bluuebunny/crossref_metadata_2025 huggingface dataset:
Strain‐specific modifier genes governing craniofacial phenotypes
Authors: Mukhopadhyay Partha , Brock Guy , Webb Cynthia , Pisano M. Michele , Greene Robert M.
Published: February 2012

BACKGROUND

The presence of strain‐specific modifier genes is known to modulate the phenotype and pathophysiology of mice harboring genetically engineered mutations. Thus, identification of genetic modifier genes is requisite to understanding control of phenotypic expression. c‐Ski is a transcriptional regulator. Ski−/− mice on a C57BL6J (B6) background exhibit facial clefting, while Ski−/− mice on a 129P3 (129) background present with exencephaly.

METHODS

In the present study, oligonucleotide‐based gene expression profiling was used to identify potential strain‐specific modifier gene candidates present in wild type mice of B6 and 129 genetic backgrounds. Changes in gene expression were verified by TaqMan quantitative real‐time PCR.

RESULTS

Steady‐state levels of 89 genes demonstrated a significantly higher level of expression, and those of 68 genes demonstrated a significantly lower level of expression in the developing neural tubes from embryonic day (E) 8.5, B6 embryos when compared to expression levels in neural tubes derived from E 8.5, 129 embryos.

CONCLUSIONS

Based on the results from the current comparative microarray study, and taking into consideration a number of relevant published reports, several potential strain‐specific gene candidates, likely to modify the craniofacial phenotypes in various knockout mouse models have been identified. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.
Selective recognition of acetate ion based on fluorescence enhancement chemosensor
Authors: Hosseini Morteza , Ganjali Mohammad Reza , Veismohammadi Bahareh , Faridbod Farnoush , Abkenar Shiva Dehghan , Salavati‐Niasari Masoud
Published: February 2012

Fluorescence study of the complexation between uranyl salophen (L) and some common anions in acetonitrile–water (90:10, v/v) solution showed a tendency of L toward acetate ion (AcO−). The fluorescence enhancement of L is attributed to a 1:1 complex formation between L and acetate ion which was utilized as the basis for the selective detection of AcO−. The association constant of the 1:1 complex formation of L–AcO− was calculated as 6.60 × 106. The linear response range of the fluorescent chemosensor covers a AcO− concentration range of 1.6 × 10−7 to 2.5 × 10−5 mol/L, with a detection limit of 2.5 × 10−8 mol/L. L showed a selective and sensitive fluorescence enhancement response toward acetate ion over I3−, NO3−, CN−, CO32−, Br−, Cl−, F−, H2PO4− and SO42−, which was attributed to the higher stability of inorganic complex between acetate and L. Copyright © 2012 John Wiley & Sons, Ltd.
Peer review in class: Metrics and variations in a senior course
Authors: Yankulov Krassimir , Couto Richard
Published: February 2012

Peer reviews are the generally accepted mode of quality assessment in scholarly communities; however, they are rarely used for evaluation at college levels. Over a period of 5 years, we have performed a peer review simulation at a senior level course in molecular genetics at the University of Guelph and have accumulated 393 student peer reviews. We have used these to generate a summary of the metrics of this exercise. Our calculations show that student peer marks are highly variable and not suitable for numerical performance evaluation at the university level. On the other hand, student peer reviews can clearly recognize substandard performance. Hence, peer reviews can be used for the assessment of “pass/fail” type of assignments. Interestingly, student peers struggle to distinguish between good and excellent performance. These finding provide provocative insight on the process of peer review in general. We comment on the implications of this in‐class simulation for research communities and on potential pitfalls of peer reviews.
The arduous journey to find a portrait of Beauchêne fils
Authors: Spinner Robert J. , Wolanskyj Alexandra P.
Published: February 2012

Earlier publications by our group have reported the major contributions of Beauchêne fils, Edme François Chauvot de Beauchêne (1778–1830), a prosector, and surgeon in Paris. These included a variety of firsts: the finding of an intraneural ganglion cyst, the description of the exploded skull (Beauchêne) technique, and the case of air pulmonary embolism. This article describes the exhaustive efforts necessary to locate a portrait of him. Information obtained along the circuitous journey through 13 generations over five centuries will clarify the important medical accomplishments by individuals of a noble family. The discovered portraits will allow scholars to honor accurately the individuals, particularly Beauchêne fils, in the future. Clin. Anat. 25:683–686, 2012. © 2012 Wiley Periodicals, Inc.
Transmetallation Versus β‐Hydride Elimination: The Role of 1,4‐Benzoquinone in Chelation‐Controlled Arylation Reactions with Arylboronic Acids
Authors: Sköld Christian , Kleimark Jonatan , Trejos Alejandro , Odell Luke R. , Nilsson Lill Sten O. , Norrby Per‐Ola , Larhed Mats
Published: February 2012

The formation of an atypical, saturated, diarylated, Heck/Suzuki, domino product produced under oxidative Heck reaction conditions, employing arylboronic acids and a chelating vinyl ether, has been investigated by DFT calculations. The calculations highlight the crucial role of 1,4‐benzoquinone (BQ) in the reaction. In addition to its role as an oxidant of palladium, which is necessary to complete the catalytic cycle, this electron‐deficient alkene opens up a low‐energy reaction pathway from the post‐insertion σ‐alkyl complex. The association of BQ lowers the free‐energy barrier for transmetallation of the σ‐alkyl complex to create a pathway that is energetically lower than the oxidative Heck reaction pathway. Furthermore, the calculations showed that the reaction is made viable by BQ‐mediated reductive elimination and leads to the saturated diarylated product.
Kinetic and Mechanistic Investigations of the Light Induced Formation of Gold Nanoparticles on the Surface of TiO2
Authors: Mohamed Hanan H. , Dillert Ralf , Bahnemann Detlef W.
Published: February 2012

The kinetics of the formation of gold nanoparticles on the surface of pre‐illuminated TiO2 have been investigated using stopped‐flow technique and steady state UV/Vis spectroscopy. Excess electrons were loaded on the employed nanosized titanium dioxide particles by UV‐A photolysis in the presence of methanol serving as hole scavenger, stored on them in the absence of oxygen and subsequently used for the reduction of AuIII ions. The formation of gold nanoparticles with an average diameter of 5 nm was confirmed after mixing of the TiO2 nanoparticles loaded with electrons with aqueous solution of tetrachloroaureate (HAuCl4) by their surface plasmon absorbance band at 530 nm, as well as by XRD and HRTEM measurements. The rate of formation of the gold nanoparticles was found to be a function of the concentration of the gold ions and the concentration of the stored electrons, respectively. The effect of PVA as a stabilizer of the gold nanoclusters was also studied. The observed kinetic behavior suggests that the formation of the gold nanoparticles on the TiO2 surface is an autocatalytic process comprising of two main steps: 1) Reduction of the gold ions by the stored electrons on TiO2 forming gold atoms that turn into gold nuclei. 2) Growth of the metal nuclei on the surface of TiO2 forming the gold particles. Interestingly, at higher TiO2 electron loading the excess electrons are subsequently transferred to the deposited gold metal particles resulting in “bleaching” of their surface plasmon band. This bleaching in the surface plasmon band is explained by the Fermi level equilibration of the Au/TiO2 nanocomposites. Finally, the reduction of water resulting in the evolution of molecular hydrogen initiated by the excess electrons that have been transferred to the previously formed gold particles has also been observed. The mechanism of the underlying multistep electron‐transfer process has been discussed in detail.
Construction of a Graphene Oxide Based Noncovalent Multiple Nanosupramolecular Assembly as a Scaffold for Drug Delivery
Authors: Yang Yang , Zhang Ying‐Ming , Chen Yong , Zhao Di , Chen Jia‐Tong , Liu Yu
Published: February 2012

A multiple supramolecular assembly, in which a folic acid‐modified β‐cyclodextrin (1) acted as a target unit, an adamantanyl porphyrin (2) acted as a linker unit, and graphene oxide acted as a carrier unit, was successfully fabricated through non‐covalent interactions and comprehensively investigated by means of UV/Vis, fluorescence, and X‐ray photoelectron spectroscopies, and electron microscopy. Significantly, the graphene oxide unit could associate with the anticancer drug doxorubicin through π–π interactions, and the folic acid‐modified β‐cyclodextrin unit could recognize the folic acid receptors in cancer cells. Owing to the cooperative contribution of these three units, the resulting multiple supramolecular assembly, after association with doxorubicin, exhibited better drug activity and much lower toxicity than free doxorubicin in vivo.
Tautomerisation of 2‐Substituted Pyridines to N‐Heterocyclic Carbene Ligands Induced by the 16 e− Unsaturated [TpMe2IrIII(C6H5)2] Moiety
Authors: Conejero Salvador , López‐Serrano Joaquín , Paneque Margarita , Petronilho Ana , Poveda Manuel L. , Vattier Florencia , Álvarez Eleuterio , Carmona Ernesto
Published: March 2012

The complex [TpMe2Ir(C6H5)2(N2)] reacts with several 2‐substituted pyridines to generate N‐heterocyclic carbenes resulting from a formal 1,2‐hydrogen shift from C6 to N. In this paper we provide a detailed report of the scope and the mechanistic aspects (both experimental and theoretical) of the tautomerisation of 2‐substituted pyridines.
A unique approach to predict accurate heavy oil density with new three parameter cubic equation of state
Authors: Kumar Ashutosh , Henni Amr
Published: February 2012

A unique approach is proposed to predict the heavy oil density using a recently developed three parameter cubic equation of state for heavy pure components. It predicts the heavy oil density with an AAD of 2.5%. The new model does not require any experimental density data for its tuning. The basic assumption in this work is that heavy oil is a mixture of n‐alkanes and aromatics as the most prominent groups. Critical pressure characterisation for pseudo fractions is done by tuning a perturbation factor (fc), also representing the aromaticity, to match the predicted saturation pressure with the experimental pressure. The parameter ‘u’ for the pseudo fractions is adjusted using another parameter ‘S’ which was found to vary linearly with fc.
The Morphology and Stability of Nanoscopic Gas States at Water/Solid Interfaces
Authors: Zhang Lijuan , Wang Chunlei , Tai Renzhong , Hu Jun , Fang Haiping
Published: February 2012

Nanoscale gas bubbles have surprising stability at water/solid surfaces. Herein, we summarize progress made on investigating gases at the water/solid interfaces on the nanometer scale. The gas states include nanobubbles, micropancakes, multiple gas layers and their coexistence; these were investigated from experimental and theoretical aspects. The stability of nanoscale gas bubbles may be attributed to high inner density, as observed in molecular dynamic simulations and theoretical analysis. Moreover, it was found that there were maximal length scales for stable nanobubbles, namely, 100 nm high and a curvature radius of 2 μm.
Analysis of Nascent Rotational Energy Distributions and Reaction Mechanisms of the Gas‐Phase Radical–Radical Reaction O(3P)+(CH3)2CH→C3H6+OH
Authors: Park Min‐Jin , Kang Kyoo‐Weon , Choi Jong‐Ho
Published: February 2012

This paper reports on the gas‐phase radical–radical dynamics of the reaction of ground‐state atomic oxygen [O(3P), from the photodissociation of NO2] with secondary isopropyl radicals [(CH3)2CH, from the supersonic flash pyrolysis of isopropyl bromide]. The major reaction channel, O(3P)+(CH3)2CH→C3H6 (propene)+OH, is examined by high‐resolution laser‐induced fluorescence spectroscopy in crossed‐beam configuration. Population analysis shows bimodal nascent rotational distributions of OH (X2Π) products with low‐ and high‐N′′ components in a ratio of 1.25:1. No significant spin–orbit or Λ‐doublet propensities are exhibited in the ground vibrational state. Ab initio computations at the CBS‐QB3 theory level and comparison with prior theory show that the statistical method is not suitable for describing the main reaction channel at the molecular level. Two competing mechanisms are predicted to exist on the lowest doublet potential‐energy surface: direct abstraction, giving the dominant low‐N′′ components, and formation of short‐lived addition complexes that result in hot rotational distributions, giving the high‐N′′ components. The observed competing mechanisms contrast with previous bulk kinetic experiments conducted in a fast‐flow system with photoionization mass spectrometry, which suggested a single abstraction pathway. In addition, comparison of the reactions of O(3P) with primary and tertiary hydrocarbon radicals allows molecular‐level discussion of the reactivity and mechanism of the title reaction.
Carbon‐Based Electrochemical Capacitors
Authors: Ghosh Arunabha , Lee Young Hee
Published: March 2012

Supercapacitors are one of the key devices for energy‐storage applications. They have energy densities much higher than those of conventional capacitors and possess much better power delivery capabilities than batteries. This makes them unique devices that can outperform both batteries and conventional capacitors under special circumstances. Nanocarbons are the main electrode materials for supercapacitors. Abundant sources of nanocarbons and facile processes of modification have led to the fabrication of cheap electrodes. In this review, we focus on the capacitance performance of highly porous activated carbons and attempt to determine the role of different pores. Elaborate discussions are presented on individual contributions from micro‐ and mesopores and their mutual dependence. This article also presents a comparative performance report for both random and ordered porous nanocarbons. Novel carbon materials, such as carbon nanotubes and graphene, and their contributions in this context are discussed. We summarize key techniques for the functionalization of nanocarbons and their pseudocapacitive charge‐storage mechanisms. Nanocarbon composites with redox‐active transition‐metal oxides and conducting polymers are highlighted along with their impact as electrode materials. Ideal composite structures are highlighted and an attempt is made to determine an ideal future electrode structure for capacitors with high energy and power density.
Physical Features of Binary Coulomb Crystals: Madelung Energy, Collective Modes and Phonon Heat Capacity
Authors: Kozhberov A. A. , Baiko D. A.
Published: February 2012

Electrostatic energy, collective modes, and thermodynamic functions of a Coulomb crystal with equal number of ions of two different types and uniform charge‐compensating electron background are studied using harmonic lattice model. Simple cubic and hexagonal lattices with two different ions in the elementary cell (we denote these lattices sc2 and h2, respectively) are considered. The static sc2 lattice is more tightly bound than the h2 one at any charge ratio of the constituent ions. The phonon spectra depend on the ion charge and mass ratio. An analysis shows that these binary Coulomb crystals are stable, if the charge ratio is not too different from 1 (about 3.6 for sc2 and 1.3 for h2 lattices) regardless of the mass ratio. Heat capacity of the sc2 lattice is obtained by numerical integration over the first Brillouin zone as a function of temperature and charge and mass ratios. Well known classic and quantum asymptotes of the heat capacity are reproduced, and the dependence of the coefficient in the Debye T3 law on charge and mass ratios is presented (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ab Initio Simulation of Complex Dielectric Function for Dense Aluminum Plasma
Authors: Povarnitsyn M. E. , Knyazev D. V. , Levashov P. R.
Published: February 2012

We present calculations of frequency‐dependent complex dielectric function of dense aluminum plasma by quantum molecular dynamics method for temperatures up to 20 kK. Analysis shows that the dependencies for real and imaginary parts can be interpolated by the Drude formula with two effective parameters: the mean charge of ions and the effective frequency of collisions. The rise of these parameters with temperature deviates from simple theoretical predictions (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
NiO Thin Films Synthesized by Atomic Layer Deposition using Ni(dmamb)2 and Ozone as Precursors
Authors: Antony Premkumar Peter , Toeller Michael , Adelmann Christoph , Meersschaut Johan , Franquet Alexis , Richard Olivier , Tielens Hilde , Brijs Bert , Moussa Alain , Conard Thierry , Bender Hugo , Schaekers Marc , Kittl Jorge A. , Jurczak Malgorzata , Van Elshocht Sven
Published: March 2012

NiO thin films are deposited by atomic layer deposition (ALD) from the Ni(dmamb)2 (dmamb = 1‐dimethylamino‐2‐methyl‐2‐butanolate) precursor using O3 as the oxidizer. The films are analyzed for wafer uniformity, structure, composition, morphology, microstructure, and homogeneity. The Ni(dmamb)2 half‐cycle shows an initial rapid partial saturation followed by slower further adsorption. By contrast, the O3 half‐cycle shows good saturation behavior. In the studied deposition temperature range for ALD, the films are polycrystalline with negligible amounts of carbon in the films. Furthermore, the films are homogeneous in thickness and composition, demonstrating that high‐quality NiO films can be deposited by ALD from Ni(dmamb)2.
Examination of the kinetic isotopic effect to the acetylation derivatization for the gas chromatographic‐combustion‐isotope ratio mass spectrometric doping control analysis of endogenous steroids
Authors: Angelis Yiannis S. , Kioussi Maroula K. , Kiousi Polyxeni , Brenna J. Thomas , Georgakopoulos Costas G.
Published: February 2012

In gas chromatographic‐combustion‐isotope ratio mass spectrometry (GC‐C‐IRMS) doping control analysis, endogenous androgenic anabolic steroids and their metabolites are commonly acetylated using acetic anhydride reagent, thus incorporating exogenous carbon that contributes to the measured isotope ratio. Comparison of the endogenous δ13C of free, mono‐, and di‐acetylated steroids requires application of corrections, typically through straightforward use of the mass balance equation. Variability in kinetic isotope effects (KIE) due to steroid structures could cause fractionation of endogenous steroid carbon, resulting in inaccurate results. To test for possible KIE influence on δ13C, acetic anhydride of graded isotope ratio within the natural abundance range was used under normal derivatization conditions to test for linearity. In all cases, plots of measured steroid acetate δ13C versus acetic anhydride δ13C were linear and slopes were not significantly different. Regression analysis of the Δδ13C of enriched acetic anhydrides versus Δδ13C of derivatized steroids shows that KIE are similar in all cases. We conclude that δ13C calculated from the mass balance equation is independent of the δ13C of the acetic anhydride reagent, and that net KIE under normal derivatization conditions do not bias the final reported steroid δ13C. Copyright © 2012 John Wiley & Sons, Ltd.
Groundwater‐dependent distribution of vegetation in Hailiutu River catchment, a semi‐arid region in China
Authors: Lv Jingjing , Wang Xu‐Sheng , Zhou Yangxiao , Qian Kaizhu , Wan Li , Eamus Derek , Tao Zhengping
Published: February 2012

In arid and semi‐arid regions, groundwater availability is one of the controls on vegetation distribution. This groundwater‐dependent distribution of vegetation has been particularly observed in the Hailiutu River catchment, a semi‐arid region in North China. We used remote sensing images of vegetation index (normalized difference vegetation index, NDVI) and field data of depth to water table (DWT) to assess the response of vegetation distribution on increase of DWT at the regional scale. The frequency distribution curves of NDVI with respect to different DWT were obtained. The statistical distributions of NDVI values at different DWT intervals indicate that higher vegetation coverage and more plant diversity exist at places of shallow groundwater. Both the mean and the standard deviation of NDVI values decrease with the increase of groundwater depth when DWT is less than 10 m. Beyond that depth, a low level of vegetation coverage and diversity is maintained. Comparisons of different sub‐areas within the region with different dominant species showed that the NDVI of shrubs is sensitive to DWT. In contrast, NDVI of herbs is not significantly influenced by DWT. The relationship between NDVI and groundwater depth in farmlands could not be reliably determined because of disturbance by human activities. We conclude that application of this methodology may significantly improve our ability on sustainable management of land and groundwater resources. Copyright © 2012 John Wiley & Sons, Ltd.
Astrocyte calcium signaling and epilepsy
Authors: Carmignoto Giorgio , Haydon Philip G.
Published: March 2012

Studies performed over the last decade, in both animal models and human epilepsy, support the view that a defective K+ buffering due to an altered expression of K+ and aquaporin channels in astrocytes represents a possible causative factor of the pathological neuronal hyperexcitability in the epileptic brain. More recent studies, however, reappraised the role of neurons in epileptogenesis and suggested that Ca2+‐dependent gliotransmission directly contributes to the excessive neuronal synchronization that predisposes the brain network to seizures. Significant support for this view comes from the finding that astrocytes from hyperexcitable networks respond to neuronal signals with massive Ca2+ elevations and generate a recurrent excitatory loop with neurons that has the potential to promote a focal seizure. The specific aim of this review is on the one hand, to provide an overview of the experimental findings that hinted at a direct role of Ca2+‐dependent gliotransmission in the generation of seizure‐like discharges in models of focal epilepsy; and on the other hand, to emphasize the importance of developing new experimental tools that could help us to understand the amazing complexity of neuron‐astrocyte partnership in brain disorders. © 2012 Wiley Periodicals, Inc.
Who worries most? Worry prevalence and patterns across the lifespan
Authors: Gonçalves Daniela C. , Byrne Gerard J.
Published: February 2012

Objective

To examine the age‐related worry patterns in a population‐based sample of self‐reported worriers.

Methods

The National Survey of Mental Health and Well‐Being is a multistage stratified epidemiologic survey of mental health conducted in Australia in 2007. Participants were surveyed using the Composite International Diagnostic Interview. All participants who reported a period of pervasive worry were included in this study (N = 3735, 16–85 years of age, 61% female).

Results

Compared with younger adults (16–29 years of age; N = 860), older adults (65–85 years of age; N = 639) reported fewer worries [odds ratio (OR) = 0.36, p < 0.01] and a lower likelihood of worrying about interpersonal relations (OR = 0.66, p < 0.01), health (OR = 0.65, p < 0.05), work (OR = 0.39, p < 0.01), and miscellaneous topics (OR = 0.57, p < 0.01), but a higher likelihood of worrying about the health and welfare of loved ones (OR = 2.46, p < 0.01) after adjusting for socio‐demographic and clinical factors. Similar patterns were seen in older persons with and without a lifetime history of generalized anxiety disorder as diagnosed by the Diagnostic and Statistical Manual of Mental Disorders.

Conclusions

The findings indicated an overall decrease in worry count with advancing age, as well as a developmental distribution of worry content, and a quantitative but not qualitative distinction between normal and pathological worriers. Overall, these findings might contribute to the understanding of worry processes and the phenomenology of generalized anxiety disorder in older cohorts. Copyright © 2012 John Wiley & Sons, Ltd.
Pregnane-x-receptor controls hepatic glucuronidation during pregnancy and neonatal development in humanized UGT1 mice
Authors: Chen Shujuan , Yueh Mei-Fei , Evans Ronald M. , Tukey Robert H.
Published: February 2012

In humanized UDP glucuronosyltransferase-1 (

hUGT1

) mice that express the entire

UGT1

locus, the maternal hepatic

UGT1A

genes are dramatically induced 12-14 days after conception. Steroid induction of the

UGT1A1

gene indicates that xenobiotic sensors, such as the pregnane X receptor (PXR) and constitutive androstane receptor (CAR), may underlie the induction process. In contrast, neonatal

hUGT1

mice display severe hyperbilirubinemia, with limited expression of the

UGT1A

genes. This study identifies PXR as both a positive and negative regulator of the

UGT1A1

gene. Pregnancy hormones, in particular the glucocorticoids, target PXR as a positive regulator of human glucuronidation. Employing reverse genetics, where PXR has been genetically deleted,

hUGT1/Pxr

−/− mice show limited induction of the liver

UGT1A

genes during pregnancy, whereas the exact opposite occurs in newborn mice. Neonatal

hUGT1

mice show delayed expression of hepatic UGT1A1 and are severely hyperbilirubinemic. However, in

hUGT1/Pxr

−/− mice, hyperbilirubinemia is greatly reduced due to induction of hepatic UGT1A1. Thus, PXR serves to repress

UGT1A1

gene expression during development. Transcriptional silencing of the

UGT1A1

gene was relieved in neonatal

hUGT1

hepatocytes through interruption of PXR by small interfering RNA.

Conclusion

: PXR is a key regulator of pregnancy induced glucuronidation capacity in addition to modulating the severity of neonatal jaundice. (HEPATOLOGY 2012)
Model to estimate survival in ambulatory patients with hepatocellular carcinoma
Authors: Yang Ju Dong , Kim Ray W. , Park Kyung Woo , Chaiteerakij Roongruedee , Kim Bohyun , Sanderson Schuyler O. , Larson Joseph J. , Pedersen Rachel A. , Therneau Terry M. , Gores Gregory J. , Roberts Lewis R. , Park Joong-Won
Published: February 2012

Survival of patients with hepatocellular carcinoma (HCC) is determined by the extent of the tumor and the underlying liver function. We aimed to develop a survival model for HCC based on objective parameters including the Model for Endstage Liver Disease (MELD) as a gauge of liver dysfunction. This analysis is based on 477 patients with HCC seen at Mayo Clinic Rochester between 1994 and 2008 (derivation cohort) and 904 patients at the Korean National Cancer Center between 2000 and 2003 (validation cohort). Multivariate proportional hazards models and corresponding risk score were created based on baseline demographic, clinical, and tumor characteristics. Internal and external validation of the model was performed. Discrimination and calibration of this new model were compared against existing models including Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), and Japan Integrated Staging (JIS) scores. The majority of the patients had viral hepatitis as the underlying liver disease (100% in the derivation cohort and 85% in the validation cohort). The survival model incorporated MELD, age, number of tumor nodules, size of the largest nodule, vascular invasion, metastasis, serum albumin, and alpha-fetoprotein. In cross-validation, the coefficients remained largely unchanged between iterations. Observed survival in the validation cohort matched closely with what was predicted by the model. The concordance (c)-statistic for this model (0.77) was superior to that for BCLC (0.71), CLIP (0.70), or JIS (0.70). The score was able to further classify patient survival within each stage of the BCLC classification.

Conclusion

: A new model to predict survival of HCC patients based on objective parameters provides refined prognostication and supplements the BCLC classification. (HEPATOLOGY 2012)
Hepatitis A virus vaccination in persons with hepatitis C virus infection: Consequences of quality measure implementation
Authors: Rowe Ian A. , Parker Richard , Armstrong Matthew J. , Houlihan Diarmaid D. , Mutimer David J.
Published: February 2012

Hepatitis A virus (HAV) superinfection in persons with hepatitis C virus (HCV) infection has been associated with a high mortality rate, and vaccination is recommended. The incidence of HAV is low, and the aim of this study was to determine the mortality risk of HAV superinfection and the consequences of routine vaccination in persons with HCV infection. To determine the mortality risk of HAV superinfection, a meta-analysis including studies reporting mortality in HCV-infected persons was performed. Data were extracted independently by two investigators and recorded on a standardized spreadsheet. The pooled mortality estimate was used to determine the number needed to vaccinate (NNV) to prevent mortality from HAV superinfection. The total vaccine cost was also calculated. A total of 239 studies were identified using a defined search strategy. Of these, 11 appeared to be relevant, and of these, 10 were suitable for inclusion in the meta-analysis. The pooled odds ratio (OR) for mortality risk in HAV superinfection of HCV-infected persons was 7.23 (95% confidence interval: 1.24-42.12) with significant heterogeneity (

I2 = 56%;

P

= 0.03) between studies. Using the pooled OR for mortality, this translates to 1.4 deaths per 1,000,000 susceptible persons with HCV per year. The NNV to prevent one death per year is therefore 814,849, assuming 90% vaccine uptake and 94.3% vaccine efficiency. The vaccine cost for this totals $162 million, or $80.1 million per death prevented per year.

Conclusion:

These data challenge the use of routine HAV vaccination in HCV-infected persons and its incorporation into clinical practice guidelines. HAV vaccination of all HCV-infected persons is costly and likely to expose many individuals to an intervention that is of no direct benefit. (HEPATOLOGY 2012)
The effect of d‐methamphetamine on simulated driving performance
Authors: Silber Beata Y. , Croft Rodney J. , Downey Luke A. , Papafotiou Katherine , Camfield David A. , Stough Con
Published: March 2012

Objectives

Methamphetamine is considered to be one of the most popularly abused drugs by drivers; however, its exact effect on driving and driving behaviour has yet to be thoroughly investigated. This being despite methamphetamine's increased prevalence in injured and deceased drivers.

Methods

Twenty healthy recreational illicit stimulant users (10 male and 10 female), aged between 21 and 32 years (mean = 25.4 years, SD = 3.3 years) attended two testing sessions involving oral consumption of 0.42 mg/kg d‐methamphetamine or a matching placebo. The drug administration was counter‐balanced, double‐blind, and medically supervised. At each session driving, performance was assessed 2.5 h post drug administration.

Results

d‐methamphetamine (0.42 mg/kg) did not significantly impair overall simulated driving performance 2.5 h post drug administration. At the individual driving variable level, participants in the d‐methamphetamine condition were observed to be driving slower when an emergency situation occurred (T = 44, p < 0.05), but interestingly, participants in both conditions recorded average speeds in excess of the speed limit (100 km/h) when the emergency situations occurred. The d‐methamphetamine condition did also produce four times more infringements where participants did not stop at red traffic light in comparison to the placebo, but this effect was only evident at a trend level (T = 7, p = 0.11).

Conclusions

The findings presented herein suggest that d‐methamphetamine administered at the levels supplied did not impair driving performance in a manner consistent with epidemiological evidence. Further research is certainly required to elucidate the effects of various doses of methamphetamine, alone and in combination with other legal and illicit substances. Copyright © 2012 John Wiley & Sons, Ltd.
Immune system inflammation in cocaine dependent individuals: implications for medications development
Authors: Fox Helen C. , D'Sa Carrol , Kimmerling Anne , Siedlarz Kristen M. , Tuit Keri L. , Stowe Raymond , Sinha Rajita
Published: March 2012

Objectives

Cocaine dependence is a chronic stress state. Furthermore, both stress and substance abuse have robust and reciprocal effects on immune system cytokines, which are known to be powerful modulators of mood. We therefore examine basal and provoked changes in peripheral cytokines in cocaine dependent individuals to better understand their role in the negative reinforcing effects of cocaine.

Methods

Twenty‐eight (16 F/12 M) treatment‐seeking cocaine dependent individuals and 27 (14 F/13 M) social drinkers were exposed to three 5‐min guided imagery conditions (stress, drug cue, relaxing) presented randomly across consecutive days. Measures of salivary cortisol, tumor necrosis factor alpha (TNFα), interleukin‐10 (IL‐10), and interleukin‐1 receptor antagonist (IL‐1ra) were collected at baseline and various post‐imagery time‐points.

Results

Cocaine abusers demonstrated decreased basal IL‐10 compared with social drinkers. They also showed significant elevations in pro‐inflammatory TNFα when exposed to stress compared with when they were exposed to relaxing imagery. This was not observed in the social drinkers. Conversely, social drinkers demonstrated increases in the anti‐inflammatory markers, IL‐10 and IL‐1ra, following exposure to cue, which were not seen in the dependent individuals.

Conclusions

Cocaine dependent individuals demonstrate an elevated inflammatory state both at baseline and following exposure to the stress imagery condition. Cytokines may reflect potentially novel biomarkers in addicted populations for treatment development. Copyright © 2012 John Wiley & Sons, Ltd.
Controlled drug delivery through a novel PEG hydrogel encapsulated silica aerogel system
Authors: Giray Seda , Bal Tuğba , Kartal Ayse M. , Kızılel Seda , Erkey* Can
Published: February 2012

A novel composite material consisting of a silica aerogel core coated by a poly(ethylene) glycol (PEG) hydrogel was developed. The potential of this novel composite as a drug delivery system was tested with ketoprofen as a model drug due to its solubility in supercritical carbon dioxide. The results indicated that both drug loading capacity and drug release profiles could be tuned by changing hydrophobicity of aerogels, and that drug loading capacity increased with decreased hydrophobicity, while slower release rates were achieved with increased hydrophobicity. Furthermore, higher concentration of PEG diacrylate in the prepolymer solution of the hydrogel coating delayed the release of the drug which can be attributed to the lower permeability at higher PEG diacrylate concentrations. The novel composite developed in this study can be easily implemented to achieve the controlled delivery of various drugs and/or proteins for specific applications. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
Preparation of a biomimetic nanocomposite scaffold for bone tissue engineering via mineralization of gelatin hydrogel and study of mineral transformation in simulated body fluid
Authors: Azami Mahmoud , Moosavifar Mir Javad , Baheiraei Nafiseh , Moztarzadeh Fathollah , Ai Jafar
Published: February 2012

In this study, double diffusion method in a physiologically relevant environment was used to prepare a biomimetic gelatin‐amorphous calcium phosphate nanocomposite scaffold. The precipitated calcium phosphate within gelatin as well as produced nanocomposite scaffolds were characterized by the commonly used bulk techniques. The results showed that nanocomposite scaffolds were porous with three‐dimensionally interconnected microstructure, pore size ranging from 150 to 350 μm. Porosity was about 82% and nanocrystalline precipitated minerals were dispersed evenly among gelatin fibers. A mineral containing amorphous calcium phosphate and brushite precipitate was formed within the gelatin matrix at 4°C. After incubation in SBF solution at 37°C for 5 days, the mineral phase was transformed to nanocrystalline hydroxyapatite. It should be noted that precursor phases inside a scaffold implanted into the body can result in biomimetic conversion of precursors to hydroxyapatite that is very similar to the bone mineral and has a profound level of biocompatibility. Thus, our results highlight the potential use of engineered biomimetic bone tissue scaffolds in the bone tissue repair process. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2012.
Ultrasensitive detection of cellular protein interactions using bioluminescence resonance energy transfer quantum dot‐based nanoprobes
Authors: Quiñones Gabriel A. , Miller Steven C. , Bhattacharyya Sukanta , Sobek Daniel , Stephan Jean‐Philippe
Published: March 2012

Sensitive detection of protein interactions is a critical step toward understanding complex cellular processes. As an alternative to fluorescence‐based detection, Renilla reniformis luciferase conjugated to quantum dots results in self‐illuminating bioluminescence resonance energy transfer quantum dot (BRET‐Qdot) nanoprobes that emit red to near‐infrared bioluminescence light. Here, we report the development of an ultrasensitive technology based on BRET‐Qdot conjugates modified with streptavidin ([BRET‐Qdot]‐SA) to detect cell‐surface protein interactions. Transfected COS7 cells expressing human cell‐surface proteins were interrogated with a human Fc tagged protein of interest. Specific protein interactions were detected using a biotinylated anti‐human Fc region specific antibody followed by incubation with [BRET‐Qdot]‐SA. The luciferase substrate coelenterazine activated bioluminescence light emission was detected with an ultra‐fast and ‐sensitive imager. Protein interactions barely detectable by the fluorescence‐based approach were readily quantified using this technology. The results demonstrate the successful application and the flexibility of the BRET‐Qdot‐based imaging technology to the ultrasensitive investigation of cell‐surface proteins and protein–protein interactions. J. Cell. Biochem. 113: 2397–2405, 2012. © 2012 Wiley Periodicals, Inc.
The ubiquitin–proteasome pathway regulates claudin 5 degradation
Authors: Mandel Ilana , Paperna Tamar , Volkowich Anat , Merhav Maayan , Glass‐Marmor Lea , Miller Ariel
Published: March 2012

The tight junctions (TJs) form continuous intracellular contacts, which help create selective barriers in epithelial and endothelial cell layers. The structures created by the TJs are very dynamic and can be rapidly remodeled in response to physiological and pathological signals. Claudin 5 is a membranal TJ protein which plays a critical role in determining the permeability of endothelial barriers. We describe the regulation of claudin 5 degradation by the ubiquitin–proteasome system (UPS). Our results indicate that claudin 5 has a relatively short half‐life and can be polyubiquitinated on lysine 199. This ubiquitination appears to trigger the proteasome‐dependent degradation of claudin 5. Other mechanisms also seem to be involved in the post‐translational regulation of claudin 5, including a ubiquitin‐independent and probably indirect lysosomal‐dependent pathway. These findings provide evidence for the involvement of the UPS in the regulation of claudin 5 levels, and set the stage for further research to determine the involvement of this pathway in the modulation of the properties of TJs and cell‐layer barriers. J. Cell. Biochem. 113: 2415–2423, 2012. © 2012 Wiley Periodicals, Inc.
Elevation of cartilage AGEs does not accelerate initiation of canine experimental osteoarthritis upon mild surgical damage
Authors: Vos Petra A.J.M. , DeGroot Jeroen , Barten‐van Rijbroek Angelique D. , Zuurmond Anne‐Marie , Bijlsma Johannes W.J. , Mastbergen Simon C. , Lafeber Floris P.J.G.
Published: March 2012

Osteoarthritis is a highly prevalent disease, age being the main risk factor. The age‐related accumulation of advanced‐glycation‐endproducts (AGEs) adversely affects the mechanical and biochemical properties of cartilage. The hypothesis that accumulation of cartilage AGEs in combination with surgically induced damage predisposes to the development of osteoarthritis was tested in vivo in a canine model. To artificially increase cartilage AGEs, right knee joints of eight dogs were repeatedly injected with ribose/threose (AGEd‐joints). Left joints with vehicle alone served as control. Subsequently, minimal surgically applied cartilage damage was induced and loading restrained as much as possible. Thirty weeks after surgery, joint tissues of all dogs were analyzed for biochemical and histological features of OA. Cartilage pentosidine levels were ∼5‐fold enhanced (p = 0.001 vs. control‐joints). On average, no statistically significant differences in joint degeneration were found between AGEd and control‐joints. Enhanced cartilage pentosidine levels did correlate with less cartilage proteoglycan release (R = −0.762 and R = −0.810 for total and newly‐formed proteoglycans, respectively; p = 0.028 and 0.015 for both). The current data support the diminished cartilage turnover, but only a tendency towards enhanced cartilage damage in AGEd articular cartilage was observed. As such, elevated AGEs do not unambiguously accelerate the development of early canine OA upon minimal surgical damage. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1398–1404, 2012
Expression of neural and neurotrophic markers in nucleus pulposus cells isolated from degenerated intervertebral disc
Authors: Navone Stefania E. , Marfia Giovanni , Canzi Laura , Ciusani Emilio , Canazza Alessandra , Visintini Sergio , Campanella Rolando , Parati Eugenio A.
Published: February 2012

Intervertebral disc (IVD) degeneration is a common disorder of the lower spine. Since it is caused by loss of cellularity, there is interest in the comprehension of the cellular phenotypes. This study aimed to verify if stem cells isolated from nucleus pulposus of intervertebral discs (NPs‐IVD), which may express neurogenic properties, may be implicated in IVD disease. NPs‐IVD isolated from 14 human pathological discs were cultured under mesenchymal and neural differentiation. An induction of the neural markers GFAP, NF, MAP2, O4, and a decrement of the expression of the immature neural markers β‐tubulin III, Nestin, NG2, occurred within the neural differentiation. The expression of TrkA and p75NGFR, the receptors of NGF, was not correlated with neural induction; in contrast, TrkB, the BDNF receptor, increased and was co‐expressed with acid sensing ion channel 3 (ASIC3). In the same condition, neuroinflammatory markers were over‐expressed. We confirm our hypothesis that stem cells within IVD degeneration acquire neurogenic phenotype, causing the induction of markers related to inflammatory condition. These cells could promote the enrolment of neurotrophines in adaptation to the acidic microenvironment in degenerative conditions. These data could improve our knowledge about IVD cellularity and eventually lead to the development of pharmacological therapies. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1470–1477, 2012
Reversible and irreversible denaturation processes in globular proteins: from collective to molecular spectroscopic analysis
Authors: Sassi Paola , Perticaroli Stefania , Comez Lucia , Lupi Laura , Paolantoni Marco , Fioretto Daniele , Morresi Assunta
Published: February 2012

Different spectroscopic techniques were applied for studying the structural properties of lysozyme in salt‐free aqueous solutions. The results of vibrational and Brillouin scattering measurements were compared to obtain both single‐molecule and collective properties of the solutions. The characterization of the protein system, from the conformation of the polypeptide chain to the exposure of side chains to the solvent and the arrangement of the solution network, was then achieved in the range 25–85 °C. Through the analysis of the indole breathing mode, a different environment for the six tryptophan residues of an unfolded lysozyme could be evidenced. Short and long exposures to high temperatures were used to modulate the competition between the thermally induced reversible and irreversible denaturation processes. These different thermal treatments were applied to distinguish between the effects of global unfolding of the single molecule from those of self‐aggregation and gel formation. It has been observed that clusterization occurs at melting temperatures with slow kinetics; also, aggregates evolve from the completely unfolded state of the protein and lead to a sensitive increase in viscosity. This effect probably hinders any further conformational rearrangement of the molecules in the aggregate; thus as a consequence, the disordered structure of clusters does not change to give the β‐sheet organization, characteristic of filaments or fibrils. Copyright © 2011 John Wiley & Sons, Ltd.
A sampling design and model for estimating abundance of Nile crocodiles while accounting for heterogeneity of detectability of multiple observers
Authors: Shirley Matthew H. , Dorazio Robert M. , Abassery Ekramy , Elhady Amr Abd , Mekki Mohammed Saad , Asran Hosni Helmy
Published: February 2012

As part of the development of a management program for Nile crocodiles in Lake Nasser, Egypt, we used a dependent double‐observer sampling protocol with multiple observers to compute estimates of population size. To analyze the data, we developed a hierarchical model that allowed us to assess variation in detection probabilities among observers and survey dates, as well as account for variation in crocodile abundance among sites and habitats. We conducted surveys from July 2008–June 2009 in 15 areas of Lake Nasser that were representative of 3 main habitat categories. During these surveys, we sampled 1,086 km of lake shore wherein we detected 386 crocodiles. Analysis of the data revealed significant variability in both inter‐ and intra‐observer detection probabilities. Our raw encounter rate was 0.355 crocodiles/km. When we accounted for observer effects and habitat, we estimated a surface population abundance of 2,581 (2,239–2,987, 95% credible intervals) crocodiles in Lake Nasser. Our results underscore the importance of well‐trained, experienced monitoring personnel in order to decrease heterogeneity in intra‐observer detection probability and to better detect changes in the population based on survey indices. This study will assist the Egyptian government establish a monitoring program as an integral part of future crocodile harvest activities in Lake Nasser. © 2012 The Wildlife Society.