bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of p21Ras‐mediated apoptosis induced by protein kinase C inhibition and application to human tumor cell lines
Authors: Liou James S. , Chen James S. , Faller Douglas V.
Published: November 2003

Suppression of PKC activity can selectively induce apoptosis in cells expressing a constitutively activated p21Ras protein. We demonstrate that continued expression of p21Ras activity is required in PKC‐mediated apoptosis because farnesyltransferase inhibitors abrogated the loss of viability in p21Ras‐transformed cells occurring following PKC inhibition. Studies utilizing gene transfer or viral vectors demonstrate that transient expression of oncogenic p21Ras activity is sufficient for induction of apoptosis by PKC inhibition, whereas physiologic activation of p21Ras by growth factor is not sufficient to induce apoptosis. Mechanistically, the p21Ras‐mediated apoptosis induced by PKC inhibition is dependent upon mitochondrial dysregulation, with a concurrent loss of mitochondrial membrane potential (ψm). Cyclosporine A, which prevented the loss of ψm, also inhibited HMG‐induced DNA fragmentation in cells expressing an activated p21Ras. Induction of apoptosis by PKC inhibition in human tumors with oncogenic p21Ras mutations was demonstrated. Inhibition of PKC caused increased apoptosis in MIA‐PaCa‐2, a human pancreatic tumor line containing a mutated Ki–ras allele, when compared to HS766T, a human pancreatic tumor line with normal Ki–ras alleles. Furthermore, PKC inhibition induced apoptosis in HCT116, a human colorectal tumor line containing an oncogenic Ki–ras allele but not in a subline (Hke3) in which the mutated Ki–ras allele had been disrupted. The PKC inhibitor 1‐O‐hexadecyl‐2‐O‐methyl‐rac‐glycerol (HMG), significantly reduced p21Ras‐mediated tumor growth in vivo in a nude mouse MIA‐PaCa‐2 xenograft model. Collectively these studies suggest the therapeutic feasibility of targeting PKC activity in tumors expressing an activated p21Ras oncoprotein. J. Cell. Physiol. 198: 277–294, 2004. © 2003 Wiley‐Liss, Inc.
Inhibition of proliferation and induction of apoptosis in breast cancer cells by the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (‘Iressa’) is independent of EGFR expression level
Authors: Campiglio Manuela , Locatelli Alberta , Olgiati Clelia , Normanno Nicola , Somenzi Giulia , Viganò Lucia , Fumagalli Marzia , Ménard Sylvie , Gianni Luca
Published: November 2003

High expression of the epidermal growth factor receptor (EGFR) in breast carcinoma confers a growth advantage to the tumor cells. The EGFR tyrosine kinase inhibitor (EGFR‐TKI) ZD1839 (‘Iressa’) has clinical activity in a wide range of tumor types, although the mechanism(s) by which it exerts its antitumor activity effects remain unclear. We analyzed the ability of ZD1839 to induce apoptosis and/or inhibition of proliferation in breast carcinoma cell lines, as well any association between this ability and the downregulation activity of MAPK and Akt, two recently proposed markers of ZD1839 activity. Proliferation, survival, and activation of Akt and MAPK were evaluated in six human breast cancer cell lines expressing various levels of EGFR and HER2 and exposed to ZD1839. EGFR and HER2 expression levels were determined using specific monoclonal antibodies and FACS analysis. The effects of ZD1839 were independent of EGFR expression levels, but were influenced by high HER2 expression. ZD1839 significantly reduced the rate of [3H]‐thymidine incorporation in the four sensitive cell lines, while apoptosis was also induced in two of these cell lines. No correlation was found between the cytostatic or cytotoxic effects of ZD1839 and its ability to downregulate MAPK and Akt activity in the tumor cell lines. Our data suggest that the antitumor activity of ZD1839 is due to a cytostatic effect, and involves apoptosis induction in a subset of sensitive cells only, and that neither MAPK nor Akt is a reliable marker of ZD1839 activity. J. Cell. Physiol. 198: 259–268, 2004© 2003 Wiley‐Liss, Inc.
Retinoic acid inhibits leukemia inhibitory factor signaling pathways in mouse embryonic stem cells
Authors: Tighe Ann P. , Gudas Lorraine J.
Published: November 2003

Retinoic acid (RA) induces the differentiation of murine embryonic stem (ES) cells to cell types resembling those found in the early embryo. When cultured in the presence of leukemia inhibitory factor (LIF), ES cells are maintained in an undifferentiated (self‐renewing) state. Addition of RA to the culture media overrides the self‐renewing effects of LIF to induce ES cell differentiation. Therefore, we hypothesized that RA‐induced differentiation of ES cells may be accomplished by antagonism of LIF‐induced signaling pathways. We demonstrate that RA‐induced differentiation of CCE ES cells is associated with (1) downregulation of the LIF receptor (LIFR); (2) decreased tyrosine phosphorylation of signal transducer and activator of transcription 3 protein (Stat3); and (3) increased activation of extracellular regulated kinase (Erk1/2). We conclude that RA induces CCE ES cell differentiation in the presence of LIF, in part, by disrupting signaling between the LIFR/gp130 receptor and nuclear targets that are required to prevent ES cell differentiation. Our data indicate that RA‐induced inhibition of LIF signaling does not involve Erk1/2‐dependent actions. J. Cell. Physiol. 198: 223–229, 2004© 2003 Wiley‐Liss, Inc.
Exposure to 900 MHz electromagnetic field induces an unbalance between pro‐apoptotic and pro‐survival signals in T‐lymphoblastoid leukemia CCRF‐CEM cells
Authors: Marinelli F. , La Sala D. , Cicciotti G. , Cattini L. , Trimarchi C. , Putti S. , Zamparelli A. , Giuliani L. , Tomassetti G. , Cinti Caterina
Published: November 2003

An Erratum has been published for this article in Journal of Cellular Physiology 198: 479–480, 2004.

It has been recently established that low‐frequency electromagnetic field (EMFs) exposure induces biological changes and could be associated with increased incidence of cancer, while the issue remains unresolved as to whether high‐frequency EMFs can have hazardous effect on health. Epidemiological studies on association between childhood cancers, particularly leukemia and brain cancer, and exposure to low‐ and high‐frequency EMF suggested an etiological role of EMFs in inducing adverse health effects. To investigate whether exposure to high‐frequency EMFs could affect in vitro cell survival, we cultured acute T‐lymphoblastoid leukemia cells (CCRF‐CEM) in the presence of unmodulated 900 MHz EMF, generated by a transverse electromagnetic (TEM) cell, at various exposure times. We evaluated the effects of high‐frequency EMF on cell growth rate and apoptosis induction, by cell viability (MTT) test, FACS analysis and DNA ladder, and we investigated pro‐apoptotic and pro‐survival signaling pathways possibly involved as a function of exposure time by Western blot analysis. At short exposure times (2–12 h), unmodulated 900 MHz EMF induced DNA breaks and early activation of both p53‐dependent and ‐independent apoptotic pathways while longer continuous exposure (24–48 h) determined silencing of pro‐apoptotic signals and activation of genes involved in both intracellular (Bcl‐2) and extracellular (Ras and Akt1) pro‐survival signaling. Overall our results indicate that exposure to 900 MHz continuous wave, after inducing an early self‐defense response triggered by DNA damage, could confer to the survivor CCRF‐CEM cells a further advantage to survive and proliferate. J. Cell. Physiol. 198: 324–332, 2004© 2003 Wiley‐Liss, Inc.
Radiosynthesis of a 2‐substituted 4,5‐dihydro‐1H‐[2‐11C] imidazole: the I2 imidazoline receptor ligand [11C] benazoline
Authors: Roeda D. , Hinnen F. , Dollé F.
Published: November 2003

Benazoline (2‐naphthalen‐2‐yl‐4,5‐dihydro‐1H‐imidazole) is a selective high‐affinity ligand for the imidazoline I2 receptor. This compound was labelled with carbon‐11 (T1/2=20.4 min) at the number two carbon atom of its 2‐imidazoline ring. Cyclotron‐produced [11C]carbon dioxide reacted with 2‐naphthylmagnesium bromide to give 2‐[carboxyl‐11C]naphthoic acid in 60% radiochemical yield. The latter was heated with a mixture of ethylenediamine and its dihydrochloride at 300°C to give [11C]benazoline in 16% overall yield, relative to [11C]carbon dioxide and with a specific radioactivity of 54 GBq/μmol, decay corrected for end of irradiation. The procedure requires about 45 min from end of cyclotron irradiation. This method should be extendable to other imidazolines. Copyright © 2003 John Wiley & Sons, Ltd.
Structures of monolayers formed from different HS—(CH2)2—X thiols on gold, silver and copper: comparitive studies by surface‐enhanced Raman scattering
Authors: Kudelski Andrzej
Published: November 2003

Molecules of 2‐aminoethanethiol (cysteamine, CYS), 2‐mercaptoethanol (MET), 3‐mercaptopropionic acid (MPA), sodium 2‐mercaptoethanesulphonate (MES) and 1‐propanethiol (PTH) were spontaneously chemisorbed on electrochemically activated silver, copper and gold surfaces. The structure of monolayers formed was studied with surface‐enhanced Raman scattering (SERS). In CYS and MPA monolayers the relative surface concentration of gauche conformers was higher than in MET, PTH and MES monolayers. This is probably due to double bonding to the metal surface by a fraction of adsorbed MPA and CYS molecules (via the sulphur moiety and the terminal carboxylic or amino group). In CYS, MET, MPA and PTH monolayers the surface concentration of trans conformers is significantly higher on Ag than on Au or Cu. The structures of MES monolayers on Ag, Au and Cu are similar, with very high surface concentrations of trans conformers. Statistically, the wavenumbers of ν(C–S) bands of both gauche and trans conformers are the highest on Au, slightly lower on Ag and the lowest for Cu. However the positions of ν(C–S) bands are also sensitive to the other parameters (e.g. C—C—S—metal torsion angle, the overall ordering of the monolayer). Therefore, the wavenumbers of ν(C–S) bands are not good indicators of differences in the interaction between chemisorbed thiols and the metal substrates. Desorption measurements suggest that part of the adsorbed molecules is bonded significantly weaker than the rest. Thiolate monolayers on Cu decomposed relatively easily, forming a layer of copper sulphide. The strength of adsorbed MPA acid is similar on all substrates. Copyright © 2003 John Wiley & Sons, Ltd.
C—H···O hydrogen bonds in liquid cyclohexanone revealed by the νCO splitting and the νC–H blue shift
Authors: Vaz Pedro D. , Ribeiro‐Claro Paulo J. A.
Published: November 2003

The presence of C—H···O hydrogen bonds in liquid cyclohexanone is concluded from a combined theoretical and vibrational spectroscopic study. The two bands present in the νCO region, clearly observed in the Raman spectrum, are assigned to ‘free’ and ‘bonded’ carbonyl groups from their temperature‐dependent and solvent‐dependent relative intensities. In addition, a band exhibiting the same intensity dependence in the νC–H region is tentatively assigned to the blue‐shifted νC–H···(O) mode. Copyright © 2003 John Wiley & Sons, Ltd.
Resonance Raman characterization of cationic Co(II) and Co(III) tetrakis(N‐methyl‐4‐pyridinyl)porphyrins in aqueous and non‐aqueous media
Authors: Terekhov Sergei N. , Kruglik Sergei G. , Malinovskii Vladimir L. , Galievsky Victor A. , Chirvony Vladimir S. , Turpin Pierre‐Yves
Published: November 2003

Resonance Raman (RR) spectra of Co(II) and Co(III) complexes of the water‐soluble cationic tetrakis(N‐methyl‐4‐pyridinyl)porphyrin [CoIITMpyP(4), CoIIITMpyP(4)] were obtained in aqueous and non‐aqueous media, using both B‐ and Q‐band excitation wavelengths. RR spectra of CoIITMpyP(4) are observed for the first time, and they are compared with those of CoIIITMpyP(4). Wavenumbers of the ν2, ν4, ν8 and ν6 oxidation state‐sensitive bands depend on pH in aqueous solution and on the nature of the solvent (methanol, ethanol, DMF, DMSO): they lie in distinct spectral ranges for Co(II) vs Co(III) porphyrins. In addition, wavenumber shifts induced by axial ligation cover regions twofold broader for CoIIITMpyP(4) than for CoIITMpyP(4). This shows that the electronic influence of axial ligands on the π‐system of the macrocycle is more effective when cobalt is in a higher oxidation state. This can be due to (i) smaller axial bond lengths of Co(III) porphyrin and, hence, more efficient cobalt–axial ligand interaction as compared with Co(II) complexes, and (ii) CoIIITMpyP(4) being involved in bis‐adducts whereas CoIITMpyP(4) is mainly bound with only one axial ligand. The response of the porphyrin ring to the binding of axial ligands having various electron‐donating–withdrawing properties was monitored by the behaviour of these oxidation‐state sensitive RR bands: their shifts observed in a series of solvents were compared with Gutmann donor and acceptor numbers (DN, AN) of the solvents. A linear positive correlation was observed between Gutmann AN and ν2, ν4, ν8 and ν6 band wavenumbers for CoIIITMpyP(4), whereas a linear negative correlation was observed for the same bands of CoIITMpyP(4) when DN increases. This means that enhanced electron‐accepting properties of axial ligand result in a scarcity of cobalt dπ‐orbitals, which in turn leads to a decrease in π back‐donation from cobalt to the porphyrin macrocycle. Copyright © 2003 John Wiley & Sons, Ltd.
Raman scattering investigation of Yb : YAG crystals grown by the Czochralski method
Authors: Chen Y. F. , Lim P. K. , Lim S. J. , Yang Y. J. , Hu L. J. , Chiang H. P. , Tse W. S.
Published: November 2003

Raman spectra of a series of Yb3+‐doped YAG crystals were obtained with Yb3+ concentrations up to 100 at.%. Single crystals were successfully grown. No abrupt change of the spectral pattern of the Raman modes as a function of Yb3+ doping concentration was observed. From the spectral changes, it is noted that the Raman peaks shift towards lower wavenumbers in the range <450 cm−1 and towards higher wavenumbers in the range >450 cm−1 with increasing Yb3+ doping concentration. It is proposed that Raman modes with wavenumbers <450 cm−1 are the yttrium or ytterbium ions lattice vibrational modes and that the other phonon peaks can then be assigned to internal modes associated with the (AlO4) tetrahedra of S4 symmetry. The doping concentration of Yb3+ does not influence the spectral properties and lattice vibrations drastically, so that a stable and more efficient Yb : YAG laser may be obtained with highly doped Yb3+ contents. Copyright © 2003 John Wiley & Sons, Ltd.
Time‐resolved resonance Raman study of S1cis‐stilbene and its deuterated isotopomers
Authors: Kwok W. M. , Ma C. , Phillips D. , Beeby A. , Marder T. B. , Thomas R. Ll. , Tschuschke C. , Baranović G. , Matousek P. , Towrie M. , Parker A. W.
Published: November 2003

We present the picosecond time‐resolved resonance Raman (ps‐TR3) spectra of the first excited singlet state (S1) of cis‐stilbene (d0), fully deuterated cis‐stilbene (d12) and α,α′‐d2‐cis‐stilbene (d2) measured in hexane at pump and probe wavelengths 267 and 630 nm, respectively. The main observation is that in the lower wavenumber region the spectra are dominated by a second‐order overtone progression originating from a 229 cm−1 fundamental band for the S1d0 cis‐stilbene. The observed low‐wavenumber modes of the excited cis‐stilbene are substantially more resonantly enhanced than the modes around 1600 cm−1. Copyright © 2003 John Wiley & Sons, Ltd.
Resonance Raman and time‐resolved resonance Raman spectra of the monomeric and dimeric complexes of ruthenium(II) with 2,3‐bis(2‐pyridyl)pyrazine (dpp)
Authors: Su Haiquan , Kincaid James R.
Published: November 2003

The electronic absorption, resonance Raman (RR) and time‐resolved resonance Raman (TR3) spectra of the monomeric and dimeric complexes of ruthenium(II) with 2,3‐bis(2‐pyridyl)pyrazine (dpp) were measured, i.e. Ru(bpy)2dpp2+ and Ru(bpy)2dppRu(bpy)24+, where bpy is 2,2′‐bipyridine. In addition, in order to facilitate definitive assignments of the observed RR spectral parameters, the corresponding selectively labeled complexes employing perdeuterated bpy (d8bpy) were also prepared and studied. It is shown that using judiciously chosen excitation lines to acquire the RR spectra permits selective enhancement of vibrational features associated with specific molecular fragments of the complexes, facilitating structural characterization of ground states of each complex. In addition, the TR3 spectrum of the monomeric complex yields vibrational signatures of its 3MLCT state, which is consistent with polarization of electron density towards the pyrazyl fragment; corresponding studies of the dimeric complex failed to provide conclusive evidence for modes attributable to an anion radical fragment, presumably owing to lack of effective enhancement with the excitation lines available. Copyright © 2003 John Wiley & Sons, Ltd.
Ray Jackendoff, Foundations of language: Brain,
meaning, grammar, evolution. Oxford and New York: Oxford
University Press. 2002. Pp. xix, 477. Hb $40.00.
Authors: Burling Robbins
Published: November 2003

In this extraordinary book, Jackendoff proposes
nothing less than a new way to understand the architecture of
language and a new way to view the relation of language to the
brain, to the mind, to behavior, and to the evolution of our
species. It is, among many other things, an invitation for
cooperation from one of the world's leading formal
syntacticians to linguists of diverse orientations and to those
from adjacent fields, including sociolinguistics and linguistic
anthropology. If we don't want to be left behind, we had
better pay close attention.
Rajend Mesthrie (ed.), Concise encyclopedia
of sociolinguistics. Amsterdam: Elsevier, 2001. Pp. xxvii,
1031. Hb $237.
Authors: Beckett Dan
Published: November 2003

Mesthrie's Concise encyclopedia of
sociolinguistics (hereafter, CESO) is a newly
edited, condensed, and updated offshoot of the Encyclopedia
of language and linguistics, originally published in ten
volumes in 1993. This laudable volume aims to “give a
comprehensive overview of the main topics in an important branch
of language study, generally known as Sociolinguistics”
(p. 1). As theoretical background, the branch is traced from the
Sanskrit scholar Pānini to more recent origins in historical
linguistics, anthropology, rural dialectology, and the study of mixed
languages. The field is further presented as the most proper of all
branches for language study today, as Mesthrie – updating
Labov's (1972) famous claim about the implications of the term
sociolinguistics – writes that “having
‘human communication’ as part of the definition
of language makes it impossible to study language comprehensively
without due regard to social contexts of speech” (1).
CESO is an attempt to catalog the relevant components
of those social contexts.
Alastair Pennycook, Critical applied linguistics:
A critical introduction. Mahwah, NJ: Lawrence Erlbaum,
2001. Pp. xv, 206. Pb $19.95.
Authors: Gray Ronald
Published: November 2003

There is little doubt that critical applied
linguistics is one of the most controversial and contentious
areas in linguistics today. This new book, Critical applied
linguistics: A critical introduction, is an attempt to
provide a much-needed detailed and comprehensive introduction
to this emergent approach. It is written by Alastair Pennycook
of the University of Technology, Sydney, who has been one of
the major proponents of critical applied linguistics during
the past decade.
Ceil Lucas (ed.), The sociolinguistics of sign
languages. New York: Cambridge University Press, 2001.
Pp. vii, 259. Hb $65.00.
Authors: Grushkin Donald A.
Published: November 2003

Although it is easy to do so, The
sociolinguistics of sign languages (henceforth SSL)
is not to be confused with Ceil Lucas's other books, The
sociolinguistics of the deaf community (1989) and its sequels,
the Sociolinguistics in Deaf Communities series. Whereas the
latter volumes aim to present new research in the area of
sociolinguistics pertaining to Deaf people and other users of
sign languages, the book under review presents almost no new
(to those already familiar with this field) information on aspects
of sociolinguistic research on members of this language community.
Instead, this book should more accurately be seen as a companion
volume to her book (with Clayton Valli) Linguistics of American
Sign Language: An introduction (2000; henceforth
LASL). Like LASL, SSL is intended
as a textbook for use in college-level courses dealing with
linguistics (or a stand-alone course in sociolinguistics, as
was Lucas's intention) of sign languages and Deaf
communities.
Salikoko Mufwene, The ecology of language
evolution. Cambridge: Cambridge University Press, 2001.
Pp. xviii, 255. Hb. $65.00, pb. $22.00.
Authors: Clements J. Clancy
Published: November 2003

In this book, author Salikoko Mufwene offers
a chronology of his views on language evolution as they have
developed over the past 12 years. Mufwene understands the
linguistic evolutionary process in terms of a language's
external ecology – that is, its position relative to other
languages with which it moves in and out of contact, the power
relations among groups of different language varieties in the
setting, and so on – as well as its internal ecology,
or the coexistence in a given setting of the linguistic features,
and their relative weight. Although Mufwene uses creole languages
as a starting point, his purpose is to highlight general
characteristics of language evolution; he argues that, in the
essentials of language change, varieties such as pidgins and
creoles differ little if at all from non-pidgins and non-creoles.
To build his case, Mufwene draws from population genetics, seeing
any given language not as an organism but rather as its own
“species.”
Ann K. Wennerstrom, The music of everyday speech:
Prosody and discourse analysis. New York: Oxford University
Press, 2001. Pp. xix, 317, Pb. $24.95.
Authors: Hellerman John
Published: November 2003

The music of everyday speech (hereafter
MES) is a book for discourse analysts interested in
incorporating a theoretically grounded account of sound production,
or, prosody, into their research. Readers of Language in
Society will find MES to be the first book of
its kind. It includes an overview of phonological, discourse
analytical, and interactional approaches to the analysis of
prosody, as well as model prosodic analyses of the major research
areas in discourse analysis. MES is a thorough
presentation of how prosodic analysis can inform discourse
analysis, unique in its coverage of material, excellence of
presentation, and theoretical and analytical depth.
Male voices and perceived sexual orientation: An experimental
and theoretical approach
Authors: SMYTH RON , JACOBS GREG , ROGERS HENRY
Published: November 2003

This article describes the development of
a data bank of 25 male voices spanning the range from very
gay-sounding to very straight-sounding, according to listener
ratings. These ratings allowed the researchers to examine the
effects of different discourse types (scientific, dramatic,
and spontaneous) and listener groups (gay males vs. a mix of
males and females of unknown sexual orientation) on how listeners
perceived the voices. The effects of lexical and pragmatic content
were explored by a comparison of spoken and written presentations
of the same spontaneous speech samples. The effect of asking
participants to rate the voices using different constructs (e.g.,
masculine/feminine vs. gay-sounding/straight-sounding)
is discussed. The ultimate goal of this research program is
to examine correlations between these ratings and a range of
phonetic variables in order to shed light on the specific features
to which listeners attend when judging whether a man's
voice sounds gay or straight.
Localizing power and solidarity: Pronoun alternation at an
all-female police station and a feminist crisis intervention
center in Brazil
Authors: OSTERMANN ANA CRISTINA
Published: November 2003

This article brings the study of language
to the social phenomenon of gender-related violence as it is
currently being dealt with in institutional settings. It
investigates the social significance of 2nd person pronoun
variation and alternation in 26 professional-victim interactions
in two parallel institutions created to address violence against
women in Brazil: a police station with an all-female staff,
and a feminist crisis intervention center. A quantitative analysis
of patterns of use is complemented by a qualitative analysis
of the interactional strategies of 2nd person pronoun alternation
in the two settings. Pronoun switching is innovatively analyzed
under the theory of code alternation developed by Auer 1995.
The qualitative analysis demonstrates how pronoun alternation
functions as a contextualization cue in face-to-face interactions.
In particular, it shows the different ways in which pronoun
alternation is used to contextualize phenomena such as preference
organization and changes in frames and footings, and locally
to exercise power and/or solidarity.
Language ideologies and practices in (en)gendering the Basque
nation
Authors: ECHEVERRIA BEGOÑA
Published: November 2003

This article argues that an androcentric Basque
nationalist pedagogy is enacted in secondary schools in San
Sebastian (Donostia), Spain. Textbooks present men as the exemplary
Basque speakers and cultural agents by erasing women's
contributions to Basque language and culture. Schools also
contribute to a recursive language ideology, linking
“authentic” ethnic identity, “naturalness,”
and solidarity with vernacular Basque, of which the most
pragmatically salient marker is the familiar form of address
hi. Hi, in turn, indirectly indexes male speakers
and masculinity, thereby creating an iconic relationship between
authentic Basque identity, Basque culture, and masculinity.
However, many women in Basque society have challenged this male
privilege in various domains, thereby opening up the possibility
of a Basque nation that embraces its female as well as its male
members. As such, the Basque case has interesting implications
for theorizing the relationships among language, gender, and
nation.
EDITOR'S NOTE
Authors: Hill Jane H.
Published: November 2003

The current issue of Language in Society
features four articles with a single topic in common –
gender and language. For this issue, I realized that by jumping
one paper already in hand over a couple of others I could achieve
the felicitous result of a relatively unified issue –
and now that Language in Society is at five issues
a year, the “jumpees” will only have to wait two
months for publication in any case. My usual practice is that
articles are published in strict order of acceptance –
very occasionally, an author will take so long to get the very
last revision – the i-dotting and t-crossing and
reference-checking – done that the article will lag in
publication. Extremely long articles sometimes get delayed an
issue. And once or twice I have speeded up publication of an
article which languished an unfairly long time in the review
process.
The /ay/ diphthong in a Martha's Vineyard
community: What can we say 40 years after Labov?
Authors: BLAKE RENÉE , JOSEY MEREDITH
Published: November 2003

This article revisits Labov's (1962,
1972a) germinal sociolinguistic work on Martha's Vineyard
speech, providing a synchronic analysis of the /ay/
diphthong in words like right and time, and,
in turn, a diachronic perspective on a sound change in progress.
Labov observed that the first element of the /ay/ diphthong
was raised in the speech of Martha's Vineyarders, particularly
fishermen, and he correlated it with social factors like identity
(i.e., local heritage) and resistance to summer visitors. The
present authors provide a sociolinguistic analysis of /ay/
from a new set of data collected in a Martha's Vineyard
speech community. The outcome suggests a change in the linguistic
pattern observed by Labov, which the authors argue is linked
to socio-economic restructuring and resulting ideological changes
taking place on the island. The acoustic and social factors
are analyzed using VARBRUL to show how /ay/ variation
today patterns with various internal and external factors found
to be salient in Labov's earlier study.
“Are you my friend?”: Negotiating friendship
in conversations between network marketers and their prospects
Authors: KONG KENNETH C.C.
Published: November 2003

Friendship is studied as a culturally and
contextually embedded entity. Focusing on the interactions between
network marketers and their prospects, this article proposes
four key central elements through which participants make sense
of themselves when their identities are in transgression and
conflict. Instead of being essentialist, the four elements of
friendship – intimacy, control, trust, and positiveness
– are highly interactional and dynamic elements that can
be negotiated by participants in a conversation. It is argued
that Grice's Cooperative Principle is valid, but this should
be enhanced by participants' specific culture and prior experience.
The notion of “face” in politeness models should be expanded
in light of its dynamic characteristics in interaction.
Linguistic capital in Taiwan: The KMT's Mandarin language
policy and its perceived impact on language practices of bilingual
Mandarin and Tai-gi speakers
Authors: Sandel Todd L.
Published: November 2003

From 1945 until 1987, the KMT (Nationalist)
government enforced its strict Mandarin Language Policy in schools
throughout Taiwan, and students were forbidden to speak local
languages or dialects. Recent reversal of this policy allows
schools to teach these formerly forbidden varieties. Despite
some attention from scholars, it remains to explore the impact
of these policies on successive generations of bilingual speakers.
This study explores the perceptions of parents, grandparents,
and young adults. The data show that school-based policies have
an impact on family-based speaking practices. They also demonstrate
the complex interplay between public and private histories in
the development of linguistic ideologies and language as capital.
Reassessing Māori
regeneration
Authors: SPOLSKY BERNARD
Published: November 2003

After nearly two centuries of contact with
Europeans, the Māori language of New Zealand was, by the 1960s,
threatened with extinction. Accompanying a movement for ethnic revival,
a series of grassroots regeneration efforts that established adult,
preschool, and autonomous school immersion programs has over
the past two decades increased substantially the number of Māori
who know and use their language, but this has not yet led to the
reestablishment of natural intergenerational transmission. More recently,
responding to growing ethnic pressures, the New Zealand government has
adopted a Māori language policy and is starting to implement it.
Seen in its widest social, political, and economic context, this process
can be understood not as colonial language loss followed by postcolonial
reversing language shift activities, but as the continuation of a long
process of negotiation of accommodation between autochthonous Māori
and European settlers.
LIFETIME COSTS FOR MEDICAL SERVICES: A METHODOLOGICAL REVIEW
Authors: Jacobs Philip , Golmohammadi Kamran , Longobardi Teresa
Published: November 2003

Objectives: Guidelines for economic evaluation studies recommend that modeling be undertaken to estimate long-term, downstream costs. In this study, we conduct a review of a sample of studies that estimated the lifetime medical care costs for a variety of conditions.

Methods: We developed a categorization of the elements for a lifetime-costing study and based on these elements, we abstracted information from a sample of 33 papers in the following areas: study subject, purpose, scope, methods (including time profile, utilization, and cost), and results.

Results: We analyzed papers that were observational, models or that combined the two approaches. The time profiles were estimated from registry and published data. Utilization data were obtained from administrative data, chart reviews, and professional opinion. Costs were obtained from administrative and financial records and were estimated using all charges, allocated costs, and provider payments. We noted wide variations in methods and reporting practices.

Conclusions: Following current guidelines (CCOHTA), lifetime models can be more easily interpreted and applied if investigators are more clear in their study aims, if they incorporate assumptions that are based on current data, if they follow current methodological practices (such as deflation, discounting, and sensitivity analyses), and if reporting is more transparent.
CONFRONTING THE “GRAY ZONES” OF TECHNOLOGY ASSESSMENT: EVALUATING GENETIC TESTING SERVICES FOR PUBLIC INSURANCE COVERAGE IN CANADA
Authors: Giacomini Mita , Miller Fiona , Browman George
Published: November 2003

We describe an evaluation model to guide public coverage of new predictive genetic tests in Ontario, Canada. The model confronts common “gray zones” in evaluation and coverage policy for challenging new technologies. Analysis addresses three domains of the evaluation picture. The first specifies evaluative criteria (purpose, effectiveness, additional effects, unit cost, demand, cost-effectiveness). The second induces or deduces acceptable cutoffs for each criterion. The third domain addresses the need to make decisions under uncertainty and to respond to “gray” evaluations with conditional-coverage decisions. The evaluation criteria should be applied within sound decision-making processes.
DAILY COST PREDICTION MODEL IN NEONATAL INTENSIVE CARE
Authors: Zupancic John A. F. , Richardson Douglas K. , O'Brien Bernie J. , Schmidt Barbara , Weinstein Milton C.
Published: November 2003

Objectives: One barrier to economic evaluation alongside neonatal randomized controlled trials is the expense of collecting detailed patient resource information. To reduce this data collection burden, we identified the key resource items that predict daily ancillary costs for extremely low birth weight infants.

Methods: Participants were 385 infants enrolled in the Trial of Indomethacin Prophylaxis for Preterms in nine tertiary level neonatal intensive care units in Canada. Information on eighty-nine nonpersonnel resource items was abstracted from the hospital chart from admission to tertiary hospital discharge. Unit costs were derived from a provincially standardized cost accounting system. Using stepwise linear regression, models correlating total daily ancillary costs with key resource items were constructed for each of five periods of admission. Models were derived in a randomly split half of the total sample of patient days and validated against the remainder.

Results: The 385 infants contributed resource information from 23,354 admission days. The regression model for weeks one to twelve included the covariates surfactant, chest radiograph, red blood cell transfusion, cranial ultrasound, abdominal radiograph, parenteral amino acid infusion, surgery, platelet transfusion, and echocardiogram and explained 91% of the variability in daily nonpersonnel costs (P<.0001). Models for other admission periods similarly included between four and eight covariates, were highly significant (P<.0001) and explained between 76% and 94% of daily ancillary cost variability. The regression equations showed excellent predictive power when applied to the second half of the patient data set.

Conclusions: Daily nonpersonnel costs for extremely low birth weight infants are driven by a limited number of key resource variables. The ability to predict total ancillary costs with minimal data collection will facilitate inclusion of economic evaluations in neonatal trials.
HYPERBARIC OXYGEN TECHNOLOGY: AN OVERVIEW OF ITS APPLICATIONS, EFFICACY, AND COST-EFFECTIVENESS
Authors: Guo Shien , Counte Michael A. , Romeis James C.
Published: November 2003

Objectives: To examine the growing evidence and the consensus in the medical community concerning the efficacy and cost-effectiveness of hyperbaric oxygen therapy (HBO2T) and to suggest future research areas to ensure the appropriate use of this technology.

Methods: A literature search of articles published between 1985 and 2000 was conducted using PubMed to describe the growth of HBO2T-related articles published over the past fifteen years. In addition, articles involving the qualitative synthesis of the efficacy and cost-effectiveness of HBO2T in thirteen major application areas were identified and compared with the changing view of the medical community toward the evidence of HBO2T.

Results: The total number of HBO2T-related articles published annually has steadily increased over the past fifteen years. This increase has gradually contributed to a consensus in the medical community concerning the evidence of efficacy in its major application areas. However, information regarding the cost-effectiveness of HBO2T is still extremely limited.

Conclusions: Although evidence concerning the efficacy of HBO2T has been growing in the past, more evidence is still needed for some of its major application areas. Moreover, there is an urgent need to shift part of the research focus on HBO2T to its cost-effectiveness to provide decision makers with relevant information to evaluate this technology objectively.
COSTS OF FLEXIBLE SIGMOIDOSCOPY SCREENING FOR COLORECTAL CANCER IN THE UNITED KINGDOM
Authors: Whynes David K. , Frew Emma J. , Edwards Robert , Atkin Wendy S.
Published: November 2003

Objectives: Colorectal cancer is one of the most commonly occurring cancers in industrialized countries, yet appears to be amenable to screening. Amongst the many possible protocols is once-only screening by means of flexible sigmoidoscopy. This protocol is currently being investigated in a UK multicenter trial and the study provides estimates of the expected resource costs.

Methods: The direct health care costs of sigmoidoscopy and of all subsequent procedures were estimated from an audit of resource use of approximately 40,000 patients at thirteen centers. Patient-borne costs were estimated from the results of surveys conducted at twelve of these centers.

Results: The health service costs of a flexible sigmoidoscopy was estimated at £56. The total costs of screening (including private costs) averaged £82 per person screened, although costs varied by center. The total health service costs of screening and subsequent management averaged approximately £91 per person screened, again with variations between centers.

Conclusions: Even within a strict trial protocol, intercenter variation in costs can be detected, ascribable to variability in local management practices, local yield, and local patient-borne costs. Other recent estimates of flexible sigmoidoscopy costs vary widely. As these costs form the basis of technology assessment simulation models which, in turn, inform policy, obtaining realistic cost estimates within the appropriate health care setting is of paramount importance.
COMPARISON OF HOSPITAL COSTING METHODS IN AN ECONOMIC EVALUATION OF A MULTINATIONAL CLINICAL TRIAL
Authors: Reed Shelby D. , Friedman Joëlle Y. , Gnanasakthy Ari , Schulman Kevin A.
Published: November 2003

Objectives: To develop and evaluate strategies for estimating hospitalization costs in multinational clinical trials.

Methods: Hospital cost estimates for eleven diagnoses were collected from twelve countries participating in a trial of therapies for congestive heart failure. Estimates were combined with U.S.-based diagnosis-related group weights to compute country-specific unit cost estimates for all reasons for hospitalization. Variations of hospital costing methods were developed. The unit cost method assigns a country-specific unit cost estimate to each hospitalization. The other methods adjust for length of stay using a daily cost (DC) estimate for each diagnosis, based on either the mean length of stay (DC-mean method) or the median length of stay (DC-median method) for each diagnosis in each country. Additional modifications were explored through adjustment of the distribution of daily costs incurred during a hospital stay.

Results: The mean cost for all hospitalizations was $10,242 (SD, 10,042) using the unit cost method, $10,242 (SD, 12,760) using the standard DC-mean method, and $13,967 (SD, 18,762) using the standard DC-median method. In comparisons of costs for all 5,486 hospitalizations incurred by a subset of 2,352 patients in the trial, the unit cost method provided 92% power to detect a $1,000 cost difference. The standard DC-mean method provided 76% power, and the standard DC-median method provided 44% power.

Conclusions: Hospital costing methods that adjust for differences in length of stay require a significantly larger sample to attain comparable statistical power as methods that assign unadjusted unit cost estimates to hospitalization events.
COST-EFFECTIVENESS ANALYSIS: CAN WE REDUCE VARIABILITY IN COSTING METHODS?
Authors: Adam Taghreed , Evans David B. , Koopmanschap Marc A.
Published: November 2003

Objectives: The need for consistency and standardization of methods for economic appraisals has been recognized for some time and has led to the development of several sets of guidelines for economic evaluations and for costs. Despite this, considerable diversity is still apparent in applied studies. Some of these diversities might be defensible, and some might not. The objectives of this study are to explore sources of variations in the methods used in applied studies and to discuss the nature of these variations and the possibility of reducing some of them.

Methods: We first use a systematic approach to identify the major sources of variation in costing methods used in applied economic evaluations. We then compare the methods used with the recommendations made in available guidelines.

Results: Four possible sources of variation are identified. The first is where guidelines do not agree in their recommendations; therefore, it is not surprising that applied studies use different methods. The second is where guidelines agree in principle but provide little detail on how to comply with their recommendations; and the third is where a particular methodological issue is not discussed in guidelines. The fourth reason is simply lack of compliance with accepted guidelines.

Conclusions: Variability in costing methods used in applied studies raises questions about the validity of their results and makes it difficult to compare the results of different studies. We discuss the implications for the transferability and generalizability of results and suggest ways to minimize the variability in the methods so that the results of costing studies and economic evaluations can be of more value to policy-makers.
EVIDENCE OF IMPROVING COST-EFFECTIVENESS OF PEDIATRIC COCHLEAR IMPLANTATION
Authors: Sach T. , O'Neill C. , Whynes D.K. , Archbold S.M. , O'Donoghue G.M.
Published: November 2003

Objectives: To examine the cost-effectiveness of pediatric cochlear implantation over time.

Methods: A prospective study based on ninety-eight children implanted between 1989 and 1996 at Nottingham's Paediatric Cochlear Implantation Programme, UK. The influence of outcomes and other variables on total costs was examined using multivariate regression analysis.

Results: Having controlled for potential confounding variables, total cost was negatively related to year of implant and positively related to the number of hours of rehabilitation (p=.000).

Conclusions: Having controlled for outcomes (Categories of Auditory Performance and Speech Intelligibility Rating), the cost-effectiveness improved over time. This finding may be due to a learning curve and have policy implications.
Configuration knowledge representations for Semantic Web applications
Authors: FELFERNIG ALEXANDER , FRIEDRICH GERHARD , JANNACH DIETMAR , STUMPTNER MARKUS , ZANKER MARKUS
Published: November 2003

Today's economy exhibits a growing trend toward highly specialized solution providers cooperatively offering configurable products and services to their customers. This paradigm shift requires the extension of current standalone configuration technology with capabilities of knowledge sharing and distributed problem solving. In this context a standardized configuration knowledge representation language with formal semantics is needed in order to support knowledge interchange between different configuration environments. Languages such as Ontology Inference Layer (OIL) and DARPA Agent Markup Language (DAML+OIL) are based on such formal semantics (description logic) and are very popular for knowledge representation in the Semantic Web. In this paper we analyze the applicability of those languages with respect to configuration knowledge representation and discuss additional demands on expressivity. For joint configuration problem solving it is necessary to agree on a common problem definition. Therefore, we give a description logic based definition of a configuration problem and show its equivalence with existing consistency-based definitions, thus joining the two major streams in knowledge-based configuration (description logics and predicate logic/constraint based configuration).
Decomposition strategies for configuration problems
Authors: MAGRO DIEGO , TORASSO PIETRO
Published: November 2003

The paper introduces and discusses the notion of decomposition of a configuration problem within the framework of a structured logical approach. The paper describes under which conditions a given configuration problem can be decomposed into a set of noninteracting subproblems and how to exploit such a decomposition, both for improving the performance of the configurator and for supporting interactive configuration. Different kinds of decomposition are considered, but all of them exploit, as much as possible, the explicit representation of the partonomic relations in thelanguage, a KL-One like representation formalism augmented with constraints for expressing complex interrole relations. The paper introduces a notion of boundness among constraints, which is used for formally specifying different types of decomposition. One decomposition strategy aims at singling out the components and subcomponents that are directly related to the constraints put by the user's requirements; the configurator exploits such decomposition by first configuring that portion of the product and then configuring the parts that are not related to the user's requirements. Another decomposition strategy verifies whether the set of constraints for the product to be configured can be split into a set of noninteracting problems. In such a case the configurator solves the configuration problem by splitting the whole search space into a set of smaller search spaces. Different combinations of these two decomposition techniques are considered, and the impact of the decomposition strategies on the performance of the configurator is evaluated via a set of experiments using the configuration of computer systems as a test bed. The results of the experiments show a significant reduction of the computational effort (both in terms of number of backtrackings and in CPU time) when decomposition strategies are used.