bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation‐based estimates of delays at freeway work zones
Authors: Chien Steven I‐Jy , Goulias Dimitrios G. , Yahalom Shmuel , Chowdhury Shoaib M.
Published: January 2010

Work zone related traffic delay is an important cost component on freeways with maintenance activities. This study demonstrates that delays may be underestimated by using the deterministic queuing theory. Computer simulation is a valuable approach of estimating delay under a variety of existing and future conditions. However, a single simulation run, which can be quite costly in terms of both computer and analyst time, produces a delay estimate for only one traffic level under one set of conditions. A method is developed in this paper to approximate delays by integrating limited simulation data, obtained from CORSIM and the concept of deterministic queuing theory, while various geometric conditions and time‐varying traffic distribution are considered. A calibrated and validated simulation model that can reflect work zone traffic operations on a segment of Interstate 1–80 in New Jersey is used to generate data for developing the proposed model. The comparison of delays estimated by the deterministic queuing model and the proposed model is conducted, while factors affecting the accuracy of the delay estimates are discussed.
Design and shared use of a terminal departure lounge for new large aircraft operations
Authors: de Barros Alexandre G. , Wirasinghe S. C.
Published: January 2010

New Large Aircraft (NLA) are new aircraft developments larger than any existing aircraft. The NLA's higher seat capacity will significantly impact passenger terminal design and operations. This paper focuses on the issues regarding the departure lounge. Deterministic queuing theory is used to determine the size and seating configuration of the lounge, as well as to decide whether a second level should be built to accommodate the increase in the number of passengers. The paper also discusses the use of the satellite section of a pier‐satellite terminal as a single lounge for the NLA. Spreadsheets are used to implement the analyses.
Power unit ‐ Cargo space link in inland waterway navigation
Authors: Radmilovic Zoran , Hrle Zlatko , Muskatirovic Jasna
Published: January 2010

This paper deals with transportation technology regarding links between power unit or motor ship and ship cargo space. These links can be divided into two groups: rigid and flexible. Rigid link, established between power unit and cargo space, is dominant in maritime and road transport (sea ships and trucks), and occasionally in transport on inland waterways (self‐propelled barges). Flexible link is used in railroad transport (between the locomotive and railroad units), partially in road transport (systems with trailers and semitrailers), and in inland waterway transport (push‐towing, pulling systems and combinations of these systems).

The main goal of this research is determination of possible link types and organization of fleet for transport on inland waterways in case of flexible link.
Fuel consumption model for bus rapid transit
Authors: Zargari Shahriar A. , Khan Ata M.
Published: January 2010

Transportation planners and policy analysts require, for scenario testing, a detailed fuel consumption model of public transit operating in multimodal corridors. Although much effort has been devoted to the development of detailed methodology for estimating fuel consumption of automobile travel on freeways and arterials, the same is not the case for public transit. This paper presents methodology for the estimation of fuel consumption for bus operation on transitways/busways serving major travel corridors. Bus fuel consumption model is reported for standard and articulated buses. This model was adapted from an existing heavy vehicle fuel use model by incorporating the transitway design and bus operational characteristics.
A fuzzy method for predicting the demand for rail freight transportation
Authors: Wong W. G. , Niu H. , Ferreira L.
Published: January 2010

The demand for rail freight transportation is a continuously changing process over space and time and is affected by many quantitative and qualitative factors. In order to develop a more rational transport planning process to be followed by railway organizations, there is a need to accurately forecast freight demand under a dynamic and uncertain environment. In conventional linear regression analysis, the deviations between the observed and the estimated values are supposed to be due to observation errors. In this paper, taking a different perspective, these deviations are regarded as the fuzziness of the system's structure. The details of fuzzy linear regression method are put forward and discussed in the paper. Based on an analyzes of the characteristics of the rail transportation problem, the proposed model was successfully applied to a real example from China. The results of that application are also presented here.
Evaluation of actuated control of diamond interchanges with advanced experimental design
Authors: Lee Sangsoo , Messer Carroll J.
Published: January 2010

Two three‐phase actuated control strategies at diamond interchanges were investigated for different ramp spacings and traffic patterns. An advanced experimental design, hardware‐in‐the‐loop control, was employed for the simulation study. Operational performance was identified in terms of cycle length, average delay and total stops.

Experimental results showed that the two phasing strategies gave similar performance in terms of cycle length and average delay, but not stops. The cycle length of three‐phase operation increased slightly as the ramp spacing became wider. The delay of each strategy was dependent on the traffic pattern, but there was a distinct movement preference for each strategy. The total stops decreased as the spacing increased, and it was the most sensitive variable for the studied traffic demand level. It was also shown that the concept of the hardware‐in‐the‐loop control provides an effective way to evaluate the signal phasing and control strategies.
Retrospect and prospect of public transit privatization in China
Authors: Chen Xueming
Published: January 2010

As the most populous country in the world with a heavy reliance on public transit, China's public transit privatization has a global significance. China's post‐Mao economic reform and establishment of market‐oriented economy have stimulated its public transit privatization at a very fast pace. The largest Chinese cities have been spearheading the implementation of different privatization measures, such as granting franchises, company merger, company reorganization, public/private partnership, responsibility systems, and many others. All these privatization efforts have yielded preliminary successful results, even though some obstacles are encountered. In the future, new privatization‐related laws are expected to be enacted, government functions and business functions would be further separated, privatizing other public transit services besides operation would take place, and some negative impacts associated with privatization would be mitigated.
Validation of a schedule‐based capacity restraint transit assignment model for a large‐scale network
Authors: Poon M. H. , Tong C. O. , Wong S. C.
Published: January 2010

This paper describes the application of a capacity restraint trip assignment algorithm to a real, large‐scale transit network and the validation of the results. Unlike the conventional frequency‐based approach, the network formulation of the proposed model is dynamic and schedule‐based. Transit vehicles are assumed to operate to a set of pre‐determined schedules. Passengers are assumed to select paths based on a generalized cost function including in‐vehicle and out‐of‐vehicle time and line change penalty. The time‐varying passenger demand is loaded onto the network by a time increment simulation method, which ensures that the capacity restraint of each vehicle during passenger boarding is strictly observed. The optimal‐path and path‐loading algorithms are applied iteratively by the method of successive averages until the network converges to the predictive dynamic user equilibrium. The Hong Kong Mass Transit Railway network is used to validate the model results. The potential applications of the model are also discussed.
The development and implementation of the operation system and data bank for the intelligent transportation system — sitcuo
Authors: Weigang Li , Yamashita Yaeko , Koendjbiharie Marlon Winston , de Moura Jucá Ricardo Cezar , Maciver Andrew
Published: January 2010

SITCUO (Sistemas de Informações de Transportes Coletivos Urbanos por Õnibus) ‐ a dynamic information system for urban bus passengers in Brasilia, using business intelligence, was developed to optimize bus operations and increase the satisfaction of urban transportation users. In order to achieve these objectives the system involves the convergence of a number of different technologies, including: Global Positioning System (GPS), Geographic Information System (GIS), database, data mining, Internet and telecommunications. The system includes communication between the GPS, the database, the Control Centre and the user interfaces, which provide estimated bus arrival times via the information display panels and the Internet. The information system at the Control Centre was implemented by applying Java, JavaServer Pages (JSP), and a Relational Database Management System (RDBMS) using an object‐oriented approach. The paper will present the general description of the system, the algorithms for estimating the arrival time of the bus at the bus stop, the implementation procedure adopted, the results of experiments undertaken on a bus route in Brasilia and the conclusions.
Multimodal traveling and its impact on urban transit network design
Authors: van Nes Rob , Bovy Piet H. L.
Published: January 2010

Multimodal trip making, that is trips using a combination of several modes between origin and destination, is expected to be beneficial to society and might offer advantages to the traveler as well. This article looks at some of the implications of multi‐modality in trip making for the design of urban transit systems since these play an important role in multi‐modal transportation systems. In this respect, the article looks at the strategic design characteristics of urban transit networks, that is line density, stop density and service frequencies for the case of multimodal access to urban transit networks and for hierarchical network structures in urban transit systems. The analyses show that multimodal access does not require alternative network structures. For hierarchical network structures it is concluded that these are primarily determined by the hierarchy in demand densities and thus by hierarchy in urban structures.
Scheduling considerations for a branching transit route
Authors: Sun Aichong , Hickman Mark
Published: January 2010

This paper addresses the impacts of different scheduling alternatives for a branching transit route. It examines different schedule alternatives that might be used to optimize the route performance in terms of the passenger traveling time distributed among branch passengers and trunk‐line passengers. The schedule alternatives considered include transit vehicle allocation to different branches, offset shifting across vehicles on different branches, and vehicle holding (slack time) in the transit vehicle schedule. With these variables, several vehicle schedules are devised and examined based on a wide variety of possible passenger boarding scenarios using deterministic service models. Test outcomes provide general conclusions about the performance of the strategies. Vehicle assignment leading to even headways among branches is generally preferred for the case of low passenger demand. However, when passenger demand is high, or the differences between the passenger demands on branches are significant, unequal vehicle assignment will be helpful to improve the overall route performance. Holding, as a proactive strategy in scheduling, has the potential to be embedded into the schedule as a type of slack time, but needs further evidence and study to determine the full set of conditions where it may be beneficial. Offset shifting does not show sufficient evidence to be an efficient strategy to improve route performance in the case of low or high passenger demand.
Interspecific resources: a major tool for quantitative trait locus cloning and speciation research
Authors: L'Hôte David , Laissue Paul , Serres Catherine , Montagutelli Xavier , Veitia Reiner A. , Vaiman Daniel
Published: January 2010

Positional cloning of the quantitative trait locus (QTL) still encounters numerous difficulties, which explains why thousands of QTL have been mapped, while only a few have been identified at the molecular level. Here, we focus on a specific mapping tool that exists in plant and animal model species: interspecific recombinant congenic strains (IRCSs) or interspecific nearly isogenic lines (NILs). Such panels exhibit a much higher sequence diversity than intraspecific sets, thus enhancing the contrasts between phenotypes. In animals, it allows statistical significance to be reached even when using a limited number of individuals. Therefore, we argue that interspecific resources may constitute a major genetic tool for positional cloning and for understanding some bases of speciation mechanisms.
Generation of branched actin networks: assembly and regulation of the N‐WASP and WAVE molecular machines
Authors: Derivery Emmanuel , Gautreau Alexis
Published: January 2010

The Arp2/3 complex is a molecular machine that generates branched actin networks responsible for membrane remodeling during cell migration, endocytosis, and other morphogenetic events. This machine requires activators, which themselves are multiprotein complexes. This review focuses on recent advances concerning the assembly of stable complexes containing the most‐studied activators, N‐WASP and WAVE proteins, and the level of regulation that is provided by these complexes. N‐WASP is the paradigmatic auto‐inhibited protein, which is activated by a conformational opening. Even though this regulation has been successfully reconstituted in vitro with isolated N‐WASP, the native dimeric complex with a WIP family protein has unique additional properties. WAVE proteins are part of a pentameric complex, whose basal state and activated state when bound to the Rac GTPase were recently clarified. Moreover, this review attempts to put together diverse observations concerning the WAVE complex in the conceptual frame of an in vivo assembly pathway that has gained support from the recent identification of a precursor.
The dynamic replicon: adapting to a changing cellular environment
Authors: Herrick John
Published: January 2010

Eukaryotic cells are often exposed to fluctuations in growth conditions as well as endogenous and exogenous stress‐related agents. During development, global patterns of gene transcription change substantially, and these changes are associated with altered patterns of DNA replication and larger distances between replication origins in somatic cells compared to embryos. Conversely, when cells experience difficulties while replicating DNA, the replication program is dramatically altered and distances between replication origins decrease. Recent evidence indicates that each unit of replication, or replicon, can correspond to one or more potential replication origins, but in the case of multiple potential origins, only one is selected to initiate replication of the replicon. How one origin is selected from multiple potential origins and how origin densities are regulated during genome duplication remains unclear. The following review addresses some of the mechanisms involved in regulating replication origins during both a normal and perturbed eukaryotic cell cycle.
Elastin‐like polypeptides: Biomedical applications of tunable biopolymers
Authors: MacEwan Sarah R. , Chilkoti Ashutosh
Published: January 2010

Artificial repetitive polypeptides have grown in popularity as a bioinspired alternative to synthetic polymers. The genetically encoded synthesis, monodispersity, potential lack of toxicity, and biocompatibility are attractive features of these biopolymers for biological applications. Elastin‐like polypeptides (ELPs) are one such class of biopolymers that are of particular interest because of their “smart”—stimuli responsive—properties. Herein, we discuss the genetically encoded design and recombinant synthesis of ELPs that enable precise control of their physicochemical properties and which have led to a wide range of biomedical applications of these biopolymers in the last decade. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94:60–77, 2010.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Domain swapping in materials design
Authors: Nagarkar Radhika P. , Hule Rohan A. , Pochan Darrin J. , Schneider Joel P.
Published: January 2010

Peptide self‐assembly can be used as a bottom–up approach to material fabrication. Although many different types of materials can be prepared from peptides, hydrogels are perhaps one of the most common. Gels typically result from the self‐assembly of peptides into fibrillar networks. Controlling the structural morphology of these fibrils and the networks they form allows direct control over a given material's bulk properties. However, exerting this control is extremely difficult as the mechanistic rules that govern peptide self‐assembly are far from being established. Conversely, several amyloidogenic proteins have been shown to self‐assemble into fibrils using a mechanism known as domain swapping. Here, discrete units of secondary structure or even whole domains are exchanged (swapped) among discrete proteins during self‐assembly to form extended networks with precise structural control. This review discusses several common mechanistic variations of domain swapping using naturally occurring proteins as examples. The possibility of using these principles to design peptides capable of controlled assembly and fibril formation leading to materials with targeted properties is explored. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 141–155, 2010.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Chemoselective ligation techniques: Modern applications of time‐honored chemistry
Authors: Tiefenbrunn Theresa K. , Dawson Philip E.
Published: January 2010

Chemoselective ligation techniques enable the selective modification of proteins and other biomolecules in dilute aqueous solution. Importantly, these reactions occur at or near physiological pH and are compatible with the complex array of functional groups commonly found in biological macromolecules including proteins, nucleotides, and carbohydrates, allowing conjugation reactions to be carried out on unprotected substrates. Recently, a growing number of reactions with established utility in synthetic organic chemistry have been shown to have surprising utility in the context of biological molecules in aqueous media. In this review we highlight several promising reactions that may have widespread applicability in the generation of new materials based on biological macromolecules. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 91:95–106, 2010.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Building fibrous biomaterials from α‐helical and collagen‐like coiled‐coil peptides
Authors: Woolfson Derek N.
Published: January 2010

Over the decade and a half, interest has soared in the development of peptide‐based biomaterials and their potential applications in biotechnology. This review outlines the advances during this time in the construction of biomaterials based on the α‐helical coiled‐coil and collagen‐like peptides. These structures and the resulting designs are distinct from the more commonly used β‐structured peptides, which often lead to hydrogels comprising amyloid‐like fibrils. The review covers basic design rules for these helical assemblies, and the various fibrous biomaterials that can be accomplished with them, which include rigid structures with straight, branched, or networked structures, decorated and functionalized systems, and most recently flexible fibers and entangled hydrogel networks. This plethora of α‐helix‐based biomaterials, together with more recent collagen‐like assemblies, that are emerging from various laboratories complement those developed using β‐structured peptides, and open exciting new avenues for biomaterials research and potential new application areas. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94:118–127, 2010.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Synthesis by native chemical ligation and crystal structure of human CCL2
Authors: Grygiel Tami L. R. , Teplyakov Alexey , Obmolova Galina , Stowell Nicole , Holland Reannon , Nemeth Jennifer F. , Pomerantz Steven C. , Kruszynski Marian , Gilliland Gary L.
Published: January 2010

The protein human CC chemokine ligand 2 (CCL2, also known as monocyte chemoattractant protein 1 or MCP‐1) has been synthesized using a combination of solid phase peptide synthesis (SPPS) and native chemical ligation (NCL). The thioester‐peptide segment was synthesized using the sulfonamide safety‐catch linker and 9‐fluorenylmethoxycarbonyl (Fmoc) SPPS, and pseudoproline dipeptides were used to facilitate the synthesis of both CCL2 fragments. After assembly of the full‐length peptide chain by NCL, a glutathione redox buffer was used to fold and oxidize the CCL2 protein. Synthetic human CCL2 binds to and activates the CCR2 receptor on THP‐1 cells, as expected. CCL2 was crystallized and the structure was determined by X‐ray diffraction at 1.9‐Å resolution. The structure of the synthetic protein is very similar to that of a previously reported structure of recombinant human CCL2, although the crystal form is different. The functional CCL2 dimer for the crystal structure reported here is formed around a crystallographic twofold axis. The dimer interface involves residues Val9‐Thr10‐Cys11, which form an intersubunit antiparallel β‐sheet. Comparison of the CCL2 dimers in different crystal forms indicates a significant flexibility of the quaternary structure. To our knowledge, this is one of the first crystal structures of a protein prepared using the sulfonamide safety‐catch linker and NCL. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 350–359, 2010.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Microporous cell‐laden hydrogels for engineered tissue constructs
Authors: Park Jae Hong , Chung Bong Geun , Lee Won Gu , Kim Jinseok , Brigham Mark D. , Shim Jaesool , Lee Seunghwan , Hwang Chang Mo , Durmus Naside Gozde , Demirci Utkan , Khademhosseini Ali
Published: January 2010

In this article, we describe an approach to generate microporous cell‐laden hydrogels for fabricating biomimetic tissue engineered constructs. Micropores at different length scales were fabricated in cell‐laden hydrogels by micromolding fluidic channels and leaching sucrose crystals. Microengineered channels were created within cell‐laden hydrogel precursors containing agarose solution mixed with sucrose crystals. The rapid cooling of the agarose solution was used to gel the solution and form micropores in place of the sucrose crystals. The sucrose leaching process generated homogeneously distributed micropores within the gels, while enabling the direct immobilization of cells within the gels. We also characterized the physical, mechanical, and biological properties (i.e., microporosity, diffusivity, and cell viability) of cell‐laden agarose gels as a function of engineered porosity. The microporosity was controlled from 0% to 40% and the diffusivity of molecules in the porous agarose gels increased as compared to controls. Furthermore, the viability of human hepatic carcinoma cells that were cultured in microporous agarose gels corresponded to the diffusion profile generated away from the microchannels. Based on their enhanced diffusive properties, microporous cell‐laden hydrogels containing a microengineered fluidic channel can be a useful tool for generating tissue structures for regenerative medicine and drug discovery applications. Biotechnol. Bioeng. 2010; 106: 138–148. © 2010 Wiley Periodicals, Inc.
Discovery and analysis of novel metabolic pathways for the biosynthesis of industrial chemicals: 3‐hydroxypropanoate
Authors: Henry Christopher S. , Broadbelt Linda J. , Hatzimanikatis Vassily
Published: January 2010

Sustainable microbial production of high‐value organic compounds such as 3‐hydroxypropanoate (3HP) is becoming an increasingly attractive alternative to organic syntheses that utilize petrochemical feedstocks. We applied the Biochemical Network Integrated Computational Explorer (BNICE) framework to the automated design and evaluation of novel biosynthetic routes for the production of 3HP from pyruvate. Among the pathways generated by the BNICE framework were all of the known pathways for the production of 3HP as well as numerous novel pathways. The pathways generated by BNICE were ranked based on four criteria: pathway length, thermodynamic feasibility, maximum achievable yield to 3HP from glucose, and maximum achievable activity at which 3HP can be produced. Four pathways emerged from this ranking as the most promising for the biosynthesis of 3HP, and three of these pathways, including the shortest pathways discovered, were novel. We also discovered novel routes for the biosynthesis of 28 commercially available compounds that are currently produced exclusively through organic synthesis. Examination of the optimal pathways for the biosynthesis of these 28 compounds in E. coli revealed pyruvate and succinate to be ideal intermediates for achieving high product yields from glucose. Biotechnol. Bioeng. 2010; 106: 462–473. © 2010 Wiley Periodicals, Inc.
A biohybrid artificial lung prototype with active mixing of endothelialized microporous hollow fibers
Authors: Polk Alexa A. , Maul Timothy M. , McKeel Daniel T. , Snyder Trevor A. , Lehocky Craig A. , Pitt Bruce , Stolz Donna Beer , Federspiel William J. , Wagner William R.
Published: January 2010

Acute respiratory distress syndrome (ARDS) affects nearly 150,000 patients per year in the US, and is associated with high mortality (≈40%) and suboptimal options for patient care. Mechanical ventilation and extracorporeal membrane oxygenation are limited to short‐term use due to ventilator‐induced lung injury and poor biocompatibility, respectively. In this report, we describe the development of a biohybrid lung prototype, employing a rotating endothelialized microporous hollow fiber (MHF) bundle to improve blood biocompatibility while MHF mixing could contribute to gas transfer efficiency. MHFs were surface modified with radio frequency glow discharge (RFGD) and protein adsorption to promote endothelial cell (EC) attachment and growth. The MHF bundles were placed in the biohybrid lung prototype and rotated up to 1,500 revolutions per minute (rpm) using speed ramping protocols to condition ECs to remain adherent on the fibers. Oxygen transfer, thrombotic deposition, and EC p‐selectin expression were evaluated as indicators of biohybrid lung functionality and biocompatibility. A fixed aliquot of blood in contact with MHF bundles rotated at either 250 or 750 rpm reached saturating pO2 levels more quickly with increased rpm, supporting the concept that fiber rotation would positively contribute to oxygen transfer. The presence of ECs had no effect on the rate of oxygen transfer at lower fiber rpm, but did provide some resistance with increased rpm when the overall rate of mass transfer was higher due to active mixing. RFGD followed by fibronectin adsorption on MHFs facilitated near confluent EC coverage with minimal p‐selectin expression under both normoxic and hyperoxic conditions. Indeed, even subconfluent EC coverage on MHFs significantly reduced thrombotic deposition adding further support that endothelialization enhances, blood biocompatibility. Overall these findings demonstrate a proof‐of‐concept that a rotating endothelialized MHF bundle enhances gas transfer and biocompatibility, potentially producing safer, more efficient artificial lungs. Biotechnol. Bioeng. 2010; 106: 490–500. © 2010 Wiley Periodicals, Inc.
The oxygen evolution methodology affects photosynthetic rate measurements of microalgae in well‐defined light regimes
Authors: Brindley Celeste , Acién Francisco G. , Fernández‐Sevilla José M.
Published: January 2010

Designing photobioreactors correctly is a must for the success of microalgal mass production. Optimal photobioreactor design requires a precise knowledge of photosynthesis dynamics in fluctuating light conditions and hence a method for the measurement of photosynthetic rates in specific light regimes. However, it is not uncommon in literature that experimental protocols used to obtain oxygen generation rates are described ambiguously and the reported rates of photosynthesis vary widely depending on the methodology. Additionally, quite a number of methods overlook certain aspects that can affect the estimated rates significantly, and can therefore affect photobioreactor design. We have developed a method based on oxygen evolution measurements that accurately determines photosynthetic rates under well‐defined light regimes. Our experimental protocol takes into account most of the issues that can affect the rates of oxygen generation, such as depletion of nutrients during the measurements and precision of the measurements. We have focused on the basic applications in photobioreactor design and used a dynamic model of photosynthesis to analyze our results and compare them with available published data. The results suggest that our oxygen evolution method is consistent. Biotechnol. Bioeng. 2010;106: 228–237. © 2010 Wiley Periodicals, Inc.
Oxygen plasma‐treated thermoresponsive polymer surfaces for cell sheet engineering
Authors: Shimizu Kazunori , Fujita Hideaki , Nagamori Eiji
Published: January 2010

Although cell sheet tissue engineering is a potent and promising method for tissue engineering, an increase of mechanical strength of a cell sheet is needed for easy manipulation of it during transplantation or 3D tissue fabrication. Previously, we developed a cell sheet–polymer film complex that had enough mechanical strength that can be manipulated even by tweezers (Fujita et al., 2009. Biotechnol Bioeng 103(2): 370–377). We confirmed the polymer film involving a temperature sensitive polymer and extracellular matrix (ECM) proteins could be removed by lowering temperature after transplantation, and its potential use in regenerative medicine was demonstrated. However, the use of ECM proteins conflicted with high stability in long‐term storage and low cost. In the present study, to overcome these drawbacks, we employed the oxygen plasma treatment instead of using the ECM proteins. A cast and dried film of thermoresponsive poly‐N‐isopropylacrylamide (PNIPAAm) was fabricated and treated with high‐intensity oxygen plasma. The cells became possible to adhere to the oxygen plasma‐treated PNIPAAm surface, whereas could not to the inherent surface of bulk PNIPAAm without treatment. Characterizations of the treated surface revealed the surface had high stability. The surface roughness, wettability, and composition were changed, depending on the plasma intensity. Interestingly, although bulk PNIPAAm layer had thermoresponsiveness and dissolved below lower critical solution temperature (LCST), it was found that the oxygen plasma‐treated PNIPAAm surface lost its thermoresponsiveness and remained insoluble in water below LCST as a thin layer. Skeletal muscle C2C12 cells could be cultured on the oxygen plasma‐treated PNIPAAm surface, a skeletal muscle cell sheet with the insoluble thin layer could be released in the medium, and thus the possibility of use of the cell sheet for transplantation was demonstrated. Biotechnol. Bioeng. 2010;106: 303–310. © 2010 Wiley Periodicals, Inc.
Targeted binding of PEG‐lipid modified polymer ultrasound contrast agents with tiered surface architecture
Authors: Duncanson Wynter J. , Oum Kelleny , Eisenbrey John R. , Cleveland Robin O. , Wheatley Margaret A. , Wong Joyce Y.
Published: January 2010

In order for site‐directed polymer ultrasound contrast agents (UCAs) to provide acoustic enhancement at disease sites to distinguish normal tissue from diseased tissue, the surface of these agents must be functionalized with mixtures of grafted polymers. Here a combination of longer liganded polyethylene glycol (PEG)‐lipids and shorter unliganded PEG‐lipids were introduced into the oil phase of a modified solvent evaporation double emulsion method for preparing UCAs. UCAs with different lengths of both liganded and unliganded lipids were imaged under 7.5 MHz ultrasound. The B‐mode image brightness of the mixed PEG‐lipid UCAs was within 1 dB the brightness of the unliganded surface. After 15 min of continuous insonation, 70% of the contrast signal remained. The peptide arginine–glycine–aspartic acid (RGD) was added to the surface of these UCAs through a biotin–avidin linkage and binding was assessed under static and shear conditions. Binding was significant after 30 min of static incubation and the adherence of the UCA increased under shear flow from 3 UCA/cell (static) to 5 UCA/cell (shear). Biotechnol. Bioeng. 2010; 106: 501–506. © 2010 Wiley Periodicals, Inc.
Larvicidal and Structure–Activity Studies of Natural Phenylpropanoids and Their Semisynthetic Derivatives against the Tobacco Armyworm Spodoptera litura (Fab.) (Lepidoptera: Noctuidae)
Authors: Bhardwaj Anu , Kumar Tewary Dhananjay , Kumar Rakesh , Kumar Vinod , Kumar Sinha Arun , Shanker Adarsh
Published: January 2010

The larvicidal activity of 18 phenylpropanoids, 1–18, including phenylpropenoate, phenylpropenal, phenylpropene, and their semisynthetic analogues, were evaluated against the tobacco armyworm, Spodoptera litura (Fab.), to identify promising structures with insecticidal activity. Amongst various phenylpropanoids, isosafrole, a phenylpropene, showed the best activity, with an LC50 value of 0.6 μg/leaf cm2, followed by its hydrogenated derivative dihydrosafrole (LC50=2.7 μg/leaf cm2). The overall larvicidal activity of various phenylpropene derivatives was observed in the following order: isosafrole (6)>dihydrosafrole (16)>safrole (12)>anethole (4)>methyl eugenol (11)>eugenol (13)>β‐asarone (8)>dihydroasarone (18)>dihydroanethole (15). Dihydrosafrole might be a promising compound, although presenting a lower larvicidal activity than isosafrole, because of its better stability and resistance to oxidative degradation (due to the removal of the extremely reactive olefinic bond) in comparison to isosafrole. Such structure–activity relationship studies promote the identification of lead structures from natural sources for the development of larvicidal products against S. litura and related insect pests.
Benzophenones from Guignardia sp. IFB‐E028, an Endophyte on Hopea hainanensis
Authors: Wang Feng‐Wu , Ye Yong‐Hao , Ding Hui , Chen Yun‐Xi , Tan Ren‐Xiang , Song Yong‐Chun
Published: January 2010

The first natural S‐containing benzophenone dimer, named guignasulfide (3), was isolated from the culture of Guignardia sp. IFB‐E028, an endophytic fungus residing in healthy leaves of Hopea hainanensis. Its structure was determined through correlative analyses of its MS, 1D‐ and 2D‐NMR spectroscopic data. Two other known benzophenone derivatives, monomethylsulochrin and rhizoctonic acid (1 and 2, resp.) were also isolated. Guignasulfide (3) was more active against the human liver cancer cell line HepG2 (IC50 value: 5.2±0.4 μM) than metabolites 1 and 2 (IC50 values: 63.5±0.6 and 60.2±0.5 μM); compounds 1–3 showed also moderately inhibitory effects on the human bacterial pathogen Helicobacter pylori with MIC values of 28.9±0.1, 60.2±0.4, and 42.9±0.5 μM, respectively.
Who Is the King? The α‐Hydroxy‐β‐oxo‐α,β‐enone Moiety or the Catechol B Ring: Relationship between the Structure of Quercetin Derivatives and Their Pro‐Oxidative Abilities
Authors: Liu Pei‐Yan , Li Kun , Zhang Ji , Zhang Da‐Wei , Lin Hong‐Hui , Yu Xiao‐Qi
Published: January 2010

Quercetin and other flavonoids have been reported to exhibit both antioxidant and pro‐oxidant properties. Most studies about the pro‐oxidative ability were conducted in the presence of metal ions, and the essential functional moiety of quercetin responsible for the pro‐oxidative effect is still unclear. In this study, we evaluated the pro‐oxidative abilities in the absence of metal ions of two quercetin derivatives, i.e., quercetin‐3′‐O‐β‐D‐glucoside (1) and quercetin‐3‐O‐β‐D‐glucoside (2), by assessing DNA cleavage and HO.‐radical production. The binding mode between these compounds and DNA was studied by fluorescence and viscometric titrations. The results showed that 1 can efficiently induce oxidative damage to plasmid DNA, while 2 shows poor activity. Both 1 and 2 bind to DNA via groove‐binding. These results proved that the α‐hydroxy‐β‐oxo‐α,β‐enone moiety contributes to the pro‐oxidative activity of quercetin.
Chiral Piperazine‐2,5‐dione Derivatives as Effective α‐Glucosidase Inhibitors. Part 4
Authors: Arcelli Antonio , Balducci Daniele , Porzi Gianni , Sandri Monica
Published: January 2010

The potential to inhibit α‐ and β‐glucosidases of a series of chiral piperazine‐2,5‐dione derivatives was investigated. Three of the seven compounds tested, viz., 1, 5b, and 5c, showed to be non competitive inhibitors of α‐glucosidase, whereas they exhibited very low inhibitory activity towards β‐glucosidase. The most active compound, 5c (KI of α‐glucosidase=5 μm), had a 100‐fold α‐glucosidase/β‐glucosidase inhibitor selectivity.
The Thioesterase Bhp is Involved in the Formation of β‐Hydroxytyrosine during Balhimycin Biosynthesis in Amycolatopsis balhimycina
Authors: Mulyani Sri , Egel Ellen , Kittel Claudia , Turkanovic Suada , Wohlleben Wolfgang , Süssmuth Roderich D. , van Pée Karl‐Heinz
Published: January 2010

The putative hydrolase gene bhp from the balhimycin biosynthetic gene cluster has been cloned and overexpressed in Escherichia coli. The corresponding enzyme Bhp was purified to homogeneity by nickel‐chelating chromatography and characterized. Although Bhp has sequence similarities to hydrolases with “haloperoxidase”/perhydrolase activity, it did not show any enzymatic activity with standard “haloperoxidase”/perhydrolase substrates (e.g., monochlorodimedone and phenol red), nonspecific esterase substrates (such as p‐nitrophenyl acetate, p‐nitrophenyl phosphate and S‐thiophenyl acetate) or the model lactonase substrate dihydrocoumarin. However, Bhp could be shown to catalyse the hydrolysis of S‐β‐hydroxytyrosyl‐N‐acetyl cysteamine thioester (β‐OH‐Tyr‐SNAC) with 15 times the efficiency of S‐L‐tyrosyl‐N‐acetyl cysteamine thioester (L‐Tyr‐SNAC). This is in agreement with the suggestion that Bhp is involved in balhimycin biosynthesis, during which it was supposed to catalyse the hydrolysis of β‐OH‐Tyr‐S‐PCP (PCP=peptidyl carrier protein) to free β‐hydroxytyrosine (β‐OH‐Tyr) and strongly suggests that Bhp is a thioesterase with high substrate specificity for PCP‐bound β‐OH‐Tyr and not a “haloperoxidase”/perhydrolase or nonspecific esterase.
Distal embolization after net protective stent (MGUARD™) implantation in a degenerated saphenous vein graft lesion
Authors: Yassin Ihab , Thuesen Leif
Published: January 2010

We describe a case of distal protection failure using the net protective stent system, MGUARD™ (InspireMD, Tel Aviv, Israel), in a degenerated saphenous vein graft (SVG) lesion. © 2010 Wiley‐Liss, Inc.
A novel concept in endovascular stenting for the treatment of old severely degenerated saphenous vein graft in the urgent setting
Authors: Hendler Alberto , Minha Saar , Krakover and Ricardo
Published: January 2010

We report a critically ill‐patient admitted for NSTEMI with acute pulmonary congestion, showing at urgent cardiac catheterization a severely diseased saphenous vein graft as the culprit vessel, with huge atherothrombotic burden. The graft was successfully revascularized by the implantation of 4 M‐Guard stent (for proximal to distal) creating a full metal jacket. The M‐Guard technology consists on a stainless steel platform wrapped by a micron‐level polymer net, that seamlessly expands when the stent is deployed, providing protection from embolic showers. © 2010 Wiley‐Liss, Inc.
Transcatheter aortic valve replacement
Authors: Dainese Luca , Fusari Melissa , Biglioli Paolo
Published: January 2010

We report a new technique of the partially and sequentially gonflage of the transcatheter balloon valve, the so called dog bone shaped technique, which allowed us to approach the aortic root by inflating the valve balloon in two different times, stabilizing the heart and deplacing the valve. © 2010 Wiley‐Liss, Inc.
Ionic Tags in Catalyst Optimization: Beyond Catalyst Recycling
Authors: Lombardo Marco , Trombini Claudio
Published: January 2010

In the pursuit of sustainability and efficiency in catalysis, the recourse to liquid–liquid biphasic homogeneous conditions is rapidly growing. In this context, the efficient entrapment of a catalyst in a solvent such as water or an ionic liquid can be achieved by installing an ionic substituent on the catalyst structure, the so called ion‐tag strategy. Little attention has been devoted in the literature to the fact that ion tags often improve catalytic performances compared to the parent tag‐free catalyst. From statistical scrutiny of literature data, a working hypothesis has been developed as a basis for further investigation and testing; a decrease of the free‐energy barrier is frequently observed as the result of an interplay of coulombic and steric interactions between developing charges in a polar transition state and the tag’s ion pair. If this is true, a way to develop more efficient catalytic protocols will entail a rational installation of an ionic group onto the structure of a known catalyst, complying with simple empirical guidelines that are discussed herein.
Metal Triflates as Highly Stable and Active Catalysts for the “Immortal” Ring‐Opening Polymerization of Trimethylene Carbonate
Authors: Helou Marion , Miserque Olivier , Brusson Jean‐Michel , Carpentier Jean‐François , Guillaume Sophie M.
Published: January 2010

The controlled “immortal” ring‐opening polymerization of trimethylene carbonate (TMC) using a two‐component catalyst system based on a metal Lewis acid, such as a metal triflate M(OTf)n (M=Ca, Sc, Zn, Al, Bi; OTf=CF3SO3−) or the metallic salt Fe(acac)3, (acac=acetylacetonate) and an alcohol (ROH) as co‐initiator and chain‐transfer agent, is carried out in bulk at 110–150 °C. As a result of the water‐tolerance of these systems, experimental operating conditions do not require any special care. The approach, valorized both with various ROH transfer agents and with either purified or unpurified monomer sources, is highly versatile. Functional telechelic polycarbonates HPTMCOR, devoid of decarboxylation sequences, are obtained [PTMC=poly(trimethylene carbonate)]. The molar mass of the PTMCs can be readily predicted by a simple model, taking into account the [TMC]0/[ROH]0 ratio and the amount of transferring impurities present in the raw/unpurified reagents. Such simple, air‐ and moisture‐robust catalytic systems, which display quite high activities (TOF up to 28 200 h−1) and productivities (TON up to 45 000) are thus extremely valuable, especially industrially. The performances of these systems are described in comparison to the previously established valuable inorganic and organometallic catalytic systems, namely metal amido complexes ([M{N(SiMe3)2}3]) and [(BDI)Zn{N(SiMe3)2}] (BDI=β‐diiminate ligand) derivatives.
Basal body duplication in Paramecium: The key role of Bld10 in assembly and stability of the cartwheel
Authors: Jerka‐Dziadosz Maria , Gogendeau Delphine , Klotz Catherine , Cohen Jean , Beisson Janine , Koll France
Published: January 2010

Basal bodies which nucleate cilia and flagella, and centrioles which organize centrosomes share the same architecture characterized by the ninefold symmetry of their microtubular shaft. Among the conserved proteins involved in the biogenesis of the canonical 9‐triplet centriolar structures, Sas‐6 and Bld10 proteins have been shown to play central roles in the early steps of assembly and in establishment/stabilization of the ninefold symmetry. Using fluorescent tagged proteins and RNAi to study the localization and function of these two proteins in Paramecium, we focused on the early effects of their depletion, the consequences of their overexpression and their functional interdependence. We find that both genes are essential and their depletion affects cartwheel assembly and hence basal body duplication. We also show that, contrary to Sas6p, Bld10p is not directly responsible for the establishment of the ninefold symmetry, but is required not only for new basal body assembly and stability but also for Sas6p maintenance at mature basal bodies. Finally, ultrastructural analysis of cells overexpressing either protein revealed two types of early assembly intermediates, hub‐like structures and generative discs, suggesting a conserved scaffolding process. © 2010 Wiley‐Liss, Inc.
Ten‐year follow‐up of a phase 2 study of dose‐intense paclitaxel with cisplatin and cyclophosphamide as initial therapy for poor‐prognosis, advanced‐stage epithelial ovarian cancer
Authors: Sarosy Gisele A. , Hussain Mahrukh M. , Seiden Michael V. , Fuller Arlan F. , Nikrui Najmosama , Goodman Annekathryn , Minasian Lori , Reed Eddie , Steinberg Seth M. , Kohn Elise C.
Published: January 2010

BACKGROUND:

The objective of this study was to assess activity and toxicity in patients with newly diagnosed, advanced‐stage epithelial ovarian cancer (EOC) who were receiving dose‐intense paclitaxel, cyclophosphamide, cisplatin, and filgrastim delivered with a flexible dosing schedule.

METHODS:

Patients with stage III/IV EOC received cyclophosphamide 750 mg/m2, followed by a 24‐hour infusion of paclitaxel 250 mg/m2 and cisplatin 75 mg/m2 on Day 2. Filgrastim began on Day 3 at 10 μg/kg daily for 9 days. Patients received 6 cycles of all drugs. Those who achieved a pathologic complete response or had microscopic residual disease at the conclusion of 6 cycles of therapy received an additional 2 to 4 cycles of paclitaxel with cyclophosphamide. Patients who had an objective response continued on cyclophosphamide and paclitaxel.

RESULTS:

Sixty‐two patients were enrolled. Thirty‐two of 62 patients had stage IIIC disease, and 26 of 62 patients had stage IV disease. According to an intent‐to‐treat analysis, 55 patients (89%) experienced a clinical complete remission. At a median potential follow‐up of 11.4 years, the median progression‐free survival was 18.9 months, and the median survival was 5.4 years. The most serious toxicity was grade 3/4 neutropenic fever (35%). Although all participants developed peripheral neuropathy, improvement in neuropathic symptoms began with the decrease or cessation of paclitaxel.

CONCLUSIONS:

The studied regimen yielded a high response rate and encouraging overall survival. The current data and those reported by the Japanese Gynecologic Oncology Group suggest that further study is warranted of dose‐dense or dose‐intense paclitaxel regimens in women with newly diagnosed, advanced‐stage EOC. Cancer 2010. © 2010 American Cancer Society.