bluuebunny/crossref_metadata_2025 huggingface dataset:
Second-order integral model for a round turbulent buoyant jet
Authors: WANG HONGWEI , WING-KEUNG LAW ADRIAN
Published: October 2002

The development of a second-order integral model for a round turbulent buoyant
jet is reported based on new experimental data on turbulent mass and momentum
transport. The mean and turbulent characteristics of a round vertical buoyant jet
covering the full range from jets to plumes were investigated using a recently developed
combined digital particle image velocimetry (DPIV) and planar laser-induced
fluorescence (PLIF) system. The system couples the two well-known techniques to
enable synchronized planar measurements of flow velocities and concentrations in
a study area. The experimental results conserved the mass and momentum fluxes
introduced at the source accurately with closure errors of less than 5%. The momentum
flux contributed by turbulence and streamwise pressure gradient was determined
to be about 10% of the local mean momentum flux in both jets and plumes. The
turbulent mass flux, on the other hand, was measured to be about 7.6% and 15%
of the mean mass flux for jets and plumes respectively. While the velocity spread
rate was shown to be independent of the flow regime, the concentration-to-velocity
width ratio λ varied from 1.23 to 1.04 during the transition from jet to plume. Based
on the experimental results, a refined second-order integral model for buoyant jets
that achieves the conservation of total mass and momentum fluxes is proposed. The
model employs the widely used entrainment assumption with the entrainment coefficient
taken to be a function of the local Richardson number. Improved prediction
is achieved by taking into account the variation of turbulent mass and momentum
fluxes. The variation of turbulent mass flux is modelled as a function of the local
Richardson number. The turbulent momentum flux, on the other hand, is treated
as a fixed percentage of the local mean momentum flux. In addition, unlike most
existing integral models that assume a constant concentration-to-velocity width ratio,
the present model adopts a more accurate approach with the ratio expressed as a
function of the local Richardson number. As a result, smooth transition of all relevant
mean and turbulent characteristics from jet to plume is predicted, which is in line
with the underlying physical processes.
Back to the Future? Implementing the Anglo-Argentine 14th July 1999 Joint Statement
Authors: DODDS KLAUS , MANÓVIL LARA
Published: October 2002

This article is concerned with the implementation of the Anglo-Argentine 14th July 1999 Joint Statement relating to the Falklands/Malvinas and the South West Atlantic. Initial consideration is given to the recent historical and political context of the Falklands/Malvinas dispute. The arrest of General Pinochet in London is shown to have been a significant factor in Anglo-Argentine relations during the period of 1998–1999. Thereafter, the background relating to the 14th July 1999 Joint Statement is considered in some detail as it relates to fishing, travel, place names, land mines and an Argentine war memorial on the Falkland Islands. Each element of the Joint Statement is shown to be problematic, and the article concludes with the belief that the provisions of the Joint Statement will continue to strengthen the rapprochement between Britain and Argentina without making any substantial progress towards the eventual solution of the dispute over the Falklands/Malvinas.
The Origin, Impact and Demise of the 1989–1990 Colombian Student Movement: Insights from Social Movement Theory
Authors: DUGAS JOHN C.
Published: October 2002

The 1989–1990 Colombian student movement played a key role in bringing about a constituent assembly to draft a new national constitution. This article utilises contemporary social movement theory, secondary sources and interviews with student activists to examine the trajectory of this movement. Key explanatory variables of social movement theory – political opportunity structure, organisational form, the framing process and the repertoire of collective action – provide useful insights into the origins, impact and ultimate demise of the Colombian student movement. Judicious use of such variables could benefit research on other social movements in Latin America.
Whither the Cuban economy after recovery? The reform process, upgrading strategies and the question of transition
Authors: BRUNDENIUS CLAES
Published: October 2002

Where is the Cuban economy heading? The economy has been recovering at an average rate of four per cent per year since 1994 (after GDP declined by 35 per cent between 1989 and 1993). Many reforms have been undertaken in the direction of a market economy, but it is far from clear what kind of economy the Cuban ruling party has in mind after recovery. This article discusses the successes and shortcomings of the reform process in Cuba since the downfall of communism in Europe and the Soviet Union. It also addresses the salient issues in what appears to be a new development strategy in Cuba, and what could be said about the reforms and the strategy in the light of the debate on transition ‘ten years after’.
Discourse markers and the PA/SN distinction
Authors: SCHWENTER SCOTT A.
Published: October 2002

Many languages have two types of adversative sentence conjunctions (e.g. Spanish, German). These are normally referred to as PA and SN conjunctions. However, while PA conjunctions can be used as discourse markers (DMs) in dialogal discourse, SN conjunctions such as those found in Spanish and German cannot be used in dialogues. Thus the PA/SN distinction does not extend fully to the dialogal realm. Using data from another Spanish DM, I argue that the PA/SN distinction can be extended beyond the monologal realm of sentence conjunction to the realm of adversative discourse markers employed in dialogal discourse. The findings have implications for the question of functional equivalence across different types of discourse.
Empty nest or revolving door? A prospective study of women's quality of life in midlife during the phase of children leaving and re-entering the home
Authors: DENNERSTEIN L. , DUDLEY E. , GUTHRIE J.
Published: October 2002

Background. This study documents changes in household composition and effects on women's quality of life of children leaving and returning home.

Methods. A 9-year annual prospective study of a population-based sample of mid-aged Australian-born women who were premenopausal at baseline (N = 438) was conducted. Documentation was made of household composition and change, well-being, bothersome symptoms, daily hassles, feelings for partner and frequency of sexual activities.

Results. There was an increase in the number of women living alone, and a reduction in number of households in which there were children or parents. Each year >25% of women reported a change in household composition. In the first year after the last child departed (N = 155), there was an improvement in women's positive mood and total well-being and a reduction in negative mood and the number of daily hassles. This improvement in mood was confined to those women who at baseline were not worried about children leaving home. In the first year after children return home there was a trend towards reduced frequency of sexual activities but no mood changes.

Conclusions. For the majority of women, the departure of the last child from the household leads to positive changes in women's mood state and a reduced number of daily hassles. Return of offspring may have an adverse effect on sexual relating of the parents.
Inter-episodic morbidity and drop-out under carbamazepine and lithium in the maintenance treatment of bipolar disorder
Authors: KLEINDIENST N. , GREIL W.
Published: October 2002

Background. Evaluation of mood-stabilizing treatment strategies usually focuses on their efficacy in preventing recurrences. The aim of this study is to supplement evaluation by two important aspects: inter-episodic morbidity and drop-out.

Methods. Using a global outcome measure, response to prophylactic lithium and carbamazepine was evaluated in N = 171 bipolar patients (DSM-IV) participating in a randomized controlled trial with an observation period of 2½ years (MAP study).

Results. The rates of re-hospitalization were similar for both treatments. However, the percentage of good clinical response (i.e. patients with a low score of inter-episodic morbidity and without both re-hospitalization and drop-out during the observation period) was significantly higher in patients randomized to lithium (40% v. 24%). This superiority of lithium resulted essentially from a lower drop-out rate in patients without re-hospitalization (17% v. 42%). Regarding severity of inter-episodic morbidity, no clear difference between the drugs was found. For both medications the predominant symptomatology was minor depressive (but not manic, mixed or schizoaffective) symptoms. In the lithium group, inter-episodic morbidity in patients without re-hospitalization significantly decreased during the first 10 months and remained on the lower level for the rest of the observation period. For carbamazepine, reduction of inter-episodic morbidity over time did not reach statistical significance. Inter-episodic morbidity was significantly related to drop-out and to re-hospitalization for both medications.

Conclusion. Taking inter-episodic morbidity, drop-out and re-hospitalization into consideration, the response rate in bipolar patients (DSM-IV) was higher for prophylactic lithium than for carbamazepine. The global outcome parameter used appears to be a valuable measure of clinical response to mood stabilizing drugs.
Reversed lateralization of temporal activation during speech production in thought disordered patients with schizophrenia
Authors: KIRCHER T. T. J. , LIDDLE P. F. , BRAMMER M. J. , WILLIAMS S. C. R. , MURRAY R. M. , McGUIRE P. K.
Published: October 2002

Background. Formal thought disorder is a core symptom of schizophrenia. It is associated with a reversed lateralization of the superior temporal cortex volume, an area that is implicated in lexical retrieval. We investigated the neural correlates of word retrieval during continuous speech in patients with formal thought disorder using functional magnetic resonance imaging (fMRI).

Methods. Blood oxygenation level dependent (BOLD) contrast was measured with fMRI while six patients with schizophrenia and six healthy control subjects spoke about seven Rorschach inkblots for 3 min each. Subjects produced varying amounts of speech during each run. In a within subject design, the number of words produced was correlated with the BOLD contrast in the two runs in each participant who showed the highest variance of speech output.

Results. In control subjects, the amount of speech produced was mainly correlated with activation in the left superior temporal gyrus. In the patient group, the main correlations were in the right superior temporal gyrus.

Conclusions. During the production of continuous speech, patients with formal thought disorder showed a reversed laterality of activation in the superior temporal cortex. This is consistent with findings of perturbed hemispheric interaction in schizophrenia, particularly in patients with formal thought disorder.
Heavy users of acute psychiatric beds: randomized controlled trial of enhanced community management in an outer London borough
Authors: HARRISON-READ P. , LUCAS B. , TYRER P. , RAY J. , SHIPLEY K. , SIMMONDS S. , KNAPP M. , LOWIN A. , PATEL A. , HICKMAN M.
Published: October 2002

Background. Heavy users of psychiatric services, often defined as the population that uses the most beds, consume a large part of the resources used by the whole service, despite being relatively small in number. Any intervention that reduces heavy use is therefore likely to lead to significant savings, and enhancement of standard care using a form of intensive case management akin to assertive community treatment was thought to be a pragmatic strategy for testing in this group.

Methods. The effectiveness of enhanced community management (ECM) was compared with standard care alone in heavy users, who represented the 10% of patients with the highest number of hospital admissions and occupied bed days over the previous 6·5 years in an outer London borough. One hundred and ninety-three patients were randomly assigned to ECM or standard care and their use of services was determined after 1 and 2 years, with assessments of costs, clinical symptoms, needs, and social function made before entry into the study and after 1 and 2 years.

Results. Despite a 2·4 fold increase in community contacts in the study group, there were no significant differences between the two groups in any of the main outcome measures. Small savings on in-patient and day-hospital service costs were counterbalanced by the increased costs of outpatient and community care for the subjects assigned to ECM. Clinical outcome data derived from interviews in two-thirds of the subjects were similar in both groups.

Conclusions. Providing additional intensive community – focused care to a group of heavy users of psychiatric in-patient services in an outer London borough does not lead to any important clinical gains or reduced costs of psychiatric care.
The concordance of ICD-10 acute and transient psychosis and DSM-IV brief psychotic disorder
Authors: PILLMANN F. , HARING A. , BALZUWEIT S. , BLÖINK R. , MARNEROS A.
Published: October 2002

Background. ICD-10 acute and transient psychotic disorder (ATPD; F23) and DSM-IV brief psychotic disorder (BPD; 298.8) are related diagnostic concepts, but little is known regarding the concordance of the two definitions.

Method. During a 5-year period all in-patients with ATPD were identified; DSM-IV diagnoses were also determined. We systematically evaluated demographic and clinical features and carried out follow-up investigations at an average of 2·2 years after the index episode using standardized instruments.

Results. Forty-two (4·1%) of 1036 patients treated for psychotic disorders or major affective episode fulfilled the ICD-10 criteria of ATPD. Of these, 61·9% also fulfilled the DSM-IV criteria of brief psychotic disorder; 31·0%, of schizophreniform disorder; 2·4%, of delusional disorder; and 4·8%, of psychotic disorder not otherwise specified. BPD showed significant concordance with the polymorphic subtype of ATPD, and DSM-IV schizophreniform disorder showed significant concordance with the schizophreniform subtype of ATPD. BPD patients had a significantly shorter duration of episode and more acute onset compared with those ATPD patients who did not meet the criteria of BPD (non-BPD). However, the BPD group and the non-BPD group of ATPD were remarkably similar in terms of sociodemography (especially female preponderance), course and outcome, which was rather favourable for both groups.

Conclusions. DSM-IV BPD is a psychotic disorder with broad concordance with ATPD as defined by ICD-10. However, the DSM-IV time criteria for BPD may be too narrow. The group of acute psychotic disorders with good prognosis extends beyond the borders of BPD and includes a subgroup of DSM-IV schizophreniform disorder.
Different negative priming impairments in schizophrenia and subgroups of obsessive–compulsive disorder
Authors: HOENIG K. , HOCHREIN A. , MÜLLER D. J. , WAGNER M.
Published: October 2002

Background. Inhibitory functioning is assumed to be deficient in some psychiatric disorders, most notably in patients with schizophrenia and obsessive–compulsive disorder (OCD). In order to investigate inhibitory functioning, priming tasks are commonly used. The present paradigm offers the opportunity to isolate specific distractor features (identity, location) for independent examination.

Methods. Negative priming (NP) for stimulus identity and location was examined in patients with schizophrenia (N = 16), patients with OCD (N = 15) and matched controls (N = 16). All groups performed a referent size-selection task in which they were instructed successively to select the larger one of two cardinal numbers. The deeper processing of both stimuli was expected to yield large NP effects that allow the detection of subtle group differences.

Results. Large NP effects were found for stimulus identity in all three groups. Schizophrenic patients differed from normal controls with respect to the amount of incidental location priming. Subgroup analyses of OCD patients showed NP impairments for checkers when the response–stimulus interval (RSI) was short, but large identity NP when the RSI was long. OCD non-checkers showed normal NP patterns with short RSI, but reduced identity NP with longer RSI.

Conclusions. Schizophrenic patients do not show the ability to use spatial selective attention in order to guide their actions as shown by normal controls. Information processing was differentially impaired in OCD subgroups (checkers and non-checkers) dependent on RSI variation. This result supports those studies that found reduced NP in OCD patients and points to the necessity of differential subgroup studies.
Characterizing the effects of sertraline in post-traumatic stress disorder
Authors: DAVIDSON J. R. T. , LANDERMAN L. R. , FARFEL G. M. , CLARY C. M.
Published: October 2002

Background. Sertraline has a proved efficacy in post-traumatic stress disorder (PTSD), but it is unknown which symptoms respond or in what sequence this occurs. Such information might be useful clinically and heuristically.

Method. The study examined the effects of sertraline on the individual symptoms of PTSD. It also examined whether early changes in anger explained drug-induced change in other symptoms over time. Mixed models analysis was applied to datasets from two 12-week placebo-controlled trials of sertraline. A validated self-rating scale (DTS) was used to assess treatment efficacy.

Results. Sertraline was superior to placebo on 15 of 17 symptoms, especially in the numbing and hyperarousal clusters. A strong effect was found on anger from week 1, which partly explained the subsequent effects of sertraline on other symptoms, some of which began to show significantly greater response to drug than to placebo at week 6 (emotional upset at reminders, anhedonia, detachment, numbness, hypervigilance) and week 10 (avoidance of activities, foreshortened future).

Conclusions. Sertraline exercises a broad spectrum effect in PTSD. Effects are more apparent on the psychological rather than somatic symptoms of PTSD, with an early modulation of anger and, perhaps, other affects, preceding improvement in other symptoms.
Wu and shaman
Authors: BOILEAU GILLES
Published: October 2002

Since Shangdai de shenhua yu wushu, Chen Mengjia's article on Shang mythology, some sinological works have proposed that the Chinese wu was an equivalent of the Siberian shaman. I examine first the issues in anthropological comparatism involved in this problem and provide up-to-date information on Siberian shamanism. It must be noted that the Chinese texts are by no means equivalent to modern anthropological data and that these texts did not originate directly from the wu themselves; they are rather a collection of opinions or stories on the wu. Detailed study of the nature and social status of the Chinese wu, either in oracular inscriptions or late Zhou received texts, shows a systematic association of the wu with non-auspicious or negative events, like funerals, death or natural catastrophes. A further analysis of the data reveals that the wu's activities in relation to natural phenomena were frequently presented in terms related to sexuality. This last point permits a comparison with Siberian shamans, whose activities are also linked to fecundity and sexuality, although the Chinese texts often associate the wu with sexual misbehaviour and blame them on moral grounds. They go as far as to treat them as dangerous sorcerers who must be weeded out. According to these data, the wu's social function is linked to the handling of misfortune, either directly or by being associated with ritually unacceptable behaviours. On the whole, my conclusion is that even the common point between wu and Siberian shaman (the link with sexuality) is not sufficient to allow for a translation of ‘wu’ by ‘shaman’, especially in view of the differences of social and historical context.
Insecure Families and Low-Paying Labour Markets:
Comments on the British Experience
Authors: DEAN HARTLEY , SHAH AMBREEN
Published: October 2002

There has been a raft of policy changes in the UK that are intended to
help low-income families engage with the labour market. Drawing in part
upon the findings of a small-scale qualitative study of the experiences of
low-income working families, this article infers that the secular trend to
working parenthood may, as matters stand, be experienced rather differently
by secure middle-class families than by poor families. It may be that
the former will benefit from policies to improve access to formal childcare,
career breaks and time off when needed. The latter are more likely to
remain dependent on informal childcare from other family members or
friends and receive minimal concessions granted by reluctant employers.
While benefits such as working families tax credit will help to secure the
material needs of low-income working families, low-paid employment
will remain no less precarious and it is possible that the insecurity experienced
by low-income working families will increase.
Changing Visions of Koreanness in Oh Tae-sok's Plays, Africa and Love with Foxes
Authors: Shim Jung-Soon
Published: October 2002

Korean playwright, Oh Tae-sok tenaciously has pursued the question of Koreanness in his uniquely experimental style of theatre since the 1970s. The changing visions of Koreanness represented in his social dramas Africa (1984) and Love with Foxes (1996) are examined from a postcolonial perspective. In Africa, Oh's early-80s vision of Korea's historical encounters with the outside world reveals a traditional sense of integrity and innocence being crushed by an increasing sense of alienating globalization. In Love with Foxes, Oh projects another vision of a globalized Korea of the mid-90s as the ‘double’ of a Western metropolitan centre, grimly replicating the dynamics of domination among Korean diasporas and other Asian peoples. Oh, however, ultimately bases his hope for an imagined community of Koreans on their traditional sense of integrity, embracing all kinds of differences.
DV8's Can We Afford This: The Cost of Devising on Site for Global Markets
Authors: Harvie Jen
Published: October 2002

London-based DV8 Physical Theatre makes company-devised hybrid dance/theatre performance which consistently is socially committed, exploring the power dynamics of different forms of social inclusion and exclusion. The company's 2000 show, Can We Afford This, focused particularly on social prejudice about ‘the body beautiful’. Using seventeen dancers of different physical and technical abilities, ages, genders, and sizes, the show both critiqued prejudices about what constitutes the body beautiful and posited other, more inclusive, images of beautiful bodies. This analysis considers how the show's argument was focused and enhanced in its original context of devising and production (Sydney, Australia, in its Olympic and Paralympic year of 2000) and, in contrast, was dissipated and generalized when it moved out of that context to tour to the international markets of London and Hong Kong.
Salt balances of inland shrimp ponds in Thailand: implications for land and water salinization
Authors: Braaten Robert O. , Flaherty Mark
Published: October 2002

Brackish water ponds for farming black tiger shrimp (Penaeus monodon) have recently proliferated in inland areas of Thailand's central plain, raising concerns about land and water salinization. The environmental impacts of inland shrimp farming were assessed by analysing the salt balance for an inland shrimp farm. Field data on water fluxes and pond salinity, collected from nine ponds in Chachoengsao Province from May–July 1999, were used to model the salt balance for a typical shrimp pond over one growout cycle. During growout, seepage represented 38% (11.5 tonnes crop−1) of salt losses, pond discharge 33% (9.7 tonnes crop−1), and accumulation of salt in pond sediment 6% (1.8 tonnes crop−1). About 23% of the initial salt content remained at harvest and could have been recycled. However, the majority (84% on average) was discharged to the irrigation canals. Much of the salt in pond sediment was also exported to the canal system through tidal flushing of the ponds. Field measurements of salinity were taken in adjacent canals and rice paddies to explore the impacts of salt exports from shrimp ponds. Pond discharge caused increases in canal salinity above levels that would impact on yields of irrigated rice and orchard crops, the main land uses in the region. Elevated soil and water salinity in adjacent rice fields was probably related to lateral seepage from the ponds. The salt budget was also modelled for a zero discharge farming system, promoted by proponents of inland shrimp farming as having few impacts. However, the results suggest that, even in zero discharge ponds, almost half of the initial pond salt content is exported through seepage (45%, 12.4 tonnes crop−1), with another 6% (1.8 tonnes crop−1) deposited in sediments. While techniques exist for mitigating much of the salt leakage, the likelihood of their uptake in Thailand is low. Further expansion of inland shrimp farming in the central plain is therefore likely to contribute substantial salt load to the area's land and water resources.
Dose-response relationships for foot and mouth disease in cattle and sheep
Authors: FRENCH N. P. , KELLY L. , JONES R. , CLANCY D.
Published: October 2002

The relationships between the inhaled dose of foot and mouth disease virus and the outcomes of infection and disease were examined by fitting dose-response models to experimental data. The parameters for both the exponential and beta-poisson models were estimated using maximum likelihood and Bayesian methods. The median probability of infection given a single inhaled TCID50 was estimated to be 0·031 with 95% Bayesian credibility intervals (CI) of 0·018–0·052 for cattle, and 0·045 (CI = 0·024–0·080) for sheep. These estimates were used to construct dose-response curves and uncertainty distributions for use in quantitative risk assessments.
Rate of inter-herd transmission of classical swine fever virus by different types of contact during the 1997–8 epidemic in The Netherlands
Authors: STEGEMAN J. A. , ELBERS A. R. W. , BOUMA A. , DE JONG M. C. M.
Published: October 2002

In this study we quantified the rate at which classical swine fever had been transmitted by several different types of inter-herd contact during the 1997–8 epidemic in The Netherlands. During that epidemic 428 CSFV-infected pig herds were detected, 403 of which were included in this study. The estimated rates of transmission were 0·065 per shipment of live pigs, 0·011 per contact by a pig transportation lorry, 0·0068 per person contact, 0·0007 per dose of semen, 0·0065 per contact with a potentially contaminated pig assembly point, 0·027 per week per infected herd within a radius of 500 metres and 0·0078 per week per infected herd at a distance between 500 and 1000 metres. These transmission rates can be used to optimize the strategy to stop future epidemics of CSF in The Netherlands. In addition, the analysis demonstrated in this paper, can be used to quantify CSFV transmission rates from other epidemics.
Prevalence of and risk factors for HIV infection in blood donors and various population subgroups in Ethiopia
Authors: SENTJENS R. E. J. H. , SISAY Y. , VRIELINK H. , KEBEDE D. , ADÈR H. J. , LECKIE G. , REESINK H. W.
Published: October 2002

The aim was to determine the prevalence of HIV infection and risk factors for HIV infection in various population subgroups in Ethiopia. Serum panels from blood donors (n = 2610), from various population subgroups in Ethiopia were tested for anti-HIV-1/2 by ELISA. All ELISA repeatedly reactive samples were subjected for confirmation by immunoblot (IB) and anti-HIV-1 and anti-HIV-2 specific ELISAs. 155/2610 (5·9%) blood donors were HIV-1 infected. Of pregnant women, 84/797 (10·5%) were HIV-1 infected, and 1/797 (0·1%) was HIV-2 infected. 1/240 (0·4%) individuals from the rural population were HIV-1 infected. 198/480 (41·3%) female attendees, and 106/419 (25·3%) male attendees at sexual transmitted disease (STD) clinics were HIV-1 infected. One (0·2%) male, and 2 (0·4%) female STD patients were infected with both HIV-1 and HIV-2. It was concluded that the prevalence of HIV-1 infection varied from 0·4% among urban residents to 25·3–41·3% among STD attendees. There is a low prevalence of HIV-2 present in Ethiopian subjects. Risky sexual behaviour is significantly associated with HIV-infection in Ethiopia.
Multilocus sequence typing of Neisseria meningitidis directly from cerebrospinal fluid
Authors: KRIZ P. , KALMUSOVA J. , FELSBERG J.
Published: October 2002

MLST typing of Neisseria meningitidis directly from clinical material was introduced in the National Reference Laboratory for Meningococcal Infections in Prague. Four cerebrospinal fluid samples were obtained from patients with suspected meningococcal invasive disease. In all samples, all classical laboratory methods gave negative results and the only positive method was PCR, which revealed Neisseria meningitidis group C (two specimens) and group B (two specimens), respectively. MLST performed directly from cerebrospinal fluid revealed that the strains causing the two group C infections were of sequence type (ST) 11, while the two group B infections were characterized as ST-32 and ST-33 respectively. Multi-locus sequence typing of meningococci directly from clinical material offers the opportunity to improve further the surveillance of meningococcal disease and has now been introduced into the routine portfolio of tests employed at the national reference laboratory of the Czech Republic.
Phage typing and PFGE pattern analysis as tools for epidemiological surveillance of Salmonella enterica serovar Bovismorbificans infections
Authors: LIESEGANG A. , DAVOS D. , BALZER J. C. , RABSCH W. , PRAGER R. , LIGHTFOOT D. , SIITONEN A. , CLAUS H. , TSCHÄPE H.
Published: October 2002

Some years ago, an increase in the number of sporadic cases and outbreaks of salmonellosis due to S. enterica serovar Bovismorbificans was observed in several European countries including Finland, Sweden, England/Wales, Austria, and Germany. In order to understand the recent spread of this serovar and to trace the route of infection back to its source, it was considered necessary to subtype S. Bovismorbificans isolates. Using phage typing (newly described here) and molecular fingerprinting (PFGE-pattern, plasmid profiles and ribotype) the isolates of European origin could be subtyped and compared to S. Bovismorbificans isolates that originated in overseas countries such as Australia, Thailand, India, etc. where this serovar was isolated more frequently. Significant clonal diversity was identified but some of the clonal types of S. Bovismorbificans dominated the epidemics and single cases in Europe as well as in overseas countries. The clonal identity among these isolates indicates an international distribution, new sources of infection, and highlights the urgent requirement for standardized laboratory based surveillance networks (e.g. Enter-Net). Moreover, it is suggested that strains of S. Bovismorbificans will continue to be of concern in public health and that phage typing together with PFGE typing can be applied as reliable and rapid tools for their future monitoring.
Pharmacological characterization of the chemokine receptor, hCCR1 in a stable transfectant and differentiated HL‐60 cells: antagonism of hCCR1 activation by MIP‐1β
Authors: Chou Chuan‐Chu , Fine Jay S , Pugliese‐Sivo Catherine , Gonsiorek Waldemar , Davies Liza , Deno Gregory , Petro Mary , Schwarz Martin , Zavodny Paul J , Hipkin R William
Published: October 2002

C‐C chemokine receptor‐1 (CCR1) has been implicated in mediating a variety of inflammatory conditions including multiple sclerosis and organ rejection. Although originally referred to as the MIP‐1α/RANTES receptor, CCR1 is quite promiscuous and can be activated by numerous chemokines.

We used radioligand binding and [35S]‐GTPγS exchange assays in membranes from a cell line transfected to express CCR1 (Ba/F3‐hCCR1) to characterize a panel of chemokines (HCC‐1, MIP‐1α, MIP‐1β, MIP‐1δ, MPIF‐1, MCP‐2, MCP‐3, and RANTES) as CCR1 ligands. In this recombinant model, these chemokines displaced 125I‐MIP‐1α with a wide range of potencies and, with the exception of MCP‐2, acted as full agonists in stimulating [35S]‐GTPγS exchange.

We then assessed the utility of HL‐60 cells cultured with known differentiating agents (PMA, DMSO, dibutyryl‐cAMP or retinoic acid) for investigating CCR1 pharmacology. In [35S]‐GTPγS exchange assays, membranes from cells cultured with retinoic acid (4–6 days) were the most responsive to activation by MIP‐1α and MPIF‐1. FACS analysis and comparative pharmacology confirmed that these activities were mediated by CCR1.

Using [35S]‐GTPγS exchange assays, intracellular calcium flux and/or whole cell chemotaxis assays in HL‐60(Rx) cells, we validated that MIP‐1α was the most potent CCR1 ligand (MIP‐1α>MPIF‐1>RANTESMIP‐1β) although the ligands differed in their efficacy as agonists. MPIF‐1 was the more efficacious (MPIF‐1>RANTES=MIP‐1α>>MIP‐1β). 125I‐MIP‐1β binding in Ba/F3‐hCCR1 and HL‐60(Rx) membranes was competitively displaced by MIP‐1α, MPIF‐1 and MIP‐1β. The binding Ki for these chemokines with 125I‐MIP‐1β were essentially identical in the two membrane systems.

Lastly, MIP‐1β antagonized [35S]‐GTPγS exchange, Ca2+ flux and chemotaxis in HL‐60(Rx) cells in response to robust agonists such as MIP‐1α, RANTES and MPIF‐1. Based on our results, we propose that MIP‐1β could function as an endogenous inhibitor of CCR1 function.

British Journal of Pharmacology (2002) 137, 663–675. doi:10.1038/sj.bjp.0704907
A novelβ‐sheet breaker, RS‐0406, reverses amyloidβ‐induced cytotoxicity and impairment of long‐term potentiationin vitro
Authors: Nakagami Yasuhiro , Nishimura Satoko , Murasugi Takako , Kaneko Isao , Meguro Masaki , Marumoto Shinji , Kogen Hiroshi , Koyama Kazuo , Oda Tomiichiro
Published: October 2002

Fibril formation of amyloid β peptide (Aβ) is considered to be responsible for the pathology of Alzheimer's disease (AD). The Aβ fibril is formed by a protein misfolding process in which intermolecular β‐sheet interactions become stabilized abnormally. Thus, to develop potential anti‐AD drugs, we screened an in‐house library to find compounds which have a profile as a β‐sheet breaker.

We searched for a β‐sheet breaker profile in an in‐house library of approximately 113,000 compounds. From among the screening hits, we focused onN,N′‐bis(3‐hydroxyphenyl)pyridazine‐3,6‐diamine (named RS‐0406), which had been newly synthesized in our laboratory. This compound (10–100 μg ml−1) was found to be capable of significantly inhibiting 25 μMAβ1–42fibrillogenesis and, furthermore, disassembling preformed Aβ1–42fibrilsin vitro.

We then investigated the effect of RS‐0406 on 111 nMAβ1–42‐induced cytotoxicity in primary hippocampal neurons, and found that 0.3–3 μg ml−1RS‐0406 ameliorates the cytotoxicity. Moreover, 3 μg ml−1RS‐0406 reversed 1 μMAβ1–42‐induced impairment of long‐term potentiation in hippocampal slices.

In this study, we have succeeded in identifying RS‐0406 which has potential to inhibit Aβ1–42fibrillogenesis, and to protect neurons against Aβ1–42‐induced biological toxicityin vitro. These results suggest that RS‐0406 or one of the derivatives could become a therapeutic agent for AD patients.

British Journal of Pharmacology(2002)137, 676–682. doi:10.1038/sj.bjp.0704911
Propofol prevents endothelial dysfunction induced by glucose overload
Authors: Karashima Yuji , Oike Masahiro , Takahashi Shosuke , Ito Yushi
Published: October 2002

Surgical operations often induce acute hyperglycemia, which is known to affect endothelial functions. In this study, we examined the effects of propofol, a commonly used general anaesthetic, on bovine aortic endothelial cell (BAEC) dysfunction induced by glucose overload.

D‐glucose overload (23 mM) induced an accumulation of superoxide anion (O2−), assessed by MCLA chemiluminescence, to a similar extent as that generated by 233 μU ml−1 xanthine oxidase (XO) and 100 μM xanthine. Propofol inhibited this accumulation with an IC50 of 0.21 μM, whereas much higher concentrations of propofol were required to scavenge O2− generated by 250 μU ml−1 XO and 100 μM xanthine (IC50: 13.5 μM).

D‐glucose overload attenuated ATP‐induced NO production which was detected using diaminofluorescence‐2 (DAF‐2). The inhibition was reversed by propofol with an EC50 of 0.60 μM. In contrast, inhibitions caused by xanthine/XO were not altered by propofol (1 μM).

D‐glucose overload suppressed ATP‐induced Ca2+ oscillations and capacitative Ca2+ entry (CCE), which were both restored by superoxide dismutase, indicating that O2− was responsible. Propofol restored these attenuated Ca2+ oscillations and CCE with EC50 of 0.31 and 1.0 μM, respectively.

D‐glucose overload (23 mM) increased the intracellular glucose concentration 4 fold, compared with cells exposed to 5.75 mM glucose, and 1 μM propofol reduced this increase to 2.8 fold.

We conclude from these results that anaesthetic concentrations of propofol prevent the impairment of Ca2+‐dependent NO production in BAEC induced by glucose overload. This effect is mainly due to the reduction of O2− accumulation, and involves, at least in part, the inhibition of cellular glucose uptake.

British Journal of Pharmacology (2002) 137, 683–691. doi:10.1038/sj.bjp.0704912
Is urotensin‐II the new endothelin?
Authors: Maguire Janet J , Davenport Anthony P
Published: October 2002

Urotensin‐II (U‐II), a peptide isolated from the urophysis of teleost fish 35 years ago, is the endogenous ligand of the mammalian orphan receptor GPR14/SENR. Recently, human homologues of both the receptor (UT‐II) and the peptide (hU‐II) have been discovered. Following de‐orphanization, hU‐II was declared the ‘new endothelin’ as initial studies suggested similarities between the peptides, and in isolated arteries of cynomolgus monkey U‐II was a more potent constrictor than endothelin‐1 (ET‐1), with equal efficacy. However, effects of U‐II in vascular tissue from other mammalian species are variable and although potent, U‐II exhibits a lesser maximal response than ET‐1. In contrast, in humans U‐II has emerged as a ubiquitious constrictor of both arteries and veins in vitro and elicits a reduction in blood flow in the forearm and skin microcirculation in vivo. In addition to direct vasoconstrictor activity on smooth muscle receptors, endothelium‐dependent U‐II‐mediated vasodilatation has also been observed. Non‐vascular, peripheral actions of U‐II include potent inotropy and airway smooth muscle constriction and U‐II and its receptor are present throughout rat brain implying a possible neurotransmitter or neuromodulatory role in the central nervous system. U‐II is proposed to contribute to human diseases including atherosclerosis, cardiac hypertrophy, pulmonary hypertension and tumour growth. The development of selective receptor antagonists should help to clarify the relative importance of hU‐II as a multifunctional peptide in mammalian systems and its role in disease. What is clear is that U‐II is emerging as a new and potentially important mammalian transmitter.

British Journal of Pharmacology (2002) 137, 579–588. doi:10.1038/sj.bjp.0704924
CD1d and invariant NKT cells at the human maternal–fetal interface
Authors: Boyson Jonathan E. , Rybalov Basya , Koopman Louise A. , Exley Mark , Balk Steven P. , Racke Frederick K. , Schatz Frederick , Masch Rachel , Wilson S. Brian , Strominger Jack L.
Published: October 2002

Invariant CD1d-restricted natural killer T (iNKT) cells comprise a small, but significant, immunoregulatory T cell subset. Here, the presence of these cells and their CD1d ligand at the human maternal–fetal interface was investigated. Immunohistochemical staining of human decidua revealed the expression of CD1d on both villous and extravillous trophoblasts, the fetal cells that invade the maternal decidua. Decidual iNKT cells comprised 0.48% of the decidual CD3+ T cell population, a frequency 10 times greater than that seen in peripheral blood. Interestingly, decidual CD4+ iNKT cells exhibited a striking Th1-like bias (IFN-γ production), whereas peripheral blood CD4+ iNKT clones exhibited a Th2-like bias (IL-4 production). Moreover, compared to their peripheral blood counterparts, decidual iNKT clones were strongly polarized toward granulocyte/macrophage colony-stimulating factor production. The demonstration of CD1d expression on fetal trophoblasts together with the differential pattern of cytokine expression by decidual iNKT cells suggests that maternal iNKT cell interactions with CD1d expressed on invading fetal cells may play an immunoregulatory role at the maternal–fetal interface.
Structural analysis of the RSC chromatin-remodeling complex
Authors: Asturias Francisco J. , Chung Wen-Hsiang , Kornberg Roger D. , Lorch Yahli
Published: October 2002

Electron microscopy of the RSC chromatin-remodeling complex reveals a ring of protein densities around a central cavity. The size and shape of the cavity correspond closely to those of a nucleosome. Results of nuclease protection analysis are consistent with nucleosome binding in the cavity. Such binding could explain the ability of RSC to expose nucleosomal DNA in the presence of ATP without loss of associated histones.
Genetic and physiological data implicating the new human gene G72 and the gene for
d
-amino acid oxidase in schizophrenia
Authors: Chumakov Ilya , Blumenfeld Marta , Guerassimenko Oxana , Cavarec Laurent , Palicio Marta , Abderrahim Hadi , Bougueleret Lydie , Barry Caroline , Tanaka Hiroaki , La Rosa Philippe , Puech Anne , Tahri Nadia , Cohen-Akenine Annick , Delabrosse Sylvain , Lissarrague Sébastien , Picard Françoise-Pascaline , Maurice Karelle , Essioux Laurent , Millasseau Philippe , Grel Pascale , Debailleul Virginie , Simon Anne-Marie , Caterina Dominique , Dufaure Isabelle , Malekzadeh Kattayoun , Belova Maria , Luan Jian-Jian , Bouillot Michel , Sambucy Jean-Luc , Primas Gwenael , Saumier Martial , Boubkiri Nadia , Martin-Saumier Sandrine , Nasroune Myriam , Peixoto Hélène , Delaye Arnaud , Pinchot Virginie , Bastucci Mariam , Guillou Sophie , Chevillon Magali , Sainz-Fuertes Ricardo , Meguenni Said , Aurich-Costa Joan , Cherif Dorra , Gimalac Anne , Van Duijn Cornelia , Gauvreau Denis , Ouelette Gail , Fortier Isabel , Realson John , Sherbatich Tatiana , Riazanskaia Nadejda , Rogaev Evgeny , Raeymaekers Peter , Aerssens Jeroen , Konings Frank , Luyten Walter , Macciardi Fabio , Sham Pak C. , Straub Richard E. , Weinberger Daniel R. , Cohen Nadine , Cohen Daniel
Published: October 2002

A map of 191 single-nucleotide polymorphism (SNPs) was built across a 5-Mb segment from chromosome 13q34 that has been genetically linked to schizophrenia. DNA from 213 schizophrenic patients and 241 normal individuals from Canada were genotyped with this marker set. Two 1,400- and 65-kb regions contained markers associated with the disease. Two markers from the 65-kb region were also found to be associated to schizophrenia in a Russian sample. Two overlapping genes G72 and G30 transcribed in brain were experimentally annotated in this 65-kb region. Transfection experiments point to the existence of a 153-aa protein coded by the G72 gene. This protein is rapidly evolving in primates, is localized to endoplasmic reticulum/Golgi in transfected cells, is able to form multimers and specifically binds to carbohydrates. Yeast two-hybrid experiments with the G72 protein identified the enzyme
d
-amino acid oxidase (DAAO) as an interacting partner. DAAO is expressed in human brain where it oxidizes
d
-serine, a potent activator of
N
-methyl-D-aspartate type glutamate receptor. The interaction between G72 and DAAO was confirmed
in vitro
and resulted in activation of DAAO. Four SNP markers from DAAO were found to be associated with schizophrenia in the Canadian samples. Logistic regression revealed genetic interaction between associated SNPs in vicinity of two genes. The association of both DAAO and a new gene G72 from 13q34 with schizophrenia together with activation of DAAO activity by a G72 protein product points to the involvement of this
N
-methyl-
d
-aspartate receptor regulation pathway in schizophrenia.
Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor
Authors: Ivan Mircea , Haberberger Thomas , Gervasi David C. , Michelson Kristen S. , Günzler Volkmar , Kondo Keiichi , Yang Haifeng , Sorokina Irina , Conaway Ronald C. , Conaway Joan W. , Kaelin William G.
Published: October 2002

The product of the von Hippel–Lindau gene, pVHL, targets the α subunits of the heterodimeric transcription factor hypoxia-inducible factor (HIF) for polyubiquitination in the presence of oxygen. The binding of pVHL to HIF is governed by the enzymatic hydroxylation of conserved prolyl residues within peptidic motifs present in the HIFα family members. By using a biochemical purification strategy, we have identified a human homolog of
Caenorhabditis elegans
Egl9 as a HIF prolyl hydroxylase. In addition, we studied the activity of a structurally diverse collection of low molecular weight inhibitors of procollagen prolyl 4-hydroxylase as potential inhibitors of the HIF hydroxylase. A model compound of this series stabilized HIF in a variety of cells, leading to the increased production of its downstream target, vascular endothelial growth factor.
X-ray structure of a bifunctional protein kinase in complex with its protein substrate HPr
Authors: Fieulaine Sonia , Morera Solange , Poncet Sandrine , Mijakovic Ivan , Galinier Anne , Janin Joël , Deutscher Josef , Nessler Sylvie
Published: October 2002

HPr kinase/phosphorylase (HprK/P) controls the phosphorylation state of the phosphocarrier protein HPr and regulates the utilization of carbon sources by Gram-positive bacteria. It catalyzes both the ATP-dependent phosphorylation of Ser-46 of HPr and its dephosphorylation by phosphorolysis. The latter reaction uses inorganic phosphate as substrate and produces pyrophosphate. We present here two crystal structures of a complex of the catalytic domain of
Lactobacillus casei
HprK/P with
Bacillus subtilis
HPr, both at 2.8-Å resolution. One of the structures was obtained in the presence of excess pyrophosphate, reversing the phosphorolysis reaction and contains serine-phosphorylated HPr. The complex has six HPr molecules bound to the hexameric kinase. Two adjacent enzyme subunits are in contact with each HPr molecule, one through its active site and the other through its C-terminal helix. In the complex with serine-phosphorylated HPr, a phosphate ion is in a position to perform a nucleophilic attack on the phosphoserine. Although the mechanism of the phosphorylation reaction resembles that of eukaryotic protein kinases, the dephosphorylation by inorganic phosphate is unique to the HprK/P family of kinases. This study provides the structure of a protein kinase in complex with its protein substrate, giving insights into the chemistry of the phospho-transfer reactions in both directions.