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BACKGROUND: Lipids play a vital role in health and disease, but changes to their circulating levels and the link with obesity remain poorly characterized in expecting mothers and their offspring in early childhood. METHODS: LC-MS/MS-based quantitation of 480 lipid species was performed on 2491 plasma samples collected at 4 time points in the mother-offspring Asian cohort GUSTO (Growing Up in Singapore Towards healthy Outcomes). These 4 time points constituted samples collected from mothers at 26-28 weeks of gestation (n=752) and 4-5 years postpartum (n=650), and their offspring at birth (n=751) and 6 years of age (n=338). Linear regression models were used to identify the pregnancy and developmental age-specific variations in the plasma lipidomic profiles, and their association with obesity risk. An independent birth cohort (n=1935), the Barwon Infant Study (BIS), comprising mother-offspring dyads of Caucasian origin was used for validation. RESULTS: Levels of 36% of the profiled lipids were significantly higher (absolute fold change > 1.5 and Padj < 0.05) in antenatal maternal circulation as compared to the postnatal phase, with phosphatidylethanolamine levels changing the most. Compared to antenatal maternal lipids, cord blood showed lower concentrations of most lipid species (79%) except lysophospholipids and acylcarnitines. Changes in lipid concentrations from birth to 6 years of age were much higher in magnitude (log2FC=-2.10 to 6.25) than the changes observed between a 6-year-old child and an adult (postnatal mother) (log2FC=-0.68 to 1.18). Associations of cord blood lipidomic profiles with birth weight displayed distinct trends compared to the lipidomic profiles associated with child BMI at 6 years. Comparison of the results between the child and adult BMI identified similarities in association with consistent trends (R2=0.75). However, large number of lipids were associated with BMI in adults (67%) compared to the children (29%). Pre-pregnancy BMI was specif

Facing the new challenges in production processes, companies should adopt lean and green practices in product development. In SMEs, the application of these practices is more complex. This work explores the maturity of lean–green methodologies in the product development process in Brazilian and Japanese SMEs. The methodology used is multicriteria, combining the analytic hierarchy process (AHP) and TOPSIS 2-tuple method, applied to four Japanese SMEs and four Brazilian SMEs in the metalworking sector. The criteria for evaluating SMEs are company flexibility, difficulties with NPD, innovation, limited resources, and personnel authority high. The TOPSIS method alternatives refer to 18 lean–green enablers. In the AHP method, the prioritisation of criteria between Japanese and Brazilian specialists presented divergences. In the Japanese context, the incidence of innovation is predominant, while in the Brazilian context, the most important is the limited resources. In the TOPSIS 2-tuple method, the results showed a higher level of maturity in lean–green methodologies in Japanese companies than in Brazilian ones. Lean practices are more evolved compared to sustainable practices in both countries. The study also addressed how open innovation adoption may contribute to innovation and NPD practices. Policymakers need to understand the heterogeneity of innovators within SMEs and how they differently innovate, developing distinct internal and external activities.

Asians are underrepresented across many omics databases, thereby limiting the potential of precision medicine in nearly 60% of the global population. As such, there is a pressing need for multi-omics derived quantitative trait loci (QTLs) to fill the knowledge gap of complex traits in populations of Asian ancestry. Here, we provide the first blood-based multi-omics analysis of Asian pregnant women, constituting high-resolution genotyping (N = 1079), DNA methylation (N = 915) and transcriptome profiling (N = 238). Integrative omics analysis identified 219 154 CpGs associated with cis-DNA methylation QTLs (meQTLs) and 3703 RNAs associated with cis-RNA expression QTLs (eQTLs). Ethnicity was the largest contributor of inter-individual variation across all omics datasets, with 2561 genes identified as hotspots of this variation; 395 of these hotspot genes also contained both ethnicity-specific eQTLs and meQTLs. Gene set enrichment analysis of these ethnicity QTL hotspots showed pathways involved in lipid metabolism, adaptive immune system and carbohydrate metabolism. Pathway validation by profiling the lipidome (~480 lipids) of antenatal plasma (N = 752) and placenta (N = 1042) in the same cohort showed significant lipid differences among Chinese, Malay and Indian women, validating ethnicity-QTL gene effects across different tissue types. To develop deeper insights into the complex traits and benefit future precision medicine research in Asian pregnant women, we developed iMOMdb, an open-access database.

BACKGROUND: In Western countries, Asian children have higher food allergy risk than Caucasian children. The early-life environmental exposures for this discrepancy are unclear. We aimed to compare prevalence of food allergy and associated risk factors between Asian children in Singapore and Australia. METHODS: We studied children in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort (n = 878) and children of Asian ancestry in the HealthNuts cohort (n = 314). Food allergy was defined as a positive SPT ≥3 mm to egg or peanut AND either a convincing history of IgE-mediated reaction at 18 months (GUSTO) or a positive oral food challenge at 14-18 months (HealthNuts). Eczema was defined as parent-reported doctor diagnosis. RESULTS: Food allergy prevalence was 1.1% in Singapore and 15.0% in Australia (P<0.001). Egg introduction was more often delayed (>10 months) in Singapore (63.5%) than Australia (16.3%; P<0.001). Prevalence of early-onset eczema (<6 months) was lower in Singapore (8.4%) than Australia (30.5%) (P<0.001). Children with early-onset eczema were more likely to have food allergy than those without eczema in Australia [aOR 5.11 (2.34-11.14); P<0.001] and Singapore [aOR4.00 (0.62-25.8); P = 0.145]. CONCLUSIONS: Among Asian children, prevalence of early-onset eczema and food allergy was higher in Australia than Singapore. Further research with larger sample sizes and harmonized definitions of food allergy between cohorts is required to confirm and extend these findings. Research on environmental factors influencing eczema onset in Australia and Singapore may aid understanding of food allergy pathogenesis in different parts of the world.

While maternal mental health strongly influences neurodevelopment and health in the offspring, little is known about the determinants of inter-individual variation in the mental health of mothers. Likewise, the in utero biological pathways by which variation in maternal mental health affects offspring development remain to be defined. Previous studies implicate lipids, consistent with a known influence on cognitive and emotional function, but the relevance for maternal mental health and offspring neurodevelopment is unclear. This study characterizes the placental and circulatory lipids in antenatal depression, as well as socio-emotional outcomes in the offspring. Targeted liquid chromatography-mass spectrometry covering 470 lipid species was performed on placenta from 186 women with low (n = 70) or high (n = 116) levels of antenatal depressive symptoms assessed using the Edinburgh Postnatal Depression Scale at 26 weeks' gestation. Child socio-emotional outcomes were assessed from the Child Behavior Check List (CBCL) at 48 months. Seventeen placental lipid species showed an inverse association with antenatal EPDS scores. Specifically, lower levels of phospholipids containing LC-PUFAs: omega-3 docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and omega-6 arachidonic acid (AA) were significantly associated with depressive symptoms. Additional measurement of LC-PUFA in antenatal plasma samples at mid-gestation confirmed the reduced circulation of these specific fatty acids in mothers. Reduced concentration of the placental phospholipids also predicted poorer socio-emotional outcomes in the offspring. This study provides new insights into the role of the materno-fetal lipid cross-talk as a mechanism linking maternal mental health to that of the offspring. These findings show the potential utility of nutritional approaches among pregnant women with depressive symptoms to reduce offspring risk for later socio-emotional problems.

A simple solution method to identify buckling resistance of reinforced concrete (RC) columns during inelastic deformation is presented. Unlike conventional buckling solution methods, this proposed method predicts inelastic buckling loads of RC columns by directly solving the equilibrium differential equation under buckling. The method considers specific deflection configuration, end restraint conditions and inelastic material properties of the deformed column. In order to evaluate the reliability and accuracy of the proposed method, the results obtained from the purposed method are compared with the test results of eccentrically loaded RC columns. In addition, by using the proposed solution procedure, a parametric study is conducted to investigate the effects of critical RC column design parameters on column buckling behavior and resistance, including slenderness ratio, concrete strength, as well as longitudinal reinforcement and stirrup ratios. The results of the parametric study show that the proposed method is rational and can be adopted to effectively identify buckling resistance of RC columns subjected to inelastic damage, especially when load redistributions have occurred in the structure during progressive collapse.

A simple yet effective method for dynamic assessment of building structures subject to a sudden column removal is presented. An equivalent single-degree-of-freedom (SDOF) dynamic model to predict the realistic dynamic response of the structure after column removal is proposed. This model considers nonzero initial conditions that are likely to occur under blast loading and structural damping, which can significantly affect the dynamic performance under large deformations. Based on the proposed method, dynamic response of a structure subject to a specific dynamic loading released from column removal is analytically solved. Four sets of physical tests of structures subject to column removal, including quasi-static tests and the corresponding multiple free-fall dynamic tests, are employed to verify the proposed assessment method. In addition, the classical pseudostatic assessment is conducted for the test series and compared with the present method. Results obtained from the verification study demonstrate the accuracy and effectiveness of the proposed simplified dynamic assessment. In addition, the proposed equivalent SDOF method is simple and can be easily implemented with a spreadsheet by practicing engineers. This advantage allows the proposed method to be employed as a routine design procedure for predicting the dynamic performance of structures subject to column removal.

Individual differences in children's eating behaviours emerge early. We examined the relationship between breastfeeding exposure and subsequent eating behaviours among children from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Children (n = 970) were grouped according to their breastfeeding exposure: high (full breastfeeding ≥ 4 months with continued breastfeeding ≥ 6 months), low (any breastfeeding < 3 months or no breastfeeding) and intermediate (between low and high breastfeeding categories). Aspects of eating behaviour from ages 15 months to 6 years were captured using a combination of maternal reports (Child Eating Behaviour Questionnaire; Infant Feeding Questionnaire; Preschooler Feeding Questionnaire) and laboratory-based measures of meal size, oral processing behaviours (e.g. average eating speed and bite size) and tendency to eat in the absence of hunger. Most children had low (44%) or intermediate (44%) breastfeeding exposure; only 12% had high exposure. After adjusting for confounders, multivariable linear regression analyses indicated the high (but not intermediate) breastfeeding group was associated with significantly lower reported food fussiness at 3 years compared to low breastfeeding group (-0.38 [-0.70, -0.06]), with similar but non-significant trends observed at 6 years (-0.27 [-0.66, 0.11]). At 3 years, mothers in the high breastfeeding group also reported the least difficulty in child feeding compared to low breastfeeding group (-0.22 [-0.43, -0.01]). However, high breastfeeding was not associated with any other maternal-reports of child feeding or eating behaviours, and no significant associations were observed between breastfeeding exposure and any of the laboratory measures of eating behaviour at any of the time points. These results do not strongly support the view that increased breastfeeding exposure alone has lasting and consistent associations with eating behaviours in early childhood.

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science.

In this study, an investigation on the deformation profiles near the plastic hinge regions of propped cantilever beams is carried out by both experiment and numerical simulation. In the experiment, two series of beams are loaded until two plastic hinges are formed at the loading point and the fixed end. In the numerical simulation, the extended finite element method formulation is employed to simulate the non-smooth displacement field resulted from the plastic hinges. The comparison on the experimental and the numerical results shows that the Hermite function is able to describe the non-smooth displacement resulted from plastic hinges in the steel beams.

To assess the robustness of reinforced concrete structures under progressive collapses, alternate load path method by introducing a single column removal has been widely adopted by structural engineers. Numerical analyses of structures under several possibilities of single column removal may be time consuming, especially when non-linear finite element analyses are employed which require high computational costs and modelling skills. Towards this end, a simplified analytical model is proposed in this paper to facilitate engineers in predicting resistance of the affected substructure (frames or frame-slabs above the removed column), and allow them to perform a quick check on the adequacy of progress collapse resistance of the structure to stop or prevent the damage propagation to the remaining structure. The proposed model considers development of different bridging mechanisms in RC structures under a concentrated loading above the removed column, including compressive arch action, catenary action, and tensile membrane action. In addition to validation against test results, applications of the proposed analytical model to predict the bridging capacities of a 2-D two-storey frame and unsymmetrical double-span beams are also presented.

AIMS: The cumulative effect of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) on postpartum cardio-metabolic diseases is equivocal. We aimed to assess the associations of GDM and HDP's individual and synergic contribution to risks of postpartum cardio-metabolic diseases (metabolic syndrome (MetS), abnormal glucose metabolism and hypertension (HTN)). METHODS: Of participants from a Singapore birth cohort, 276 mothers attending the 5-year postpartum visit were included in this study. During this visit, we collected mothers' history of GDM and HDP in all live births in a chronicle sequence and assessed the cardio-metabolic risks based on blood pressure, anthropometry and a panel of serum biomarkers. We diagnosed MetS, abnormal glucose metabolism and HTN according to Adult Treatment Panel III 2000 and World Health Organization guidelines. RESULTS: Of 276 mothers, 157 (56.9%) had histories of GDM while 23 (8.3%) had histories of HDP. After full adjustment, we found associations of GDM episodes with postpartum abnormal glucose metabolism (single episode: relative risk (RR) 2.9 (95% CI: 1.7, 4.8); recurrent episodes (≥2): RR = 3.8 (2.1-6.8)). Also, we found association between histories of HDP and HTN (RR = 3.6 (1.5, 8.6)). Having either (RR 2.6 (1.7-3.9)) or both gestational complications (RR 2.7 (1.6-4.9)) was associated with similar risk of postpartum cardio-metabolic disease. CONCLUSIONS: Mothers with GDM or HDP had a threefold increased risk of postpartum abnormal glucose metabolism or HTN, respectively. Having both GDM and HDP during past pregnancies was not associated with additional risk of postpartum cardio-metabolic diseases beyond that associated with either complication alone.

Research studies on 2-D reinforced concrete (RC) beams under middle column removal scenarios have found that catenary action (CA) can significantly increase structural resistance and deflection beyond flexural capacity. However, development of CA is highly dependent on the rotational capacity of RC beams and the degree of horizontal restraints from adjacent structures. Previous studies have identified the effect of varying beam details, (such as geometry and reinforcement ratio) on CA, but very few publications focused on the beneficial effect of rotational capacity on CA. To the authors’ best knowledge, there has not been any publication on quantifying the effect of rotational capacity on CA. Moreover, experimental studies of CA have so far been conducted on RC beams with full restraints at the two supporting ends. Hence, in this study, five RC frame specimens were tested to study the effects of rotational capacity and degree of horizontal restraint on CA. One frame served as a control specimen, two specimens for improvement in rotational capacity, and another two with inadequate horizontal restraint. Improvement in rotational capacity was engineered in one frame through provision of closer-spaced stirrups near to the joints and another frame through substitution of deformed bars with smooth round bars. Adverse effect of inadequate horizontal restraint was investigated under penultimate column removal scenarios. Through the testing and analysis of the five frames, the effects of improvement in rotational capacity and inadequate horizontal restraint on CA could be quantified and discussed. Finally, practical suggestions on enhancing CA through detailing were provided.

© Springer International Publishing AG 2018. The survivability of a structure under progressive collapse highly relies on its toughness (energy absorption prior to failure). In a 2-D Reinforced Concrete (RC) frame for example, if catenary action is developed, the provision of greater rotational capacity at the support interface would contribute to larger deformations (improving toughness) and longer surviving time of the frame. Previous tests on 2-D RC frames have shown that under large deformations, concrete surrounding the rebar was highly damaged due to cracking, spalling or splitting, reducing the frame capacity. It has also been realised that one way to increase the deformation limit of frames is by allowing more slip or elongation of reinforcement. Based on these two observations, alterations to the conventional reinforcement detailing are devised to improve the frame deformation capacity, i.e. provision of stirrups in accordance to seismic detailing rule to minimise concrete damage and substitution of deformed bars with round bars as longitudinal reinforcement to facilitate greater rotation and slip. Three frame specimens are presented in this paper, the first frame with conventional detailing as the control specimen (FR), the second frame with higher shear reinforcement ratio based on seismic detailing (FR-S), and the last frame with round bars as longitudinal reinforcement (FR-R). Through this study, the effects of modified detailing towards the load resistance and deformation capacity of 2-D RC frames can be quantified.

© Springer International Publishing AG 2018. In the design of structures against progressive collapse, tie-force method under missing corner column is deemed to be ineffective in providing resistance and integrity to the structures. This is because the structure is left with inadequate horizontal restraints to develop catenary action. Previous tests on Reinforced concrete (RC) beam-slab specimens under corner column removal scenarios subject to point load have identified little development of catenary action in the beam and tensile membrane action (TMA) in the slab, and the beam-slab specimens mainly relied on flexural capacity to resist the point loads. But in reality, the beam-slab system is subjected to uniform distributed load (UDL), and not point loads. It is only due to expediency in testing that researchers subject the beam-slab specimen to point loads. Thus, there have not been any beam-slab system tests under corner column removal scenarios subjected to UDL. The novelty of this paper is to conduct one such test with the beam-slab specimen subjected to UDL. The surprising finding was that TMA was developed in the beam-slab specimen. The inclusion of TMA may provide an upper bound or a more realistic prediction in progressive collapse analysis of corner beam-slab systems subject to UDL. The test result of the beam-slab specimen subject to UDL was also compared with that of the specimen subject to point loads, to understand the differences in load-carrying mechanisms and capacities between the two types of loadings.

© 2016 Elsevier Ltd. Due to increasing threats from terrorism, progressive collapse modeling is gaining popularity with the objective of simulating the collapse process of the whole or partial structural system. In order to conduct an accurate progressive collapse modeling, one needs to identify damaged members and to trace the propagation of damage. Hence, good damage assessment criteria are vital to the modeling and analysis. Only with reliable damage assessment criteria, realistic collapse mechanisms of structures can be simulated. It can then provide useful guidance for a better and more economic structural design against progressive collapse. This paper presents a set of damage assessment criteria that can be easily implemented for progressive collapse analysis of reinforced concrete (RC) frames. Flexural, shear and axial damage criteria for RC members are separately proposed incorporating axial-shear-flexural interactions in the analysis. Three scaled moment-resisting RC frame tests were conducted to validate the proposed flexural and axial damage criteria. Three shear-dominant damaged tests were also modeled to assess the proposed shear damage criteria. The results obtained show that the proposed damage assessment criteria are effective and reliable for progressive collapse analysis of RC frames.

A new adaptive superelement procedure for progressive collapse analysis of 2D reinforced concrete frames under column removal scenario is proposed. Superelement formulation is employed to reduce the computational cost. In addition, a new procedure for rigid body rotation correction is proposed to improve the accuracy of the superelement formulation. An error indicator is developed to monitor the propagation of the nonlinear zone during analysis. The adaptive analysis procedure is then formed by combining the error indicator with a reliable member and substructure collapse identification algorithm. Numerical examples are given to demonstrate the accuracy, robustness and efficiency of the modeling procedure. As the work involves establishing a novel concept to reduce computational effort when simulating the whole process of collapse, the authors only consider the impact energy of falling objects in a quasi-static manner through the use of dynamic increase factors, thereby obviating the need for time-consuming nonlinear structural dynamic analysis.

In this study, a new modeling procedure for progressive collapse analysis of 2D reinforced concrete (RC) frames subject to single or multiple column removal scenario is proposed. Different from traditional pushdown analysis, the proposed method incorporates the effects of service loads before column removal into the analysis. To trace the collapse sequence of the structure, a member removal algorithm based on combined actions of flexural/shear/axial failures is employed. For detecting substructure collapse mechanisms, a specially designed searching algorithm is developed. Furthermore, the locations and magnitudes of collapse impacts are respectively determined by rigid-body kinematics and energy principle with both inelastic and oblique impact effects considered. Numerical examples with different loading and column removal scenarios are given to validate the suggested damage assessment procedure, the member failures identification procedure and the collapse searching algorithms as well as to demonstrate the effectiveness of the proposed modeling approach.

In a cast in-situ reinforced concrete (RC) beam-slab system, concurrent development of secondary mechanisms, i.e. catenary action in beams and tensile membrane action in slabs, may significantly increase load-carrying and deformation capacities of structures under missing column scenarios. Previous researches mainly focused on structural behaviour of individual RC beams, slabs or beam-slab systems, without clearly defining structural interactions among slabs, beams and columns. To obtain a better understanding of these complex interactions, a systematic study starting from RC skeletal frames and culminating in frame-slab systems is conducted under corner and exterior column removal scenarios, which are among the most critical scenarios for analysis of structural resistance towards progressive collapse. Four specimens were included in this programme, i.e. under corner column loss event, one skeletal frame (COR) and one frame-slab (S-COR) specimens were tested to failure, while one skeletal frame (EXT) and one frame-slab (S-EXT) specimens were loaded to collapse under exterior column loss scenario. In 3D beam-slab tests, it is very challenging to design a test setup with complete measurements of all support reactions due to a great number of statical indeterminacies. The novelty of the paper is to address this aspect. Through the proper test setup and instrumentation of structural behaviour of RC 3-D skeletal frames under corner and exterior column loss scenarios, interactions between the columns and beams could be elucidated. In turn, the slab contributions could be isolated and quantified through direct comparisons between skeletal frame and frame-slab specimens for both scenarios.

Azithromycin has recently gained popularity for the treatment of periodontal disease, despite sparse literature supporting efficiency in treating periodontal bacterial biofilms. The aim of this study was to evaluate the effect of azithromycin on biofilms comprised of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia in comparison to an amoxicillin and metronidazole combination. P. gingivalis W50, T. denticola ATCC35405, and T. forsythia ATCC43037 grown under anaerobic conditions at 37°C were aliquoted into 96-well flat-bottom plates in different combinations with addition of azithromycin or amoxicillin + metronidazole at various concentrations. For the biofilm assay, the plates were incubated at 37°C anaerobically for 48 h, after which the biofilms were stained with crystal violet and measured for absorbance at AU620. In this model, polymicrobial biofilms of P. gingivalis + T. denticola, P. gingivalis + T. forsythia, and T. denticola + T. forsythia were cultured. Combination of all three bacteria enhanced biofilm biomass. Azithromycin demonstrated a minimal biofilm inhibitory concentration (MBIC) of 10.6 mg/L, while the amoxicillin + metronidazole combination was more effective in inhibiting biofilm formation with a MBIC of 1.63 mg/L. Polymicrobial biofilm formation was demonstrated by combination of all three red complex bacteria. Azithromycin was ineffective in preventing biofilm formation within a clinically achievable concentration, whereas the combination of amoxicillin and metronidazole was more effective for this purpose.

OBJECTIVES: To determine the potential acidogenicy of liquid breakfasts. METHODS: In vitro acid production by Streptococcus mutans was measured in the beverages at a pH of 5.5, as was the fall in pH over 10min. The buffering capacity was determined, as well as the calcium, inorganic phosphate and fluoride concentrations (total and soluble) of the beverages. Bovine milk (UHT) was used for comparison. RESULTS: The rate of acid production by S. mutans, and pH fall over 10min was greater in liquid breakfasts compared to bovine milk. All beverages except one demonstrated a significantly lower buffering capacity than bovine milk. All beverages contained significantly greater concentrations of soluble calcium than bovine milk, and all except two contained significantly more soluble inorganic phosphate. CONCLUSIONS: S. mutans was able to generate significantly more acid in the liquid breakfasts than in bovine milk, indicating these drinks may contribute to a cariogenic diet. In general, the liquid breakfasts required significantly less acid than bovine milk to reduce their pH to the approximate critical pH for enamel demineralisation. However, the liquid breakfasts also tended to contain significantly more soluble calcium and inorganic phosphate than bovine milk. CLINICAL SIGNIFICANCE: The substantial amounts and various types of sugars found within liquid breakfast beverages may result in a significant pH drop in dental plaque following consumption of these products.

For several decades, p53 has been detected in cancer biopsies by virtue of its high protein expression level which is considered indicative of mutation. Surprisingly, however, mouse genetic studies revealed that mutant p53 is inherently labile, similar to its wild type (wt) counterpart. Consistently, in response to stress conditions, both wt and mutant p53 accumulate in cells. While wt p53 returns to basal level following recovery from stress, mutant p53 remains stable. In part, this can be explained in mutant p53-expressing cells by the lack of an auto-regulatory loop with Mdm2 and other negative regulators, which are pivotal for wt p53 regulation. Further, additional protective mechanisms are acquired by mutant p53, largely mediated by the co-chaperones and their paralogs, the stress-induced heat shock proteins. Consequently, mutant p53 is accumulated in cancer cells in response to chronic stress and this accumulation is critical for its oncogenic gain of functions (GOF). Building on the extensive knowledge regarding wt p53, the regulation of mutant p53 is unraveling. In this review, we describe the current understanding on the major levels at which mutant p53 is regulated. These include the regulation of p53 protein levels by microRNA and by enzymes controlling p53 proteasomal degradation.

Objective We aimed to study the maternal retinal microvasculature at mid-trimester and its relationship with subsequent fetal growth and birth size. Methods We recruited 732 pregnant women aged 18-46 years in the first trimester with singleton pregnancies. All had retinal photography and fetal scan performed at 26-28 weeks gestation, and subsequent fetal scan at 32-34 weeks gestation. Infant anthropometric measurements were done at birth. Retinal microvasculature was measured using computer software from the retinal photographs. Results In multiple linear regression models, each 10 mu m narrowing in maternal retinal arteriolar caliber was associated with decreases of 1.36 mm in fetal head circumference at 32-34 weeks gestation, as well as decreases of 1.50 mm and 2.30 mm in infant head circumference and birth length at delivery, respectively. Each standard deviation decrease in maternal retinal arteriolar fractal dimension was associated with decreases of 1.55 mm in fetal head circumference at 32-34 weeks gestation, as well as decreases of 1.08 mm and 46.42 g in infant head circumference and birth weight at delivery, respectively. Conclusions Narrower retinal arteriolar caliber and a sparser retinal vascular network in mothers, reflecting a suboptimal uteroplacental microvasculature during mid-pregnancy, were associated with poorer fetal growth and birth size.

Porphyromonas gingivalis and Treponema denticola are strongly associated with chronic periodontitis. These bacteria have been co-localized in subgingival plaque and demonstrated to exhibit symbiosis in growth in vitro and synergistic virulence upon co-infection in animal models of disease. Here we show that during continuous co-culture a P. gingivalis:T. denticola cell ratio of 6∶1 was maintained with a respective increase of 54% and 30% in cell numbers when compared with mono-culture. Co-culture caused significant changes in global gene expression in both species with altered expression of 184 T. denticola and 134 P. gingivalis genes. P. gingivalis genes encoding a predicted thiamine biosynthesis pathway were up-regulated whilst genes involved in fatty acid biosynthesis were down-regulated. T. denticola genes encoding virulence factors including dentilisin and glycine catabolic pathways were significantly up-regulated during co-culture. Metabolic labeling using 13C-glycine showed that T. denticola rapidly metabolized this amino acid resulting in the production of acetate and lactate. P. gingivalis may be an important source of free glycine for T. denticola as mono-cultures of P. gingivalis and T. denticola were found to produce and consume free glycine, respectively; free glycine production by P. gingivalis was stimulated by T. denticola conditioned medium and glycine supplementation of T. denticola medium increased final cell density 1.7-fold. Collectively these data show P. gingivalis and T. denticola respond metabolically to the presence of each other with T. denticola displaying responses that help explain enhanced virulence of co-infections.

The cAMP response element binding protein 1 (Creb1) transcription factor regulates cellular gene expression in response to elevated levels of intracellular cAMP. Creb1(-/-) fetal mice are phenotypically smaller than wildtype littermates, predominantly die in utero and do not survive after birth due to respiratory failure. We have further investigated the respiratory defect of Creb1(-/-) fetal mice during development. Lungs of Creb1(-/-) fetal mice were pale in colour and smaller than wildtype controls in proportion to their reduced body size. Creb1(-/-) lungs also did not mature morphologically beyond E16.5 with little or no expansion of airway luminal spaces, a phenotype also observed with the Creb1(-/-) lung on a Crem(-/-) genetic background. Creb1 was highly expressed throughout the lung at all stages examined, however activation of Creb1 was detected primarily in distal lung epithelium. Cell differentiation of E17.5 Creb1(-/-) lung distal epithelium was analysed by electron microscopy and showed markedly reduced numbers of type-I and type-II alveolar epithelial cells. Furthermore, immunomarkers for specific lineages of proximal epithelium including ciliated, non-ciliated (Clara), and neuroendocrine cells showed delayed onset of expression in the Creb1(-/-) lung. Finally, gene expression analyses of the E17.5 Creb1(-/-) lung using whole genome microarray and qPCR collectively identified respiratory marker gene profiles and provide potential novel Creb1-regulated genes. Together, these results demonstrate a crucial role for Creb1 activity for the development and differentiation of the conducting and distal lung epithelium.

A vernalization-related gene VER2 was isolated from winter wheat (Triticum aestivum L.) using a differential screening approach. The deduced VER2 is a lectin-like protein of 300 amino acids, which contains the presence of a jacalin-like GWG domain. RNA in situ hybridization results demonstrated that VER2 gene expression is restricted to the marginal meristems of immature leaves in vernalized wheat seedlings. No hybridization signal was detected in the epidermal tissue and vascular bundles. However, `devernalization' resulted in the silencing of VER2 gene activity. The gene expression pattern of VER2 induced by jasmonate was similar to that induced by vernalization. Antisense inhibition of VER2 in transgenic wheat showed that heading and maturation time were delayed up to 6 weeks compared with non-transformed wheat and the pBI121empty-vector-transformed wheat. Tissue degeneration at the top of the spike was also noticed in the antisense inhibited transgenic wheat. These results suggest that VER2 plays an important role in vernalization signaling and spike development in winter wheat.

A vernalization-related gene VER2 was isolated from winter wheat (Triticum aestivum L.) using a differential screening approach. The deduced VER2 is a lectin-like protein of 300 amino acids, which contains the presence of a jacalin-like GWG domain. RNA in situ hybridization results demonstrated that VER2 gene expression is restricted to the marginal meristems of immature leaves in vernalized wheat seedlings. No hybridization signal was detected in the epidermal tissue and vascular bundles. However, `devernalization' resulted in the silencing of VER2 gene activity. The gene expression pattern of VER2 induced by jasmonate was similar to that induced by vernalization. Antisense inhibition of VER2 in transgenic wheat showed that heading and maturation time were delayed up to 6 weeks compared with non-transformed wheat and the pBI121empty-vector-transformed wheat. Tissue degeneration at the top of the spike was also noticed in the antisense inhibited transgenic wheat. These results suggest that VER2 plays an important role in vernalization signaling and spike development in winter wheat.

A vernalization-related gene VER2 was isolated from winter wheat (Triticum aestivum L.) using a differential screening approach. The deduced VER2 is a lectin-like protein of 300 amino acids, which contains the presence of a jacalin-like GWG domain. RNA in situ hybridization results demonstrated that VER2 gene expression is restricted to the marginal meristems of immature leaves in vernalized wheat seedlings. No hybridization signal was detected in the epidermal tissue and vascular bundles. However, `devernalization' resulted in the silencing of VER2 gene activity. The gene expression pattern of VER2 induced by jasmonate was similar to that induced by vernalization. Antisense inhibition of VER2 in transgenic wheat showed that heading and maturation time were delayed up to 6 weeks compared with non-transformed wheat and the pBI121empty-vector-transformed wheat. Tissue degeneration at the top of the spike was also noticed in the antisense inhibited transgenic wheat. These results suggest that VER2 plays an important role in vernalization signaling and spike development in winter wheat.

Determination of injection molding machine setting is usually carried out by an experienced machine operator. By considering the mold geometry, polymer type and machine model, the operator decides an initial setting based on his own knowledge. This knowledge could include material and machine data, empirical rules and simple formulae. A computer system based on this knowledge is developed for computing an initial setting for an injection molding machine. The system first determines the possible processing conditions by considering only the material type and machine model. Then an initial processing condition is determined from these possible conditions by reasoning using the empirical rules. This reasoning is formalized by fuzzy logic. Finally, the machine setting corresponds to the determined initial processing condition is calculated by simple formulae. The performance of the system has been verified by experiments. Results show that the computed setting is acceptable for simple geometry.

Determination of injection molding machine setting is usually carried out by an experienced machine operator. By considering the mold geometry, polymer type and machine model, the operator decides an initial setting based on his own knowledge. This knowledge could include material and machine data, empirical rules and simple formulae. A computer system based on this knowledge is developed for computing an initial setting for an injection molding machine. The system first determines the possible processing conditions by considering only the material type and machine model. Then an initial processing condition is determined from these possible conditions by reasoning using the empirical rules. This reasoning is formalized by fuzzy logic. Finally, the machine setting corresponds to the determined initial processing condition is calculated by simple formulae. The performance of the system has been verified by experiments. Results show that the computed setting is acceptable for simple geometry.

Determination of injection molding machine setting is usually carried out by an experienced machine operator. By considering the mold geometry, polymer type and machine model, the operator decides an initial setting based on his own knowledge. This knowledge could include material and machine data, empirical rules and simple formulae. A computer system based on this knowledge is developed for computing an initial setting for an injection molding machine. The system first determines the possible processing conditions by considering only the material type and machine model. Then an initial processing condition is determined from these possible conditions by reasoning using the empirical rules. This reasoning is formalized by fuzzy logic. Finally, the machine setting corresponds to the determined initial processing condition is calculated by simple formulae. The performance of the system has been verified by experiments. Results show that the computed setting is acceptable for simple geometry.