Base-induced decomposition of alkyl hydroperoxides in the gas phase. Part 3. Kinetics and dynamics in HO-+CH3OOH, C2H5OOH, and tert-C4H9OOH reactions

The E-CO(2) elimination reactions of alkyl hydroperoxides proceed via abstraction of an (x-hydrogen by a base: X- + (RRHCOOH)-R-1-H-2 -> HX + (RRC)-R-1-C-2=O + HO-. Efficiencies and product distributions for the reactions of the hydroxide anion with methyl, ethyl, and tert-butyl hydroperoxides are studied in the gas phase. On the basis of experiments using three isotopic analogues, HO- + CH3OOH, HO- + CD3OOH, and H18O- + CH3OOH. the overall intrinsic reaction efficiency is determined to be 80% or greater. The E(CO)2 decomposition is facile for these methylperoxide reactions, and predominates over competing proton transfer at the hydroperoxide moiety. The CH3CH2OOH reaction displays a similar E(CO)2 reactivity, whereas proton transfer and the formation of HOO- are the exclusive pathways observed for (CH3)(3)COOH, which has no (x-hydrogen. All results are consistent with the E-CO(2) mechanism, transition state structure, and reaction energy diagrams calculated using the hybrid density functional B3LYP approach. Isotope labeling for HO- + CH3OOH also reveals some interaction between H2O and HO- within the E(CO)2 product complex [H2O center dot center dot center dot CH2=O center dot center dot center dot HO-]. There is little evidence, however. for the formation of the most exothermic products H2O + CH2(OH)O-, which would arise from nuclephilic condensation of CH2=O and HO-. The results suggest that the product dynamics are not totally statistical but are rather direct after the E-CO(2) transition state. The larger HO- + CH3CH2OOH system displays more statistical behavior during complex dissociation.

Comparison of 3 accelerometer data reduction approaches, step counts, and 2 self-report measures for estimating physical activity in free-living adults

Background Accelerometers have become one of the most common methods of measuring physical activity (PA). Thus, validity of accelerometer data reduction approaches remains an important research area. Yet, few studies directly compare data reduction approaches and other PA measures in free-living samples. Objective To compare PA estimates provided by 3 accelerometer data reduction approaches, steps, and 2 self-reported estimates: Crouter's 2-regression model, Crouter's refined 2-regression model, the weighted cut-point method adopted in the National Health and Nutrition Examination Survey (NHANES; 2003-2004 and 2005-2006 cycles), steps, IPAQ, and 7-day PA recall. Methods A worksite sample (N = 87) completed online-surveys and wore ActiGraph GT1M accelerometers and pedometers (SW-200) during waking hours for 7 consecutive days. Daily time spent in sedentary, light, moderate, and vigorous intensity activity and percentage of participants meeting PA recommendations were calculated and compared. Results Crouter's 2-regression (161.8 +/- 52.3 minutes/day) and refined 2-regression (137.6 +/- 40.3 minutes/day) models provided significantly higher estimates of moderate and vigorous PA and proportions of those meeting PA recommendations (91% and 92%, respectively) as compared with the NHANES weighted cut-point method (39.5 +/- 20.2 minutes/day, 18%). Differences between other measures were also significant. Conclusions When comparing 3 accelerometer cut-point methods, steps, and self-report measures, estimates of PA participation vary substantially.

Bimolecular interaction of Insulin-Like Growth Factor (IGF) binding protein-2 with αvβ3 negatively modulates IGF-I-Mediated migration and tumor growth

Both the integrin and insulin-like growth factor binding protein (IGFBP) families independently play important roles in modulating tumor cell growth and progression. We present evidence for a specific cell surface localization and a bimolecular interaction between the αvβ3 integrin and IGFBP-2. The interaction, which could be specifically perturbed using vitronectin and αvβ3 blocking antibodies, was shown to modulate IGF-mediated cellular migration responses. Moreover, this interaction was observed in vivo and correlated with reduced tumor size of the human breast cancer cells, MCF-7β3, which overexpressed the αvβ3 integrin. Collectively, these results indicate that αvβ3 and IGFBP-2 act cooperatively in a negative regulatory manner to reduce tumor growth and the migratory potential of breast cancer cells.

Epidermal growth factor promotes MDA-MB-231 breast cancer cell migration through a phosphatidylinositol 3'-kinase and phospholipase C-dependent mechanism

Epidermal growth factor receptor (EGFR) levels predict a poor outcome in human breast cancer and are most commonly associated with proliferative effects of epidermal growth factor (EGF), with little emphasis placed on motogenic responses to EGF. We found that MDA-MB-231 human breast cancer cells elicited a potent chemotactic response despite their complete lack of a proliferative response to EGF. Antagonists of EGFR ligation, the EGFR kinase, phosphatidylinositol 3'-kinase, and phospholipase C, but not the mitogen- activated protein kinases (extracellular signal-regulated protein kinase 1 and 2), blocked MDA-MB-231 chemotaxis. These findings suggest that EGF may influence human breast cancer progression via migratory pathways, the signaling for which appears to be dissociated, at least in part, from the proliferative pathways.

Validation of a 3-day physical activity recall instrument in female youth

The purpose of this study was to examine the validity of the 3-Day Physical Activity Recall (3DPAR) self-report instrument in a sample of eighth and ninth grade girls (n = 70, 54.3% white, 37.1% African American). Criterion measures of physical activity were derived using the CSA 7164 accelerometer. Participants wore a CSA monitor for 7 consecutive days and completed the self-report physical activity recall for the last 3 of those days. Self-reported total METs, 30-min blocks of MVPA, and 30-min blocks of VPA were all significantly correlated with analogous CSA variables for 7 days (r = 0.35-0.51; P < 0.01) and 3 days (r = 0.27-0.46; P < 0.05) of monitoring. The results indicate that the 3DPAR is a valid instrument for assessing overall, vigorous, and moderate to vigorous physical activity in adolescent girls.

Validity and reliability of the 3-day physical activity recall in Singaporean adolescents

Childhood obesity and physical inactivity are major health concerns for the Singaporean government (Ministry of Health, Singapore [MOH], 2001). Data from the 1998 Singaporean National Health Survey indicate that 10.8–14.7% of Singaporean children ages 6–16 years are either overweight or obese (MOH, 2001). Although true population estimates of youth physical activity are not available, descriptive epidemiological studies conducted in the 1990s suggest that a large percentage of school-aged children in Singapore fail to meet established guidelines for participation in physical activity...

Bone sialoprotein supports breast cancer cell adhesion proliferation and migration through differential usage of the αvβ3 and αvβ5 integrins

Bone sialoprotein (BSP), a secreted glycoprotein found in bone matrix, has been implicated in the formation of mammary microcalcifications and osteotropic metastasis of human breast cancer (HBC). BSP possesses an integrin-binding RGD (Arg-Gly-Asp) domain, which may promote interactions between HBC cells and bone extracellular matrix. Purified BSP, recombinant human BSP fragments and BSP-derived RGD peptides are shown to elicit migratory, adhesive, and proliferative responses in the MDA-MB-231 HBC cell line. Recombinant BSP fragment analysis localized a significant component of these activities to the RGD domain of the protein, and synthetic RGD peptides with BSP flanking sequences (BSPRGD) also conferred these responses. The fibronectin-derived RGD counterpart, GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro), could not support these cellular responses, emphasizing specificity of the BSP configuration. Although most of the proliferative and adhesive responses could be attributed to RGD interactions, these interactions were only partly responsible for the migrational responses. Experiments with integrin-blocking antibodies demonstrated that BSP-RGD-induced migration utilizes the αvβ3 vitronectin receptor, whereas adhesion and proliferation responses were αvβ5-mediated. Using fluorescence activated cell sorting, we selected two separate subpopulations of MDA-MB-231 cells enriched for αvβ3 or αvβ5 respectively. Although some expression of the alternate αv integrin was still retained, the αvβ5-enriched MDA-MB-231 cells showed enhanced proliferative and adhesive responses, whereas the αvβ3-enriched subpopulation was suppressed for proliferation and adhesion, but showed enhanced migratory responses to BSP-RGD. In addition, similar analysis of two other HBC cell lines showed less marked, but similar RGD-dependent trends in adhesion and proliferation to the BSP fragments. Collectively, these data demonstrate BSP effects on proliferative, migratory, and adhesive functions in HBC cells and that the RGD-mediated component differentially employs αvβ3 and αvβ5 integrin receptors.

Physical activities and sedentary pursuits in African American and Caucasian girls

The purposes of this study were to describe and compare the specific physical activity choices and sedentary pursuits of African American and Caucasian American girls. Participants were 1,124 African American and 1,068 Caucasian American eighth grade students from 31 middle schools. The 3-Day Physical Activity Recall (3DPAR) was used to measure participation in physical activities and sedentary pursuits. The most frequently reported physical activities were walking, basketball, jogging or running, bicycling, and social dancing. Differences between groups were found in 11 physical activities and 3 sedentary pursuits. Participation rates were higher in African American girls (p<.001)for social dancing, basketball, watching television, and church attendance but lower in calisthenics, ballet and other dance, jogging or running, rollerblading, soccer, softball or baseball, using an exercise machine, swimming, and homework. Cultural differences of groups should be considered when planning interventions to promote physical activity.

Induction of tumorigenicity by galectin-3 in a nontumorigenic human breast-carcinoma cell-line

The human galectin-3 is a galactoside-binding protein of 31 kDa which functions as a receptor for glycoproteins containing poly N-acetyllactosamine side chains and as a substrate for matrix metalloproteinases-2 and -9. We studied its expression by flow cytofluorimetry, Western, Northern and Southern analyses, in five cultured human breast carcinoma cell lines previously characterized as non-tumorigenic, poorly metastatic or metastatic in nude mice. The expression of galectin-3 correlated with the reported tumorigenicity of the cells. The introduction of recombinant galectin-3 into the null expressing non-tumorigenic BT-549 cells resulted in the acquisition of anchorage-independent growth properties in alland tumorigenicity in 3/4 sense transfected cell crones. The data indicate a relationship between galectin-3 expression and malignancy of human breast carcinoma cell lines.

Physical activity and overweight in children aged 3-5 : relationship to parental activity and obesity

OBJECTIVE To compare the physical activity levels of overweight and non overweight 3- to 5-y-old children while attending preschool. A secondary aim was to evaluate weight-related differences in hypothesized parental determinants of child physical activity behavior. DESIGN Cross-sectional study. SUBJECTS A total of 245, 3- to 5-y-olds (127 girls, 118 boys) and their parent(s) (242 mothers, 173 fathers) recruited from nine preschools. Overweight status determined using the age- and sex-specific 85th percentile for body mass index (BMI) from CDC Growth Charts. MEASUREMENTS Physical activity during the preschool day was assessed on multiple days via two independent objective measures direct observation using the observation system for recording activity in preschools (OSRAP) and real-time accelerometry using the MTI/CSA 7164 accelerometer. Parents completed a take-home survey assessing sociodemographic information, parental height and weight, modeling of physical activity, support for physical activity, active toys and sporting equipment at home, child’s television watching, frequency of park visitation, and perceptions of child competence. RESULTS Overweight boys were significantly less active than their nonoverweight peers during the preschool day. No significant differences were observed in girls. Despite a strong association between childhood overweight status and parental obesity, no significant differences were observed for the hypothesized parental influences on physical activity behavior. CONCLUSIONS Our results suggest that a significant proportion of overweight children may be at increased risk for further gains in adiposity because of low levels of physical activity during the preschool day.

The type I collagen induction of MT1-MMP-mediated MMP-2 activation is repressed by αVβ3 integrin in human breast cancer cells

The influence of αVβ3 integrin on MT1-MMP functionality was studied in human breast cancer cells of differing β3 integrin status. Overexpression of β3 integrin caused increased cell surface expression of αV integrin and increased cellular adhesion to extracellular matrix (ECM) substrates in BT-549, MDA-MB-231 and MCF-7 cells. β3 integrin expression also enhanced the migration of breast cancer cells on ECM substrates and enhanced collagen gel contraction. In vivo, αVβ3 cooperated with MT1-MMP to increase the growth of MCF-7 cells after orthotopic inoculation in immunocompromised mice, but had no influence on in vitro proliferation. Despite these stimulatory effects, overexpression of β3 integrin suppressed the type I collagen (Col I) induced MMP-2 activation in all breast cancer cell lines analyzed. This was also evident in extracts from the MCF-7 tumors in vivo, where MMP-2 activation was stimulated by MT1-MMP transfection, but attenuated with β3 integrin expression. Although our studies confirm important biological effects of αVβ3 integrin on enhancing cell adhesion and migration, ECM remodeling and tumor growth, β3 integrin caused reduced MMP-2 activation in response to Col I in vitro, which appears to be physiologically relevant, as it was also seen in tumor xenografts in vivo. The reduction of MMP-2 activation (and thus MT1-MMP activity) by αVβ3 in response to Col I may be important in scenarios where cells which are activated for matrix degradation need to preserve some pericellular collagen, perhaps as a substrate for cell adhesion and migration, thus maintaining a balanced level of proteolysis required for efficient tumor growth.

The role of vascularization in 3-D tissue engineering

The role of vascularization in 3-D tissue engineering was studied. Mouse fat, angiogenic growth factors, adult human stem cells and fat tissue have been inserted and subsequent tissue growth was monitored. Human fat grafts or human lipoaspirates in SCID mouse chambers induced mouse fat generation at 6 weeks. Tissue engineering models utilizing intrinsic vascularization have major advantages including rapid and appropriate vascularization of new tissues.

Thoracoscopic scoliosis surgery – a cheaper option? A cost analysis of 189 consecutive cases

INTRODUCTION: Increasing health care costs, limited resources and increased demand makes cost effective and cost-efficient delivery of Adolescent Idiopathic Scoliosis (AIS) management paramount. Rising implant costs in deformity correction surgery have prompted analysis of whether high implant densities are justified. The objective of this study was to analyse the costs of thoracoscopic scoliosis surgery, comparing initial learning curve costs with those of the established technique and to the costs involved in posterior instrumented fusion from the literature. METHODS: 189 consecutive cases from April 2000 to July 2011 were assessed with a minimum of 2 years follow-up. Information was gathered from a prospective database covering perioperative factors, clinical and radiological outcomes, complications and patient reported outcomes. The patients were divided into three groups to allow comparison; 1. A learning curve cohort, 2. An intermediate cohort and 3. A third cohort of patients, using our established technique. Hospital finance records and implant manufacturer figures were corrected to 2013 costs. A literature review of AIS management costs and implant density in similar curve types was performed. RESULTS: The mean pre-op Cobb angle was 53°(95%CI 0.4) and was corrected postop to mean 22.9°(CI 0.4). The overall complication rate was 20.6%, primarily in the first cohort, with a rate of 5.6% in the third cohort. The average total costs were $46,732, operating room costs of $10,301 (22.0%) and ICU costs of $4620 (9.8%). The mean number of screws placed was 7.1 (CI 0.04) with a single rod used for each case giving average implant costs of $14,004 (29.9%). Comparison of the three groups revealed higher implant costs as the technique evolved to that in use today, from $13,049 in Group 1 to $14577 in Group 3 (P<0.001). Conversely operating room costs reduced from $10,621 in Group 1 to $7573 (P<0.001) in Group 3. ICU stay was reduced from an average of 1.2 to 0 days. In-patient stay was significantly (P=0.006) lower in Groups 2 and 3 (5.4 days) than Group 1 (5.9 days) (i.e. a reduction in cost of approximately $6,140). CONCLUSIONS: The evolution of our thoracoscopic anterior scoliosis correction has resulted in an increase in the number of levels fused and reduction in complication rate. Implant costs have risen as a result, however, there has been a concurrent decrease in those costs generated by operating room use, ICU and in-patient stay with increasing experience. Literature review of equivalent curve types treated posteriorly shows similar perioperative factors but higher implant density, 69-83% compared to the 50% in this study. Thoracoscopic Scoliosis surgery presents a low density, reliable, efficient and effective option for selected curves. A cost analysis of Thoracoscopic Scoliosis Surgery using financial records and a prospectively collected database of all patients since 2000, demonstrating a clear cost advantage compared to equivalent posterior instrumentation and fusion.

Homogeneous bent functions of degree n in 2n variables do not exist for n>3

We prove that homogeneous bent functions f:GF(2)^2n --> GF(2) of degree n do not exist for n>3. Consequently homogeneous bent functions must have degree 3.