bluuebunny/crossref_metadata_2025 huggingface dataset:
Gambogic acid, a novel ligand for transferrin receptor, potentiates TNF-induced apoptosis through modulation of the nuclear factor-κB signaling pathway
Authors: Pandey Manoj K. , Sung Bokyung , Ahn Kwang Seok , Kunnumakkara Ajaikumar B. , Chaturvedi Madan M. , Aggarwal Bharat B.
Published: August 2007

Gambogic acid (GA), a xanthone derived from the resin of the Garcinia hanburyi, has been recently demonstrated to bind transferrin receptor and exhibit potential anticancer effects through a signaling mechanism that is not fully understood. Because of the critical role of NF-κB signaling pathway, we investigated the effects of GA on NF-κB–mediated cellular responses and NF-κB–regulated gene products in human leukemia cancer cells. Treatment of cells with GA enhanced apoptosis induced by tumor necrosis factor (TNF) and chemotherapeutic agents, inhibited the expression of gene products involved in antiapoptosis (IAP1 and IAP2, Bcl-2, Bcl-xL, and TRAF1), proliferation (cyclin D1 and c-Myc), invasion (COX-2 and MMP-9), and angiogenesis (VEGF), all of which are known to be regulated by NF-κB. GA suppressed NF-κB activation induced by various inflammatory agents and carcinogens and this, accompanied by the inhibition of TAK1/TAB1-mediated IKK activation, inhibited IκBα phosphorylation and degradation, suppressed p65 phosphorylation and nuclear translocation, and finally abrogated NF-κB–dependent reporter gene expression. The NF-κB activation induced by TNFR1, TRADD, TRAF2, NIK, TAK1/TAB1, and IKKβ was also inhibited. The effect of GA mediated through transferrin receptor as down-regulation of the receptor by RNA interference reversed its effects on NF-κB and apoptosis. Overall our results demonstrate that GA inhibits NF-κB signaling pathway and potentiates apoptosis through its interaction with the transferrin receptor.
Impaired T-cell priming in vivo resulting from dysfunction of WASp-deficient dendritic cells
Authors: Bouma Gerben , Burns Siobhan , Thrasher Adrian J.
Published: August 2007

The Wiskott-Aldrich syndrome (WAS) is characterized by defective cytoskeletal dynamics affecting multiple immune cell lineages, and leading to immunodeficiency and autoimmunity. The contribution of dendritic cell (DC) dysfunction to the immune dysregulation has not been defined, although both immature and mature WAS knockout (KO) DCs exhibit significant abnormalities of chemotaxis and migration. To exclude environmental confounders as a result of WAS protein (WASp) deficiency, we studied migration and priming activity of WAS KO DCs in vivo after adoptive transfer into wild-type recipient mice. Homing to draining lymph nodes was reduced and WAS KO DCs failed to localize efficiently in T-cell areas. Priming of both CD4+ and CD8+ T lymphocytes by WAS KO DCs preloaded with antigen was significantly decreased. At low doses of antigen, activation of preprimed wild-type CD4+ T lymphocytes by WAS KO DCs in vitro was also abrogated, suggesting that there is a threshold-dependent impairment even if successful DC–T cell colocalization is achieved. Our data indicate that intrinsic DC dysfunction due to WASp deficiency directly impairs the T-cell priming response in vivo, most likely as a result of inefficient migration, but also possibly influenced by suboptimal DC-mediated cognate interaction.
Glycogen synthase kinase 3α and 3β have distinct functions during cardiogenesis of zebrafish embryo
Authors: Lee Huang-Chieh , Tsai Jen-Ning , Liao Pei-Yin , Tsai Wei-Yuan , Lin Kai-Yen , Chuang Chung-Cheng , Sun Chi-Kuang , Chang Wen-Chang , Tsai Huai-Jen
Published: August 2007

Background

Glycogen synthase kinase 3 (GSK3) encodes a serine/threonine protein kinase, is known to play roles in many biological processes. Two closely related GSK3 isoforms encoded by distinct genes: GSK3α (51 kDa) and GSK3β (47 kDa). In previously studies, most GSK3 inhibitors are not only inhibiting GSK3, but are also affecting many other kinases. In addition, because of highly similarity in amino acid sequence between GSK3α and GSK3β, making it difficult to identify an inhibitor that can be selective against GSK3α or GSK3β. Thus, it is relatively difficult to address the functions of GSK3 isoforms during embryogenesis. At this study, we attempt to specifically inhibit either GSK3α or GSK3β and uncover the isoform-specific roles that GSK3 plays during cardiogenesis.

Results

We blocked gsk3α and gsk3β translations by injection of morpholino antisense oligonucleotides (MO). Both gsk3α- and gsk3β-MO-injected embryos displayed similar morphological defects, with a thin, string-like shaped heart and pericardial edema at 72 hours post-fertilization. However, when detailed analysis of the gsk3α- and gsk3β-MO-induced heart defects, we found that the reduced number of cardiomyocytes in gsk3α morphants during the heart-ring stage was due to apoptosis. On the contrary, gsk3β morphants did not exhibit significant apoptosis in the cardiomyocytes, and the heart developed normally during the heart-ring stage. Later, however, the heart positioning was severely disrupted in gsk3β morphants. bmp4 expression in gsk3β morphants was up-regulated and disrupted the asymmetry pattern in the heart. The cardiac valve defects in gsk3β morphants were similar to those observed in axin1 and apc

mcr
mutants, suggesting that GSK3β might play a role in cardiac valve development through the Wnt/β-catenin pathway. Finally, the phenotypes of gsk3α mutant embryos cannot be rescued by gsk3β mRNA, and vice versa, demonstrating that GSK3α and GSK3β are not functionally redundant.

Conclusion

We conclude that (1) GSK3α, but not GSK3β, is necessary in cardiomyocyte survival; (2) the GSK3β plays important roles in modulating the left-right asymmetry and affecting heart positioning; and (3) GSK3α and GSK3β play distinct roles during zebrafish cardiogenesis.
Influence of maternal and social factors as predictors of low birth weight in Italy
Authors: Nobile Carmelo GA , Raffaele Gianluca , Altomare Carlo , Pavia Maria
Published: August 2007

Background

The purpose of this study is to provide insight into the determinants of low birth weight (LBW) in Italy.

Methods

The study was carried out in a non-teaching hospital in Catanzaro (Italy). All LBW and very LBW newborns (200) were included in the study and a random sample of 400 newborns weighing ≥ 2500 g was selected. Data were collected from the delivery certificates during one year. Smoking activity of mother and familiar and/or social support during pregnancy was gathered through telephone interviews.

Results

Overall annual LBW rate was 11.8%. Among LBW newborn there were 125 preterm and 75 term. Younger mothers, those who smoked during pregnancy, and had fewer prenatal care visits were more likely to deliver a LBW child; moreover, preterm newborns, delivered by caesarean section, and twin or multiple birth were significantly more likely to have a LBW. The comparison of very LBW (<1500 g) to LBW newborns showed that a very LBW was significantly more likely in newborns delivered by less educated mothers, those who work outside the home, live in smaller towns, and had less echographies; moreover, as expected, very LBW newborns were more likely to be preterm.

Conclusion

Several modifiable factors affect the risk of LBW, even when universal access to health care is freely available, but socio-economic status appears to correlate only to very LBW.
ABO blood group phenotypes influence parity specific immunity to Plasmodium falciparum malaria in Malawian women
Authors: Senga Edward , Loscertales Maria-Paz , Makwakwa KEB , Liomba George N , Dzamalala Charles , Kazembe Peter N , Brabin Bernard J
Published: August 2007

Background

Blood group O has been significantly associated with increased placental malaria infection in primiparae and reduced risk of infection in multiparae in the Gambia, an area with markedly seasonal malaria transmission. This study analyses the association between ABO blood group phenotypes in relation to placental malaria pathology and birth outcomes in southern Malawi, an area with perennial malaria transmission.

Methods

A cross-sectional study of 647 mother/child pairs delivering in Montfort Hospital, Chikwawa District between February-June 2004 and January-July 2005 was undertaken. Maternal peripheral and cord blood samples were obtained at delivery. Placental tissue was obtained and malaria histology classified as active, past or no malaria infection. Birth anthropometry was recorded. ABO blood group was measured by agglutination.

Results

In primiparae, blood group O was significantly associated with increased risk of active placental infection (OR 2.18, 95% CI 1.15–4.6, p = 0.02) and an increased foetal-placental weight ratio compared to non-O phenotypes (5.68 versus 5.45, p = 0.03) In multiparae blood group O was significantly associated with less frequent active placental infection (OR 0.59, 95% CI 0.36–0.98, p = 0.04), and a higher newborn ponderal index compared to non-O phenotypes (2.65 versus 2.55, p = 0.007). In multivariate regression parity was independently associated with increased risk of placental malaria (active andpast infection) in primiparae with blood group O (p = 0.034) and reduced risk in multiparae with the same phenotype (p = 0.015).

Conclusion

Parity related susceptibility to placental malaria is associated with the mothers ABO phenotype. This interaction influences foetal and placental growth and could be an important modifying factor for pregnancy outcomes. The biological explanation could relate to sialic acid dependent placental membrane differences which vary with ABO blood group.
Dermoid cyst of the pancreas: presentation and management
Authors: Tucci Gianfranco , Muzi Marco Gallinella , Nigro Casimiro , Cadeddu Federica , Amabile Dalia , Servadei Francesca , Farinon Attilio M
Published: August 2007

Background

Dermoid cyst of the pancreas is a benign, well-differentiated, extremely rare germ cell neoplasm. Published data indicate that differential diagnosis of cystic lesions of the pancreas is challenging and although ultrasonography, computed tomography and magnetic resonance may be useful, radiological findings are often inconclusive and the diagnosis is intraoperative. We report a case of a dermoid cyst of the tail of the pancreas intraoperatively diagnosed and successfully treated with left pancreatectomy. Further, characteristics, preoperative detection and differential diagnosis of this rare pathology are also discussed.

Case presentation

This report documents the findings of a 64-year-old male presenting with a well defined echogenic pancreatic mass on ultrasonography. Computerized Tomography (CT) showed a 5 cm cystic tumor arising from pancreatic tail and Magnetic Resonance Imaging (MRI) suggested a tumor extension to the middle side of the stomach without defined margins. A left pancreatectomy was performed. On surgical specimen, histological evaluation revealed a dermoid cyst of the tail of the pancreas measuring 8.5 × 3.0 cm.

Conclusion

Given the benign nature of the dermoid cyst, surgical resection most likely represents the definitive treatment and cure. In addition, resection is indicated in consideration of the difficulty in diagnosing dermoid cyst preoperatively. However, endoscopic ultrasound and fine needle aspiration cytology have recently been shown to be effective, safe, reliable and cost-saving preoperative diagnostic tools. Therefore, until more cases of dermoid cyst are identified to further elucidate its natural history and improve the reliability of the preoperative diagnostic tools, surgical resection should be considered the standard therapy in order to exclude malignancy.
The global role of ppGpp synthesis in morphological differentiation and antibiotic production in Streptomyces coelicolor A3(2)
Authors: Hesketh Andrew , Chen Wenqiong Joan , Ryding Jamie , Chang Sherman , Bibb Mervyn
Published: August 2007

Background

Regulation of production of the translational apparatus via the stringent factor ppGpp in response to amino acid starvation is conserved in many bacteria. However, in addition to this core function, it is clear that ppGpp also exhibits genus-specific regulatory effects. In this study we used Affymetrix GeneChips to more fully characterize the regulatory influence of ppGpp synthesis on the biology of Streptomyces coelicolor A3(2), with emphasis on the control of antibiotic biosynthesis and morphological differentiation.

Results

Induction of ppGpp synthesis repressed transcription of the major sigma factor hrdB, genes with functions associated with active growth, and six of the thirteen conservons present in the S. coelicolor genome. Genes induced following ppGpp synthesis included the alternative sigma factor SCO4005, many for production of the antibiotics CDA and actinorhodin, the regulatory genes SCO4198 and SCO4336, and two alternative ribosomal proteins. Induction of the CDA and actinorhodin clusters was accompanied by an increase in transcription of the pathway regulators cdaR and actII-ORF4, respectively. Comparison of transcriptome profiles of a relA null strain, M570, incapable of ppGpp synthesis with its parent M600 suggested the occurrence of metabolic stress in the mutant. The failure of M570 to sporulate was associated with a stalling between production of the surfactant peptide SapB, and of the hydrophobins: it overproduced SapB but failed to express the chaplin and rodlin genes.

Conclusion

In S. coelicolor, ppGpp synthesis influences the expression of several genomic elements that are particularly characteristic of streptomycete biology, notably antibiotic gene clusters, conservons, and morphogenetic proteins.
Aktuelle Entwicklungen im vorgeburtlichen Screening auf chromosomale Störungen / Recent developments in antenatal screening for chromosomal abnormalities
Authors: Knippel Alexander-Johannes , Kozlowski Peter , Stressig Rüdiger
Published: August 2007

Das klassische Ersttrimesterscreening (ETS) liefert eine durch unabhängige prospektive Studien validierte Nachweisrate für ein fetales Down-Syndrom von 86–90% bei einer falsch-positiv Rate von 5%. Durch eine Kombination von Erst- und Zweittrimestermarkern (Integrated Screening) kann eine Verbesserung der Nachweisrate auf 94–96% erreicht werden, wenn das Gesamttestergebnis erst nach Vorliegen der Zweittrimesterwerte mitgeteilt wird. Die frühe Diagnostik des klassischen Ersttrimesterscreenings und die bessere Testgenauigkeit des Integrierten Screenings können durch ein sequentielles Screening kombiniert werden, bei dem man in Fällen mittlerer Risiken eine zusätzliche Zweittrimesterbiochemie durchführt. Patientinnen mit hohen Risiken im Ersttrimesterscreening würde direkt eine invasive Diagnostik empfohlen, Patientinnen mit sehr niedrigen Risiken benötigten keine weitere Untersuchung. Genaue Zahlen für einen Risikogrenzwert ab dem eine Zweittrimesterbiochemie empfohlen wird und prospektive Studien zu diesem sequentiellen Screening liegen jedoch noch nicht vor. Sind über die Risikoangabe für eine fetale Trisomie 21 hinaus weitere Informationen zum Gesundheitszustand des Kindes gewünscht, ist ein erweitertes Ultraschallscreening im ersten Trimenon eine gute Alternative. Quantitative Aussagen zur Screeningperformance des erweiterten Ultraschallscreenings für ein fetales Down-Syndrom sind zurzeit noch nicht möglich.
Invasive Pränataldiagnostik / Invasive methods in prenatal diagnostics
Authors: Rost Imma , Schiessl Barbara , Heinrich Uwe , Rupprecht Wolfgang , Wagner Annett , Klein Hanns-Georg
Published: August 2007

Unter den Begriff der Invasiven Pränataldiagnostik fallen Eingriffe bzw. Verfahren, die auf der Untersuchung von Zellen des Ungeborenen, Fruchtwasser- bzw. Blutproben basieren. Die Eingriffe zur Gewinnung dieser Zellen bzw. Flüssigkeiten beinhalten ein Eingriffsrisiko, vor allem das einer Fehlgeburt bzw. eines intrauterinen Fruchttodes. Daher ist die Invasive Pränataldiagnostik im Gegensatz zu den nicht-invasiven Screeningmethoden, die zum Teil auch Bestandteil der allgemeinen Mutterschaftsrichtlinien sind, grundsätzlich an eine Indikation gebunden. Diese Indikation ergibt sich in der Regel aus einem individuellen Risiko für eine bestimmte Erkrankung beim Ungeborenen.
Nicht-invasive Pränataldiagnostik durch Analyse fetaler DNA im mütterlichen Blut / Non-invasive prenatal diagnosis by genetic analysis of maternal blood
Authors: Zimmermann Bernhard G.
Published: August 2007

Seit Jahrzehnten gab es Bestrebungen Informationen aus dem Blut der werdenden Mutter zur nicht-invasiven Schwangerschaftsdiagnostik zu nutzen. Das Ziel waren in den Neunzigerjahren fetale Zellen und deren Anreicherung; die hochgesteckten Hoffnungen haben sich jedoch nicht erfüllt. Eine routinemäßige Anwendung der entwickelten Methoden ist nicht absehbar. Mit der Entdeckung fetaler DNS und RNS im mütterlichen Plasma boten sich diagnostische Anwendungen an. Die auf DNS-Tests basierende Bestimmung des Rhesus-Genotyps und des Geschlechts des Kindes halten europaweit Einzug in die klinische Praxis. Zudem kann das Risiko von bestimmten Erbkrankheiten durch den Nachweis der väterlich vererbten Mutationen vorbestimmt werden und wird in Zukunft helfen, invasive Eingriffe zur Fruchtwasser- oder Chorionentnahme zu reduzieren. Die Forschung kommt dem Ziel des nicht-invasiven Nachweises fetaler Aneuploidien immer näher, dennoch ist es bis zur routinemäßigen Anwendung noch ein weiter Weg.
Relationship of Aggregate Microtexture to Asphalt Pavement Skid Resistance
Authors: Luce Anthony , Mahmoud Enad , Masad Eyad , Chowdhury Arif
Published: August 2007

Aggregate properties are one of the important factors that influence the asphalt pavement skid resistance. This paper presents a detailed analysis of aggregate texture and its relationship to pavement skid resistance. A new method is developed for the evaluation of aggregate resistance to polishing. This method relies on the Micro-Deval test as the mechanism for polishing aggregates and the Aggregate Imaging System (AIMS) for quantifying the change in texture due to polishing. The results show that the Micro-Deval test is an effective method for polishing aggregates within a short time. Also, the AIMS texture analysis is able to rapidly and accurately quantify the influence of polishing on texture. The verification of the new method was achieved through measuring the skid resistance of pavements constructed using three different aggregate sources and three different aggregate gradations. The skid resistance was found to be related not only to average aggregate texture, but also to the texture distribution within an aggregate sample. The developed method can be used in models for predicting the change in asphalt pavement skid resistance as a function of aggregate texture, mixture properties, and environmental conditions.
The fate of ‘redundant’ verbal forms – Double perfect constructions in the languages of Europe
Authors: Ammann Andreas
Published: August 2007

German and other languages of Europe have supercomposed tenses which are the result of a twofold application of the strategy that forms perfects. Based on their low frequency in the written registers, these constructions are considered marginal. In spoken German double perfects often compete with the pluperfect. But I argue that their use in literary German is motivated, so that double perfect constructions are indeed members of the tense inventory. Elsewhere in Europe, we find similar con-structions associated with rather specific (and similar) meanings, both where synthetic past tenses are on the decline and where they are preserved.
Efficient and Stable Transgene Expression in Human Embryonic Stem Cells Using Transposon-Mediated Gene Transfer
Authors: Wilber Andrew , Linehan Jonathan L. , Tian Xinghui , Woll Petter S. , Morris Julie K. , Belur Lalitha R. , McIvor R. Scott , Kaufman Dan S.
Published: August 2007

Efficient and stable genetic modification of human embryonic stem (ES) cells is required to realize the full scientific and potential therapeutic use of these cells. Currently, only limited success toward this goal has been achieved without using a viral vector. The Sleeping Beauty (SB) transposon system mediates nonviral gene insertion and stable expression in target cells and tissues. Here, we demonstrate use of the nonviral SB transposon system to effectively mediate stable gene transfer in human ES cells. Transposons encoding (a) green fluorescent protein coupled to the zeocin gene or (b) the firefly luciferase (luc) gene were effectively delivered to undifferentiated human ES cells with either a DNA or RNA source of transposase. Only human ES cells cotransfected with transposon- and transposase-encoding sequences exhibited transgene expression after 1 week in culture. Molecular analysis of transposon integrants indicated that 98% of stable gene transfer resulted from transposition. Stable luc expression was observed up to 5 months in human ES cells cotransfected with a transposon along with either DNA or RNA encoding SB transposase. Genetically engineered human ES cells demonstrated the ability to differentiate into teratomas in vivo and mature hematopoietic cells in vitro while maintaining stable transgene expression. We conclude that the SB transposon system provides an effective approach with several advantages for genetic manipulation and durable gene expression in human ES cells.

Disclosure of potential conflicts of interest is found at the end of this article.
Briefing: The Public Contracts Regulations 2006
Authors: Williams R.
Published: August 2007

The procurement of work, goods and services by public authorities is subject to a new EU Directive and new implementing Regulations in the UK. The aim of the new laws is to bring the legislative framework into line with practical developments in procurement and new European case law. The changes are also intended to simplify the law for lawyers and construction professionals alike. Have the new Regulations achieved these aims? This briefing suggests that the answer is a qualified yes, and explains some of the most important changes brought about by the new laws.
Optimising flow–sediment transport parameters for rivers
Authors: Akbari G.
Published: August 2007

The unsteady flow–sediment transport equations for a real river–reservoir system contain unknown hydraulic, sediment and geometric parameters. Knowledge of these parameters and input data comprising initial and boundary conditions is required to simulate flow–sediment transport, water surface and river bed profiles. The sensitivity analysis and optimisation procedure, which involves determining these parameters by fitting a model with real river field data, is an important tool for finding the best-fit values of each parameter in a river–reservoir sediment transport model. Sensitivity analysis and optimisation methods have been found to be very useful when applied to sediment routeing problems in river–reservoir systems. This technique was employed for optimisation of some of the important parameters involved in graded sediment routeing and bed armouring processes using a non-linear coupled model (NCMG). The particular parameters studied in this investigation are degradation, bed armouring and grain size distribution of bed material in a river bed downstream of a dam. The effects of bed roughness, sediment parameters and thickness of the active layer on bed level changes are studied. A combined Gauss–Newton and modified Newton method are employed to calculate optimised parameters.
Local scour by submerged offset jets
Authors: Karki R. , Faruque M. A. A. , Balachandar R.
Published: August 2007

In this paper an effort is made to understand the scour caused by submerged offset jets impinging on a cohesionless sand bed. A square cross-section nozzle and a two-dimensional (2D) nozzle spanning the width of the flume were used to generate the jets. The 2D offset jet experiments were conducted at two values of the densimetric Froude number (F0 = 5·5 and 10) and two receiving water depths corresponding to shallow and deep tailwater conditions. The square offset jet tests were conducted at F0 = 10 and correspond to deep tailwater conditions. Velocity measurements were conducted using a laser Doppler anemometer. For both jet types, at a given densimetric Froude number, progressing from the start of the test towards asymptotic conditions, the geometric parameters used to describe scour were found to be sensitive to the offset distance. Offset refers to the vertical distance between the nozzle invert and the initial sand bed and an asymptotic state refers to the situation where no significant change in the scour geometry was noticed with increasing time. For the 2D zero-offset jet condition, a backward-facing step was formed at the invert of the nozzle and the general flow features resembled those of an offset jet. At the lower value of the relative tailwater depth, the flow and the corresponding scour pattern was different from that found at the deep tailwater condition. For the square jet, the shape of the scour hole and the corresponding mound were elongated longitudinally and decreased laterally as the offset distance was increased. The distance between the nozzle and the point of the beginning of the scour hole was found to increase with increasing offset distance. Turbulent bursts were noted to occur and to influence the scour process. By proper choice of scaling variables, the centreline scour profiles in the hole region were collapsed onto a single curve.
Cost-effective leakage reduction through district metering
Authors: Janković-Nišić B. , Graham N. J. D. , Maksimovič Č. , Butler D.
Published: August 2007

A new stochastic water distribution network (WDN) modelling tool has been developed with the aim of providing a sound basis for cost-effective strategic planning of WDN monitoring schemes in terms of quantifiable leakage. Through an analysis of uncertainties in water demand and its propagation through a WDN, the developed computer tool recommends the most cost-effective solution in terms of the number and location of monitoring sites necessary to increase the probability of identifying the location of leaks (or other system anomalies). The methodology was tested on a medium-sized WDN in the UK and the results are presented in this paper.
The sex ratio and age‐specific male mortality: Evidence for culling in utero
Authors: Bruckner Tim , Catalano Ralph
Published: August 2007

While adverse conditions early in life reportedly predispose individuals to increased mortality in adulthood, controversy remains as to whether exogenous insults in utero, especially among male fetuses, induce similar cohort “damage” in populations. A rival theory postulates that exogenous stressors in gestation may “cull” frail male members of the cohort before birth, leaving a smaller but hardier cohort with improved survival. Recent tests, which use the sex ratio (i.e., the odds of a male live birth) as a gauge of insults inflicted upon cohorts in gestation, support the culled cohort argument. These tests, however, examined only aggregate male lifespan, thereby obscuring potential heterogeneity of both damaged and culled cohorts at specific ages over the life course. Using time‐series methods, we explore associations between the sex ratio and cohort male mortality in infancy (before age 1), childhood (1–4 years), youth (5–19 years), adulthood (20–54 years), and old‐age (55–79 years). We examine males born in Sweden (1751–1913), Denmark (1835–1913), and England and Wales (1841–1912). Our findings generally support culled cohorts in that male mortality across all ages fell below its expected value among cohorts in which the sex ratio dropped below its expected level. These findings suggest that exogenous shocks to gestation, as measured by a lower than expected sex ratio, may cull males in utero, leaving behind a less frail cohort over the entire life course. Am. J. Hum. Biol., 2007. © 2007 Wiley‐Liss, Inc.
Gender differences in growth and nutrition in a sample of rural ontario schoolchildren
Authors: Galloway Tracey
Published: August 2007

This paper reports findings of a cross‐sectional study of the growth and nutrition of children living in rural Ontario, Canada. The objectives of the research were threefold: (1) to obtain data on obesity prevalence and nutrient intake in a sample of rural Canadian schoolchildren, (2) to compare findings with rural and national‐level data on obesity prevalence and nutrient intake, and (3) to provide data to school board and public health agencies planning and implementing nutrition policy and programs to this population. Measures of height and weight were obtained for 504 children ages 7–13 years. Height for age and body mass index scores were calculated and compared with 2000 data from the Centers for Disease Control (Kuczmarski et al. [2002]: Vital Health Stat 246:1–190). Weekday 24‐h dietary recall was conducted on a subsample of 352 children and the results compared with Canada's Food Guide (Health Canada,1997) and dietary reference data from the US Institute of Medicine (2000). Prevalence of overweight and obesity were high in this sample, with 17.7% of children classified as overweight and 10.9% of children classified as obese. Fifteen percent of boys were classified as obese, compared to 6.8% of girls. Boys consumed significantly more servings from the grain and meat food groups than girls. While mean daily intake of fiber and micronutrients was significantly low for both boys and girls, there were significant gender differences in nutrient intake, with boys consuming greater energy, protein, carbohydrate, calcium, iron, phosphorus, and sodium than girls. A number of limitations are discussed, in particular issues arising from the use of Dietary Reference Intakes. Am. J. Hum. Biol., 2007. © 2007 Wiley‐Liss, Inc.
Urinary 1‐hydroxypyrene concentrations in Chinese coke oven workers relative to job category, respirator usage, and cigarette smoking
Authors: Chen Bo , Hu Yunping , Zheng Lixing , Wang Qiangyi , Zhou Yuanfen , Jin Taiyi
Published: August 2007

Background

1‐Hydroxypyrene (1‐OHP) is a biomarker of recent exposure to polycyclic aromatic hydrocarbons (PAHs). We investigated whether urinary 1‐OHP concentrations in Chinese coke oven workers (COWs) are modulated by job category, respirator usage, and cigarette smoking.

Methods

The present cross‐sectional study measured urinary 1‐OHP concentrations in 197 COWs from Coking plant I and 250 COWs from Coking plant II, as well as 220 unexposed referents from Control plant I and 56 referents from Control plant II.

Results

Urinary 1‐OHP concentrations (geometric mean, µmol/mol creatinine) were 5.18 and 4.21 in workers from Coking plants I and II, respectively. The highest 1‐OHP levels in urine were found among topside workers including lidmen, tar chasers, and whistlers. Benchmen had higher 1‐OHP levels than other workers at the sideoven. Above 75% of the COWs exceeded the recommended occupational exposure limit of 2.3 µmol/mol creatinine. Respirator usage and increased body mass index (BMI) slightly reduced 1‐OHP levels in COWs (P < 0.1). Cigarette smoking significantly increased urinary 1‐OHP levels in unexposed referents (P < 0.005), but had no effect in COWs (P > 0.1).

Conclusions

Chinese COWs, especially topside workers and benchmen, are exposed to high levels of PAHs. Urinary 1‐OHP concentrations appear to be modulated by respirator usage and BMI in COWs, as well as by smoking in unexposed referents. Am. J. Ind. Med. 50:657–663, 2007. © 2007 Wiley‐Liss, Inc.
Primary amenorrhea and absent uterus in the 22q11.2 deletion syndrome
Authors: Sundaram Usha T. , McDonald‐McGinn Donna M. , Huff Dale , Emanuel Beverly S. , Zackai Elaine H. , Driscoll Deborah A. , Bodurtha Joann
Published: August 2007

The classic clinical features in the 22q11.2 deletion syndrome are congenital heart defects, hypocalcemia, immunodeficiency, learning, speech, and behavioral difficulties. The phenotype is highly variable and continues to expand. We present two cases of absent uterus and unilateral renal agenesis in females with the 22q11.2 deletion. Clinicians caring for these adolescents should be aware of the possibility of renal anomalies and Mullerian agenesis. The diagnosis of 22q11.2 deletion may be considered in a female with Mullerian agenesis, particularly, in association with a history of learning difficulties and speech delay. © 2007 Wiley‐Liss, Inc.
Association between 49 infant gene polymorphisms and preterm delivery
Authors: Chen Brian H. , Carmichael Suzan L. , Shaw Gary M. , Iovannisci David M. , Lammer Edward J.
Published: August 2007

The occurrence of preterm delivery has been increasing in the U.S. Previous studies have identified risk factors for preterm delivery that may have genetic influences. We conducted a case–control study comparing the frequencies of 49 genetic polymorphisms among 62 preterm infants and 553 term infants. The polymorphisms that we examined were involved in xenobiotic‐metabolism, blood pressure, coagulation, the inflammatory response, cell–cell interaction, or folate‐homocysteine metabolism. Univariate analyses on the individual polymorphisms revealed a statistically significant effect for the variant genotypes compared to the wildtype genotypes in SERPINE1 11053G > T (OR = 0.4, 95% CI = 0.2–0.8). This finding suggests the coagulation/thrombophilic pathway may influence the development of preterm delivery. © 2007 Wiley‐Liss, Inc.
Familial thoracic aortic dilation and bicommissural aortic valve: A prospective analysis of natural history and inheritance
Authors: Loscalzo Melissa L. , Goh Denise LM , Loeys Bart , Kent Kathleen C. , Spevak Philip J. , Dietz Harry C.
Published: August 2007

The autosomal dominant inheritance of bicommissural aortic valve (BAV) (Online Mendelian Inheritance in Man #109730) in some families is well‐documented; however, the inheritance of BAV with thoracic aortic aneurysm (TAA) is less clear. Whether the aneurysm is secondary to hemodynamic perturbation related to the valve abnormality or a primary manifestation of the disorder remains controversial. Guidelines are needed regarding the follow‐up and treatment of these patients and their families. Thirteen families with at least one individual with TAA and BAV (BAV/TAA) were evaluated prospectively by standard echocardiographic methods or clinical history. Affected status was determined by the presence of BAV or TAA or a history of dissection, rupture, or surgical repair. Six of 13 families had at least two family members with both BAV and TAA, often in successive generations. Informatively, all 13 families had at least one family member with TAA in the absence of BAV. Thirty‐five percent (39/110) of family members had BAV/TAA or TAA, and the majority of families (11/13) had maximal dilatation above the sinotubular junction (STJ). Vascular dissection or rupture occurred in seven of 13 families and in individuals with structurally normal aortic valves. Two families had non‐manifesting, obligate carriers. Three families have members with other left heart outflow tract anomalies. This study confirms autosomal dominant inheritance with incomplete penetrance for BAV/TAA in these families. Furthermore, our data suggest that the component features, BAV and TAA, are independent manifestations of a single gene defect. To avoid the risk of early death, it is essential that all first‐degree relatives receive echocardiographic follow‐up at regular intervals regardless of the presence or absence of a BAV. This assessment must include imaging of the aortic region above the STJ. © 2007 Wiley‐Liss, Inc.
Severe fatal course of axial mesodermal dysplasia spectrum associated with complex cardiac defect in an infant of a mother with insulin dependent diabetes
Authors: Dinleyici Ener Cagri , Tekin Neslihan , Dinleyici Meltem , Kilic Zubeyir , Adapinar Baki , Aksit M. Arif
Published: August 2007

Axial mesodermal dysplasia spectrum (AMDS) includes the features of other malformation complexes or sequences, such as oculo‐auriculo‐vertebral spectrum (OAVS) and sacral dysgenesis. We describe a new patient, an infant born to a type 1 diabetic mother, with the phenotype of AMDS as well as severe congenital cardiac anomalies including transposition of the great arteries and an atrioventricular septal defect. Congenital heart defects had been reported with OAVS, sacral dysgenesis, and in an infant born to a diabetic mother and combinations of these findings have been reported in the same patient. To our knowledge, this is the first patient with AMDS with transposition of great arteries and an atrioventricular septal defect and the second patient with AMDS who had history of parental consanguinity. The mechanism through which maternal diabetes mellitus leads to malformations is not entirely clear, but the glycemic control is essential in the care of mothers. © 2007 Wiley‐Liss, Inc.
Contributions of ethnobiology to the conservation of tropical rivers and streams
Authors: Silvano R.A.M. , Silva A.L. , Ceroni M. , Begossi A.
Published: August 2007

This study aimed to link basic ethnobiological research on local ecological knowledge (LEK) to the conservation of Brazilian streams, based on two case studies: original data on LEK of fishermen about freshwater fish in the Negro River, Amazon, and previously published data about LEK of farmers on the ecological relationship between forest and streams in the Macabuzinho catchment, Atlantic Forest.

Information was obtained from fishermen through interviews using standard questionnaires containing open‐ended questions. Informants for interview were selected either following some defined criteria or applying the ‘snowball’ method.

Fishermen's LEK about the diets and habitats of 14 fish species in the Negro River provided new biological information on plant species that are eaten by fish, in addition to confirming some ecological patterns from the biological literature, such as dependence of fish on forests as food sources.

In the Atlantic Forest, a comparison between farmers' LEK and a rapid stream assessment in the farmers' properties indicated that farmers tended to overestimate the ecological integrity of their streams. Farmers recognized at least 11 forest attributes that correspond to the scientific concept of ecosystem services. Such information may be useful to promote or enhance dialogue among farmers, scientists and managers.

These results may contribute to the devising of ecosystem management measures in the Negro River, aimed to conserve both rivers and their associated floodplain forests, involving local fishermen. In the Atlantic Forest, we proposed some initiatives, such as to allow direct economic use of their forests to conciliate conflicting perceptions of farmers about ecological benefits versus economic losses from reforestation. Despite their cultural, environmental and geographical differences, the two study cases are complementary and cost‐effective and promising approaches to including LEK in the design of ecological research.

Copyright © 2007 John Wiley & Sons, Ltd.
Multirotations of (Anilinium)([18]Crown‐6) Supramolecular Cation Structure in Magnetic Salt of [Ni(dmit)2]−
Authors: Nishihara Sadafumi , Akutagawa Tomoyuki , Sato Daisuke , Takeda Sadamu , Noro Shin‐ichiro , Nakamura Takayoshi
Published: August 2007

A solid‐state dynamic supramolecular structure consisting of (anilinium)([18]crown‐6) was arranged as the cation in a salt of [Ni(dmit)2]− (dmit=2‐thioxo‐1,3‐dithiole‐4,5‐dithiolate). With the ammonium moiety of anilinium located within the cavity of [18]crown‐6, a hydrogen‐bonded supramolecular structure is formed, with an orthogonal arrangement between the π plane of anilinium and the mean O6 plane of [18]crown‐6. In this supramolecular cation, both anilinium and [18]crown‐6 act as dynamic units with different rotational modes in the solid state. The uniform stacks of cations form an antiparallel arrangement, thus producing a layer structure. Sufficient space for the 180° flip‐flop motion of the phenyl ring and the rotation of [18]crown‐6 was observed in the cation layer. Thermally activated 180° flip‐flop motions, with a frequency of 6 MHz at room temperature and an activation energy of 31 kJ mol−1, were confirmed by temperature‐dependent 2H NMR spectra of ([D5]anilinium)‐([18]crown‐6)[Ni(dmit)2]. A double‐minimum potential for the molecular rotation of anilinium, with a barrier of approximately 40 kJ mol−1, was indicated by ab initio calculations. The wide‐line 1H NMR spectra indicated a thermally activated rotation of [18]crown‐6 at temperatures above 250 K. Therefore, multiple molecular motions of the 180° flip‐flop motion of the phenyl ring and the rotation of [18]crown‐6 occur simultaneously in the solid state. The temperature‐dependent dielectric constants revealed that the molecular motion of [18]crown‐6, other than the flip‐flop motion, dominates the dielectric response in the measured temperature and frequency range.
Erläuterungen und Beispiele zur Lastnorm DIN 1055 neu
Authors: Schroeter Heinrich
Published: August 2007

In diesem Aufsatz wird die Gruppe der neu gefassten Normen über Lastannahmen aus der Sicht des Anwenders kritisch betrachtet. Es werden die wesentlichen nderungen gegenüber den alten Fassungen herausgestellt und auch auf die dadurch häufig vorkommenden Fehlinterpretationen der neuen Normen hingewiesen. Da der Verfasser nicht an der Neufassung mitgearbeitet hat, werden auch keine Auslegungen gegeben. Aus Platzgründen werden die Teile7, 8 und 10 nicht näher behandelt, da diese Teil e nicht bauaufsichtlich eingeführt wurden.
Perturbation of retinoic acid (RA)‐mediated limb development suggests a role for diminished RA signaling in the teratogenesis of ethanol
Authors: Johnson Corey S. , Zucker Robert M. , Hunter Edward Sidney , Sulik Kathleen K.
Published: August 2007

BACKGROUND:

A proposed mechanism for ethanol teratogenicity entails ethanol‐mediated reductions in retinoic acid (RA). This premise was investigated utilizing a mouse model, with limb reduction defects as the teratogenic end point.

METHODS:

Ethanol, Disulfiram, or BMS‐189453 was administered to C57BL/6J mice on the 9th day of pregnancy. Forelimb morphology was assessed on gestation day 18 using Alcian blue and Alizarin red staining. Nile blue sulfate or LysoTracker Red (LTR) vital staining identified cell death in the limb bud. The ability of RA to prevent ethanol‐induced cell death was assessed by coadministration followed by laser scanning confocal microscopic examination of LTR‐staining. In situ hybridization and qPCR were used to examine gene expression in treated limb buds.

RESULTS:

Ethanol, Disulfiram, and BMS‐189453 resulted in postaxial ectrodactyly, intermediate ectrodactyly, and other digital defects. Excessive Nile blue sulfate staining was evident in the presumptive AER following each of the three exposures. Ethanol‐induced LTR staining was prevented by RA supplementation. Both in situ hybridization and qPCR illustrated decreases in Shh and Tbx5 in ethanol‐exposed embryos as compared to control.

CONCLUSIONS:

Contrary to studies of prolonged RA deficiency, acute exposure to functional antagonists of RA results in limb defects that are morphologically similar to those caused by ethanol. The rescue of ethanol‐induced cell death by RA and similar changes in Shh transcription further suggest that RA contributes to ethanol‐induced limb dysmorphology. Moreover, the repression of key mediators of limb development soon after ethanol exposure adds to the existing knowledge of the pathogenic effects of ethanol. Birth Defects Research (Part A), 2007. © 2007 Wiley‐Liss, Inc.
The model space in partial least squares regression
Authors: Pell Randy J. , Ramos L. Scott , Manne Rolf
Published: August 2007

This paper documents an inconsistency caused by truncation in the conventional partial least squares (PLS) regression algorithm with one dependent variable. It is shown that the conventional PLS algorithm with orthogonal score vectors uses one model space to compute the regression vector but another model space to represent the reconstructed data. In comparison, the Bidiag2 bidiagonalization algorithm and the non‐orthogonal PLS algorithm of Martens are consistent in using the same space for the regression vector and for the reconstructed data, while the SIMPLS algorithm has the same inconsistency as the conventional PLS algorithm. The magnitude of the difference depends on the degree of truncation of the model space: it is generally larger with greater truncations but is not a monotonic function of the truncation. A numerical example demonstrates implications for outlier detection. Consistent behavior upon truncation may be important when PLS regression is implemented as part of standardized analytical procedures. Copyright © 2007 John Wiley & Sons, Ltd.
Novel Synthetic Strategy for Developing an Isospecific Unbridged Metallocene System for Propylene Polymerization
Authors: Kim Seong Kyun , Kim Hwa Kyu , Lee Min Hyung , Yoon Seung Woong , Do Youngkyu
Published: August 2007

New unbridged zirconocenes functionalized with a Lewis base, [{1‐(E‐C6H4)‐3,4‐Me2C5H2}2ZrCl2] (E = p‐NMe2 (3); p‐OMe (4); p‐SMe (5)) were prepared and their propylene polymerization behavior was examined. Under methylaluminoxane (MAO) activation at atmospheric monomer pressure, these complexes afford mixtures of polymers exhibiting multimelting transition temperatures and broad molecular weight distribution, whereas they produce completely atactic polypropylenes under [Ph3C][B(C6F5)4] activation. Stepwise solvent extraction of the polymer mixtures reveals that the polymers consist of amorphous, moderately isotactic, as well as, highly isotactic portions and the weight ratio of each portion is dependent upon reaction temperature. The generation of rigid rac‐like cationic active species in situ by the interaction between basic sites of catalysts and acidic sites of the [Me‐MAO]− counter anion is considered to be the origin of the observed isospecificity. Further investigation of bulk polymerization in liquid propylene shows not only a considerable increase of the isotactic portion of the obtained polypropylenes but also apparent isospecificity of 4 and 5/MAO systems even at high temperature. Variation of the Lewis basic center leads to a dramatic change in stereoselectivity of the catalyst in the decreasing order of 3>4≫5, in spite of their structural similarity.
PKC 412 small‐molecule tyrosine kinase inhibitor
Authors: El Fitori Jamael , Su Yun , Büchler Peter , Ludwig Roman , Giese Nathalia A. , Büchler Markus W. , Quentmeier Hilmar , Hines Oscar J. , Herr Ingrid , Friess Helmut
Published: August 2007

BACKGROUND.

PKC412 is a kinase inhibitor that blocks protein kinase C (PKC), vascular endothelial growth factor receptors, platelet‐derived growth factor receptor FLT3, and other class III receptor tyrosine kinases. The enthusiasm for this compound is based on its inhibitory effect even in the case of FLT3 mutations. The aim of this study was to analyze the role of FLT3 in pancreatic cancer and to study the biological activity of combined inhibition of neovascularization and mitogenesis in this disease.

METHODS.

FLT3 expression was analyzed in 18 pancreatic cancer specimens by real‐time quantitative polymerase chain reaction (RTQ‐PCR) and immunohistochemistry. Sixteen pancreatic cancer cell lines were screened for ITD and D835 point mutations of the FLT3 gene. MTT assays and anchorage‐independent growth assays were used to study cell growth. Flow cytometry was used for cell cycle analysis and apoptosis quantification. In vivo AsPC‐1 and HPAF‐II cells were used for orthotopic tumor modeling. Immunohistochemistry was used to quantify tumor angiogenesis.

RESULTS.

FLT3 expression is down‐regulated in pancreatic cancer. Activating FLT3 mutations (ITD, D835) were not detectable in any of the pancreatic cancer cell lines. Cell growth was significantly inhibited as cell‐cycle progression was reduced and programmed cell death increased. In vivo PKC412 therapy resulted in a significant inhibition of orthotopic tumor growth with abrogation of tumor angiogenesis.

CONCLUSIONS.

These data highlight that PKC412 may be a new compound in target therapy of inoperable pancreatic cancer patients and suggest a potential role for the combined use of broad spectrum kinase inhibitors in the management of these patients. Cancer 2007. © 2007 American Cancer Society.