bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive Quality of a Time-Dependent Sequential Logit Evacuation Demand Model
Authors: Gudishala Ravindra , Wilmot Chester
Published: January 2014

This study examines the predictive accuracy of a time-dependent sequential logit evacuation demand model. The model was estimated on revealed preference data and applied to stated choice data collected in the same survey. The survey was conducted in New Orleans, Louisiana, after Hurricane Gustav; 300 households participated. The stated choice scenarios of the survey consisted of nine hypothetical storms of varying strength, direction, forward speed, and time at which the storm made landfall, as well as decisions made by emergency managers on the type and timing of evacuation orders. The model was applied to each hypothetical storm, and the predicted evacuation demand from the model was compared with the response from the stated choice survey. The predictive performance of the model varied by hypothetical storm with a percentage root mean square error of 10.4 to 26.7 evacuations per 6-h period over 3 days. The model overpredicted total evacuation on all nine hypothetical storms by an average of 35.6%, with a range of 8.1% to 83.0%. The overprediction may be a result of the Katrina effect. After Hurricane Katrina, evacuation was more readily adopted. The model was estimated on the first major hurricane to hit New Orleans after Hurricane Katrina. Errors in predictions in individual periods are considered to be primarily a result of the limited number of stated choice scenarios used in the survey and the coarse representation of the storm these scenarios represent in the input to the model.
Modeling of Bus Transit Driver Availability for Effective Emergency Evacuation in Disaster Relief
Authors: Morgul Ender Faruk , Cavus Ozlem , Ozbay Kaan , Iyigun Cem
Published: January 2014

Potential evacuees without access to personal automobiles are expected to use transit, especially buses, to reach safer regions. For a transit agency, operation problems to be considered include establishing bus launch areas, positioning the minimum number of required buses, and coordinating transit operators, especially determining whether the number of drivers will be sufficient to cover the number of vehicles (i.e., buses) to be used during the evacuation. It is also highly probable that during an emergency, absenteeism rates for bus drivers might increase. In this study, the authors developed two stochastic models to determine the need for extra drivers during an emergency evacuation and to provide optimal solutions using well-established concepts in mathematical programming. First, the authors reviewed the literature to develop an effective methodology for the development of optimal extraboard management strategies. The authors found that although several recent reports clearly mentioned the problem of not having enough bus drivers during emergency evacuation operations, no analytical study incorporated the optimal extraboard size problem into emergency evacuation operations. Second, two mathematical models are presented in this paper. The aim of the developed models is to fill the gap in the literature for determining optimal extraboard size for transit operations during emergency evacuations. The models are specifically designed to capture risk-averse behavior of decision makers. Finally, these models were tested with hypothetical examples from real-world data from New Jersey. Results show that both models give reasonable extraboard size estimates, and under different conditions, these models are responsive to the changes in cost and quality of service preferences. The results are encouraging in terms of the models' usefulness for real-world applications.
Roundabout Performance Evaluation in a Network Evacuation
Authors: Eshragh Sepideh , Faghri Ardeshir , DuRoss Michael
Published: January 2014

This paper presents a methodology to simplify network performance evaluations during hurricane evacuations. The approach is geared toward traffic planners in small towns who have to deal with such scenarios. In such settings, roundabouts are usually a favorite intersection control. Roundabouts usually operate in low-volume traffic areas, whereas high traffic volumes are expected during an evacuation. This paper develops a framework to evaluate the traffic impacts of evacuations in roundabouts within a network. A methodology based on a relaxed discrete network design problem is presented, along with a decomposition approach to simplify the solution strategy. Two volume adjustment strategies are proposed to maintain the interactions of neighboring intersections and take advantage of the simplicity of traffic analysis at isolated intersections. A case study from a subnetwork of the city of Newark, Delaware, is presented. The applicability and the future directions of this research are discussed.
Using National Household Travel Survey Data for the Assessment of Transportation System Vulnerabilities
Authors: Kim Karl , Pant Pradip , Yamashita Eric
Published: January 2014

This paper describes how the National Household Travel Survey (NHTS) data can be used within the framework of the Threat and Hazard Identification and Risk Assessment, recently promulgated by the Federal Emergency Management Agency, to assess transportation system vulnerability. The purpose of this paper is threefold: identify common ground between the Department of Homeland Security and the Department of Transportation in methods of risk assessment; look specifically at transportation vulnerabilities by shifting the focus from transportation system infrastructure to the travel patterns and attributes of individuals; and with data from Honolulu, Hawaii, evaluate the vulnerability of transportation assets. The proposed transportation system vulnerability assessment method uses data from the 2001 NHTS Oahu, Hawaii, add-on survey and probable coastal inundation scenario for events caused by hurricane storm surge, inland flooding, and sea level rise. A geographic information system approach is used to simulate travel routes and assess the transportation system vulnerabilities for individuals and households. The NHTS data contain vital information regarding home, work, and other travel locations. The data also contain travel mode information that can be used to produce quantitative indices for exposure and vulnerability, which can be overlaid with plausible hazard and threat scenarios. Recommendations are made for improving the quality, availability, and usefulness of NHTS data for the reduction of risks. The findings are relevant to transportation research on risk assessment and threat and hazard reduction.
Strategic Rail Network Optimization Model for Freight Transportation
Authors: Maia Luís Couto , Couto António
Published: January 2014

An optimization model for a rail freight network was developed as a support tool for planning and policy decisions involved in the improvement of rail networks on a regional and national level. The model was based on a strategic traffic assignment model, which was designed to model macronetworks with a high aggregation level, and was exclusively designed for freight traffic. The model contemplates road and rail transport modes and considers two types of cargo: intermodal cargo, which is generally transported in containers and is easily interchanged between different modes at intermodal terminals, and general cargo, which represents all the remaining cargo. The optimization process was based on a local search heuristic that delivers good solutions in a reasonable computing time. The quality of each network improvement solution was assessed on the basis of the reductions in total generalized costs and carbon dioxide emissions. This optimization model for a freight network is innovative because it is not limited: both the improvement of existing links and the construction of new ones are allowed, and the model does not have a limit on the number or variety of possibilities for network improvement. The adaptability to different conditions was emphasized when the model was applied to two networks under different investment scenarios because the model delivered considerably different solutions adapted to the conditions of each scenario.
Estimation of an Inventory Theoretical Model of Mode Choice in Freight Transport
Authors: Lloret-Batlle Roger , Combes François
Published: January 2014

A model of freight mode choice was developed on the basis of the economic order quantity model, an inventory theoretical model of optimal shipment size. Shipment size is not explicit in the mode choice model; however, the specifications of the utilities associated with each transport mode account for shipment size and transport mode, which are two related decisions that depend on transport costs and on the logistics costs of shippers. The explanatory variables of the mode choice model are the total commodity flow between the shipper and the receiver, the distance between the origin and the destination, the value density of the commodity, and a few additional variables. No transport supply data are used. Four versions of the model were estimated with the use of the French shipper survey ECHO. As a result of these estimations, the terms of the utility functions inspired from inventory theory substantially improved the statistical goodness of fit of the models. This finding tends to confirm the potential of inventory theory to improve freight mode choice modeling. The finding also shows that the commodity flow between the shipper and the receiver is an important explanatory variable of mode choice and indicates that this variable should be observed in shipper surveys.
Ancillary Functions for Smartphone Weight–Mile Tax Truck Data
Authors: Bell Katherine E. , Figliozzi Miguel A.
Published: January 2014

Oregon is one of the few states that currently charge a weight–mile tax (WMT) on commercial trucks. This research evaluated ancillary applications for a system developed by the Oregon Department of Transportation (DOT) to simplify WMT collection. The data collection system developed by Oregon DOT—truck road use electronics (TRUE)—includes a smartphone application with a Global Positioning System (GPS) device and microprocessor. The TRUE data have enormous advantages over the GPS data used in previous research because of TRUE's level of disaggregation and potential to differentiate between vehicle and commodity types. This research evaluated the accuracy of the TRUE data and demonstrated the successful application of the data to develop trip generation rates for a variety of truck types and land use categories. This research confirms the value of the TRUE data to enhance existing Oregon DOT transportation planning models and performance measures.
Inventory Routing Problem with Route Duration Limits and Stochastic Inventory Capacity Constraints
Authors: Karoonsoontawong Ampol , Unnikrishnan Avinash
Published: January 2014

This paper studies the inventory management and routing problem in a two-level supply chain in which a single plant serves a set of warehouses, which in turn serve a set of customers with stochastic demands. A nonlinear integer program based on set partitioning and probabilistic chance constraint is proposed. The program accounts for the probabilities of inventory capacity violation, order quantity capacity, service levels, vehicle capacity restrictions, and route duration limits in the combined continuous inventory control and multidepot vehicle routing problem. Two tabu search heuristics differing in the way in which initial solutions were generated were applied to solve the problem. Computational tests on standard test networks revealed that the integration of the inventory management and routing decisions by solution of the combined inventory management and routing problem might yield cost savings of up to 14% over the cost of the sequential approach in which both problems were solved separately. The best objective function value obtained by the tabu search heuristic was found to increase with an increase in customer demand variance but decrease with an increase in order quantity capacity and route duration limit. Variance of the customer demand was found to have a significant impact on the quality of the solution.
Incorporating Urban-Area Truck Freight Value into the Urban Mobility Report
Authors: Eisele William L. , Schrank David L. , Bittner Jason , Larson Gregory
Published: January 2014

For more than 30 years, the Texas A&M Transportation Institute (TTI) has developed methodologies and appropriate performance measures for estimating congestion performance and communicating them to technical and nontechnical audiences. TTI's Urban Mobility Report (UMR) has historically focused on passenger car congestion (i.e., congestion caused by the average commuter). However, roadway traffic congestion certainly affects both commuters and goods movement. With the documented growth of freight shipments and value, particularly in trucking, researchers developed and applied a methodology to include in UMR the truck freight commodity value that is affected by congestion in urban areas. The methodology uses data from FHWA's Freight Analysis Framework (FAF) and Highway Performance Monitoring System (HPMS). Commodity values supplied by the FAF are integrated into truck vehicle miles of travel calculated from the HPMS roadway inventory. Researchers estimated that $7 trillion worth of commodities were trucked on America's urban streets and highways during 2010. At the urban-area level, the results of the truck value measure appear to be intuitive, as bigger cities consume more goods and the greater consumption means a higher value of freight movement. The addition of a truck value to the UMR provides another dimension to inform policy makers and decision makers about the congestion problem. This addition also serves to inform trucking stakeholders with an estimate of the amount of truck value that is affected by congestion. Researchers will continue to include the truck freight value performance measure in subsequent releases of the UMR.
Structural Commodity Generation Model that Uses Public Data
Authors: Ranaiefar Fatemeh , Chow Joseph Y. J. , Rodriguez-Roman Daniel , Camargo Pedro V. , Ritchie Stephen G.
Published: January 2014

Freight forecasting models are data intensive and require many explanatory variables to be accurate. One problem, particularly in the United States, is that public data sources are mostly at highly aggregate geographic levels but models with more disaggregate geographic levels are required for regional freight transportation planning. A second problem is that supply chain effects are often ignored or modeled with economic input–output models that lack explanatory power. This study addressed these challenges with a structural equation modeling approach that was not confined to a specific spatial structure, as spatial regression models would have been, and allowed correlations between commodities. A model for structural commodity generation that was based on freight analysis framework was specified, estimated, and shown to provide a better fit to the data than did independent regression models for each commodity. Three features of the model are discussed: indirect effects, supply chain elasticity, and intrazonal supply–demand interactions. A goal programming method was used with imputed data to validate the geographic scalability of the model.
Joint Model of Freight Mode and Shipment Size Choice
Authors: Pourabdollahi Zahra , Karimi Behzad , Mohammadian Abolfazl (Kouros)
Published: January 2014

Mode and shipment size choice are among the most critical logistics decisions but are typically studied separately in freight demand studies despite their strong correlations. The study described in this paper used an innovative copula-based framework to model freight mode and shipment size choice simultaneously as a joint decision-making problem. The study used a copula-based joint multinomial logit–multinomial logit model in which both mode choice and shipment size were modeled as discrete choices in a multinomial logit structure. The proposed copula-based model was intended to capture the potential effects of observed and unobserved factors that jointly affect both choices. The data used in this study were gathered through a large-scale establishment survey conducted in 2011 in the United States. The survey provided detailed information on more than 1,840 individual shipments that were used to develop the disaggregate models. Results of the estimated model underline the importance of the interrelationship between freight mode choice and shipment size and suggest that common unobserved factors influencing mode and shipment size choices exist. The model provides a better way to capture the effects of observed and unobserved factors that affect both choices simultaneously.
Scheduled Hyperpath
Authors: Kanturska Urszula , Trozzi Valentina , Bell Michael G. H.
Published: January 2014

This paper presents a new method for improving the on-time arrival reliability of deliveries. A dispatcher wishes to minimize the total expected travel time and determines a set of attractive links before the trip. Drivers choose between them en route on the basis of the traffic conditions that they observe on immediate successor links. Such a set of attractive paths with associated departure time and decision rule collectively offers a better expected travel time than any single path on its own and is referred to as a “scheduled hyperpath.” The hyperpath concept was exploited by drawing of a parallel between the wait for randomly arriving public transport services and the wait for available capacity in traffic networks with random delays. Adaptation of those methods to the just-in-time delivery context follows from established assertions that consideration of multiple paths and adaptive path selection in networks with random travel times offers shorter travel times than selection of an a priori path with the least expected travel time. The HyperDOT algorithm presented identifies an optimal scheduled hyperpath sequentially in reverse topological and chronological order by use of the historical distributions of link travel times for discrete time intervals as inputs. Two areas of application are discussed: multiple simultaneous deliveries and repetitive shipments. Although the proposed strategy is advantageous in networks with multiple delays, it may lead to the discarding of routes that remain the shortest even when they are delayed because of the myopic character of information about network conditions.
Network Flow Methodology for Estimating Empty Trips in Freight Transportation Models
Authors: Mesa-Arango Rodrigo , Ukkusuri Satish , Sarmiento Ivan
Published: January 2014

Commodity-based freight transportation models, for example, the Freight Analysis Framework, transform volumes of commodities into traffic flow by the application of vehicle use factors. However, these models cannot accurately capture the number of empty trips that result as a consequence of the movement of these commodities. Previous research has proposed a number of methodologies to incorporate empty trips as a function of loaded trips and some assumptions about the trip chains. Parameters in these models are calibrated with extensive origin–destination surveys. However, freight transportation data are usually scarce or not available in proper form for use in models. This paper presents a novel methodology to estimate the number of empty trips on the basis of a time-expanded network flow approach that captures the behavioral and operational characteristics of the carriers. The model was formulated as a linear optimization problem that minimized the system costs associated with truck trips. The model was validated with a commercial vehicle survey from Colombia. The results showed that under some operational assumptions, the model appropriately represented the amount of empty vehicle hours in a freight transportation network.
Vehicle Routing Problem
Authors: Wang Yong , Ma Xiaolei , Lao Yunteng , Wang Yinhai , Mao Haijun
Published: January 2014

The vehicle routing problem with simultaneous deliveries and pickups (VRPSDP) has attracted much research interest because of the potential to provide cost savings to transportation and logistics operators. Several extensions of VRPSDP exist. Of these extensions, the simultaneous deliveries and pickups with split loads problem (SDPSLP) has been proposed to eliminate vehicle capacity constraints, as well as allow the deliveries or pickups for a customer to be split into multiple visits. Although delivery and pickup activities are often constrained by time windows, few studies have considered such constraints when SDPSLP has been addressed. To fill the gap, this paper formulates the vehicle routing problem of simultaneous deliveries and pickups with split loads and time windows (VRPSDPSLTW) as a mixed-integer programming problem. A hybrid heuristic algorithm was developed to solve this problem. Solomon data sets with minor modifications were applied to test the effectiveness of the solution algorithm. The results of a computational experiment demonstrated that use of the proposed algorithms to solve VRPSDPSLTW had advantages for minimization of the total travel cost, number of vehicles, and loading rate. The proposed formulation and solution algorithm for VRPSDPSLTW may serve as a general analytical tool for the optimization of vehicle routing in practice.
Utility of the Biosynthetic Folate Pathway for Targets in Antimicrobial Discovery
Authors: Bourne Christina
Published: January 2014

The need for new antimicrobials is great in face of a growing pool of resistant pathogenic organisms. This review will address the potential for antimicrobial therapy based on polypharmacological activities within the currently utilized bacterial biosynthetic folate pathway. The folate metabolic pathway leads to synthesis of required precursors for cellular function and contains a critical node, dihydrofolate reductase (DHFR), which is shared between prokaryotes and eukaryotes. The DHFR enzyme is currently targeted by methotrexate in anti-cancer therapies, by trimethoprim for antibacterial uses, and by pyrimethamine for anti-protozoal applications. An additional anti-folate target is dihyropteroate synthase (DHPS), which is unique to prokaryotes as they cannot acquire folate through dietary means. It has been demonstrated as a primary target for the longest standing antibiotic class, the sulfonamides, which act synergistically with DHFR inhibitors. Investigations have revealed most DHPS enzymes possess the ability to utilize sulfa drugs metabolically, producing alternate products that presumably inhibit downstream enzymes requiring the produced dihydropteroate. Recent work has established an off-target effect of sulfonamide antibiotics on a eukaryotic enzyme, sepiapterin reductase, causing alterations in neurotransmitter synthesis. Given that inhibitors of both DHFR and DHPS are designed to mimic their cognate substrate, which contain shared substructures, it is reasonable to expect such “off-target” effects. These inhibitors are also likely to interact with the enzymatic neighbors in the folate pathway that bind products of the DHFR or DHPS enzymes and/or substrates of similar substructure. Computational studies designed to assess polypharmacology reiterate these conclusions. This leads to hypotheses exploring the vast utility of multiple members of the folate pathway for modulating cellular metabolism, and includes an appealing capacity for prokaryotic-specific polypharmacology for antimicrobial applications.
Dating Petroglyphs from Fugoppe Cave, Japan
Authors: Ogawa Masaru
Published: January 2014

For over 20 years, I have tried to establish a relative date for petroglyphs in Fugoppe Cave, Japan. Unsuspected amidst debris accumulating from about 1300 years ago, the petroglyphs were rediscovered accidentally in 1950. From an analysis of petroglyphs on fallen rocks scattered randomly on the site floor, I argue that the artworks date from ca.1900 years ago. The cave itself, formed by wave action, saw its main occupation by pottery-making people from 1700–1500 years ago; although the petroglyphs on the rock walls predated their occupation, it seems unlikely that the occupants attached any meaning to them.
Gene Expression Profiling Identifies Important Genes Affected by R2 Compound Disrupting FAK and P53 Complex
Authors: Golubovskaya Vita , Ho Baotran , Conroy Jeffrey , Liu Song , Wang Dan , Cance William
Published: January 2014

Focal Adhesion Kinase (FAK) is a non-receptor kinase that plays an important role in many cellular processes: adhesion, proliferation, invasion, angiogenesis, metastasis and survival. Recently, we have shown that Roslin 2 or R2 (1-benzyl-15,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane) compound disrupts FAK and p53 proteins, activates p53 transcriptional activity, and blocks tumor growth. In this report we performed a microarray gene expression analysis of R2-treated HCT116 p53+/+ and p53−/− cells and detected 1484 genes that were significantly up- or down-regulated (p < 0.05) in HCT116 p53+/+ cells but not in p53−/− cells. Among up-regulated genes in HCT p53+/+ cells we detected critical p53 targets: Mdm-2, Noxa-1, and RIP1. Among down-regulated genes, Met, PLK2, KIF14, BIRC2 and other genes were identified. In addition, a combination of R2 compound with M13 compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm-2 and p53 decreased clonogenicity of HCT116 p53+/+ colon cancer cells more significantly than each agent alone in a p53-dependent manner. Thus, the report detects gene expression profile in response to R2 treatment and demonstrates that the combination of drugs targeting FAK, Mdm-2, and p53 can be a novel therapy approach.
Expressed Sequence Tag-Simple Sequence Repeat (EST-SSR) Marker Resources for Diversity Analysis of Mango (Mangifera indica L.)
Authors: Dillon Natalie , Innes David , Bally Ian , Wright Carole , Devitt Luke , Dietzgen Ralf
Published: January 2014

In this study, a collection of 24,840 expressed sequence tags (ESTs) generated from five mango (Mangifera indica L.) cDNA libraries was mined for EST-based simple sequence repeat (SSR) markers. Over 1,000 ESTs with SSR motifs were detected from more than 24,000 EST sequences with di- and tri-nucleotide repeat motifs the most abundant. Of these, 25 EST-SSRs in genes involved in plant development, stress response, and fruit color and flavor development pathways were selected, developed into PCR markers and characterized in a population of 32 mango selections including M. indica varieties, and related Mangifera species. Twenty-four of the 25 EST-SSR markers exhibited polymorphisms, identifying a total of 86 alleles with an average of 5.38 alleles per locus, and distinguished between all Mangifera selections. Private alleles were identified for Mangifera species. These newly developed EST-SSR markers enhance the current 11 SSR mango genetic identity panel utilized by the Australian Mango Breeding Program. The current panel has been used to identify progeny and parents for selection and the application of this extended panel will further improve and help to design mango hybridization strategies for increased breeding efficiency.
Three-Phase Harmonic Analysis Method for Unbalanced Distribution Systems
Authors: Teng Jen-Hao , Liao Shu-Hung , Leou Rong-Ceng
Published: January 2014

Due to the unbalanced features of distribution systems, a three-phase harmonic analysis method is essential to accurately analyze the harmonic impact on distribution systems. Moreover, harmonic analysis is the basic tool for harmonic filter design and harmonic resonance mitigation; therefore, the computational performance should also be efficient. An accurate and efficient three-phase harmonic analysis method for unbalanced distribution systems is proposed in this paper. The variations of bus voltages, bus current injections and branch currents affected by harmonic current injections can be analyzed by two relationship matrices developed from the topological characteristics of distribution systems. Some useful formulas are then derived to solve the three-phase harmonic propagation problem. After the harmonic propagation for each harmonic order is calculated, the total harmonic distortion (THD) for bus voltages can be calculated accordingly. The proposed method has better computational performance, since the time-consuming full admittance matrix inverse employed by the commonly-used harmonic analysis methods is not necessary in the solution procedure. In addition, the proposed method can provide novel viewpoints in calculating the branch currents and bus voltages under harmonic pollution which are vital for harmonic filter design. Test results demonstrate the effectiveness and efficiency of the proposed method.
Distributed Load-Shedding System for Agent-Based Autonomous Microgrid Operations
Authors: Lim Yujin , Kim Hak-Man , Kinoshita Tetsuo
Published: January 2014

A microgrid is an eco-friendly power system because renewable sources are used as main power sources. In the islanded operation mode of a microgrid, maintaining the balance between power supply and power demand is a very important problem. In the case of surplus supply, decreased generation output and/or charge of distributed storages can be applied to solve the imbalance between power supply and demand. In the case of supply shortages, increased generation output and/or discharge of distributed storages can be applied. Especially in the case of critical supply shortages, load shedding should be applied. In a distributed load-shedding approach, microgrid components need to make decisions autonomously. For autonomous microgrid operation, a multi-agent system has been investigated. In this paper, a distributed load-shedding system for agent-based autonomous operation of a microgrid is designed. The designed system is implemented and tested to show the functionality and feasibility of the proposed system.
Estimating Cyanobacteria Community Dynamics and its Relationship with Environmental Factors
Authors: Luo Wenhuai , Chen Huirong , Lei Anping , Lu Jun , Hu Zhangli
Published: January 2014

The cyanobacteria community dynamics in two eutrophic freshwater bodies (Tiegang Reservoir and Shiyan Reservoir) was studied with both a traditional microscopic counting method and a PCR-DGGE genotyping method. Results showed that cyanobacterium Phormidium tenue was the predominant species; twenty-six cyanobacteria species were identified in water samples collected from the two reservoirs, among which fourteen were identified with the morphological method and sixteen with the PCR-DGGE method. The cyanobacteria community composition analysis showed a seasonal fluctuation from July to December. The cyanobacteria population peaked in August in both reservoirs, with cell abundances of 3.78 × 108 cells L-1 and 1.92 × 108 cells L-1 in the Tiegang and Shiyan reservoirs, respectively. Canonical Correspondence Analysis (CCA) was applied to further investigate the correlation between cyanobacteria community dynamics and environmental factors. The result indicated that the cyanobacteria community dynamics was mostly correlated with pH, temperature and total nitrogen. This study demonstrated that data obtained from PCR-DGGE combined with a traditional morphological method could reflect cyanobacteria community dynamics and its correlation with environmental factors in eutrophic freshwater bodies.
Molecular Basis of Cardiac Myxomas
Authors: Singhal Pooja , Luk Adriana , Rao Vivek , Butany Jagdish
Published: January 2014

Cardiac tumors are rare, and of these, primary cardiac tumors are even rarer. Metastatic cardiac tumors are about 100 times more common than the primary tumors. About 90% of primary cardiac tumors are benign, and of these the most common are cardiac myxomas. Approximately 12% of primary cardiac tumors are completely asymptomatic while others present with one or more signs and symptoms of the classical triad of hemodynamic changes due to intracardiac obstruction, embolism and nonspecific constitutional symptoms. Echocardiography is highly sensitive and specific in detecting cardiac tumors. Other helpful investigations are chest X-rays, magnetic resonance imaging and computerized tomography scan. Surgical excision is the treatment of choice for primary cardiac tumors and is usually associated with a good prognosis. This review article will focus on the general features of benign cardiac tumors with an emphasis on cardiac myxomas and their molecular basis.
In Silico Discovery of Aminoacyl-tRNA Synthetase Inhibitors
Authors: Zhao Yaxue , Meng Qingqing , Bai Linquan , Zhou Huchen
Published: January 2014

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that catalyze the transfer of amino acids to their cognate tRNA. They play a pivotal role in protein synthesis and are essential for cell growth and survival. The aaRSs are one of the leading targets for development of antibiotic agents. In this review, we mainly focused on aaRS inhibitor discovery and development using in silico methods including virtual screening and structure-based drug design. These computational methods are relatively fast and cheap, and are proving to be of great benefit for the rational development of more potent aaRS inhibitors and other pharmaceutical agents that may usher in a much needed generation of new antibiotics.
Phenoxybenzamine Is Neuroprotective in a Rat Model of Severe Traumatic Brain Injury
Authors: Rau Thomas , Kothiwal Aakriti , Rova Annela , Rhoderick Joseph , Poulsen David
Published: January 2014

Phenoxybenzamine (PBZ) is an FDA approved α-1 adrenergic receptor antagonist that is currently used to treat symptoms of pheochromocytoma. However, it has not been studied as a neuroprotective agent for traumatic brain injury (TBI). While screening neuroprotective candidates, we found that phenoxybenzamine reduced neuronal death in rat hippocampal slice cultures following exposure to oxygen glucose deprivation (OGD). Using this system, we found that phenoxybenzamine reduced neuronal death over a broad dose range (0.1 µM–1 mM) and provided efficacy when delivered up to 16 h post-OGD. We further tested phenoxybenzamine in the rat lateral fluid percussion model of TBI. When administered 8 h after TBI, phenoxybenzamine improved neurological severity scoring and foot fault assessments. At 25 days post injury, phenoxybenzamine treated TBI animals also showed a significant improvement in both learning and memory compared to saline treated controls. We further examined gene expression changes within the cortex following TBI. At 32 h post-TBI phenoxybenzamine treated animals had significantly lower expression of pro-inflammatory signaling proteins CCL2, IL1β, and MyD88, suggesting that phenoxybenzamine may exert a neuroprotective effect by reducing neuroinflammation after TBI. These data suggest that phenonxybenzamine may have application in the treatment of TBI.
Circulating MicroRNAs as Biomarkers of Acute Stroke
Authors: Sepramaniam Sugunavathi , Tan Jun-Rong , Tan Kay-Sin , DeSilva Deidre , Tavintharan Subramaniam , Woon Fung-Peng , Wang Chee-Woon , Yong Fung-Lin , Karolina Dwi-Setyowati , Kaur Prameet , Liu Fu-Jia , Lim Kai-Ying , Armugam Arunmozhiarasi , Jeyaseelan Kandiah
Published: January 2014

MicroRNAs have been identified as key regulators of gene expression and thus their potential in disease diagnostics, prognosis and therapy is being actively pursued. Deregulation of microRNAs in cerebral pathogenesis has been reported to a limited extent in both animal models and human. Due to the complexity of the pathology, identifying stroke specific microRNAs has been a challenge. This study shows that microRNA profiles reflect not only the temporal progression of stroke but also the specific etiologies. A panel of 32 microRNAs, which could differentiate stroke etiologies during acute phase was identified and verified using a customized TaqMan Low Density Array (TLDA). Furthermore we also found 5 microRNAs, miR-125b-2*, -27a*, -422a, -488 and -627 to be consistently altered in acute stroke irrespective of age or severity or confounding metabolic complications. Differential expression of these 5 microRNAs was also observed in rat stroke models. Hence, their specificity to the stroke pathology emphasizes the possibility of developing these microRNAs into accurate and useful tools for diagnosis of stroke.
Secondary Plant Products Causing Photosensitization in Grazing Herbivores: Their Structure, Activity and Regulation
Authors: Quinn Jane , Kessell Allan , Weston Leslie
Published: January 2014

Photosensitivity in animals is defined as a severe dermatitis that results from a heightened reactivity of skin cells and associated dermal tissues upon their exposure to sunlight, following ingestion or contact with UV reactive secondary plant products. Photosensitivity occurs in animal cells as a reaction that is mediated by a light absorbing molecule, specifically in this case a plant-produced metabolite that is heterocyclic or polyphenolic. In sensitive animals, this reaction is most severe in non-pigmented skin which has the least protection from UV or visible light exposure. Photosensitization in a biological system such as the epidermis is an oxidative or other chemical change in a molecule in response to light-induced excitation of endogenous or exogenously-delivered molecules within the tissue. Photo-oxidation can also occur in the plant itself, resulting in the generation of reactive oxygen species, free radical damage and eventual DNA degradation. Similar cellular changes occur in affected herbivores and are associated with an accumulation of photodynamic molecules in the affected dermal tissues or circulatory system of the herbivore. Recent advances in our ability to identify and detect secondary products at trace levels in the plant and surrounding environment, or in organisms that ingest plants, have provided additional evidence for the role of secondary metabolites in photosensitization of grazing herbivores. This review outlines the role of unique secondary products produced by higher plants in the animal photosensitization process, describes their chemistry and localization in the plant as well as impacts of the environment upon their production, discusses their direct and indirect effects on associated animal systems and presents several examples of well-characterized plant photosensitization in animal systems.
Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism
Authors: Yang Wanchun , Jiang Wanxiang , Luo Liping , Bu Jicheng , Pang Dejiang , Wei Jing , Du Chongyangzi , Xia Xiaoqiang , Cui Yiyuan , Liu Shuang , Mao Qing , Chen Mina
Published: January 2014

Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral metabolism need to be better understood for developing pharmacological interventions to manage eating behavior and obesity. Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a master regulator of cellular metabolism in different cell types. Pharmacological manipulations of mTOR complex 1 (mTORC1) activity in hypothalamic neurons alter food intake and body weight. Our previous study identified Rheb1 (Ras homolog enriched in brain 1) as an essential activator of mTORC1 activity in the brain. Here we examine whether central Rheb1 regulates food intake and peripheral metabolism through mTORC1 signaling. We find that genetic deletion of Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid mobilization in adipose tissue and ketogenesis in the liver. Our work highlights the importance of central Rheb1 signaling in euglycemia and energy homeostasis in animals.
Role of Insulin-Transferrin-Selenium in Auricular Chondrocyte Proliferation and Engineered Cartilage Formation in Vitro
Authors: Liu Xia , Liu Jinchun , Kang Ning , Yan Li , Wang Qian , Fu Xin , Zhang Yuanyuan , Xiao Ran , Cao Yilin
Published: January 2014

The goal of this study is to determine the effects of Insulin-Transferrin-Selenium (ITS) on proliferation of auricular chondrocytes and formation of engineered cartilage in vitro. Pig auricular monolayer chondrocytes and chondrocyte pellets were cultured in media containing 1% ITS at different concentrations of fetal bovine serum (FBS, 10%, 6%, 2%, 0%), or 10% FBS alone as a control for four weeks. Parameters including cell proliferation in monolayer, wet weight, collagen type I/II/X (Col I, II, X) and glycosaminoglycan (GAG) expression, GAG content of pellets and gene expression associated with cartilage formation/dedifferentiation (lost cartilage phenotype)/hypertrophy within the chondrocyte pellets were assessed. The results showed that chondrocytes proliferation rates increased when FBS concentrations increased (2%, 6%, 10% FBS) in ITS supplemented groups. In addition, 1% ITS plus 10% FBS significantly promoted cell proliferation than 10% FBS alone. No chondrocytes grew in ITS alone medium. 1% ITS plus 10% FBS enhanced cartilage formation in terms of size, wet weight, cartilage specific matrices, and homogeneity, compared to 10% FBS alone group. Furthermore, ITS prevented engineered cartilage from dedifferentiation (i.e., higher index of Col II/Col I mRNA expression and expression of aggrecan) and hypertrophy (i.e., lower mRNA expression of Col X and MMP13). In conclusion, our results indicated that ITS efficiently enhanced auricular chondrocytes proliferation, retained chondrogenic phenotypes, and promoted engineered cartilage formation when combined with FBS, which is potentially used as key supplementation in auricular chondrocytes and engineered cartilage culture.
The Influence of Small Quantities of Oxygen in the Structure, Microstructure, Hardness, Elasticity Modulus and Cytocompatibility of Ti-Zr Alloys for Dental Applications
Authors: Vicente Fábio , Correa Diego , Donato Tatiani , Arana-Chavez Victor , Buzalaf Marília , Grandini Carlos
Published: January 2014

The mechanical properties of Ti alloys are changed significantly with the addition of interstitial elements, such as oxygen. Because oxygen is a strong stabilizer of the α phase and has an effect on hardening in a solid solution, it has aroused great interest in the biomedical area. In this paper, Ti-Zr alloys were subjected to a doping process with small amounts of oxygen. The influence of interstitial oxygen in the structure, microstructure and some selected mechanical properties of interest for use as biomaterial and biocompatibility of the alloys were analyzed. The results showed that in the range of 0.02 wt% to 0.04 wt%, oxygen has no influence on the structure, microstructure or biocompatibility of the studied alloys, but causes hardening of the alloys, increasing the values of the microhardness and causing variation in the elasticity modulus values.
Identification and Biochemical Characterization of Halisulfate 3 and Suvanine as Novel Inhibitors of Hepatitis C Virus NS3 Helicase from a Marine Sponge
Authors: Furuta Atsushi , Salam Kazi , Hermawan Idam , Akimitsu Nobuyoshi , Tanaka Junichi , Tani Hidenori , Yamashita Atsuya , Moriishi Kohji , Nakakoshi Masamichi , Tsubuki Masayoshi , Peng Poh , Suzuki Youichi , Yamamoto Naoki , Sekiguchi Yuji , Tsuneda Satoshi , Noda Naohiro
Published: January 2014

Hepatitis C virus (HCV) is an important etiological agent that is responsible for the development of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV nonstructural protein 3 (NS3) helicase is a possible target for novel drug development due to its essential role in viral replication. In this study, we identified halisulfate 3 (hal3) and suvanine as novel NS3 helicase inhibitors, with IC50 values of 4 and 3 µM, respectively, from a marine sponge by screening extracts of marine organisms. Both hal3 and suvanine inhibited the ATPase, RNA binding, and serine protease activities of NS3 helicase with IC50 values of 8, 8, and 14 µM, and 7, 3, and 34 µM, respectively. However, the dengue virus (DENV) NS3 helicase, which shares a catalytic core (consisting mainly of ATPase and RNA binding sites) with HCV NS3 helicase, was not inhibited by hal3 and suvanine, even at concentrations of 100 µM. Therefore, we conclude that hal3 and suvanine specifically inhibit HCV NS3 helicase via an interaction with an allosteric site in NS3 rather than binding to the catalytic core. This led to the inhibition of all NS3 activities, presumably by inducing conformational changes.
Magnetism-Structure Correlations during the ε→τ Transformation in Rapidly-Solidified MnAl Nanostructured Alloys
Authors: Jiménez-Villacorta Felix , Marion Joshua , Oldham John , Daniil Maria. , Willard Matthew , Lewis Laura
Published: January 2014

Magnetic and structural aspects of the annealing-induced transformation of rapidly-solidified Mn55Al45 ribbons from the as-quenched metastable antiferromagnetic (AF) ε-phase to the target ferromagnetic (FM) L10 τ-phase are investigated. The as-solidified material exhibits a majority hexagonal ε-MnAl phase revealing a large exchange bias shift below a magnetic blocking temperature TB~95 K (Hex~13 kOe at 10 K), ascribed to the presence of compositional fluctuations in this antiferromagnetic phase. Heat treatment at a relatively low annealing temperature Tanneal ≈ 568 K (295 °C) promotes the nucleation of the metastable L10 τ-MnAl phase at the expense of the parent ε-phase, donating an increasingly hard ferromagnetic character. The onset of the ε→τ transformation occurs at a temperature that is ~100 K lower than that reported in the literature, highlighting the benefits of applying rapid solidification for synthesis of the rapidly-solidified parent alloy.
Anticholinesterase Inhibitory Activity of Quaternary Alkaloids from Tinospora crispa
Authors: Yusoff Mashitah , Hamid Hazrulrizawati , Houghton Peter
Published: January 2014

Quaternary alkaloids are the major alkaloids isolated from Tinospora species. A previous study pointed to the necessary presence of quaternary nitrogens for strong acetylcholinesterase (AChE) inhibitory activity in such alkaloids. Repeated column chromatography of the vine of Tinospora crispa extract led to the isolation of one new protoberberine alkaloid, 4,13-dihydroxy-2,8,9-trimethoxydibenzo[a,g]quinolizinium (1), along with six known alkaloids—dihydrodiscretamine (2), columbamine (3), magnoflorine (4), N-formylannonaine (5), N-formylnornuciferine (6), and N-trans-feruloyltyramine (7). The seven compounds were isolated and structurally elucidated by spectroscopic analysis. Two known alkaloids, namely, dihydrodiscretamine and columbamine are reported for the first time for this plant. The compounds were tested for AChE inhibitory activity using Ellman’s method. In the AChE inhibition assay, only columbamine (3) showed strong activity with IC50 48.1 µM. The structure–activity relationships derived from these results suggest that the quaternary nitrogen in the skeleton has some effect, but that a high degree of methoxylation is more important for acetylcholinesterase inhibition.