bluuebunny/crossref_metadata_2025 huggingface dataset:
Composite Nearest Neighbor Nonparametric Regression to Improve Traffic Prediction
Authors: Kindzerske Matthew D. , Ni Daiheng
Published: October 2007

The ability to predict traffic conditions accurately is of paramount importance in effective management of a highway network. A more accurate prediction will allow for better allocation of resources, which may reduce experienced travel times. This paper introduces a composite approach to the already popular nonparametric regression used in predicting traffic conditions. The composite approach performs a nearest neighbor search for each loop detector station using only data that are in proximity to the detector's position on the roadway. This method accommodates every detector station individually to minimize the forecast error on the entire roadway. A case study using data from the Next Generation Simulation program recorded on US Highway 101 demonstrates that the composite approach significantly mitigates forecast error and performs the forecast in a reasonable amount of computational time. The case study also shows the ability of the composite approach to predict the onset and propagation of traffic shock waves.
Impact of Data Integration on Some Important Travel Behavior Indicators
Authors: Nakamya Juliet , Moons Elke , Koelet Suzana , Wets Geert
Published: October 2007

Travel surveys are one of the most important ways of obtaining the critical information needed for transportation planning and decision making today. Reliable and quality data from household travel surveys also demand large sample sizes. These surveys are notoriously expensive, however, and highly time-consuming, and they are faced with a high response burden and subsequent low response rates. Although methodological and technological survey techniques have become increasingly refined, high unit costs and public resistance will continue to plague future survey efforts. This paper investigates the impact of combining survey data from different sources on some important travel behavior indicators. Given the availability of other types of surveys such as time use surveys, which tend to collect a great deal of important data in regard to people's travel, a wealth of information can be obtained through combining these data with the available travel survey data. Initially, survey data were weighted on the basis of census data on some important socio-demographic characteristics that had been shown to have an impact on travel. Hereby, the fact that census data had the required sample size but generally did not have the required information on travel was exploited. The Flemish travel survey data were then combined with the Flemish time use survey data. The resultant combined data set offered a larger and more representative sample of the population, which gave more reliable travel information on the population. The larger sample was valuable in the prediction of travel demand and can also be used as a base for simulating travel data.
Numerical Characterization of Gross Vehicle Weight Distributions from Weigh-in-Motion Data
Authors: Nichols Andrew P. , Cetin Mecit
Published: October 2007

This paper presents a method for quantifying gross vehicle weight (GVW) distributions of commercial vehicles using weigh-in-motion (WIM) data. Finite mixture models are used to fit a combination of normal distributions to the overall GVW distribution to identify peak parameters more precisely. The GVW distribution is commonly bimodal or trimodal with prominent peaks occurring in the loaded and unloaded weight ranges. The GVW characteristics of FHWA Class 9 vehicles are commonly used for assessing WIM accuracy by visual interpretation of frequency histograms. Temporal changes in the GVW distribution are difficult to detect using common visualization techniques. Mixture models enable the statistical identification of the modal peaks and the proportion of traffic belonging to those peaks for ongoing monitoring purposes. Mixture models are applied to a WIM site in Indiana to illustrate the analysis method and benefits. Numerical monitoring of the GVW distribution is shown to have some advantages over the widely accepted metric based on the Class 9 steer axle weight. The proposed metric should not be used singularly, rather as an additional tool to complement existing metrics.
Masculinity, Emotion and Subjectivity: Introduction
Authors: Peel Mark , Caine Barbara , Twomey Christina
Published: October 2007

This introduction summarizes the key themes raised in a symposium on masculinity, emotion and subjectivity at Monash University in 2006. These include ways of writing about the lived experience of masculinity in the past as well as the present, especially in terms of how men understand and use the “scripts” that prescribe and describe manliness, and questions of sources and approaches for the study of masculinity as a performance.
Emaciation or Emasculation: Photographic Images, White Masculinity and Captivity by the Japanese in World War Two
Authors: Twomey Christina
Published: October 2007

This article argues for the need to historicize the use and reception of photographs taken of Allied POWs upon release from Japanese prison camps at the end of World War Two. Photographs of semi-naked, emaciated POWs at the time of their liberation were extremely unusual images of white men in a state of almost complete abjection. They provide an opportunity to explore the links between masculinity and war with particular reference to the way visual images—in this case photography—inform and shape that relationship. The images convey contradictory messages to the viewer. They undermine the hegemonic masculinity of the virile male warrior yet unmistakably invoke the power of a quite singular cultural referent: the suffering body of Christ. The argument to be explored here is that this duality of transgression and redemption has contributed to the images' iconic status in collective memories of Australian participation in the Pacific War.
“I Ain't Queer”: Love, Masculinity and History in Brokeback Mountain
Authors: Boucher Leigh , Pinto Sarah
Published: October 2007

Ang Lee's big gay tragic historical love story, Brokeback Mountain, was released internationally in late 2005 and early 2006. Lee's film told the story of two cowboys who fell in love while shepherding on Brokeback Mountain in Wyoming in 1963. Although the film narrated a demonstrably American story, appeals to a socio-historical connection were widespread in Australia. Indeed, Brokeback Mountain's cinematic release in this country coincided with “Australia Day,” a national day of celebration in which beginnings, nationhood, and “settlement” are reaffirmed. In this article, we track the explosion of publicly-audible conversations that took place in Brokeback Mountain's wake in Australia in 2006. On the one hand, we seek to historicize this film; on the other, we also consider the political ways in which it historicized. As the “noise” about Brokeback Mountain became almost impossible to ignore in Australia, we noticed the film tended to be viewed as a cause for celebration. Through an analysis of the politics of historical stories and the gendered politics of emotion, we seek to complicate the notion that this film signified a radical departure from homophobic cinematic and cultural traditions.
Subjectivity under Erasure: Adolescent Sexuality, Gender, and Teacher-Student Sex
Authors: Angelides Steven
Published: October 2007

This article offers a reading of a recent Australian teacher-student sex scandal in order to interrogate the relationship between gendered subjectivity and cultural codes of gender. The questions of whether gender ought to make a difference to how we understand instances of so-called “intergenerational sex” and whether cultural codes accurately reflect sexual subjectivity are posed. It is argued that while cultural codes are not external or equivalent to subjectivity, this does not mean that they are not expressive of elements of subjectivity. The article concludes with the suggestion that the failure to attend to the nexus of the social and the psychical not only serves to strengthen a very recent and particular set of historical, political, and ideological forces but also risks creating foundations for misreadings of the history of male adolescent subjectivities.
The Wende in GDR Research
Authors: Baylis Thomas A.
Published: October 2007

Laurence McFalls and Lothar Probst, eds., After the GDR: New Perspectives on the Old GDR and the Young Länder. German Monitor No. 54 (Amsterdam: Editions Rodopi, 2001)

Corey Ross, The East German Dictatorship: Problems and Perspectives in the Interpretation of the GDR (London: Arnold Publishers, 2002)
Protest and Reform in Asylum Policy: Citizen Initiatives versus Asylum Seekers in German Municipalities, 1989-1994
Authors: Karapin Roger
Published: October 2007

Many writers have argued that anti-immigration politics in Germany

and other West European countries have been driven by radical-right

parties or the electoral maneuvering of national politicians

from established parties. Others have argued that waves of violence

against immigrants and ethnic minorities have spurred anti-immigration

politics, or that racist ideologies and socioeconomic inequality

are the root causes. By comparison, authors have paid relatively little

attention to anti-immigration mobilization at subnational levels,

including the public positions taken by subnational politicians and

the activities of movement groups, or “challengers.” Nonetheless,

research has shown that subnational politicians are often important

in pressing national campaigns for immigration controls. Moreover,

as I have argued elsewhere, anti-immigration politicians in Britain

and Germany have responded in large part to local challengers, who

were aided by political elites at local and regional levels.
Wähler als Wandervögel: Dealignment and the German Voter
Authors: Dalton Russell J. , Bürklin Wilhelm
Published: October 2007

The 2002 Bundestag elections demonstrate the emerging new style

of German electoral politics. Where once party competition was

built upon a stable base of Stammwähler, the catchword for 2002 was

the Wechselwähler—the changing voter. The traditional bonds to social

groups, such as class and religion, have steadily eroded across Bundestag

elections in the late twentieth century, and these bonds had a

diminished impact in 2002. Similarly, this chapter will demonstrate

that affective psychological ties that once connected citizens to their

preferred party have also weakened. Certainly some German voters

remain connected to a social milieu or a habitual party tie, but the

number of these voters is steadily decreasing.
The Frankfurt School's Invitation from Columbia University: How the Horkheimer Circle Settled on Morningside Heights
Authors: Wheatland Thomas
Published: October 2007

Oddly enough, the Frankfurt School’s relationship to Columbia University

has been somewhat neglected by its many historians. It is not

hard to understand why the Horkheimer circle would have desired

to settle at Columbia, but it is peculiar that the Frankfurt School

would have received an invitation from Columbia. After all, why

would Columbia University’s conservative president, Nicholas Murray

Butler, and its sociology department extend an invitation to a

group of predominantly German-speaking social philosophers with

strong links to the Marxian left?
Winning by Priming? Campaign Strategies, Changing Determinants of Voting Intention, and the Outcome of the 2002 German Federal Election
Authors: Schoen Harald
Published: October 2007

Although governing coalitions in Germany often win reelection,

many observers were surprised by the victory of the red-green coalition

in 2002. Earlier that year, the polls had shown strong support

for a potential coalition of the Christian Democratic Union (CDU)

and the Christian Social Union (CSU), together with the Free Democratic

Party (FDP). In the summer of 2002, however, the SPD and

the Greens began to gain ground; and finally, the red-green coalition

won the majority of seats in the election to the German parliament,

the Bundestag, on 22 September 2002.
Still Connected to Home: The Politics of Immigrant Transnationalism in Germany
Authors: Brady John
Published: October 2007

Betigül Ercan Argun, Turkey in Germany: The Transnational Space of Deutschkei (New York: Routledge, 2003)

Eva Østergaard-Nielsen, Transnational Politics: Turks and Kurds in Germany (New York: Routledge, 2003)
Sequence evaluation of FGF and FGFR gene conserved non‐coding elements in non‐syndromic cleft lip and palate cases
Authors: Riley Bridget M. , Murray Jeffrey C.
Published: October 2007

Non‐syndromic cleft lip and palate (NS CLP) is a complex birth defect resulting from multiple genetic and environmental factors. We have previously reported the sequencing of the coding region of genes in the fibroblast growth factor (FGF) signaling pathway, in which missense and non‐sense mutations contribute to approximately 5%–6% NS CLP cases. In this article we report the sequencing of conserved non‐coding elements (CNEs) in and around 11 of the FGF and FGFR genes, which identified 55 novel variants. Seven of variants are highly conserved among ≥8 species and 31 variants alter transcription factor binding sites, 8 of which are important for craniofacial development. Additionally, 15 NS CLP patients had a combination of coding mutations and CNE variants, suggesting that an accumulation of variants in the FGF signaling pathway may contribute to clefting. © 2007 Wiley‐Liss, Inc.
On the normalization and visualization of author co‐citation data: Salton's Cosine versus the Jaccard index
Authors: Leydesdorff Loet
Published: October 2007

The debate about which similarity measure one should use for the normalization in the case of Author Co‐citation Analysis (ACA) is further complicated when one distinguishes between the symmetrical co‐citation—or, more generally, co‐occurrence—matrix and the underlying asymmetrical citation—occurrence—matrix. In the Web environment, the approach of retrieving original citation data is often not feasible. In that case, one should use the Jaccard index, but preferentially after adding the number of total citations (i.e., occurrences) on the main diagonal. Unlike Salton's cosine and the Pearson correlation, the Jaccard index abstracts from the shape of the distributions and focuses only on the intersection and the sum of the two sets. Since the correlations in the co‐occurrence matrix may be spurious, this property of the Jaccard index can be considered as an advantage in this case.
Destruction and reconstruction: Hypoxia and the developing brain
Authors: Barrett Robert D. , Bennet Laura , Davidson Joanne , Dean Justin M. , George Sherly , Emerald Bright S. , Gunn Alistair Jan
Published: October 2007

Preterm infants have a high rate of neurodevelopmental handicap. Recent imaging studies have revealed that adverse outcomes are strongly associated with reduced brain growth and neural complexity in later life. Increasing data suggest that these chronic deficits primarily reflect acute neuronal and glial injury sustained during adverse in utero events, such as exposure to severe hypoxia–ischemia and inflammation. In the present review we examine recent evidence that this chronic impairment is partly due to upregulation of physiological apoptosis, related to input deprivation, and output isolation secondary to acute white and gray matter damage and axonal injury. However, progenitor cells in the subventricular zone (SVZ) are also vulnerable to injury, and loss of part of this critical population likely further compromises brain development. Based on these concepts the impact of proposed interventions such as induced hypothermia and endogenous growth factors are likely to be complex, but potentially offer focused ways of improving the outcomes of premature birth. Birth Defects Research (Part C) 81:163–176, 2007. © 2007 Wiley‐Liss, Inc.
Effects of oxidative stress on embryonic development
Authors: Dennery Phyllis A.
Published: October 2007

Oxygen radicals, or reactive oxygen species (ROS) act as primary or secondary messengers to promote cell growth or death. Many instances demonstrate an important direct role of ROS in development because redox status regulates key transcription factors that influence cell signaling pathways involved in proliferation, differentiation, and apoptosis. Therefore, oxidative stress can alter many important reactions that affect embryonic development both positively and negatively. During particular periods in development, the embryo is more or less susceptible to oxidative stress, and teratogens, which can modify redox status, such as thalidomide, phenytoin, and ethanol, will disrupt fetal development. Various events in pregnancy such as diabetes also alter the redox state. Fortunately, antioxidants can obviate these effects through modification of gene expression, transcription factor signaling, and cell cycle alterations. A better understanding of ROS‐mediated reactions and their impact on embryonic development is important to ensure optimal outcomes. Birth Defects Research (Part C) 81:155–162, 2007. © 2007 Wiley‐Liss, Inc.
Folate‐mediated one‐carbon metabolism and neural tube defects: Balancing genome synthesis and gene expression
Authors: Beaudin Anna E. , Stover Patrick J.
Published: October 2007

Neural tube defects (NTDs) refer to a cluster of neurodevelopmental conditions associated with failure of neural tube closure during embryonic development. Worldwide prevalence of NTDs ranges from approximately 0.5 to 60 per 10,000 births, with regional and population‐specific variation in prevalence. Numerous environmental and genetic influences contribute to NTD etiology; accumulating evidence from population‐based studies has demonstrated that folate status is a significant determinant of NTD risk. Folate‐mediated one‐carbon metabolism (OCM) is essential for de novo nucleotide biosynthesis, methionine biosynthesis, and cellular methylation reactions. Periconceptional maternal supplementation with folic acid can prevent occurrence of NTDs in the general population by up to 70%; currently several countries fortify their food supply with folic acid for the prevention of NTDs. Despite the unambiguous impact of folate status on NTD risk, the mechanism by which folic acid protects against NTDs remains unknown. Identification of the mechanism by which folate status affects neural tube closure will assist in developing more efficacious and better targeted preventative measures. In this review, we summarize current research on the relationship between folate status and NTDs, with an emphasis on linking genetic variation, folate nutriture, and specific metabolic and/or genomic pathways that intersect to determine NTD outcomes. Birth Defects Research (Part C) 81:183–203, 2007. © 2007 Wiley‐Liss, Inc.
Circadian clocks during embryonic and fetal development
Authors: Seron‐Ferre Maria , Valenzuela Gullermo J. , Torres‐Farfan Claudia
Published: October 2007

Circadian rhythmicity is a fundamental characteristic of organisms, which helps ensure that vital functions occur in an appropriate and precise temporal sequence and in accordance with cyclic environmental changes. Living beings are endowed with a system of biological clocks that measure time on a 24‐hr basis, termed the circadian timing system. In mammals, the system is organized as a master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus, commanding peripheral clocks located in almost every tissue of the body. At the cell level, interlocking transcription/translation feedback loops of the genes Bmal‐1, Clock, Per1–2, and Cry1–2, named clock genes, and their protein products results in circadian oscillation of clock genes and of genes involved in almost every cellular function. During gestation, the conceptus follows a complex and dynamic program by which it is simultaneously fit to develop and live in a circadian environment provided by its mother and to prepare for the very different environment that it will experience after birth. It has been known for a number of years that the mother tells the fetus the time of day and season of the year, and that the fetus uses this information to set the phase of fetal and neonatal circadian rhythms. There is evidence that the maternal rhythm of melatonin is one of the time signals to the fetus. In the last few years, the study of the development of the circadian system has turned to the investigation of the oscillatory expression of clock genes and their possible role in development, and to answering questions on the organization of the fetal circadian system. Emerging evidence shows that clock genes are expressed in the oocyte and during early and late development in embryo/fetal organs in the rat and in a fetal primate. The data available raise the intriguing possibility that the fetal SCN and fetal tissues may be peripheral clocks commanded by separate maternal signals. The rapid methodological and conceptual advances on chronobiology may help to unravel how the developing embryo and fetus faces time in this plastic period of life. Birth Defects Research (Part C) 81:204–214, 2007. © 2007 Wiley‐Liss, Inc.
Kammerbetonierte Verbundträger
Authors: Hegger Josef , Goralski Claus
Published: October 2007

Mit Einführung der modernen Verbundbaunorm DIN 18800‐5 können unter bestimmten Voraussetzungen plastische Bemessungsverfahren für den Nachweis der Momenten‐ und Querkrafttragfähigkeit kammerbetonierter Verbundträger angewandt werden. Aufgrund fehlender mechanischer Modelle und Bemessungsregeln, insbesondere bei hochfesten Baustoffen, wurde die traglaststeigernde Wirkung des Kammerbetons in der Praxis bisher häufig nicht genutzt. Die rechnerische Erfassung des Kammerbetons erfordert weiter die Beschreibung der Verbundmechanismen zwischen Kammerbeton und Stahlprofil. Dieser Beitrag gibt einen Einblick in die Lastabtragungsmechanismen kammerbetonierter Verbundträger und beschreibt Bemessungsansätze zum wirtschaftlichen und sicheren Einsatz von hochfesten Baustoffen. Anhand einer Parameteruntersuchung zum Einfluss von hochfestem Kammerbeton und hochfestem Stahl auf die Querschnittstragfähigkeit des Verbundträgers wird ein plastisches Bemessungsverfahren für kammerbetonierte Verbundträger im positiven und negativen Momentenbereich hergeleitet. Die Verbundmechanismen am Biegeträger wurden anhand experimenteller Untersuchungen und dreidimensionaler nicht‐linearer Finite Elemente Modelle lokalisiert und quantifiziert.
Zur maximalen Durchstanztragfähigkeit von Flachdecken.
Authors: Hegger Josef , Häusler Frank , Ricker Marcus
Published: October 2007

In Eurocode 2 wird die maximale Durchstanztragfähigkeit abweichend von DIN 1045‐1 und anderen internationalen Normen in Analogie zur Druckstrebentragfähigkeit von Balken ermittelt. Die in Versuchen erzielten Durchstanzlasten liegen i. d. R. deutlich unterhalb der rechnerischen Tragfähigkeit nach Eurocode 2, der für bügelbewehrte Platten größere Traglasten ausweist als die Zulassungen für Platten mit Doppelkopfankern. Um die Größe des maximalen Durchstanzwiderstands von Flachdecken zu überprüfen, wurden am Institut für Massivbau der RWTH Aachen ein Durchstanzversuch an einem bügelbewehrten Plattenausschnitt und eine Datenbankauswertung durchgeführt.
Macrocyclic Statine‐Based Inhibitors of BACE‐1
Authors: Barazza Alessandra , Götz Marion , Cadamuro Sergio A. , Goettig Peter , Willem Michael , Steuber Holger , Kohler Tanja , Jestel Anja , Reinemer Peter , Renner Christian , Bode Wolfram , Moroder Luis
Published: October 2007

Minimal sequence requirements for binding of substrate‐derived statine peptides to the aspartyl enzyme were established on the basis of the X‐ray cocrystal structure of the hydroxyethylene‐octapeptide OM00‐3 in complexation with BACE‐1. With this information to hand, macrocyclic compounds that conformationally restrict and preorganize the peptide backbone for an entropically favoured binding to the enzyme active site cleft were designed. By means of a side chain‐to‐side chain ring closure between two aspartyl residues in the P2 and P3′ positions through phenylene‐1,3‐dimethanamine, a 23‐membered ring structure was obtained; this structure retained an extended conformation of the peptide backbone, including the transition state analogue statine for tight interactions with the two aspartyl residues of the active centre. The conformational preorganization of the inhibitor molecule was verified by NMR structural analysis and was then confirmed by the crystal structure of the BACE‐1/inhibitor complex. Detailed insights into the binding mode of this macrocyclic inhibitor explained its moderate binding affinity in cell‐free assays (Ki=2.5 μM) and yielded precious information for possible structural optimization in view of the lack of steric clashes of the macrocycle with the flap domain of the enzyme.
Desorption and Biofiltration for the Treatment of Residual Organic Gases Evolved in Soil Decontamination Processses
Authors: Barona A. , Elías A. , Arias R. , Acha E. , Cano I.
Published: October 2007

In order to analyze the combination of a rotary kiln and a biofilter in soil decontamination processes, a previously characterized soil was artificially contaminated with toluene, ethylbenzene or p‐xylene. The desorption peak of the three compounds occurred very quickly at 20 °C, and consequently, the outlet gas flow from the rotary kiln was initially divided into two different flows. One of them was reduced to a 1/9th fraction of the total flow to be treated in an independent biofiltration system specially acclimated to each contaminant. The sharp desorption peak observed for the three compounds at the outlet of the kiln involved a very high inlet concentration fed into the biofilters in a very short period of time (shorter than 3 h). Consequently, the removal efficiency for toluene was lower than 70 %. However, the removal efficiencies for ethylbenzene and xylene were always higher than 65 %.
Mathematical Modeling of the Fluidized Bed Drying of Cubic Materials
Authors: Hatamipour M. S. , Jazini M. H.
Published: October 2007

The unsteady‐state simultaneous heat and mass transfer between gas and potato cubes during the drying process in a batch fluidized bed was described by a mathematical model. Mass transfer was considered to occur in three dimensions whereas heat transfer between the gas and dried material was assumed to be lumped. It was found that the model could describe the drying process with acceptable accuracy. The moisture profile inside the material at any cross‐section and at any time can be predicted by the model.
Ammonium, Alkylammonium, and Amino Acid Complexes of a Hexacopper Fluoro‐Metallacrown Cavitand
Authors: Jones Leigh F. , Barrett Simon A. , Kilner Colin A. , Halcrow Malcolm A.
Published: October 2007

Reaction of CuF2 with one equivalent of 3{5}‐(pyrid‐2‐yl)‐5{3}‐(tertbutyl)pyrazole (HL) and excess NH4OH in MeOH affords crystalline [NH4{Cu(μ‐F)(μ‐L)}6(CH2Cl2)2]HF2 in moderate yield. This compound contains the 12‐MC‐6 metallacrown [{Cu(μ‐F)(μ‐L)}6] (1) with a NH4+ ion at its center, and CH2Cl2 molecules complexed in bowl‐shaped cavities above and below the Cu6F6 ring. Similar reactions using the bases MeNH2, glycine, l‐alanine or β‐alanine afforded solvated crystals of [1(H3NMe)2]Cl2, [1(gly)2], [1(l‐ala)2], and [1(β‐ala)2], respectively. The metallacrown 1 in these products contains methylammonium and zwitterionic amino‐acid guests in its two bowl‐shaped cavities; each of the amino acids hydrogen‐bonds to three F atoms. A related reaction using 1,6‐diaminohexane resulted in fixation of CO2 from the air to give solvated [1(H3NC6H12NHCO2)2], again with a zwitterionic guest. NMR, ESI‐MS and UV/vis measurements suggest that the metallacrown 1 retains its integrity in several organic solvents, although it is unclear to what extent guest binding takes place in solution.
Prodrug Strategies in Anticancer Chemotherapy
Authors: Kratz Felix , Müller Ivonne A. , Ryppa Claudia , Warnecke André
Published: October 2007

The majority of clinically approved anticancer drugs are characterized by a narrow therapeutic window that results mainly from a high systemic toxicity of the drugs in combination with an evident lack of tumor selectivity. Besides the development of suitable galenic formulations such as liposomes or micelles, several promising prodrug approaches have been followed in the last decades with the aim of improving chemotherapy. In this review we elucidate the two main concepts that underlie the design of most anticancer prodrugs: drug targeting and controlled release of the drug at the tumor site. Consequently, active and passive targeting using tumor‐specific ligands or macromolecular carriers are discussed as well as release strategies that are based on tumor‐specific characteristics such as low pH or the expression of tumor‐associated enzymes. Furthermore, other strategies such as ADEPT (antibody‐directed enzyme prodrug therapy) and the design of self‐eliminating structures are introduced. Chemical realization of prodrug approaches is illustrated by drug candidates that have or may have clinical importance.
Secondary or concomitant neoplasms among adults diagnosed with acute lymphoblastic leukemia and treated according to the LALA‐87 and LALA‐94 trials
Authors: Tavernier Emmanuelle , Le Quoc‐Hung , de Botton Stéphane , Dhédin Nathalie , Bulabois Claude‐Eric , Reman Oumedaly , Vey Norbert , Lhéritier Véronique , Dombret Hervé , Thomas Xavier
Published: October 2007

BACKGROUND.

Second malignant neoplasms are a serious complication after successful treatment of childhood acute lymphoblastic leukemia (ALL). Although treatment intensity and outcome were not comparable, with improvements in survival it is important to evaluate the rate and the type of second neoplasms in adults with ALL.

METHODS.

The data from the GET‐LALA group were analyzed. A cohort of 1494 patients, aged 15 to 60 years and enrolled in 2 successive multicenter protocols between 1987 and 2002, was observed to determine the incidence of second neoplasms and associated risk factors. The median follow‐up from diagnosis was 6 years.

RESULTS.

By February 2005 secondary or concomitant neoplasms were documented in 23 patients, including 9 acute myeloid leukemias (AML) or myelodysplasias (MDS), 4 non‐Hodgkin lymphomas (NHL), 5 skin tumors, and 5 other solid tumors (1 lung cancer, 1 tongue carcinoma, 1 thymoma, 1 condrosarcoma, 1 histiocytosis). Neoplasms developed 0.5 to 13.8 years (median, 4.5 years) after the diagnosis of ALL. There were 22 patients in first remission and 1 was in second remission. The overall cumulative risk of secondary neoplasms was 2.1% at 5 years, 4.9% at 10 years, and 9.4% at 15 years. The cumulative risk of developing a second hematologic malignancy was 1.8% at 5 years, 2.2% at 10 years, 3.3% at 18 years; that of developing a solid tumor was 0.2% at 5 years, 2.8% at 10 years, 6.2% at 15 years. The development of secondary neoplasm was not associated with the use of any specific cytotoxic agent. However, the risk of skin tumor increased with radiation dose and transplantation (P = .01). Overall survival (OS) after the diagnosis of a second malignant neoplasm was 55% at 10 years. However, the median OS in patients developing AML/MDS was 5.7 months.

CONCLUSIONS.

The data document that adult ALL survivors are at an increased risk of later malignancy. The risk of secondary or concomitant neoplasm appeared higher than that of childhood ALL previously reported in the literature. Considering the low survival rate of this large unselected adult ALL cohort (32% at 10 years) as compared with that observed in childhood ALL, the risk of second malignancy remains underestimated. Larger series with long‐term follow‐up are necessary, as well as methods of screening and identification of patients at increased risk. Cancer 2007. © 2007 American Cancer Society.
Conflict resolution education and antisocial behavior in U.S. schools: A meta‐analysis
Authors: Garrard Wendy M. , Lipsey Mark W.
Published: October 2007

This meta‐analysis examines more than twenty‐five years of evidence to determine whether participation in school‐based conflict resolution education (CRE) contributes to reduced antisocial behaviors among youth in kindergarten through twelfth grade in U.S. schools. Evidence from thirty‐six studies, representing 4,971 students, shows improvements in antisocial behaviors in CRE participants compared to control groups (Effect Size = .26), with larger effects observed during midadolescence ( ES = .53) and early adolescence ( ES = .22) compared to middle childhood ( ES = .06). Improvements in antisocial behavior outcomes attributable to CRE are significant in both practical and statistical terms and are similar for different CRE program approaches.
Novel therapeutics with enhanced biological activity generated by the strategic introduction of silicon isosteres into known drug scaffolds
Authors: Gately Stephen , West Robert
Published: October 2007

The strategic replacement of carbon with silicon within biologically prevalidated drug scaffolds can generate focused libraries of pharmaceutically relevant agents with novel, durable and marketable intellectual property. This approach can be cost‐effective and of lower developmental risk because known drugs have recognized pharmacology and toxicity profiles, proven safety in humans, and established manufacturing and formulation methods. The change in shape, charge, and lipophilicity that can result from the addition of silicon can favorably alter the biological activity and toxicology of the parent drug. Silicon‐containing derivatives of indomethacin are COX‐2 selective, suggesting they will not be associated with the classical toxicities associated with nonselective inhibition of the cyclooxygenases. The silicon‐indomethacin derivatives also demonstrated superior anti‐cancer activity at clinically achievable concentrations when tested in vitro against a human pancreatic cancer cell line, MiaPaCa‐2, and a panel of 14 human multiple myeloma cell lines. Bioorganosilicon chemistry represents an attractive approach for emerging biopharmaceutical organizations seeking to rapidly develop a portfolio of novel pharmacological agents that have the potential for enhanced therapeutic and pharmacological benefit. Drug Dev Res 68:156–163, 2007. ©2007 Wiley‐Liss, Inc.
UNBS1450: A new hemi‐synthetic cardenolide with promising anti‐cancer activity
Authors: Mijatovic Tatjana , Lefranc Florence , Van Quaquebeke Eric , Van Vynckt Frank , Darro Francis , Kiss Robert
Published: October 2007

Several reports suggest the sodium pump as an interesting oncology target, given that its subunit expression is markedly altered in cancer. By binding to the sodium pump, cardiotonic steroids, notably cardenolides, the natural high‐affinity Na+/K+‐ATPase ligands, elicit marked effects on cancer cell behavior and a number of studies have emphasized their potential use in oncology. Chemical modifications of 2″‐oxovoruscharin (a novel cardenolide extracted from Calotropis procera) based on an understanding of the structure–activity relationship within the series, has led to the identification of UNBS1450, a molecule characterized by more potent anti‐proliferative activity and lower toxicity than classic cardenolides. In aggressive and metastatic orthotopic NSCLC, refractory prostate cancer, and glioma models, UNBS1450 is more potent than tested reference compounds, including taxol, irinotecan, oxaliplatin, mitoxantrone, and temozolomide. The general mechanism of action associated with UNBS1450‐mediated anti‐cancer effects relates to the disorganization of the actin cytoskeleton. UNBS1450 can thus be considered both anti‐proliferative (cytotoxic) and anti‐migratory, given that the actin cytoskeleton is essential to cytokinesis and to cancer cell migration. UNBS1450 also induces non‐apoptotic cell death processes (e.g., lysosome membrane permeabilization and autophagy) and thus may overcome major apoptosis resistance pathways responsible for the failure of therapeutics in certain cancers. UNBS1450 is currently in preclinical development and should reach Phase I clinical trials in 2008. Drug Dev Res 68:164–173, 2007. ©2007 Wiley‐Liss, Inc.
Building systems to support development of drugs for biodefense
Authors: Taylor Katherine A.
Published: October 2007

The mission of the National Institute of Allergy and Infectious Diseases (NIAID), Division of Microbiology and Infectious Diseases (DMID), is to support research and product development that addresses the control and prevention of infectious diseases. This mission includes the development of new drugs to mitigate illness, suffering, and death resulting from an expanding spectrum of naturally emerging diseases and potential biological weapons. DMID has established new resources and additional infrastructure to address these challenges. In addition, DMID plans to transition to a new paradigm for research and development approaches based on three concepts that comprise a broad spectrum approach: products with broad spectrum activity; broad spectrum technology that can be applied to improve specific drug characteristics (e.g., shelf life); and broad spectrum platforms that will reduce the time and cost to manufacture and evaluate products. Drug Dev Res 68:183–185, 2007. © 2007 Wiley‐Liss, Inc.
Nonprofit model for drug discovery and development
Authors: Frank Gregory Daniel , Jong Ling , Collins Nathan , Spack Edward G.
Published: October 2007

SRI International, a nonendowed, nonprofit research institution, has developed a successful model for drug discovery and development using funding from a variety of sources. We have vertically integrated basic and applied research, drug discovery, and preclinical drug development expertise and capabilities. Funding sources include state and federal government grants and contracts, and our unique model allows us to translate our discoveries into clinical‐ready drug candidates. Drug Dev Res 68:186–196, 2007. © 2007 Wiley‐Liss, Inc.
Circulating adiponectin and adiponectin receptor expression in skeletal muscle: effects of exercise
Authors: Vu Vivian , Riddell Michael C. , Sweeney Gary
Published: October 2007

Excess visceral fat can regulate insulin sensitivity and energy metabolism by releasing adipokines into the circulation which then bind with their cognate receptors in various tissues and alter glucose and lipid metabolism. Circulating levels of adiponectin, which promotes glucose uptake into skeletal muscle and increases fat oxidation rates, are decreased in obesity. Strategies to enhance the insulin‐like and insulin‐sensitizing actions of adiponectin have been shown to be effective in improving metabolic abnormalities associated with obesity and diabetes. Interestingly, the insulin‐sensitizing effects of exercise have similar metabolic effects as adiponectin in that exercise also promotes glucose uptake into muscle and increases rates of fatty acid oxidation. Recent studies have begun to examine the potential role of adiponectin in mediating the insulin‐sensitizing action of exercise by investigating changes in plasma adiponectin levels and tissue‐specific adiponectin receptor (AdipoR) expression. In this review, we have summarized the key findings to date which suggest that changes in expression of AdipoR isoforms in skeletal muscle, rather than circulating total adiponectin levels, may be of physiological importance. Copyright © 2007 John Wiley & Sons, Ltd.
The N‐Acylated Derivatives of Parent Complex [{(μ‐SCH2)2NH}Fe2(CO)6] as Active Site Models of Fe‐Only Hydrogenases: Synthesis, Characterization, and Related Properties
Authors: Song Li‐Cheng , Wang Liang‐Xing , Yin Bang‐Shao , Li Yu‐Long , Zhang Xiao‐Guang , Zhang Yuan‐Wei , Luo Xiang , Hu Qing‐Mei
Published: October 2007

A series of N‐acylated diiron azadithiolate complexes as H‐cluster models was synthesized and structurally characterized. Treatment of parent complex [{(μ‐SCH2)2NH}Fe2(CO)6] (A) with 2‐chloroacetic acid in the presence of dicyclohexylcarbodiimide or with 2‐chloroacetyl chloride in the presence of Et3N gave N‐chloroacetyl complex [{(μ‐SCH2)2NC(O)CH2Cl}Fe2(CO)6] (1). Further treatment of 1 with MeC(O)SK afforded N‐acetylthioacetyl complex [{(μ‐SCH2)2NC(O)CH2SC(O)Me}Fe2(CO)6] (2). N‐Ethoxylcarbonylacetyl complex [{(μ‐SCH2)2NC(O)CH2CO2Et}Fe2(CO)6] (3) and N‐heterocyclic complexes [{(μ‐SCH2)2NC(O)C4H3Y‐2}Fe2(CO)6] (4, Y = O; 5, Y = S) were produced by reactions of A with EtO2CCH2C(O)Cl, 2‐furancarbonyl chloride, and 2‐thiophenecarbonyl chloride in the presence of pyridine or Et3N. Similarly, N‐malonyl complex [{Fe2(CO)6(μ‐SCH2)2NC(O)}2CH2] (6) and N‐carbonylbenzaldehyde complex [{(μ‐SCH2)2NC(O)C6H4CHO‐p}Fe2(CO)6] (7) could be obtained by reaction of A with malonyl dichloride in the presence of pyridine and with p‐CHOC6H4C(O)Cl in the presence of Et3N. More interestingly, further reaction of 7 with PhCHO and pyrrole in a 1:3:4 molar ratio in the presence of BF3·OEt2 followed by p‐chloranil yielded the first light‐driven type of model complex containing an N‐carbonylphenylporphyrin moiety [{(μ‐SCH2)2NC(O)(TPP)}Fe2(CO)6] (8, TPP = tetraphenylporphyrin group). Whereas the molecular structures of 2, 5, and 7 were established by X‐ray crystallography, the electrochemical properties of 2–5 as well as the proton reduction to hydrogen gas catalyzed by 2 and 3 were studied by CV techniques.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Tissue engineering with electric fields: Investigation of the shape of mammalian cell aggregates formed at interdigitated oppositely castellated electrodes
Authors: Sebastian Anil , Venkatesh Alagarswamy G. , Markx Gerard H.
Published: October 2007

The shape of aggregates of cells formed by positive dielectrophoresis (DEP) at interdigitated oppositely castellated electrodes under different conditions was investigated and compared with calculations of the electric field gradient |∇E2|, and the electric field E, and E2. The results confirm that at low field strength the cells predominantly accumulate above the tips of the electrodes, but at higher electric field strengths the cells predominantly accumulate in the middle of the aggregate. For a given electrode size, a higher applied voltage significantly increases the aggregate footprint. Higher flow rates distort this pattern, with more cells accumulating at the electrodes that are upstream. Calculation of the electric field strength E, E2 and the electric field strength gradient |∇E2| in the interdigitated oppositely castellated electrode array shows that, at low flow rates, there is a strong correlation between the aggregate shape and the distribution of the electric field E and E2, but not so between the aggregate shape and |∇E2|. The results indicate that interparticle forces such as pearlchain formation strongly affect the aggregation process, but that, when positive DEP is used to make the aggregates, the distribution of the electric field E, or better E2, can be used as a useful guide to the final aggregate shape.
Adaptive shifts in osmoregulatory strategy and the invasion of freshwater by brachyuran crabs: evidence from Dilocarcinus pagei (Trichodactylidae)
Authors: Augusto Alessandra , Greene Lewis J. , Laure Helen J. , Mcnamara John C.
Published: October 2007

To evaluate putative adaptive changes underpinning the invasion of freshwater by the Brachyura, this investigation examines anisosmotic extra and isosmotic intracellular osmoregulatory capabilities in Dilocarcinus pagei, a neotropical, hololimnetic crab, including its embryonic and juvenile phases. All ontogenetic stages show a remarkable ability to survive a high salinity medium (25‰, 750 mOsm/kg H2O, 350 mm Na+, 400 mM Cl−). Adults hyper‐regulate hemolymph osmolality up to isosmoticity at 744 mOsm kg/H2O (24‰), [Na+] and [Cl−] becoming isoionic at 449 (22‰) and 256 mM (16‰), respectively. Hemolymph (420±39 mOsm/kg H2O) and urine (384±44 mOsm/kg H2O) are isosmotic in adults held in freshwater, and after 5‐days exposure to 25‰ (787±9 mOsm/kg H2O and 777±43 mOs/kg H2O, respectively); D. pagei does not produce dilute urine. Total free amino acid (FAA) concentrations in embryos (14.9±1.2), juveniles (32.8±0.1) and adult muscle (10.9±2.1 mmol/kg wet weight) in freshwater are 30‐fold less than in brackish/marine Crustacea, suggesting that FAA constitute a useful parameter to evaluate adaptation to freshwater. On acclimation to 25‰, total FAA increase by ≈100% in embryos and in adult muscle and nerve tissue and hemolymph, owing to large increases in proline, arginine and/or alanine. However, effective FAA contribution to intracellular osmolality increases only in embryos, from 3 to 4.5%. These findings suggest that gill‐based, anisosmotic extracellular regulation has supplanted isosmotic intracellular regulatory mechanisms during the conquest of freshwater by the Brachyura, and indicate that D. pagei may be an old, well‐adapted inhabitant of this biotope. J. Exp. Zool. 307A:688–698, 2007. © 2007 Wiley‐Liss, Inc.
Inter‐decadal variation of the summer precipitation in East China and its association with decreasing Asian summer monsoon. Part I: Observed evidences
Authors: Ding Yihui , Wang Zunya , Sun Ying
Published: October 2007

In recent two decades, North and Northeast China have suffered from severe and persistent droughts while the Yangtze River basin and South China have undergone much more significant heavy rainfall/floods events. This long‐term change in the summer precipitation and associated large‐scale monsoon circulation features have been examined by using the new dataset of 740 surface stations for recent 54 years (1951–2004) and about 123‐yr (1880–2002) records of precipitation in East China. The following new findings have been highlighted: (1) One dominating mode of the inter‐decadal variability of the summer precipitation in China is the near‐80‐yr oscillation. Other modes of 12‐yr and 30–40‐yr oscillations also play an important role in affecting regional inter‐decadal variability. (2) In recent 54 years, the spatial pattern of the inter‐decadal variability of summer precipitation in China is mainly structured with two meridional modes: the dipole pattern and the positive‐negative‐positive (“+ − + ” pattern). In this period, a regime transition of meridional precipitation mode from “+ − + ” pattern to dipole pattern has been completed. In the process of southward movement of much precipitation zone, two abrupt climate changing points that occurred in 1978 and 1992, respectively, were identified. (3) Accompanying the afore‐described precipitation changes, the East Asian summer monsoon have experienced significant weakening, with northward moisture transport and convergence by the East Asian summer monsoon greatly weakened, thus leading to much deficient moisture supply for precipitation in North China. (4) The significant weakening of the component of the tropical upper‐level easterly jet (TEJ) has made a dominating contribution to the weakening of the Asian summer monsoon system. The cooling in the high troposphere at mid‐ and high latitudes and the possible warming at low latitude in the Asian region is likely to be responsible for the inter‐decadal weakening of the TEJ. Copyright © 2007 Royal Meteorological Society