Investigation on parameters used in warning systems for rain-induced embankment instability

A number of instrumented laboratory-scale soil embankment slopes were subjected to artificial rainfall until they failed. The factor of safety of the slope based on real-time measurements of pore-water pressure (suction) and laboratory measured soil properties were calculated as the rainfall progressed. Based on the experiment measurements and slope stability analysis, it was observed that slope displacement measurements can be used to warn the slope failure more accurately. Further, moisture content/pore-water pressure measurements near the toe of the slope and the real-time factor of safety can also be used for prediction of rainfall-induced embankment failures with adequate accuracy.

Gaseous air pollution and emergency hospital visits for hypertension in Beijing, China : a time-stratified case-crossover study

Background: A number of epidemiological studies have been conducted to research the adverse effects of air pollution on mortality and morbidity. Hypertension is the most important risk factor for cardiovascular mortality. However, few previous studies have examined the relationship between gaseous air pollution and morbidity for hypertension. ---------- Methods: Daily data on emergency hospital visits (EHVs) for hypertension were collected from the Peking University Third Hospital. Daily data on gaseous air pollutants (sulfur dioxide (SO2) and nitrogen dioxide (NO2)) and particulate matter less than 10 μm in aerodynamic diameter (PM10) were collected from the Beijing Municipal Environmental Monitoring Center. A time-stratified case-crossover design was conducted to evaluate the relationship between urban gaseous air pollution and EHVs for hypertension. Temperature and relative humidity were controlled for. ---------- Results: In the single air pollutant models, a 10 μg/m3 increase in SO2 and NO2 were significantly associated with EHVs for hypertension. The odds ratios (ORs) were 1.037 (95% confidence interval (CI): 1.004-1.071) for SO2 at lag 0 day, and 1.101 (95% CI: 1.038-1.168) for NO2 at lag 3 day. After controlling for PM10, the ORs associated with SO2 and NO2 were 1.025 (95% CI: 0.987-1.065) and 1.114 (95% CI: 1.037-1.195), respectively.---------- Conclusion: Elevated urban gaseous air pollution was associated with increased EHVs for hypertension in Beijing, China.

Insulin-like growth factor-i : vitronectin complex-induced changes in gene expression effect breast cell survival and migration

Recent studies have demonstrated that IGF-I associates with VN through IGF-binding proteins (IGFBP) which in turn modulate IGF-stimulated biological functions such as cell proliferation, attachment and migration. Since IGFs play important roles in transformation and progression of breast tumours, we aimed to describe the effects of IGF-I:IGFBP:VN complexes on breast cell function and to dissect mechanisms underlying these responses. In this study we demonstrate that substrate-bound IGF-I:IGFBP:VN complexes are potent stimulators of MCF-7 breast cell survival, which is mediated by a transient activation of ERK/MAPK and sustained activation of PI3-K/AKT pathways. Furthermore, use of pharmacological inhibitors of the MAPK and PI3-K pathways confirms that both pathways are involved in IGF-I:IGFBP:VN complex-mediated increased cell survival. Microarray analysis of cells stimulated to migrate in response to IGF-I:IGFBP:VN complexes identified differential expression of genes with previously reported roles in migration, invasion and survival (Ephrin-B2, Sharp-2, Tissue-factor, Stratifin, PAI-1, IRS-1). These changes were not detected when the IGF-I analogue (\[L24]\[A31]-IGF-I), which fails to bind to the IGF-I receptor, was substituted; confirming the IGF-I-dependent differential expression of genes associated with enhanced cell migration. Taken together, these studies have established that IGF-I:IGFBP:VN complexes enhance breast cell migration and survival, processes central to facilitating metastasis. This study highlights the interdependence of ECM and growth factor interactions in biological functions critical for metastasis and identifies potential novel therapeutic targets directed at preventing breast cancer progression.

Apoptosis is induced in Chlamydia trachomatis infected HEp-2 cells by the addition of a combination innate immune activation compounds and the inhibitor wedelolactone

Problem: Innate immune activation of human cells, for some intracellular pathogens, is advantageous for vacuole morphology and pathogenic viability. It is unknown whether innate immune activation is advantageous to Chlamydia trachomatis viability. ----- ----- Method of study: Innate immune activation of HEp-2 cells during Chlamydia infection was conducted using lipopolysaccharide (LPS), polyI:C, and wedelolactone (innate immune inhibitor) to investigate the impact of these conditions on viability of Chlamydia. ----- ----- Results: The addition of LPS and polyI:C to stimulate activation of the two distinct innate immune pathways (nuclear factor kappa beta and interferon regulatory factor) had no impact on the viability of Chlamydia. However, when compounds targeting either pathway were added in combination with the specific innate immune inhibitor (wedelolactone) a major impact on Chlamydia viability was observed. This impact was found to be due to the induction of apoptosis of the HEp-2 cells under these conditions. ----- ----- Conclusion: This is the first time that induction of apoptosis has been reported in C. trachomatis-infected cells when treated with a combination of innate immune activators and wedelolactone.

Involvement of Exo1b in DNA damage-induced apoptosis

Apoptosis is essential for the maintenance of inherited genomic integrity. During DNA damage-induced apoptosis, mechanisms of cell survival, such as DNA repair are inactivated to allow cell death to proceed. Here, we describe a role for the mammalian DNA repair enzyme Exonuclease 1 (Exo1) in DNA damage-induced apoptosis. Depletion of Exo1 in human fibroblasts, or mouse embryonic fibroblasts led to a delay in DNA damage-induced apoptosis. Furthermore, we show that Exo1 acts upstream of caspase-3, DNA fragmentation and cytochrome c release. In addition, induction of apoptosis with DNA-damaging agents led to cleavage of both isoforms of Exo1. The cleavage of Exo1 was mapped to Asp514, and shown to be mediated by caspase-3. Expression of a caspase-3 cleavage site mutant form of Exo1, Asp514Ala, prevented formation of the previously observed fragment without any affect on the onset of apoptosis. We conclude that Exo1 has a role in the timely induction of apoptosis and that it is subsequently cleaved and degraded during apoptosis, potentially inhibiting DNA damage repair.

Ureaplasma colonization of amniotic fluid and efficacy of antenatal corticosteroids for preterm lung maturation in sheep

Objective: To assess the efficacy of maternal betamethasone for improving preterm lung function, in the presence of inflammation induced by amniotic fluid ureaplasma colonization. ----- ----- Study design: Ewes bearing single fetuses were randomized to receive an intra-amniotic injection of Ureaplasma parvum (serovar 6; 2×107 colony forming units) or vehicle at 86±2 days of pregnancy (mean±SD: term is 150d), followed by maternal intramuscular betamethasone (0.5mg/kg) or saline, either 2 or 7 days before delivery of lambs at 123±1d. ----- ----- Results: Amniotic fluid IL-8 was elevated by ureaplasmas (p=0.049) but unaffected by betamethasone. Lung inflammation induced by ureaplasmas was not affected by betamethasone. Lung compliance was increased by ureaplasma colonization (p=0.009) and betamethasone (p=0.042), and effects were additive. Lung surfactant was increased by ureaplasma colonization (p<0.001) and betamethasone 7 days (p=0.001), but not 2 days, before delivery. ----- ----- Conclusion: Inflammation improves preterm lung function due to increases in surfactant. Antenatal corticosteroids further augment lung function, through an apparently independent mechanism.

Vibration characteristics of slender structures under human induced loads

This paper presents the outcome of investigations and studies of the vibratioon characteristics and response of low frequency structural systems for a composite concrete steel floor plate and a reverse profiled cable tensioned foot bridge. These highly dynamic and slender structure are the engineering response to planning, aesthetic and environmental influences, but are prone to excessive and complex vibration. A number of design codes and practice guides provided information to engineers for vibration mitigation However, they are limited to very simple load function applied to a few uncoupled translational modes of excitation. Motivated by the need to address the knowledge gaps in this area, the investigations described in this paper focused on synchronous multi-modal and coupled excitation of the floor plate and footbridge with considerations for torsinal effects. The results showed the potential for adverse dynamic response from multi-modal and coupled excitation influenced by patterned loading, structure geometry, stiffness distribution, directional effects, forcing functions based on activity frequency and duration of foot contact, and modal participation. It was also shown that higher harmonics of the load frequency can excite higher modes in the composite floor structure. Such responsive behaviour is prevalent mainly in slender and lightweight construction and not in stiffer and heavier structural systems. The analytical techniques and methods used in these investigations can supplement the current limited code and best practice provisions for mitigating the impact of human induced vibrations in slender structural systems.

Porphyromonas gingivalis lipopolysaccharide alters atherosclerotic-related gene expression in oxidized low-density-lipoprotein-induced macrophages and foam cells

The molecular mechanism between atherosclerosis formation and periodontal pathogens is not clear although positive correlation between periodontal infections and cardiovascular diseases has been reported. Objective: To determine if atherosclerosis related genes were affected in foam cells during and after its formation by P. gingivalis lipopolysaccharide (LPS) stimulation. Methods: Macrophages from human THP-1 monocytes were treated with oxidized low density lipoprotein (oxLDL) to induce the formation of foam cells. P. gingivalis LPS was added to cultures of either oxLDL-induced macrophages or foam cells. The expression of atherosclerosis related genes was assayed by quantitative real time PCR and the protein production of granulocyte-macrophage colony-stimulating factor（GM-CSF）, monocyte chemotactic protein-1 (MCP-1), IL-1β, IL-10 and IL-12 was determined by ELISA. Nuclear translocation of NF-κB P65 was detected by immunocytochemistry and western blot was used to evaluate IKB-α degradation to confirm the NF-κB pathway activation. Results: P. gingivalis LPS stimulated atherosclerosis related gene expression in foam cells and increased oxLDL induced expression of chemokines, adhesion molecules, growth factors, apoptotic genes, and nuclear receptors in macrophages. Transcription of the pro-inflammatory cytokines IL-1β and IL-12 was elevated in response to LPS in both macrophages and foam cells, whereas the anti-inflammatory cytokine IL-10 was not affected. Increased NF-κB pathway activation was also observed in LPS and oxLDL co-stimulated macrophages. Conclusion: P. gingivalis LPS appears to be an important factor in the development of atherosclerosis by stimulation of atherosclerosis related gene expression in both macrophages and foam cells via activation of the NF-κB pathway.

Development and validation of a pregnancy symptoms inventory

BACKGROUND. Physical symptoms are common in pregnancy and are predominantly associated with normal physiological changes. These symptoms have a social and economic cost, leading to absenteeism from work and additional medical interventions. There is currently no simple method for identifying common pregnancy related problems in the antenatal period. A validated tool, for use by pregnancy care providers would be useful. AIM: The aim of the project was to develop and validate a Pregnancy Symptoms Inventory for use by healthcare professionals (HCPs). METHODS: A list of symptoms was generated via expert consultation with midwives and obstetrician gynaecologists. Focus groups were conducted with pregnant women in their first, second or third trimester. The inventory was then tested for face validity and piloted for readability and comprehension. For test-re-test reliability, it was administered to the same women 2 to 3 days apart. Finally, outpatient midwives trialled the inventory for 1 month and rated its usefulness on a 10cm visual analogue scale (VAS). The number of referrals to other health care professionals was recorded during this month. RESULTS: Expert consultation and focus group discussions led to the generation of a 41-item inventory. Following face validity and readability testing, several items were modified. Individual item test re-test reliability was between .51 to 1 with the majority (34 items) scoring .0.70. During the testing phase, 211 surveys were collected in the 1 month trial. Tiredness (45.5%), poor sleep (27.5%) back pain (19.5%) and nausea (12.6%) were experienced often. Among the women surveyed, 16.2% claimed to sometimes or often be incontinent. Referrals to the incontinence nurse increased > 8 fold during the study period. The median rating by midwives of the ‘usefulness’ of the inventory was 8.4 (range 0.9 to 10). CONCLUSIONS: The Pregnancy Symptoms Inventory (PSI) was well accepted by women in the 1 month trial and may be a useful tool for pregnancy care providers and aids clinicians in early detection and subsequent treatment of symptoms. It shows promise for use in the research community for assessing the impact of lifestyle intervention in pregnancy.

Changes in resting and walking energy expenditure and walking speed during pregnancy in obese women

Background Energy conserving processes reported in undernourished women during pregnancy are a recognised strategy to provide energy required to support fetal development. Women who are obese before conceiving arguably have sufficient fat stores to support the energy demands of pregnancy without the need to provoke energy conserving mechanisms. Objective We tested the hypothesis that obese women would demonstrate behavioural adaptation (i.e. decrease in self-selected walking (SSW) speed) but not metabolic compensation (i.e. decrease in resting metabolic rate (RMR) or metabolic cost of walking) during gestation. Design RMR, SSW speed, metabolic cost of walking, and anthropometry were measured in 23 women (BMI: 33.6 ± 2.5 kg/m2; 31 ± 4 years) at approximately weeks 15 (wk 15) and 30 (wk 30) of gestation. RMR was also measured in two cohorts of non-pregnant controls matched for age, weight and height of the pregnant cohort at wk 15 (N=23) and wk 30 (N=23). Results GWG varied widely (11.3 ± 5.4 kg) and 52% of women gained more weight than is recommended. RMR increased significantly by an average 177 ± 176 kcal/d (11±12%; P<0.0001); however the within-group variability was large. Both the metabolic cost of walking and SSW speed decreased significantly (P<0.01). While RMR increased in >80% of the cohort, the net oxygen cost of walking decreased in the same proportion of women. Conclusions While the increase in RMR was greater than was explained by weight gain, there was evidence of both behavioural and biological compensation in the metabolic cost of walking in obese women during gestation.