bluuebunny/crossref_metadata_2025 huggingface dataset:
Cooperation of Ras‐ and c‐Myc–dependent pathways in regulating the growth and invasiveness of synovial fibroblasts in rheumatoid arthritis
Authors: Pap Thomas , Nawrath Michael , Heinrich Jochen , Bosse Magnus , Baier Anja , Hummel Klaus M. , Petrow Peter , Kuchen Stefan , Michel Beat A. , Gay Renate E. , Müller‐Ladner Ulf , Moelling Karin , Gay Steffen
Published: September 2004

Objective

To study the specific contribution of MAP kinase activator c‐Raf‐1 and one of its downstream transcription factors, c‐Myc, to the growth and invasive behavior of rheumatoid arthritis synovial fibroblasts (RASFs).

Methods

RASFs were transduced with retroviral constructs expressing dominant‐negative mutants of c‐Raf‐1 or c‐Myc (DN c‐Raf‐1 or DN c‐Myc, respectively) or with the mock vector. The expression of wild‐type and mutant proteins was confirmed by Western blotting. Growth curves of RASFs were recorded, and apoptosis was measured by flow cytometry. Invasiveness of RASFs was assessed in the SCID mouse model of RA. Immunohistochemistry was used to study the effects of DN c‐Raf‐1 on phosphorylated c‐Jun and matrix metalloproteinase 1 (MMP‐1) in RASFs implanted into SCID mice. The phosphorylation of ERK and JNK in DN c‐Raf‐1– and mock‐transduced RASFs was determined in vitro by Western blotting. The levels of MMPs in these cells were measured by quantitative polymerase chain reaction (PCR).

Results

Neither DN c‐Raf‐1 alone nor DN c‐Myc alone significantly altered proliferation or apoptosis of RASFs, but both mutants together rapidly induced apoptosis. Inhibition of c‐Raf‐1 or c‐Myc significantly reduced the invasiveness of RASFs in the SCID mouse model. DN c‐Raf‐1 decreased the phosphorylation of ERK and JNK in vitro and reduced the in vivo expression of phosphorylated c‐Jun as well as the expression of disease‐relevant MMPs. As determined by quantitative PCR, the inhibition was most pronounced for MMP‐1 and MMP‐3.

Conclusion

The data demonstrate that Ras‐ and c‐Myc–dependent signaling events cooperate to regulate the growth and invasiveness of RASFs. Targeting of both c‐Raf‐1 and c‐Myc may constitute an interesting therapeutic approach in RA.
Successful treatment of SAPHO syndrome with zoledronic acid
Authors: Kopterides Petros , Pikazis Dimitrios , Koufos Christos
Published: September 2004

The SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a chronic, relapsing, inflammatory condition with skin and osteoarticular manifestations. Its etiology remains unclear, and various treatment regimens with steroids and nonsteroidal antiinflammatory drugs frequently fail to control the disease, while exposing patients to the side effects of these drugs. Because the SAPHO syndrome manifests as a destructive inflammatory bone disease, use of bisphosphonates that possess antiosteoclastic and probably antiinflammatory properties has been suggested to be helpful. To our knowledge, this is the first reported case of successful treatment with zoledronic acid of SAPHO syndrome that was resistant to conventional treatment.
Antineutrophil cytoplasmic antibodies reacting with human neutrophil elastase as a diagnostic marker for cocaine‐induced midline destructive lesions but not autoimmune vasculitis
Authors: Wiesner Olaf , Russell Kimberly A. , Lee Augustine S. , Jenne Dieter E. , Trimarchi Matteo , Gregorini Gina , Specks Ulrich
Published: September 2004

Objective

Human neutrophil elastase (HNE) and proteinase 3 (PR3) are structurally and functionally related. PR3 is the prominent target antigen for antineutrophil cytoplasmic antibodies (ANCAs) in Wegener's granulomatosis (WG). Reported frequencies of HNE ANCAs in WG and other autoimmune diseases range from 0% to 20%. We previously detected HNE ANCAs in patients with cocaine‐induced midline destructive lesions (CIMDL). We tested the hypothesis that discrepancies in the reported frequencies of HNE ANCAs in patients with vasculitis may be related to differences in detection methods, and that HNE ANCA may be a marker for CIMDL.

Methods

HNE ANCA reactivity in 25 patients with CIMDL was characterized and compared with that in a control cohort of 604 consecutive patients (64 with WG, 14 with microscopic polyangiitis [MPA], and 526 others) and 45 healthy volunteers. HNE ANCAs were measured by indirect immunofluorescence using a previously undescribed expression system for recombinant HNE and by direct and capture enzyme‐linked immunosorbent assays using purified native HNE as target antigen.

Results

Among patients with CIMDL, HNE ANCAs were detectable by 1 assay in 84%, by 2 assays in 68%, and by all 3 assays in 36%. Fifty‐seven percent of HNE ANCA–positive CIMDL sera were also PR3 ANCA–positive by at least 1 assay. In contrast, only 8 (1.3%) of 604 control sera reacted with HNE in at least 1 assay, 3 (0.5%) reacted in 2 assays, and only 1 serum sample (0.16%) reacted in all 3 assays. Sera obtained from patients with WG or MPA were universally HNE ANCA–negative, as were sera obtained from healthy controls.

Conclusion

Optimal sensitivity for HNE ANCA requires multimodality testing. HNE ANCAs are frequent in CIMDL but not in other autoimmune diseases, including classic ANCA‐associated vasculitis. HNE ANCAs may discriminate between CIMDL and WG, whereas a positive test result for PR3 ANCA may not.
Design of bioactive and structurally well‐defined peptides from conformationally restricted libraries
Authors: Pastor M. Teresa , Mora Puig , Ferrer‐Montiel Antonio , Pérez‐Payá Enrique
Published: September 2004

Libraries of peptides and proteins can be categorized according to the function of their origin in gene‐ and synthetic‐based libraries. Both kinds of libraries have the potential to generate the same grade of molecular diversity, although the limits imposed by the synthetic methods have been lately a matter of discussion. However, the use of synthetic strategies allows incorporation of non‐natural amino acids. The development of conformationally restricted synthetic peptide libraries can be considered as a point of convergence of the two methodologies. In these libraries the diversity is grafted into scaffolds that are defined by stable secondary structural motifs, and the deconvolution protocols can be directed towards the identification of biologically active molecules and the analysis of determinants of folding of protein domains. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004
Ligand‐Binding Modes in Cationic Biogenic Amine Receptors
Authors: Ishiguro Masaji
Published: September 2004

The binding site in G protein‐coupled cationic biogenic amine receptors is formed in the cleft of the seven transmembrane segments. Upon binding the ligand, the receptors are activated or inactivated through the conformational changes of the transmembrane segments. G protein‐coupled receptors bind four functionally distinct ligands; inverse agonists, antagonists, partial agonists, and full agonists. Hence, putative structural models for biogenic amine receptors corresponding to the ligand function (inverse agonist‐, antagonist‐, partial agonist‐, and full agonist‐bound receptor models) were built by using photointermediate models in the rhodopsin photocascade (M. Ishiguro et al. ChemBioChem. 2004, 5, 298–310). The ligand–receptor recognition of each was examined by modeling receptor–ligand complexes with functional ligands. The complex models suggested that each functional ligand binds the corresponding receptor structure and that ligand‐specific interactions contribute to stabilization of the corresponding receptor structure.
An Approach towards the Quantitative Structure–Activity Relationships of Caffeic Acid and its Derivatives
Authors: Verma Rajeshwar P. , Hansch Corwin
Published: September 2004

Caffeic acid and its derivatives are already known to possess a wide range of biological activities. We have developed quantitative structure–activity relationships (QSARs) for different series of caffeic acid derivatives (including caffeic acid) in order to understand the chemical–biological interactions governing antitumor activity against six different tumor cell lines, nitric oxide production, anti‐HIV and enzymatic activities, and binding affinity to the lck domain. QSAR results have shown that the different activities of caffeic acid and its derivatives are largely dependent on their hydrophobicity or molar refractivity, with a bilinear correlation being the most important.
Understanding the Molecular Mechanism of the 1,3‐Dipolar Cycloaddition between Fulminic Acid and Acetylene in Terms of the Electron Localization Function and Catastrophe Theory
Authors: Polo Victor , Andres Juan , Castillo Raquel , Berski Slawomir , Silvi Bernard
Published: September 2004

The potential‐energy profile of the 1,3‐dipolar cycloaddition of fulminic acid and ethyne has been investigated theoretically within the framework provided by the electron localization function (ELF) analysis. This has been achieved by carrying out density functional theory (B3 LYP approach) calculations using the bonding evolution theory. Eight different domains of structural stability have been identified along the reaction path, as well as the bifurcation catastrophes responsible for the changes in the topology of the system. The analysis provides a chemical description of the reaction mechanism in terms of heterolytic concerted nonsynchronous bond formation: the first four catastrophes enable the simultaneous formation of the CC bond and a lone pair on the nitrogen atom, whereas the remaining ones lead to the ring closure. The valence basin populations calculated along the reaction path do not support any mechanism involving pentavalent nitrogen. The simulation of the solvent effect, by means of a continuum model, does not indicate any significant difference of the mechanism of reaction between the gas phase and solution.
Efficient Synthesis and Structure—Activity Relationship of Honokiol, a Neurotrophic Biphenyl‐Type Neolignan.
Authors: Esumi Tomoyuki , Makado Gouki , Zhai Haifeng , Shimizu Yasuhiro , Mitsumoto Yasuhide , Fukuyama Yoshiyasu
Published: September 2004

For Abstract see ChemInform Abstract in Full Text.
The Development of A3‐Coupling (Aldehyde‐Alkyne‐Amine) and AA3‐Coupling (Asymmetric Aldehyde‐Alkyne‐Amine)
Authors: Wei Chunmei , Li Zigang , Li Chao‐Jun
Published: September 2004

For Abstract see ChemInform Abstract in Full Text.
Evidence that certain retinal bipolar cells use both glutamate and GABA
Authors: Kao Yen‐Hong , Lassová Luisa , Bar‐Yehuda Tehilla , Edwards Robert H. , Sterling Peter , Vardi Noga
Published: September 2004

Retinal bipolar neurons release the excitatory transmitter, glutamate. However, certain bipolar cells contain GABA, raising the question whether a neuron might release both transmitters and, if so, what function might the inhibitory transmitter play in a particular circuit? Here we identify a subset of cone bipolar cells in cat retina that contain glutamate, plus its vesicular transporter (VGLUT1), and GABA, plus its synthetic enzyme (GAD65) and its vesicular transporter (VGAT). These cells are negative for a marker of ON bipolar cells and restrict their axons to the OFF strata of the inner synaptic layer. They do not colocalize with the neurokinin 3 receptor that stains a type (or two) of OFF bipolar cells. By “targeted injection,” we identified two types of OFF bipolar cell with the machinery to make and package both transmitters. One of these types costratifies with a dopamine plexus. J. Comp. Neurol. 478:207–218, 2004. © 2004 Wiley‐Liss, Inc.
Collapse load factor of planar frames using a modified genetic algorithm
Authors: Kaveh A. , Khanlari K.
Published: September 2004

In this article an analytical method is developed for identifying basic collapse mechanisms of rigid‐jointed two‐dimensional frames. In this approach, the deformation of each member is completely defined by four translations and one rotation. The behaviour of such an element lies in between that of a truss element and a flexural one.

Once the basic collapse mechanisms are identified, the genetic algorithm is used to identify the mechanism corresponding to the least possible load factor. Examples are included to illustrate the efficiency of the present method compared to the use of a simple genetic algorithm. Copyright © 2004 John Wiley & Sons, Ltd.
Eco‐psychological profiling: an oil company example
Authors: Ketola Tarja
Published: September 2004

When organizational image is being challenged, use of psychological defences may become excessive. In this paper 18 defences that appeared in an oil company during an oil spill are studied. All defences except sublimation contributed to the deterioration of corporate image. Sublimation allowed the company to take responsibility. Other defences simply put off facing the truth.

 The selection of defences used during crises reveals organizations' true personalities. Twelve different organizational personality types are discussed. Use of certain defences leads to the development of a neurotic personality. The case company turned out to be normally and neurotically demanding, paranoid, narcissistic and attention seeking, and normally depressive. Organizations constantly using primitive defences are borderline personalities. Excessively defensive organizations may turn psychotic.

 The case company's reactions to the incident were psychologically revealing. Finding defences characteristic of the company allowed us to build its eco‐psychological profile. Based on this case study an eco‐psychological profiling model is proposed. Copyright © 2004 John Wiley & Sons, Ltd and ERP Environment.
Atomic Layer Deposition of Ruthenium Thin Films from Ru(thd)3 and Oxygen
Authors: Aaltonen T. , Ritala M. , Arstila K. , Keinonen J. , Leskelä M.
Published: September 2004

Ruthenium thin films were grown by atomic layer deposition (ALD) from tris(2,2,6,6‐tetramethyl‐3,5‐heptanedionato)ruthenium [Ru(thd)3] and oxygen, at temperatures between 325 °C and 450 °C. All the films were polycrystalline metallic ruthenium as analyzed by X‐ray diffraction (XRD). Impurity contents of the films (< 2.9 at.‐% H, < 1.9 at.‐% C, and < 5.5 at.‐% O) were nearly independent of the Ru(thd)3 pulse time as analyzed by time of flight elastic recoil detection analysis (TOF‐ERDA). The films had resistivities below 20 μΩ cm and they adhered well to a thin Al2O3 film on glass. Growth rates of 0.36 Å per cycle were obtained at a deposition temperature of 350 °C. The gaseous reaction by‐products were analyzed in situ by quadrupole mass spectrometry (QMS).
On the performance of recursive space–frequency codes and iterative decoding in wideband OFDM‐MIMO systems: simulated and measured results
Authors: Fletcher Paul N. , McNamara Darren P. , Piechocki Robert J. , Nix Andrew R. , Dean Michael
Published: September 2004

In this paper, we study the performance of a bandwidth efficient space–frequency turbo encoding scheme over wideband channels. Results are presented for simulated wideband MIMO channels consisting of two transmit antennas and up to two receive antennas. In addition, wideband channel measurements undertaken with practical multi‐element antenna structures at both the access point (AP) and mobile terminal (MT) are presented. Analysis is in terms of channel capacity, 10% channel outage capacity and space–frequency iterative decoding for an lEEE802.11a physical layer complaint modem. It is shown when operating with a spectral efficiency of 1.2 bits/s/Hz, the iterative decoded space–time codes comes within approximately 4.7 dB of 10% outage capacity over Rayleigh fading wideband channels with two transmit and two receive antennas. Over measured channels the iterative decoding scheme performs within 7.7 dB 10% of outage capacity. Losses due to channel state information estimation are also investigated. Copyright © 2004 John Wiley & Sons, Ltd.
A new delay‐constrained algorithm for multicast routing tree construction
Authors: Aissa Mohamed , Ben Mnaouer Adel
Published: September 2004

New multimedia applications provide guaranteed end‐to‐end quality of service (QoS) and have stringent constraints on delay, delay‐jitter, bandwidth, cost, etc. The main task of QoS routing is to find a route in the network, with sufficient resources to satisfy the constraints. Most multicast routing algorithms are not fast enough for large‐scale networks and where the source node uses global cost information to construct a multicast tree. We propose a fast and simple heuristic algorithm (EPDT) for delay‐constrained routing problem for multicast tree construction. This algorithm uses a greedy strategy based on shortest‐path and minimal spanning trees. It combines the minimum cost and the minimum radius objectives by combining respectively optimal Prim's and Dijkstra's algorithms. It biases routes through destinations. Besides, it uses cost information only from neighbouring nodes as it proceeds, which makes it more practical, from an implementation point of view. Copyright © 2004 John Wiley & Sons, Ltd.
Reading comprehension and reading related abilities in adolescents with reading disabilities and attention‐deficit/hyperactivity disorder
Authors: Ghelani Karen , Sidhu Robindra , Jain Umesh , Tannock Rosemary
Published: September 2004

Reading comprehension is a very complex task that requires different cognitive processes and reading abilities over the life span. There are fewer studies of reading comprehension relative to investigations of word reading abilities. Reading comprehension difficulties, however, have been identified in two common and frequently overlapping childhood disorders: reading disability (RD) and attention‐deficit/hyperactivity disorder (ADHD). The nature of reading comprehension difficulties in these groups remains unclear. The performance of four groups of adolescents (RD, ADHD, comorbid ADHD and RD, and normal controls) was compared on reading comprehension tasks as well as on reading rate and accuracy tasks. Adolescents with RD showed difficulties across most reading tasks, although their comprehension scores were average. Adolescents with ADHD exhibited adequate single word reading abilities. Subtle difficulties were observed, however, on measures of text reading rate and accuracy as well as on silent reading comprehension, but scores remained in the average range. The comorbid group demonstrated similar difficulties to the RD group on word reading accuracy and on reading rate but experienced problems on only silent reading comprehension. Implications for reading interventions are outlined, as well as the clinical relevance for diagnosis. Copyright © 2004 John Wiley & Sons, Ltd.
The (Chloromethyl)dihalosilanes X2HSiCH2Cl (X = F, Cl, Br, I): Synthesis, Multinuclear NMR Spectroscopy and Rotational Isomerism Examined by Raman Spectroscopy
Authors: Hassler Karl , Hummeltenberg Reinhard , Tekautz Günter
Published: September 2004

(Chloromethyl)diphenylsilane Ph2HSiCH2Cl (1) was prepared from Ph2SiHCl and LiCH2Cl, in situ, and was then treated with CF3SO3H/LiCl and CF3SO3H/LiBr to give the (chloromethyl)dihalosilanes Cl2HSiCH2Cl (2) and Br2HSiCH2Cl (3). I2HSiCH2Cl (4) was formed quantitatively in a protodearylation reaction between liquid hydrogen iodide and 1. Fluorination of 4 with ZnF2 gave F2HSiCH2Cl (5), albeit in low yields. Compounds 1−5 were characterised by multinuclear NMR spectroscopy (29Si, 13C, 19F) and vibrational spectroscopy. The temperature‐dependent vibrational Raman spectra of 2, 3 and 4 prove that they are mixtures of gauche and anti rotamers in the liquid state. Enthalpy differences, ΔH (Hanti − Hgauche), were determined for the liquids by applying the van’t Hoff relation, with the gauche rotamer being lower in energy for 3 and 4, and the anti rotamer for 2. The vibrational spectra were assigned with the help of ab initio calculations of equilibrium geometries and harmonic fundamental frequencies. Harmonic symmetry force constants and potential energy distributions were calculated from the ab initio Hessian matrices. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Chemical Vapor Deposition of Niobium Disulfide Thin Films
Authors: Carmalt Claire J. , Peters Emily S. , Parkin Ivan P. , Manning Troy D. , Hector Andrew L.
Published: September 2004

Atmospheric pressure chemical vapor deposition (APCVD) of niobium sulfide coatings was achieved on glass substrates from the reaction of NbCl5 and S(SiMe3)2, tBu2S2, tBuSH, or HSCH2CH2SH at 250−600 °C. The niobium sulfide films grown at temperatures above 500 °C were crystalline, and powder X‐ray diffraction showed that two polytypes of NbS2 were produced. The sulfur precursor used is fundamental to the polytype of NbS2 obtained; films that are grown from the APCVD reaction of NbCl5 and S(SiMe3)2 or tBu2S2 at 500−600 °C crystallize into the 1T structure, whereas those grown from the APCVD reaction of NbCl5 and tBuSH or HSCH2CH2SH at 500−600 °C crystallize into the 3R structure. Energy dispersive X‐ray analysis (EDXA) studies gave elemental ratios close to the expected 1:2 ratio for Nb:S. Scanning electron microscopy (SEM) revealed surface morphologies consistent with an island growth mechanism. The films were also characterized using Raman and X‐ray photoelectron spectroscopy, both of which showed differences consistent with the formation of the two polytypes, 1T and 3R‐NbS2. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Tetranuclear Copper(II) and Nickel(II) Complexes Incorporating a New Imidazole‐Containing Ligand
Authors: Mukherjee Soumen , Weyhermüller Thomas , Bill Eckhard , Chaudhuri Phalguni
Published: September 2004

The ligating properties of a new tridentate imidazole‐ and phenol‐containing ligand H3L towards nickel(II) and copper(II) ions have been studied. The ligand generates, in the presence of air and base, iminosemiquinone radical anions, which are not stable in the presence of the metal ions. The amine bond >C−NH− of the parent ligand becomes oxidized to >C=N− bonds upon coordination with NiII or CuII. The imidazole N atom becomes deprotonated and the resulting imidazolate group acts as a bridging ligand to generate tetranuclear complexes [CuII4L′4] and [NiII4L′4], where [L′]2− is the dianionic new Schiff base formed after oxidation of the parent ligand. The square‐planar tetranickel(II) complex is diamagnetic, as expected, whereas the four copper centres bridged by imidazolate anions in the complex [CuII4L′4] are antiferromagnetically exchange coupled (J = −49 cm−1), which has been supported by the EPR measurements. A simple magnetostructural correlation for the imidazolate‐bridged copper(II) complexes is yet to emerge. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Structural Variety and Multiple Isomerism in 1‐(Dimethylamino)propyl‐2‐chalcogenolate and 2‐(Dimethylamino)propyl‐1‐chalcogenolate Complexes of Palladium(II) and Platinum(II): Synthesis, Spectroscopy and Structures
Authors: Dey Sandip , Kumbhare Liladhar B. , Jain Vimal K. , Schurr Thilo , Kaim Wolfgang , Klein Axel , Belaj Ferdinand
Published: September 2004

Isomeric dichalcogenides [Me2NCH(Me)CH2E]2[(N∩E**)2] and [Me2NCH2CH(Me)E]2[(N∩E*)2] (E = S, Se, Te) have been obtained by the reactions of NaSH or M′2E2(M′ = Na or K) with Me2NCH2CHMeCl. The former reaction affords mainly (N∩E**)2(E = S) while from the latter mixtures of (N∩E**)2and (N∩E*)2[referred to as (N∩E)2, E = S, Se, Te] were isolated, the ratios in the mixtures depending on the chalcogen. Reactions of (N∩E)Na with [M2Cl2(μ‐Cl)2(PR3)2] gave complexes [MCl(N∩E)(PR3)] (M = Pd or Pt). These chiral, mixed‐ligand complexes have been characterised by elemental analysis, IR, UV/Vis and NMR (1H,13C,31P,77Se,125Te,195Pt) spectroscopy, and, in part, by X‐ray structure analysis. The complexes display a typical pattern of mutuallytrans‐oriented neutral (P and N) and anionic (Cl and E) donor atoms in an approximately square‐planar environment. In contrast to the platinum(II) analogues, the X‐ray structures of the complexes [PdCl(N∩E)(PMePh2)] (E = S or Se) revealed both a conformational isomerism of the five‐membered chelate ring and, for Se, the co‐crystallisation of complexes with both the N∩E* and N∩E** isomeric ligands. The thermal behaviour of some complexes has been investigated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Differential temperature regulation of three sunflower microsomal oleate desaturase (FAD2) isoforms overexpressed in Saccharomyces cerevisiae
Authors: Sánchez‐García Alicia , Mancha Manuel , Heinz Ernst , Martínez‐Rivas José M.
Published: September 2004

The oxygen‐independent temperature regulation of three sunflower microsomal oleate desaturase (FAD2) isoforms has been investigated using Saccharomyces cerevisiae cells expressing each FAD2 gene. Yeast cells transformed with the FAD2‐1 gene showed the highest percentage of dienoic acids when they were grown at 10–15 °C. In contrast, the maximal level of dienoic acids for S. cerevisiae cells expressing the FAD2‐2 and FAD2‐3 genes were obtained at 30 and 35 °C, respectively. Temperature shifts in the phase of exponential growth, from 30 to 15 °C or from 15 to 30 °C, produced changes in the final percentage of dienoic acids, mostly in yeast cells transformed with the FAD2‐1 gene, to reach the content corresponding to the new temperature. Low temperature (15 °C) increased the amount of neutral lipids in all transformed yeast cells, mainly because it favored triacylglycerol accumulation. In addition, the FAD2‐expressing yeast cells showed a higher polar lipid content than those transformed with the empty vector. Dienoic acids were present in all lipids, although high temperature (30 °C) favored their accumulation in neutral lipids. As the main conclusion, the low thermal stability observed for the major and seed specific isoform (FAD2‐1) is the key factor controlling the direct temperature regulation in sunflower seeds.
Voice perception: Sex, pitch, and the right hemisphere
Authors: Lattner Sonja , Meyer Martin E. , Friederici Angela D.
Published: September 2004

The present functional magnetic resonance imaging (fMRI) study examined the neurophysiological processing of voice information. The impact of the major acoustic parameters as well as the role of the listener's and the speaker's gender were investigated. Male and female, natural, and manipulated voices were presented to 16 young adults who were asked to judge the naturalness of each voice. The hemodynamic responses were acquired by a 3T Bruker scanner utilizing an event‐related design. The activation was generally stronger in response to female voices as well as to manipulated voice signals, and there was no interaction with the listener's gender. Most importantly, the results suggest a functional segregation of the right superior temporal cortex for the processing of different voice parameters, whereby (1) voice pitch is processed in regions close and anterior to Heschl's Gyrus, (2) voice spectral information is processed in posterior parts of the superior temporal gyrus (STG) and areas surrounding the planum parietale (PP) bilaterally, and (3) information about prototypicality is predominately processed in anterior parts of the right STG. Generally, by identifying distinct functional regions in the right STG, our study supports the notion of a fundamental role of the right hemisphere in spoken language comprehension. Hum Brain Mapp 24:11–20, 2005. © 2004 Wiley‐Liss, Inc.
Deriving welfare measures from discrete choice experiments: inconsistency between current methods and random utility and welfare theory
Authors: Lancsar Emily , Savage Elizabeth
Published: September 2004

Discrete choice experiments (DCEs) are being used increasingly in health economics to elicit preferences for products and programs. The results of such experiments have been used to calculate measures of welfare or more specifically, respondents' ‘willingness to pay’ (WTP) for products and programs and their ‘marginal willingness to pay’ (MWTP) for the attributes that make up such products and programs. In this note we show that the methods currently used to derive measures of welfare from DCEs in the health economics literature are not consistent with random utility theory (RUT), or with microeconomic welfare theory more generally. The inconsistency with welfare theory is an important limitation on the use of such WTP estimates in cost–benefit analyses. We describe an alternative method of deriving measures of welfare (compensating variation) from DCEs that is consistent with RUT and is derived using welfare theory. We demonstrate its use in an empirical application to derive the WTP for asthma medication and compare it to the results elicited from the method currently used in the health economics literature. Copyright © 2004 John Wiley & Sons, Ltd.
The effect of welfare reform on prenatal care and birth weight
Authors: Kaestner Robert , Chan Lee Won
Published: September 2004

Welfare reform has resulted in a dramatic decline in welfare caseloads and some have claimed that a significant number of low‐income women may be without health insurance as a result. The loss of insurance may reduce low‐income, pregnant women's health care utilization, and this may adversely affect infant health. Welfare reform also may affect healthcare utilization and health of pregnant women and infants because of welfare‐induced changes in family disposable income, time available for health investments, and levels of stress. In this paper we examine the effect of welfare reform on prenatal care utilization and birth weight of low‐educated women and their infants. We find that a 50% reduction in the caseload, which is similar to that which occurred in the 1990s, is associated with a zero to seven percent decrease in first trimester prenatal care; a zero to five percent decrease in the number of prenatal care visits; and a zero to 10% increase in low birth weight. Since welfare reform was responsible for only part of the decline in the caseload, welfare reform per se had even smaller effects. Copyright © 2004 John Wiley & Sons, Ltd.
The effect of work on mental health: does occupation matter?
Authors: Llena‐Nozal Ana , Lindeboom Maarten , Portrait France
Published: September 2004

This paper considers the effect of work choices on mental health and looks at whether this differs across occupations. This requires a model that can deal with the endogeneity in the relationship between health, occupation and work choices. We specify such a model and estimate it on a unique UK panel survey. The survey, called the National Child development Survey (NCDS), follows a cohort since their birth in 1958 until age 42. The analyses show us that early childhood health and ability have long lasting consequences for the mental health at the later ages. Females have lower levels of mental health. Mental health deteriorates with age for males and females, but the rate of deterioration is substantially lower for females. We also find that the rate of depreciation is lower when individuals work. For females we find large effects of occupation, for males we do not find this. Employment status is important for males, but not for females. For both genders we find very large effects of the onset of a long‐standing illness. The probability of experiencing such an event depends on employment status, occupation and life style variables. Copyright © 2004 John Wiley & Sons, Ltd.
Warm glow, free‐riding and vehicle neutrality in a health‐related contingent valuation study
Authors: Hackl Franz , Pruckner Gerald J.
Published: September 2004

Criticism of contingent valuation (CV) stresses warm glow and free‐riding as possible causes for biased willingness to pay figures. We present an empirical framework to study the existence of warm glow and free‐riding in hypothetical WTP answers based on a CV survey for the measurement of health‐related Red Cross services. Both in conventional double‐bounded and spike models we do not find indication of warm glow phenomena and free‐riding behaviour. The results are very robust and insensitive to the applied payment vehicles. Theoretical objections against CV do not find sufficient empirical support. Copyright © 2004 John Wiley & Sons, Ltd.
What went where? Impaired object‐location learning in patients with right hippocampal lesions
Authors: Crane Joelle , Milner Brenda
Published: September 2004

The role of the right medial temporal‐lobe structures in memory for object location was investigated in three studies. In the first two studies, 118 patients with selective amygdalo‐hippocampectomy or with anterior temporal lobectomy (either invading or largely sparing the hippocampal region) and 33 healthy participants were tested on array learning. Groups with extensive right hippocampal lesions were impaired on immediate and delayed recall and on learning to criterion. In the third study, magnetic resonance imaging (MRI) was used in 75 of these patients to measure the extent of tissue remaining in the various medial temporal‐lobe structures. The extent of right hippocampus remaining was found to be the best predictor of array‐learning performance, underlining its critical role in building a representation of objects in space. © 2004 Wiley‐Liss, Inc.
Inhibition of Ras oncogenic activity by Ras protooncogenes
Authors: Diaz Roberto , Lue Jeffrey , Mathews Jeremy , Yoon Andrew , Ahn Daniel , Garcia‐España Antonio , Leonardi Peter , Vargas Marcelo P. , Pellicer Angel
Published: September 2004

Point mutations in ras genes have been found in a large number and wide variety of human tumors. These oncogenic Ras mutants are locked in an active GTP‐bound state that leads to a constitutive and deregulated activation of Ras function. The dogma that ras oncogenes are dominant, whereby the mutation of a single allele in a cell will predispose the host cell to transformation regardless of the presence of the normal allele, is being challenged. We have seen that increasing amounts of Ras protooncogenes are able to inhibit the activity of the N‐Ras oncogene in the activation of Elk in NIH 3T3 cells and in the formation of foci. We have been able to determine that the inhibitory effect is by competition between Ras protooncogenes and the N‐Ras oncogene that occurs first at the effector level at the membranes, then at the processing level and lastly at the effector level in the cytosol. In addition, coexpression of the N‐Ras protooncogene in thymic lymphomas induced by the N‐Ras oncogene is associated with increased levels of p107, p130 and cyclin A and decreased levels of Rb. In the present report, we have shown that the N‐Ras oncogene is not truly dominant over Ras protooncogenes and their competing activities might be depending on cellular context.
Localization of tissue inhibitor of metalloproteinases 1 (TIMP‐1) in human colorectal adenoma and adenocarcinoma
Authors: Holten‐Andersen Mads N. , Hansen Ulla , Brünner Nils , Nielsen Hans Jørgen , Illemann Martin , Nielsen Boye Schnack
Published: September 2004

Tissue inhibitor of matrix metalloproteases 1 (TIMP‐1) inhibits the proteolytic activity of matrix metalloproteases and hereby prevents cancer invasion. However, TIMP‐1 also possesses other functions such as inhibition of apoptosis, induction of malignant transformation and stimulation of cell‐growth. We have previously demonstrated that TIMP‐1 is elevated in blood from colorectal cancer patients and that high TIMP‐1 levels predict poor prognosis. To clarify the role of TIMP‐1 in colorectal tumorigenesis, the expression pattern of TIMP‐1 in benign and malignant colorectal tumors was studied. In all of 24 cases of colorectal adenocarcinoma TIMP‐1 mRNA was detected by in situ hybridization. In all cases TIMP‐1 expression was found in fibroblast‐like cells located at the invasive front but was seen only sporadically in normal mucosa. No TIMP‐1 mRNA was seen in any of the cases in benign or malignant epithelial cells, in vascular cells or smooth muscle cells. Comparison of sections processed for TIMP‐1 in situ hybridization with sections immunohistochemically stained with antibodies against TIMP‐1 showed good correlation between TIMP‐1 mRNA and immunoreactivity. Combining TIMP‐1 in situ hybridization with immunohistochemical staining for α‐smooth muscle actin or CD68 showed TIMP‐1 mRNA in myofibroblasts but not in macrophages. TIMP‐1 mRNA was detected in 2 of 7 adenomatous polyps in the adenoma area: in both cases associated with focal stromal inflammation at the epithelial‐stromal interface. In conclusion, TIMP‐1 expression is a rare event in benign human colon tissue but is highly expressed by myofibroblasts in association with invading colon cancer cells.
Fathers and families: Locating the ghost in the nursery
Authors: Barrows Paul
Published: September 2004

Infant mental‐health clinicians and researchers have tended to focus particularly on the mother–infant dyad and, in Fraiberg's terms, on the “ghosts” that the mother brings to the nursery. This article begins by reiterating the case for paying as much attention to the “ghosts” that the father brings if we are to maximize our therapeutic impact. It is argued further, however, that over and above the father's individual role, what is more critical for the developing infant's future mental health is the nature of the parental couple that he/she encounters. That is, it is the relationship between the parents and their interactions that creates the emotional climate into which the infant is born and that determines the nature of the “internal” parental couple that they in turn will acquire. It is argued that the couple's relationship therefore needs to be the primary focus for our therapeutic interventions. Clinical material is presented to illustrate these points.
The impact of college on character development
Authors: Astin Helen S. , Antonio Anthony Lising
Published: September 2004

The authors assess the kinds of college experience that affect students' development of character.
Citizenship development and the American college student
Authors: Sax Linda J.
Published: September 2004

This chapter explores civic commitment among college students and offers strategies for how colleges can best prepare students for a life as a caring and involved citizen.
Effects of collagen type on the behavior of adult canine annulus fibrosus cells in collagen–glycosaminoglycan scaffolds
Authors: Saad L. , Spector M.
Published: September 2004

The healing of intervertebral disc defects may be improved by the implantation of cell‐seeded collagen‐based scaffolds. The present study evaluated in vitro the effects of the collagen type (type I vs type II) from which the scaffolds were fabricated on the behavior of adult canine annulus fibrosus cell‐seeded collagen–glycosaminoglycan (GAG) scaffolds. Protein and GAG biosynthesis continued through the 8‐week period of the experiment, demonstrating the viability of the cells in type I and type II collagen–GAG scaffolds. Statistical analysis revealed no significant effect of the type of collagen that makes up the scaffold on the biosynthetic activity. For both scaffold types, the amount of retained newly synthesized proteins increased from 1 to 2 weeks and from 6 to the 8 weeks. In contrast, the rate of GAG retention increased to a maximum at 4 weeks for both types of scaffolds, then decreased to about 50% of that level after 8 weeks. The number of cells generally increased the first week but then decreased in type I scaffolds while remaining constant in type II scaffolds. It could be assumed that most newly synthesized protein was lost to the medium, as the quantity of protein and collagen remained constant. Cell‐mediated contraction of the scaffolds contributed to folds that formed in the constructs and to create an oriented architecture tissue. These findings commend the use of a type II collagen–GAG scaffold for further study on the basis of its maintenance of cell number and the slightly higher accumulated GAG content. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 233–241, 2004
To go or not to go: Migration of human mesenchymal progenitor cells stimulated by isoforms of PDGF
Authors: Fiedler Jörg , Etzel Nadine , Brenner Rolf E.
Published: September 2004

The recruitment of mesenchymal progenitor cells (MPCs) and their subsequent differentiation to osteoblasts is mandatory for bone development, remodeling, and repair. To study the possible involvement of platelet‐derived growth factor (PDGF) isoforms, primary human MPCs and osteogenic differentiated progenitor cells (dOB) were examined for chemotaxic response to homodimeric human platelet‐derived growth factor AA, ‐BB, and heterodimeric PDGF‐AB. The role of PDGF receptors was addressed by preincubation with PDGF receptor alpha and beta chain specific antibodies. Migration of MPCs, dOB, and primary osteoblasts (OB) was stimulated by the addition of rhPDGF‐AA, rhPDGF‐BB, and rhPDGF‐AB. The effect was highest in MPCs and for rhPDGF‐BB, and declining with osteogenic differentiation. Preincubation with the receptor alpha specific antibody decreased the CI to borderline values while pretreatment with the receptor beta specific antibody led to a complete loss of chemotactic response to PDGF isoforms. In control experiments, basal migration values and rhBMP‐2 as well as rxBMP‐4 induced chemotaxis of MPC were not influenced by the addition of receptor alpha or beta antibodies. Interestingly, without preincubation the parallel exposure of MPC to rhTGF‐β1 instantaneously leads to a selective loss of migratory stimulation by rhPDGF‐AA. The chemotactic effect of PDGF isoforms for primary human MPCs and the influence of osteogenic differentiation suggest a functional role for recruitment of MPCs during bone development and remodeling. Moreover, these observations may be useful for novel approaches towards guided tissue regeneration or tissue engineering of bone. © 2004 Wiley‐Liss, Inc.
CCAAT/enhancer binding protein δ (C/EBPδ) regulation and expression in human mammary epithelial cells: I. “Loss of function” alterations in the C/EBPδ growth inhibitory pathway in breast cancer cell lines
Authors: Sivko G.S. , DeWille J.W.
Published: September 2004

“Loss of function” alterations in growth inhibitory signal transduction pathways are common in cancer cells. In this study, we show that growth arrest (GA) treatments—serum and growth factor withdrawal and growth inhibitory IL‐6 family cytokines (Interleukin‐6 and Oncostatin M (OSM))—increase STAT3 phosphorylation (pSTAT3), increase CCAAT enhancer binding protein δ (C/EBPδ) gene expression and induce GA of primary, finite‐lifespan human mammary epithelial cells (HMECs), and immortalized breast cell lines (MCF‐10A and MCF‐12A). In contrast, serum and growth factor withdrawal from human breast cancer cell lines (MCF‐7, SK‐BR‐3, T‐47D, and MDA‐MB‐231) for up to 48 h induced a relatively modest increase in pSTAT3 levels and C/EBPδ gene expression and resulted in varying levels of GA. In most breast cancer cell lines, IL‐6 family cytokine treatment increased pSTAT3 levels and C/EBPδ gene expression, however, growth inhibition was cell line dependent. In addition to “loss of function” alterations in growth inhibitory pathways, breast cancer cell lines also exhibit “gain of function” alterations in growth signaling pathways. The Akt growth/survival pathway is constitutively activated in T‐47D and MCF‐7 breast cancer cells. The Akt inhibitor LY 294,002 significantly enhanced T‐47D growth inhibition by serum and growth factor withdrawal or IL‐6 family cytokine treatment. Finally, we show that activation of the pSTAT3/C/EBPδ growth control pathway is independent of estrogen receptor status. These results demonstrate that “loss of function” alterations in the pSTAT3/C/EBPδ growth inhibitory signal transduction pathway are relatively common in human breast cancer cell lines. Defective activation of the pSTAT3/ C/EBPδ growth inhibitory signal transduction pathway, in conjunction with constitutive activation of the Akt growth stimulatory pathway, may play a synergistic role in the etiology or progression of breast cancer. © 2004 Wiley‐Liss, Inc.
Comparison of conventional tube test technique and gel microcolumn assay for direct antiglobulin test: A large study
Authors: Novaretti M.C.Z. , Jens E. , Pagliarini T. , Bonifacio S.L. , Dorlhiac‐Llacer P.E. , Chamone D.A.F.
Published: September 2004

Gel microcolumn assay (GMA) is a modified serological technique that has been used for ABO and Rh typing, direct antiglobulin test (DAT), detecting alloantibodies, red cell phenotyping, and other applications. However, for DAT, the role of GMA is controversial. The purpose of this large study was to compare the performance of the conventional tube test (CTT) to GMA for detecting potentially significant antibodies coating red blood cells in vivo. From January 1996 to May 2002, we performed DATs by GMA and CTT on 9,862 blood samples submitted to our reference laboratory, using LISS/Coombs cards (DiaMed‐Latino America, Lagoa Santa‐MG, Brazil) for GMA and polyspecific and monospecific anti‐IgG reagents for CTT. Acid eluates were prepared from all positive DAT samples. The specificity of eluates was determined by GMA. We detected nonconcordant results in 2,079 out of 3,163 positive DATs (65.7%). All of these tests were only positive in GMA. Sensitivity and specificity for DATs was 100% and 83.0% for gel, and 50.7% and 97.8% for tube, respectively. Based on this study GMA showed to be more sensitive than CTT for detecting potentially significant antibodies coating red blood cells in vivo. J. Clin. Lab. Anal. 18:255–258, 2004. © 2004 Wiley‐Liss, Inc.
Pronto® ThromboRisk™—A novel primer‐extension ELISA based assay for the detection of mutations associated with increased risk for thrombophilia
Authors: Carmi Noga , Cohen Dana , Zvang Eti , Naparstek Elizabeth , Deutsch Varda
Published: September 2004

The role of inherited thrombophilias in the pathogenesis of thrombosis, and their relation to thromboembolic events and pregnancy complications, has escalated the demand for molecular testing. We employed the new Pronto® ThromboRisk™ kit (Pronto Diagnostics Ltd., Rehovot, Israel), which is based on a novel primer‐extension ELISA assay, for the simultaneous detection of three genetic mutations. These are Factor V Leiden G1691A (R506Q), prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T, which are known to have increased incidence in patients with thromboembolic events and pregnancy complications. We examined 284 randomly selected patient samples from the special coagulation hospital laboratory. The results using the new assay were compared to those obtained by routinely employed conventional molecular techniques. The ThromboRisk™ kit provided identical results with no false–negative results and with a high specificity of over 99% for all three mutations. We conclude that the Pronto® ThromboRisk™ kit allows fast, precise, and reliable testing for the three genetic mutations. The assay is easy to perform and provides a useful tool for screening high risk populations, such as patients with a personal or family history of venous thromboembolism, women with pregnancy complications, or users of oral contraceptives. J. Clin. Lab. Anal. 18:259–264, 2004. © 2004 Wiley‐Liss, Inc.
Rapid detection of bordetella pertussis by real‐time PCR using SYBR green I and a LightCycler instrument
Authors: Poddar S. K.
Published: September 2004

A polymerase chain reaction (PCR) assay in real‐time for detection of B. pertussis using SYBR green I as the reporter fluorophore and LightCycler instrument (a thermocycler coupled to a fluorescence detection device) was established and evaluated. The amplified amplicon using series diluted control prototype strain (ATCC strain #9797) of B. pertussis was analyzed for the fluorescent melting profile, and melting temperature (Tm) was determined. When examined, amplicons using a representative set of clinical isolates of B. pertussis were found to have the same Tm value (86 ± 0.5°C, the specificity parameter of detection) as the control prototype strain as expected. Amplified product was also analyzed and detected by agarose gel electrophoresis. The detection limit by fluorescent profile and Tm analysis was 10‐fold better than that detected by agarose gel analysis. J. Clin. Lab. Anal. 18:265–270, 2004. © 2004 Wiley‐Liss, Inc.