bluuebunny/crossref_metadata_2025 huggingface dataset:
Age at diagnosis of birth defects
Authors: Bower Carol , Rudy Edwina , Callaghan Ann , Quick Jennifer , Nassar Natasha
Published: March 2010

BACKGROUND:

Many birth defects surveillance programs ascertain cases of birth defects diagnosed beyond 1 year of age. The Western Australian (WA) Birth Defects Registry includes cases diagnosed up to 6 years of age, but the value of extending ascertainment beyond 1 year has not been assessed.

METHODS:

We examined the age at diagnosis for all cases and all birth defects notified to the WA Birth Defects Registry for births and terminations of pregnancy in 2000 and 2001 and estimated the amount of person time needed to ascertain cases diagnosed beyond 1 year of age.

RESULTS:

Of the 3294 cases of birth defects, 616 (18.7%) had at least one birth defect diagnosed prenatally, 1574 cases (47.8%) were first diagnosed by 1 month of age, 671 infants (20.4%) were first diagnosed with a birth defect from 1 month up to 1 year, and 400 cases (12.1%) were first diagnosed between 1 and 6 years of age. Two thirds of children diagnosed with Fetal Alcohol Syndrome, and one quarter of those with congenital hearing loss were diagnosed beyond 1 year of age. We estimated that it took 1.76 person weeks work per annum to ascertain cases diagnosed between 1 and 6 years of age.

CONCLUSIONS:

One in eight cases of birth defects were ascertained beyond 1 year of age. We consider that the additional work required to include these cases in Western Australia is outweighed by the benefit of more complete ascertainment. Birth Defects Research (Part A) 2010. © 2010 Wiley‐Liss, Inc.
Prüfung von Spannbetonbauteilen mit magnetischen Methoden
Authors: Sawade Gottfried , Krause Hans‐Joachim
Published: March 2010

Die Methoden der magnetischen Streufeldmessung und der magnetischen Restfeldmessung eignen sich gut zur zerstörungsfreien Detektion von Spanndrahtbrüchen in Spannbetonbauteilen. Unter Verwendung eines Jochmagneten mit integrierten Magnetfeldsensoren werden die Bauteile mit mehreren Messfahrten bei verschiedenen Magnetisierungsfeldstärken abgescannt. Die Auswertung basiert auf dem Vergleich von Messungen nach verschiedenen Vormagnetisierungen sowie der Bestimmung der Korrelation mit idealisierten Bügel‐ und Bruchsignalen. Die Nachweisgrenze des Verfahrens wird fallabhängig diskutiert. Die Anwendung in der Prüfpraxis wird an drei Beispielen illustriert.

Inspection of Prestressed Concrete Structural Members with Magnetic Methods

The methods of magnetic stray field measurement and of magnetic remanence measurment are well suited for nondestructive detection of ruptures in prestressing wires of concrete structural members. Using a yoke magnet with integrated magnetic field sensors, the members are scanned several times with varying magnetization field strength. The signal analysis is based on the comparison of measurements after different premagnetizations as well as on the determination of the correlation with idealized rebar and crack signals. The limits of detection are discussed on a case‐by‐case basis. The application in inspection practice is illustrated with three examples.
Die Scherkondetalbrücke, die erste semi‐integrale Talbrücke der DB AG auf der Neubaustrecke Erfurt – Leipzig/Halle VDE 8.2
Authors: Marx Steffen , Krontal Ludolf , Bätz Steffen , Vehlow Anja
Published: March 2010

Auf der Neubaustrecke Erfurt – Leipzig/Halle werden zurzeit einige Talbrücken realisiert, die einen neuen, ganzheitlich orientierten Entwurfsansatz verfolgen. Bei diesen integralen bzw. semi‐integralen Bauwerken sind die Überbauten monolithisch mit den Pfeilern und teilweise mit den Widerlagern verbunden. Sie können deshalb schlanker und mit stetigen Übergängen zwischen den Bauteilen ausgeführt werden. Durch den weitgehenden Verzicht auf Lager und Fugen und durch die robuste Bauweise besitzen integrale Bauwerke eine wesentlich längere Lebenserwartung als herkömmliche Talbrücken. Am Beispiel der Scherkondetalbrücke werden in diesem Beitrag die Unterschiede zwischen den konventionellen und den semi‐integralen Tragwerken erläutert sowie die Voraussetzungen und die Vorteile der Anwendung von integralen Bauwerken für die DB AG herausgearbeitet.

Bridge over Scherkonde Valley – the First Large Semi‐Integral Bridge on High‐Speed Railway Route Erfurt – Leipzig/Halle

Currently some large valley bridges are under construction on high‐speed railway route Erfurt‐Leipzig/Halle. These bridges follow a new holistic design philosophy. The superstructure of those integral or semi‐integral bridges is rigidly connected to the abutments and the columns. Therefore they are more slender than conventional bridges, and the bridges are very robust and durable because of the omitting of bearings and dilatation joints. The bridge over the Scherkonde valley is taken as an example for explaining the differences between conventional and semi‐integral bridges in this paper. This example shows the advantages and the requirements of integral buildings for high‐speed railway bridges.
A Hierarchical Model to Estimate Fish Abundance in Alpine Streams by using Removal Sampling Data from Multiple Locations
Authors: Laplanche Christophe
Published: March 2010

The author compares 12 hierarchical models in the aim of estimating the abundance of fish in alpine streams by using removal sampling data collected at multiple locations. The most expanded model accounts for (i) variability of the abundance among locations, (ii) variability of the catchability among locations, and (iii) residual variability of the catchability among fish. Eleven model reductions are considered depending which variability is included in the model. The more restrictive model considers none of the aforementioned variabilities. Computations of the latter model can be achieved by using the algorithm presented by Carle and Strub (Biometrics1978,34, 621–630). Maximum a posteriori and interval estimates of the parameters as well as the Akaike and the Bayesian information criterions of model fit are computed by using samples simulated by a Markov chain Monte Carlo method. The models are compared by using a trout (Salmo trutta fario) parr (0+) removal sampling data set collected at three locations in the Pyrénées mountain range (Haute‐Garonne, France) in July 2006. Results suggest that, in this case study, variability of the catchability is not significant, either among fish or locations. Variability of the abundance among locations is significant. 95% interval estimates of the abundances at the three locations are [0.15, 0.24], [0.26, 0.36], and [0.45, 0.58] parrs per m2. Such differences are likely the consequence of habitat variability.
Systemic lupus erythematosus and C1q: A quantitative ELISA for determining C1q levels in serum
Authors: Dillon Skyler P. , D'Souza Anil , Kurien Biji T. , Scofield R. Hal
Published: March 2010

The authors would like to acknowledge the National Institutes of Health for funding (grant number 5R01AR053734).
Counterion condensation and shape within Poisson–Boltzmann theory
Authors: Lamm Gene , Pack George R.
Published: March 2010

An analytical approximation to the nonlinear Poisson–Boltzmann (PB) equation is applied to charged macromolecules that possess one‐dimensional symmetry and can be modeled by a plane, infinite cylinder, or sphere. A functional substitution allows the nonlinear PB equation subject to linear boundary conditions to be transformed into an approximate linear (Debye‐Hückel‐type) equation subject to nonlinear boundary conditions. A simple analytical result for the surface potential of such polyelectrolytes follows, leading to expressions for the amount of condensed (or renormalized) charge and the electrostatic Helmholtz energy for polyelectrolytes. Analytical high‐charge/low‐salt and low‐charge/high‐salt limits are shown to be similar to results obtained by others based on PB or counterion condensation theory. Several important general observations concerning polyelectrolytes treated within the context of PB theory can be made including: (1) all charged surfaces display some counterion condensation for finite electrolyte concentration, (2) the effect of surface geometry is described primarily by the sum of the Debye constant and the mean curvature of the surface, (3) two surfaces with the same surface charge density and mean curvature condense approximately identical fractions of counterions, (4) the amount of condensation is not determined by a predefined “condensation distance” although such a distance can be determined uniquely from it, and (5) substantial condensation occurs if the Debye constant of the electrolyte is much less than the mean curvature of a highly charged polyelectrolyte. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 619–639, 2010.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Investigation of enzymatic biodiesel production using ionic liquid as a co‐solvent
Authors: Ruzich Nicholas Ivan , Bassi Amarjeet S.
Published: March 2010

In this study, the lipase catalysed esterification reaction for biodiesel production was investigated in the presence of the ionic liquid [BMIM][PF6]. Unlike regular organic solvents, many ionic liquids have no vapour pressure, and are therefore considered non‐volatile. When used in systems with enzyme catalysts, ionic liquids may enhance their activity, selectivity, and stability. The use of an enzyme (lipase) as a catalyst, and the ionic liquid as a solvent/immobilization agent also represents an environmentally friendly, “green” technology. Methyl acetate was used as the acyl acceptor as opposed to the more commonly used methanol due to the negative effects methanol and the glycerol by‐product has on lipase enzyme activity. The results of this research indicate that methyl oleate (i.e., biodiesel) was successfully produced, with an 80% overall biodiesel yield in the presence of ionic liquid, at a 1:1 ratio (v/v) to the amount of oil. This verified that the presence of an ionic liquid, at a specified amount, improved the activity of the lipase and the overall biodiesel yield. Results also indicate the addition of ionic liquid facilitated the separation of the methyl esters from the triacetylglycerol by‐product. The best conditions investigated was found to be: 14:1 molar ratio between oil and acyl acceptor; 20% (w immobilised lipase/w of oil; and a temperature in the range of 48–55°C. However, additional purification is required in order for the produced biodiesel to meet ASTM standards.
Comparison of stochastic methods with respect to performance and reliability of low‐temperature gas separation processes
Authors: Tahouni Nassim , Smith Robin , Panjeshahi M. Hassan
Published: March 2010

In this paper, the performances of two popular stochastic methods, the genetic algorithm (GA) and simulated annealing (SA), are verified in the optimization of low‐temperature gas separation processes. While the feasibility of GA optimization of low‐temperature processes has recently been addressed, our work studied the quality of GA solutions. Having optimized the solutions of three different case studies, it was observed that SA is more robust and reliable than GA when applied to such systems, and by adjusting the key parameters in the SA method, the optimization process can avoid pre‐mature convergence and is able to give the best near‐global results.
Energy efficient high solids loading agitation for the mineral industry
Authors: Wu Jie , Nguyen Bon , Graham Lachlan
Published: March 2010

This paper presents results of a study on minimising the specific power for off‐bottom solids suspension in mixing tanks at a high solids concentration. It was found that major savings in the specific power required to suspend solids at high concentrations can be achieved by removal of baffles. This is particularly relevant to applications where chemical reaction rate is not affected by the mixing rate, such as that often occurs in the mineral industry. The specific power at the just off‐bottom solids suspension condition was found to decrease with the tank diameter at a rate a lot faster than previously reported in the literature. It appears that a larger power number axial flow impeller is more energy efficient than a lower power one to suspend solids at a very high solids loading. A mineral processing full‐scale tank is used as a benchmark in the study. Emphasis was placed on applications to the mineral industry, although results are also relevant to other industrial applications.
High‐yield synthesis of multi‐walled carbon nanotube by hydrothermal method
Authors: Manafi Sahebali , Rahaei Mohammad Bagher , Elli Yaghoob , Joughehdoust Sedigheh
Published: March 2010

The evolution of multi‐walled carbon nanotubes (MWCNTs) under hydrothermal condition was investigated, because the hydrothermal method (HTM) has been utilised for commercial production of advanced engineering materials. To synthesise MWCNTs by hydrothermal process using mixed aqueous solution diethylenetriamine, polyethyleneglycol (PEG) and NaOH were used as starting materials. We investigated the effect of hydrothermal temperature, time, and amount of formative compounds. Hydrothermal reaction temperature was in the range from 150 to 180°C. The aim of the present work is to presentation hydrothermal synthesis as a new processing method for fabrication of MWCNTs, without the addition of metal catalyst. The homogeneity of hydrothermal processes, cheapness, and availability of amorphous carbon materials, without the need of catalyst, are advantages favouring the scaling‐up of the new method. The treatment of higher volumes would only require autoclaves with increasing load‐bearing capacity. Synthesised MWCNTs were analysed with a scanning electron microscope (SEM), a high resolution transmission electron microscope (HRTEM), thermo‐gravimetric analysis (TGA), and Raman spectroscopy. This result also presented a controllable way to synthesise MWCNTs with high purity. Indeed, present work will introduce new chapter in synthesising MWCNTs for scientific and engineering.
Understanding High‐Resolution Spectra of Nonrigid Molecules Using Group Theory
Authors: Schnell Melanie
Published: March 2010

Permutation‐inversion group theory has developed to become an important tool in the high‐resolution spectroscopy of nonrigid molecules. This large class of molecules is very intriguing to study. Small molecules such as ammonia or Na3 are known to be nonrigid. With increasing size, however, several large‐amplitude motions are possible in a molecule, and can even interact with each other. The high‐resolution spectra of nonrigid molecules are known to be quite complicated and very rich in information. Details about the molecule and its internal dynamics can be extracted, such as the molecular structure, the character of the chemical bonds, and the barrier heights to internal rotation and their dependence on the chemical bonds. However, due to the nonrigidity of the molecule and the complexity of such spectra, their analysis is usually quite challenging. Theoretical methods are needed for their prediction and analysis. This Review concentrates on permutation‐inversion group theory and its usefulness for the analysis of high‐resolution spectra of nonrigid molecules, which is examined in more detail using different examples. In a separate section, a special aspect of molecular symmetry is discussed: the breakdown of symmetry principles. Special emphasis is placed on the breakdown of space inversion symmetry (parity violation) in chiral molecules and its possible implications in high‐resolution spectroscopy.
A Theoretical Study on the Mechanism of C2H4 Oxidation over a Neutral V3O8 Cluster
Authors: Ma Yan‐Ping , Ding Xun‐Lei , Zhao Yan‐Xia , He Sheng‐Gui
Published: March 2010

Density functional theory (DFT) calculations are used to investigate the reaction mechanism of V3O8+C2H4. The reaction of V3O8 with C2H4 produces V3O7CH2+HCHO or V3O7+CH2OCH2 overall barrierlessly at room temperature, whereas formation of hydrogen‐transfer products V3O7+CH3CHO is subject to a tiny overall free energy barrier (0.03 eV), although the formation of the last‐named pair of products is thermodynamically more favorable than that of the first two. These DFT results are in agreement with recent experimental observations. The (Ob)2V(OtOt). (b=bridging, t=terminal) moiety containing the oxygen radical in V3O8 is the active site in the reaction with C2H4. Similarities and differences between the reactivities of (Ob)2V(OtOt). in V3O8 and the small VO3 cluster [(Ot)2VOt.] are discussed. Moreover, the effect of the support on the reactivity of the (Ob)2V(OtOt). active site is evaluated by investigating the reactivity of the cluster VX2O8, which is obtained by replacing the V atoms in the (Ob)3VOt support moieties of V3O8 with X atoms (X=P, As, Sb, Nb, Ta, Si, and Ti). Support X atoms with different electronegativities influence the oxidative reactivity of the (Ob)2V(OtOt). active site through changing the net charge of the active site. These theoretical predictions of the mechanism of V3O8+C2H4 and the effect of the support on the active site may be helpful for understanding the reactivity and selectivity of reactive O. species over condensed‐phase catalysts.
Sustained parenting and college drinking in first‐year students
Authors: Turrisi Rob , Ray Anne E.
Published: March 2010

Research indicates that for many students excessive drinking in college is a continuation of high school drinking tendencies. However, there have been limited theory‐driven, systematic interventions targeting students so as to prevent alcohol misuse in their transition to college. Almost all current prevention approaches tend to be focused on younger populations and college‐drinking interventions are typically delivered to students when they are already on campus. These analyses draw from a novel program of research involving parents of college freshmen based on the work of Turrisi et al. [Turrisi et al. [2001] Psychology of Addictive Behaviors, 15(4), 366–372; Turrisi, et al. [2009] Journal of Applied Social Psychology, 7, 315–326] and focuses on examining: (1) the relationship between parenting and student drinking tendencies during the transitional period between high school and college and into the first year of college, and (2) the mediation process by which sustained parenting throughout the first year is related to college‐drinking outcomes and consequences so as to inform future intervention efforts. The empirical evidence from this study suggests that sustained parental efforts have a beneficial effect on reducing high‐risk drinking and preventing harm even at this late stage of late adolescent/early adult development. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 286–294, 2010
Psychobiological models of adolescent risk: Implications for prevention and intervention
Authors: Calkins Susan D.
Published: March 2010

The papers in this special section address the phenomena of observed increases in risky behavior during the adolescent period of development. Authors provide well‐documented evidence that adolescents are at greater risk for a range of psychological and behavioral problems during this period than at any other time in development. The papers share a developmental and psychobiological perspective on this period, noting that biological, social, and contextual factors interact to produce heightened risk for problematic behavior during this period. This perspective suggests several points of entry for intervention and prevention efforts aimed at reducing both mental and behavioral health problems. Gaps in current research efforts are noted, as is the need for more research focusing on mechanisms of change prior to and during adolescence. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 213–215, 2010
α‐Dystroglycan is essential for the induction of Egr3, a transcription factor important in muscle spindle formation
Authors: Williams Stacey , Jacobson Christian
Published: March 2010

Muscle spindle fibers are specialized stretch receptors that allow the perception and coordination of limb movement. The differentiation of these specialized structures is initiated by signals derived from the in growing Ia sensory neurons during development. While the direct molecular signaling mechanisms between sensory neurons and developing muscle at nascent spindle fibers have been well documented in past studies the roles of muscle basal lamina components on this process have not previously been described. As such, our initial experiments addressed potential roles for agrin (AGRN) and laminin (LN) in the expression of the transcription factor Egr3. Levels of Egr3 were monitored using immunoblot analysis and both basal lamina molecules proved effective in inducing Erg3 expression. Previous work had established neuregulin (NRG) as a critical signaling component in spindle fiber development so blocking experiments with NRG and ErbB inhibitors were then used to determine if LN‐induced Egr3 expression was occurring as a result of NRG‐ErbB signaling and not via other, novel pathway. Inhibiting signaling through this pathway did indeed reduce the expression of Egr3. Finally, we looked at α‐dystrogylcan, a shared receptor for AGRN and LN at neuromuscular junctions. Using a α‐dystroglycan (α‐DG) silenced muscle cell line and an anti‐α‐DG antibody we attempted to block basal lamina/α‐DG interactions. Again, and in both instances, Egr3 expression was significantly decreased. Taken together, analysis of the results from these experiments revealed that indeed AGRN, LN, and α‐DG influence Egr3 levels and therefore may play an important role in spindle fiber differentiation. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70:498–507, 2010
Altered effector functions of virus‐specific and virus cross‐reactive CD8+ T cells in mice immunized with related flaviviruses
Authors: Trobaugh Derek W. , Yang Liyan , Ennis Francis A. , Green Sharone
Published: March 2010

Memory cross‐reactive CD8+ T‐cell responses may induce protection or immunopathology upon secondary viral challenge. To elucidate the potential role of T cells in sequential flavivirus infection, we characterized cross‐reactive CD4+ and CD8+ T‐cell responses between attenuated and pathogenic Japanese encephalitis virus (JEV) and pathogenic West Nile virus (WNV). A previously reported WNV NS4b CD8+ T‐cell epitope and its JEV variant elicited CD8+ T‐cell responses in both JEV‐ and WNV‐infected mice. The peptide variant homologous to the immunizing virus induced greater cytokine secretion and activated higher frequencies of epitope‐specific CD8+ T cells. However, there was a virus‐dependent, peptide variant‐independent pattern of cytokine secretion; the IFNγ+‐to‐IFNγ+TNFα+ CD8+ T‐cell ratio was greater in JEV‐ than in WNV‐infected mice. Despite similarities in viral burden for pathogenic WNV and JEV viruses, CD8+ T cells from pathogenic JEV‐immunized mice exhibited functional and phenotypic profiles similar to those seen for the attenuated JEV strain. Patterns of killer cell lectin‐like receptor G1 (KLRG1) and CD127 expression differed by virus type, with a rapid expansion and contraction of short‐lived effector cells in JEV infection and persistence of high levels of short‐lived effector cells in WNV infection. Such cross‐reactive T‐cell responses to primary infection may affect the outcomes of sequential flavivirus infections.
The synthetic TLR2 agonist BPPcysMPEG leads to efficient cross‐priming against co‐administered and linked antigens
Authors: Prajeeth Chittappen K. , Jirmo Adan Chari , Krishnaswamy Jayendra Kumar , Ebensen Thomas , Guzman Carlos A. , Weiss Siegfried , Constabel Hannelore , Schmidt Reinhold E. , Behrens Georg M. N.
Published: March 2010

The property of DC to generate effective CTL responses is influenced by TLR signaling. TLR ligands contain molecular signatures associated with pathogens, have an impact on the antigen processing and presentation by DC, and are being exploited as potential adjuvants. We hypothesized that the TLR2/6 heterodimer agonist S‐[2,3‐bispalmitoyiloxy‐(2R)‐propyl]‐R‐cysteinyl‐amido‐monomethoxyl polyethylene glycol (BPP), a synthetic derivative of the Mycoplasma macrophage activating lipopeptide‐2, is a potent adjuvant for cross‐priming against cellular antigens. Systemic administration of BPP‐induced maturation of CD8α+ DC and CD8α− DC in the spleen and resulted in enhanced cross‐presentation of intravenously co‐administered antigen in mice. In addition, administration of BPP and cell‐associated OVA generated an effective CTL response against OVA in vivo in a CD4+ T helper cell‐dependent manner, but independent of IFN‐α. Delivering antigenic peptides directly linked to BPP led to superior CTL immunity as compared to giving antigens and adjuvants admixed. In contrast to other TLR ligands, such as CpG, systemic activation of DC with BPP did not result in shut‐down of antigen presentation by splenic DC subsets, although cross‐priming against subsequently encountered antigens was reduced. Together, our data provide evidence that BPP is a potent stimulus to generate CTL via cross‐priming.
Mice lacking C1q or C3 show accelerated rejection of minor H disparate skin grafts and resistance to induction of tolerance
Authors: Baruah Paramita , Simpson Elizabeth , Dumitriu Ingrid E. , Derbyshire Katy , Coe David , Addey Caroline , Dyson Julian , Chai Jian‐Guo , Cook Terence , Scott Diane , Botto Marina
Published: March 2010

Complement activation is known to have deleterious effects on organ transplantation. On the other hand, the complement system is also known to have an important role in regulating immune responses. The balance between these two opposing effects is critical in the context of transplantation. Here, we report that female mice deficient in C1q (C1qa−/−) or C3 (C3−/−) reject male syngeneic grafts (HY incompatible) at an accelerated rate compared with WT mice. Intranasal HY peptide administration, which induces tolerance to syngeneic male grafts in WT mice, fails to induce tolerance in C1qa−/− or C3−/− mice. The rejection of the male grafts correlated with the presence of HY DbUty‐specific CD8+ T cells. Consistent with this, peptide‐treated C1qa−/− and C3−/− female mice rejecting male grafts exhibited more antigen‐specific CD8+IFN‐γ+ and CD8+IL‐10+ cells compared with WT females. This suggests that accumulation of IFN‐γ‐ and IL‐10‐producing T cells may play a key role in mediating the ongoing inflammatory process and graft rejection. Interestingly, within the tolerized male skin grafts of peptide‐treated WT mice, IFN‐γ, C1q and C3 mRNA levels were higher compared to control female grafts. These results suggest that C1q and C3 facilitate the induction of intranasal tolerance.
Nonlinear analysis of the deformation and breakup of viscous microjets using the method of lines
Authors: Furlani E. P. , Hanchak M. S.
Published: March 2010

We present a numerical model for predicting the instability and breakup of viscous microjets of Newtonian fluid. We adopt a one‐dimensional slender‐jet approximation and obtain the equations of motion in the form of a pair of coupled nonlinear partial differential equations (PDEs). We solve these equations using the method of lines, wherein the PDEs are transformed to a system of ordinary differential equations for the nodal values of the jet variables on a uniform staggered grid. We use the model to predict the instability and satellite formation in infinite microthreads of fluid and continuous microjets that emanate from an orifice. For the microthread analysis, we take into account arbitrary initial perturbations of the free‐surface and jet velocity, as well as Marangoni instability that is due to an arbitrary variation in the surface tension. For the continuous nozzle‐driven jet analysis, we take into account arbitrary time‐dependent perturbations of the free‐surface, velocity and/or surface tension as boundary conditions at the nozzle orifice. We validate the model using established computational data, as well as axisymmetric, volume of fluid (VOF) computational fluid dynamic (CFD) simulations. The key advantages of the model are its ease of implementation and speed of computation, which is several orders of magnitude faster than the VOF CFD simulations. The model enables rapid parametric analysis of jet breakup and satellite formation as a function of jet dimensions, modulation parameters, and fluid rheology. Copyright © 2010 John Wiley & Sons, Ltd.
Potential role of micro‐RNAs in head and neck tumorigenesis
Authors: Tran Nham , O'Brien Christopher J. , Clark Jonathan , Rose Barbara
Published: March 2010

A new class of regulatory molecules known as microRNAs (miRNAs) is redefining our understanding of the molecular pathways associated with tumorigenesis. These miRNAs are small noncoding RNA (ncRNA) sequences with potent regulatory potential. The aberrant expression of miRNAs has been associated with the development of various tumors. It has been suggested that miRNAs can both regulate and act as tumor‐suppressor genes and oncogenes. Our understanding of the role of miRNAs in head and neck tumorigenesis is in its infancy. However, several recent studies have revealed extensive dysregulation of miRNA in head and neck tumors and have highlighted the potential of certain miRNAs to act as diagnostic and prognostic markers and targets for new therapeutic agents. The intent of this review is to discuss and summarize current findings that point to a significant role for miRNAs in head and neck tumorigenesis. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Knockout of Secretin Receptor Reduces Large Cholangiocyte Hyperplasia in Mice With Extrahepatic Cholestasis Induced by Bile Duct Ligation
Authors: Glaser Shannon , Lam Ian P. , Franchitto Antonio , Gaudio Eugenio , Onori Paolo , Chow Billy K. , Wise Candace , Kopriva Shelley , Venter Julie , White Mellanie , Ueno Yoshiyuki , Dostal David , Carpino Guido , Mancinelli Romina , Butler Wendy , Chiasson Valorie , DeMorrow Sharon , Francis Heather , Alpini Gianfranco
Published: March 2010

During bile duct ligation (BDL), the growth of large cholangiocytes is regulated by the cyclic adenosine monophosphate (cAMP)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and is closely associated with increased secretin receptor (SR) expression. Although it has been suggested that SR modulates cholangiocyte growth, direct evidence for secretin-dependent proliferation is lacking. SR wild-type (WT) (SR+/+) or SR knockout (SR−/−) mice underwent sham surgery or BDL for 3 or 7 days. We evaluated SR expression, cholangiocyte proliferation, and apoptosis in liver sections and proliferating cell nuclear antigen (PCNA) protein expression and ERK1/2 phosphorylation in purified large cholangiocytes from WT and SR−/− BDL mice. Normal WT mice were treated with secretin (2.5 nmoles/kg/day by way of osmotic minipumps for 1 week), and biliary mass was evaluated. Small and large cholangiocytes were used to evaluate the

in vitro

effect of secretin (100 nM) on proliferation, protein kinase A (PKA) activity, and ERK1/2 phosphorylation. SR expression was also stably knocked down by short hairpin RNA, and basal and secretin-stimulated cAMP levels (a functional index of biliary growth) and proliferation were determined. SR was expressed by large cholangiocytes. Knockout of SR significantly decreased large cholangiocyte growth induced by BDL, which was associated with enhanced apoptosis. PCNA expression and ERK1/2 phosphorylation were decreased in large cholangiocytes from SR−/− BDL compared with WT BDL mice.

In vivo

administration of secretin to normal WT mice increased ductal mass.

In vitro

, secretin increased proliferation, PKA activity, and ERK1/2 phosphorylation of large cholangiocytes that was blocked by PKA and mitogen-activated protein kinase kinase inhibitors. Stable knockdown of SR expression reduced basal cholangiocyte proliferation. SR is an important trophic regulator sustaining biliary growth.

Conclusion:

The current study provides strong support for the potential use of secretin as a therapy for ductopenic liver diseases. Hepatology 2010
Surveillance of systemic trafficking of macrophages induced by UHMWPE particles in nude mice by noninvasive imaging
Authors: Ren Pei‐Gen , Huang Zhinong , Ma Ting , Biswal Sandip , Smith Robert L. , Goodman Stuart B.
Published: March 2010

Macrophages constitute a major part of the cell response to wear particles produced at articulating and nonarticulating interfaces of joint replacements. This foreign body reaction can result in periprosthetic osteolysis and implant loosening. We demonstrate that ultra‐high molecular weight polyethylene (UHMWPE) particles induce systemic trafficking of macrophages by noninvasive in vivo imaging and immunohistochemistry. The distal femora of nude mice were injected with 60 mg/mL UHMWPE suspension or saline alone. Reporter RAW264.7 macrophages that stably expressed the bioluminescent reporter gene and the fluorescence reporter gene were injected intravenously. Bioluminescence imaging was performed using an in vivo imaging system immediately after macrophage injection and at 2‐day intervals. Compared with the nonoperated contralateral femora, at day 4, 6, and 8, the bioluminescent signal of femora containing UHMWPE suspension increased 1.30 ± 0.09‐, 2.36 ± 0.92‐, and 10.32 ± 7.61‐fold, respectively. The values at same time points for saline‐injected control group were 1.08 ± 0.07‐, 1.14 ± 0.27‐, and 1.14 ± 0.35‐fold, respectively. The relative bioluminescence of the UHMWPE group was higher at all postinjection days and significantly greater than the saline group at day 8 (p < 0.05). Histological analysis confirmed the presence of reporter macrophages within the medullary canal of mice with implanted UHMWPE particles. The presence of UHMWPE particles induced enhanced bone remodeling activity. Clinically relevant UHMWPE particles stimulated the systemic recruitment of macrophages during an early time course using the murine femoral implant model. Interference with systemic macrophage trafficking may potentially mitigate UHMWPE particle‐induced periprosthetic osteolysis. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
TAK1 regulates cartilage and joint development via the MAPK and BMP signaling pathways
Authors: Gunnell Lea M , Jonason Jennifer H , Loiselle Alayna E , Kohn Anat , Schwarz Edward M , Hilton Matthew J , O'Keefe Regis J
Published: March 2010

The importance of canonical transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling during cartilage and joint development is well established, but the necessity for noncanonical (SMAD-independent) signaling during these processes is largely unknown. TGF-β activated kinase 1 (TAK1) is a MAP3K activated by TGF-β, BMP, and other mitogen-activated protein kinase (MAPK) signaling components. We set out to define the potential role for noncanonical, TAK1-mediated signaling in cartilage and joint development via deletion of Tak1 in chondrocytes (Col2Cre;Tak1f/f) and the developing limb mesenchyme (Prx1Cre;Tak1f/f). Deletion of Tak1 in chondrocytes resulted in novel embryonic developmental cartilage defects including decreased chondrocyte proliferation, reduced proliferating chondrocyte survival, delayed onset of hypertrophy, reduced Mmp13 expression, and a failure to maintain interzone cells of the elbow joint, which were not observed previously in another Col2Cre;Tak1f/f model. Deletion of Tak1 in limb mesenchyme resulted in widespread joint fusions likely owing to the differentiation of interzone cells to the chondrocyte lineage. The Prx1Cre;Tak1f/f model also allowed us to identify novel columnar chondrocyte organization and terminal maturation defects owing to the interplay between chondrocytes and the surrounding mesenchyme. Furthermore, both our in vivo models and in vitro cell culture studies demonstrate that loss of Tak1 results in impaired activation of the downstream MAPK target p38, as well as diminished activation of the BMP/SMAD signaling pathway. Taken together, these data demonstrate that TAK1 is a critical regulator of both MAPK and BMP signaling and is necessary for proper cartilage and joint development. © 2010 American Society for Bone and Mineral Research
The evolutionary mechanism of cancer
Authors: Heng Henry H.Q. , Stevens Joshua B. , Bremer Steven W. , Ye Karen J. , Liu Guo , Ye Christine J.
Published: March 2010

Identification of the general molecular mechanism of cancer is the Holy Grail of cancer research. Since cancer is believed to be caused by a sequential accumulation of cancer gene mutations, the identification, characterization, and targeting of common genetic alterations and their defined pathways have dominated the field for decades. Despite the impressive data accumulated from studies of gene mutations, epigenetic dysregulation, and pathway alterations, an overwhelming amount of diverse molecular information has offered limited understanding of the general mechanisms of cancer. To solve this paradox, the newly established genome theory is introduced here describing how somatic cells evolve within individual patients. The evolutionary mechanism of cancer is characterized using only three key components of somatic cell evolution that include increased system dynamics induced by stress, elevated genetic and epigenetic heterogeneity, and genome alteration mediated natural selection. Cancer progression represents a macro‐evolutionary process where karyotype change or genome replacement plays the key dominant role. Furthermore, the recently identified relationship between the evolutionary mechanism and a large number of diverse individual molecular mechanisms is discussed. The total sum of all the individual molecular mechanisms is equal to the evolutionary mechanism of cancer. Individual molecular mechanisms including all the molecular mechanisms described to date are stochastically selected and unpredictable and are therefore clinically impractical. Recognizing the fundamental importance of the underlying basis of the evolutionary mechanism of cancer mandates the development of new strategies in cancer research. J. Cell. Biochem. 109: 1072–1084, 2010. © 2010 Wiley‐Liss, Inc.
Oxygen tension differentially influences osteogenic differentiation of human adipose stem cells in 2D and 3D cultures
Authors: He Jiawei , Genetos Damian C. , Yellowley Clare E. , Leach J. Kent
Published: March 2010

Skeletal defects commonly suffer from poor oxygen microenvironments resulting from compromised vascularization associated with injury or disease. Adipose stem cells (ASCs) represent a promising cell population for stimulating skeletal repair by differentiating toward the osteogenic lineage or by secreting trophic factors. However, the osteogenic or trophic response of ASCs to reduced oxygen microenvironments is poorly understood. Moreover, a direct comparison between 2D and 3D response of ASCs to hypoxia is lacking. Thus, we characterized the osteogenic and angiogenic potential of human ASCs under hypoxic (1%), normoxic (5%), and atmospheric (21%) oxygen tensions in both 2D and 3D over 4 weeks in culture. We detected greatest alkaline phosphatase activity and extracellular calcium deposition in cells cultured in both 2D and 3D under 21% oxygen, and reductions in enzyme activity corresponded to reductions in oxygen tension. ASCs cultured in 1% oxygen secreted more vascular endothelial growth factor (VEGF) over the 4‐week period than cells cultured in other conditions, with cells cultured in 2D secreting VEGF in a more sustained manner than those in 3D. Expression of osteogenic markers revealed temporal changes under different oxygen conditions with peak expression occurring earlier in 3D. In addition, the increase of most osteogenic markers was significantly higher in 2D compared to 3D cultures at 1% and 5% oxygen. These results suggest that oxygen, in conjunction with dimensionality, affects the timing of the differentiation program in ASCs. These findings offer new insights for the use of ASCs in bone repair while emphasizing the importance of the culture microenvironment. J. Cell. Biochem. 110: 87–96, 2010. © 2010 Wiley‐Liss, Inc.
CDK5 phosphorylates eNOS at Ser‐113 and regulates NO production
Authors: Lee Chien‐Hsing , Wei Yin‐Win , Huang Yi‐Ting , Lin Yuh‐Te , Lee Yu‐Cheng , Lee Kuen‐Haur , Lu Pei‐Jung
Published: March 2010

Phosphorylation of endothelial nitric oxide synthase (eNOS) is key mechanism in response to various forms of cellular stimulation. Through protein nitration by peroxynitrite, eNOS is believed to be responsible for the major abnormalities in several important neurodegenerative diseases including Alzheimer's (AD) and Parkinson's diseases (PD). Recent studies provide important in vivo evidence that hyperactivation of Cdk5 by p25 plays an essential role in the cell death of neurons in experimental models of AD and PD. This study focuses on the functional regulation of eNOS by Cdk5/p35 complex in a phosphorylation dependent manner. Our results showed that Cdk5 can phosphorylate eNOS both in vitro and in vivo. In vitro kinase assay together with the bioinformatic analysis and site direct mutagenesis revealed that Ser‐113 is the major phosphorylation site for Cdk5. Most interestingly, the nitrite production was significantly reduced in eNOS and Cdk5/p35 co‐transfected SH‐SY5Y cells when compared with co‐transfection of Cdk5/p35 and S113A. Together, our data suggest that Cdk5 can phosphorylate eNOS at the Ser‐113 site and down‐regulate eNOS‐derived NO levels. J. Cell. Biochem. 110: 112–117, 2010. © 2010 Wiley‐Liss, Inc.
Concurrent inhibition of NF‐κB, cyclooxygenase‐2, and epidermal growth factor receptor leads to greater anti‐tumor activity in pancreatic cancer
Authors: Ali Shadan , Banerjee Sanjeev , Schaffert Jacqueline M. , El‐Rayes Bassel F. , Philip Philip A. , Sarkar Fazlul H.
Published: March 2010

Inactivation of survival pathways such as NF‐κB, cyclooxygenase (COX‐2), or epidermal growth factor receptor (EGFR) signaling individually may not be sufficient for the treatment of advanced pancreatic cancer (PC) as suggested by recent clinical trials. 3,3′‐Diindolylmethane (B‐DIM) is an inhibitor of NF‐κB and COX‐2 and is a well‐known chemopreventive agent. We hypothesized that the inhibition of NF‐κB and COX‐2 by B‐DIM concurrently with the inhibition of EGFR by erlotinib will potentiate the anti‐tumor effects of cytotoxic drug gemcitabine, which has been tested both in vitro and in vivo. Inhibition of viable cells in seven PC cell lines treated with B‐DIM, erlotinib, or gemcitabine alone or their combinations was evaluated using 3‐(4,5‐dimetylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Significant inhibition in cell viability was observed in PC cells expressing high levels of COX‐2, EGFR, and NF‐κB proteins. The observed inhibition was associated with an increase in apoptosis as assessed by ELISA. A significant down‐regulation in the expression of COX‐2, NF‐κB, and EGFR in BxPC‐3, COLO‐357, and HPAC cells was observed, suggesting that simultaneous targeting of EGFR, NF‐κB, and COX‐2 is more effective than targeting either signaling pathway separately. Our in vitro results were further supported by in vivo studies showing that B‐DIM in combination with erlotinib and gemcitabine was significantly more effective than individual agents. Based on our preclinical in vitro and in vivo results, we conclude that this multi‐targeted combination could be developed for the treatment of PC patients whose tumors express high levels of COX‐2, EGFR, and NF‐κB. J. Cell. Biochem. 110: 171–181, 2010. © 2010 Wiley‐Liss, Inc.
The Kaposi's sarcoma‐associated herpesvirus G protein‐coupled receptor: Lessons on dysregulated angiogenesis from a viral oncogene
Authors: Jham Bruno C. , Montaner Silvia
Published: March 2010

Tumor viruses can induce cell transformation by overcoming cellular defense mechanisms and promoting the ungoverned proliferation of infected cells. To this end, functionally related viral oncogenes have evolved in disparate viruses to over‐ride key proliferative and survival intracellular pathways, thus assuring efficient viral replication and contributing to tumor formation. Indeed, the study of viral oncogenes has been a powerful tool for disclosing fundamental insights into these basic cellular processes. In this regard, the Kaposi's sarcoma‐associated herpesvirus (KSHV or HHV8), the etiological agent of Kaposi's sarcoma (KS), is an exemplary model of an oncogenic virus that includes within its genome several homologues of cellular genes implicated in the regulation of cell proliferation and apoptosis. However, emerging evidence now points to a single KSHV gene, ORF74, encoding for the viral G protein‐coupled receptor (vGPCR), as essential for KS development. Expressed in only a fraction of cells within KS lesions, this viral receptor induces tumorigenesis through both autocrine and paracrine mechanisms. Indeed, work from several laboratories has demonstrated that vGPCR can promote cell proliferation, enhance cell survival, modulate cell migration, stimulate angiogenesis, and recruit inflammatory cells, both in expressing cells, as well as in neighboring (bystander) cells. Examination of this powerful viral oncogene may expose novel targets for the treatment of patients with KS and could ultimately provide a unique perspective into how GPCRs, and specifically chemokine receptors, contribute to angiogenesis and tumorigenesis. J. Cell. Biochem. 110: 1–9, 2010. © 2010 Wiley‐Liss, Inc.
ATM is involved in cell‐cycle control through the regulation of retinoblastoma protein phosphorylation
Authors: Pizarro Javier G. , Folch Jaume , de la Torre Aurelio Vazquez , Junyent Felix , Verdaguer Ester , Jordan Joaquin , Pallas Merce , Camins Antoni
Published: March 2010

Ataxia telangiectasia mutated protein (ATM) is a member of the phosphatidylinositol‐3 kinase (PI3K) family, which has a role in the cellular response to DNA double‐strand breaks (DSBs). In the present study, we evaluated the role of ATM in cell‐cycle control in dopaminergic rat neuroblastoma B65 cells. For this purpose, ATM activity was either inhibited pharmacologically with the specific inhibitor KU‐55933, or the ATM gene was partially silenced by transfection with small interfering RNA (siRNA). Our data indicate that although ATM inhibition did not affect the cell cycle, both treatments specifically decreased the levels of cyclin A and retinoblastoma protein (pRb), phosphorylated at Ser780. Furthermore, ATM inhibition decreased the active form of p53, which is phosphorylated at Ser15, and also decreased Bax and p21 expression. Using H2O2 as a positive control of DSBs, caused a rapid pRb phosphorylation, this was prevented by KU‐55933 and siRNA treatment. Collectively, our data demonstrate how a new molecular network on ATM regulates the cell cycle through the control of pRb phosphorylation. These findings support a new target of ATM. J. Cell. Biochem. 110: 210–218, 2010. © 2010 Wiley‐Liss, Inc.