bluuebunny/crossref_metadata_2025 huggingface dataset:
Religion and the pursuit of truth
Authors: ZAMULINSKI BRIAN
Published: May 2003

This is a new argument to the effect that religions are not truth-oriented. In other words, it is not a fundamental function of religion to represent the world accurately. I compare two hypotheses with respect to their likelihood (in A. W. F. Edwards's technical sense). The one which entails that religion is not truth-oriented is a better explanation than its competitor for a number of empirical observations about religion. It is also at least as probable. I point out that, once one has established that religions are not truth-oriented, it is possible to argue that religions are false and it is possible to run a sound ad hominem argument against religious believers who advance religious claims. I suggest that the results are early ones and that what matters is evaluating religion in the way I illustrate in this paper. The ad hominem argument shows that the question of whether religion is truth-oriented is particularly important.
The grounding objection to middle knowledge revisited
Authors: COWAN STEVEN B.
Published: May 2003

The Molinist doctrine that God has middle knowledge requires that God knows the truth-values of counterfactuals of freedom, propositions about what free agents would do in hypothetical circumstances. A well-known objection to middle knowledge, the grounding objection, contends that counterfactuals of freedom have no truth-value because there is no fact to the matter as to what an agent with libertarian freedom would do in counterfactual circumstances. Molinists, however, have offered responses to the grounding objection that they believe are adequate for maintaining the coherence of middle knowledge. I argue that these responses to the grounding objection are not adequate, and that what I call the ‘generic grounding objection’ still poses a serious challenge to middle knowledge.
Experimental investigation of ion beam transport in laser
initiated plasma channels
Authors: PENACHE D. , NIEMANN C. , TAUSCHWITZ A. , KNOBLOCH R. , NEFF S. , BIRKNER R. , GEIßEL M. , HOFFMANN D.H.H. , PRESURA R. , PENACHE C. , ROTH M. , WAHL H.
Published: May 2003

The aim of the presented experiments is to study the transport
of a heavy ion beam in a high-current plasma channel. The discharge
is initiated in NH3 gas at pressures between 2 and
20 mbar by a line-tuned CO2 laser. A stable discharge
over the entire electrode gap (0.5 m) was achieved for currents
up to 60 kA. Concerning the ion beam transport, the magnetic
field distribution inside the plasma channel has to be known.
The ion-optical properties of the plasma channel have been
investigated using different species of heavy ions (C, Ni, Au,
U) with 11.4 MeV/u during six runs at the Gesellschaft für
Schwerionenforschungs-UNILAC linear accelerator. The high magnetic
field allowed the accomplishment of one complete betatron
oscillation along the discharge channel. The results obtained
up to now are very promising and suggest that, by scaling the
discharge gap to longer distances, the beam transport over several
meters is possible with negligible losses.
Bunching dynamics and transport window of intense ion beams
in final beam buncher
Authors: KIKUCHI TAKASHI , NAKAJIMA MITSUO , HORIOKA KAZUHIKO
Published: May 2003

A longitudinal compression is indispensable in a final stage
of the heavy ion driver system using a particle accelerator.
For the beam compression, an induction buncher applies the bunching
voltage so as to make a considerable velocity tilt between the
head and the tail of the beam bunch. However, the velocity tilt
induces mismatch oscillation of the beam envelope due to the
nonconformity between the beam particle velocity and the
confinement force of the lens system. At the first step of design
works for the beam transport line, the initial phase advance
is decided to avoid resonance lines on the tune diagram. However,
as the phase advance changes in the buncher by the velocity
tilt, the beam bunch reenters in the resonance condition under
certain circumstances. The transport region for avoiding the
resonance condition is discussed on a phase diagram, as a function
of the phase advance and the velocity tilt.
Measurement of temperature evolution for the laser ion source
plasma
Authors: STEPANOV A.E. , VOLKOV G.S. , ZAITSEV V.I. , MAKAROV K.N. , SATOV YU.A. , ROERICH V.C.
Published: May 2003

Temporal evolution of X-ray spectra of lead plasma produced
by a CO2 laser pulse with energy of 100 J and a duration
of 15 ns has been measured using a six-channel X-ray polychromator.
The polychromator registered the radiation intensity in the
range from 180 to 1850 eV. Plasma temperature was determined
by comparison of measured results with radiation spectra obtained
by numerical simulation. The values of electron temperature
are in good agreement with results of hydro simulations.
Beam losses in heavy ion drivers
Authors: MUSTAFIN E. , BOINE-FRANKENHEIM O. , HOFMANN I. , SPILLER P.
Published: May 2003

While beam loss issues have hardly been considered in detail
for heavy ion fusion scenarios, recent heavy ion machine
developments in different labs (European Organization for Nuclear
Research(CERN), Gesellschaft für Schwerionenforschung (GSI),
Institute for Theoretical and Experimental Physics (ITEP),
Relativistic Heavy-Ion Collider (RHIC)) have shown the great
importance of beam current limitations due to ion losses. Two
aspects of beam losses in heavy ion accelerators are theoretically
considered: (1) secondary neutron production due to lost ions,
and (2) vacuum pressure instability due to charge exchange losses.
Calculations are compared and found to be in good agreement
with measured data. The application to a Heavy-Ion Driven Inertial
Fusion (HIDIF) scenario is discussed.
Laser-produced protons and their application as a particle probe
Authors: BORGHESI M. , CAMPBELL D.H. , SCHIAVI A. , WILLI O. , MACKINNON A.J. , HICKS D. , PATEL P. , GIZZI L.A. , GALIMBERTI M. , CLARKE R.J.
Published: May 2003

Due to an error, the published version of the paper differed from the final
version submitted by the authors. The section starting at page 271 with
“The beams are well collimated …” and finishing at the end
of the page, and the caption for figure 4 were to be replaced with an updated
version, submitted on 20 May 2002, which follows underneath.
On cost-effectiveness of human-centered and socially acceptable robot and automation
systems
Authors: Cernetic Janko
Published: May 2003

This paper considers human-centered and socially appropriate robots as well as automation systems within the context of their cost-effectiveness. Usually, the objection of system designers is that approaches for human-centered and socio-technical design result in systems that are more expensive than those made by traditional methods, and are therefore not truly affordable, in particular for small and medium sized enterprises (SMEs). This widespread opinion is challenged in the paper by some arguments supporting the forecast that human-centered and socio-technical design will soon become
justifiable in tangible (economic) as well as intangible benefits for all involved partners, including society at large.
Book reviews
Authors: Andrew Alex M.
Published: May 2003

FAULT DIAGNOSIS AND FAULT TOLERANCE FOR MECHATRONIC SYSTEMS: RECENT ADVANCES, edited by Fabrizio Caccavale and Luigi Villani, Springer, Berlin, 2003, pp.
xii, 191. ISBN 3-540-44159-X. Springer Tracts in Advanced Robotics (STAR), Vol.
1 (Hardback, £49.00).
Ælfric on the creation and fall of the angels
Authors: Fox Michael
Published: May 2003

Ælfric, in the Preface to Genesis, comments about what we do not find in the first
book of the Old Testament: ‘Seo boc ys gehaten Genesis, Þæt ys
“Gecyndboc”, for Þam Þe heo ys firmest boca and spricÞ be ælcum gecinde
(ac heo ne spricð na be Þæra engla gesceapenisse).’ Although he proceeds to
explain what is contained in the opening verse, noting that creation ‘on
annginne’ refers at once to the literal act of creation and, ‘æfter gastlicum
andgite’, to Christ through whom all creation was formed, he makes no further
comment here upon the angels. In other works, however, where the topic
could be more appropriately introduced, Ælfric enthusiastically engages with
the problem of angelic history. The sermon De initio creaturae, the Interrogationes
Sigewulfi, the Exameron, the Letter to Sigeweard and the Letter to Wulfgeat all
contain accounts of the angelic creation and fall. Because Ælfric is a writer actively concerned with orthodoxy and sound doctrine, we would do well to
ask why he has such an interest in the angels–about whom such an authority as
Bede would say almost nothing–and to investigate precisely how, and from
what sources, he presents their extra-scriptural history.
LANGUAGE CONTACT AND CHANGE: SUMMARY OBSERVATIONS
Authors: Tucker G. Richard
Published: May 2003

Various facets of the general topic of multilingualism, including language contact, have been dealt with in previous ARAL volumes (e.g., under separate entries in volumes 1, 2, 4, 5, 10, 12, 13, and 15) and as a major substantive focus in volumes 6, 14 and 17. Nonetheless, it does not seem at all surprising that we return to the specific topic of language contact and change in volume 23 given the worldwide incidence of the phenomenon and the attention, and often controversy, which various aspects of language contact, language change or language loss arouses. Thus, I find it interesting that, within the past 12 months, issues related to language contact and derivative implications have surfaced as important factors in public discussions in such disparate settings as the November 2002 elections in several of the states in the United States, the admission of new members to the European Union, and immigration to Australia. Clearly, the topics of language contact and language change are salient and likely to remain so for the foreseeable future.
An Extended Kalman Filter Algorithm for Integrating GPS and Low Cost Dead Reckoning System Data for Vehicle Performance and Emissions Monitoring
Authors: Zhao L. , Ochieng W. Y. , Quddus M. A. , Noland R. B.
Published: May 2003

This paper describes the features of an extended Kalman filter algorithm designed to support the navigational function of a real-time vehicle performance and emissions monitoring system currently under development. The Kalman filter is used to process global positioning system (GPS) data enhanced with dead reckoning (DR) in an integrated mode, to provide continuous positioning in built-up areas. The dynamic model and filter algorithms are discussed in detail, followed by the findings based on computer simulations and a limited field trial carried out in the Greater London area. The results demonstrate that use of the extended Kalman filter algorithm enables the integrated system employing GPS and low cost DR devices to meet the required navigation performance of the device under development.
Sligo Air
Authors: Parque Lawrence
Published: May 2003

The performance piece Flux in the Sligo Air is a suite for movement artists and electro-acoustic music. It was composed in response to the unique atmosphere of Sligo, a town of 16,000 inhabitants in the northwest of Ireland, and its place within the surrounding landscape. I was inspired by Sligo's architecture and the sky, landscape and sea into which the town is so naturally and uniquely integrated. My study of space perception in architectural terms and its correlation with musical processes led to a contemplation of the relationship of the town's buildings to each other and the spaces (streets) they inhabit in the same manner as tonal phrases might become related to each other, or to a drone. Flux in the Sligo Air is not an analogous translation of architecture into music, however, but an attempt to capture those ever-changing senses which one may experience within a space. The town's natural condition and evolution, the new and the old at many points in time, serve as carriers of ideas of sense and felt knowledge which transcend the purely physical.
Research and the RIBA. Lea's Pottery: From assertion to rational discourse
Authors: Saxon Richard
Published: May 2003

Following up both your leader (p99) and Alan Jones' letter (p105) in arq 6/2, the arrival of Jack Pringle as RIBA Vice President for Education and myself as Hon Vice President for Practice does indeed reinforce the moves already in progress to create an RIBA voice in architectural research and to connect it to education and practice. Council has now created the necessary resources, but full approval of the initiative is still in the pipeline.
SIMPLE PROOF OF EXISTENCE OF EQUILIBRIUM IN A ONE-SECTOR GROWTH MODEL WITH BOUNDED OR UNBOUNDED RETURNS FROM BELOW
Authors: Durán Jorge , Le Van Cuong
Published: May 2003

We analyze a Ramsey economy in which gross investment is constrained to be nonnegative. We prove the existence of a competitive equilibrium for the case in which utility need not be bounded from below and the Inada-type conditions need not hold. The analysis is carried out by means of a direct and technically standard approach. This direct approach allows us to obtain detailed results concerning properties of competitive equilibria, and is easily adapted for the analysis of analogous models often found in macroeconomics.
Directionality in transfer?
Authors: SCHLYTER SUZANNE
Published: May 2003

Natascha Müller discusses a question which in recent years – after a period of focus on cross-linguistic principles of language acquisition – has regained its position as a current topic, namely transfer, and here in bilingual children. One of her points is that for transfer to take place, the transferred construction must have some correspondence in the target language, a position similar to the “transfer to somewhere” principle often advocated in the L2 acquisition literature (cf. Gass & Selinker, 1983). The specific structure studied is the lack of Verb-End in the German of a bilingual German-French child.
Producing words in a foreign language: Can speakers prevent interference from their first language?
Authors: HERMANS DAAN , BONGAERTS THEO , DE BOT KEES , SCHREUDER ROBERT
Published: May 2003

Two picture-word interference experiments were conducted to investigate whether or not words from a first and more dominant language are activated during lexical access in a foreign and less dominant language. Native speakers of Dutch were instructed to name pictures in their foreign language English. Our experiments show that the Dutch name of a picture is activated during initial stages of the process of lexical in English as a foreign language. We conclude that bilingual speakers cannot suppress activation from their first language while naming pictures in a foreign language. The implications for bilingual speech production theories are discussed.
“Schwierige Klassen” in der Wahrnehmung von Lehrkräften
Authors: Tiedemann Joachim , Billmann-Mahecha Elfriede
Published: May 2003

Zusammenfassung: Die Studie hat zum Ziel, psychologische Umwelten, die durch die Wahrnehmung der Lehrkräfte konstituiert werden, zu analysieren und in ihrer Beziehung zur Schülerwahrnehmung zu evaluieren. Auf der Basis von offenen, themenzentrierten Lehrerinterviews in 15 vierten Grundschulklassen wurde ein Klassenkontext-Index gewonnen, der die Schwierigkeit der Unterrichtung und Führung einer Schulklasse aus der Lehrerperspektive widerspiegelt. Über Schülerfragebogen wurde die Wahrnehmung der Direktivität der Lehrkraft ermittelt. Die Auswertung der Daten erfolgte auf der Basis mehrebenenanalytischer Methoden. Der Klassenkontext-Index erweist sich als konstruktvalide: Schüler in schwierigen Klassen weisen eine geringere selbstperzipierte Sozialkompetenz und verminderte Schulleistungen auf. Weiterhin werden Lehrkräfte in schwierigen Klassen von ihren Schülern als eher direktiver und die Autonomie der Schüler stärker einschränkend wahrgenommen. Die Implikationen der vorliegenden Befunde werden auch unter dem Blickwinkel der Akzentuierung einer transaktionalen Perspektive in der Unterrichtsforschung diskutiert.
Buchstabenlücken ausfüllen und andere Rechtschreibübungen: Wirksamkeit und Wirkfaktoren
Authors: Tacke Gero
Published: May 2003

Zusammenfassung: Rechtschreibübungen, bei denen Schüler aus vorgegebenen Buchstaben (z.B. “z” oder “tz”) die richtige Alternative in Lückenwörter einzusetzen haben (z.B. schwi_en), sind in der Praxis weit verbreitet. In einer ersten Studie wurde überprüft, ob die Kritik an Lückenübungen zutrifft, dass die Vorgabe von einander ähnlichen Lückenwörtern (z.B. schwi_en, hei_en) zu einer pro- und retroaktiven Gedächtnishemmung (Ranschburgsche Hemmung) führt. Es zeigte sich, dass Lückenübungen weder nach einem einmaligen, noch nach einem dreimaligen Lerndurchgang zu erkennbaren Leistungsveränderungen führten. In einer zweiten Studie, bei der die Lernzeit bei Lückenübungen und beim Diktieren von Wörtern konstant gehalten wurde, waren Lückenübungen ebenso erfolgreich wie das Diktieren von Wörtern. In einer dritten Studie wurde die Rechtschreibung unter Ausschaltung der visuellen Wahrnehmung mündlich geübt. Dieses Vorgehen erwies sich bei identischer Lernzeit als genauso effektiv wie das Diktieren von Wörtern, allerdings nur, wenn beim mündlichen Üben die Wörter zu Beginn in kurzen und später in zunehmenden Intervallen systematisch wiederholt wurden.
Frei selektierbarer vs. linear vorgegebener Textabruf in Computerlernprogrammen
Authors: Stiller Klaus , Mate Gergely
Published: May 2003

Zusammenfassung: Gegenüber einer vorgegebenen Informationsabfolge in Computerlernprogrammen wird von einer freien Auswahl erwartet, dass sie die Lernenden motivational fördert, in ihren Verarbeitungsprozessen positiv beeinflusst und so den Lernerfolg steigert. Ein differierendes Nutzungsverhalten wird wegen des ungleichen Nutzungsangebots als zwingend angenommen. In dieser Studie werden die Effekte eines über Vor- und Zurück-Buttons linearen vs. eines über anklickbare Bildteile selektierbaren Textabrufs auf bildbezogene Lernstrategien, Lernleistung, Programmnutzung und -akzeptanz geprüft. Das Nutzungsverhalten wurde vom Computer protokolliert, alle weiteren Variablen wurden mittels Fragebogen erfasst. 39 Gymnasiasten aus 11ten Klassen bearbeiteten die Programme für 30 Minuten. Der bildzentrierte Textabruf erzielte höhere Akzeptanzwerte, förderte den Einsatz aller Lernstrategien und führte zu einem besseren Abschneiden im Bildbeschriftungstest, wogegen der lineare Abruf Vorteile im Textwissen produzierte. Mit dem linearen Programm wurde mehr Zeit für Einleitungen und Zusammenfassungen und weniger Zeit für die Detailtexte aufgebracht, wobei dies nicht ganz darauf gründet, dass mehr der Einleitungen und Zusammenfassungen bearbeitet wurden.
Dermatofibrosarcoma protuberans of the vulva and groin: detection of COL1A1‐PDGFB fusion transcripts by RT‐PCR
Authors: Gökden Neriman , Dehner Louis P. , Zhu Xiaopei , Pfeifer John D.
Published: May 2003

Background:  Dermatofibrosarcoma protuberans (DFSP) is an uncommon infiltrative tumor of the dermis with characteristic cytogenetic features, specifically the translocation t(17;22)(q22;q13) which often manifests as a supernumerary ring chromosome r(17;22). The translocation results in the fusion of two genes, collagen type I alpha 1(COL1A1) and platelet‐derived growth factor B‐chain (PDGFB). The trunk and extremities are the anatomic sites of predilection for DFSP, whereas the vulva and groin are quite uncommon sites of involvement.

Methods:  This investigation evaluated seven DFSPs (four vulvar and three groin) for the presence of COL1A1‐PDGFB fusion transcripts by reverse transcriptase‐polymerase chain reaction (RT‐PCR), using archival formalin‐fixed, paraffin‐embedded tissue.

Results:  Six of seven cases (three vulvar, three groin) contained a COL1A1‐PDGFB fusion transcript. Sequence analysis of the PCR products revealed that the break‐point of the COL1A1 gene was located after exon 40 in two patients, after exon 42 in one patient, after exon 44 in one patient, and after exon 47 in two patients; the break‐point in the PDGFB gene was before exon 2 in all cases. No fusion transcript could be amplified in one case.

Conclusions:  As in DFSP at other sites, COL1A1‐ PDGFB chimeric fusion transcripts are present in vulvar and groin DFSP. The transcripts can be detected in formalin‐fixed, paraffin‐embedded tumor tissues, and have the same general pattern of exon boundaries as in DFSP at other sites.
Carcinomatous transformation of eccrine syringofibroadenoma
Authors: Katane M. , Akiyama M. , Ohnishi T. , Watanabe S. , Matsuo I.
Published: May 2003

Background: While squamous cell carcinoma and pseudocarcinomatous hyperplasia have been documented as pre‐existing lesions in cases of reactive eccrine syringofibroadenoma (ESFA), to the best of our knowledge carcinoma occurring in a solitary ESFA has not yet been reported. We present one such case in a 91‐year‐old female who had a dome‐shaped, reddish tumor on the extensor side of the left forearm.

Methods: We review the histopathological, immunophenotypical and ultrastructural findings of this tumor, including the keratin expression profile.

Results: Histopathologically, long, branching, anastomosing, thin and thick strands of small cuboidal epithelial cells were extending from the surface epidermis into the dermis. In the center of the tumor, there were irregular‐shaped nests of atypical tumor cells invading downward into the dermis. Ultrastructurally, duct‐like lumina lined with cuboidal tumor cells were present in the epithelial cords. From these findings, the present case was diagnosed as solitary eccrine syringofibroadenocarcinoma (ESFAC). Keratin expression studies revealed that cells of the thick strands, except for the luminal and basal cells, were positive for differentiation‐specific keratins, keratins 1 and 10, and that cells of the thin strands were positive for keratins 5 and 14.

Conclusions: Histopathological, immunophenotypical and ultrastructural evidence, as well as the pattern of keratin expression, suggest differentiation of the present malignant tumor towards the eccrine dermal duct. This case is the first reported case of ESFAC as far as we know.
CD44 and hyaluronate in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans
Authors: Calikoglu Emel , Augsburger Eric , Chavaz Pierre , Saurat Jean‐Hilaire , Kaya Gürkan
Published: May 2003

The histological distinction between dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) may be extremely difficult. CD34 and Factor XIIIa have been used to differentiate DF from DFSP. However, there is an overlap and relative lack of specificity of their expressions. CD44 is a widely distributed integral membrane glycoprotein, which is expressed as a multitude of isoforms generated by alternative splicing of at least 10 different variant exons and post‐translational modifications. CD44 is currently thought to be the principal cell surface receptor for hyaluronate (HA), the major component of the extracellular matrix. In this study we aimed to assess the expression of standard CD44 (CD44s) and its isoforms (CD44v3, CD44v4, CD44v5, CD44v6, CD44v7, CD44v7v8, and CD44v10), and HA in DF and DFSP. Immunohistochemical staining was performed on the biopsy specimens of 15 cases of DF and four cases of DFSP, using antibodies that recognize the CD44s, different CD44 isoforms and the hyaluronate binding protein (HABP). Tumor cells displayed a strong CD44s immunoreactivity in all cases of DF whereas a faint HA positivity was observed in the tumor stroma. The DF cells were negative for CD44v3, CD44v4, CD44v6, CD44v7 and CD44v7v8 but showed a strong reactivity for CD44v5 and CD44v10. In contrast, CD44s' expression was significantly reduced or absent in all DFSP lesions and the tumor stroma displayed strong staining for HA. Our results indicate that CD44 and HA can be used as additional diagnostic markers to distinguish DF from DFSP.
Identification of landscape units from an insect perspective
Authors: Chust Guillem , Pretus Joan L. , Ducrot Danielle , Bedòs Anne , Deharveng L.
Published: May 2003

Habitat patches vary as a function of an organism's perception. The response of species to patch mosaic may depend on the scale of observation by which the spatial pattern is perceived. A hierarchical view of landscapes is proposed to define the optimal grain of landscape affecting soil fauna (Collembola). A multilevel approach is developed to quantify the landscape grain based on the concept of contrast, that is, the magnitude of difference in measures across a given boundary between adjacent patch types. An image segmentation procedure was firstly applied to satellite images to detect edges, and this defines “homogeneous” regions at multiple contrast levels. Spatial features (number of patches, diversity of patches and edge length) were then derived from segmented images to characterise the spatial pattern that surrounds Collembola sampling sites. These landscape descriptors were computed at different levels of contrast and at three spatial scales. The statistical dependence between species occurrence and landscape descriptors was assessed by means of the Mantel test. Biodiversity, estimated by species richness and the number of endemic species, was analysed by stepwise multiple linear regression.  The multilevel approach permitted a definition of the landscape units based on the response of the assemblage to landscape heterogeneity. The effect of landscape heterogeneity was especially evident on species composition and on endemic richness when patches are defined at fine grain. The heterogeneity descriptor “number of patches”, calculated at the optimal contrast level, explained 72% of the endemic richness variance. This spatial feature constituted a reliable inverse indicator of endemic richness that was extrapolated to the pixels of the image providing a spatial model.
Structure of a plant–flower‐visitor network in the high‐altitude sub‐alpine desert of Tenerife, Canary Islands
Authors: Dupont Yoko L. , Hansen Dennis M. , Olesen Jens M.
Published: May 2003

Confined within a volcanic caldera at 2000 m a.s.l., the sub‐alpine desert of Tenerife, Canary Islands, harbors a distinct biota. At this altitude the climate is harsh and the growing season short. Hence, plant and animal communities, constituting the sub‐alpine plant–flower‐visitor network, are clearly delimited, both spatially and temporally. We investigated species composition and interaction structure of this system. A total of 11 plant species (91% endemics) and 37 flower‐visiting animal species (62% endemics) formed 108 interactions. Numbers of interactions among species varied ten‐fold within both plant and animal communities. Generalization level of a species was positively correlated with its local abundance. Two separate network analyses revealed a significantly nested structure. In relation to a plant–flower‐visitor system, nestedness implies that specialized species (animals or plants) interact with a subset of the species pool visiting (animals) or being visited (plants) by more generalized species. Therefore, specialized, locally rare plants tend to be visited by generalized, locally abundant animals, and specialized, locally rare animals tend to utilize generalized, locally abundant food plants. Such patterns could have implications for conservation of the sub‐alpine network, and stress the importance of preserving not only rare species, but also the more abundant ones, which may be key food resources or pollinators in the plant–flower‐visitor network.
DNA Microarrays and Likelihood Ratio Bioinformatic Methods: Discovery of Human Melanocyte Biomarkers
Authors: Dooley Thomas P. , Curto Ernest V. , Davis Richard L. , Grammatico Paola , Robinson Edward S. , Wilborn Teresa W.
Published: May 2003

In this article, some of the advantages and limitations of DNA microarray technologies for gene expression profiling are summarized. As a model experiment, DermArray® DNA microarrays were utilized to identify potential biomarkers of cultured normal human melanocytes in two different experimental comparisons. In the first case, melanocyte RNA was compared with vastly dissimilar non‐melanocytic RNA samples of normal skin keratinocytes and fibroblasts. In the second case, melanocyte RNA was compared with a primary cutaneous melanoma line (MS7) and a metastatic melanoma cell line (SKMel‐28). The alternative approaches provide dramatically different lists of ‘normal melanocyte’ biomarkers. The most robust biomarkers were identified using principal component analysis bioinformatic methods related to likelihood ratios. Only three of 25 robust biomarkers in the melanocyte‐proximal study (i.e. melanocytes vs. melanoma cells) were coincidentally identified in the melanocyte‐distal study (i.e. melanocytes vs. non‐melanocytic cells). Selected up‐regulated biomarkers of melanocytes (i.e. TRP‐1, melan‐A/MART‐1, silver/Pmel17, and nidogen‐2) were validated by qRT‐PCR. Some of the melanocytic biomarkers identified here may be useful in molecular diagnostics, as potential molecular targets for drug discovery, and for understanding the biochemistry of melanocytic cells.
A Chemist's View of Melanogenesis
Authors: Ito Shosuke
Published: May 2003

The significance of our understanding of the chemistry of melanin and melanogenesis is reviewed. Melanogenesis begins with the production of dopaquinone, a highly reactive o‐quinone. Pulse radiolysis is a powerful tool to study the fates of such highly reactive melanin precursors. Based on pulse radiolysis data reported by Land et al. (J Photochem Photobiol B: Biol 2001;64:123) and our biochemical studies, a pathway for mixed melanogenesis is proposed. Melanogenesis proceeds in three distinctive steps. The initial step is the production of cysteinyldopas by the rapid addition of cysteine to dopaquinone, which continues as long as cysteine is present (1 μM). The second step is the oxidation of cysteinyldopas to give pheomelanin, which continues as long as cysteinyldopas are present (10 μM). The last step is the production of eumelanin, which begins only after most cysteinyldopas are depleted. It thus appears that eumelanin is deposited on the preformed pheomelanin and that the ratio of eu‐ to pheomelanin is determined by the tyrosinase activity and cysteine concentration. In eumelanogenesis, dopachrome is a rather stable molecule and spontaneously decomposes to give mostly 5,6‐dihydroxyindole. Dopachrome tautomerase (Dct) catalyses the tautomerization of dopachrome to give mostly 5,6‐dihydroxyindole‐2‐carboxylic acid (DHICA). Our study confirmed that the role of Dct is to increase the ratio of DHICA in eumelanin and to increase the production of eumelanin. In addition, the cytotoxicity of o‐quinone melanin precursors was found to correlate with binding to proteins through the cysteine residues. Finally, it is still unknown how the availability of cysteine is controlled within the melanosome.
Nitric oxide at a low concentration protects murine macrophage RAW264 cells against nitric oxide‐induced death via cGMP signaling pathway
Authors: Yoshioka Y , Yamamuro A , Maeda S
Published: May 2003

We investigated the cytoprotective effect of low‐dose nitric oxide (NO) on NO‐induced cell death in mouse macrophage‐like cell line RAW264.

Sodium nitroprusside (SNP), an NO donor, at a high concentration (4 mM) released cytochrome c from mitochondria and induced death in RAW264 cells. Acetyl‐L‐aspartyl‐L‐glutamyl‐L‐valyl‐L‐aspart‐1‐al (Ac‐DEVD‐CHO, 100–200 μM), a caspase‐3 inhibitor, attenuated the SNP‐induced cell death in a concentration‐dependent manner.

Pretreatment with 100 μM SNP for 24 h, which had no effect on cell viability, attenuated the cell death and reduced cytochrome c release from mitochondria to the cytosol induced by 4 mM SNP.

LY83583 (1–3 μM) and 1H‐[1,2,4]oxadiazolo[4,3,‐a]quinoxalin‐1‐one (ODQ, 30–100 μM), soluble guanylate cyclase inhibitors, negated the protective effect of the 100 μM SNP pretreatment.

Pretreatment with 1 mM dibutylyl guanosine‐3′,5′‐cyclic monophosphate (DBcGMP), a cell‐permeable guanosine‐3′,5′‐cyclic monophosphate (cGMP) analogue, for 24 h inhibited both cytochrome c release and cell death induced by SNP.

Protein kinase G inhibitor KT5823 (10 μM) significantly reduced the cytoprotective effects of low‐dose SNP and DBcGMP.

These results indicate that low‐dose NO protects RAW264 cells from NO‐induced apoptosis through cGMP production and activation of protein kinase G.

British Journal of Pharmacology (2003) 139, 28–34. doi:10.1038/sj.bjp.0705206
Proteinase‐activated receptor‐1 (PAR‐1) activation contracts the isolated human renal artery in vitro
Authors: Tognetto Michele , D'Andrea Michael R , Trevisani Marcello , Guerrini Remo , Salvadori Severo , Spisani Lorella , Daniele Carlo , Andrade‐Gordon Patricia , Geppetti Pierangelo , Harrison Selena
Published: May 2003

The in vitro motor function of protease‐activated recepter‐1 (PAR‐1), PAR‐2 and PAR‐4 and the presence by immunohistochemistry of PAR‐1 in the human renal artery have been investigated.

Thrombin and the human PAR‐1 (SFLLRN‐NH2) activating peptide, but not the PAR‐1 reverse peptide (NRLLFS‐NH2), contracted both endothelial‐intact and endothelial‐denuded human renal artery strips, whereas no relaxation was observed either in strips non‐precontracted or precontracted with phenylephrine. Maximum contraction by thrombin or SFLLRN‐NH2 was about 60% of phenylephrine. However, thrombin was approximately 1000‐fold more potent than SFLLRN‐NH2.

PAR‐1 desensitisation, using repeated applications of SFLLRN‐NH2, almost completely blocked the response to thrombin. The contractile effect produced by thrombin and SFLLRN‐NH2 was not affected by nitric oxide synthase inhibition, but was significantly reduced by cyclooxygenase blockade.

Trypsin, the PAR‐2 (SLIGKV‐NH2 and SLIGRL‐NH2) and PAR‐4 (GYPGQV‐NH2 and AYPGKF‐NH2) activating peptides did not produce any significant contraction or relaxation.

In agreement with the motor function data immunohistochemistry showed specific staining patterns for PAR‐1 in the human renal artery.

Combined, these studies would suggest a possible role for PAR‐1 in renal vascular homeostasis.

British Journal of Pharmacology (2003) 139, 21–27. doi:10.1038/sj.bjp.0705215
SR33805, a Ca2+ antagonist with length‐dependent Ca2+‐sensitizing properties in cardiac myocytes
Authors: Cazorla Olivier , Lacampagne Alain , Fauconnier Jeremy , Vassort Guy
Published: May 2003

This study examined the effects of SR33805, a fantofarone derivative with reported strong Ca2+ ‐antagonistic properties, on the contractile properties of intact and skinned rat ventricular myocytes.

On intact cells loaded with the Ca2+‐fluorescent indicator Indo‐1, the application of low concentrations of SR33805 enhanced the amplitude of unloaded cell shortening and decreased the duration of cell shortening. Amplitude of the Ca2+ transient was also decreased.

These effects were accompanied with a shortening of the action potential and a dose‐dependent blockade of L‐type calcium current (IC50=2.4 × 10−8 M).

On skinned cardiac cells, the application of a low SR33805 concentration (10−8 M) induced a significant increase in maximal Ca2+‐activated force at the two‐tested sarcomere lengths (SLs), 1.9 and 2.3 μm.

The application of a larger dose of SR33805 (10−6–10−5 M) induced a significant leftward shift of the tension–pCa relation that accounts for Ca2+‐sensitization of the myofilaments, particularly at 2.3 μm SL.

In conclusion, despite its strong Ca2+‐antagonistic properties SR33805 increases cardiac cell contractile activity as a consequence of its Ca2+‐sensitizing effects. These effects are attributable to both an increase in the maximal Ca2+‐activated force and a length‐dependent Ca2+‐sensitization.

British Journal of Pharmacology (2003) 139, 99–108. doi:10.1038/sj.bjp.0705221
Macrophage migration inhibitory factor exhibits a pronounced circadian rhythm relevant to its role as a glucocorticoid counter‐regulator
Authors: Petrovsky Nikolai , Socha Luis , Silva Diego , Grossman Ashley B , Metz Christine , Bucala Richard
Published: May 2003

In humans, maximal expression of T helper 1 cytokines coincide with the nocturnal nadir of plasma cortisol, whereas T helper 2 cytokine responses are dominant during day‐time. The pro‐inflammatory cytokine, macrophage migration inhibitory factor counter‐regulates glucocorticoid‐mediated immune suppression. To determine the relationship between cortisol and macrophage migration inhibitory factor, healthy volunteers had blood drawn hourly for 24 h for measurement of plasma cortisol and basal‐ and stimulated‐macrophage migration inhibitory factor. Similar to cortisol, macrophage migration inhibitory factor peaked during the late morning whereas interferon‐γ, tumour necrosis factor‐α, interleukin‐1 and interleukin‐12 demonstrated a nocturnal peak. After oral cortisone, plasma macrophage migration inhibitory factor rose 2–4‐fold, whereas the other cytokines decreased. There was no correlation between cortisol during the insulin tolerance test and plasma macrophage migration inhibitory factor. The late morning peak of macrophage migration inhibitory factor, by antagonizing cortisol‐mediated pro‐inflammatory cytokine suppression may prolong the duration of early morning inflammation. These observations explain the beneficial role of macrophage migration inhibitory factor neutralization in models of inflammatory arthritis.
A new therapeutical approach: Topotecan plus gemcitabine in the treatment of patients with relapsed ovarian cancer after failure of first‐line chemotherapy with paclitaxel and platinum
Authors: Sehouli Jalid , Stengel Dirk , Oskay Gülten , Blohmer Jens , Kaubitzsch Sabine , Lichtenegger Werner
Published: May 2003

Aim:  Topotecan and gemcitabine have demonstrated mono‐activity against recurrent ovarian cancer. Both drugs affect DNA replication; in addition, topotecan inhibits DNA repair. Based on the efficacy profiles and different mechanisms of action, a phase‐I study was conducted to determine the maximum tolerated dose (MTD) of topotecan (day 1–5) and the dose‐limiting toxicities (DLT) in combination with gemcitabine (day 1 + 8) every 21 days.

Methods:  Three to six patients were treated per dose‐level. Patients with ovarian cancer who had failed a platinum and paclitaxel‐containing therapy were enrolled. No individual dose escalation or use of cytokines were allowed.

Results:  Twenty‐three patients were recruited. Fifty percent of all patients were pretreated with at least two platinum‐containing therapies. Eighty courses were assessable for toxicity. The MTD was reached at a dosage of 0.75 mg/m2 topotecan in combination with 800/600 mg/m2 gemcitabine. Thrombocytopenia and leucopenia were the major DLTs. The dose for phase‐II trials is 0.50 mg/m2 topotecan given with 800/600 mg/m2 gemcitabine. In this dose‐level only one related non‐haematological adverse event> grade 2 was observed (grade 3 mycotic stomatitis) and one grade 4 thrombocytopenia occurred. Responses were observed in six patients and stable disease in four out of 12 assessable patients. Median survival time was 15.3 (95% CI: 13.21–28.64) months.

Conclusion:  The results demonstrate feasibility and the tolerability of topotecan in combination with gemcitabine in recurrent ovarian cancer patients. Based on these results a phase‐II study was conducted to evaluate the efficacy of this new combination.
Effect of fundal pressure on maternal to fetal microtransfusion at the time of cesarean delivery
Authors: Owens Michelle , Bhullar Amanpreet , Carlan Stephen J. , O'Brien William F. , Hirano Kazuyuki
Published: May 2003

Aim:  To determine if fundal pressure at the time of cesarean delivery increases the amount of transplacental microtransfusion from mother to infant.

Methods:  Pregnant women undergoing cesarean delivery were randomized to the standard uterine fundal pressure at the time of hysterotomy versus no fundal pressure. Babies of patients randomized to no fundal pressure were delivered with either vacuum or forceps. The proportion of placental alkaline phosphatase between maternal and cord blood was then determined and compared between the groups.

Results:  Eighty‐four women were randomized into two groups (44 in the pressure and 40 in the no pressure groups). There was no difference between the groups in demographic variables, or indications for cesarean. There was no difference in percentage of umbilical cord blood placental alkaline phosphatase between the pressure and no pressure groups (0.06 ± 0.2 vs 10 ± 0.29 IU, P = 0.43).

Conclusions:  Fundal pressure at the time of cesarean delivery does not increase the amount of transplacental microtransfusion, suggesting that modifying the method of cesarean would not decrease the chances of vertical transmission in HIV positive pregnant women.
Mid‐trimester fracture of femur in a normal fetus
Authors: Senanayake Hemantha , Anandakumar Chinnaiah , De Silva M.V. Chandu
Published: May 2003

We report a case of an intrauterine fracture of the femur detected at routine mid‐trimester sonography in an otherwise normal fetus. There was no associated maternal trauma. At birth, callus formation was palpable and confirmed by radiography. Absence of further fractures despite normal childhood activity and other features precluded a diagnosis of skeletal dysplasia. Although such an event is extremely rare, the possibility of an intrauterine origin should be considered in the differential diagnosis of battered baby syndrome presenting with a single fracture.
Adrenergic control of post‐exercise metabolism
Authors: BØRSHEIM E. , KNARDAHL S. , HØSTMARK A. T. , BAHR R.
Published: May 2003

After strenuous exercise there is a sustained increase in resting O2 consumption. The magnitude and duration of the excess post‐exercise O2 consumption (EPOC) is a function of exercise intensity and exercise duration. Some of the mechanisms underlying the rapid EPOC component (<1 h) are well defined, while the mechanisms causing the prolonged EPOC component (>1 h) are not fully understood. It has been suggested that β‐adrenergic stimulation is of importance for the prolonged component. There is an increased level of plasma adrenaline and noradrenaline during exercise, and it is shown that catecholamines stimulate energy expenditure through β‐adrenoceptors. After exercise an increased fat oxidation and an increased rate of triglyceride fatty acid (TG–FA) cycling may account for a significant part of the prolonged EPOC component. These processes may be stimulated by catecholamines. However, the return of plasma concentration of catecholamines to resting levels after exercise is more rapid than the return of O2 uptake. But plasma concentration of catecholamines may be an insensitive indicator of sympathetic activity, since the clearance rate of catecholamines is high. Also, the sensitivity to catecholamines may be increased after exercise. A decreased post‐exercise O2 uptake has been shown when β‐blockade is administered in dogs before the exercise bout. In a pilot study in humans, administration of β‐antagonist after exercise did not seem to change EPOC.
Glucose utilization during exercise: influence of endurance training
Authors: WOJTASZEWSKI J. F. P. , RICHTER E. A.
Published: May 2003

During exercise skeletal muscle glucose utilization is higher than at rest. This is due to the combined effect of an increase in glucose supply, increased surface membrane glucose transport capacity and increased muscle glucose metabolism during exercise. The kinetics of glucose utilization in skeletal muscle during exercise in humans show an apparent Km of ∼10 mM, indicating that changes in the blood glucose concentration around the physiological level of ∼5 mM almost linearly translate into changes in muscle glucose utilization. The signalling events responsible for increased glucose transport in contracting muscle are not well understood, although calcium seems to be involved. Contractions do not utilize the proximal part of the insulin signalling cascade to activate glucose transport, because contractions do not cause phosphorylation of insulin receptor substrate 1 or activation of phosphatidylinositol 3‐kinase. Endurance training leads to a decrease in glucose utilization during submaximal exercise of a given absolute submaximal power output in spite of a large increase in the total muscle GLUT4 content. The molecular mechanism behind this decrease in glucose utilization seems to be blunted exercise‐induced translocation of GLUT4 protein to the sarcolemma, in turn blunting the exercise‐induced increase in sarcolemmal glucose transport capacity.
New evidence for similarities in excitation–contraction coupling in skeletal and cardiac muscle
Authors: WASSERSTROM J. A.
Published: May 2003

This review describes several new experimental observations indicating that some of the differences thought to distinguish activation of contraction in skeletal and cardiac muscle may be in fact much less profound than are currently considered. Three such areas are considered in particular. First, it now appears that activation of the elementary units of Ca2+ release from the sarcoplasmic reticulum (`Ca2+sparks') in skeletal muscle may occur not only as the result of voltage activation but also of Ca2+ activation in a process very much like Ca2+‐induced Ca2+ release (CICR) in cardiac muscle. Second, there is new evidence that activation of contraction in cardiac muscle may be partly reliant on a voltage‐sensitive release mechanism (VSRM) similar to that in skeletal muscle. Third, digitalis binds to a high affinity site on the cardiac sarcoplasmic reticulum Ca2+ release channel (ryanodine receptor RyR) causing an increase in single channel open probability which could contribute to its positive inotropic action; although mammalian skeletal muscle does not appear to share this sensitivity to cardiac glycosides, amphibian skeletal muscle has both cardiac and skeletal isoforms of the channel and does indeed demonstrate a positive inotropic action in response to digitalis. These results raise the possibility that several differences thought to represent `fundamental' distinctions between the two muscle types and how they generate and regulate contraction, as well as pharmacological sensitivities, may be more similar than are currently considered.
Effect of recombinant human growth hormone in elderly osteoporotic women
Authors: Sugimoto Toshitsugu , Nakaoka Daiki , Nasu Masamichi , Kanzawa Michiko , Sugishita Takeshi , Chihara Kazuo
Published: May 2003

OBJECTIVE

Bone mineral density and growth hormone (GH) secretion rate both decline during normal human ageing. We evaluated the effects of recombinant human GH on markers of body composition and bone turnover in an open study in 8 elderly osteoporotic women aged 68–75 years (mean age 71 years).

DESIGN

Subjects were treated with GH as a single daily subcutaneous injection (0.125 IU/kg/week for the first 4 weeks and subsequently 0.25 IU/kg/week) for 48 weeks.

RESULTS

GH treatment caused a rapid (within 2 weeks) increase in serum levels of IGF‐I and IGF‐binding protein‐3 (IGFBP‐3) which was sustained throughout the study. Markers of bone formation and resorption were both gradually increased up to 24 weeks of GH treatment. The bone formation markers, osteocalcin (OC) and bone alkaline phosphatase, remained high during GH treatment, while the bone resorption marker, deoxypyridinoline (D‐Pyr), tended to return to baseline levels after 24 weeks of GH therapy. GH treatment for 48 weeks caused a significant increase in hand grip and a decrease in waist/hip ratio. The mean percentage changes in bone mineral density (BMD) of mid‐radius and lumbar spine were + 2.1% and + 1.2%, respectively, although they were not statistically significant. GH treatment was well tolerated and no major side‐effects except mild oedema and joint pain were found. Since GH treatment produced durable increases in bone formation markers, BMD continued to be monitored after discontinuation of GH treatment for another 48 weeks, during which significant increases in radial and lumbar BMD (8.1 ± 2.1 and 3.8 ± 1.4% above pre‐ treatment values, respectively) were recorded.

CONCLUSION

These results indicate that GH attenuates the decrease in muscle strength and bone mass as well as the gain of abdominal fat with ageing in elderly women. The present data provide useful information about the application of GH treatment in elderly women.