bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of Attributes Determining Trip Chaining Behavior in Hybrid Microsimulation Urban Freight Models
Authors: Wang Qian , Holguín-Veras José
Published: January 2009

A hybrid microsimulation modeling framework is proposed to construct goods-related vehicle tours that satisfy a known commodity flow origin–destination (O-D) matrix in an urban freight network. One distinct issue of urban freight systems—trip chaining behavior—is addressed in the modeling procedure. To shed light on the variables that play significant roles in affecting trip chaining behavior, two types of discrete choice models are estimated by using a data set from the integrative freight market simulation. These models generate probabilities that help choose destination locations and make the decision about whether to return to the base or not for each tour until the known commodity O-D matrix is satisfied. The proposed modeling framework was applied to an 84-node test network. Results show that the estimated trip length distribution is consistent with the underlying data set. Meanwhile, several attributes are found to have significant effects on the trip chaining behavior. The choice of the next destination is negatively affected by the distance from the current location to the potential destination and positively affected by the amount of cargo available for pickup and delivery. For the tour termination decision, the perceived utility of returning decreases with the increase of the return distance and increases with the accumulation of cargoes delivered.
Application and Validation of Dynamic Freight Simulation–Assignment Model to Large-Scale Intermodal Rail Network
Authors: Zhang Kuilin , Nair Rahul , Mahmassani Hani S. , Miller-Hooks Elise D. , Arcot Vishnu Charan , Kuo April , Dong Jing , Lu Chung-Cheng
Published: January 2009

A dynamic intermodal multiproduct freight network simulation–assignment model is presented with application to a large-scale inter-modal rail network. Methodology pertaining to the simulation–assignment framework and representation and implementation considerations in dealing with large networks are discussed. The model is applied to a pan-European rail network spanning 11 countries from Scandinavia to Greece. Shipper decisions are disaggregated to an individual shipment level using a dynamic microassignment methodology in which a joint mode, path, service, and carrier choice is made. A mode choice function for this joint choice is calibrated, and issues relating to heterogeneity of freight characteristics are discussed. The model is validated by analyzing convergence patterns and measures of performance, namely, mode splits, compared with other studies. Two examples demonstrate the role of the model as a policy and decision support tool. The impact of expedited operations at international borders and infrastructure improvements on rail services is quantified.
Methodology of Hinterland Strategy Selection for Container Port Based on GE Matrix and Fuzzy TOPSIS
Authors: Zhang Yong , Ma Chenglin , Li Xuhong , Wang Sufang , Mao Haijun
Published: January 2009

Hinterland strategy selection is used to determine a sound marketing plan and resource allocation for ports in their own hinterlands to compete for container traffic. There are three types of hinterland strategies that ports can employ: expansive strategy, maintenance strategy, and recovery strategy. The aim of this paper is to develop a decision-making methodology for container ports to establish a logical international container hinterland strategy under a fuzzy environment based on the business strength and industry attractiveness matrix (GE matrix) and fuzzy technique for order performance by similarity to ideal solution (TOPSIS), in which the vagueness and subjectivity are handled with linguistics variables parameterized by triangular fuzzy numbers. This methodology took the attractiveness of international container hinterland units and a port's relative strength in every hinterland unit as the main assessing dimension to select a hinterland strategy. A fuzzy TOPSIS approach was used to evaluate the attractiveness of every international container hinterland unit and a port's relative competition in every hinterland unit. Furthermore, the GE matrix was erected to determine the hinterland strategy for a container port in every hinterland unit. Finally, the approach was demonstrated using the case of Lianyungang Port, China, which involved 30 international container hinterland units and 27 evaluation criteria. The application of a practical case indicates that this approach can provide effective decision support for container ports to establish an international container hinterland strategy.
Iterated Cooperation and Possible Deviations between Liner Shipping Carriers Based on Noncooperative Game Theory
Authors: Shi Xiaoning , Voss Stefan
Published: January 2009

The top liner shipping carriers have already established alliances in the shipping industry and are investigating new business connections with customers, suppliers, competitors, consultants, and other companies. Several studies have attempted to explain this phenomenon using a variety of conceptual and theoretical frameworks. This paper focuses on liner shipping strategic alliances and their establishment and transformation within the framework of noncooperative game theory, which is considered an effective tool to analyze motivations, competitive structures, strategies, and potential payoffs in a number of industries, including the turbulent liner shipping industry. Not only can a liner shipping company be seen as a player in a shipping alliance, but a liner shipping strategic alliance itself can be viewed as a player when it competes with other alliances. In this paper, more attention is paid to the former situation by assuming that those liner companies are unable to make enforceable contracts through outside parties. This paper aims to (a) indicate the motivations for short-term cooperation among several liner carriers, (b) analyze the pros and cons of being a member of a liner shipping strategic alliance, (c) explain a player's deviation or departure behavior when it faces turbulence and unpredictable shipping circumstances, and (d) recommend ways to enhance long-term alliance stability by increasing benefits while decreasing drawbacks. Of those four main points, the differences between short-term cooperation and long-term alliance are the number of subgames and the potential future payoff. Specific models based on the assumption of noncooperative behavior are set up as iterated games to give those differences clear explanations. The outcome of this paper will be helpful for liner shipping carriers attempting to succeed in the shipping industry with greater efficiency, better customer service, and lower cost.
Molecular Neuropathology of Gliomas
Authors: Riemenschneider Markus , Reifenberger Guido
Published: January 2009

Gliomas are the most common primary human brain tumors. They comprise a heterogeneous group of benign and malignant neoplasms that are histologically classified according to the World Health Organization (WHO) classification of tumors of the nervous system. Over the past 20 years the cytogenetic and molecular genetic alterations associated with glioma formation and progression have been intensely studied and genetic profiles as additional aids to the definition of brain tumors have been incorporated in the WHO classification. In fact, first steps have been undertaken in supplementing classical histopathological diagnosis by the use of molecular tests, such as MGMT promoter hypermethylation in glioblastomas or detection of losses of chromosome arms 1p and 19q in oligodendroglial tumors. The tremendous progress that has been made in the use of array-based profiling techniques will likely contribute to a further molecular refinement of glioma classification and lead to the identification of glioma core pathways that can be specifically targeted by more individualized glioma therapies.
New technologies and tools for study management: Lessons learned from designing and implementing a web-based data management system for a multisite longitudinal intervention study
Authors: Courtney Lauren , Warmoth Emily , Rodan Margaret , Katz Kathy
Published: January 2009

In epidemiologic research, effective tools for study management improve data quality, staff/time efficiency, and cost-effectiveness and strengthen study outcomes. The Web-based data management system (DMS) is a relatively new technology in epidemiologic research which provides significant benefits of these kinds. This paper addresses the design, technical implementation, and field experiences of using a Web-based DMS for the GirlTalk for Teen Moms Study, conducted as part of the NIH-DC Initiative to Reduce Infant Mortality in Minority Populations in Washington, DC (the NIH-DC Initiative).
RTI developed a Web-based DMS for the GirlTalk study to assist field staff from multiple sites in efficiently managing participant activities and data collection for this multiple component, multisite longitudinal study. The GirlTalk DMS monitors all activities for screening, recruitment, enrollment, in-depth interviews, randomization, interventions, repeated measures, outcomes, adverse events, and follow-up activities for each participant over the course of her 2-year enrollment in the study. Field staff from multiple sites use the DMS to manage more than 100 possible activities with a complex series of dependencies between activities that lead from one activity to the next.
We compare the features of the Web-based DMS used for GirlTalk with those of a personal computer (PC)-based DMS used previously by this research group. Our comparison presents the efficiencies obtained, including real-time data access, simplified software management, data security, and anytime/anywhere access for all users. We outline cost considerations for the Web-based DMS versus the PC-based system in terms of study size, study duration, number of sites, and technical infrastructure. We illustrate several features of the DMS, including the role-based menu, events tracking, appointment scheduling, shared calendars, report generation, access to study documents, and uploading of data files to RTI International secure servers. Finally, we compare the value of the Web-based tool versus the PC-based tool for study management.
Procesos de fabricación de metales celulares. Parte I: Procesos por vía líquida
Authors: Fernández P. , Cruz L. J. , Coleto J.
Published: January 2009

Los metales celulares, con sus interesantes y particulares características, constituyen parte de la gran familia de los nuevos materiales. Ellos pueden ser de porosidad abierta o cerrada. En la actualidad, el gran reto para los investigadores en materiales se fundamenta, aún, en el perfeccionamiento de las técnicas de fabricación que permitan obtener metales celulares reproducibles, confiables y de calidad. Por tal motivo, en el presente trabajo, se revisan los diferentes métodos de producción por vía líquida, haciendo una breve descripción de los principales parámetros involucrados y las ventajas y desventajas de cada uno de ellos.
Unique Identification of Supramolecular Structures in Amyloid Fibrils by Solid‐State NMR Spectroscopy
Authors: Nielsen Jakob T. , Bjerring Morten , Jeppesen Martin D. , Pedersen Ronnie O. , Pedersen Jan M. , Hein Kim L. , Vosegaard Thomas , Skrydstrup Troels , Otzen Daniel E. , Nielsen Niels C.
Published: January 2009

Die Fibrillenstruktur, die das amyloidogene Fragment SNNFGAILSS des menschlichen Insel‐Amyloid‐Polypeptids (hIAPP) bildet, wurde mit einer Auflösung von 0.52 Å bestimmt. Aus den Festkörper‐NMR‐Spektren einfach erhältliche Symmetrieinformationen (siehe Bild) können zusammen mit langreichweitigen Randbedingungen genutzt werden, um die supramolekulare Organisation von Fibrillen eindeutig zu identifizieren.

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A Selective Fluoroionophore Based on BODIPY‐functionalized Magnetic Silica Nanoparticles: Removal of Pb2+ from Human Blood
Authors: Lee Hye Young , Bae Doo Ri , Park Ji Chan , Song Hyunjoon , Han Won Seok , Jung Jong Hwa
Published: January 2009

Weg mit Blei: Der Fluoreszenzrezeptor im Titel zeichnet sich durch eine hohe Affinität und Selektivität für Pb2+ gegenüber konkurrierenden Metallionen in Wasser aus (siehe Bild), wobei der Faktor der gesamten Emissionsänderung am Emissionsmaximum für Pb2+ etwa 8 beträgt. Der Fluoreszenzrezeptor kann 96 % von 100 ppb Pb2+ aus menschlichem Blut entfernen und eignet sich für die effektive, selektive und schnelle Entfernung von Pb2+ in vivo.

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Proton‐Detected Solid‐State NMR Spectroscopy of Natural‐Abundance Peptide and Protein Pharmaceuticals
Authors: Zhou Donghua H. , Shah Gautam , Mullen Charles , Sandoz Dennis , Rienstra Chad M.
Published: January 2009

The natural way: A sensitive NMR spectroscopic method is developed to obtain well‐resolved two‐dimensional spectra (15N–1H and 13C–1H) for natural‐abundance (that is, without the need for isotopic enrichment) large‐molecule samples, such as biopharmaceuticals. This method gives structural insights on two lyophilized aprotinin samples and three insulin samples in lyophilized, microcrystalline suspension formulation (red; see picture) and fibril (green) forms.

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Structural and Electronic Properties of Ultrathin Tin–Phthalocyanine Films on Ag(111) at the Single‐Molecule Level
Authors: Wang Yongfeng , Kröger Jörg , Berndt Richard , Hofer Werner
Published: January 2009

Heads or tails? The evolution of structural and electronic properties of tin–phthalocyanine films has been analyzed for sub‐monolayer to multilayer coverage using low‐temperature scanning tunneling microscopy. Two molecular conformations are observed: randomly dispersed for the first layer, and islands with a single conformation in subsequent layers.

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Unique Identification of Supramolecular Structures in Amyloid Fibrils by Solid‐State NMR Spectroscopy
Authors: Nielsen Jakob T. , Bjerring Morten , Jeppesen Martin D. , Pedersen Ronnie O. , Pedersen Jan M. , Hein Kim L. , Vosegaard Thomas , Skrydstrup Troels , Otzen Daniel E. , Nielsen Niels C.
Published: January 2009

The fibril structure formed by the amyloidogenic fragment SNNFGAILSS of the human islet amyloid polypeptide (hIAPP) is determined with 0.52 Å resolution. Symmetry information contained in the easily obtainable resonance assignments from solid‐state NMR spectra (see picture), along with long‐range constraints, can be applied to uniquely identify the supramolecular organization of fibrils.

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A Selective Inhibitor Gal‐PUGNAc of Human Lysosomal β‐Hexosaminidases Modulates Levels of the Ganglioside GM2 in Neuroblastoma Cells
Authors: Stubbs Keith A. , Macauley Matthew S. , Vocadlo David J.
Published: January 2009

Gal‐PUGNAc (see picture), a highly selective inhibitor for β‐hexosaminidases HEXA and HEXB is cell‐permeable and modulates the activity of HEXA and HEXB in tissue culture, increasing ganglioside GM2 levels. Gal‐PUGNAc should allow the role of these enzymes to be studied at the cellular level without generating a complex chemical phenotype from concomitant inhibition of O‐GlcNAcase.

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A Selective Fluoroionophore Based on BODIPY‐functionalized Magnetic Silica Nanoparticles: Removal of Pb2+ from Human Blood
Authors: Lee Hye Young , Bae Doo Ri , Park Ji Chan , Song Hyunjoon , Han Won Seok , Jung Jong Hwa
Published: January 2009

Get the lead out: The title fluorescence receptor exhibits a high affinity and selectivity for Pb2+ over competing metal ions in water (see picture) with an overall emission change of approximately 8‐fold at the emission maximum for Pb2+. The fluorescence receptor can remove 96 % of 100 ppb Pb2+ from human blood, and can be useful and effective for the selective and rapid removal of Pb2+ in vivo.

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Professionelles Management im Verkehrsanlagenbau – Planen und Bauen unter rollendem Rad
Authors: Schönthaler Carmen
Published: January 2009

Im Rahmen dieses Beitrages wird das Projekt der Deutschen Bahn AG “Drei Brücken für Besigheim” vorgestellt. Es wird ein Überblick zur Gesamtbaumaßnahme gegeben. Die Bauwerke werden im Einzelnen aus bauwerkstechnischer Sicht betrachtet. Es werden Probleme in der Abwicklung beleuchtet und gefundene Lösungen aufgezeigt.

Die Thematik “Bauen unter rollenden Rad” und ein immens hoher Termindruck für die Inbetriebnahme der neuen Bauwerke bildeten dabei einen ganz eigenen komplexen Rahmen im Gesamtprojekt. Um der Komplexität zu begegnen, wurde der Einsatz eines professionellen Projekt‐ und Kommunikationsmanagements erforderlich: Um etwas gemeinsam zu tun, musste kommuniziert werden. Um das zu bewältigen, strebte man nach Exzellenz im Sinne des Total Quality Managements. Das Zusammenspiel aller Beteiligten trat in den Fokus. Als Lösungsansatz für einen hohen Zielerreichungsgrad diente eine effiziente und effektive Kommunikation. Erst die daraus resultierenden Synergieeffekte garantierten eine positive Umsetzung der Aufgabenstellung und führten zu einem qualitativ gelungenen Ergebnis (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Multinuclear Non‐Heme Iron Complexes for Double‐Strand DNA Cleavage
Authors: Megens Rik P. , van den Berg Tieme A. , de Bruijn A. Dowine , Feringa Ben L. , Roelfes Gerard
Published: January 2009

Bleomycin mimics: Efficient oxidative double‐strand DNA cleavage has been achieved with multinuclear non‐heme iron complexes (see scheme). These complexes therefore represent model compounds that mimic the mode of action of the anti‐tumor drug bleomycin.

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The cytotoxicity of the anti‐tumor drug BLM is believed to be related to the ability of the corresponding iron complex (Fe‐BLM) to engage in oxidative double‐strand DNA cleavage. The iron complex of the ligand N4Py (Fe‐N4Py; N4Py=N,N‐bis(2‐pyridyl)‐N‐bis(2‐pyridyl)methylamine) has proven to be a particularly valuable spectroscopic and functional model for Fe‐BLM. It is also a very active oxidative DNA‐cleaving agent. However, like all other synthetic Fe‐BLM mimics, it gives only single‐strand DNA cleavage. Since double‐strand DNA cleavage requires the delivery of two oxidizing equivalents to the DNA, it was envisaged that multinuclear iron complexes might be capable of effecting double‐strand cleavage. For this purpose, a series of ditopic and tritopic N4Py‐derived ligands has been synthesized and the corresponding iron complexes have been evaluated for their efficacy in the oxidative cleavage of supercoiled pUC18 plasmid DNA. The dinuclear iron complexes showed significantly enhanced double‐strand cleavage activity compared to mononuclear Fe‐N4Py, which was relatively independent of the structure of the linking moiety. Covalent attachment of a 9‐aminoacridine intercalator to a dinuclear complex did not give rise to improved double‐strand DNA cleavage. The most efficient oxidative double‐strand cleavage agents proved to be the trinuclear iron complexes. This is presumably the result of increased probability of the simultaneous delivery of two oxidizing equivalents to the DNA.
Do We Understand the Recyclability of Ionic Liquids?
Authors: Wu Bo , Liu WeiWei , Zhang YuMei , Wang HuaPing
Published: January 2009

Recycling of “green” solvents: Recycling of ionic liquids with high efficiency is of key importance on going from the laboratory‐scale to large‐scale industrial application of these solvents.

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Recyclability is one of the reasons why ionic liquids (ILs) are attracting the attention of a growing number of scientists and engineers, but do we understand the recyclability of ILs in a real sense? For this purpose, this review focuses on the methods need for their separation from their “working” environment. Here we proposed that the appropriate separation method should be selected according to different systems. To better understand the separation of ILs, fundamental research on the existence forms (ions, ion pairs or supermolecule) of ILs in solvents is vitally important.
Gated and Differently Functionalized (New) Porous Capsules Direct Encapsulates' Structures: Higher and Lower Density Water
Authors: Mitra Tamoghna , Miró Pere , Tomsa Adrian‐Raul , Merca Alice , Bögge Hartmut , Ávalos Josep Bonet , Poblet Josep Maria , Bo Carles , Müller Achim
Published: January 2009

Either more or less neighbors favored? By deliberate choice of the internal ligands of the porous nanocapsules [{(Mo)Mo5}12{Mo2(ligand)}30]n−, the respective cavities can be differently sized/functionalized. This allows one to trap, in two different corresponding capsules, 100 water molecules arranged in shells that exhibit more and less dense packing, respectively—the latter type in a capsule with smaller internal ligands; the picture shows the related 100 O atoms at the vertices of the four polyhedra, while two dodecahedra (shown in pale green and red) have only 10 H2O molecules instead of 20.

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By the deliberate choice of the internal ligands of the porous nanocapsules [{(Mo)Mo5}12{Mo2(ligand)}30]n−, the respective cavities' shells can be differently sized/functionalized. This allows one to trap the same large number of water molecules, that is, 100 in a capsule cavity with formate ligands having a larger space available, as well as in a cavity containing sulfates and hypophosphites, that is, with less space. Whereas the 100 molecules fill the space completely in the second case in which they are organized in three shells, a four‐shell system with underoccupation and broken hydrogen bonds is observed in the other case. This is an unprecedented result in terms of the structurally well defined special forms of “higher and lower density” water molecule assemblies. Precisely, by replacing the larger ligands in the mentioned nanocapsule type by formates, voids in the capsule cavity of (HC(NH2)2)22[{(HC(NH2)2)20+(H2O)100}⊂{(Mo)Mo5O21(H2O)6}12{Mo2O4(HCO2)}30]⋅ca. 200 H2O are generated that get filled with water molecules concomitant with an expansion of the three to four shell {H2O}100 cluster. The water shells in both capsules containing different ligands are organized in the form of dodecahedra (partly with underoccupation) and a strongly distorted rhombicosidodecahedron spanned by a {H2O}60={(H2O)5}12 aggregate. The well‐defined water shells only emerge if cations cannot enter into the capsules, which is achieved by closing the pores with plugs/guests such as formamidinium cations. The work is based on the syntheses of two new compounds, related single‐crystal X‐ray diffraction studies, and molecular dynamics simulations, which show remarkably that water molecule shell structuring occurs in the capsules due to the confined conditions even in the case of open pores and at room temperature if cation uptake is prevented.
Equilibrium and Kinetic Properties of the Lanthanoids(III) and Various Divalent Metal Complexes of the Heptadentate Ligand AAZTA
Authors: Baranyai Zsolt , Uggeri Fulvio , Giovenzana Giovanni B. , Bényei Attila , Brücher Ernő , Aime Silvio
Published: January 2009

Towards improved kinetic stability: A detailed account of the complexation properties of the ligand 1,4‐bis(hydroxycarbonylmethyl)‐6‐[bis(hydroxycarbonylmethyl)]amino‐6‐methylperhydro‐1,4‐diazepine (AAZTA; see figure) is reported. Its Gd3+ complex shows a kinetic stability superior to that of complexes formed by higher denticity ligands and opens the way for a new reference structure for MRI contrast agents.

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The heptadentate ligand 1,4‐bis(hydroxycarbonylmethyl)‐6‐[bis(hydroxycarbonylmethyl)]amino‐6‐methylperhydro‐1,4‐diazepine (AAZTA) and its derivatives were recently reported to give stable complexes with Gd3+ with superior efficiency as MRI contrast agents. Nevertheless, only preliminary data are available on the coordination behavior of this interesting ligand. In this work, thermodynamic and kinetic stability data are determined for the formation of complexes with AAZTA and the lanthanoid metal ions, and other divalent metal ions of interest for this application. The AAZTA ligand binds the lanthanoid ions with log KML values of 17.53–21.85 with its affinity steadily increasing from La3+ to Lu3+, suggesting that the seven‐membered skeleton is better suited to accommodate smaller metal ions. Even though the denticity is lower, the stability of the heavier lanthanoid complexes is comparable to those of the classical ligand diethylenetriaminepentaacetic acid (DTPA). The transmetalation reactions of [Gd(AAZTA)]− with Cu2+ and Eu3+ predominantly occur through proton‐assisted dissociation of the complex. The role of the direct attack of Cu2+ or Eu3+ in the exchange reactions is limited, although the formation of dinuclear complexes decreases the proton‐assisted dissociation. Near physiological conditions, [Gd(AAZTA)]− is significantly more inert than [Gd(DTPA)]2−, allowing its potentially safe use as contrast agent in magnetic resonance imaging.
In vivo analysis of MT‐based vesicle transport by confocal reflection microscopy
Authors: Gáspár Imre , Szabad János
Published: January 2009

The use of confocal reflection microscopy (CRM) for the in vivo analysis of microtubule (MT) mediated transport of lipid droplets in the developing Drosophila egg primordia is described here. The developing Drosophila oocytes are ideal objects to study MT‐mediated transport in vivo: transport of e.g. the lipid droplets can be conveniently, selectively and sensitively monitored through CRM and the egg primordia are readily available for physical, chemical and/or genetic manipulations. CRM is a non‐destructive way to follow vesicle movement and allows high frame rate image recording. When combined with fluorescence imaging, CRM offers simultaneous visualization of the cargo and the protein(s) of interest, i.e. a motor or a cargo adapter, thus allowing a better understanding of MT‐mediated transport and spatiotemporal coordination of the transport machinery. Cell Motil. Cytoskeleton 2009. © 2009 Wiley‐Liss, Inc.
Pancreatic neuroendocrine tumors
Authors: Hill Joshua S. , McPhee James T. , McDade Theodore P. , Zhou Zheng , Sullivan Mary E. , Whalen Giles F. , Tseng Jennifer F.
Published: January 2009

BACKGROUND:

Although surgical resection is generally recommended for patients with localized pancreatic neuroendocrine tumors (PNETs), the impact of resection on overall survival is unknown. The authors investigated the survival advantage of pancreatic resection using a national database.

METHODS:

This is a retrospective survival analysis of patients with PNETs from the Surveillance, Epidemiology, and End Results database (1988‐2002).

RESULTS:

A total of 728 patients with PNETs were identified with a median survival of 43 months using Kaplan‐Meier survival methods. Resection of tumor was associated with significantly improved survival compared with those patients who were recommended for but did not undergo resection (114 months vs 35 months; P < .0001). This survival benefit was demonstrated for patients with localized, regional, and metastatic disease. A multivariable Cox proportional hazards model was constructed to assess the overall effect of surgical resection on survival, and demonstrated an adjusted odds ratio of 0.48 (95% confidence interval, 0.35‐0.66) compared with those who were recommended for surgery but did not proceed to surgery.

CONCLUSIONS:

The authors have demonstrated in a large national study that resection of primary tumor in patients with PNETs is associated with improved survival across all disease stages. Patients with localized, regional, and metastatic PNETs who are reasonable operative candidates should be considered for resection of their primary tumors. Cancer 2009. © 2009 American Cancer Society.
Racial disparities in the development of breast cancer metastases among older women
Authors: Schootman Mario , Jeffe Donna B. , Gillanders William E. , Aft Rebecca
Published: January 2009

BACKGROUND:

Distant metastases are the most common and lethal type of breast cancer relapse. The authors examined whether older African American breast cancer survivors were more likely to develop metastases compared with older white women. They also examined the extent to which 6 pathways explained racial disparities in the development of metastases.

METHODS:

The authors used 1992‐1999 Surveillance, Epidemiology, and End Results (SEER) data with 1991‐1999 Medicare data. They used Medicare's International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify metastases of respiratory and digestive systems, brain, bone, or other unspecified sites. The 6 pathways consisted of patient characteristics, tumor characteristics, type of treatment received, access to medical care, surveillance mammography use, and area‐level characteristics (poverty rate and percentage African American) and were obtained from the SEER or Medicare data.

RESULTS:

Of the 35,937 women, 10.5% developed metastases. In univariate analysis, African American women were 1.61 times (95% confidence interval [CI], 1.54‐1.83) more likely to develop metastasis than white women. In multivariate analysis, tumor grade, stage at diagnosis, and census‐tract percentage African American explained why African American women were more likely to develop metastases than white women (hazard ratio, 0.84; 95% CI, 0.68‐1.03).

CONCLUSIONS:

Interventions to reduce late‐stage breast cancer among African Americans also may reduce racial disparities in subsequent increased risk of developing metastasis. African Americans diagnosed with high‐grade breast cancer could be targeted to reduce their risk of metastasis. Future studies should identify specific reasons why the racial distribution in census tracts was associated with racial disparities in the risk of breast cancer metastases. Cancer 2009. © 2009 American Cancer Society.
A possible association between aprotinin and improved survival after radical surgery for mesothelioma
Authors: Norman Peter H. , Thall Peter F. , Purugganan Ronaldo V. , Riedel Bernhard J. C. J. , Thakar Dilip R. , Rice David C. , Huynh Lisa , Qiao Wei , Wen Sijin , Smythe W. Roy
Published: January 2009

BACKGROUND:

Aprotinin has been used to decrease blood loss with complicated cardiac surgery but has not been investigated in extrapleural pneumonectomy, an operation that does not use cardiopulmonary bypass. In this prospective, randomized, placebo‐controlled, double‐blind trial, the authors investigated whether aprotinin decreased blood loss in patients who underwent this operation.

METHODS:

After appropriate statistical design and institutional review board approval, eligible patients who were scheduled for extrapleural pneumonectomy were randomized to receive either aprotinin or placebo during the operation. Blood loss and survival data were obtained from electronic medical records and surgical databases.

RESULTS:

Of 20 patients who were enrolled, 16 patients met criteria for blood loss analysis. Four patients were excluded from the blood loss analysis: Three patients were inoperable because of tumor spread and underwent limited surgery, and 1 patient died intraoperatively because of acute, massive hemorrhage. The mean blood loss was 769 mL with aprotinin versus 1832 mL with placebo (P = .05; Wilcoxon test). All 20 patients were included in survival analyses. All 9 patients who received placebo died. In contrast, 7 of 11 patients who received aprotinin remained alive at the time of the current report. Kaplan‐Meier survival curves differed significantly between the 2 groups (P = .0004). A Bayesian multivariate survival analysis of 18 patients who had complete data available on 8 prognostic variables indicated a posterior probability of .99 that aprotinin was beneficial.

CONCLUSIONS:

Aprotinin decreased blood loss. After accounting for covariate effects, there was a significant comparative benefit with aprotinin in postoperative survival. This finding was unexpected and could not be considered conclusive because of the small size of the current study. A confirmatory study may be warranted. Cancer 2009. © 2009 American Cancer Society.
Electron and X‐Ray Methods of Ultrafast Structural Dynamics: Advances and Applications
Authors: Chergui Majed , Zewail Ahmed H.
Published: January 2009

In this contribution, we highlight the state of the art in the determination of structures with ultrafast electrons and X‐rays. We provide our perspectives and reflections on the principles, techniques and methods, and on applications from different disciplines, with some focus on physical, chemical and biological structures. Although this article is not a survey of all the work done with these techniques, it provides a comprehensive referencing to current research.
3D image stack reconstruction in live cell microscopy ofDrosophilamuscles and its validation
Authors: Du Tiehua , Wasser Martin
Published: January 2009

Rapid movements of live tissues during the acquisition of 3D image stacks can result in misalignments between successive image slices. The remodeling of the muscles inDrosophilametamorphosis is an example where sporadic motion during image acquisition impede image analysis and volume visualization. Most of the image stack registration algorithms applied in microscopy are aimed at the linear alignment of fixed histological sections. However, live muscles are nonrigid objects and their contractions and relaxations represent nonlinear transformations that cannot be properly rectified by applying purely linear registration methods. We developed a fully automated area‐based nonrigid stack registration (NSR) method that minimizes the mean square error of intensities between successive image slices. The mapping function is formulated using the thin plate spline (TPS). A hierarchical linear to nonlinear, coarse to fine matching strategy is applied to ensure stability and fast convergence. Topological structure is preserved by constraining the step size of the nonlinear transformation. To assess the accuracy of 3D reconstruction, we propose a new benchmarking method that measures geometrical features of restored nuclei. We tested our algorithm on image stacks generated by laser scanning confocal microscopy that show live muscles during the prepupal stage ofDrosophilametamorphosis. Our registration algorithm is able to restore image stacks that are distorted by periodic contraction of muscles. Quantitative assessment of registration performance agrees well with qualitative visual inspection. Our NSR method is able to restore image stacks for the purpose of visualization and quantitative analysis ofDrosophilametamorphosis and, potentially, various other processes in developmental biology studied by 3D live cell microscopy. © 2009 International Society for Advancement of Cytometry
Development of olfactory ability in children: Sensitivity and identification
Authors: Monnery‐Patris S. , Rouby C. , Nicklaus S. , Issanchou S.
Published: January 2009

This study assessed the influence of school level and gender on odor sensitivity and identification, and the role of verbal capacity on odor identification in children (4–12 years) by using a revised version of an olfactory test designed for adults [Rouby et al. (1997). Connaissance et reconnaissance d'une série olfactive chez l'enfant préscolaire. Enfance, 1, 152–171]. We found that odor sensitivity and identification scores increased with school level, and that identification performance was better in girls than in boys. However, when we controlled verbal ability, the gender differences disappeared and the school level differences remained. This result indicates that the effect of gender on identification was probably due to the greater verbal ability of girls rather than to their greater olfactory ability per se. In addition, we found that general verbal ability is independent of olfactory fluency and that their influence on olfactory perception is different. Thus, this study illuminates the role of cognitive/verbal factors in the development of odor perception and knowledge. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 268–276, 2009
Binge‐like eating in mice
Authors: Consoli Daniele , Contarino Angelo , Tabarin Antoine , Drago Filippo
Published: January 2009

Objective

Given the lack of reliable murine model of binge‐like eating, we tried to induce this pathological behavior in mice.

Method

We used an experimental protocol mimicking the etiological factors involved in the development of binge eating in humans, that is, food restriction, refeeding (R‐R) in presence of high palatable food, and stress (S).

Results

Mice subjected to at least three cycles of R‐R plus S (forced swimming stress), showed a binge‐like behavior evident as early as 4 h, persisting 24 h after stress application and not associated to depressive‐like behavior. However, after the third R‐R/S cycle, food intakes of mice returned to normal levels.

Discussion

(i) at least three cycles of R‐R plus S are required to promote abnormal eating in mice, (ii) this is not associated to depressive‐like behaviors, and (iii) the enhanced pathological behavior showed a transient nature not persisting after the third R‐R/S cycle. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord, 2009
Anthrax protective antigen administered by DNA vaccination to distinct subcellular locations potentiates humoral and cellular immune responses
Authors: Midha Shuchi , Bhatnagar Rakesh
Published: January 2009

Based on the hypothesis that immune outcome can be influenced by the form of antigen administered and its ability to access various antigen‐processing pathways, we targeted the 63 kDa fragment of protective antigen (PA) of Bacillus anthracis to various subcellular locations by DNA chimeras bearing a set of signal sequences. These targeting signals, namely, lysosome‐associated membrane protein 1 (LAMP1), tissue plasminogen activator (TPA) and ubiquitin, encoded various forms of PA viz. lysosomal, secreted and cytosolic, respectively. Examination of IgG subclass distribution arising as a result of DNA vaccination indicated a higher IgG1:IgG2a ratio whenever the groups were immunized with chimeras bearing TPA, LAMP1 signals alone or when combined together. Importantly, high end‐point titers of IgG antibodies were maintained until 24 wk. It was paralleled by high avidity toxin neutralizing antibodies (TNA) and effective cellular adaptive immunity in the systemic compartment. Anti‐PA and TNA titers of ≈105 and ≈103, respectively, provided protection to ≈90% of vaccinated animals in the group pTPA‐PA63‐LAMP1. A significant correlation was found between survival percentage and post‐challenge anti‐PA titers and TNA titers. Overall, immune kinetics pointed that differential processing through various compartments gave rise to qualitative differences in the immune response generated by various chimeras.
IL‐4 blocks M‐CSF‐dependent macrophage proliferation by inducing p21Waf1 in a STAT6‐dependent way
Authors: Arpa Luis , Valledor Annabel F. , Lloberas Jorge , Celada Antonio
Published: January 2009

Macrophages are recruited from the blood stream to the inflammatory loci to carry out their functional activities. In an early phase of the cell cycle, macrophages become activated by Th1‐type cytokines (i.e. IFN‐γ), thereby producing several factors (cytokines, NO, etc.) and developing pro‐inflammatory activities. When bacteria and apoptotic bodies are removed, through the interaction with Th2‐type cytokines (i.e. IL‐4), macrophages become anti‐inflammatory and repair damaged tissues. Incubation of bone‐marrow‐derived macrophages with IFN‐γ or IL‐4 blocked their proliferation. While M‐CSF withdrawal caused cell cycle arrest at the early G1 phase, treatment of macrophages with IFN‐γ or IL‐4 caused this arrest later, at the G1/S boundary. Proliferation arrest was not due to an induction of apoptosis. IFN‐γ and IL‐4 induced the expression of the cyclin‐dependent kinase (Cdk) inhibitor p21Waf1. Using KO mice and iRNA experiments, we found that p21Waf1is required for IL‐4‐ but not for IFN‐γ‐dependent inhibition of macrophage proliferation. IL‐4 inhibited M‐CSF‐dependent Cdk‐2 and Cdk‐4 activities, which are necessary for entry and passage through the S phase of the cell cycle. The signal transduction used to induce the expression of p21Waf1after interaction of IL‐4 with the corresponding receptor was mediated by STAT6. Thus, IL‐4 and IFN‐γ blocked M‐CSF‐induced macrophage proliferation through distinct mechanisms.
Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergy
Authors: Lönnqvist Anna , Östman Sofia , Almqvist Nina , Hultkrantz Susanne , Telemo Esbjörn , Wold Agnes E. , Rask Carola
Published: January 2009

The hygiene hypothesis suggests that lack of microbial stimulation in early infancy may lead to allergy, but it has been difficult to identify particular protective microbial exposures. We have observed that infants colonised in the first week(s) of life with Staphylococcus aureus have lower risk of developing food allergy. As many S. aureus strains produce superantigens with T‐cell stimulating properties, we here investigate whether neonatal mucosal exposure to superantigen could influence the capacity to develop oral tolerance and reduce sensitisation and allergy. BALB/c mice were exposed to staphylococcal enterotoxin A (SEA) as neonates and fed with OVA as adults, prior to sensitisation and i.n. OVA challenge. Our results show that SEA pre‐treated mice are more efficiently tolerised by OVA feeding, as shown by lower lung‐cell infiltration and antigen‐specific IgE response in the SEA pre‐treated mice, compared with sham‐treated mice. This was not due to deletion or anergy of lymphocytes by SEA treatment, because the SEA pre‐treated mice that were fed with PBS showed similar inflammatory response as the sham‐treated PBS‐fed mice. Our results suggest that strong T‐cell activation in infancy conditions the mucosal immune system and promotes development of oral tolerance.
Th17 cells promote pancreatic inflammation but only induce diabetes efficiently in lymphopenic hosts after conversion into Th1 cells
Authors: Martin‐Orozco Natalia , Chung Yeonseok , Chang Seon Hee , Wang Yi‐Hong , Dong Chen
Published: January 2009

IDDM is characterized by leukocyte invasion to the pancreatic tissues followed by immune destruction of the islets. Despite the important function of Th17 cells in other autoimmune disease models, their function in IDDM is relatively unclear. In this study, we found association of elevated Th17 cytokine expression with diabetes in NOD mice. To understand the function of Th17 cells in IDDM, we differentiated islet‐reactive BDC2.5 TcR transgenic CD4+ cells in vitro into Th17 cells and transferred them into NOD.scid and neonate NOD mice. NOD.scid recipient mice developed rapid onset of diabetes with extensive insulitic lesions, whereas in newborn NOD mice, despite extensive insulitis, most recipient mice did not develop diabetes. Surprisingly, BDC2.5+ cells recovered from diabetic NOD.scid mice, in comparison with those from neonate NOD mice, showed predominant IFN‐γ over IL‐17 expression, indicating conversion of donor cells into Th1 cells. Moreover, diabetes progression in NOD.scid recipients was dependent on IFN‐γ while anti‐IL‐17 treatment reduced insulitic inflammation. These results indicate that islet‐reactive Th17 cells promote pancreatic inflammation, but only induce IDDM upon conversion into IFN‐γ producers.
Phosphorylation of the HuR ligand APRIL by casein kinase 2 regulates CD83 expression
Authors: Chemnitz Jan , Pieper Dorothea , Grüttner Cordula , Hauber Joachim
Published: January 2009

Fully mature DC and, to a lesser extent, activated T and B cells express CD83, a surface molecule that appears to fulfil an important role in efficient T‐cell activation. Recently, it has been shown that CD83 mRNA is transported from the nucleus to the cytoplasm by an uncommon route, involving the cellular RNA‐binding protein HuR and the nuclear export receptor CRM1. Moreover, the shuttle phosphoprotein APRIL (ANP32B) has been shown to be required for HuR‐mediated nucleocytoplasmic translocation of the CD83 mRNA by acting as an adaptor that links HuR and CRM1. Here, we are able to report that casein kinase 2 (CK2) phosphorylates APRIL on residue threonine244 (Thr244) and demonstrate that the CK2‐specific inhibitor 4,5,6,7‐tetrabromo‐2‐azabenzimidazole abolishes CD83 expression in activated Jurkat T cells by interfering with the nucleocytoplasmic translocation of CD83 mRNA. Depletion and knockdown studies demonstrate that the CK2 α′ subunit is necessary for this regulation, whereas the CK2 α subunit seems to be dispensable. Taken together, the data presented significantly extend our knowledge of the complex regulation of CD83 mRNA processing and provides a novel strategy to interfere with CD83 expression.
Long‐lasting cross‐presentation of tumor antigen in human DC
Authors: Faure Florence , Mantegazza Adriana , Sadaka Charlotte , Sedlik Christine , Jotereau Francine , Amigorena Sebastian
Published: January 2009

DC cross‐present exogenous antigens on MHC class I molecules, a process required for the onset of anti‐tumor immune responses. In order to study the cross‐presentation of tumor antigens by human DC, we compared the pathways of cross‐presentation of long peptides requiring internalization and intracellular processing with the direct presentation of short peptides, which does not require intracellular processing. We found that, after brief incubations with DC, short peptides were presented to CD8+ T cells with higher efficiencies than long peptides. After longer times of chase in the absence of peptide, however, the efficiency of presentation of the two types of peptides was reversed. After 2–3 days, DC pulsed with long peptides still activated T cells efficiently, while DC pulsed with short peptides failed to do so. Long‐lasting presentation of the long peptides was, at least in part, due to a stored persistent pool of antigen, which was still available for loading on MHC class I molecules after several days of chase. These results show that the use of long synthetic peptides allows the efficient, long‐lasting, presentation of tumor antigens, suggesting that long peptides represent an interesting approach for active anti‐tumor vaccination.
Triacylglycerols of Apiaceae seed oils: Composition and regiodistribution of fatty acids
Authors: Ngo‐Duy Cam‐Chi , Destaillats Frédéric , Keskitalo Marjo , Arul Joseph , Angers Paul
Published: January 2009

Oils from the seeds of caraway (Carum carvi), carrot (Daucus carota), celery (Apium graveolens) and parsley (Petroselinum crispum), all from the Apiaceae family, were analyzed by gas chromatography for their triacylglycerol (TAG) composition and fatty acid (FA) distribution between the sn‐1(3) and sn‐2 positions of TAG. Twenty‐two TAG species were quantified. Glyceryl tripetroselinate was the major TAG species in seed oils of carrot, celery and parsley, with levels ranging from 38.7 to 55.3%. In caraway seed oil, dipetroselinoyllinoleoylglycerol was the major TAG species at 21.2%, while the glyceryl tripetroselinate content was 11.4%. Other TAG species were linoleoyloleoylpetroselinoylglycerol and dipetroselinoyloleoylglycerol. Predominantly, TAG were triunsaturated (72.2–84.0%) with diunsaturates at 14.4–25.9%, and small amounts of monounsaturated TAG. Results for regiospecific analysis showed a non‐random FA distribution in Apiaceae for palmitic, petroselinic, linoleic and oleic acids. Petroselinic acid was predominantly located at the sn‐1(3) position in carrot, celery and parsley seed oils, while it was mainly at the sn‐2 position in caraway seed oil. The distribution of linoleic acid was opposite to that of petroselinic acid. Oleic acid was mostly located at the sn‐2 position, except for caraway, where it was evenly distributed between the sn‐1(3) and sn‐2 positions. Both the saturated FA, palmitic and stearic acid, were located mainly at the sn‐1(3) position. The presence of a high level of tripetroselinin in parsley seed oil (55.3%) makes it a potential source for the production of petroselinic acid.