bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental and comparative aspects of posterior medial thalamocortical innervation of the barrel cortex in mice and rats
Authors: Kichula Elizabeth A. , Huntley George W.
Published: June 2008

Confocal laser scanning microscope image of a tangential section through layer IV of barrel cortex taken from a rat pup aged postnatal day 6. Thalamocortical axons (TCAs) from the VPM nucleus are labeled by DiD (blue); their terminations form whisker‐related clusters that occupy the barrels. TCAs from the POm nucleus are labeled by DiI (red). By this age, their terminations mostly occupy the intervening septa that separate the barrels, although a few axons are found within the barrels. Thus, by the end of the first postnatal week, an adult‐like pattern of interdigitated thalamocortical projections is largely established. J. Comp. Neurol. 509:239‐258, 2008. © 2008 Wiley‐Liss, Inc.
Experimental determination of laws of color harmony. Part 2: Harmony content of different monochrome color pairs
Authors: Nemcsics Antal
Published: June 2008

In 1956, we came to the decision at the Budapest Technical University to start large scale experiments on color harmony. The experiments and the processing of the experimental results have been completed in 2006, after 50 years of research work. The focal point of the experiments published in the current article has been the practical experience that the span of intervals between saturations and brightnesses of the compositions influence the harmony content of the composition, namely they determine in what extent we perceive the color composition as a harmonic one. Within the framework of experiments compositions have been shown to the participants, first those consisting of color pairs featuring the same hues and saturations but different brightnesses then those consisting of the same hues and brightnesses but different saturations. The method of experiments consisted of comparisons in pairs. There were 780 compositions prepared for the tests. The number of elementary observations during the tests comprised 544 000. It has been established that the variation of harmony content as a function of brightness‐ and saturation‐intervals could be described by a harmony function. It has been established that the variation of harmony content depending on brightness‐intervals is not, but that of depending on saturation intervals is being influenced by the hues of colors of the color pair in the composition. It has been established that in case of compositions with the maximum harmony content the interval of brightnesses of the colors making the color pair in each case gives d30V (d9Y), the interval of saturations gives d30T or is near to it. © 2008 Wiley Periodicals, Inc. Col Res Appl, 33, 262–270, 2008.
The total colorant sensitivity of a color matching recipe: An approach to colorant weighting and tinctorial strength errors
Authors: Peyvandi Shahram , Amirshahi Seyed Hossein , Sluban Boris
Published: June 2008

The repeatability of the recipe color can be affected by several different types of inevitable inaccuracies in the coloration process. Two of the major causes of poor target‐color reproducibility are the (random) weighing and (proportional) strength errors. This article describes alternative definitions of colorant strength sensitivity and total colorant sensitivity of a dyeing recipe. The influences of the maximal colorant weighing and strength errors are taken into account in order to bring the magnitudes of the two treated types of sensitivity into a mutually realistic balance between each other. The quantifications of precision and accuracy of a color matching recipe are also developed and combined into a single‐number measure of recipe quality. The listed quantities are expected to be useful in selecting the most reliable one(s) among the different formulations for the same standard color. The methods are presented for calculating numerical estimates of the newly introduced quantities. The precision and accuracy of the coloration process are investigated in laboratory experiments involving repeated dyeings. © 2008 Wiley Periodicals, Inc. Col Res Appl, 33, 300–306, 2008.
Grassmann's laws and individual color‐matching functions for non‐spectral primaries evaluated by maximum saturation technique in foveal vision
Authors: Oleari Claudio , Pavesi Maura
Published: June 2008

Over time, much work has been carried out to ascertain the validity of Grassmann's laws, Abney's law, CIE standard color‐matching functions and, up to now, no definitive answer has been given. Some of the phenomena subject of this debate are considered. An apparatus for color matching in 1.8° visual field has been realized with two sets of primary lights with broad spectral bands. This kind of primaries is the great difference with respect to other laboratories because it allows an indirect check of the Grassmann additivity law on the basis of the spectra and individual color‐matching functions by evaluating: (1) the tristimulus values of the primary lights; (2) the transformation matrices between the two reference frames defined by the two primary sets; and (3) the tristimulus values associated to all the pairs of matching lights in the bipartite field produced in the evaluation of the two sets of color‐matching function. The discrepancies of the data resulting in the check (1) and (2) are all compatible with the range defined by the uncertainty propagation of the individual color‐matching functions. In the check (3) fifteen tristimulus values over 18 have a discrepancy lower than one standard uncertainty. Grassmann's proportionality law is checked directly by reducing the matching lights with a neutral filter and holds true. © 2008 Wiley Periodicals, Inc. Col Res Appl, 33, 271–281, 2008.
Book review: Colouring the Past—On colour in archaeological research
Authors: Fridell Anter Karin
Published: June 2008

The book, Colouring the Past. The Significance of Colour in Archaeological Research, is an anthology discussing various aspects of colour from an archaeological viewpoint. This article presents some of its main topics and discusses a few issues more in length. One starting point for this is the criticism on Berlin and Kay's theory of basic color terms and the Munsell Book of Colors that is launched in some of the articles in the book. The article concludes in summing up some areas where archaeologists and color researchers from other fields could have a mutual interest of further exchange. © 2008 Wiley Periodicals, Inc. Col Res Appl, 33, 327–334, 2008.
Spectral color management using interim connection spaces based on spectral decomposition
Authors: Tsutsumi Shohei , Rosen Mitchell R. , Berns Roy S.
Published: June 2008

A feasible approach to spectral color management was previously defined to include lookups performed within an interim connection space (ICS). ICS is relatively low in dimensions and is situated between a high‐dimensional spectral profile connection space and output units. The definition of ICS axes and the minimum number of ICS dimensions are explored here by considering the LabPQR, an ICS described in earlier research. LabPQR has three colorimetric dimensions (CIE L*a*b*) and additional dimensions to describe a metameric black (PQR). Several versions of LabPQR are explored. One type defines PQR axes based on metameric blacks generated from Cohen and Kappauf's spectral decomposition. The second type is constructed in an unconstrained way where metameric blacks are statistically derived based on the spectral characteristics of the target output device. For a six‐dimensional LabPQR, one that uses three colorimetric and three metameric black dimensions, it was found that Cohen and Kappauf‐based LabPQR was inferior for estimating the spectra when compared with the unconstrained method. However, when the limited spectral gamut of an output device was introduced through printer simulation and necessary spectral gamut mapping, the disadvantage of the six‐dimensional Cohen and Kappauf‐based LabPQR dissipated. On the other hand, reducing LabPQR to only five‐dimensions (two metameric black dimensions) reintroduced the advantage of the unconstrained approach even after simulated printing including spectral gamut mapping. Importantly, it was found that the five‐dimensional unconstrained approach achieved equivalent levels of performance to a full 31‐dimensional approach within simulated printer spectral gamut limitations. © 2008 Wiley Periodicals, Inc. Col Res Appl, 33, 282–299, 2008.
Lentivector immunization induces tumor antigen‐specific B and T cell responses in vivo
Authors: Garcia Casado Javier , Janda Jozef , Wei Joe , Chapatte Laurence , Colombetti Sara , Alves Pedro , Ritter Gerd , Ayyoub Maha , Valmori Danila , Chen Weisan , Lévy Frédéric
Published: June 2008

Expression of the cancer/germ‐line antigen NY‐ESO‐1 by tumors elicits spontaneous humoral and cellular immune responses in some cancer patients. Development of vaccines capable of stimulating such comprehensive immune responses is desirable. We have produced recombinant lentivectors directing the intracellular synthesis of NY‐ESO‐1 (rLV/ESO) and have analyzed the in vivo immune response elicited by this vector. Single injection of rLV/ESO into HLA‐A2‐transgenic mice elicited long‐lasting B and T cell responses against NY‐ESO‐1. CD8+ T cells against the HLA‐A2‐restricted peptide NY‐ESO‐1157–165 were readily detectable ex vivo and showed restricted TCR Vβ usage. Moreover, rLV/ESO elicited a far greater anti‐NY‐ESO‐1157–165 CD8+ T cell response than peptide‐ or protein‐based vaccines. Anti‐NY‐ESO‐1 antibodies were rapidly induced after immunization and their detection preceded that of the antigen‐specific CD8+ T cells. The rLV/ESO also induced CD4+ T cells. These cells played an essential role as their depletion completely abrogated B cell and CD8+ T cell responses against NY‐ESO‐1. The induced CD4+ T cells were primarily directed against a single NY‐ESO‐1 epitope spanning amino acids 81–100. Altogether, our study shows that rLV/ESO induces potent and comprehensive immune responses in vivo.
IL‐21 and IL‐21R are not required for development of Th17 cells and autoimmunity in vivo
Authors: Sonderegger Ivo , Kisielow Jan , Meier Reto , King Cecile , Kopf Manfred
Published: June 2008

Th17 cells have been recognized as the central effectors in organ‐related autoimmune diseases. IL‐6 is a key factor that reciprocally regulates Th17 and Foxp3+ Treg differentiation by inhibition of TGF‐β induced Foxp3 and induction of RORγt, a Th17 lineage‐specific transcription factor. Recently IL‐21 has been suggested to induce RORγt and Th17 development in the absence of IL‐6. However, the relevance of IL‐21 for Th17‐dependent inflammatory responses in vivo remains unclear. In this study, we demonstrate that differentiation of IL‐17‐producing CD4 T cells, their recruitment to inflamed organs, and the development of autoimmune disease was not affected in il21R–/– and il21–/– mice in models of myelin oligodendrocyte glycoprotein‐induced autoimmune encephalitis and autoimmune myocarditis. IL‐6 induced Th17 differentiation independent of and much more potently than IL‐21 in vitro. These data suggest that IL‐6 is sufficient to drive Th17 development and associated autoimmunity in vivo in the absence of IL‐21 or IL‐21R.

See accompanying Commentary http:dx.doi.org/10.1002/eji.200838529

Supporting information for this article is available at http://www.wiley‐vch.de/contents/jc_2040/2008/38511_s.pdf
Palladacyclic Complexes Containing C,N‐Type Ligands as Catalysts in Cross‐Coupling Reactions
Authors: Chen Ming‐Tsz , Huang Chi‐An , Chen Chi‐Tien
Published: June 2008

Four ligand precursors, namely PhN=C(CMe2)(NPh)C=N(E) [E = –(CH2)2OMe (1); –(CH2)C(O)OMe (2); –(CH2)2CH3 (3);–C6H5 (4)], are described. Treatment of 1, 2, 3 or 4 with 1–1.1 molar equivalents of Pd(OAc)2 in THF or CH3CN affords the orthometallated palladium(II) complexes [{[PhN=C(CMe2)(N‐η1‐Ph)C=N(E)]Pd(OAc)}2] [E = –(CH2)2OMe (5); –(CH2)C(O)OMe (6); –(CH2)2CH3 (7); –C6H5 (8)], respectively. The reaction of 5 or 6 with an excess of NaCl(aq.) in acetoneaffords the orthometallated palladium(II) complexes [{PhN=C(CMe2)(N‐η1‐Ph)C=N(E)}PdCl] [E = –(CH2)2OMe (9); –(CH2)C(O)OMe (10)], whereas the reaction of 7 with an excess of NaCl(aq.) in acetone affords the dinuclear palladium(II) complex [{[PhN=C(CMe2)(N‐η1‐Ph)C=N(CH2)2CH3]PdCl}2] (11). The crystal and molecular structures of compounds 2, 4, 5, 7, 8 and 9 are reported The application of those novel palladacyclic complexes to the Suzuki and Heck reactions with aryl halide substrates is examined.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Synthesis of Spherical Down‐ and Up‐Conversion NaYF4‐Based Nanophosphors with Tunable Size in Ethylene Glycol without Surfactants or Capping Additives
Authors: Nuñez Nuria O. , Míguez Hernán , Quintanilla Marta , Cantelar Eugenio , Cussó Fernando , Ocaña Manuel
Published: June 2008

A very simple route for the synthesis of spherical down‐conversion (DC) and up‐conversion (UC) NaYF4‐based nanophosphors is described which consists of a precipitation reaction at rather low temperature (max. 120 °C) from solutions containing sodium fluoride and appropriate Ln precursors in a common solvent (ethylene glycol/water mixtures), without the use of any other additive (complexing agent or surfactant). The role played by the nature of the yttrium precursor and the solvent on the morphological characteristics of the nanoparticles is discussed. The size of the nanospheres, which crystallized in the cubic α‐NaYF4 phase, could be tuned within the 45–155 nm range by adjusting the reaction parameters (temperature and ethylene glycol/water ratio). The applicability of this method is illustrated for the synthesis of EuIII‐doped (DC), TbIII‐doped (DC) and YbIII/ErIII codoped (UC) NaYF4 nanophosphors, whose luminescent properties were also analysed.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Oil yield and compressibility modeling during microscale expression: Criteria for linseed breeding
Authors: Savoire Raphaëlle , Lanoisellé Jean‐Louis , Ducatel Hélène , Vorobiev Eugène
Published: June 2008

Seven linseed varieties were harvested at seven times before complete maturity. Microscale oilseed expressions were subsequently carried out on it. A pressure of 10 MPa was applied for 1 h under uniaxial stress. The results were characterized in terms of oil, water and mucilage content, harvest date and oil yield. The piston displacement versus time (creep curves) was described by a four‐Kelvin‐Voigt elements viscoelastic model. Parameters were derived from the model, such as the mechanical properties of seeds (compressibility moduli), showing that the viscoelastic model fits well the experimental data (R² ≈ 0.999). The modeling parameters were combined with some biochemical data in order to predict the kinetics of oil extraction.
A Chiral “Frozen” Hydrogen Bonding in C4‐Symmetric Inherently Chiral Resorcin[4]arenes: NMR, X‐ray, Circular Dichroism, and Theoretical Study (Eur. J. Org. Chem. 18/2008)
Authors: Kuberski Bogumił , Pecul Magdalena , Szumna Agnieszka
Published: June 2008

The cover picture shows the X‐ray structure of CC4‐symmetric, chiral resorcinarene substituted with L‐leucine at the upper rim. The molecule is held in the inherently chiral conformation (resembling a chiral CC4‐symmetric propeller) by means of twelve intramolecular hydrogen bonds. The seams of hydrogen bonds can be directed in one particular direction because of diastereomeric preferences. The determination of the direction of the hydrogen‐bonding seam and the correlation with CD spectra is discussed in the article by A. Szumna et al. on p. 3069 ff.
Study of interaction between drug enantiomers and human serum albumin by flow injection‐capillary electrophoresis frontal analysis
Authors: Liu Xiumei , Chen Xingguo , Yue Yuanyuan , Zhang Jingshu , Song Yuqin
Published: June 2008

Flow injection (FI)‐CE coupled with frontal analysis (FA) was applied to the study of stereoselectivity binding of amlodipine (AL) to HSA. Under protein‐drug binding equilibrium, the unbound concentrations of drug enantiomers were measured by plateau height. The stereoselectivity of AL binding to HSA was proved by the different free fractions of two enantiomers. In physiological phosphate solution (pH 7.4, ionic strength 0.17) when 200 μM (±)AL was equilibrated with 300 μM HSA, the concentration of unbound R‐AL was about 1.5 times higher than that of its antipode. The binding constants of two enantiomers, KR‐AL and KS‐AL, were 9910–11200 and 90200–104000 M−1, respectively. The results obtained by the method were compared with those determined by conventional equilibrium dialysis (ED)‐CE and fluorescence spectra. Hydroxypropyl‐β‐CD (HP‐β‐CD) (10 mM) was used as a chiral selector in pH 3.7 phosphate buffer. L‐Tryptophan (L‐try) and ketoprofen (Ket) were used as displacement reagents to investigate the binding sites of AL to HSA. A binding synergism effect between hydrochlorothiazide (QL) and AL was observed and the results suggested that QL can destroy binding equilibrium of R‐AL and S‐AL toward HSA and they can occupy the same binding site of HSA (site I). The reproducibility was confirmed by RSD (RSD<1.5%) of the plateau height determined by FI‐CE frontal analysis (FI‐CE‐FA). The FI‐CE‐FA was a good method to study protein–drug interaction.
Determination of ascorbic acid in individual rat hepatocyte cells based on capillary electrophoresis with electrochemiluminescence detection
Authors: Sun Xuemei , Niu Yan , Bi Sai , Zhang Shusheng
Published: June 2008

A novel method to detect ascorbic acid (AA) in individual rat hepatocyte cells was developed by combining CE with electrochemiluminescence (ECL) based on tris(2,2′‐bipyridine) ruthenium(II) ($\displaystyle {Ru\left( {bpy} \right)_3^{2 + } } $). A single cell, followed by 0.1% SDS as cell lysis solution, was injected into the inlet of the separation capillary by electromigration. After optimizing the analytical conditions, the RSDs of migration time and peak height were 0.38% and 2.6% for 1.0×10−5 M AA (n = 10), respectively. The linear range of AA was from 1.0×10−8 to 5.0×10−5 M with a correlation coefficient of 0.9979 and the LOD (S/N = 3) was estimated to be 1.0×10−8 M. This method has been successfully applied to determine AA in single rat hepatocytes and the amount of AA in seven rat hepatocytes ranged from 16 to 62 fmol. The above results demonstrated that CE coupled with ECL is convenient, sensitive, and will become an attractive alternative method for single‐cell analysis.
Pattern recognition in capillary electrophoresis data using dynamic programming in the wavelet domain
Authors: Ceballos Gerardo A. , Paredes Jose L. , Hernández Luis F.
Published: June 2008

A novel approach for CE data analysis based on pattern recognition techniques in the wavelet domain is presented. Low‐resolution, denoised electropherograms are obtained by applying several preprocessing algorithms including denoising, baseline correction, and detection of the region of interest in the wavelet domain. The resultant signals are mapped into character sequences using first derivative information and multilevel peak height quantization. Next, a local alignment algorithm is applied on the coded sequences for peak pattern recognition. We also propose 2‐D and 3‐D representations of the found patterns for fast visual evaluation of the variability of chemical substances concentration in the analyzed samples. The proposed approach is tested on the analysis of intracerebral microdialysate data obtained by CE and LIF detection, achieving a correct detection rate of about 85% with a processing time of less than 0.3 s per 25 000‐point electropherogram. Using a local alignment algorithm on low‐resolution denoised electropherograms might have a great impact on high‐throughput CE since the proposed methodology will substitute automatic fast pattern recognition analysis for slow, human based time‐consuming visual pattern recognition methods.
Modeling the migration behavior of rabbit liver apothioneins in capillary electrophoresis
Authors: Benavente Fernando , Andón Balbina , Giménez Estela , Barbosa José , Sanz‐Nebot Victoria
Published: June 2008

Metallothioneins (MTs) are a group of low‐molecular‐mass proteins (6–7 kDa) characterized by their great affinity for heavy metal ions. At acidic pH, the bound metal ions are released from the amino acidic structure and MTs lead to apothioneins. In this study, a general equation is used to model the electrophoretic mobility of rabbit liver apothioneins as a function of the pH of the separation electrolyte. The ability of these relationships to explain the migration behavior of these relatively complex polyprotic proteins in the pH range between 2 and 6 has been investigated. Their relevant ionization constant values in the studied pH range were estimated and employed for molecular charge calculations. The classical semiempirical relationships between electrophoretic mobility and charge‐to‐mass ratio (me vs. q/Mα) were tested for prediction of their electrophoretic separations. The accuracy of the separations predicted at acidic pH was confirmed by CE‐ESI‐MS.
Micro‐high‐performance liquid chromatography platform for the depletion of high‐abundance proteins and subsequent on‐line concentration/capturing of medium and low‐abundance proteins from serum. Application to profiling of protein expression in healthy and osteoarthritis sera by 2‐D gel electrophoresis
Authors: Jmeian Yazen , El Rassi Ziad
Published: June 2008

In this investigation, an integrated microcolumn‐based fluidic platform for the simultaneous depletion of high‐abundance proteins and the subsequent on‐line concentration/capturing of medium‐ and low‐abundance proteins from human serum has been introduced. The platform consists of on‐line coupling of tandem affinity micorcolumns to an RP microcolumn to achieve first the depletion of high‐abundance proteins by the tandem affinity microcolumns followed by the concentration and capturing of medium‐ and low‐abundance proteins by the RP microcolumn. The tandem affinity microcolumns are based on macroporous monoliths characterized by their relatively high permeability in pressure‐driven flow while the RP microcolumn is packed with polymeric particles with an average particle diameter of 20 µm giving rise to a very little back pressure, thus allowing fast flow velocity across the coupled columns format and consequently short processing time of serum samples prior to analysis by 2‐DE. The microcolumn‐based fluidic platform was applied to serum samples from osteoarthritis (OA) donors before and after soy protein (SP) supplementation, and from healthy donors, and the resulting depleted serum samples from high‐abundance proteins were profiled for protein expression by 2‐DE. In general, the protein expression was lower in serum of the same OA patient after soy treatment than before soy treatment. Several proteins were down‐regulated after soy treatment with transthyretin being the most affected by the SP supplementation. In addition, with respect to serum from healthy donors, the sera from OA patients showed difference in proteins expression.
Plasmodium falciparum growth is arrested by monoterpenes from eucalyptus oil
Authors: Su Vanessa , King Drew , Woodrow Ian , McFadden Geoffrey , Gleadow Roslyn
Published: June 2008

Cerebral malaria is a major health problem in the developing world. Widespread resistance to existing drugs by the parasite Plasmodium falciparum has coincided with an increase in mortality, particularly in children. One potential source of new drugs comes from plant natural products. We found that commercially available, pharmaceutical grade eucalyptus oil and its principal component 1,8‐cineole inhibited the growth and development of chloroquine‐sensitive and chloroquine‐resistant P. falciparum. This was true both when the oil was added directly to the parasite cultures and when cultures were exposed to the vapours. The development of the parasite was arrested at the early trophozoite stage, irrespective of when the oil was introduced. We used a new approach where the concentration of monoterpenes actually taken up by the cultures was measured directly using HS–GC. We found that the critical concentration required to inhibit and kill the parasite did not adversely affect the host erythrocytes, placing it in the range suitable for drug development. Given the ready availability and existing quality control of eucalyptus oils, this may represent an economically viable adjunct to current antimalarial therapies. Copyright © 2008 John Wiley & Sons, Ltd.
Different sample preparation methods combined with LC–MS/MS and LC–UV for determination of some furocoumarin compounds in products containing citruses
Authors: Prosen Helena , Kočar Drago
Published: June 2008

Furocoumarins are a group of naturally occurring oxygen heterocyclic compounds synthesized by different plants (mainly Citrus species). They have several physiological effects, e.g. photoreactivity and inhibition of intestinal and liver drug metabolism, which imply the need to control their concentration in products intended for human use. We tested different sample preparation approaches and LC with different detection modes: UV, APCI–MS/MS and ESI–MS/MS for the determination of bergapten (BGPT) and bergamottin (BGMT) in different samples of beverages and cosmetics. Direct injection of sample solutions was applicable only for essential oils, while liquid–liquid extraction proved to be time‐consuming and unsuitable for our samples. Solid‐phase extraction with a preconcentration factor of 20 yielded repeatable recoveries for aqueous solutions (97.4% for BGPT, 64.6% for BGMT) and the concentration range was > 0.1 mg/l for UV detection and 2–1000 µg/l for MS/MS detection. Results of sample analysis indicated some problems connected both to detection and the extraction. The standard addition method for quantification yielded the most reliable results. Copyright © 2008 John Wiley & Sons, Ltd.
Synthesis of flavour esters using free Candida antarctica lipase B in ionic liquids
Authors: de los Ríos A. P. , Hernández‐Fernández F. J. , Tomás‐Alonso F. , Gómez D. , Víllora G.
Published: June 2008

The enzymatic synthesis of flavour esters by trans‐esterification from vinyl esters and alcohols catalysed by free Candida antarctica lipase B (CaLB) in ionic liquids has been studied. The influence of different parameters, such us pH, temperature and ionic liquid nature, on activity and selectivity has been carefully analysed, using as reaction model the synthesis of butyl butanoate. Finally, a broad range of flavour esters were sucessfully synthesized using the optimal operation conditions previously established. Copyright © 2008 John Wiley & Sons, Ltd.
Scalar BEKK and indirect DCC
Authors: Caporin Massimiliano , McAleer Michael
Published: June 2008

The paper derives the scalar special case of the well‐known BEKK multivariate GARCH model using a multivariate extension of the random coefficient autoregressive (RCA) model. This representation establishes the relevant structural and asymptotic properties of the scalar BEKK model using the theoretical results available in the literature for general multivariate GARCH. Sufficient conditions for the (direct) DCC model to be consistent with a scalar BEKK representation are established. Moreover, an indirect DCC model that is consistent with the scalar BEKK representation is obtained, and is compared with the direct DCC model using an empirical example. The paper shows, within an asset allocation and risk measurement framework, that the two models are similar in terms of providing parameter estimates and forecasting value‐at‐risk thresholds for equally weighted and minimum variance portfolios. Copyright © 2008 John Wiley & Sons, Ltd.
Elders with first psychiatric hospitalization for depression
Authors: Choi Sunha , Rozario Philip , Morrow‐Howell Nancy , Proctor Enola
Published: June 2008

Objective

Little is known about the first psychiatric hospitalization episode of older adults with depression. The purpose of this study is to describe the proportion and characteristics of first‐time inpatients admitted for late‐life depression.

Methods

Guided by the Network Episode Model and the Andersen model, this study identifies and compares the characteristics of depressed older adults with (n = 108) and those without (n = 77) prior psychiatric hospitalization, upon admission into the geropsychiatric unit, using logistic regression. Data on a lifetime history of inpatient psychiatric treatment, clinical characteristics, demographics, social resources, and psychosocial/medical service use were obtained from patients' medical records and self‐reports.

Results

Compared with patients who had prior psychiatric admission, first‐time inpatients were associated with having: (1) late‐onset depression (OR = 14.99); (2) no lifetime psychotic symptoms (OR = 0.21); (3) lower scores on the Brief Psychiatric Rating Scale (BPRS) at admission (OR = 0.96); (4) higher numbers of doctors seen (OR = 1.46); and (5) lower use of senior centers 6 months prior to the admission (OR = 0.12).

Conclusions

Depressed older adults' prior psychiatric inpatient service utilization is closely related to their past and current psychiatric needs. Also, the two groups show significant differences in health and social service use prior to the psychiatric hospitalization. However, severity of depression at admission was not different. Copyright © 2008 John Wiley & Sons, Ltd.
Effectiveness of a training program for carers to recognize depression among older people
Authors: McCabe Marita P. , Russo Sarah , Mellor David , Davison Tanya E. , George Kuruvilla
Published: June 2008

Objective

Depression is a mental disorder that is frequently not detected among older people. The current study was designed to evaluate the effectiveness of a training program to assist carers to better recognize depression among older people in both community and residential care settings.

Methods

In total, 52 professional carers (26 in community care, 26 in residential care) across a range of occupations completed a four session (for personal care attendants) or six session (for registered nurses or managers) training program. The program provided training for staff to identify and respond appropriately to signs of depression. In addition, nurses and managers were trained on the use of screening tools and referral processes. Outcomes were evaluated at post‐test, and 6‐month follow‐up.

Results

The results demonstrated that for all groups training was effective in increasing carers' knowledge of depression and self‐efficacy in detecting depression, as well as reducing the barriers to care at both post‐test and 6‐month follow‐up.

Conclusions

The training program evaluated in the current study was effective in increasing the level of skills necessary for care staff to better detect depression among older people in both community and residential care settings. Further research is needed to determine if these improved skills are sustained over time, and if they actually improve the level of recognition of depression among older people. Copyright © 2008 John Wiley & Sons, Ltd.
Expression of cannabinoid receptors type 1 and type 2 in non‐Hodgkin lymphoma: Growth inhibition by receptor activation
Authors: Gustafsson Kristin , Wang Xiao , Severa Denise , Eriksson Maeve , Kimby Eva , Merup Mats , Christensson Birger , Flygare Jenny , Sander Birgitta
Published: June 2008

Endogenous and synthetic cannabinoids exert antiproliferative and proapoptotic effects in various types of cancer and in mantle cell lymphoma (MCL). In this study, we evaluated the expression of cannabinoid receptors type 1 and type 2 (CB1 and CB2) in non‐Hodgkin lymphomas of B cell type (n = 62). A majority of the lymphomas expressed higher mRNA levels of CB1 and/or CB2 as compared to reactive lymphoid tissue. With the exception of MCL, which uniformly overexpresses both CB1 and CB2, the levels of cannabinoid receptors within other lymphoma entities were highly variable, ranging from 0.1 to 224 times the expression in reactive lymph nodes. Low levels of the splice variant CB1a, previously shown to have a different affinity for cannabinoids than CB1, were detected in 44% of the lymphomas, while CB1b expression was not detected. In functional studies using MCL, Burkitt lymphoma (BL), chronic lymphatic leukemia (CLL) and plasma cell leukemia cell lines, the stable anandamide analog R(+)‐methanandamide (R(+)‐MA) induced cell death only in MCL and CLL cells, which overexpressed both cannabinoid receptors, but not in BL. In vivo treatment with R(+)‐MA caused a significant reduction of tumor size and mitotic index in mice xenografted with human MCL. Together, our results suggest that therapies using cannabinoid receptor ligands will have efficiency in reducing tumor burden in malignant lymphoma overexpressing CB1 and CB2. © 2008 Wiley‐Liss, Inc.
Synergistic inhibition of head and neck tumor growth by green tea (−)‐epigallocatechin‐3‐gallate and EGFR tyrosine kinase inhibitor
Authors: Zhang Xin , Zhang Hongzheng , Tighiouart Mourad , Lee John E. , Shin Hyung J. , Khuri Fadlo R. , Yang Chung S. , Chen Zhuo (Georgia) , Shin Dong M.
Published: June 2008

One of the mechanisms of the antitumor activity of green tea (−)‐epigallocatechin‐3‐gallate (EGCG) is associated with its effect on epidermal growth factor receptor (EGFR)‐mediated signaling transduction pathways. We investigated whether combining EGCG with the EGFR‐tyrosine kinase inhibitor (EGFR‐TKI) erlotinib may augment erlotinib‐induced cell growth inhibition of squamous cell carcinoma of the head and neck (SCCHN) in a mouse xenograft model. In vitro studies with 5 head and neck cancer cell lines revealed that synergistic cell growth inhibition by the combination of EGCG and erlotinib was associated with significantly greater inhibition of pEGFR and pAKT, increased activation of caspases 9, 3 and PARP compared to the inhibition induced by EGCG or erlotinib alone. Erlotinib inhibited phosphorylation of EGFR, stabilizing EGFR at the plasma membrane, whereas EGCG induced EGFR internalization and ubiquitin‐degradation, ultimately undermining EGFR signaling. The efficacy of the combination treatment was investigated with nude mice (n = 25) orally gavaged with vehicle control, EGCG, erlotinib or the combination at the same doses for 7 days, followed by subcutaneous injection with Tu212 cells. Animals were continuously administered the agents 5 days weekly for 7 weeks. The combined treatment resulted in significantly greater inhibition of tumor growth and delayed tumor progression as a result of increased apoptosis, decreased cell proliferation and reduced pEGFR and pAKT compared to the single agent treatment groups. Our results suggest a synergistic antitumor effect of a combined treatment with EGCG and erlotinib, and provide a promising regimen for future chemoprevention and treatment of SCCHN. © 2008 Wiley‐Liss, Inc.
Increased risk of colon cancer after external radiation therapy for prostate cancer
Authors: Rapiti Elisabetta , Fioretta Gerald , Verkooijen Helena M. , Zanetti Roberto , Schmidlin Franz , Shubert Hyma , Merglen Arnaud , Miralbell Raymond , Bouchardy Christine
Published: June 2008

Radiotherapy can induce second cancers. Controversies still exist regarding the risk of second malignancies after irradiation for prostate cancer. We evaluated the risk of developing colon and rectum cancers after prostate cancer in irradiated and nonirradiated patients. Using data from the population‐based Geneva cancer registry, we included in the study all men with prostate cancer diagnosed between 1980 and 1998 who survived at least 5 years after diagnosis. Of the 1,134 patients, 264 were treated with external radiotherapy. Patients were followed for occurrence of colorectal cancer up to 31 December, 2003. We calculated standardized incidence ratios (SIR) using incidence rates for the general population to obtain the expected cancer incidence. The cohort yielded to 3,798 person‐years. At the end of follow‐up 19 patients had developed a colorectal cancer. Among irradiated patients the SIR for colorectal cancer was 3.4 (95% confidence intervals [CI] 1.7–6.0). Compared to the general population, the risk was significantly higher for colon cancer (SIR = 4.0, 95% CI: 1.8–7.6), but not for rectal cancer (SIR = 2.0, 95% CI: 0.2–7.2). The risk of colon cancer was increased in the period of 5–9 years after diagnosis (SIR = 4.7, 95% CI: 2.0–9.2). The overall SIR of secondary cancer in patients treated with radiotherapy was 1.35 (p = 0.056). Nonirradiated patients did not have any increased risk of rectal or colon cancer. This study shows a significant increase of colon but not rectum cancer after radiotherapy for prostate cancer. The risk of second cancer after irradiation, although probably small, needs nevertheless to be carefully monitored. © 2008 Wiley‐Liss, Inc.
Podoplanin expression by cancer associated fibroblasts predicts poor prognosis of lung adenocarcinoma
Authors: Kawase Akikazu , Ishii Genichiro , Nagai Kanji , Ito Takeo , Nagano Tatsuya , Murata Yukinori , Hishida Tomoyuki , Nishimura Mitsuyo , Yoshida Junji , Suzuki Kazuya , Ochiai Atsushi
Published: June 2008

Recent studies have reported increased podoplanin expression by cancer cells and stromal cells, but little is known about its expression and biological significance in adenocarcinoma of the lung. We examined podoplanin expression by both cancer cells and stromal cells in 177 consecutive lung adenocarcinoma cases and analyzed relations between podoplanin expression and both clinicopathological factors and outcome. Podoplanin expression was observed on the apical membrane of the cancer cells in only 9 of the 177 (5.1%) cases. By contrast, cancer‐associated fibroblasts (CAFs) were found to express podoplanin in 54 cases (30.5%). Podoplanin (+) CAFs were found only in invasive adenocarcinoma and none were found in noninvasive adenocarcinoma. Conventional prognostic factors were significantly correlated with podoplanin expression by CAFs. The univariate analyses and log‐rank test showed that podoplanin expression was significantly associated with shorter survival time (p < 0.001 and p < 0.001, respectively). We divided the cases into 3 groups according grade based on the proportion of CAFs expressing podoplanin [a grade 0 group (n = 123), a grade 1 group (n = 36) and a grade 2 group (n = 18)]. The result showed that conventional prognostic factors were significantly correlated with the grade of podoplanin expression by CAFs. Furthermore, the grade 2 group tended to have a shorter survival time than the grade 1 group (p = 0.092). The results of this study highlight the importance of podoplanin expression by CAFs and provide new insights into the biology of the cancer microenvironment in adenocarcinoma of the lung. © 2008 Wiley‐Liss, Inc.
Prospective weight change and colon cancer risk in male US health professionals
Authors: Thygesen Lau Caspar , Grønbæk Morten , Johansen Christoffer , Fuchs Charles S. , Willett Walter C. , Giovannucci Edward
Published: June 2008

Epidemiological studies are remarkably consistent, especially among men, in showing that overweight and obesity [body mass index (BMI) >25] are associated with increased risk of colon cancer. However, no prospective studies address the influence of weight change in adulthood on subsequent colon cancer risk. In this study, we investigated whether weight change influences colon cancer risk utilizing prospectively collected weight data. We included 46,349 men aged 40–75 participating in the Health Professionals Follow‐Up Study. Questionnaires including items on weight were completed every second year during follow‐up from 1986 to 2004. Updated weight change between consecutive questionnaires during follow‐up and recalled weight gain since age 21 was evaluated. All eligible men were cancer‐free at baseline. Proportional hazard and restricted spline regression models were implemented. Over an 18‐year period, we documented 765 cases of colon cancer. Cumulative mean BMI >22.5 was associated with significantly increased risk of colon cancer. The short‐term weight change in the prior 2 to 4 years was positively and significantly associated with risk [HR = 1.14 (95% confidence interval, 1.00–1.29) for 4.54 kg (10 pounds) increment, p = 0.04 for overall trend]. Weight gain per 10 years since age 21 was associated with significantly increased risk [HR = 1.33 (1.12–1.58) for 4.54 kg increase per 10 years, p = 0.001]. We estimated that 29.5% of all colon cancer cases was attributable to BMI above 22.5. Our results add support that overweight and obesity are modifiable risk factors for colon cancer among men and suggest that weight has an important influence on colon cancer risk even in later life. © 2008 Wiley‐Liss, Inc.
Spontaneous T cell responses to Epstein‐Barr virus‐encoded BARF1 protein and derived peptides in patients with nasopharyngeal carcinoma: Bases for improved immunotherapy
Authors: Martorelli Debora , Houali Karim , Caggiari Laura , Vaccher Emanuela , Barzan Luigi , Franchin Giovanni , Gloghini Annunziata , Pavan Alessandro , Da Ponte Alessandro , Tedeschi Rosa Maria , De Re Valli , Carbone Antonino , Ooka Tadamasa , De Paoli Paolo , Dolcetti Riccardo
Published: June 2008

Immunotherapy approaches targeting Epstein‐Barr virus (EBV)‐encoded antigens induce objective clinical responses only in a fraction of patients with undifferentiated nasopharyngeal carcinoma (UNPC). In the present study, we have characterized the immunogenicity of the EBV‐encoded BARF1 oncogene with the aim to assess whether this protein could constitute a new target antigen for immunotherapy in this setting. Spontaneous CD4+ and CD8+ T cell responses specific for the recombinant p29 BARF1 protein were detected by IFNγ‐ELISPOT in both EBV‐seropositive donors and UNPC patients, but not in EBV‐seronegative individuals. Using immunoinformatic prediction tools, we have selected 5 different candidate BARF1 T cell epitopes presented by HLA‐A*0201. Although only one of these peptides was able to bind HLA‐A2 with low affinity in the T2 stabilization assay, all 5 BARF1 nonamers readily elicited specific CD8+ T cell responses in EBV‐seropositive HLA‐A*0201+ donors and UNPC patients. Notably, the magnitude of CD8+ T cell responses to the whole BARF1 protein and derived A*0201 peptides was significantly higher in UNPC patients than in healthy donors. Moreover, cytotoxic T lymphocytes specific for the p2–10, p23–31, or p49–57 BARF1 peptides were easily obtained from HLA‐A*0201+ donors. These cultures were not only able to lyse autologous targets loaded with the antigenic peptide, but also recognized tumor cells endogenously expressing BARF1 in an antigen‐specific and HLA‐A2‐restricted manner. These findings, indicate that BARF1 is a particularly attractive antigen with immunogenic properties in most UNPC patients and provide valuable information to develop new strategies to improve the efficacy of EBV‐targeting immunotherapy of UNPC patients. © 2008 Wiley‐Liss, Inc.
Breast cancer‐derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: Implication for breast cancer osteolytic bone metastases
Authors: Bu Guojun , Lu Wenyan , Liu Chia‐Chen , Selander Katri , Yoneda Toshiyuki , Hall Christopher , Keller Evan T. , Li Yonghe
Published: June 2008

Most breast cancer metastases in bone form osteolytic lesions, but the mechanisms of tumor‐induced bone resorption and destruction are not fully understood. Although it is well recognized that Wnt/β‐catenin signaling is important for breast cancer tumorigenesis, the role of this pathway in breast cancer bone metastasis is unclear. Dickkopf1 (Dkk1) is a secreted Wnt/β‐catenin antagonist. In the present study, we demonstrated that activation of Wnt/β‐catenin signaling enhanced Dkk1 expression in breast cancer cells and that Dkk1 overexpression is a frequent event in breast cancer. We also found that human breast cancer cell lines that preferentially form osteolytic bone metastases exhibited increased levels of Wnt/β‐catenin signaling and Dkk1 expression. Moreover, we showed that breast cancer cell‐produced Dkk1 blocked Wnt3A‐induced osteoblastic differentiation and osteoprotegerin (OPG) expression of osteoblast precursor C2C12 cells and that these effects could be neutralized by a specific anti‐Dkk1 antibody. In addition, we found that breast cancer cell conditioned media were able to block Wnt3A‐induced NF‐kappaB ligand reduction in C2C12 cells. Finally, we demonstrated that conditioned media from breast cancer cells in which Dkk1 expression had been silenced via RNAi were unable to block Wnt3A‐induced C2C12 osteoblastic differentiation and OPG expression. Taken together, these results suggest that breast cancer‐produced Dkk1 may be an important mechanistic link between primary breast tumors and secondary osteolytic bone metastases. © 2008 Wiley‐Liss, Inc.
Infrequent promoter methylation of the MGMT gene in liver metastases from uveal melanoma
Authors: Voelter Verena , Diserens Annie‐Claire , Moulin Alexandre , Nagel Georg , Yan Pu , Migliavacca Eugenia , Rimoldi Donata , Hamou Marie‐France , Kaina Bernd , Leyvraz Serge , Hegi Monika E.
Published: June 2008

Uveal melanoma is associated with a high mortality rate once metastases occur, with over >90% of metastatic patients dying within less than 1 year from metastases to the liver. The intraarterial hepatic (iah) administration of the alkylating agent fotemustine holds some promise with response rates of 36% and median survival of 15 months. Here, we investigated whether the DNA‐repair‐protein MGMT may be involved in the variability of response to fotemustine and temozolomide in uveal melanoma. Epigenetic inactivation of MGMT has been demonstrated to be a predictive marker for benefit from alkylating agent therapy in glioblastoma. We found a methylated MGMT promoter in 6% of liver metastases from 34 uveal melanoma patients. The mean MGMT activity measured in liver metastases with negligible liver tissue content was significantly lower than in liver tissue (146 versus 523 fmol/mg protein, p = 0.002). Expression of the MGMT protein was detectable in 50% of 88 metastases by immunohistochemistry on a tissue microarray. Expression was heterogeneous, and in accordance with MGMT activity data, usually lower than in the surrounding liver. Differential MGMT activity/expression between metastasis and liver tissue and more efficient depletion of MGMT with higher doses of alkylating agent therapy using iah delivery may provide the pharmacologic window for the higher response rate. However, these results do not support MGMT methylation status or protein expression as predictive markers for treatment outcome to iah chemotherapy with alkylating agents. © 2008 Wiley‐Liss, Inc.