bluuebunny/crossref_metadata_2025 huggingface dataset:
The Future of Humanitarian Action: Mapping the Implications of Iraq and Other Recent Crises
Authors: Donini Antonio , Minear Larry , Walker Peter
Published: June 2004

In late 2003 the Feinstein International Famine Center, in partnership with institutions in London, Geneva and Washington, organised a series of consultations on the future of humanitarian action post‐Iraq. This article is based on those discussions. A number of recurring concerns are elaborated, ranging from the perception of humanitarianism as a Northern‐driven and Northern‐controlled enterprise, through the politicisation of security and the devaluation of the protective power of emblems, to the very nature of how the crisis in Iraq is perceived. The article explores the implications of such issues for humanitarian workers and their institutions. It concludes by framing an agenda for action by the humanitarian sector.
An investigation of the role of auditory cortex in sound localization using muscimol‐releasing Elvax
Authors: Smith Adam L. , Parsons Carl H. , Lanyon Richard G. , Bizley Jennifer K. , Akerman Colin J. , Baker Gary E. , Dempster Amanda C. , Thompson Ian D. , King Andrew J.
Published: June 2004

Lesion studies suggest that primary auditory cortex (A1) is required for accurate sound localization by carnivores and primates. In order to elucidate further its role in spatial hearing, we examined the behavioural consequences of reversibly inactivating ferret A1 over long periods, using Elvax implants releasing the GABAA receptor agonist muscimol. Sub‐dural polymer placements were shown to deliver relatively constant levels of muscimol to underlying cortex for >5 months. The measured diffusion of muscimol beneath and around the implant was limited to 1 mm. Cortical silencing was assessed electrophysiologically in both auditory and visual cortices. This exhibited rapid onset and was reversed within a few hours of implant removal. Inactivation of cortical neurons extended to all layers for implants lasting up to 6 weeks and throughout at least layers I–IV for longer placements, whereas thalamic activity in layer IV appeared to be unaffected. Blockade of cortical neurons in the deeper layers was restricted to ≤ 500 µm from the edge of the implant, but was usually more widespread in the superficial layers. In contrast, drug‐free Elvax implants had little discernible effect on the responses of the underlying cortical neurons. Bilateral implants of muscimol–Elvax over A1 produced significant deficits in the localization of brief sounds in horizontal space and particularly a reduced ability to discriminate between anterior and posterior sound sources. The performance of these ferrets gradually improved over the period in which the Elvax was in place and attained that of control animals following its removal. Although similar in nature, these deficits were less pronounced than those caused by cortical lesions and suggest a specific role for A1 in resolving the spatial ambiguities inherent in auditory localization cues.
An impaired neocortical Ih is associated with enhanced excitability and absence epilepsy
Authors: Strauss Ulf , Kole Maarten H. P. , Bräuer Anja U. , Pahnke Jens , Bajorat Rika , Rolfs Arndt , Nitsch Robert , Deisz Rudolf A.
Published: June 2004

Neuronal subthreshold excitability and firing behaviour are markedly influenced by the activation and deactivation of the somato‐dendritic hyperpolarization‐activated cation current (Ih). Here, we evaluated possible contributions of Ih to hyperexcitability in an animal model of absence seizures (WAG/Rij rats). We investigated pyramidal neurons of the somatosensory neocortex, the site of generation of spike–wave discharges. Ih‐mediated functions in neurons from WAG/Rij rats, Wistar rats (sharing the same genetic background with WAG/Rij, but less epilepsy‐prone) and ACI rats (an inbred strain, virtually free of seizures) were compared. We complemented whole‐cell recordings from layer 2–3 pyramidal neurons with immunohistochemistry, Western blot and RT‐PCR analysis of the h‐channel subunits HCN1–4. The fast component of Ih activation in WAG/Rij neurons was significantly reduced (50% reduction in the h‐current density) and four times slower than in neurons from nonepileptic Wistar or ACI rats. The results showing decreases in currents corresponded to a 34% reduction in HCN1 protein in the WAG/Rij compared to the Wistar neocortex, but HCN1 mRNA showed stable expression. The other three Ih subunit mRNAs and proteins (HCN2–4) were not affected. The alterations in Ih magnitude and kinetics of gating in WAG/Rij neurons may contribute to augmented excitatory postsynaptic potentials, the increase in their temporal summation and the facilitation of burst firing of these neurons because each of these effects could be mimicked by the selective Ih antagonist ZD 7288. We suggest that the deficit in Ih‐mediated functions may contribute to the development and onset of spontaneously occurring hyperexcitability in a rat model of absence seizures.
The role of V5 (hMT+) in visually guided hand movements: an fMRI study
Authors: Oreja‐Guevara C. , Kleiser R. , Paulus W. , Kruse W. , Seitz R. J. , Hoffmann K. P.
Published: June 2004

Electrophysiological studies in animals suggest that visuomotor control of forelimb and eye movements involves reciprocal connections between several areas (striate, extrastriate, parietal, motor and premotor) related to movement performance and visuospatial coding of movement direction. The extrastriate area MT [V5 (hMT+) in humans] located in the ‘dorsal pathway’ of the primate brain is specialized in the processing of visual motion information. The aim of our study was to investigate the functional role of V5 (hMT+) in the control of visually guided hand movements and to identify the corresponding cortex activation implicated in the visuomotor tasks using functional magnetic resonance imaging. Eight human subjects performed visually guided hand movements, either continuously tracking a horizontally moving target or performing ballistic tracking movements of a cursor to an eccentric stationary target while fixating a central fixation cross. The tracking movements were back‐projected onto the screen using a cursor which was moved by an MRI‐compatible joystick. Both conditions activated area V5 (hMT+), right more than left, particularly during continuous tracking. In addition, a large‐scale sensorimotor circuit which included sensorimotor cortex, premotor cortex, striatum, thalamus and cerebellum as well as a number of cortical areas along the intraparietal sulcus in both hemispheres were activated. Because activity was increased in V5 (hMT+) during continuous tracking but not during ballistic tracking as compared to motion perception, it has a pivotal role during the visual control of forelimb movements as well.
Neuronal activation of Ras regulates synaptic connectivity
Authors: Arendt Thomas , Gärtner Ulrich , Seeger Gudrun , Barmashenko Gleb , Palm Kirstin , Mittmann Thomas , Yan Li , Hümmeke Markus , Behrbohm Julia , Brückner Martina K. , Holzer Max , Wahle Petra , Heumann Rolf
Published: June 2004

A synRas mouse model was used expressing constitutively activated Ha‐Ras (Val12 mutation) in neurons to investigate the role of Ras‐MAPkinase signalling for neuronal connectivity in adult brain. Expression of the transgene in the cortex of these mice starts after neuronal differentiation is completed and allows to directly investigate the effects of enhanced Ras activity in differentiated neurons. Activation of Ha‐Ras induced an increase in soma size which was sensitive to MEK inhibitor in postnatal organotypic cultures. Adult cortical pyramidal neurons showed complex structural rearrangements associated with an increased size and ramification of dendritic arborization. Dendritic spine density was elevated and correlated with a twofold increase in number of synapses. In acute brain slices of the somatosensory and of the visual cortex, extracellular field potentials were recorded from layer II/III neurons. The input–output relation of synaptically evoked field potentials revealed a significantly higher basal excitability of the transgenic mice cortex compared to wild‐type animals. In whole cell patch clamp preparations, the frequency of AMPA receptor‐mediated spontaneous excitatory postsynaptic currents was increased while the ratio between NMDA and AMPA‐receptor mediated signal amplitude was unchanged. A pronounced depression of paired pulse facilitation indicated that Ras contributes to changes at the presynaptic site. Furthermore, synRas mice showed an increased synaptic long‐term potentiation, which was sensitive to blockers of NMDA‐receptors and of MEK. We conclude that neuronal Ras is a common switch of plasticity in adult mammalian brain sculpturing neuronal architecture and synaptic connectivity in concert with tuning synaptic efficacy.
Neural correlates of error detection and error correction: is there a common neuroanatomical substrate?
Authors: Fiehler Katja , Ullsperger Markus , Von Cramon D. Yves
Published: June 2004

Successful behaviour requires error detection resulting in remedial actions, such as immediate error correction. The present event‐related functional magnetic resonance imaging study in humans examined the neural correlates of error detection and error correction using a speeded modified flankers task. In order to investigate corrective behaviour, participants were randomly divided into two groups. The correction instructed group was asked to correct all encountered errors immediately. The correction not instructed group was unaware that corrective responses were recorded. The intention to correct errors significantly increased the correction rate. Brain activations correlating with error detection were isolated in the rostral cingulate zone and in the pre‐supplementary motor area, supporting their important role in error processing. Error correction activated similar brain regions, suggesting a common neuroanatomical substrate. Additional activations were found in the parietal cortex, representing an interconnected cortical network, which processes somatosensory information of tactile stimuli.
Sleep deprivation impairs hippocampus‐mediated contextual learning but not amygdala‐mediated cued learning in rats
Authors: Ruskin David N. , Liu Caiqin , Dunn Kelly E. , Bazan Nicolas G. , LaHoste Gerald J.
Published: June 2004

Prolonged sleep deprivation results in cognitive deficits. In rats, for example, sleep deprivation impairs spatial learning and hippocampal long‐term potentiation. We tested the effects of sleep deprivation on learning in a Pavlovian fear conditioning paradigm, choosing a sleep deprivation paradigm in which REM sleep was completely prevented and non‐REM sleep was strongly decreased. During conditioning, rats were given footshocks, either alone or paired with a tone, and tested 24 h later for freezing responses to the conditioning context, and to the tone in a novel environment. Whereas control animals had robust contextual learning in both background and foreground contextual conditioning paradigms, 72 h of sleep deprivation before conditioning dramatically impaired both types of contextual learning (by more than 50%) without affecting cued learning. Increasing the number of footshocks did not overcome the sleep deprivation‐induced deficit. The results provide behavioural evidence that REM/non‐REM sleep deprivation has neuroanatomically selective actions, differentially interfering with the neural systems underlying contextual learning (i.e. the hippocampus) and cued learning (i.e. the amygdala), and support the involvement of the hippocampus in both foreground and background contextual conditioning.
Synchronization of gamma oscillations increases functional connectivity of human hippocampus and inferior‐middle temporal cortex during repetitive visuomotor events
Authors: Claudio Babiloni , Martin Bares , Fabrizio Vecchio , Milan Brazdil , Pavel Jurak , Vito Moretti Davide , Alessandra Ubaldi , Maria Rossini Paolo , Ivan Rektor
Published: June 2004

Do recency processes associated with repetitive sensorimotor events modulate the magnitude and functional coupling of brain rhythmicity in human temporal cortex? Intracranial stereo electroencephalographic activity (SEEG; 256 Hz sampling rate) was recorded from hippocampus, and inferior (BA20) and middle (BA21) temporal cortex in four epilepsy patients. The repetitive events were represented by predicted imperative somatosensory stimuli (CNV paradigm) triggering hand movements (‘repetitive visuomotor’) or counting (‘repetitive counting’). The non‐repetitive events were ‘rare’ (P3 paradigm) somatosensory stimuli triggering hand movements (‘non‐repetitive visuomotor’) or counting (‘non‐repetitive counting’). Brain rhythmicity was indexed by event‐related desynchronization/synchronization (ERD/ERS) of SEEG data, whereas the functional coupling was evaluated by spectral SEEG coherence between pairs of the mentioned areas. The frequency bands of interest were theta (4–8 Hz), alpha (8–12 Hz), beta (14–30 Hz), and gamma (32–46 Hz). Compared to the non‐repetitive events, the ‘repetitive visuomotor’ events showed a significant beta and gamma ERS in the hippocampus and a significant theta ERD in the inferior temporal cortex. Furthermore, the ‘repetitive visuomotor’ events induced a task‐specific significant gamma coherence among the examined areas. These results suggest that recency processes do modulate the magnitude and functional coupling of brain rhythmicity (especially gamma) in the human temporal cortex.
Intracuneate mechanisms underlying primary afferent cutaneous processing in anaesthetized cats
Authors: Soto Cristina , Aguilar Juan , Martín‐Cora Francisco , Rivadulla Casto , Canedo Antonio
Published: June 2004

The cutaneous primary afferents from the upper trunk and forelimbs reach the medial cuneate nucleus in their way towards the cerebral cortex. The aim of this work was twofold: (i) to study the mechanisms used by the primary afferents to relay cutaneous information to cuneate cuneolemniscal (CL) and noncuneolemniscal (nCL) cells, and (ii) to determine the intracuneate mechanisms leading to the elaboration of the output signal by CL cells. Extracellular recordings combined with microiontophoresis demonstrated that the primary afferent cutaneous information is communicated to CL and nCL cells through AMPA, NMDA and kainate receptors. These receptors were sequentially activated: AMPA receptors participated mainly during the initial phase of the response, whereas kainate‐ and NMDA‐mediated activity predominated during a later phase. The involvement of NMDA receptors was confirmed by in vivo intracellular recordings. The cutaneous‐evoked activation of CL cells was decreased by GABA and increased by glycine acting at a strychnine‐sensitive site, indicating that glycine indirectly affects CL cells. Two subgroups of nCL cells were distinguished based on their sensitivity to iontophoretic ejection of glycine and strychnine. Overall, the results support a model whereby the primary afferent cutaneous input induces a centre‐surround antagonism in the cuneate nucleus by activating (via AMPA, NMDA and kainate receptors) and disinhibiting (via serial glycinergic–GABAergic interactions) a population of CL cells with overlapped receptive fields that at the same time inhibit (via GABAergic cells) other neighbouring CL cells with different receptive fields.
Measurement of coronary flow reserve in isolated hearts from mice
Authors: Bratkovsky S. , Aasum E. , Birkeland C. H. , Riemersma R. A. , Myhre E. S. P. , Larsen T. S.
Published: June 2004

Aim:  Langendorff‐perfused murine hearts are increasingly used in cardiovascular research, but coronary cardiovascular haemodynamics vary considerably from one research group to another. The aim of this study was to establish an isolated, retrogradely perfused mouse heart preparation for the simultaneous measurement of left ventricular haemodynamics and of coronary flow (CF).

Methods:  Heart rate was controlled by right atrial pacing (480 beats min−1) and heart temperature was kept constant. Accurate flow values of <0.5 mL min−1 could be determined, and this methodology was then used to study the stability of this preparation, as well as coronary response to vasoactive drugs and to short‐term ischaemia.

Results:  The CF and maximum systolic pressure were well maintained over a 2‐h perfusion period, both showing a 10% decline per hour. Sodium‐nitroprusside (endothelium‐independent) and adenosine (endothelium‐dependent) increased CF relatively modest (30–50% above baseline values). Short‐term no‐flow ischaemia caused a transient 40–50% increase in CF on reperfusion. Peak reflow occurred approximately 15 s after start of reperfusion and flow returned to baseline during the following 1–2 min. Increased coronary blood flow following infusion of vasoactive drugs (nitroprusside or adenosine) or short‐term ischaemia were associated with minor changes in ventricular pressure development.

Conclusions:  Blood flow and haemodynamics can readily be determined in this isolated perfused mouse heart model, but CF reserve is relatively small, compared with blood‐perfused organs.
Coexpression after electroporation of plasmid mixtures into muscle in vivo
Authors: Rana Z. A. , Ekmark M. , Gundersen K.
Published: June 2004

Aim:  Muscle is perhaps the most frequently considered tissue for non‐viral gene therapy, in particular after gene transfer by electroporation. Expression in muscle is stable, but since the cell turnover is so slow incorporation in the host genome is not required. This raises interesting practical and theoretical questions related to the behaviour of the transgenic DNA under such conditions.

Methods:  We have investigated expression of reporter genes from plasmid mixtures electroporated into the extensor digitorum longus (EDL) muscle in mice in order to assess the degree of coexpression.

Results:  Under conditions where the reporter is easily identified the coexpression rate was 100%, as none of 287 fibres from five different muscles expressing blue fluorescent protein (BFP) failed to express green fluorescent protein (GFP). With other reporter combinations the rate was lower, but this we attribute to marginal sensitivity for fluorescent proteins, or from reporter protein degradation for β‐galactosidase.

Conclusions:  The high degree of coexpression suggests that a large copy number takes part in the final transcription with this system. The finding also enhances the usefulness of muscle and electroporation for gene therapy and experimental biology.
Marked Prolongation of Murine Cardiac Allograft Survival Using Recipient Immature Dendritic Cells Loaded with Donor‐Derived Apoptotic Cells
Authors: Xu Dong‐Liang , Liu Yong , Tan Jian‐Ming , Li Bo , Zhong Cui‐Ping , Zhang Xin‐Hua , Wu Chao‐Qun , Tang Xiao‐Da
Published: June 2004

We investigated whether recipient dendritic cells (DCs), pretreated with nuclear factor‐κB oligodeoxyribonucleotide decoy (NF‐κB ODN decoy) and loaded with ultraviolet B‐irradiated donor apoptotic splenocytes (Apo‐SCs), were able to induce murine cardiac allograft tolerance. Heterotopic vascularized heart transplantation was performed from BALB/c to C57BL/6 mice, and recipients (C57BL/6) were given one injection of recipient DCs pretreated with NF‐κB ODN decoy and loaded with donor (BALB/c) apoptotic SCs (decoy Apo‐SCs DCs) through the portal vein at 7 days, before heart transplantation in the absence of immunosuppression. The cardiac allograft survival time and the expressive levels of intragraft cytokine genes [interleukin (IL)‐2, IL‐10, and interferon‐γ] were evaluated. Our results indicated that injection of decoy Apo‐SCs DCs significantly prolonged vascularized heart allograft survival and led to skewing of intragraft cytokine expression towards T helper 2 (IL‐10). The mechanisms can be useful for therapy of allograft rejection with minimization of systemic immunosuppression.
Distinct Functions of Vav1 in JNK1 Activation in Jurkat T Cells Versus Non‐Haematopoietic Cells
Authors: Kaminski S. , Del Pozo M. A. , Hipskind R. A. , Altman A. , Villalba M.
Published: June 2004

Vav1, the 95‐kDa protein encoded by the vav1 proto‐oncogene, is expressed exclusively in haematopoietic cells, where it becomes phosphorylated on tyrosine residues in response to antigen receptor ligation. Vav1 was found to act as a Rac1‐specific guanine nucleotide exchange factor and to activate c‐Jun N‐terminal kinase (JNK1) in vitro and in ectopic expression systems using non‐haematopoietic cells. Here, we studied the role of Vav1 in JNK1 activation in T cells versus non‐haematopoietic cells. Vav1 overexpression activated JNK1 in COS7 and 293T cells but not in Jurkat T lymphocytes. In contrast, constitutively activated Rac1 efficiently stimulated JNK1 in both cell types under the same conditions. Vav1 did function in T cells because it clearly stimulated the activity of a nuclear factor of activated T‐cell reporter plasmid in the same cells. Moreover, Vav1 induction of JNK1 in T cells required coexpression with calcineurin. This cooperation was cell type specific because it was not observed in COS7 or 293T cells. In contrast, Vav1 did not cooperate with calcineurin to activate either extracellular signal‐regulated kinase 2 or p38. These findings demonstrate that Vav1 alone is a poor activator of the JNK1 pathway in T cells and emphasize the importance of studying the physiological functions of Vav1 in haematopoietic cells.
Identification of a Type 1 Diabetes‐Associated CD4 Promoter Haplotype with High Constitutive Activity
Authors: Kristiansen O. P. , Karlsen A. E. , Larsen Z. M. , Johannesen J. , Pociot F. , Mandrup‐Poulsen T. ,   The Danish IDDM Epidemiology and Genetics Group & The Danish Study Group of IDDM in Childhood
Published: June 2004

CD4 is a candidate gene in autoimmune diseases, including Type 1 diabetes mellitus (T1DM), because the CD4 receptor is crucial for appropriate antigen responses of CD4+ T cells. We previously found linkage between a CD4‐1188(TTTTC)5−14 promoter polymorphism and T1DM. In the present study, we screened the human CD4 promoter for mutations and identified three frequent single nucleotide polymorphisms (SNPs): CD4‐181C/G, CD4‐521C/G and CD4‐1050T/C. The SNPs are in strong linkage disequilibrium (LD) and association with the CD4‐1188(TTTTC)5−14 alleles, and we observed nine CD4 promoter haplotypes, of which four are frequent. We genotyped the SNPs in 253 Danish T1DM families (1129 individuals) and found evidence for linkage and association of a CD4 (A4‐1188T‐1050G‐521C‐181) haplotype to T1DM. In reporter studies, we show that (1) the T1DM‐associated CD4 haplotype encodes high constitutive promoter activity and (2) the CD4‐181G variant encodes higher stimulated promoter activity than the CD4‐181C variant. This difference is in part neutralized in the frequently occurring CD4 promoter haplotypes by the more upstream genetic variants. Thus, we report functional impact of a novel CD4‐181C/G SNP on stimulated CD4 promoter activity and the identification of a novel CD4 haplotype with high constitutive promoter activity that is linked and associated with T1DM.
Interleukin‐10‐Modulated Immature Dendritic Cells Control the Proinflammatory Environment in Multiple Sclerosis
Authors: Adikari S. B. , Pettersson A. , Soderstrom M. , Huang Y.‐M. , Link H.
Published: June 2004

Multiple sclerosis (MS) is a disabling, inflammatory, demyelinating disease of the central nervous system considered to be mediated by autoreactive T cells. Dendritic cells (DC), being professional antigen‐presenting cells, play a pivotal role in the decision between T‐cell activation and anergy. It has been suggested that mature DC (mDC) induce immunity, whereas immature DC (imDC) have the potential to induce tolerance. In this study, we investigated the effects of autologous imDC versus autologous mDC on lymphocytes with respect to the expression of functionally important cell‐surface molecules and production of cytokines. Our aims were to investigate whether the maturation status of DC differs between MS and healthy controls (HC) and to explore whether the effects of DC on T‐cell responses differ between MS and HC. DC were generated from adherent blood mononuclear cells from patients with MS and HC. imDC were obtained by culture with either granulocyte–macrophage colony‐stimulating factor (GM‐CSF) + interleukin‐4 (IL‐4) or GM‐CSF + IL‐4 + IL‐10. mDC were obtained by adding lipopolysaccharide to DC cultures. Upon coculture with autologous lymphocytes, mDC activated the autologous T cells as reflected by increased CD25 and cytotoxic T‐lymphocyte antigen‐4 expression on CD4+ T cells together with the increased production of both T helper 1 (Th1) (IL‐2 and interferon‐γ) and Th2 (IL‐10 and IL‐4) cytokines. Unmodulated naïve imDC induced the production of only IL‐4. An exposure of imDC to IL‐10 induced the production of IL‐4 as well as IL‐10 by autologous lymphocytes. We hypothesize that such imDC are important in controlling the proinflammatory environment in vivo in patients with MS.
Waxy proteins and amylose content in diploid Triticeae species with genomes A, S and D
Authors: Rodriguez‐Quijano M. , Vázquez J. F. , Carrillo J. M.
Published: June 2004

A collection of 89 accessions of diploid species of wheat was analysed for waxy protein in the grain: 39 accessions of Einkorn wheats, 41 accessions of Sitopsis section wheat and nine accessions of Triticum tauschii. The electrophoretic patterns showed low polymorphism. In each group of wheat, a single and different allele was detected. In accessions of Einkorn wheats that allele had a similar electrophoretical mobility to the Wx‐A1a allele of the bread wheat ‘Chinese Spring’, in accessions of the Sitopsis section it had a similar mobility to that of the Wx‐B1f allele of tetraploid wheat, and in the accessions of T. tauschii, it was similar to the Wx‐D1a allele of the bread wheat ‘Chinese Spring’. The accessions were also analysed for apparent amylose content. Results showed that amylose content ranged from 22 to 35% in Einkorn wheats, from 28 to 41% in the Sitopsis section and from 26 to 35% in accessions of T. tauschii.
Chromosomal location of genes for carotenoid pigments in Hordeum chilense
Authors: Atienza S. G. , Ramírez C. M. , Hernández P. , Martín A.
Published: June 2004

In wheat, carotenoids are very important for end‐use quality in noodle production. Hexaploid tritordeums are the amphiploids derived from the cross between a wild diploid barley (Hordeum chilense) and durum wheat. Hexaploid tritordeums exhibit a higher carotenoid content than their respective wheat parents. The cross between H1 and H7 lines of H. chilense was used in order to map quantitative trait loci (QTL) for carotenoid content. Multiple interval mapping identified one QTL mapped on chromosome 2. This knowledge is helpful to transfer this favourable trait to other cereal genomes because of the high crossability of H. chilense with other members of the tribe Triticeae.
RAPD and SCAR markers for powdery mildew resistance gene er in pea
Authors: Janila P. , Sharma B.
Published: June 2004

In pea, a single recessive gene (er) on linkage group 6 confers resistance to powdery mildew caused by Erysiphe pisi. The present study aims to identify molecular markers linked to the er gene. Screening of the powdery mildew‐resistant cultivar ‘DMR11’ and its susceptible nearisogenic line for polymorphism revealed linkage of two RAPD primers (OPO‐02 and OPU‐17) to the er gene and a sequence characterized polymorphic region (SCAR) primer, ScOPD‐10650 with er in a population of 83 F2 plants in the order: OPU‐17 ‐ er ‐ ScOPD‐10650 ‐ OPO‐02. The markers ScOPD‐10650 and OPU‐17 being coupled with the allele causing resistance would substantially increase the efficiency of marker‐assisted selection in peabreeding for powdery mildew.
Using Multinomial Mixture Models to Cluster Internet Traffic
Authors: Jorgensen Murray
Published: June 2004

The paper considers the clustering of two large sets of Internet traffic data consisting of information measured from headers of transmission control protocol packets collected on a busy arc of a university network connecting with the Internet. Packets are grouped into 'flows' thought to correspond to particular movements of information between one computer and another. The clustering is based on representing the flows as each sampled from one of a finite number of multinomial distributions and seeks to identify clusters of flows containing similar packet‐length distributions. The clustering uses the EM algorithm, and the data‐analytic and computational details are given.
Criteria for Linear Model Selection Based on Kullback's Symmetric Divergence
Authors: Cavanaugh Joseph E.
Published: June 2004

Model selection criteria are frequently developed by constructing estimators of discrepancy measures that assess the disparity between the 'true' model and a fitted approximating model. The Akaike information criterion (AIC) and its variants result from utilizing Kullback's directed divergence as the targeted discrepancy. The directed divergence is an asymmetric measure of separation between two statistical models, meaning that an alternative directed divergence can be obtained by reversing the roles of the two models in the definition of the measure. The sum of the two directed divergences is Kullback's symmetric divergence.

In the framework of linear models, a comparison of the two directed divergences reveals an important distinction between the measures. When used to evaluate fitted approximating models that are improperly specified, the directed divergence which serves as the basis for AIC is more sensitive towards detecting overfitted models, whereas its counterpart is more sensitive towards detecting underfitted models. Since the symmetric divergence combines the information in both measures, it functions as a gauge of model disparity which is arguably more balanced than either of its individual components. With this motivation, the paper proposes a new class of criteria for linear model selection based on targeting the symmetric divergence. The criteria can be regarded as analogues of AIC and two of its variants: 'corrected' AIC or AICc and 'modified' AIC or MAIC. The paper examines the selection tendencies of the new criteria in a simulation study and the results indicate that they perform favourably when compared to their AIC analogues.
Continuous‐Time Stochastic Processes with Cyclical Long‐Range Dependence
Authors: Anh V.V. , Knopova V.P. , Leonenko N.N.
Published: June 2004

This paper introduces continuous‐time random processes whose spectral density is unbounded at some non‐zero frequencies. The discretized versions of these processes have asymptotic properties similar to those of discrete‐time Gegenbauer processes. The paper presents some properties of the covariance function and spectral density as well as a theory of statistical estimation of the mean and covariance function of such processes. Some directions for further generalizations of the results are indicated.
Modelling Social Infrastructure and Economic Growth
Authors: Chin Martin S. , Chou Yuan K.
Published: June 2004

This paper develops a growth model with a public sector and a human capital sector to explore the impact of social infrastructure on investment in physical capital, the accumulation of skills, output, and consumption. We show that the implications of the model are consistent with the empirical observations ofHall and Jones (1999). Economies where government policies and institutions encourage production over diversion have a larger ‘stock’ of social infrastructure, conditional on population size and sophistication of diversion technologies, which raises output per worker by increasing the extent of participation in market, rather than diversive, activities. The magnitude of these effects depends on economic agents’ inherent propensity for rent‐seeking. In addition, economies with unstable governments may suffer from an under‐provision of social infrastructure and, consequently, have reduced levels of capital and output per worker.
Modelling Students at Risk
Authors: Dancer Diane M. , Fiebig Denzil G.
Published: June 2004

Using a sample of several hundred students we model progression in a first‐year econometrics course. Our primary interest is in determining the usefulness of these models in the identification of ‘students at risk’. This interest highlights the need to distinguish between students who drop the course and those who complete but who ultimately fail. Such models allow identification and quantification of the factors that are most important in determining student progression and thus make them a potentially useful aid in educational decision making. Our main findings are that Tertiary Entrance Rank (TER), mathematical aptitude, being female and attendance in tutorials are all good predictors of success but amongst these factors only attendance is significant in discriminating between students who fail and those who discontinue. Also, there are differences across degree programs and, in particular, students in Combined Law are very likely to pass but, if they are at risk, they are much more likely to discontinue than to fail.
COPPER AGE DITCHED ENCLOSURES IN CENTRAL IBERIA
Authors: DÍAZ‐DEL‐RÍO PEDRO
Published: June 2004

Summary.  The interpretation of European Neolithic enclosures must take account of their wide variability in chronology, size, shape, topographical position and material. Such interpretations should rely on the comparative analysis of the processes at work in particular regions. Newly recovered data from small early third millennium cal BC ditched enclosures in central Iberia, with high densities of features and domestic refuse, support the hypothesis of permanent habitation. This paper argues that the variability in late Neolithic–Chalcolithic enclosures throughout Iberia is a result of the cycling of fission and fusion characteristic of segmentary social dynamics.
Speaking of Tongues
Authors: Fussner Hannah
Published: June 2004

In this paper I reflect on claims that artefacts, as alternatives to texts, can provide an effective means of access to learning. With reference to the work of Walter Benjamin, I analyse the role the “aura” of a ritual object played in engaging a group of Year 6 students, all of whom experienced various degrees of delayed literacy. Drawing on Levi‐Strauss' essay “On the Effectiveness of Symbols”, I consider how far a unit of work involving aspects of a ritual against slander allowed the students to develop their understanding of how perfomative language might function.
The Rehabilitative Role of Arts Education in Prison: Accommodation or Enlightenment?
Authors: Clements Paul
Published: June 2004

The prisoner constituency is one of the most excluded in society. Addressing recidivism requires amongst other considerations, an enabling of these individuals to fulfil rehabilitative intent. The article argues that this necessitates an educational discourse and methodology that is embedded in concepts of emancipation and empowerment, where creativity and heuristic learning enable personal transformation. The arts are one of the agents that can naturally encourage spontaneous and participatory learning, enabling a more liberating and self‐directed rehabilitative process. Notwithstanding, arts education in prison illuminates the struggle between individual creative needs and social accommodation. Historically the shifting paradigm of penal policy has reflected a wider political intention. But there is an irony as the New Labour government that champions social inclusion has overseen the reduction of opportunity in prison to engage with the arts, replaced by an instrumental agenda concerning basic, key and cognitive skills. Furthermore, this has arguably been costly and ineffectual, hence the need to accommodate a more creative and expressive curriculum. The article has been divided into two parts. The first examines competing discourses of penal educational provision in order to assess the role of the arts. The second part examines a radical educational agenda of inclusion based on emancipatory theory, as a conduit for personal transformation, in which the creative arts have a central role.
The Status of Graphical Presentation in Interior/Architectural Design Education
Authors: Gurel Meltem O. , Basa Inci
Published: June 2004

This article argues that interior/architectural design education favours a dominance of final presentation over the design process in the studio environment, particularly in the evaluation of a project. It suggests that the appeal of design juries for pleasant drawings, which may shift the emphasis from the project itself to its representation, may be recognized as a discursive habit with limited contribution for educational concerns. The theoretical stance argues that the interest for graphical presentation has primarily remained within a formalist aesthetic agenda and has rarely been conceptualized beyond this convention. With this in mind a series of questions is developed in order to reform the relationship between graphical presentation and the design education process.
Ergonomic Pain––Part 2: Differential Diagnosis and Management Considerations
Authors: Sizer Phillip S. , Phelps Valerie , Brismée Jean Michél , Cook Chad , Dedrick Leslie
Published: June 2004

Abstract: Work‐related musculoskeletal disorders (MSDs) can produce ergonomic pain in several different regions of the body, including the shoulder, elbow, wrist and hand, lumbar spine, knee, and ankle/foot. Each family of disorders is distinctive in presentation and requires diagnosis‐specific interventions. Because of the complex nature of these disorders, management approaches may not always eliminate symptoms and or completely restore patient function to a level found prior to symptom onset. As a consequence, ergonomic measures should be implemented to reduce the overload on tissue and contribute to patient recovery. However, functional limits may persist and the clinician must make further decisions regarding a person's functional status in the chronic stages of the patient's care.
The Type II Protein Secretion System of
Legionella pneumophila
Promotes Growth at Low Temperatures
Authors: Söderberg Maria A. , Rossier Ombeline , Cianciotto Nicholas P.
Published: June 2004

The gram-negative bacterium
Legionella pneumophila
grows in both natural and man-made water systems and in the mammalian lung as a facultative intracellular parasite. The PilD prepilin peptidase of
L. pneumophila
promotes type IV pilus biogenesis and type II protein secretion. Whereas pili enhance adherence,
Legionella
type II secretion is critical for intracellular growth and virulence. Previously, we observed that
pilD
transcript levels are greater in legionellae grown at 30 versus 37°C. Using a new
pilD
::
lacZ
fusion strain, we now show that
pilD
transcriptional initiation increases progressively as
L. pneumophila
is grown at 30, 25, and 17°C.
Legionella pilD
mutants also had a dramatically reduced ability to grow in broth and to form colonies on agar at the lower temperatures. Whereas strains specifically lacking type IV pili were not defective for low-temperature growth, mutations in type II secretion (
lsp
) genes greatly impaired the capacity of
L. pneumophila
to form colonies at 25, 17, and 12°C. Indeed, the
lsp
mutants were completely unable to grow at 12°C. The growth defect of the
pilD
and
lsp
mutants was complemented by reintroduction of the corresponding intact gene. Interestingly, the
lsp
mutants displayed improved growth at 25°C when plated next to a streak of wild-type but not mutant bacteria, implying that a secreted, diffusible factor promotes low-temperature growth. Mutants lacking either the known secreted acid phosphatases, lipases, phospholipase C, lysophospholipase A, or protease grew normally at 25°C, suggesting the existence of a critical, yet-to-be-defined exoprotein(s). In summary, these data document, for the first time, that
L. pneumophila
replicates at temperatures below 20°C and that a bacterial type II protein secretion system facilitates growth at low temperatures.
Regulatory Elements of theStaphylococcus aureusProtein A (Spa) Promoter
Authors: Gao Jinxin , Stewart George C.
Published: June 2004

Staphylococcal protein A (Spa) is an important virulence factor ofStaphylococcus aureus. Transcription of thespadeterminant occurs during the exponential growth phase and is repressed when the cells enter the postexponential growth phase. Regulation ofspaexpression has been found to be complicated, with regulation involving multiple factors, including Agr, SarA, SarS, SarT, Rot, and MgrA. Our understanding of how these factors work on thespapromoter to regulatespaexpression is incomplete. To identify regulatory sites within thespapromoter, analysis of deletion derivatives of the promoter in host strains deficient in one or more of the regulatory factors was undertaken, and several critical features ofsparegulation were revealed. The transcriptional start sites ofspawere determined by primer extension. Thespapromoter sequences were subcloned in front of a promoterless chloramphenicol acetyltransferase reporter gene. Various lengths ofspatruncations with the same 3′ end were constructed, and the resultant plasmids were transduced into strains with different regulatory genetic backgrounds. Our results identified upstream promoter sequences necessary for Agr system regulation ofspaexpression. Theciselements for SarS activity, an activator ofspaexpression, and for SarA activity, a repressor ofspaexpression, were identified. The well-characterized SarA consensus sequence on thespapromoter was found to be insufficient for SarA repression of thespapromoter. Full repression required the presence of a second consensus site adjacent to the SarS binding site. Sequences directly upstream of the core promoter sequence were found to stimulate transcription.
Membrane Restructuring by
Bordetella pertussis
Adenylate Cyclase Toxin, a Member of the RTX Toxin Family
Authors: Martín César , Requero M.-Asunción , Masin Jiri , Konopasek Ivo , Goñi Félix M. , Sebo Peter , Ostolaza Helena
Published: June 2004

Adenylate cyclase toxin (ACT) is secreted by
Bordetella pertussis
, the bacterium causing whooping cough. ACT is a member of the RTX (repeats in toxin) family of toxins, and like other members in the family, it may bind cell membranes and cause disruption of the permeability barrier, leading to efflux of cell contents. The present paper summarizes studies performed on cell and model membranes with the aim of understanding the mechanism of toxin insertion and membrane restructuring leading to release of contents. ACT does not necessarily require a protein receptor to bind the membrane bilayer, and this may explain its broad range of host cell types. In fact, red blood cells and liposomes (large unilamellar vesicles) display similar sensitivities to ACT. A varying liposomal bilayer composition leads to significant changes in ACT-induced membrane lysis, measured as efflux of fluorescent vesicle contents. Phosphatidylethanolamine (PE), a lipid that favors formation of nonlamellar (inverted hexagonal) phases, stimulated ACT-promoted efflux. Conversely, lysophosphatidylcholine, a micelle-forming lipid that opposes the formation of inverted nonlamellar phases, inhibited ACT-induced efflux in a dose-dependent manner and neutralized the stimulatory effect of PE. These results strongly suggest that ACT-induced efflux is mediated by transient inverted nonlamellar lipid structures. Cholesterol, a lipid that favors inverted nonlamellar phase formation and also increases the static order of phospholipid hydrocarbon chains, among other effects, also enhanced ACT-induced liposomal efflux. Moreover, the use of a recently developed fluorescence assay technique allowed the detection of trans-bilayer (flip-flop) lipid motion simultaneous with efflux. Lipid flip-flop further confirms the formation of transient nonlamellar lipid structures as a result of ACT insertion in bilayers.
Mutational Analysis of the
Myxococcus xanthus
Ω4499 Promoter Region Reveals Shared and Unique Properties in Comparison with Other C-Signal-Dependent Promoters
Authors: Yoder Deborah R. , Kroos Lee
Published: June 2004

The bacterium
Myxococcus xanthus
undergoes multicellular development during times of nutritional stress and uses extracellular signals to coordinate cell behavior. C-signal affects gene expression late in development, including that of Ω4499, an operon identified by insertion of Tn
5 lac
into the
M. xanthus
chromosome. The Ω4499 promoter region has several sequences in common with those found previously to be important for expression of other C-signal-dependent promoters. To determine if these sequences are important for Ω4499 promoter activity, the effects of mutations on expression of a downstream reporter gene were tested in
M. xanthus
. Although the promoter resembles those recognized by
Escherichia coli
σ
54
, mutational analysis implied that a σ
70
-type σ factor likely recognizes the promoter. A 7-bp sequence known as a C box and a 5-bp element located 6 bp upstream of the C box have been shown to be important for expression of other C-signal-dependent promoters. The Ω4499 promoter region has C boxes centered at −33 and −55 bp, with 5-bp elements located 7 and 8 bp upstream, respectively. A multiple-base-pair mutation in any of these sequences reduced Ω4499 promoter activity more than twofold. Single base-pair mutations in the C box centered at −33 bp yielded a different pattern of effects on expression than similar mutations in other C boxes, indicating that each functions somewhat differently. An element from about −81 to −77 bp exerted a twofold positive effect on expression but did not appear to be responsible for the C-signal dependence of the Ω4499 promoter. Mutations in
sigD
and
sigE
, which are genes that encode σ factors, reduced expression from the Ω4499 promoter. The results provide further insight into the regulation of C-signal-dependent genes, demonstrating both shared and unique properties among the promoter regions so far examined.
Role of RepA and DnaA Proteins in the Opening of the Origin of DNA Replication of an IncB Plasmid
Authors: Betteridge T. , Yang J. , Pittard A. J. , Praszkier J.
Published: June 2004

The replication initiator protein RepA of the IncB plasmid pMU720 was shown to induce localized unwinding of its cognate origin of replication in vitro. DnaA, the initiator protein of
Escherichia coli
, was unable to induce localized unwinding of this origin of replication on its own but enhanced the opening generated by RepA. The opened region lies immediately downstream of the last of the three binding sites for RepA (RepA boxes) and covers one turn of DNA helix. A 6-mer sequence, 5′-TCTTAA-3′, which lies within the opened region, was essential for the localized unwinding of the origin in vitro and origin activity in vivo. In addition, efficient unwinding of the origin of replication of pMU720 in vitro required the native positioning of the binding sites for the initiator proteins. Interestingly, binding of RepA to RepA box 1, which is essential for origin activity, was not required for the localized opening of the origin in vitro.