bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a definition of pre‐eclampsia
Authors: North Robyn A. , Taylor Rennae S. , Schellenberg Jean‐Claude
Published: August 2005

Objectives
To determine: 1. whether an alternative definition of gestational hypertension and pre‐eclampsia stratifies women according to their risk of maternal and fetal complications; 2. whether pregnancy outcome in women with gestational hypertension differs in the presence or absence of ‘+’ proteinuria; and 3. whether a blood pressure rise of ≥ 30/15 mmHg during pregnancy is associated with adverse outcome in women who remain normotensive.

Design
Prospective, nested case–control study.

Setting
Community based.

Population
Healthy, nulliparous women (n= 1496).

Methods
Women recruited into a study investigating serum markers predictive of pre‐eclampsia were classified as having gestational hypertension (systolic blood pressure ≥ 140 mmHg with a rise of ≥ 30 mmHg and/or diastolic blood pressure ≥ 90 mmHg with a rise of ≥ 15 mmHg) or pre‐eclampsia (gestational hypertension plus proteinuria ≥ 2+on dipstick or > 0.3 g/24 h). Maternal and fetal complications in gestational hypertension or pre‐eclampsia were compared with a control group of 223 randomly selected normotensive women. The main outcome measures were severe maternal disease, preterm birth and small for gestational age infant.

Results
A stepwise increase in adverse maternal and fetal outcomes occurred in gestational hypertension (n= 117, 743%) and pre‐eclampsia (n= 71, 4.8%). Severe maternal disease developed in 26.5% (21.4% severe hypertension alone, 5.1% multisystem disease) of women with gestational hypertension and 63.4% (21.1% severe hypertension alone, 42.3% multisystem disease) of women with pre‐eclampsia (OR 4.8; 95% CI 2.4–9.5). Preterm birth and small for gestational age infants were more frequent in gestational hypertension (OR 1.7; 95% CI 0.5–5.4, and OR 2.0; 95% CI 1.0–3.7, respectively) and pre‐eclampsia (OR 14.6; 95% CI 5.8–37.8, and OR 2.6; 95% CI 1.2–5.3) than in the normotensive group. Among women with gestational hypertension severe maternal disease was more common in women with ‘+’ proteinuria (41.7%) than in those with no proteinuria (15.9%): OR 3–8; 95% CI 1.5–9.8. Pregnancies were uncomplicated in the 27% of normotensive women who had a rise of ≥ 30 mmHg systolic blood pressure and/or ≥ 15 mmHg rise in diastolic blood pressure.

Conclusions
In the nulliparous population studied our definition of gestational hypertension and pre‐eclampsia identified women at increasing risk of maternal and fetal complications. In gestational hypertension, the presence of proteinuria ‘+’ was associated with a 3.8‐fold increase in severe maternal disease. Normotensive women who have a rise in blood pressure ≥ 30/15 mmHg had uncomplicated pregnancies.
Placental apoptosis is increased in post‐term pregnancies
Authors: Smith Stephen C. , Baker Philip N.
Published: August 2005

Placentae were obtained at delivery in 14 pregnancies complicated by post maturity (gestational age ≥ 40 weeks and 10 days) and in 23 uncomplicated pregnancies (gestational age c 40 weeks). The incidence of apoptotic nuclei was significantly greater in the placentae from the postmature pregnancies.
Two trials of antenatal thyrotrophin‐releasing hormone for fetal maturation: stopping before the due date
Authors: Alfirevic Z. , Boer K. , Brocklehurst P. , Buimer M. , Elbourne D. , Kok J. , Tansey S. ,   on behalf of the Antenatal TRH Trial and the Thyroneth Trial Groups
Published: August 2005

Objectives
To determine whether the addition of antenatal thyrotrophin‐releasing hormone (TRH) to corticosteroids, given to women at risk of preterm delivery, would decrease the risk of death and severe morbidity associated with prematurity.

Design
Two concurrent multicentre, double blind, randomised, placebo‐controlled trials were designed with a common core dataset to be analysed as a single large pragmatic trial.

Setting
Hospital maternity units.

Populations
Pregnant women at risk of preterm delivery who had been prescribed a course of corticosteroids to enhance fetal maturation.

Interventions
Antenatal administration of TRH 400 μg every eight hours for four doses versus matching placebo.

Main outcome measures
Primary: death of the baby or chronic lung disease (defined as oxygen dependency at 28 days after birth). Secondary: other measures of respiratory morbidity, in particular respiratory distress syndrome. Other measures of short term neonatal morbidity including intraventricular haemorrhage and necrotising enterocolitis. Measures of maternal side effects.

Results
The antenatal TRH trial was halted early on the basis of external evidence. Overall a total of 225 women were recruited who delivered 275 babies. The primary outcome of death or chronic lung disease occurred in 33 babies in the TRH group and 43 babies in the placebo group (RR 0.8, 95% CI 0.5–1.2). There were no other differences between the two groups. Stratified analysis did not reveal any differences between the two groups depending on how long before the time of delivery the mother had received the TRH or placebo.

Conclusions
These trials are too small to provide convincing evidence of the effect of antenatal TRH on neonatal outcome. When added to the existing systematic review and meta‐analysis, however, these data should provide evidence on which subsequent practice can be based. The process by which the trials were monitored and stopped is of relevance to future trials.
The value of sonography in early pregnancy for the detection of fetal abnormalities in an unselected population
Authors: Whitlow B. J. , Chatzipapas I. K. , Lazanakis M. L. , Kadir R. A. , Economides D. L.
Published: August 2005

Objective
To determine the value of early pregnancy sonography in detecting fetal abnormalities in an unselected obstetric population.

Design
Prospective cross‐sectional study. All women initially underwent transabdominal sonography and when the anatomical survey was considered to be incomplete, transvaginal sonography was also performed (20.1 %). Nuchal translucency was measured and karyotyping was performed as appropriate.

Setting
University Department of Obstetrics and Gynaecology.

Participants
6634 sequential unselected women (mean maternal age 29–9 years, range 13–50; mean gestational age 12+4 weeks, range 11+0‐14+6), carrying 6443 live fetuses participated in this study.

Main outcome measure
Detection rate of fetal anomalies and the associated cost per case detected in early pregnancy.

Results
The incidence of anomalous fetuses was 1.4% (926443) including 43 chromosomal abnormalities. The detection rate for structural abnormalities was 59.0% (37/63, 95% CI 46.5–72.4) and the specificity was 99.9% in early pregnancy. When the first and second trimester scans were combined, the detection for structural abnormalities was 8 1.0% (5 1/63, 95% CI 67.7–89.2). Seventy‐eight percent (31/40) of chromosomal abnormalities (excluding three cases of XXY) were diagnosed at 11–14 weeks, either because of a nuchal translucency greater than or equal to the 99th centile for gestational age (43%; 17/40,95% CI 27‐4–60.4), or due to the presence of structural abnormalities (35%; 14/40, 95% CI 21.2–52.8). Sixty‐five percent (15/23) of cases of trisomy 21 were also diagnosed either because of having a nuchal translucency greater than or equal to the 99th centile (57.0%; 13/23) or due to the presence of a structural abnormality (9.0%; 2/23). Overall, the detection rate of structurally abnormal fetuses was 59% (37/63) in early pregnancy and 81% in combination with the second trimester scan. The cost per abnormality diagnosed in early pregnancy is estimated to be f6258 per structurally abnormal fetus, £7470 per chromosomal abnormality and f4453 per anomalous fetus.

Conclusion
The majority of fetal structural and chromosomal abnormalities can be detected by sonographic screening at 11–14 weeks, but the second trimester scan should not be abandoned.
Trends in births at and beyond term: evidence of a change?
Authors: Roberts Christine L. , Taylor Lee , Henderson‐Smart David
Published: August 2005

Objective
To examine trends in the distribution of births at and beyond term in New South Wales and in particular, to determine whether any changes are associated with changes in the obstetric practices of induction and elective caesarean section.

Design
Cross‐sectional analytic study.

Setting
New South Wales, Australia.

Population
All 540,162 women delivering a singleton cephalic‐presenting infant of gestational age ≥ 37 weeks from 1 January 1990 to 31 December 1996.

Methods
Data were obtained from the New South Wales midwives data collection, a population‐based surveillance system covering all births in New South Wales. The data were analysed to examine changes over time and associations between gestational age, maternal factors and onset of labour.

Main outcome measures
Induction of labour and elective caesarean section rates.

Results
From 1990 to 1996 there was a significant decrease in births reported as 40 weeks of gestation, from 35,670 (46.3%) to 30,651 (40.3%). These declines were offset by significant increases in births at 38 and 39 weeks. Births ≥ 42 weeks declined from 3321 (4.6%) to 2132 (2.8%). The decline in prolonged pregnancies was associated with increasing induction rates at 41 weeks. The re‐distribution of some births from 40 to 38–39 weeks was associated with increasing rates of elective caesarean sections and induction at 38 and 39 weeks, and increasing maternal age.

Conclusions
Clinicians appear to be implementing the recommendations of randomised controlled trials to offer induction after 41 weeks of gestation. However the trend of performing elective caesarean sections at earlier gestational ages may be unnecessarily putting some infants at increased risk of respiratory morbidity.
Gastrostomy tubes in patients with recurrent gynaecological cancer and intestinal obstruction
Authors: Tsahalina Efthalia , Woolas Robert P. , Carter Paul G. , Chan Felix , Gore Martin E. , Blake Peter M. , Shepherd John H. , Barton Desmond P. J.
Published: August 2005

Objective
Women with recurrent gynaecological cancers who are not suitable for exenterative surgery commonly present with gastrointestinal dysfunction. This paper is a retrospective review of the use of gastrostomy tubes in such women.

Methods
We performed a chart review of women with recurrent gynaecological cancer who had a gastrostomy tube placed between January 1991 and April 1998.

Results
Thirty‐nine women (mean age 53.2 years, range 17–82) had a gastrostomy tube placed. Twenty‐eight (72%) had ovarian cancer, eight (21%) had cervical cancer, two had endometrial cancer and one had vaginal cancer. In 14 women a gastrostomy tube was placed as the sole procedure for palliation (11 elective, 3 emergency). In the remaining 25 women, who underwent major surgery, a gastrostomy tube was placed in anticipation of, or in the presence of, significant intestinal distension and expected prolonged post‐operative ileus. eleven women (28%) died without leaving hospital after their operation (median 11 days, range 2–36). All but one of the 28 women who left hospital had satisfactory oral intake. Twenty‐one women (54%) died with the gastrostomy tube in place (median 28 days, range 2–157) and 18 (46%) had the gastrostomy tube removed (median 14.5 days, range 9–180), 13 of whom (33%) have since died (median 167 days, range 77 days–7 years). Five women (13%) are alive (median 2.2 years, range 10 months–4.5 years). There were no problems which required the gastrostomy tube to be removed.

Conclusion
Gastrostomy tubes have an important role in the treatment of women with recurrent gynaecological cancer, allowing gastric drainage and decompression without the disadvantages of nasogastric tubes.
Association Between Mind‐Body and Cardiovascular Exercises and Memory in Older Adults
Authors: Chan Agnes S. , Ho Yim‐chi , Cheung Mei‐chun , Albert Marilyn S. , Chiu Helen F. K. , Lam Linda C. W.
Published: August 2005

Objectives: To compare the memory function of older adults who regularly practiced mind‐body (MB) or cardiovascular (CV) exercises with that of those who did not engage in regular exercise. Older adults who engaged in both types of exercise were also included to examine the combined effects.

Design: Cross‐sectional study between 2002 and 2003.

Setting: Older adults from a local community in Hong Kong.

Participants: One hundred forty adults aged 56 and older.

Measurements: The Hong Kong List Learning Test was used to assess the memory of all participants. It is a clinically validated Chinese verbal‐memory test that measures various aspects of memory processing, including learning, retention, and retrieval abilities. MB and CV exercises were defined using three dimensions: motion speed, emphasis on relaxing the mind, and conscious control of movement.

Results: Older adults who practiced MB or CV exercises demonstrated a similar level of memory function, and their learning and memory was better than that of individuals who did not exercise regularly. Those who practiced both types of exercises outperformed all other groups, even after corrected for the total hours of exercise. Although memory change across age was found in older adults who did not exercise, this trend was not observed in individuals who practiced MB exercises.

Conclusion: Practicing both MB and CV exercises appears to have a combined effect that might help to preserve memory in older adults. In addition, MB exercises may be considered as an alternative training for older adults who cannot practice strenuous physical exercise.
A Community‐Based Fitness and Mobility Exercise Program for Older Adults with Chronic Stroke: A Randomized, Controlled Trial
Authors: Pang Marco Y. C. , Eng Janice J. , Dawson Andrew S. , McKay Heather A. , Harris Jocelyn E.
Published: August 2005

Objectives: To examine the effects of a community‐based group exercise program for older individuals with chronic stroke.

Design: Prospective, single‐blind, randomized, controlled intervention trial.

Setting: Intervention was community‐based. Data collection was performed in a research laboratory located in a rehabilitation hospital.

Participants: Sixty‐three older individuals (aged≥50) with chronic stroke (poststroke duration≥1 year) who were living in the community.

Intervention: Participants were randomized into intervention group (n=32) or control group (n=31). The intervention group underwent a fitness and mobility exercise (FAME) program designed to improve cardiorespiratory fitness, mobility, leg muscle strength, balance, and hip bone mineral density (BMD) (1‐hour sessions, three sessions/week, for 19 weeks). The control group underwent a seated upper extremity program.

Measurements: Cardiorespiratory fitness (maximal oxygen consumption), mobility (6‐minute walk test), leg muscle strength (isometric knee extension), balance (Berg Balance Scale), activity and participation (Physical Activity Scale for Individuals with Physical Disabilities), and femoral neck BMD (using dual‐energy x‐ray absorptiometry).

Results: The intervention group had significantly more gains in cardiorespiratory fitness, mobility, and paretic leg muscle strength than controls. Femoral neck BMD of the paretic leg was maintained in the intervention group, whereas a significant decline of the same occurred in controls. There was no significant time‐by‐group interaction for balance, activity and participation, nonparetic leg muscle strength, or nonparetic femoral neck BMD.

Conclusion: The FAME program is feasible and beneficial for improving some of the secondary complications resulting from physical inactivity in older adults living with stroke. It may serve as a good model of a community‐based fitness program for preventing secondary diseases in older adults living with chronic conditions.
Phase Diagram of the Bi4Ti3O12–BaTiO3–(Na1/2Bi1/2)TiO3 System
Authors: Sanson A. , Whatmore R. W.
Published: August 2005

The phases formed in the ternary system (Na1/2Bi1/2)TiO3–Bi4Ti3O12–BaTiO3 (NBT–BTO–BT) were studied at 1150°C in air. A very accurate picture of the ternary phase diagram was obtained examining almost 90 different compositions, exploiting low‐angle XRD analyses to study the layer compounds. New compounds with five perovskite blocks (m=5) were discovered deep in the phase diagram. No compounds with m>5 were found. It was also established that pure perovskite compounds can be obtained only at compositions very close to the NBT–BT line. The relationships between the phases is discussed and it is hypothesized that the number of perovskite blocks in the system is determined by charged sites being created by the progressive substitution of Bi3+ in the A site of the perovskite blocks of BTO with the A cations of the perovskite end‐member.
Anatase‐Type TiO2 and ZrO2‐Doped TiO2 Directly Formed from Titanium(III) Sulfate Solution by Thermal Hydrolysis: Effect of the Presence of Ammonium Peroxodisulfate on their Formation and Properties
Authors: Hirano Masanori , Ota Keisuke , Ito Takaharu
Published: August 2005

Anatase‐type TiO2 powder containing sulfur with absorption in the visible region was directly formed as particles with crystallite in the range 15–88 nm by thermal hydrolysis of titanium(III) sulfate (Ti2(SO4)3) solution at 100°–240°C. Because of the presence of ammonium peroxodisulfate ((NH4)2S2O8), the yield of anatase‐type TiO2 from Ti2(SO4)3 solution was accelerated, and anatase with fine crystallite was formed. Anatase‐type TiO2 doped with ZrO2 up to 9.8 mol% was directly precipitated as nanometer‐sized particles from the acidic precursor solutions of Ti2(SO4)3 and zirconium sulfate in the presence and the absence of (NH4)2S2O8 by simultaneous hydrolysis under hydrothermal conditions at 200°C. By doping ZrO2 into TiO2 and with increasing ZrO2 content, the crystallite size of anatase was decreased, and the anatase‐to‐rutile phase transformation was retarded as much as 200°C. The anatase‐type structure of ZrO2‐doped TiO2 was maintained after heating at 1000°C for 1 h. The favorable effect of doping ZrO2 to anatase‐type TiO2 on the photocatalytic activity was observed.
Effects of Preparation Conditions on the Structural and Optical Properties of Spark Plasma‐Sintered PLZT (8/65/35) Ceramics
Authors: Wu Yong Jun , Li Juan , Kimura Ryo , Uekawa Naofumi , Kakegawa Kazuyuki
Published: August 2005

Transparent lanthanum‐doped lead zirconate titanate (PLZT) ceramics with high density were fabricated using spark plasma sintering (SPS), a recently developed hot‐pressing method. A wet–dry combination method was used to prepare the fine PLZT powders. The average grain size of the PLZT ceramics was less than 1 μm, because of a relatively low sintering temperature and a very short sintering time. The transmittance of PLZT ceramics increased with an increase of calcination temperature up to 700°C and then it slightly decreased with further increase of calcination temperature. The transmittance strongly depended on the SPS temperature and heat‐treatment temperature. The pellet sintered at 900°C for 10 min and heat treated at 800°C for 1 h with a thickness of 0.5 mm showed a transmittance of 31% at a wavelength of 700 nm. The relationships between the transmittance and the microstructure were investigated.
Prevalence of subjects with progressive bone loss at implants
Authors: Fransson Christer , Lekholm Ulf , Jemt Torsten , Berglundh Tord
Published: August 2005

Aim: The aim of the present study was to assess the prevalence of subjects with progressive bone loss at implants with a function time of at least 5 years.

Material and methods: Radiographs of 1346 patients who had attended annual follow‐up visits at the Brånemark Clinic, Public Dental Services, Gothenburg, Sweden were retrieved. Six hundred and sixty‐two subjects fulfilled the inclusion criteria. Thus, they all had been provided with implant‐supported (Brånemark System® Nobel BioCare, Gothenburg, Sweden) fixed partial or complete dentures or single‐tooth replacements with a documented function time in radiographs of at least 5 years. Implants that demonstrated progressive bone loss to a level of ≥3 threads of an implant were detected. The number of subjects who exhibited one or more implants with progressive bone loss to the threshold level was recorded.

Results: Twenty‐eight percent of 662 included subjects had one or more implants with progressive bone loss. A logistic regression analysis revealed that the individuals in this group carried a significantly larger number of implants than the subjects in whom no implants with progressive loss were detected (6 vs. 4.8). Furthermore, >30% of the subjects in the group with progressive bone loss had ≥3 identified implants and that about 33% of all such implants in this group exhibited extensive bone loss. Out of the total 3413 implants included in the study, 423 implants (12.4%) demonstrated progressive bone loss.

Conclusion: It is suggested that the prevalence of progressive bone loss at implants assessed from subject‐based data is higher than that evaluated from implant‐based data.
Load‐related implant reaction of mini‐implants used for orthodontic anchorage
Authors: Büchter André , Wiechmann Dirk , Koerdt Stefan , Wiesmann Hans Peter , Piffko Josef , Meyer Ulrich
Published: August 2005

Abstract: The purpose of this study was to determine the clinical and biomechanical outcome of two different titanium mini‐implant systems activated with different load regimens. A total of 200 mini‐implants (102 Abso Anchor® and 98 Dual Top®) were placed in the mandible of eight Göttinger minipigs. Two implants each were immediately loaded in opposite direction by various forces (100, 300 or 500 cN) through tension coils. Additionally, three different distances between the neck of the implant and the bone rim (1, 2 and 3 mm) were used. The different load protocols were chosen to evaluate the load‐related implant performance. The load was provided by superelastic tension coils, which are known to develop a virtually constant force. Non‐loaded implants were used as a reference. Following an experimental loading period of 22 and 70 days half of the minipigs were sacrificed, and implant containing bone specimens evaluated for clinical performance and implant stability. Implant loosing was found to be statistically dependent on the tip moment (TM) at the bone rim. Clinical implant loosing were only present when load exceeded 900 cN mm. No movement of implants through the bone was found in the experimental groups, for any applied loads. Over the two experimental periods the non‐loaded implants of one type of implant had a higher stability than those of the loaded implants. Dual Top® implants revealed a slightly higher removal torque compared with Abso Anchor® implants. Based on the results of this study, immediate loading of mini‐implants can be performed without loss of stability when the load‐related biomechanics do not exceed an upper limit of TM at the bone rim.
Resonance frequency analysis and damping capacity assessment
Authors: Lachmann Stefan , Jäger Berthold , Axmann Detlef , Gomez‐Roman German , Groten Martin , Weber Heiner
Published: August 2005

Objectives: The aims of this in vitro study were to evaluate reliability of the Osstell™ and Periotest™ devices in the assessment of implant stability and to perform a method comparison.

Material and methods: Commercial dental implants were inserted into bovine rib segments of different anatomical origins and densities. Repeated measurements were performed, varying (a) the torque‐in force of the devices' attachment screw (the Osstell™ transducer and the ball attachment, insert for the Periotest™ device), (b) the insertion site bone quality, and (c) the thread exposure in simulated peri‐implant bone defects.

Results: Both methods were comparably reliable and showed a strong association to each other in the classification of implant stability. As opposed to torque‐forced screw attachment, the variations in bone composition, differences in inter‐implant stability of adjacent implants, and peri‐implant bone reduction were statistically significant for both methods.

Conclusions: Both non‐invasive diagnostic devices seem to be useful in the long‐term follow‐up of implant integration.
Resonance frequency analysis and damping capacity assessment
Authors: Lachmann Stefan , Yves Laval Johannes , Jäger Berthold , Axmann Detlef , Gomez‐Roman German , Groten Martin , Weber Heiner
Published: August 2005

Objective: We compared the performance of damping capacity assessment (Periotest™ device) to resonance frequency analysis (Osstell™ device) in the assessment of peri‐implant bone loss in an in vitro experiment.

Material and methods: Screw‐type oral implants were polymerized into acrylic blocks. Peri‐implant bone loss was simulated by successively removing defined portions of material surrounding the implants in millimeter increments. Measurement values of both devices were compared by assessing the associated measurement errors, by calculating correlation analyses and drawing scatterplots, and by means of regression analysis referring to increasing bone loss.

Results: Both devices produced comparable results suggesting agreement of the measured implant stability values to the actual loss of peri‐implant resin. There was a noticeable correlation of the Periotest™ and Osstell™ implant stability values.

Conclusion: The results of this experiment suggest agreement in predicting the actual implant stability with both the instruments with the Osstell™ instrument being the more precise device.
Induction and maintenance of late‐phase long‐term potentiation in isolated dendrites of rat hippocampal CA1 pyramidal neurones
Authors: Vickers Catherine A. , Dickson Kirsten S. , Wyllie David J A.
Published: August 2005

Expression of N‐methyl‐d‐aspartate (NMDA) receptor‐dependent long‐term potentiation (LTP) in the CA1 region of the hippocampus can be divided into an early (1–2 h), protein synthesis‐independent phase and a late (>4 h), protein synthesis‐dependent phase. In this study we have addressed whether the de novo protein synthesis required for the expression of late‐LTP can be sustained solely from the translation of mRNAs located in the dendrites of CA1 pyramidal neurones. Our results show that late‐LTP, lasting at least 5 h, can be maintained in hippocampal slices where the dendrites located in stratum radiatum have been isolated from their cell bodies by a microsurgical cut. The magnitude of the potentiation of the slope of field EPSPs in these ‘isolated’ slices was similar to that recorded in ‘intact’ slices. Incubation of the slices with the mRNA translation inhibitor cycloheximide or the mammalian target of rapamycin (mTOR) inhibitor rapamycin blocked late‐LTP in both ‘intact’ and ‘isolated’ slice preparations. In contrast, incubation of slices with the transcription inhibitor, actinomycin D, resulted in a reduction of sustained potentiation, at 4 h, in ‘intact’ slices while in ‘isolated’ slices the magnitude of potentiation was similar to that seen in untreated slices. These results indicate that late‐LTP can be induced and maintained in ‘isolated’ dendritic preparations via translation of pre‐existing mRNAs.
Application of Constrained H∞ Control to Active Suspension Systems on Half-Car Models
Authors: Chen H. , Liu Z. -Y. , Sun P. -Y.
Published: August 2005

This paper formulates the active suspension control problem as disturbance attenuation problem with output and control constraints. The H∞ performance is used to measure ride comfort such that more general road disturbances can be considered, while time-domain hard constraints are captured using the concept of reachable sets and state-space ellipsoids. Hence, conflicting requirements are specified separately and handled in a nature way. In the framework of Linear Matrix Inequality (LMI) optimization, constrained H∞ active suspensions are designed on half-car models with and without considering actuator dynamics. Analysis and simulation results show a promising improvement on ride comfort, while keeping suspension strokes and control inputs within bounds and ensuring a firm contact of wheels to road.
Control of an Electrostatic Microelectromechanical System Using Static and Dynamic Output Feedback
Authors: Maithripala D. H. S. , Berg Jordan M. , Dayawansa W. P.
Published: August 2005

This paper examines control strategies for electrostatically actuated microelectromechanical systems (MEMS), with the goals of using feasible measurements to eliminate the pull-in bifurcation, robustly stabilize any desired operating point in the capacitive gap, decrease settling time, and reduce overshoot. We show that input-output linearization, passivity-based design, and the theory of port-controlled Hamiltonian systems lead naturally to static output feedback of device charge. This formalizes and extends previously reported results from the MEMS literature. Further analysis suggests that significantly improving transient behavior in lightly damped MEMS requires dynamic estimation of electrode velocity. We implement output-feedback control using a reduced-order nonlinear observer. Simulations predict greatly improved transient behavior, and large reductions in control voltage.
Circadian Clock Control by SUMOylation of BMAL1
Authors: Cardone Luca , Hirayama Jun , Giordano Francesca , Tamaru Teruya , Palvimo Jorma J. , Sassone-Corsi Paolo
Published: August 2005

The molecular machinery that governs circadian rhythmicity is based on clock proteins organized in regulatory feedback loops. Although posttranslational modification of clock proteins is likely to finely control their circadian functions, only limited information is available to date. Here, we show that BMAL1, an essential transcription factor component of the clock mechanism, is SUMOylated on a highly conserved lysine residue (Lys
259
) in vivo. BMAL1 shows a circadian pattern of SUMOylation that parallels its activation in the mouse liver. SUMOylation of BMAL1 requires and is induced by CLOCK, the heterodimerization partner of BMAL1. Ectopic expression of a SUMO-deficient BMAL1 demonstrates that SUMOylation plays an important role in BMAL1 circadian expression and clock rhythmicity. This reveals an additional level of regulation within the core mechanism of the circadian clock.
Gliding Motility Leads to Active Cellular Invasion byCryptosporidium parvumSporozoites
Authors: Wetzel Dawn M. , Schmidt Joann , Kuhlenschmidt Mark S. , Dubey J. P. , Sibley L. David
Published: August 2005

We examined gliding motility and cell invasion by an early-branching apicomplexan,Cryptosporidium parvum, which causes diarrheal disease in humans and animals. Real-time video microscopy demonstrated thatC. parvumsporozoites undergo circular and helical gliding, two of the three stereotypical movements exhibited byToxoplasma gondiitachyzoites.C. parvumsporozoites moved more rapidly thanT. gondiisporozoites, which showed the same rates of motility as tachyzoites. Motility byC. parvumsporozoites was prevented by latrunculin B and cytochalasin D, drugs that depolymerize the parasite actin cytoskeleton, and by the myosin inhibitor 2,3-butanedione monoxime. Imaging of the initial events in cell entry byCryptosporidiumrevealed that invasion occurs rapidly; however, the parasite does not enter deep into the cytosol but rather remains at the cell surface in a membrane-bound compartment. Invasion did not stimulate rearrangement of the host cell cytoskeleton and was inhibited by cytochalasin D, even in host cells that were resistant to the drug. Our studies demonstrate thatC. parvumrelies on a conserved actin-myosin motor for motility and active penetration of its host cell, thus establishing that this is a widely conserved feature of the Apicomplexa.
Concurrent Infection with an Intestinal Helminth Parasite Impairs Host Resistance to EntericCitrobacter rodentiumand EnhancesCitrobacter-Induced Colitis in Mice
Authors: Chen Chien-Chang , Louie Steve , McCormick Beth , Walker W. Allan , Shi Hai Ning
Published: August 2005

Infections with intestinal helminth and bacterial pathogens, such as enteropathogenicEscherichia coli, continue to be a major global health threat for children. To test the hypothesis that intestinal helminth infection may be a risk factor for enteric bacterial infection, a murine model was established by using the intestinal helminthHeligomosomoides polygyrus. To analyze the modulatory effect of a Th2-inducing helminth on the outcome of enteric bacteriumCitrobacter rodentiuminfection, BALB/c and STAT 6 knockout (KO) mice were infected withH. polygyrus,C. rodentium, or both. We found that only BALB/c mice coinfected withH. polygyrusandC. rodentiumdisplayed a marked morbidity and mortality. The enhanced susceptibility toC. rodentiumand intestinal injury of coinfected BALB/c mice were shown to be associated with a significant increase in helminth-driven Th2 responses, mucosally and systemically, and correlated with a significant downregulation of protective gamma interferon and with a dramatic upregulation of the proinflammatory tumor necrosis factor alpha response. In addition,C. rodentium-associated colonic pathology in coinfected BALB/c mice was significantly enhanced, whereas bacterial burden was increased and clearance was delayed. In contrast, coinfection in STAT 6 KO mice failed to promoteC. rodentiuminfection or to induce a more severe intestinal inflammation and tissue injury, demonstrating a mechanism by which helminth influences the development of host protective immunity and susceptibility to bacterial infections. We conclude thatH. polygyruscoinfection can promoteC. rodentium-associated disease and colitis through a STAT 6-mediated immune mechanism.
Host Immune Status Influences the Development of Attaching and Effacing Lesions in Weaned Pigs
Authors: Girard Francis , Oswald Isabelle P. , Taranu Ionélia , Hélie Pierre , Appleyard Greg D. , Harel Josée , Fairbrother John M.
Published: August 2005

Attaching and effacing
Escherichia
coli (AEEC) has been associated with naturally occurring attaching and effacing (A/E) lesions in weaned pigs, and although A/E lesions have been experimentally reproduced in newborn piglets, such lesions have been much more difficult to induce in older conventional pigs. Hence, the aim of this study was to examine the effect of oral administration of dexamethasone on the development of A/E lesions in weaned pigs challenged with a porcine enteropathogenic
E. coli
(PEPEC) strain and to investigate the involvement of local intestinal cytokine response. Dexamethasone, given orally at a dosage of 3 mg kg of body weight
−1
, significantly enhanced both the colonization of the challenge strain and the prevalence of foci of intimately adherent bacteria, resulting in extensive A/E lesions in the ileum, cecum, and colon of challenged pigs. We also confirmed the expression of both intimin and Tir by PEPEC strain ECL1001 in A/E lesions in vivo, which is, to our knowledge, the first report of the involvement of the latter proteins in any AEEC infections in vivo. Moreover, semiquantitative reverse transcription-PCR demonstrated that interleukin 1β (IL-1β), IL-6, IL-8, and, to a lesser extent, IL-12p40 are significantly upregulated in the ileum following challenge with strain ECL1001, whereas dexamethasone blocks such upregulation. Taken together, our results strongly suggested that host immune status influences the development of A/E lesions in weaned pigs, and it appears that IL-1β, IL-6, IL-8, and, to a lesser extent, IL-12p40 are expressed during infection of weaned pigs by PEPEC and may contribute to the natural resistance of the host against PEPEC infection.
Systematic Targeted Mutagenesis ofBrucella melitensis16M Reveals a Major Role for GntR Regulators in the Control ofVirulence
Authors: Haine Valérie , Sinon Audrey , Van Steen Frédéric , Rousseau Stéphanie , Dozot Marie , Lestrate Pascal , Lambert Christophe , Letesson Jean-Jacques , De Bolle Xavier
Published: August 2005

In order to identify transcriptional regulators involved in virulence gene control inBrucella melitensis, we generated a collection of 88 mutants in the AraC, ArsR, Crp, DeoR, GntR, IclR, LysR, MerR, RpiR, and TetR families of regulators. This collection was named LiMuR (library ofmutants forregulators). We developed a method to test several mutants simultaneously in one animal in order to identify those unable to survive. This method, called the plasmid-tagged mutagenesis method, was used to test the residual virulence of mutants after 1 week in a mouse model of infection. Ten attenuated mutants, of which six and three belong to the GntR and LysR families, respectively, were identified and individually confirmed to replicate at lower rates in mice. Among these 10 mutants, onlygntR10andarsR6are attenuated in cellular models. The LiMuR also allows simple screenings to identify regulators of a particular gene or operon. As a first example, we analyzed the expression of thevirBoperon in the LiMuR mutants. We carried out Western blottings of whole-cell extracts to analyze the production of VirB proteins using polyclonal antisera against VirB proteins. Four mutants produced small amounts of VirB proteins, and one mutant overexpressed VirB proteins compared to the wild-type strain. In these five mutants, reporter analysis using thevirBpromoter fused tolacZshowed that three mutants controlvirBat the transcriptional level. The LiMuR is a resource that will provide straightforward identification of regulators involved in the control of genes of interest.
SalmonellaPathogenicity Island 2-Dependent Expression of Suppressor of Cytokine Signaling 3 in Macrophages
Authors: Uchiya Kei-ichi , Nikai Toshiaki
Published: August 2005

Salmonellapathogenicity island 2 (SPI-2), which is located at centisome 30.7 on the chromosome ofSalmonella entericaserovar Typhimurium, is required for growth within macrophages and systemic infection in mice. We recently reported that the infection of macrophages withSalmonellainduces the expression of cyclooxygenase-2 in a manner dependent on SPI-2 (K. Uchiya and T. Nikai, Infect. Immun.72:6860-6869, 2004). In the present study, gene expression analysis using a cDNA array further showed the involvement of SPI-2 in the expression of suppressor of cytokine signaling 3 (SOCS-3), which is involved in the inhibition of cytokine signaling via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. A high level of SOCS-3 expression was induced in J774 macrophages infected with wild-typeSalmonellacompared to that in macrophages infected with a strain carrying a mutation in thespiCgene within SPI-2. Other members of the SOCS family were not detected inSalmonella-infected macrophages. The SPI-2-induced up-regulation of SOCS-3 expression was dependent on activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Furthermore, the inhibition of gamma-interferon-induced STAT-1 and interleukin-6-induced STAT-3 tyrosine phosphorylation correlated with the expression of SOCS-3. Taken together, these results indicate thatSalmonellacauses SPI-2-dependent activation of ERK1/2, leading to SOCS-3 expression, which in turn inhibits cytokine signaling via the JAK/STAT pathway.
Experimental Infection Model for Johne's Disease in Sheep
Authors: Begg D. J. , O'Brien R. , Mackintosh C. G. , Griffin J. F. T.
Published: August 2005

Johne's disease in ruminants results in chronic enteritis caused by the pathogenic bacteriumMycobacterium aviumsubsp.paratuberculosis. This study examined twoM. aviumsubsp.paratuberculosisstrains (JD3 and W), using different doses and routes of infection, to establish the optimal time postchallenge when predictable levels of infection, gut lesions, and clinical disease occur in a large proportion of sheep. While a small proportion (25%) of sheep challenged with a low-passage-number laboratory culture ofM. aviumsubsp.paratuberculosis(strain W) became infected, no infection was found in animals exposed to a high-passage-number culture isolate of strain W. In contrast, a primary tissue homogenate ofM. aviumsubsp.paratuberculosis(JD3) resulted in high (90%) infection rates and gut histopathology following oral or intratonsillar challenge. The optimal conditions necessary to produce Johne's disease involve oral inoculation of 3-month-old lambs with four doses of 5 × 108CFU ofM. aviumsubsp.paratuberculosisisolated directly from the gut lymphatic tissues of clinically affected sheep. This resulted in consistent gut histopathology at 9 months and the onset of clinical disease by 11 months postchallenge.
Bovine NK Cells Can Produce Gamma Interferon in Response to the Secreted Mycobacterial Proteins ESAT-6 and MPP14 but Not in Response to MPB70
Authors: Olsen Ingrid , Boysen Preben , Kulberg Siri , Hope Jayne C. , Jungersen Gregers , Storset Anne K.
Published: August 2005

Bovine NK cells have recently been characterized and the present study describes the interaction between NK cells, antigen-presenting cells, and secreted mycobacterial proteins. Gamma interferon (IFN-γ) production by NK cells was seen in approximately 30% of noninfected calves in response to theMycobacterium tuberculosiscomplex-specific protein ESAT-6, MPP14 fromMycobacterium aviumsubsp.paratuberculosis, and purified protein derivative (PPD) fromM. tuberculosis. In contrast, no response was induced by MPB70, which is anotherM. tuberculosiscomplex-specific secreted antigen. The production of IFN-γ by NK cells in whole blood in response to ESAT-6 and MPP14 was demonstrated using intracellular staining together with surface labeling for the NK cell-specific receptor, NKp46, or CD3. Furthermore, the depletion of NK cells from peripheral blood mononuclear cells completely abolished the IFN-γ production. The response was mediated through stimulation of adherent cells and was largely independent of contact between adherent cells and the NK cells. Neutralization of interleukin-12 only partly inhibited IFN-γ production, showing that other cytokines were also involved. The demonstration of NK cell-mediated IFN-γ production in young cattle provides an explanation for the nonspecific IFN-γ response frequently encountered in young cattle when using the IFN-γ test in diagnosis of mycobacterial infections.
Characterization of
Vibrio cholerae
RyhB: the RyhB Regulon and Role of
ryhB
in Biofilm Formation
Authors: Mey Alexandra R. , Craig Stephanie A. , Payne Shelley M.
Published: August 2005

Vibrio cholerae
encodes a small RNA with homology to
Escherichia coli
RyhB. Like
E. coli ryhB
,
V. cholerae ryhB
is negatively regulated by iron and Fur and is required for repression of genes encoding the superoxide dismutase SodB and multiple tricarboxylic acid cycle enzymes. However,
V. cholerae
RyhB is considerably longer (>200 nucleotides) than the
E. coli
RNA (90 nucleotides), and it regulates the expression of a variety of genes that are not known to be regulated by RyhB in
E. coli
, including genes involved in motility, chemotaxis, and biofilm formation. A mutant with a deletion in
ryhB
had reduced chemotactic motility in low-iron medium and was unable to form wild-type biofilms. The defect in biofilm formation was suppressed by growing the mutant in the presence of excess iron or succinate. The wild-type strain showed reduced biofilm formation in iron-deficient medium, further supporting a role for iron in normal biofilm formation. The
ryhB
mutant was not defective for colonization in a mouse model and appeared to be at a slight advantage when competing with the wild-type parental strain. Other genes whose expression was influenced by RyhB included those encoding the outer membrane porins OmpT and OmpU, several iron transport systems, and proteins containing heme or iron-sulfur clusters. These data indicate that
V. cholerae
RyhB has diverse functions, ranging from iron homeostasis to the regulation of biofilm formation.
Pathogenicity and Immunogenicity of a Vaccine Strain ofListeria monocytogenesThat Relies on a Suicide Plasmid To Supply an Essential Gene Product
Authors: Zhao Xinyan , Li Zhongxia , Gu Baiyan , Frankel Fred R.
Published: August 2005

Listeria monocytogenesis a bacterial pathogen that elicits a strong cellular immune response and thus has potential use as a vaccine vector. An attenuated strain,L. monocytogenes dal dat, produced by deletion of two genes (dalanddat) used ford-alanine synthesis, induces cytotoxic T lymphocytes and protective immunity in mice following infection in the presence ofd-alanine. In order to obviate the dependence ofL. monocytogenes dal daton supplementald-alanine yet retain its attenuation and immunogenicity, we explored mechanisms to allow transient endogenous synthesis of the amino acid. Here, we report on a derivative strain,L. monocytogenes dal dat/pRRR, that expresses adalgene and synthesizesd-alanine under highly selective conditions. We constructed the suicide plasmid pRRR carrying adalgene surrounded by twores1sites and a resolvase gene,tnpR, which acts at theres1sites. The resolvase gene is regulated by a promoter activated upon exposure to host cell cytosol.L. monocytogenes dal dat/pRRR was thus able to grow in liquid culture and to infect host cells withoutd-alanine supplementation. However, after infection of these cells, resolvase-mediated excision of thedalgene resulted in strong down-regulation of racemase expression. As a result, this system allowed only transient growth ofL. monocytogenes dal dat/pRRR in infected cells and survival in animals for only 2 to 3 days. Nevertheless, mice immunized withL. monocytogenes dal dat/pRRR generated listeriolysin O-specific effector and memory CD8+T cells and were protected against lethal challenge by wild-typeListeria. This vector may be an attractive vaccine candidate for the induction of protective cellular immune responses.
Vaccination with theLeishmania infantumAcidic Ribosomal P0 Protein plus CpG Oligodeoxynucleotides Induces Protection against Cutaneous Leishmaniasis in C57BL/6 Mice but Does Not Prevent Progressive Disease in BALB/c Mice
Authors: Iborra Salvador , Carrión Javier , Anderson Charles , Alonso Carlos , Sacks David , Soto Manuel
Published: August 2005

We have examined the efficacy of the administration in mice of a molecularly defined vaccine based on theLeishmania infantumacidic ribosomal protein P0 (rLiP0). Two different challenge models of murine cutaneous leishmaniasis were used: (i) subcutaneous inoculation ofL. majorparasites in susceptible BALB/c mice (a model widely used for vaccination analysis) and (ii) the intradermal inoculation of a low infective dose in resistant C57BL/6 mice (a model that more accurately reproduces theL. majorinfection in natural reservoirs and in human hosts). First, we demonstrated that C57BL/6 mice vaccinated with LiP0-DNA or rLiP0 protein plus CpG oligodeoxynucleotides (ODN) were protected against the development of dermal pathology and showed a reduction in the parasite load. This protection was associated with production of gamma interferon (IFN-γ) in the dermal site. Secondly, we showed that immunization with rLiP0 plus CpG ODN is able to induce only partial protection in BALB/c, since these mice finally developed a progressive disease. Further, we demonstrated that LiP0 vaccination induces a Th1 immunological response in both strains of mice. In both cases, the antibodies against LiP0 were predominantly of the immunoglobulin G2a isotype, which was correlated with an rLiP0-stimulated production of IFN-γ in draining lymph nodes. Finally, we demonstrated that LiP0 vaccination does not prevent the Th2 response induced byL. majorinfection in BALB/c mice. Taken together, these data indicate that the BALB/c model of cutaneous leishmaniasis may undervalue the potential efficacy of some vaccines based on defined proteins, making C57BL/6 a suitable alternative model to test vaccine candidates.