bluuebunny/crossref_metadata_2025 huggingface dataset:
mRNA Transport in Dendrites: RNA Granules, Motors, and Tracks
Authors: Hirokawa Nobutaka
Published: July 2006

The targeting of mRNAs to neuronal dendrites is an important protein sorting mechanism. Recent studies have revealed that mRNAs are transported by molecular motors. The kinesin superfamily protein KIF5 transports mRNAs such as calcium/calmodulin-dependent kinase IIα (CaMKIIα) and Arc mRNAs along microtubules in large granules containing proteins involved in RNA transport, protein synthesis, RNA helicases, heterogeneous nuclear ribonucleoproteins (hnRNPs), and RNA-associated proteins. This transport is fundamental to local protein synthesis and to the regulation of neuronal function.
Scotopic Visual Signaling in the Mouse Retina Is Modulated by High-Affinity Plasma Membrane Calcium Extrusion
Authors: Duncan Jacque L. , Yang Haidong , Doan Thuy , Silverstein Robert S. , Murphy Gabe J. , Nune George , Liu Xiaorong , Copenhagen David , Tempel Bruce L. , Rieke Fred , Križaj David
Published: July 2006

Transmission of visual signals at the first retinal synapse is associated with changes in calcium concentration in photoreceptors and bipolar cells. We investigated how loss of plasma membrane Ca2+ATPase isoform 2 (PMCA2), the calcium transporter isoform with the highest affinity for Ca2+/calmodulin, affects transmission of rod- and cone-mediated responses. PMCA2 expression in the neuroblast layer was observed soon after birth; in the adult, PMCA2 was expressed in inner segments and synaptic terminals of rod photoreceptors, in rod bipolar cells, and in most inner retinal neurons but was absent from cones. To determine the role of PMCA2 in retinal signaling, we compared morphology and light responses of retinas from control mice and deafwaddlerdfw2Jmice, which lack functional PMCA2 protein. The cytoarchitecture of retinas from control anddfw2Jmice was indistinguishable at the light microscope level. Suction electrode recordings revealed no difference in the sensitivity or amplitude of outer segment light responses of control anddfw2Jrods. However, rod-mediated ERG b-wave responses indfw2Jmice were ∼45% smaller and significantly slower than those of control mice. Furthermore, recordings from individual rod bipolar cells showed that the sensitivity of transmission at the rod output synapse was reduced by ∼50%. No changes in the amplitude or timing of cone-mediated ERG responses were observed. These results suggest that PMCA2-mediated Ca2+extrusion modulates the amplitude and timing of the high-sensitivity rod pathway to a much greater extent than that of the cone pathway.
The Role of Contemporary Family Behaviors in Nonmarital Conception Outcomes of Nonmetro Women: Comments on Albrecht and Albrecht (2004)*
Authors: Snyder Anastasia R.
Published: July 2006

Abstract  Recent research by Albrecht and Albrecht (2004) on nonmarital conception outcomes is extended using data from the 1995 cycle of the National Survey of Family Growth. Residential differences in nonmarital conception outcomes are examined, including nonmarital conception, live birth outcomes, and marital status at birth following a nonmarital conception. Analyses emphasize the role of more contemporary family behaviors in conception outcomes and the importance of distinguishing suburban‐metro from central city‐metro residence in studies that emphasize residential variation in family outcomes. Findings are that (1) nonmetro women have retained more traditional family behavior with regards to marriage following a nonmarital conception, (2) nonmetro and suburban women, however, have equally traditional family patterns and behaviors on many of the outcomes of interest, and (3) it is important to include contemporary family behaviors, such as nonmarital cohabitation, in studies that evaluate traditional family behavior among nonmetro populations.
Use of 2-Channel Bedside Electroencephalogram Monitoring in Term-Born Encephalopathic Infants Related to Cerebral Injury Defined by Magnetic Resonance Imaging
Authors: Shah Divyen K. , Lavery Shelly , Doyle Lex W. , Wong Connie , McDougall Peter , Inder Terrie E.
Published: July 2006

OBJECTIVE. Single-channel amplitude-integrated electroencephalography has been shown to be predictive of neurodevelopmental outcome in term infants with hypoxic-ischemic encephalopathy. We describe the relationship of quantifiable electroencephalogram (EEG) measures, obtained using a 2-channel digital bedside EEG monitor from term newborn infants with encephalopathy and/or seizures, to cerebral injury defined qualitatively by MRI.

METHODS. Median values of minimum, mean, and maximum EEG amplitude were obtained from term-born encephalopathic infants during a 2-hour seizure-free period obtained within 72 hours of admission. Infants underwent MRI with images qualitatively scored for abnormalities of cortex, white matter, deep nuclear gray matter, and posterior limb of the internal capsule. Eighty-six infants had EEG measures related to qualitative MRI outcomes.

RESULTS. The most common diagnosis was hypoxic ischemic encephalopathy (n = 40). For all infants there was a negative relationship between EEG amplitude measures and MRI abnormality scores assessed on a scale from 4 to 15, with a higher score indicating more abnormalities. This relationship was strongest for the minimum amplitude measures in both hemispheres; that is, for every unit increase in score there was a mean drop of 0.41 μv for the left cerebral hemisphere, with 35% of variance explained. This relationship persisted on sub-group analyses for infants with hypoxic-ischemic encephalopathy, infants with other diagnoses and infants monitored after the first 24 hours of life. Using an MRI abnormality score cutoff of 8 or worse for cerebral injury in infants with hypoxic-ischemic encephalopathy, a minimum amplitude of 4 μV showed a higher specificity (80%: left hemisphere), whereas a minimum amplitude of 6 μV showed a higher sensitivity (92%: left hemisphere).

CONCLUSIONS. Bedside EEG measures in term-born encephalopathic infants are related to the severity of cerebral injury as defined by qualitative MRI. A minimum amplitude of <4 μV appears useful in predicting outcome.
Tympanometric Findings and the Probability of Middle-Ear Effusion in 3686 Infants and Young Children
Authors: Smith Clyde G. , Paradise Jack L. , Sabo Diane L. , Rockette Howard E. , Kurs-Lasky Marcia , Bernard Beverly S. , Colborn D. Kathleen
Published: July 2006

OBJECTIVE. We examined relationships between tympanometric findings and the presence or absence of middle-ear effusion in a population-based sample of children under the age of 3 years.

METHODS. In a study of children’s development in relation to early-life otitis media, we enrolled 6350 infants soon after birth and evaluated them regularly for the presence of middle-ear effusion. In 3686 of the children, we compared tympanometric findings with otoscopic diagnoses. We categorized tympanograms according to varying combinations of tympanometric peak height, peak pressure, and width, and calculated for each resulting category the percentage of the associated ears diagnosed as having effusion. Using these findings we developed algorithms for estimating the probability of middle-ear effusion associated with tympanograms of any configuration.

RESULTS. For tympanograms generally, the lower their height and the greater their width, the greater was the probability of associated middle-ear effusion; the probability also was greater when peak pressure was negative rather than positive. Among children ≥6 months of age, effusion was diagnosed in only 2.7% of ears with tympanometric height ≥0.6 mL, but in 80.2% of ears with flat tympanograms. Relationships among younger infants were similar but less consistent. In both age groups, the tympanographic configurations most commonly encountered were associated with either a relatively low probability (<30%) or a relatively high probability (>70%) of the presence of middle-ear effusion.

The receiver operating characteristic curve we generated using the algorithm we developed for children ≥6 months of age gave an area under the curve of 0.84. The algorithm performed equally well when applied to a separate group of children, suggesting that it is generalizable to other unselected populations.

CONCLUSIONS. The present report offers two alternative methods for estimating the probability of middle-ear effusion in children aged 6 through 35 months, given any combination of tympanometric values.
Quantifying the Association Between Physical Activity and Injury in Primary School–Aged Children
Authors: Spinks Anneliese B. , McClure Roderick J. , Bain Chris , Macpherson Alison K.
Published: July 2006

BACKGROUND. Regular physical activity is strongly advocated in children, with recommendations suggesting up to several hours of daily participation. However, an unintended consequence of physical activity is exposure to the risk of injury. To date, these risks have not been quantified in primary school–aged children despite injury being a leading cause for hospitalization and death in this population.

OBJECT. Our goal was to quantify the risk of injury associated with childhood physical activity both in and out of the school setting and calculate injury rates per exposure time for organized and non–organized activity outside of school.

METHODS. The Childhood Injury Prevention Study prospectively followed a cohort of randomly selected Australian primary school–and preschool-aged children (4 to 12 years). Over 12 months, each injury that required first aid attention was registered with the study. Exposure to physical activity outside school hours was measured by using a parent-completed 7-day diary. The age and gender distribution of injury rates per 10 000 hours of exposure were calculated for all activity and for organized and non–organized activity occurring outside school hours. In addition, child-based injury rates were calculated for physical activity–related injuries both in and out of the school setting.

RESULTS. Complete diary and injury data were available for 744 children. There were 504 injuries recorded over the study period, 396 (88.6%) of which were directly related to physical activity. Thirty-four percent of physical activity–related injuries required professional medical treatment. Analysis of injuries occurring outside of school revealed an overall injury rate of 5.7 injuries per 10000 hours of exposure to physical activity and a medically treated injury rate of 1.7 per 10000 hours.

CONCLUSION. Injury rates per hours of exposure to physical activity were low in this cohort of primary school–aged children, with <2 injuries requiring medical treatment occurring for every 10000 hours of activity participation outside of school.
Analysis of Clinical Features Predicting Etiologic Yield in the Assessment of Global Developmental Delay
Authors: Srour Myriam , Mazer Barbara , Shevell Michael I.
Published: July 2006

OBJECTIVE. Global developmental delay is a common reason for presentation for neurologic evaluation. This study examined the role of clinical features in predicting the identification of an underlying cause for a child's global developmental delay.

METHODS. Over a 10-year inclusive interval, the case records of all consecutive children <5 years of age referred to a single ambulatory practice setting for global developmental delay were systematically reviewed. The use of clinical features in predicting the identification of a specific underlying cause for a child's delay was tested using χ2 analysis.

RESULTS. A total of 261 patients eventually met criteria for study inclusion. Mean age at initial evaluation was 33.6 months. An underlying cause was found in 98 children. Commonest etiologic groupings were genetic syndrome/chromosomal abnormality, intrapartum asphyxia, cerebral dysgenesis, psychosocial deprivation, and toxin exposure. Factors associated with the ability to eventually identify an underlying cause included female gender (40 of 68 vs 58 of 193), abnormal prenatal/perinatal history (52 of 85 vs 46 of 176), absence of autistic features (85 of 159 vs 13 of 102), presence of microcephaly (26 of 40 vs 72 of 221), abnormal neurologic examination (52 of 71 vs 46 of 190), and dysmorphic features (44 of 84 vs 54 of 177). In 113 children without any abnormal features identified on history or physical examination, routine screening investigations (karyotype, fragile X molecular genotyping, and neuroimaging) revealed an underlying etiology in 18.

CONCLUSIONS. Etiologic yield in an unselected series of young children with global developmental delay is close to 40% overall and 55% in the absence of any coexisting autistic features. Clinical features are readily apparent that may enhance an expectation of a successful etiologic search. Screening investigations may yield an underlying cause.
Development of Measures of the Quality of Emergency Department Care for Children Using a Structured Panel Process
Authors: Guttmann Astrid , Razzaq Asma , Lindsay Patty , Zagorski Brandon , Anderson Geoffrey M.
Published: July 2006

BACKGROUND. Performance measures are essential components of public reporting and quality improvement. To date, few such measures exist to provide a comprehensive assessment of the quality of emergency department services for children.

OBJECTIVES. Our goal was to use a systematic process to develop measures of emergency department care for children (0–19 years) that are (1) based on research evidence and expert opinion, (2) representative of a range of conditions treated in most emergency departments, (3) related to links between processes and outcomes, and (4) feasible to measure.

METHODS. We presented a panel of providers and managers data from emergency department use to identify common conditions across levels of patient acuity, which could be targets for quality improvement. We used a structured panel process informed by a literature review to (1) identify condition-specific links between processes of care and defined outcomes and (2) select indicators to assess these process-outcome links. We determined the feasibility of calculating these indicators using an administrative data set of emergency department visits for Ontario, Canada.

RESULTS. The panel identified 18 clinical conditions for indicator development and 61 condition-specific links between processes of care and outcomes. After 2 rounds of ratings, the panel defined 68 specific clinical indicators for the following conditions: adolescent mental health problems, ankle injury, asthma, bronchiolitis, croup, diabetes, fever, gastroenteritis, minor head injury, neonatal jaundice, seizures, and urinary tract infections. Visits for these conditions account for 23% of all pediatric emergency department use. Using an administrative data set, we were able to calculate 19 indicators, covering 9 conditions, representing 20% of all emergency department visits by children.

CONCLUSIONS. Using a structured panel process, data on emergency department use, and literature review, it was possible to define indicators of emergency department care for children. The feasibility of these indicators will depend on the availability of high-quality data.
Effects of Open-Loop Feedback on Physical Activity and Television Viewing in Overweight and Obese Children: A Randomized, Controlled Trial
Authors: Goldfield Gary S. , Mallory Risa , Parker Torrey , Cunningham Terrell , Legg Christine , Lumb Andrew , Parker Kasey , Prud'homme Denis , Gaboury Isabelle , Adamo Kristi B.
Published: July 2006

OBJECTIVES. Television viewing and physical inactivity increase the risk of obesity in youth. Thus, identifying new interventions that increase physical activity and reduce television viewing would be helpful in the prevention and treatment of pediatric obesity. This study evaluated the effects of open-loop feedback plus reinforcement versus open-loop feedback alone on physical activity, targeted sedentary behavior, body composition, and energy intake in youth.

METHODS. Thirty overweight or obese 8- to 12-year-old children were randomly assigned to an intervention (n = 14) or control group (n = 16). Participants wore accelerometers every day for 8 weeks and attended biweekly meetings to download the activity monitors. For children in the open-loop feedback plus reinforcement (intervention) group, accumulating 400 counts of physical activity on pedometers earned 1 hour of television/VCR/DVD time, which was controlled by a Token TV electronic device. Open-loop feedback control subjects wore activity monitors but had free access to targeted sedentary behavior.

RESULTS. Compared with controls, the open-loop feedback plus reinforcement group demonstrated significantly greater increases in daily physical activity counts (+65% vs +16%) and minutes per day of moderate-to-vigorous physical activity (+9.4 vs +0.3) and greater reductions in minutes per day spent in television viewing (−116.1 vs +14.3). The intervention group also showed more favorable changes in body composition, dietary fat intake, and energy intake from snacks compared with controls. Reductions in sedentary behavior were directly related to reductions in BMI, fat intake, snack intake, and snack intake while watching television.

CONCLUSIONS. Providing feedback of physical activity in combination with reinforcing physical activity with sedentary behavior is a simple method of modifying the home environment that may play an important role in treating and preventing child obesity.
Cartilage-derived biomarkers and lipid mediators of inflammation in horses with osteochondritis dissecans of the distal intermediate ridge of the tibia
Authors: de Grauw Janny C. , Brama Pieter A. , Wiemer Peter , Brommer Harold , van de Lest Chris H. , van Weeren P. Rene
Published: July 2006

Objective—To assess whether reported alterations in metabolism of cartilage matrix in young (0 to 24 months old) horses with osteochondritis dissecans (OCD) may also be found in older (24 to 48 months old) horses with clinical signs of OCD and to investigate the role of eicosanoids in initiating these clinical signs.

Sample Population—Synovial fluid was collected from 38 tarsocrural joints of 24 warmblood horses with (22 joints of 16 horses) or without (16 joints of 8 horses) clinical signs and a radiographic diagnosis of OCD of the distal intermediate ridge of the tibia.

Procedures—Turnover of type II collagen was investigated by use of specific immunoassays for synthesis (carboxypropeptide of type II collagen [CPII]) and degradation (collagenase-cleaved fragments of type II collagen [C2C]) products. Furthermore, glycosaminoglycan (GAG), leukotriene (LT) B4, cysteinyl LTs, and prostaglandin (PG) E2 concentrations were determined, and concentrations in joints with OCD were compared with those in joints without OCD.

Results—Concentrations of CPII, C2C, and GAG did not differ significantly between affected and nonaffected joints. Fluid from joints with OCD had significantly higher LTB4 and PGE2 concentrations than did fluids from nonaffected joints.

Conclusions and Clinical Relevance—Altered collagen or proteoglycan turnover was not detected in 24- to 48-month-old horses at the time they developed clinical signs of OCD of the distal intermediate ridge of the tibia. However, increased concentrations of LTB4 and PGE2 in fluid of joints with OCD implicate these mediators in the initiation of clinical signs of OCD.
Induction of antigen-specific T-cell subset activation to bovine respiratory disease viruses by a modified-live virus vaccine
Authors: Platt Ratree , Burdett William , Roth James A.
Published: July 2006

Objective—To determine the efficacy of a modified-live virus vaccine containing bovine herpes virus 1 (BHV-1), bovine respiratory syncytial virus (BRSV), parainfluenza virus 3, and bovine viral diarrhea virus (BVDV) types 1 and 2 to induce neutralizing antibodies and cell-mediated immunity in naïve cattle and protect against BHV-1 challenge.

Animals—17 calves.

Procedures—8 calves were mock-vaccinated with saline (0.9% NaCl) solution (control calves), and 9 calves were vaccinated at 15 to 16 weeks of age. All calves were challenged with BHV-1 25 weeks after vaccination. Neutralizing antibodies and T-cell responsiveness were tested on the day of vaccination and periodically after vaccination and BHV-1 challenge. Specific T-cell responses were evaluated by comparing CD25 upregulation and intracellular interferon-γ expression by 5-color flow cytometry. Titration of BHV-1 in nasal secretions was performed daily after challenge.

Results—Vaccinated calves seroconverted by week 4 after vaccination. Antigen-specific cell-mediated immune responses, by CD25 expression index, were significantly higher in vaccinated calves than control calves. Compared with control calves, antigen-specific interferon-γ expression was significantly higher in calves during weeks 4 to 8 after vaccination, declining by week 24. After BHV-1 challenge, both neutralizing antibodies and T-cell responses of vaccinated calves had anamnestic responses to BHV-1. Vaccinated calves shed virus in nasal secretions at significantly lower titers for a shorter period and had significantly lower rectal temperatures than control calves.

Conclusion and Clinical Relevance—A single dose of vaccine effectively induced humoral and cellular immune responses against BHV-1, BRSV, and BVDV types 1 and 2 and protected calves after BHV-1 challenge for 6 months after vaccination.
Demographic trends for animal care and control agencies in Ohio from 1996 to 2004
Authors: Lord Linda K. , Wittum Thomas E. , Ferketich Amy K. , Funk Julie A. , Rajala-Schultz Paivi , Kauffman Ross M.
Published: July 2006

Objective—To examine changes between 1996 and 2004 in regard to numbers of animals handled, medical care provided, expenses, numbers of employees, and agency policies for animal care and control agencies in Ohio.

Design—Cross-sectional survey.

Sample Population—223 animal care and control agencies.

Procedures—A questionnaire was mailed to animal care and control agencies in Ohio to collect information for 2004; results were compared with published results of a similar survey.

Results—165 of the 223 (74%) agencies responded. Estimated total number of animals handled in 2004 was 315,519, which represented a decrease of 7% compared with 1996. However, although number of dogs taken in decreased 17%, number of cats taken in increased 20%. Between 1996 and 2004, the euthanasia rate decreased from 65.3% to 56.8%, and the adoption rate increased from 24.5% to 33.6%. Number of dogs euthanatized decreased 39%, but number of cats euthanatized increased 14%. The proportion of agencies with a spay-neuter policy increased from 56% to 71%, and the proportion that maintained an association with a veterinarian increased from 39% to 80%. For dogs handled by county dog warden agencies, the odds of euthanasia were higher if the agency did not have a spay-neuter policy (odds ratio, 1.36).

Conclusions—Results suggest that the status of dogs handled by animal care and control agencies in Ohio improved between 1996 and 2004, but that the status of cats deteriorated.
Self‐Assembly of m‐Diethynylbenzene Macrocycles Containing Exoannular Chiral Side Chains
Authors: Tobe Y. , Nagai T. , Araki S. , Ichikawa T. , Nomoto A. , Sonoda M. , Hirose K.
Published: July 2006

Induced circular dichroism (CD) spectra of the m‐diethynylbenzene macrocycles (S)‐2 and (R)‐2 that have exoannular chiral side chains are observed in a methanol/chloroform (8:2) solution, indicating the formation of chiral, helical aggregates in solution. Solid films prepared on the surface of quartz substrates by spin‐coating solutions of (S)‐2 also exhibit CD signals that are remarkably dependent on the solvent used for the spin‐coating. The relationship between the CD spectra and the morphology of the solid films observed by atomic force microscopy is discussed.
Study of bubbling and slugging fluidized beds by simulation and ECT
Authors: Wang Haigang , Yang Wuqiang , Dyakowski Tom , Liu Shi
Published: July 2006

Fluidization conditions in a circulating‐fluidized bed (CFB) can vary dramatically, from bubbling to circulating regimes. The granular Eurlerian models have been used to simulate the bubbling and slugging behavior of gas and solids in CFB. Considering the dielectric properties and rapid movement of solids in CFB, electrical capacitance tomography (ECT) is particularly suitable for measuring the concentration and distribution of solids in CFB to verify the simulation results. The simulation results by computational fluid dynamics (CFD) analysis and experimental results obtained by ECT are reported, and compares the simulation and experimental results first time, including the solids concentration profile, temporal variation of average‐solids concentration, autocorrelation coefficient and frequency spectrum. © 2006 American Institute of Chemical Engineers AIChE J, 2006
What the other children are thinking: Brothers and sisters of persons with Down syndrome
Authors: Skotko Brian G. , Levine Susan P.
Published: July 2006

Brothers and sisters are obligatorily welcomed to the disability community when a person with Down syndrome (DS) is part of the family unit. How they react to such an invitation is the focus of this investigation. Here, we review the most current research on brothers and sisters of persons with DS, and comment on our own experience in facilitating sibling workshops at the local, state, and national levels. The evidence, to date, seems clear: brothers and sisters experience a wide range of emotions, but typically the positive feelings outweigh the negative ones. Further, siblings find rich value in having a family member with DS, and most will assume positions of advocacy at some level in their lives. Recommendations for physicians on how parents can nurture healthy relationships among their children are offered. © 2006 Wiley‐Liss, Inc.
Materials for Fluorescence Resonance Energy Transfer Analysis: Beyond Traditional Donor–Acceptor Combinations
Authors: Sapsford Kim E. , Berti Lorenzo , Medintz Igor L.
Published: July 2006

The use of Förster or fluorescence resonance energy transfer (FRET) as a spectroscopic technique has been in practice for over 50 years. A search of ISI Web of Science with just the acronym “FRET” returns more than 2300 citations from various areas such as structural elucidation of biological molecules and their interactions, in vitro assays, in vivo monitoring in cellular research, nucleic acid analysis, signal transduction, light harvesting and metallic nanomaterials. The advent of new classes of fluorophores including nanocrystals, nanoparticles, polymers, and genetically encoded proteins, in conjunction with ever more sophisticated equipment, has been vital in this development. This review gives a critical overview of the major classes of fluorophore materials that may act as donor, acceptor, or both in a FRET configuration. We focus in particular on the benefits and limitations of these materials and their combinations, as well as the available methods of bioconjugation.
Ermüdungsfestigkeit von hochfestem Beton unter Druckbeanspruchung
Authors: Tue Nguyen Viet , Mucha Stephan
Published: July 2006

Das Verhalten von hochfestem Beton unter Druckbeanspruchung wurde experimentell mit rund 170 Versuchskörpern untersucht. Die Ergebnisse zeigen, daß die Erkenntnisse von normalfestem Beton bezüglich des Ermüdungsverhaltens nicht ohne weiteres auf hochfesten Beton zu übertragen sind. Im Bereich mit Oberlast größer als die Elastizitätsgrenze ist das Ermüdungsverhalten von hochfestem Beton eher ungünstiger als das des normalfesten Betons. Im Bereich geringerer Oberlast ist dagegen vergleichbares Verhalten zu erwarten. Auch die Spannungsumlagerung in der Druckzone mit unterschiedlicher Beanspruchung scheint geringer, als bei normalfesten Beton zu erwarten. Um einen sicheren Ermüdungsnachweis für Konstruktionen aus hochfestem Beton zu formulieren, sind weitere Untersuchen erforderlich.
Effect of Polarity and Structural Design on Molecular Photorefractive Properties of Heteroaromatic‐Based Push–Pull Dyes
Authors: Archetti Graziano , Abbotto Alessandro , Wortmann Rüdiger
Published: July 2006

A combined experimental (optical and electro‐optical absorption measurements) and computational (ab initio RHF and DFT) approach has been used to investigate the molecular low‐ and high‐Tg photorefractive (PR) performances of neutral and zwitterionic heteroaromatic dipolar chromophores in terms of structural and solvent‐polarity effects. We have found that the nature of the building units (donor, acceptor, and spacer) and the polarity of the surrounding medium strongly affect all the relevant ground‐state and nonlinear optical properties involved in the PR activity, that is, the dipole moment, the polarizability anisotropy, and first hyperpolarizability of the electronic ground‐state. The variation of these properties is in turn transferred to molecular low‐ and high‐Tg PR figures of merit. It is shown that PR molecular performance not only relies on a proper choice of structural components but varies by orders of magnitude as a function of the medium polarity, and this suggests that a combination of molecular design and host‐matrix engineering is required for optimized performances of PR materials.
Efficient Synthesis of Calix[6]tmpa: A New Calix[6]azacryptand with Unique Conformational and Host–Guest Properties
Authors: Zeng Xianshun , Coquière David , Alenda Aurélie , Garrier Eva , Prangé Thierry , Li Yun , Reinaud Olivia , Jabin Ivan
Published: July 2006

A new C3v‐symmetrical calix[6]azacryptand, that is, calix[6]tmpa (11), was synthesized by efficient [1+1] macrocyclization reactions. Remarkably, both linear and convergent synthetic strategies that were applied lead to equally good overall yields. Calix[6]tmpa behaves as a single proton sponge and appeared reluctant to undergo polyprotonation, unlike classical tris(2‐pyridylmethyl)amine (tmpa) derivatives. It also acts as a good host for ammonium ions. Interestingly, it strongly binds a sodium ion and a neutral guest molecule, such as a urea, an amide, or an alcohol, in a cooperative way. A 1H NMR study indicated that the ligand, as well as its complexes, adopt a major flattened cone conformation that is the opposite of that observed with the previously reported calix[6]cryptands. Characterization of the monoprotonated derivative 11⋅H+ by X‐ray diffraction also revealed the presence of a 1,3‐alternate conformation, which is the first example of its kind in the calix[6]arene family. This conformer is probably also present in solution as a minor species. The important covalent constraint induced by the polyaromatic tmpa cap on the calixarene skeleton, and conversely from the calix core onto the tmpa moiety, is the likely basis for the unique conformational and chemical properties of this host.
Reactions of μ3‐Alkenyl Triruthenium Carbonyl Clusters with Alkynes: Synthesis of Trinuclear μ‐//‐Alkyne, μ‐Vinylidene, and μ‐Dienoyl Derivatives
Authors: Cabeza Javier A. , del Río Ignacio , Martínez‐Méndez Lorena , Pérez‐Carreño Enrique
Published: July 2006

The reactions of doubly face‐capped triruthenium cluster complexes of the type [Ru3(μ3‐κ2‐HNNMe2)(μ3‐κ2‐R2CCHR1)(μ‐CO)2(CO)6] (HNNMe2 = 1,1‐dimethylhydrazide; R2CCHR1 = alkenyl ligand) with terminal and internal alkynes have been studied in refluxing toluene. The following derivatives have been isolated from these reactions: [Ru3(μ3‐κ2‐HNNMe2)(μ3‐κ2‐R2CCHR1)(μ‐κ2‐//‐HCCH)(CO)7] (R1 = R2 = H, 5; R1 = Ph, R2 = H, 6; R1 = CH2OMe, R2 = H, 7 a; R1 = H, R2 = CH2OMe, 7 b) from acetylene, [Ru3(μ3‐κ2‐HNNMe2)(μ3‐κ2‐HCCH2)(μ‐κ2‐//‐PhCCPh)(CO)7] (11) from diphenylacetylene, and three isomers of [Ru3(μ3‐κ2‐HNNMe2)(μ3‐κ2‐HCCH2)(μ‐κ2‐//‐PhCCH)(CO)7] (14, 15 a, and 15 b) from phenylacetylene. These products result from substitution of a CO ligand by the alkyne and contain an RuRu edge bridged by the alkyne ligand in a parallel manner. DFT calculations on selected isomeric products have helped to establish that the type of RuRu edge bridged by the alkyne depends more on kinetic factors related to the size of the alkyne substituents than on the thermodynamic stability of the final products. The preparation of triruthenium cluster complexes with μ‐//‐alkyne ligands is unprecedented and seems to relate to the fact that the starting trinuclear complexes have their two triangular faces protected by capping ligands. The clusters bearing μ‐//‐acetylene (5–7) are thermodynamically unstable with respect to their transformation into edge‐bridging vinylidene derivatives, [Ru3(μ3‐κ2‐HNNMe2)(μ3‐κ2‐HCCHR)(μ‐κ1‐CCH2)(CO)7] (R = H, 8; Ph, 9; CH2OMe, 10). DFT calculations have shown that complex 8 is 11.2 kcal mol−1 more stable than its precursor 5. The thermolysis of compound 11 leads to [Ru3(μ3‐κ2‐HNNMe2)(μ‐κ4‐H2CCHCPhCPhCO)(μ‐CO)2(CO)5] (12), which contains a novel edge‐bridging dienoyl ligand that arises from an unusual coupling of diphenylacetylene, carbon monoxide, and the ethenyl ligand of complex 11. A chloro‐bridged dimer of trinuclear clusters, [Ru6(μ‐Cl)2(μ3‐κ2‐HNNMe2)2(μ3‐κ2‐HCCH2)2(μ‐κ2‐PhCCHPh)2(μ‐CO)2(CO)10] (13), has been prepared by treating compound 11 with hydrogen chloride. Therefore, edge‐bridging parallel alkynes are susceptible to protonation to give edge‐bridging alkenyl ligands. Compound 13 is the first complex to contain two alkenyl ligands on a trinuclear cluster, one face‐capping and the other edge‐bridging.
Chiral inversion of RS‐8359: A selective and reversible MAO‐A inhibitor via oxido‐reduction of keto‐alcohol
Authors: Itoh Kunio , Hoshino Kouichi , Endo Asuka , Asakawa Tasuku , Yamakami Kazumi , Noji Chisa , Kosaka Toshiyuki , Tanaka Yorihisa
Published: July 2006

RS‐8359, (±)‐4‐(4‐cyanoanilino)‐5,6‐dihydro‐7‐hydroxy‐7H‐cyclopenta[d]‐pyrimidine is a selective and reversible MAO‐A inhibitor. The (S)‐enantiomer of RS‐8359 has been demonstrated to be inverted to the (R)‐enantiomer after oral administration to rats. In the current study, we investigated the chiral inversion mechanism and the properties of involved enzymes using rat liver subcellular fractions. The 7‐hydroxy function of RS‐8359 was oxidized at least by the two different enzymes. The cytosolic enzyme oxidized enantiospecifically the (S)‐enantiomer with NADP as a cofactor. On the other hand, the microsomal enzyme catalyzed more preferentially the oxidation of the (S)‐enantiomer than the (R)‐enantiomer with NAD as a cofactor. With to product enantioselectivity of reduction of the 7‐keto derivative, it was found that only the alcohol bearing (R)‐configuration was formed by the cytosolic enzyme with NADPH and the microsomal enzyme with NADH at almost equal rate. The reduction rate was much larger than the oxidation rate of 7‐hydroxy group. The results suggest that the chiral inversion might occur via an enantioselectivity of consecutive two opposing reactions, oxidation and reduction of keto‐alcohol group. In this case, the direction of chiral inversion from the (S)‐enantiomer to the (R)‐enantiomer is governed by the enantiospecific reduction of intermediate 7‐keto group to the alcohol with (R)‐configuration. The enzyme responsible for the enantiospecific reduction of the 7‐keto group was purified from rat liver cytosolic fractions and identified as 3α‐hydroxysteroid dehydrogenase (3α‐HSD) via database search of peptide mass data obtained by nano‐LC/MS/MS. Chirality, 2006. © 2006 Wiley‐Liss, Inc.
Nickel‐catalyzed Electrochemical Coupling of Phenyl Halide and Study of Mechanism
Authors: Zhao Peng , Luo Yi‐Wen , Xue Teng , Zhang Ai‐Jian , Lu Jia‐Xing
Published: July 2006

Electrochemical coupling of phenyl halide catalyzed by NiCl2bpy in DMF has been investigated in this paper. Stainless steel was used as cathode and zinc as anode. Effects of potential, temperature and catalyst on electrolyses were studied to optimize the electrolytic conditions, with the maximal isolated yield under potentiostatic electrolysis to be 85%. Cyclic voltammetry of NiCl2bpy in the presence of phenyl bromide has been studied and mechanisms, concerned with several kinds of nickel complex, have been summarized.
The relation between hypoxia‐inducible factor (HIF)‐1α and HIF‐2α expression with anemia and outcome in surgically treated head and neck cancer
Authors: Winter Stuart C. , Shah Ketan A. , Han Cheng , Campo Leticia , Turley Helen , Leek Russell , Corbridge Rogan J. , Cox Graham J. , Harris Adrian L.
Published: July 2006

BACKGROUND.

Hypoxia promotes tumorigenesis through the hypoxia‐inducible factor (HIF) pathway. There are 2 main homologues of the regulatory proteins, HIF‐1α and HIF‐2α, which have different effects in genetic knock‐out experiments. Anemia may contribute to hypoxia by reducing oxygen delivery, but it is not known whether this influences HIF‐α expression in tumors.

METHODS.

The expression of HIF‐1α, HIF‐2α, carbonic anhydrase‐9 (CA‐9), and peripheral hemoglobin (Hb) levels in 151 patients who underwent surgery for head and neck squamous cell carcinoma (HNSCC) were analyzed and related to outcome.

RESULTS.

High HIF‐1α was expressed in 45 of 140 tumors (30%), HIF‐2α was expressed in 21 of 139 tumors (14%), and CA‐9 was expressed in 56 of 149 tumors (62%). There was a positive correlation between HIF‐1α expression and HIF‐2α expression (P = .0001). HIF‐1α alone was associated with a worse disease‐specific survival (DSS) (P = .05) and disease‐free survival (DFS) (P = .03) in multivariate analyses. Nine percent of tumors expressed both high HIF‐1α and high HIF‐2α. High HIF‐1α/high HIF‐2α expression was an independent prognostic factors in DSS (P = .04) and DFS (P = .005) in multivariate analyses. There was no correlation noted between Hb and HIF‐1α, HIF‐2α, or CA‐9.

CONCLUSIONS.

HIF‐1α alone was correlated with DSS and DFS. The additive effect of HIF‐2α on poor prognosis suggested that different pathways may be regulated by HIF‐2α. Anemia that was not related to HIF‐α expression suggests that tumor intrinsic factors regulate HIF‐α; therefore, anemia may be a surrogate marker for other factors that affect outcome. Cancer 2006. © 2006 American Cancer Society.
Inhibition of survivin reduces cell proliferation and induces apoptosis in human endometrial cancer
Authors: Ai Zhihong , Yin Lianhua , Zhou Xianrong , Zhu Ying , Zhu Dongmei , Yu Yinhua , Feng Youji
Published: July 2006

BACKGROUND

Endometrial cancer is a common gynecologic malignancy among women. The molecular mechanisms involved in the progression of endometrial cancer are unclear, which has hampered the development of an effective treatment. Survivin, a newly identified member of the inhibitor of apoptosis (IAP) family, regulates 2 critical processes in neoplastic transformation: cell proliferation and apoptosis.

METHODS

Survivin mRNA and protein expression levels were analyzed in human normal cycling endometrium, atypical endometrium, and endometrial adenocarcinoma by immunohistochemical, reverse‐transcriptase polymerase chain reaction (RT‐PCR), and Western blot analyses. To study the biological function of survivin in endometrial cancer, RNA interference was applied to knock down survivin expression in the Ishikawa endometrial cancer cell line by recombinant plasmids producing survivin small hairpin RNA. Furthermore, the signal pathway that regulates survivin expression was investigated.

RESULTS

Higher levels of survivin mRNA and protein expression were observed in endometrial adenocarcinomas than in atypical or normal endometrium. Immunohistochemical staining revealed that 83.3% (50 of 60) of endometrial adenocarcinoma samples, 55.0% (11 of 20) of atypical endometrium samples, and 25.0% (5 of 20) of normal endometrium samples were positive for survivin protein. Inhibition of survivin by RNA interference reduced cell proliferation and induced apoptosis in Ishikawa cells by down‐regulating cyclin D1 and phosphorylated RB and activating caspase‐3 and caspase‐8. The authors also found that the MAPK pathway was a signal transduction pathway upstream of survivin. Epidermal growth factor (EGF) and transforming growth factor‐α (TGF‐α) up‐regulated survivin protein expression by activating the MAPK pathway in endometrial cancer cells.

CONCLUSIONS

Survivin is an attractive target for endometrial cancer treatment. Growth factors could regulate survivin expression by activating the MAPK pathway. Cancer 2006. © 2006 American Cancer Society.
A phase II study of irinotecan plus cisplatin for patients with advanced stage IIIB or IV NSCLC previously treated with nonplatinum‐based chemotherapy
Authors: Kim Heung T. , Han Ji‐Youn , Lee Dae H. , Chun Jong H. , Lee Hong G. , Lee Jae J. , Kim Hyae Y. , Lee Sung Y. , Lee Jin S.
Published: July 2006

BACKGROUND.

Irinotecan (I) and cisplatin (P) are active chemotherapy agents with clinical synergy in non–small‐cell lung cancer (NSCLC). We evaluated the efficacy of IP regimen as a salvage treatment of patients with NSCLC that progressed after nonplatinum‐containing regimen(s).

METHODS.

Eligibility required histologically confirmed NSCLC, bidimensionally measurable disease, ECOG PS 0‐2, and progressive disease after nonplatinum‐based chemotherapy. Treatment consisted of I (65 mg/m2) and P (30 mg/m2) i.v. on Days 1 and 8 of a 21‐day cycle, for a maximum of 6 cycles. An informed consent was obtained from all patients.

RESULTS.

Between August 2002 and May 2004, 32 patients with median age of 56 years (range, 42–74) were enrolled. Twenty‐four (75%) patients were men, and 28 (88%) had ECOG PS 0 or 1. Twenty‐five patients had adenocarcinoma and 6 had squamous‐cell carcinoma. All patients were evaluated for response and toxicity, and the response rate was 40.6%. After a median follow‐up of 18.5 months, the median survival time was found to be 9.3 months, with a 1‐year survival rate of 43.8%. Toxicities were moderate and manageable, with 47% G3 and 9% G4 neutropenia, 19% G3 diarrhea, and 22% G3 asthenia. There was no G4 nonhematologic toxicity.

CONCLUSIONS.

The irinotecan and cisplatin combination is an active and well‐tolerated regimen for the patients with advanced NSCLC that progressed after nonplatinum‐containing regimen(s). Cancer 2006. © 2006 American Cancer Society.
Recommendations for the use of Yttrium‐90 ibritumomab tiuxetan in malignant lymphoma
Authors: Weigert Oliver , Illidge Tim , Hiddemann Wolfgang , Dreyling Martin
Published: July 2006

Radioimmunotherapy (RIT) with Yttrium‐90 (90Y) ibritumomab tiuxetan (Zevalin®) combines the tumor targeting attributes of a monoclonal antibody against the CD20 antigen and the pure β‐radiation of 90Y. High efficacy and a favorable safety profile have been demonstrated in Phase II and III clinical trials enrolling patients with CD20+ B‐cell non‐Hodgkin lymphoma (B‐NHL). On the basis of these results, 90Y‐ibritumomab tiuxetan was approved in the United States for the treatment of patients with follicular lymphoma (FL) or transformed B‐NHL. In the European Union its use was restricted to FL, refractory to or relapsed after rituximab. There are a number of important clinical trials currently evaluating 90Y‐ibritumomab tiuxetan in other subtypes of lymphoma such as diffuse large‐cell and mantle‐cell lymphoma, as consolidation therapy or as part of myeloablative regimens. In light of the constantly increasing clinical experience with RIT, clinicians face the challenge of how to best integrate this promising new treatment option into existing established treatment algorithms. By incorporating the most recent data in this rapidly developing field, this review article focuses on current recommendations for the use of 90Y‐ibritumomab tiuxetan in patients with malignant lymphoma, outlines future perspectives, and provides practical recommendations for patient management. Cancer 2006. © 2006 American Cancer Society.
Iridium Metal Thin Films and Patterned IrO2 Nanowires Deposited Using Iridium(I) Carbonyl Precursors
Authors: Chen Y.‐L. , Hsu C.‐C. , Song Y.‐H. , Chi Y. , Carty A. J. , Peng S.‐M. , Lee G.‐H.
Published: July 2006

Highly volatile iridium(I) carbonyl complexes (1–5) with three anionic fluorinated chelates, namely ketoiminate, aminoalkoxide, or iminoalkoxide, have been synthesized and their physical properties relevant to CVD are evaluated. A single‐crystal X‐ray diffraction (XRD) study on Ir(CO)2(amakNMe2) (3) confirms a square‐planar geometry with two cis‐orientated carbonyl ligands. Metallic iridium, polycrystalline IrO2 thin films, or even patterned IrO2 nanowires are deposited using Ir(CO)2(hfdaNnPr) (5) as the CVD precursor. A systematic investigation of the deposition of IrO2 nanowires is conducted, showing a close correlation of observed crystallite morphology with applied system pressure, underlying growth surface, and deposition temperature. Of particular importance, tilted and vertically aligned IrO2 nanowires are obtained on LiTaO3(012) and LiNbO3(100) surfaces under a pressure of 30 Torr of oxygen at 425 °C. The morphology and structural composition of the IrO2 are confirmed by scanning electron microscopy, transmission electron microscopy, X‐ray photoelectron spectroscopy, and XRD analyses.
Numerical modelling of complex turbulent free‐surface flows with the SPH method: an overview
Authors: Violeau D. , Issa R.
Published: July 2006

The gridless smoothed particle hydrodynamics (SPH) method is now commonly used in computational fluid dynamics (CFD) and appears to be promising in predicting complex free‐surface flows. However, increasing flow complexity requires appropriate approaches for taking account of turbulent effects, whereas some authors are still working without any turbulence closure in SPH. A review of recently developed turbulence models adapted to the SPH method is presented herein, from the simplistic point of view of a one‐equation model involving mixing length to more sophisticated (and thus realistic) models like explicit algebraic Reynolds stress models (EARSM) or large eddy simulation (LES). Each proposed model is tested and validated on the basis of schematic cases for which laboratory data, theoretical or numerical solutions are available in the general field of turbulent free‐surface incompressible flows (e.g. open‐channel flow and schematic dam break). They give satisfactory results, even though some progress should be made in the future in terms of free‐surface influence and wall conditions. Recommendations are given to SPH users to apply this method to the modelling of complex free‐surface turbulent flows. Copyright © 2006 John Wiley & Sons, Ltd.
Taphonomy and site formation on California's Channel Islands
Authors: Rick Torben C. , Erlandson Jon M. , Vellanoweth René L.
Published: July 2006

Inhabited by humans for over 12,000 calendar years, California's Channel Islands contain thousands of archaeological sites, ranging from dense shell middens and villages to small lithic scatters and camps. Similar to many islands around the world, the Channel Islands have a dearth of burrowing animals and limited historical development leading to generally good preservation of archaeological constituents and relatively high stratigraphic integrity. Despite these favorable preservation conditions, numerous natural and cultural processes have impacted the island's archaeological record. Channel Islands archaeologists, however, have given relatively limited attention to the effects of taphonomic and formation processes. The authors provide an overview of taphonomic and formation processes affecting Channel Islands archaeology, illustrating the importance of regional taphonomic syntheses in the management, preservation, and interpretation of archaeological sites. These data also demonstrate the significance of detailing formation processes in islands and other areas where burrowing rodents and other disturbances are thought to be absent or limited. © 2006 Wiley Periodicals, Inc.