, P. Corbeau

Collection of EBioMedicine (2017).

Abstract
Immune activation in HIV-1-infected individuals is reduced under antiretroviral therapies, but persists, resulting in various morbidities. To better characterize this phenomenon, using a panel of 68 soluble and cell surface markers, we measured the level of activation in circulating CD4+ and CD8+ T cells, B cells, monocytes, NK cells, polynuclear and endothelial cells as well as of inflammation and fibrinolysis in 120 virologic responders over 45 years of age. As compared with age- and sex-matched uninfected individuals, we observed a persistence of activation in all the cell subpopulations analyzed, together with marks of inflammation and fibrinolysis. Two independent hierarchical clustering analyses allowed us to identify five clusters of markers that varied concurrently, and five patient groups, each with the same activation profile. The five groups of patients could be characterized by a marker of CD4+ T cell, CD8+ T cell, NK cell, monocyte activation or of inflammation, respectively. One of these profiles was strongly associated with marks of metabolic syndrome, particularly with hyperinsulinemia (OR 12.17 [95% CI 1.79–82.86], p = 0.011). In conclusion, our study unveils biomarkers linked to metabolic syndrome that could be tested as predictive markers, and opens the way to new therapeutic approaches tailored to each patient group.
Abstract
Immune activation in HIV-1-infected individuals is reduced under antiretroviral therapies, but persists, resulting in various morbidities. To better characterize this phenomenon, [...]
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Chronic Kidney Disease, Time in Therapeutic Range and Adverse Clinical Outcomes in Anticoagulated Patients with Non-valvular Atrial Fibrillation: Observations from the SPORTIF Trials
M. Proietti, D. Lane, G. Lip

Collection of EBioMedicine (2017).

Abstract
Chronic kidney disease (CKD) is highly prevalent in atrial fibrillation (AF) patients and associated with an increased risk of adverse outcomes. Our objectives were to study clinical features associated with CKD in AF patients and the impact of CKD on anticoagulation control, as reflected by time in therapeutic range (TTR). We also determined the impact of CKD and TTR in predicting adverse outcomes. We analysed pooled datasets from SPORTIF III and V trials, including 3646 patients assigned to warfarin with data on renal function. CKD (creatinine clearance < 60 ml/min) was present in 952 (26%) patients. TTR was higher in patients with normal renal function compared to those with CKD (p < 0.001). On logistic analysis, chronic AF and male sex were associated with TTR > 70%, whilst diabetes mellitus, aspirin use and CKD were inversely associated with TTR > 70%. On Cox regression analysis, CKD was an independent predictor for stroke (p = 0.006) and death (p < 0.001). TTR > 70% was independently associated with a lower risk of stroke (p = 0.024), death (p = 0.001) and major bleeding (p = 0.001). CKD is highly prevalent amongst AF patients and a risk factor for stroke and death. Adjusting for CKD, good quality anticoagulation control (TTR > 70%) was an independent predictor for lower risks of stroke, death and major bleeding.
Abstract
Chronic kidney disease (CKD) is highly prevalent in atrial fibrillation (AF) patients and associated with an increased risk of adverse outcomes. Our objectives were to study [...]
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Liver Flukes and the Microbiota in Cancer
L. Osborne, L. WegenerParfrey

Collection of EBioMedicine (2017).
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Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability
J. Munkley, D. Vodak, K. Livermore, K. James, B. Wilson, B. Knight, P. Mccullagh, J. Mcgrath, M. Crundwell, L. Harries, H. Leung, C. Robson, I. Mills, P. Rajan, D. Elliott

Collection of EBioMedicine (2017).

Abstract
Steroid androgen hormones play a key role in the progression and treatment of prostate cancer, with androgen deprivation therapy being the first-line treatment used to control cancer growth. Here we apply a novel search strategy to identify androgen-regulated cellular pathways that may be clinically important in prostate cancer. Using RNASeq data, we searched for genes that showed reciprocal changes in expression in response to acute androgen stimulation in culture, and androgen deprivation in patients with prostate cancer. Amongst 700 genes displaying reciprocal expression patterns we observed a significant enrichment in the cellular process glycosylation. Of 31 reciprocally-regulated glycosylation enzymes, a set of 8 (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3) were significantly up-regulated in clinical prostate carcinoma. Androgen exposure stimulated synthesis of glycan structures downstream of this core set of regulated enzymes including sialyl-Tn (sTn), sialyl LewisX (SLeX ), O -GlcNAc and chondroitin sulphate, suggesting androgen regulation of the core set of enzymes controls key steps in glycan synthesis. Expression of each of these enzymes also contributed to prostate cancer cell viability. This study identifies glycosylation as a global target for androgen control, and suggests loss of specific glycosylation enzymes might contribute to tumour regression following androgen depletion therapy.
Abstract
Steroid androgen hormones play a key role in the progression and treatment of prostate cancer, with androgen deprivation therapy being the first-line treatment used to control [...]
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Decreased Usage of Specific Scrib Exons Defines a More Malignant Phenotype of Breast Cancer With Worsened Survival
G. Metodieva, S. Adoki, B. Lausen, M. Metodiev

Collection of EBioMedicine (2017).

Abstract
SCRIB is a polarity regulator known to be abnormally expressed in cancer at the protein level. Here we report that, in breast cancer, an additional and hidden dimension of deregulations exists: an unexpected SCRIB exon usage pattern appears to mark a more malignant tumor phenotype and significantly correlates with survival. Conserved exons encoding the leucine-rich repeats tend to be overexpressed while others are underused. Mechanistic studies revealed that the underused exons encode part of the protein necessary for interaction with Vimentin and Numa1, a protein which is required for proper positioning of the mitotic spindle. Thus, the inclusion/exclusion of specific SCRIB exons is a mechanistic hallmark of breast cancer, which could potentially be exploited to develop more efficient diagnostics and therapies.
Abstract
SCRIB is a polarity regulator known to be abnormally expressed in cancer at the protein level. Here we report that, in breast cancer, an additional and hidden dimension of [...]
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Will LEDGIN molecules be able to play a role in a cure for HIV infection?
T. Mesplède, M. Wainberg

Collection of EBioMedicine (2017).
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Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor
M. Martínez-Hoyos, E. Perez-Herran, G. Gulten, L. Encinas, D. Álvarez-Gómez, E. Alvarez, S. Ferrer-Bazaga, A. García-Pérez, F. Ortega, I. Angulo-Barturen, J. Rullas-Trincado, D. Ruano, P. Torres, P. Castañeda, S. Huss, R. Menéndez, S. Valle, L. Ballell, D. Barros, S. Modha, N. Dhar, F. Signorino-Gelo, J. McKinney, J. García-Bustos, J. Lavandera, J. Sacchettini, M. Jimenez, N. Martín-Casabona, J. Castro-Pichel, A. Mendoza-Losana

Collection of EBioMedicine (2017).

Abstract
Despite being one of the first antitubercular agents identified, isoniazid (INH) is still the most prescribed drug for prophylaxis and tuberculosis (TB) treatment and, together with rifampicin, the pillars of current chemotherapy. A high percentage of isoniazid resistance is linked to mutations in the pro-drug activating enzyme KatG, so the discovery of direct inhibitors (DI) of the enoyl-ACP reductase (InhA) has been pursued by many groups leading to the identification of different enzyme inhibitors, active against Mycobacterium tuberculosis (Mtb ), but with poor physicochemical properties to be considered as preclinical candidates. Here, we present a series of InhA DI active against multidrug (MDR) and extensively (XDR) drug-resistant clinical isolates as well as in TB murine models when orally dosed that can be a promising foundation for a future treatment.
Abstract
Despite being one of the first antitubercular agents identified, isoniazid (INH) is still the most prescribed drug for prophylaxis and tuberculosis (TB) treatment and, together [...]
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Alcohol and Steatosis: The Japanese Paradox
A. Lonardo, S. Ballestri, D. Romagnoli, F. Nascimbeni

Collection of EBioMedicine (2017).
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Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia
Y. Liu, B. Wang, W. Zhang, J. Huang, B. Li, M. Zhang, L. Jiang, J. Li, M. Wang, Y. Dai, Z. Zhang, Q. Wang, J. Kong, B. Chen, Y. Zhu, X. Weng, Z. Shen, J. Li, J. Wang, X. Yan, Y. Li, Y. Liang, L. Liu, X. Chen, W. Zhang, J. Yan, J. Hu, S. Shen, J. Chen, L. Gu, D. Pei, Y. Li, G. Wu, X. Zhou, R. Ren, . Cheng, J. Yang, K. Wang, S. Wang, J. Zhang, J. Mi, C. Pui, J. Tang, Z. Chen, S. Chen

Collection of EBioMedicine (2017).

Abstract
Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice. Eight gene expression subgroups associated with characteristic genetic abnormalities were identified, including leukemia with MEF2D and ZNF384 fusions in two distinct clusters. In subgroup G4 which was characterized by ERG deletion, DUX4 -IGH fusion was detected in most cases. This comprehensive dataset allowed us to compare the features of molecular pathogenesis between adult and pediatric B-ALL and to identify signatures possibly related to the inferior outcome of adults to that of children. We found that, besides the known discrepancies in frequencies of prognostic markers, adult patients had more cooperative mutations and greater enrichment for alterations of epigenetic modifiers and genes linked to B-cell development, suggesting difference in the target cells of transformation between adult and pediatric patients and may explain in part the disparity in their responses to treatment.
Abstract
Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) were investigated using next-generation sequencing and copy number [...]
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Humoral Immune Pressure Selects for HIV-1 CXC-chemokine Receptor 4-using Variants
N. Lin, O. Gonzalez, L. Registre, C. Becerril, B. Etemad, H. Lu, X. Wu, S. Lockman, M. Essex, S. Moyo, D. Kuritzkes, M. Sagar

Collection of EBioMedicine (2017).

Abstract
Although both C-C chemokine receptor 5 (CCR5)- and CXC chemokine receptor 4 (CXCR4)-using HIV-1 strains cause AIDS, the emergence of CXCR4-utilizing variants is associated with an accelerated decline in CD4 + T cells. It remains uncertain if CXCR4-using viruses hasten disease or if these variants only emerge after profound immunological damage. We show that exclusively CXCR4- as compared to cocirculating CCR5-utilizing variants are less sensitive to neutralization by both contemporaneous autologous plasma and plasma pools from individuals that harbor only CCR5-using HIV-1. The CXCR4-utilizing variants, however, do not have a global antigenic change because they remain equivalently susceptible to antibodies that do not target coreceptor binding domains. Studies with envelope V3 loop directed antibodies and chimeric envelopes suggest that the neutralization susceptibility differences are potentially influenced by the V3 loop. In vitro passage of a neutralization sensitive CCR5-using virus in the presence of autologous plasma and activated CD4 + T cells led to the emergence of a CXCR4-utilizing virus in 1 of 3 cases. These results suggest that in some but not necessarily all HIV-1 infected individuals humoral immune pressure against the autologous virus selects for CXCR4-using variants, which potentially accelerates disease progression. Our observations have implications for using antibodies for HIV-1 immune therapy.
Abstract
Although both C-C chemokine receptor 5 (CCR5)- and CXC chemokine receptor 4 (CXCR4)-using HIV-1 strains cause AIDS, the emergence of CXCR4-utilizing variants is associated [...]
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Small Molecule Inhibitor of CBFβ-RUNX Binding for RUNX Transcription Factor Driven Cancers
A. Illendula, J. Gilmour, J. Grembecka, V. Tirumala, A. Boulton, A. Kuntimaddi, C. Schmidt, L. Wang, J. Pulikkan, H. Zong, M. Parlak, C. Kuscu, A. Pickin, Y. Zhou, Y. Gao, L. Mishra, M. Adli, L. Castilla, R. Rajewski, K. Janes, M. Guzman, C. Bonifer, J. Bushweller

Collection of EBioMedicine (2017).

Abstract
Transcription factors have traditionally been viewed with skepticism as viable drug targets, but they offer the potential for completely novel mechanisms of action that could more effectively address the stem cell like properties, such as self-renewal and chemo-resistance, that lead to the failure of traditional chemotherapy approaches. Core binding factor is a heterodimeric transcription factor comprised of one of 3 RUNX proteins (RUNX1-3) and a CBFβ binding partner. CBFβ enhances DNA binding of RUNX subunits by relieving auto-inhibition. Both RUNX1 and CBFβ are frequently mutated in human leukemia. More recently, RUNX proteins have been shown to be key players in epithelial cancers, suggesting the targeting of this pathway could have broad utility. In order to test this, we developed small molecules which bind to CBFβ and inhibit its binding to RUNX. Treatment with these inhibitors reduces binding of RUNX1 to target genes, alters the expression of RUNX1 target genes, and impacts cell survival and differentiation. These inhibitors show efficacy against leukemia cells as well as basal-like (triple-negative) breast cancer cells. These inhibitors provide effective tools to probe the utility of targeting RUNX transcription factor function in other cancers.
Abstract
Transcription factors have traditionally been viewed with skepticism as viable drug targets, but they offer the potential for completely novel mechanisms of action that could [...]
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“Universal Flu Vaccine”: Can NK Cell-mediated ADCC Tip the Scales?
M. Hassane, C. Paget

Collection of EBioMedicine (2017).
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Gap Junctions and Epileptogenesis: No Laughing Matter
E. Gazzerro, P. Striano

Collection of EBioMedicine (2017).
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Subcellular compartmentalization of docking protein-1 contributes to progression in colorectal cancer
T. Friedrich, M. Söhn, T. Gutting, K. Janssen, H. Behrens, C. Röcken, M. Ebert, E. Burgermeister

Collection of EBioMedicine (2017).

Abstract
Full-length (FL) docking protein-1 (DOK1) is an adapter protein which inhibits growth factor and immune response pathways in normal tissues, but is frequently lost in human cancers. Small DOK1 variants remain in cells of solid tumors and leukemias, albeit, their functions are elusive. To assess the so far unknown role of DOK1 in colorectal cancer (CRC), we generated DOK1 mutants which mimic the domain structure and subcellular distribution of DOK1 protein variants in leukemia patients. We found that cytoplasmic DOK1 activated peroxisome-proliferator-activated-receptor-gamma (PPARγ) resulting in inhibition of the c-FOS promoter and cell proliferation, whereas nuclear DOK1 was inactive. PPARγ-agonist increased expression of endogenous DOK1 and interaction with PPARγ. Forward translation of this cell-based signaling model predicted compartmentalization of DOK1 in patients. In a large series of CRC patients, loss of DOK1 protein was associated with poor prognosis at early tumor stages (*p = 0.001, n = 1492). In tumors with cytoplasmic expression of DOK1, survival was improved, whereas nuclear localization of DOK1 correlated with poor outcome, indicating that compartmentalization of DOK1 is critical for CRC progression. Thus, DOK1 was identified as a prognostic factor for non-metastatic CRC, and, via its drugability by PPARγ-agonist, may constitute a potential target for future cancer treatments.
Abstract
Full-length (FL) docking protein-1 (DOK1) is an adapter protein which inhibits growth factor and immune response pathways in normal tissues, but is frequently lost in human [...]
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Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma
K. Chng, S. Chan, A. Ng, C. Li, A. Jusakul, D. Bertrand, A. Wilm, S. Choo, D. Tan, K. Lim, R. Soetinko, C. Ong, D. Duda, S. Dima, I. Popescu, C. Wongkham, Z. Feng, K. Yeoh, B. Teh, P. Yongvanit, S. Wongkham, V. Bhudhisawasdi, N. Khuntikeo, P. Tan, C. Pairojkul, J. Ngeow, N. Nagarajan

Collection of EBioMedicine (2017).

Abstract
Cholangiocarcinoma (CCA) is the primary cancer of the bile duct system. The role of bile duct tissue microbiomes in CCA tumorigenesis is unestablished. To address this, sixty primary CCA tumors and matched normals, from both liver fluke (Opisthorchis viverrini ) associated (OVa, n = 28) and non-O. viverrini associated (non-OVa, n = 32) cancers, were profiled using high-throughput 16S rRNA sequencing. A distinct, tissue-specific microbiome dominated by the bacterial families Dietziaceae, Pseudomonadaceae and Oxalobacteraceae was observed in bile duct tissues. Systemic perturbation of the microbiome was noted in tumor and paired normal samples (vs non-cancer normals) for several bacterial families with a significant increase in Stenotrophomonas species distinguishing tumors vs paired normals. Comparison of parasite associated (OVa) vs non-associated (non-OVa) groups identified enrichment for specific enteric bacteria (Bifidobacteriaceae, Enterobacteriaceae and Enterococcaceae ). One of the enriched families, Bifidobacteriaceae, was found to be dominant in the O. viverrini microbiome, providing a mechanistic link to the parasite. Functional analysis and comparison of CCA microbiomes revealed higher potential for producing bile acids and ammonia in OVa tissues, linking the altered microbiota to carcinogenesis. These results define how the unique microbial communities resident in the bile duct, parasitic infections and the tissue microenvironment can influence each other, and contribute to cancer.
Abstract
Cholangiocarcinoma (CCA) is the primary cancer of the bile duct system. The role of bile duct tissue microbiomes in CCA tumorigenesis is unestablished. To address this, sixty [...]
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Upregulated LINE-1 Activity in the Fanconi Anemia Cancer Susceptibility Syndrome Leads to Spontaneous Pro-inflammatory Cytokine Production
C. Brégnard, J. Guerra, S. Déjardin, F. Passalacqua, M. Benkirane, N. Laguette

Collection of EBioMedicine (2017).

Abstract
Fanconi Anemia (FA) is a genetic disorder characterized by elevated cancer susceptibility and pro-inflammatory cytokine production. Using SLX4FANCP deficiency as a working model, we questioned the trigger for chronic inflammation in FA. We found that absence of SLX4 caused cytoplasmic DNA accumulation, including sequences deriving from active Long INterspersed Element-1 (LINE-1), triggering the cGAS-STING pathway to elicit interferon (IFN) expression. In agreement, absence of SLX4 leads to upregulated LINE-1 retrotransposition. Importantly, similar results were obtained with the FANCD2 upstream activator of SLX4. Furthermore, treatment of FA cells with the Tenofovir reverse transcriptase inhibitor (RTi), that prevents endogenous retrotransposition, decreased both accumulation of cytoplasmic DNA and pro-inflammatory signaling. Collectively, our data suggest a contribution of endogenous RT activities to the generation of immunogenic cytoplasmic nucleic acids responsible for inflammation in FA. The additional observation that RTi decreased pro-inflammatory cytokine production induced by DNA replication stress-inducing drugs further demonstrates the contribution of endogenous RTs to sustaining chronic inflammation. Altogether, our data open perspectives in the prevention of adverse effects of chronic inflammation in tumorigenesis.
Abstract
Fanconi Anemia (FA) is a genetic disorder characterized by elevated cancer susceptibility and pro-inflammatory cytokine production. Using SLX4FANCP deficiency as a working [...]
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Cognitive Enhancement in Infants Associated with Increased Maternal Fruit Intake During Pregnancy: Results from a Birth Cohort Study with Validation in an Animal Model
F. Bolduc, A. Lau, C. Rosenfelt, S. Langer, N. Wang, L. Smithson, D. Lefebvre, R. Alexander, C. Dickson, A. Li, A. Becker, P. Subbarao, S. Turvey, J. Pei, M. Sears, P. Mandhane

Collection of EBioMedicine (2017).

Abstract
In-utero nutrition is an under-studied aspect of cognitive development. Fruit has been an important dietary constituent for early hominins and humans. Among 808 eligible CHILD-Edmonton sub-cohort subjects, 688 (85%) had 1-year cognitive outcome data. We found that each maternal daily serving of fruit (sum of fruit plus 100% fruit juice) consumed during pregnancy was associated with a 2.38 point increase in 1-year cognitive development (95% CI 0.39, 4.37, p < 0.05). Consistent with this, we found 30% higher learning Performance index (PI) scores in Drosophila offspring from parents who consumed 30% fruit juice supplementation prenatally (PI: 85.7, SE 1.8, p < 0.05) compared to the offspring of standard diet parents (PI: 65.0 SE 3.4). Using the Drosophila model, we also show that the cyclic adenylate monophosphate (cAMP) pathway may be a major regulator of this effect, as prenatal fruit associated cognitive enhancement was blocked in Drosophila rutabaga mutants with reduced Ca2 + -Calmodulin-dependent adenylyl cyclase. Moreover, gestation is a critical time for this effect as postnatal fruit intake did not enhance cognitive performance in either humans or Drosophila . Our study supports increased fruit consumption during pregnancy with significant increases in infant cognitive performance. Validation in Drosophila helps control for potential participant bias or unmeasured confounders.
Abstract
In-utero nutrition is an under-studied aspect of cognitive development. Fruit has been an important dietary constituent for early hominins and humans. Among 808 eligible CHILD-Edmonton [...]
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Non-specific Effects of Vaccines and Stunting: Timing May Be Essential
M. Berendsen, J. Smits, M. Netea, A. Ven

Collection of EBioMedicine (2017).

Abstract
Bacillus Calmette-Guérin (BCG) vaccination possesses effects on health beyond its target disease, the so called “non-specific effects”. We evaluate these effects, as well as the effect of timing of BCG and other vaccinations, on stunting in Sub-Saharan African (SSA) children under five. We use a Big Data design, including cross-sectional data for 368, 450 children from 33 SSA countries. Logistic regression analysis is used with control factors at child, mother, household and context level. Overall, BCG vaccination did not affect stunting in SSA children (OR 1.00 [0.98–1.03]). Timing of BCG vaccination was of importance (βtime = 0.067 [0.061–0.073]): compared to unvaccinated children, BCG was associated with lower odds on stunting for children vaccinated early in life (OR 0.92 [0.89–0.94]) and higher odds for children vaccinated later in infancy (OR 1.64 [1.53–1.76]). Similar findings were done for diphtheria-tetanus-pertussis (DTP)1 and measles vaccination, and when hemoglobin concentration was used as outcome variable. We found a general time-dependent pattern of non-specific effects of vaccination, with positive associations for vaccinations given early in life and negative associations for vaccinations given later in infancy. If confirmed in further research, our findings may provide a new perspective on the non-specific effects of vaccination.
Abstract
Bacillus Calmette-Guérin (BCG) vaccination possesses effects on health beyond its target disease, the so called “non-specific effects”. We evaluate these effects, as [...]
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Nanobodies as Versatile Tools to Understand, Diagnose, Visualize and Treat Cancer
I. Audenhove, J. Gettemans

Collection of EBioMedicine (2017).

Abstract
Since their discovery, nanobodies have been used extensively in the fields of research, diagnostics and therapy. These antigen binding fragments, originating from Camelid heavy-chain antibodies, possess unusual hallmarks in terms of (small) size, stability, solubility and specificity, hence allowing cost-effective production and sometimes outperforming monoclonal antibodies. In this review, we evaluate the current status of nanobodies to study, diagnose, visualize or inhibit cancer-specific proteins and processes. Nanobodies are highly adaptable tools for cancer research as they enable specific modulation of targets, enzymatic and non-enzymatic proteins alike. Molecular imaging studies benefit from the rapid, homogeneous tumor accumulation of nanobodies and their fast blood clearance, permitting previously unattainable fast tumor visualization. Moreover, they are endowed with considerable therapeutic potential as inhibitors of receptor-ligand pairs and deliverers of drugs or drug-loaded nanoparticles towards tumors. More in vivo and clinical studies are however eagerly awaited to unleash their full potential.
Abstract
Since their discovery, nanobodies have been used extensively in the fields of research, diagnostics and therapy. These antigen binding fragments, originating from Camelid [...]
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Leaving History Behind: CD4/CD8 Ratio as a Diagnostic Tool in Sarcoidosis
W. James

Collection of EBioMedicine (2017).
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Gut Bacteria Metabolism Impacts Immune Recovery in HIV-infected Individuals
S. Serrano-Villar, D. Rojo, M. Martínez-Martínez, S. Deusch, J. Vázquez-Castellanos, R. Bargiela, T. Sainz, M. Vera, S. Moreno, V. Estrada, M. Gosalbes, A. Latorre, J. Seifert, C. Barbas, A. Moya, M. Ferrer

Collection of EBioMedicine (2017).

Abstract
While changes in gut microbial populations have been described in human immuno-deficiency virus (HIV)-infected patients undergoing antiretroviral therapy (ART), the mechanisms underlying the contributions of gut bacteria and their molecular agents (metabolites and proteins) to immune recovery remain unexplored. To study this, we examined the active fraction of the gut microbiome, through examining protein synthesis and accumulation of metabolites inside gut bacteria and in the bloodstream, in 8 healthy controls and 29 HIV-infected individuals (6 being longitudinally studied). We found that HIV infection is associated to dramatic changes in the active set of gut bacteria simultaneously altering the metabolic outcomes. Effects were accentuated among immunological ART responders, regardless diet, subject characteristics, clinical variables other than immune recovery, the duration and type of ART and sexual preferences. The effect was found at quantitative levels of several molecular agents and active bacteria which were herein identified and whose abundance correlated with HIV immune pathogenesis markers. Although, we cannot rule out the possibility that some changes are partially a random consequence of the disease status, our data suggest that most likely reduced inflammation and immune recovery is a joint solution orchestrated by both the active fraction of the gut microbiota and the host.
Abstract
While changes in gut microbial populations have been described in human immuno-deficiency virus (HIV)-infected patients undergoing antiretroviral therapy (ART), the mechanisms [...]
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Functional Rescue of Dopaminergic Neuron Loss in Parkinsons Disease Mice After Transplantation of Hematopoietic Stem and Progenitor Cells
W. Altarche-Xifro, U. Vicino, M. Muñoz-Martin, A. Bortolozzi, J. Bové, M. Vila, M. Cosma

Collection of EBioMedicine (2017).

Abstract
Parkinsons disease is a common neurodegenerative disorder, which is due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and for which no definitive cure is currently available. Cellular functions in mouse and human tissues can be restored after fusion of bone marrow (BM)-derived cells with a variety of somatic cells. Here, after transplantation of hematopoietic stem and progenitor cells (HSPCs) in the SNpc of two different mouse models of Parkinsons disease, we significantly ameliorated the dopaminergic neuron loss and function. We show fusion of transplanted HSPCs with neurons and with glial cells in the ventral midbrain of Parkinsons disease mice. Interestingly, the hybrids can undergo reprogramming in vivo and survived up to 4 weeks after transplantation, while acquiring features of mature astroglia. These newly generated astroglia produced Wnt1 and were essential for functional rescue of the dopaminergic neurons. Our data suggest that glial-derived hybrids produced upon fusion of transplanted HSPCs in the SNpc can rescue the Parkinsons disease phenotype via a niche-mediated effect, and can be exploited as an efficient cell-therapy approach.
Abstract
Parkinsons disease is a common neurodegenerative disorder, which is due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and for which no definitive [...]
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Pedestrian Traffic Operations in Urban Networks
M. Zheng, T. Chase, J. Yan, S. Jun, V. Sisiopiku, L. Tian, Y. Zheng, X. Wang, B. Schroeder, Z. Qiu, L. Elefteriadou

Collection of Transportation Research Procedia (2017).

Abstract
The pedestrian mode is an important component of urban networks, and greatly affects the performance of the sidewalks and crosswalks, as well as the entire network traffic operations by interacting with other traffic modes (automobile, bicycle, transit). There have been many studies concerning different aspects of pedestrian behaviors, such as pedestrian walking speed, pedestrian delay, gap acceptance, signal compliance, route choice, etc. The Highway Capacity Manual (HCM) included the pedestrian mode in the HCM 1994 (update to the HCM 1985) and the HCM, 2010 provided several basic technical methodologies for evaluating the pedestrian level of service (LOS) of different urban street facilities. However, it does not fully cover the pedestrian operation in a great detail and it is missing some important findings in recent studies. The objective of this paper is to provide an overview of pedestrian operations in urban networks, to identify the important aspects of pedestrian operation analysis and to provide recommendations for pedestrian facilities in the HCM on the basis of a summary of available U.S. and international literature. The following topics will be discussed: pedestrian movement models, pedestrian delay estimation, pedestrian-vehicle interactions, and pedestrian travel time estimation. The major features of pedestrian movement along urban segments are the walking speed and available space, which were well examined in past studies. Pedestrian delay is one important measure of pedestrian operation, and its estimation models at signalized/unsignalized intersections are presented with respect to different scenarios. Modifications to the delay model in the HCM, 2010 are highlighted. Pedestrian-vehicle interactions highly affect traffic operations. Both driver and pedestrian behaviors in such an interaction were observed in the field and were examined quantitatively. Pedestrian jaywalking behavior was also observed and its impact on traffic is discussed. Pedestrian route choice at the strategic level and crossing location selection at the operational level jointly determine the pedestrian moving path and further affect the travel time at path-level. A model for estimating pedestrian travel time in an urban network is developed and presented. Such a model can be used to evaluate the facility performance as well as serve for pedestrian route selection. This paper identifies the important aspects of pedestrian operation analysis in an urban network and provides several recommendations to the HCM.
Abstract
The pedestrian mode is an important component of urban networks, and greatly affects the performance of the sidewalks and crosswalks, as well as the entire network traffic [...]
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Advanced Evaluation Methods for Variable Speed Limit Systems
W. Ackaah, K. Bogenberger

Collection of Transportation Research Procedia (2017).

Abstract
The variable speed limit (VSL) system has been implemented on many freeways and urban arterials as a link control strategy. Objectives for deploying VSL systems may include giving advance warning, stabilize and smooth traffic (i.e. harmonization). Accuracy and reliability of the messages displayed by VSL systems can “make or break” its successful implementation. The aim of this paper was to present methods for evaluating VSL systems. As VSL systems may be implemented with different control strategies, an approach for assessing different features of the system independently was adopted. In this way, systems with different control strategies can be evaluated. Methods for assessing incident detection, warning and harmonization abilities were presented. A case study on the VSL system on the Autobahn A99 near Munich, Germany was also discussed.
Abstract
The variable speed limit (VSL) system has been implemented on many freeways and urban arterials as a link control strategy. Objectives for deploying VSL systems may include [...]
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Operational Impact of Horizontal and Vertical Alignment of Two-Lane Highways
A. Moreno, C. Llorca, A. Garcia

Collection of Transportation Research Procedia (2017).

Abstract
The Highway Capacity Manual (HCM) defines the level-of-service criteria for two-lane highways based on three performance measures: average travel speed (ATS), percent time spend following (PTSF) and percent of free-flow speed (PFFS). The performance measures are affected by the lack of passing opportunities, which is quantified through adjustment factors depending on the percentage of no passing zones. Passing zones are provided where available sight distance is greater than the minimum passing sight distance, and their length and frequency depend mainly on the physical constrains and cost limitations. HCM current evaluation of traffic performance excludes horizontal alignment variations, which could produce more or less sinuous alignments and thus affect potentially to both average travel speed and percentage time spent following. Moreover, HCM considers terrain type rather than the actual vertical profile, which could overestimate or underestimate the expected traffic performance depending on how accurately the roadway was adapted to the terrain. The objective of the research is to analyze the relationship between highway horizontal alignment, characterized by curvature change rate (CCR), highway vertical alignment, characterized by the gradient change rate, and traffic performance, based on ATS and PTSF. For the research, 25 Spanish two-lane rural highways were selected. Horizontal geometry was obtained from Google Earth using an azimuth-based restitution program. CCR was calculated and used to identify homogenous segments. Vertical alignment was recreated from GPS data. The sample included 112 homogeneous segments and 451 passing zones. After the geometry-based characterization, 20 homogeneous segments were introduced and simulated in the TWOPAS simulation model. TWOPAS was previously calibrated and validated with passing maneuvers data from Spanish highways. Traffic conditions (directional traffic volume, directional split and percentage of heavy vehicles) were varied. The analysis of the simulation results provided models of PTSF and ATS depending on CCR and gradient change rate, among other parameters. The results of this research will help highway designers and practitioners to predict operational performance based on CCR, type of gradient and expected hourly traffic volume, and could be used as management and design criteria.
Abstract
The Highway Capacity Manual (HCM) defines the level-of-service criteria for two-lane highways based on three performance measures: average travel speed (ATS), percent time [...]
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A Local Non-restrictive Ramp Metering Strategy Based on Stochasticity of Capacity
R. Trapp

Collection of Transportation Research Procedia (2017).

Abstract
A local non-restrictive ramp metering strategy PRO is introduced. It is based on the stochasticity of capacity. The ramp metering algorithm shows innovative features: • upstream time shifted measurements for anticipation • measurements are actuated every second • up to three vehicles per green are allowed Details of the theory of this strategy are described in the first part. At freeway B27 three ramp meters with the PRO algorithm were installed. In the second part, based on extensive detailed traffic and accident data the effects on traffic flow and safety are described. The impact is positive regarding vehicle speed, queue duration and length as well as capacity and traffic safety. The improvements of speeds, travel times and capacities are statistically significant. The ramp metering systems are highly cost effective.
Abstract
A local non-restrictive ramp metering strategy PRO is introduced. It is based on the stochasticity of capacity. The ramp metering algorithm shows innovative features: • [...]
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2+1-roads Recent Swedish Capacity and Level-of-Service Experience
T. Bergh, M. Remgård, A. Carlsson, J. Olstam, P. Strömgren

Collection of Transportation Research Procedia (2017).

Abstract
The first Swedish 2+1 median barrier road was opened in 1998. The concept was to retrofit the standard existing two-lane 13 m paved width cross-section at 90 and 110 kph posted speed limit without widening. This design has one continuous lane in each direction, a middle lane changing direction every one to three kilometres with a median barrier separating the two traffic directions. Today over 2 700 km 2+1 median barrier roads are opened for traffic. AADT’s vary from some 3 000 to 20 000 with an average just below 10 000 nowadays normally with 100 kph. The concept has lately been enhanced also to cover the existing 9 m paved width cross-section. The design concept is the same from a driver’s viewpoint, one continuous lane in each direction with a middle lane changing direction and a separating median barrier. This is created by introducing a continuous median barrier and adding overtaking lanes within an overtaking strategy. The differences are the existence of 1+1-sections, less overtaking opportunities and a slightly more narrow cross-section. Some 15 projects are opened. The purpose of this paper is to summarize present knowledge on level-of-service issues as they are presented in Swedish design and assessment guidelines and to give an overview of field measurements and theoretical analytical and simulation studies supporting the recommendations.
Abstract
The first Swedish 2+1 median barrier road was opened in 1998. The concept was to retrofit the standard existing two-lane 13 m paved width cross-section at 90 and 110 kph posted [...]
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Influence of Dynamic Traffic Control Systems and Autonomous Driving on Motorway Traffic Flow
T. Wietholt, J. Harding

Collection of Transportation Research Procedia (2017).

Abstract
As in many other countries, traffic demand on German motorways is continuously rising, especially during peak hours. Enhancing the road infrastructure by building additional lanes or new motorways is cost-intensive and - due to the complex planning process in Germany – extremely tedious. Thus, the government tries to maximise the performance of the existing infrastructure using dynamic control systems. The development and deployment of autonomous driven vehicles can have positive effects on the capacity of road elements. In this study the effect of dynamic control systems on the traffic flow on motorways is analysed in case studies using microscopic traffic simulation. Furthermore it is outlined that autonomous driving in an environment where access to the motorway is limited to autonomous vehicles only can have a positive effect in terms of higher capacities and more harmonized traffic resulting in fewer traffic breakdowns.
Abstract
As in many other countries, traffic demand on German motorways is continuously rising, especially during peak hours. Enhancing the road infrastructure by building additional [...]
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Proposal and Application of Parking Area Performance Measurement Methodology
T. Muramatsu, T. Oguchi

Collection of Transportation Research Procedia (2017).

Abstract
The function of parking areas at expressway rest stops is to provide drivers with opportunities to park their vehicles for their own purposes, so the number of parking spots has been discussed. However, as the number of parking spots increases, the parking area becomes maze-like and the use of the parking spots becomes inefficient. This leads to skepticism that an increase in parking area capacity will contribute to enhancing parking area performance. Meanwhile, one vehicle is able to park in a parking spot when another vehicle exits the area that is fully occupied, so the condition of drop-by traffic at a rest stop can be discussed using the queuing theory by viewing a rest stop as a warehouse. Thus, this study aims to determine the applicability of the queuing theory when discussing drop-by traffic situations, while assuming a first-in first-out (FIFO) condition. For the applicability of the queuing theory of describing parking area performance, this study employed the ETC probe time-stamp data. The observed values from the ETC probe time-stamp data and FIFO assumed time lags are described, and the applicability of the observed ETC time-stamp data to representing the exact conditions was determined by comparing the number of vehicles parked on the hour every hour and those counted by the observed ETC probe time-stamp data. Finally, the applicability of the FIFO assumption was discussed using the correlation between the observed ETC probe time-stamp data and the FIFO assumed time lags calculated by the data. The results indicate that a FIFO assumption could alternate the observed the ETC probe time-stamp data. The number of vehicles staying on the hour every hour can be represented by the calculation results from FIFO assuming time lags. These findings show that it could be possible to determine the congregative situations of an expressway rest stop analyzed by the ingress and egress time-stamp records. Also, this result assumes any contribution to assessing the functional performance by measuring only the number of vehicles entering and exiting a parking area.
Abstract
The function of parking areas at expressway rest stops is to provide drivers with opportunities to park their vehicles for their own purposes, so the number of parking spots [...]
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A Model for Capacity Reduction at Roadwork Zone
P. Strömgren, J. Olstam

Collection of Transportation Research Procedia (2017).

Abstract
This paper presents an investigation of capacity reduction in connection with roadwork. The paper presents a state-of-the-art description on roadwork effects on capacity. The state-of-the art has been used to develop a model for estimation of capacity reduction at roadwork zone on Swedish roads. The model has partly been validated with empirical data from a full scale test at the freeway network in Gothenburg. The studies presented in the literature shows that capacity differs not only between different roadwork designs but also between roadwork with similar design. Thus, one can conclude that there is a high variation between the roadwork zone due to effects of surrounding elements, such as the type of work and external effects such as rain (which affects the capacity even under normal conditions). The differences that exist in the estimation of capacity for motorway sections next to a roadwork zone can be said to consist of four situation-specific variables. These four variables are: the percentage of heavy vehicles, type of road, the width of the remaining lanes and diversion of traffic to the opposite carriageway. An increasing proportion of heavy vehicles have a negative impact on roadwork zone capacity. An increasing complexity of work, from light barrier works to extensive bridge repair, has a negative impact on performance. An increased lane width has a positive effect on capacity. The diversion of traffic to the opposite carriageway is often the cause of the bottleneck and therefore has a significance effect on capacity. The conclusion from the literature review is that the most important parameters that should be incorporated in a Swedish capacity manual for the operation and maintenance of roadwork are: the proportion of heavy traffic, lane width, type of roadwork, number of closed lanes, closed road shoulder, proportion of commuter traffic and length of roadwork zone. In general, there have been (too) few empirical studies focusing on the differences in capacity caused by these situation-specific variables. The paper presents a comparison between the Dutch model for computation of capacity reduction and a composite model of reduction factors from Germany, USA and Denmark. The comparison show that the two models essentially gives the same results. Based on these results a new model was developed. In the developed model, the capacity for the remaining lane is calculated. The paper presents results from a field study in Gothenburg where throughput was measured in three cases during a morning hour and one afternoon hour. The capacity was calculated from the normal site conditions according to historical traffic flow and speed data. The result shows that the empirically estimated confidence interval of capacity reduction is consistent with the reduction calculated with the new model for the different cases. The conclusion is that the model can be used to calculate capacity reductions for different roadwork zone configurations but that validation for more configurations is desirable.
Abstract
This paper presents an investigation of capacity reduction in connection with roadwork. The paper presents a state-of-the-art description on roadwork effects on capacity. [...]
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Harmonization with Variable Speed Limits on Motorways
P. Strömgren, G. Lind

Collection of Transportation Research Procedia (2017).

Abstract
This paper presents an investigation and a state-of-the-art description of traffic effects of harmonization with variable speed limits. Expansion of the E4 south of Stockholm has been carried out during the years 2009-2013. The expansion includes a rearranged lane configuration within the existing road section (25 m) and traffic management systems. Previous design with two lanes and hard shoulder has been replaced with three lanes without shoulder. In addition, the road has been equipped with variable speed limits (with red ring), queue warning system with recommended speed and emergency refuge areas (ERAs). The queue warning functionality was activated in 2011 and harmonization in 2013. Reduced speed variance is an important goal for the traffic management system and is considered to both reduce rear-end collisions and the risk of capacity breakdown. German experience shows that harmonization affects capacity down to about 80 kph. English experience is that the harmonization and monitoring can reduce accidents by 40% at normal speed of 70 mph (112 kph). Germany and England decrease the speed with approximately 20 kph at the degree of saturation of 0.7 to let the flow be harmonized before the traffic density has increased too much. A measure to describe disturbed and undisturbed traffic can be the relative change in the standard deviation of the average speed for 5-minutes periods updated each minute, called CVS. In case of accidents, CVS may be twice as high as normal. The standard deviation of all vehicles is calculated for each minute and aggregated into five-minute periods. The harmonization settings on E4 south of Stockholm has been iteratively designed and ultimately set to 325 vehicles/5 min, which has worked well. The variable speed limit is reduced to 80 kph and stabilizes the flow. The harmonization indicates a potential risk of queue for the road users, which becomes more prepared if the queue warning is activated further along the road due low speed and the risk of sudden braking. The main results can be summarized as follows: • The average speed during rush hour on weekdays has increased by 2.5 kph after the installation of the traffic control system, of which 25% is assumed to be attributable to the traffic management system • The harmonization has delayed the onset of collapse. During the periods in which harmonization has not been activated but there has been a breakdown, it is considered that harmonisation would have passed the half period and then collapse would occurred. • The accidents have been reduced by half, of which 25% is assumed to depend on traffic management (harmonization, queue warning and VMS) The queue warning has worked well, but could be improved by also exploiting the so-called CVS. The measure reveals the instabilities in the flow, sometimes tens of minutes before the AID-alarm due low speeds is enabled. In rush hour when traffic is dense (> 325 vehicles/5 min) and harmonization has already been activated the CVS measure gives further information, which could be exploited to improve the queue warning algorithm.
Abstract
This paper presents an investigation and a state-of-the-art description of traffic effects of harmonization with variable speed limits. Expansion of the E4 south of Stockholm [...]
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A Methodology for Signal Timing Estimation Based on Low Frequency Floating Car Data: Analysis of Needed Sample Sizes and Influencing Factors
S. Axer, B. Friedrich

Collection of Transportation Research Procedia (2017).

Abstract
The objective of this paper is to analyze the estimation quality of a staged methodology, that allows the estimation of signal timing information like cycle length, green and red time intervals for time-dependent fixed-time controlled and actuated intersections based on low-frequency and sparse floating car data (FCD). The paper exemplifies, based on simulated dataset, the estimation approach, which assumes as a principle condition the daily repetition of similar signal plans, whereby identical daytime and workday periods are aggregated to reach a sufficient trajectory density. The established concept utilizes efficiently small amounts of FCD trajectories that cover typical sampling intervals between 15-45 seconds. The introduced approach considers three processing stages. Firstly, map matching, data decomposition and stop line estimation are required. Secondly, trajectories’ stop line crossing times are calculated, whereby crossing times of all trajectories are iteratively projected by the application of a modulo operation into the time scale of potential cycle lengths. A statistical data analysis is carried out to estimate cycle lengths and daytime slices with similar signal program patterns. Finally, the last stage of the used approach considers the precise estimation of red and green time intervals based on a histogram analysis. The paper conclusively analyzes the signal program estimation quality considering different degrees of saturation and trajectory sample sizes.
Abstract
The objective of this paper is to analyze the estimation quality of a staged methodology, that allows the estimation of signal timing information like cycle length, green [...]
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Traffic Flow Quality from the Users Perspective
S. Hohmann, J. Geistefeldt

Collection of Transportation Research Procedia (2017).

Abstract
Achieving the maximum utilization of the existing infrastructure is an essential goal of traffic management for both freeways and the urban road network. Reliable and explicit information about the current traffic condition are required for using the road network efficiently. So far, the lack of a uniform classification scheme results in a time consuming process of coordination between different stakeholders developing and implementing control strategies and providing traffic information. In this study, a uniform concept is developed defining the traffic conditions on freeways and urban roads. This classification scheme is applicable for all stakeholders (e.g. road authorities, broadcasting services, private service providers) and can be used in both infrastructure-based and vehicle-based applications. In order to determine an appropriate traffic flow parameter for a comprehensible representation of the traffic condition, extensive data from freeways and urban roads in Germany were collected and analyzed. The empirical basis is provided by segment-based and local data obtained with different detection methods. As expected, the average speed per segment leads to a more precise description of the traffic condition than local speed values from stationary detectors. Test runs with probe vehicles were made using a GPS tracking device to record the floating cars driving speed. During the test runs, a subjective evaluation of the traffic flow quality was provided by different passengers (probands) in the vehicle. In total, over 15000 sets of travel speed data with associated grading of the experienced traffic flow quality were analyzed to develop a six-step classification scheme. Based on different approaches, threshold values of the average travel speed were determined depending on the type of road and the speed limit. This uniform classification scheme can offer valuable decision guidance for traffic management strategies. For providing more comprehensible traffic information for the road users, the developed scheme was transferred to a three-step system, easily illustrated by the colors green, yellow and red.
Abstract
Achieving the maximum utilization of the existing infrastructure is an essential goal of traffic management for both freeways and the urban road network. Reliable and explicit [...]
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The Development and Practice of China Highway Capacity Research
R. Zhou, L. Zhong, N. Zhao, J. Fang, H. Chai, J. Zhou, W. Li, B. Li

Collection of Transportation Research Procedia (2017).

Abstract
The achievements of the project “highway capacity research” in the “9th Five-Year” period in China have supported the current “Highway Engineering Technical Standard” and “The Specification of Highway Design”, which are the most important specifications for the design and construction of highway in China and strongly supported the construction and operation of tens of thousands of kilometers of highway. At present, Chinas highway industry is still in a period of rapid development. By the end of 2014, the total mileages of highway network exceeds 4, 400, 000 kilometers, and the freeway’s mileage is 112, 000 kilometers. With this rapid development of highway system, since the “9th Five-Year”, the highway capacity research in China is still ongoing. The report “Development and Practice of China Highway Capacity Research” provides a brief introduction of research history, on-going research and future work of highway capacity research and application in China. Firstly, four main stages of highway capacity research in China are proposed. Stage 1 (before 1990) is called the beginning stage. Stage 2 (1991-2000) is extensive research stage, in which large-scale research is conducted based on the foreign advanced practical experience, such as USA’s. Stage 3 (2001-2010) is in-depth focus on important facilities, and stage 4 (2011 till now) is the adjustment and updating of achievements stage. The report introduces the main representative research projects of each stage and corresponding achievements. Besides, the report also presents the current achievements of China Highway Capacity Manual (CHCM) which is still written. The structure of the manual as well as the new added content such as the capacity analysis of work zone is introduced. The report mainly introduces the achievements of the chapter of basic expressway section in CHCM, which include the new speed – volume relationship of freeway, and the level of service index and classification, and vehicle classification and equivalent coefficients as well as capacity analysis procedure and method. Finally, the report introduces the prospect of future direction of capacity research in China, such as traffic characteristics and capacity dynamic change patterns in huge volume of free pass in holidays etc.
Abstract
The achievements of the project “highway capacity research” in the “9th Five-Year” period in China have supported the current “Highway Engineering Technical Standard” [...]
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