The loss of CO from the ortho, meta and para forms of deprotonated methyl benzoate in the gas phase

The ortho, meta and para anions of methyl benzoate may be made in the source of a mass spectrometer by the S(N)2(Si) reactions between HO- and methyl (o-, m-, and p-trimethylsilyl)benzoate respectively. All three anions lose CO upon collisional activation to form the ortho anion of anisole in the ratio ortho>>meta > para. The rearrangement process is charge directed through the ortho anion. Theoretical calculations at the B3LYP/6-311++G(d,p)//HF/6-31+G(d) level of theory indicate that the conversion of the meta and para anions to the ortho anion prior to loss of CO involve 1,2-H transfer(s), rather than carbon scrambling of the methoxycarbonylphenyl anion. There are two mechanisms which can account for this rearrangement, viz. (A) cyclisation of the ortho anion centre to the carbonyl group of the ester to give a cyclic carbonyl system in which the incipient methoxide anion substitutes at one of the two equivalent ring carbons of the three membered ring to yield an intermediate which loses CO to give the ortho anion of anisole, and (B) an elimination reaction to give an intermediate benzyne-methoxycarbonyl anion complex in which the MeOCO- species acts as a MeO- donor, which then adds to benzyne to yield the ortho anion of anisole. Calculations at the B3LYP/6-311++G(d,p)//HF/6-31+G(d) level of theory indicate that (i) the barrier in the first step (the rate determining step) of process A is 87 kJ mol(-1) less than that for the synchronous benzyne process B, and (ii) there are more low frequency vibrations in the transition state for benzyne process B than for the corresponding transition state for process A. Stepwise process A has the lower barrier for the rate determining step, and the lower Arrhenius factor: we cannot differentiate between these two mechanisms on available evidence.

Loss of epithelial markers and acquisition of vimentin expression in adriamycin- and vinblastine-resistant human breast cancer cell lines

We have previously observed that breast cancer cell lines could exhibit either epithelial or fibroblastic phenotypes as reflected by their morphologies and intermediate filament protein expression (C. L. Sommers, D. Walker-Jones, S. E. Heckford, P. Worland, E. Valverius, R. Clark, M. Stampfer, and E. P. Gelmann, Cancer Res., 49: 4258-4263, 1989). Fibroblastoid, vimentin-expressing breast cancer cell lines are more invasive in vitro and in vivo (E. W. Thompson, S. Paik, N. Brunner, C. L. Sommers, G. Zugmaier, R. Clarke, T. B. Shima, J. Torri, S. Donahue, M. E. Lippman, G. R. Martin, and R. B. Dickson, J. Cell. Physiol., 150: 534-544, 1992). We hypothesized that a breast cancer cell with an epithelial phenotype could undergo a transition to a fibroblastic phenotype, possibly resulting in more invasive capacity. We now show that two Adriamycin-resistant MCF-7 cell lines and a vinblastine-resistant ZR-75-B cell line have undergone such a transition. Adriamycin-resistant MCF-7 cells express vimentin, have diminished keratin 19 expression, have lost cell adhesion molecule uvomorulin expression, and have reduced formation of desmosomes and tight junctions as determined by reduced immunodetection of their components desmoplakins I and II and zonula occludens (ZO)-1. Other MCF-7 cell lines selected for resistance to vinblastine and to Adriamycin and verapamil did not have these characteristics, indicating that drug selection does not invariably cause these phenotypic changes. In addition, to determine if vimentin expression in MCF-7 cells alone could manifest a fibroblastic phenotype, we transfected the full-length human vimentin complementary DNA into MCF-7 cells. Although vimentin expression was achieved in MCF-7 cells, it did not affect the phenotype of the cells in terms of the distribution of keratins, desmoplakins I and II, ZO-1, or uvomorulin or in terms of in vitro invasiveness. We conclude that vimentin expression is a marker for a fibroblastic and invasive phenotype in breast cancer cells but does not by itself give rise to this phenotype.

The loss of carbon dioxide from activated perbenzoate anions in the gas phase : Unimolecular rearrangement via epoxidation of the benzene ring

The unimolecular reactivities of a range of perbenzoate anions (X-C6H5CO3-), including the perbenzoate anion itself (X=H), nitroperbenzoates (X=para-, meta-, ortho-NO2), and methoxyperbenzoates (X=para-, meta-OCH3) were investigated in the gas phase by electrospray ionization tandem mass spectrometry. The collision-induced dissociation mass spectra of these compounds reveal product ions consistent with a major loss of carbon dioxide requiring unimolecular rearrangement of the perbenzoate anion prior to fragmentation. Isotopic labeling of the perbenzoate anion supports rearrangement via an initial nucleophilic aromatic substitution at the ortho carbon of the benzene ring, while data from substituted perbenzoates indicate that nucleophilic attack at the ipso carbon can be induced in the presence of electron-withdrawing moieties at the ortho and para positions. Electronic structure calculations carried out at the B3LYP/6311++G(d,p) level of theory reveal two competing reaction pathways for decarboxylation of perbenzoate anions via initial nucleophilic substitution at the ortho and ipso positions, respectively. Somewhat surprisingly, however, the computational data indicate that the reaction proceeds in both instances via epoxidation of the benzene ring with decarboxylation resulting-at least initially-in the formation of oxepin or benzene oxide anions rather than the energetically favored phenoxide anion. As such, this novel rearrangement of perbenzoate anions provides an intriguing new pathway for epoxidation of the usually inert benzene ring.

Developing a framework of effective prevention and response strategies in workplace sexual harassment

Sexual harassment remains a widespread workplace phenomenon, despite laws that proscribe it. Drawing initially on a typology from the violence prevention literature that conceptualizes prevention and response approaches according to when they occur, the paper synthesizes strategies identified in literature addressing workplace sexual harassment, as well as other workplace injustices or grievances. The paper utilizes this previous research to develop a framework of sexual harassment prevention strategies along two dimensions: functions and timing. The framework offers a research-informed set of organization-wide preventative and remedial approaches, a systemic approach to what is often seen as an individual problem, and a means to better focus interventions that are often disparate and unco-ordinated. The paper also highlights important areas for future research including a stronger focus on longer-term (tertiary) corrective actions.

Sports participation and health-related behaviors among US youth

Objective To examine the relationship between sports participation and health-related behaviors among high school students. Design Cross-sectional design using data from the 1997 Centers for Disease Control and Prevention Youth Risk Behavior Survey. Participants A nationally representative sample of 14221 US high school students. Main Outcome Measures Prevalence of sports participation among males and females from 3 ethnic groups and its associations with other health behaviors, including diet, tobacco use, alcohol and illegal drug use, sexual activity, violence, and weight loss practices. Results Approximately 70% of male students and 53% of female students reported participating on 1 or more spores teams in school and/or nonschool settings; rates varied substantially by age, sex, and ethnicity. Male sports participants were more likely than male nonparticipants to report fruit and vegetable consumption on the previous day and less likely to report cigarette smelting, cocaine and other illegal drug use, and trying to lose weight. Compared with female nonparticipants, female sports participants were more likely to report consumption of vegetables on the previous day and less likely to report having sexual intercourse in the past 3 months. Among white males and females, several other beneficial health behaviors were associated with sports participation. A few associations with. negative health behaviors were observed in African American and Hispanic subgroups. Conclusion Sports participation is highly prevalent among US high school students, and is associated with numerous positive health behaviors and few negative health behaviors.

Encouragement of physical activity for weight loss may lead to negative psychological outcomes among girls

PURPOSE To examine correlates and consequences of parents' encouragement of girls' physical activity (PA) for weight loss (ENCLOSS). METHODS Data were collected for 181 girls, mothers and fathers when girls were 9, 11, and 13 years old. Mothers and fathers completed a self-report questionnaire of ENCLOSS (e.g., “I have talked to my daughter about how to exercise to lose weight”). Correlates of ENCLOSS that were assessed include girls' Body Mass Index (BMI) z-score and parents' modeling of and logistic support for PA. Dependent variables assessed at age 13 include girls' self-reported and objectively-measured PA, enjoyment of physical activity, and weight concerns. Associations between ENCLOSS, girls' BMI, and parent's support for PA were assessed using spearman rank correlations. To examine links between ENCLOSS and the outcome variables, scores for ENCLOSS were divided into tertiles at each age. Three groups were created including girls who were in the highest tertile at each age (high ENCLOSS), girls who were in the lowest tertile at each age (low ENCLOSS), and girls who varied in their tertile ranking (mid ENCLOSS). Group differences in the outcome variables were assessed using regression analysis (referent group: low ENCLOSS), controlling for girls' BMI and the outcome variable at age 9. RESULTS Girls' with higher BMI had mothers and fathers who reported higher ENCLOSS (r = .61-. 69, p<. 0001). Parents'reports of ENCLOSS were not associated with modeling of or logistic support for PA. Girls in the high ENCLOSS group reported significantly lower enjoyment of PA and higher weight concerns at age 13, independent of covariates. No differences in PA were noted. CONCLUSION Parents who encourage their daughters to be active for weight loss do not model PA or facilitate girls' PA. Persistent encouragement of PA for weight loss may lead to low enjoyment of PA and higher weight concerns among adolescent girls.

Using police crash databases for injury prevention research - a comparison of opt-out and opt-in approaches to study recruitment

Objective: The study aimed to examine the difference in response rates between opt-out and opt-in participant recruitment in a population-based study of heavy-vehicle drivers involved in a police-attended crash. Methods: Two approaches to subject recruitment were implemented in two different states over a 14-week period and response rates for the two approaches (opt-out versus opt-in recruitment) were compared. Results: Based on the eligible and contactable drivers, the response rates were 54% for the optout group and 16% for the opt-in group. Conclusions and Implications: The opt-in recruitment strategy (which was a consequence of one jurisdiction’s interpretation of the national Privacy Act at the time) resulted in an insufficient and potentially biased sample for the purposes of conducting research into risk factors for heavy-vehicle crashes. Australia’s national Privacy Act 1988 has had a long history of inconsistent practices by state and territory government departments and ethical review committees. These inconsistencies can have profound effects on the validity of research, as shown through the significantly different response rates we reported in this study. It is hoped that a more unified interpretation of the Privacy Act across the states and territories, as proposed under the soon-to-be released Australian Privacy Principles will reduce the recruitment challenges outlined in this study.

A qualitative investigation of adolescents’ perceived mechanisms of change from a universal school-based depression prevention program

A recent meta-analysis provides evidence supporting the universal application of school-based prevention programs for adolescent depression. The mechanisms underlying such successful interventions, however, are largely unknown. We report on a qualitative analysis of 109 Grade 9 students’ beliefs about what they gained from an evidence-based depression prevention intervention, the Resourceful Adolescent Program (RAP-A). Fifty-four percent of interviewees articulated at least one specific example of program benefit. A thematic analysis of responses revealed two major themes, improved interpersonal relationships and improved self-regulation, both stronger than originally assumed. A more minor theme also emerged—more helpful cognitions. It is postulated that both improved interpersonal relationships and improved self-regulation are likely to enhance one another, and more helpful cognitions may express its contribution through enhanced self-regulation. These findings broaden our understanding of the impact of depression prevention programs, beginning to illuminate how such programs benefit participants.

Engendering the responsibility to protect : women and the prevention of mass atrocities

This article explores the relationship between the Responsibility to Protect (R2P) and the pursuit of the so-called ‘Women, Peace and Security’ (WPS) agenda at the UN. We ask whether the two agendas should continue to be pursued separately or whether each can make a useful contribution to the other. We argue that while the history of R2P has not included language that deliberately evokes the protection of women and the promotion of gender in preventing genocide and mass atrocities, this does not preclude the R2P and WPS agendas becoming mutually reinforcing. The article identifies cross-cutting areas where the two agendas may be leveraged for the UN and member states to address the concerns of women as both actors in need of protection and active agents in preventing and responding to genocide and mass atrocities, namely in the areas of early warning.

Cheating prevention in linear secret sharing

Cheating detection in linear secret sharing is considered. The model of cheating extends the Tompa-Woll attack and includes cheating during multiple (unsuccessful) recovery of the secret. It is shown that shares in most linear schemes can be split into subshares. Subshares can be used by participants to trade perfectness of the scheme with cheating prevention. Evaluation of cheating prevention is given in the context of different strategies applied by cheaters.

Cheating prevention in secret sharing over GF(pt)

The work investigates cheating prevention in secret sharing. It is argued that cheating is immune against cheating if the cheaters gain no advantage over honest participants by submitting invalid shares to the combiner. This work addresses the case when shares and the secret are taken from GF(pt). Two models are considered. The first one examines the case when cheaters consistently submit always invalid shares. The second modeldeal s with cheaters who submit a mixture of valid and invalid shares. For these two models, cheating immunity is defined, properties of cheating immune secret sharing are investigated and their constructions are given.

Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of cancer stem cell-like characteristics and a reduced tumor burden

Background Current treatment of ovarian cancer patients with chemotherapy leaves behind a residual tumor which results in recurrent ovarian cancer within a short time frame. We have previously demonstrated that a single short-term treatment of ovarian cancer cells with chemotherapy in vitro resulted in a cancer stem cell (CSC)-like enriched residual population which generated significantly greater tumor burden compared to the tumor burden generated by control untreated cells. In this report we looked at the mechanisms of the enrichment of CSC-like residual cells in response to paclitaxel treatment. Methods The mechanism of survival of paclitaxel-treated residual cells at a growth inhibitory concentration of 50% (GI50) was determined on isolated tumor cells from the ascites of recurrent ovarian cancer patients and HEY ovarian cancer cell line by in vitro assays and in a mouse xenograft model. Results Treatment of isolated tumor cells from the ascites of ovarian cancer patients and HEY ovarian cancer cell line with paclitaxel resulted in a CSC-like residual population which coincided with the activation of Janus activated kinase 2 (JAK2) and signal transducer and activation of transcription 3 (STAT3) pathway in paclitaxel surviving cells. Both paclitaxel-induced JAK2/STAT3 activation and CSC-like characteristics were inhibited by a low dose JAK2-specific small molecule inhibitor CYT387 (1 μM) in vitro. Subsequent, in vivo transplantation of paclitaxel and CYT387-treated HEY cells in mice resulted in a significantly reduced tumor burden compared to that seen with paclitaxel only-treated transplanted cells. In vitro analysis of tumor xenografts at protein and mRNA levels demonstrated a loss of CSC-like markers and CA125 expression in paclitaxel and CYT387-treated cell-derived xenografts, compared to paclitaxel only-treated cell-derived xenografts. These results were consistent with significantly reduced activation of JAK2 and STAT3 in paclitaxel and CYT387-treated cell-derived xenografts compared to paclitaxel only-treated cell derived xenografts. Conclusions This proof of principle study demonstrates that inhibition of the JAK2/STAT3 pathway by the addition of CYT387 suppresses the ‘stemness’ profile in chemotherapy-treated residual cells in vitro, which is replicated in vivo, leading to a reduced tumor burden. These findings have important implications for ovarian cancer patients who are treated with taxane and/or platinum-based therapies. Keywords: Ovarian carcinoma, Cancer stem cell, Metastasis, Ascites, Chemoresistance, Recurrence, JAK2/STAT3 pathway

Electron/ion energy loss to discharge walls revised : a case study in low-temperature, thermally nonequilibrium plasmas

Reliable calculations of the electron/ion energy losses in low-pressure thermally nonequilibrium low-temperature plasmas are indispensable for predictive modeling related to numerous applications of such discharges. The commonly used simplified approaches to calculation of electron/ion energy losses to the chamber walls use a number of simplifying assumptions that often do not account for the details of the prevailing electron energy distribution function (EEDF) and overestimate the contributions of the electron losses to the walls. By direct measurements of the EEDF and careful calculation of contributions of the plasma electrons in low-pressure inductively coupled plasmas, it is shown that the actual losses of kinetic energy of the electrons and ions strongly depend on the EEDF. It is revealed that the overestimates of the total electron/ion energy losses to the walls caused by improper assumptions about the prevailing EEDF and about the ability of the electrons to pass through the repulsive potential of the wall may lead to significant overestimates that are typically in the range between 9 and 32%. These results are particularly important for the development of power-saving strategies for operation of low-temperature, low-pressure gas discharges in diverse applications that require reasonably low power densities. © 2008 American Institute of Physics.

A typology of technological enablers of website service failure prevention

An increasing range of services are now offered via online applications and e-commerce websites. However, problems with online services still occur at times, even for the best service providers due to the technical failures, informational failures, or lack of required website functionalities. Also, the widespread and increasing implementation of web services means that service failures are both more likely to occur, and more likely to have serious consequences. In this paper we first develop a digital service value chain framework based on existing service delivery models adapted for digital services. We then review current literature on service failure prevention, and provide a typology of technolo- gies and approaches that can be used to prevent failures of different types (functional, informational, system), that can occur at different stages in the web service delivery. This makes a contribution to theory by relating specific technologies and technological approaches to the point in the value chain framework where they will have the maximum impact. Our typology can also be used to guide the planning, justification and design of robust, reliable web services.

A comparative study of Sr-incorporated mesoporous bioactive glass scaffolds for regeneration of osteopenic bone defects

SUMMARY: Recently, the use of the pharmacological agent strontium ranelate has come to prominence for the treatment of osteoporosis. While much investigation is focused on preventing disease progression, here we fabricate strontium-containing scaffolds and show that they enhance bone defect healing in the femurs of rats induced by ovariectomy. INTRODUCTION: Recently, the use of the pharmacological agent strontium ranelate has come to prominence for the treatment of osteoporosis due to its ability to prevent bone loss in osteoporotic patients. Although much emphasis has been placed on using pharmacological agents for the prevention of disease, much less attention has been placed on the construction of biomaterials following osteoporotic-related fracture. The aim of the present study was to incorporate bioactive strontium (Sr) trace element into mesoporous bioactive glass (MBG) scaffolds and to investigate their in vivo efficacy for bone defect healing in the femurs of rats induced by ovariectomy. METHODS: In total, 30 animals were divided into five groups as follows: (1) empty defect (control), (2) empty defects with estrogen replacement therapy, (3) defects filled with MBG scaffolds alone, (4) defects filled with MBG + estrogen replacement therapy, and (5) defects filled with strontium-incorporated mesopore-bioglass (Sr-MBG) scaffolds. RESULTS: The two groups demonstrating the highest levels of new bone formation were the defects treated with MBG + estrogen replacement therapy and the defects receiving Sr-MBG scaffolds as assessed by μ-CT and histological analysis. Furthermore, Sr scaffolds had a reduced number of tartrate-resistant acid phosphatase-positive cells when compared to other modalities. CONCLUSION: The results from the present study demonstrate that the local release of Sr from bone scaffolds may improve fracture repair. Future large animal models are necessary to investigate the future relationship of Sr incorporation into biomaterials.