Managing vasomotor symptoms in women after cancer.

Women with estrogen-sensitive cancer or survivors of these neoplasms are generally not candidates for systemic menopausal hormone therapy or tibolone for the treatment of bothersome vasomotor symptoms (hot flashes or night sweats). However, menopausal symptoms negatively affect quality of life and need to be addressed by clinicians. For mild vasomotor symptoms, optimizing lifestyle changes or mind-brain behavior may be sufficient. For women with moderate to severe vasomotor symptoms unresponsive to these measures, non-hormone pharmacologic therapy may be needed. Randomized controlled trials have shown efficacy for vasomotor symptoms with selective serotonin reuptake inhibitors (paroxetine, citalopram, and escitalopram) and serotonin-norepinephrine reuptake inhibitors (venlafaxine and desvenlafaxine), as well as gabapentin, pregabalin, and clonidine. Therapies in development include neurokinin B inhibitors (neurokinin 3 receptor), stellate ganglion blockade, and a natural estrogen, estetrol. Individualizing therapy is important. As the physiology of menopausal hot flashes becomes better understood, it will drive development of future non-hormone pharmacotherapies.

Cause or prevention of breast cancer with estrogens: analysis from tumor biologic data, growth kinetic model and Women's Health Initiative study.

The existing medical literature suggests that estrogens may cause breast cancer but, paradoxically, can also prevent this neoplasm under specific circumstances. Appropriate interpretation of this complex data requires an understanding of emerging concepts of tumor biology. A substantial body of data, including animal models and epidemiologic studies, suggests that estrogens contribute to the development of breast cancer. Additionally, pre-clinical experiments indicate that the responsible mechanisms include both estrogen receptor α-dependent and -independent effects (ERα-dependent and ERα-independent effects). We recently developed two models to describe the growth kinetics of occult breast tumors, one based on autopsy studies and tumor doubling time and the other, computer-based. Validation of the models involved comparison of the predicted incidence of breast cancer with the actual incidence in population-based studies. Utilization of these models allowed us to determine that 16 years on average are required for tumors to undergo the 30 doubling times necessary for the occult tumors to reach the threshold for clinical detection. These models suggest that menopausal hormone therapy with estrogen plus a progestogen in the Women's Health Initiative (WHI) study accelerated the doubling time of occult, pre-existing tumors from 200 to 150 days and thus, increased the rate of tumor diagnosis. Based on estrogen-induced apoptosis data, the model accurately predicted the prevention of diagnosed breast cancer in the estrogen-alone arm of the WHI. Notably, pre-clinical studies demonstrated that conjugated equine estrogen, as used in the WHI, has unique, pro-apoptotic properties compared to the anti-apoptotic effects of estradiol, a finding providing an explanation for the reduction in breast cancer with conjugated equine estrogen.

A density functional theory study of propylene epoxidation mechanism on Ag2O(001) surface.

Propylene oxide (PO) is one of the 50 most produced chemicals according to the production volume. Environmental and economic drawbacks of conventional PO production processes necessitate new production methods. Among the new production alternatives, direct epoxidation of propylene to propylene oxide by molecular oxygen is a highly desired method and seen as the holy grail of propylene epoxidation studies. In this study, the propylene epoxidation mechanism on an Ag2O(001) surface is investigated computationally by means of density functional theory (DFT) calculations using the Vienna Ab-initio Simulation Package (VASP). A perfect Ag2O(001) surface and a surface with one O vacancy are utilized for this purpose. It is found that propylene oxide can be directly formed on an Ag2O(001) surface whether there is an oxygen vacancy or not. The rate controlling step is PO desorption from both surfaces. PO isomers, i.e. acetone and propanal, can also be formed on these surfaces. However, activation barriers do exist for these molecules. Direct allyl formation on the Ag2O(001) surface is found to be unfavorable unlike what is proposed in the literature. On the other hand, it is observed that an allyl radical can be formed either via an oxametallocycle path or after the formation of propylene oxide. In fact, the discovered allyl radical formation pathway from propylene oxide is found as the most probable successive reaction pathway because of the high desorption barrier of PO.

Aromatase expression in atypical ductal hyperplasia in women.

PURPOSE: To determine the levels of aromatase in atypical ductal hyperplasia (ADH) lesions, tissue surrounding the ADH, and in dense and non-dense normal breast tissue. We postulated that excess aromatase in breast tissue might, through production of increased estrogen, drive the carcinogenic process. Estrogens and their metabolites are thought to contribute to the development of breast cancer through estrogen receptor-mediated mechanisms and genotoxic effects of estrogen metabolites. ADH is a benign lesion of the breast which is associated with substantially increased risk for subsequent development of breast cancer. After 25 years, approximately 30% of women with ADH develop breast cancer. In women with three or more separate ADH lesions at the same time, 47% will develop breast cancer over that time period. Another important risk factor for breast cancer is the presence of mammographically dense breast tissue. METHODS: We utilized quantitative immunochemical analysis of aromatase in biopsy tissue to test this possibility. Previously published results comparing dense with non-dense breast tissue in normal women (Vachon et al. Breast Cancer Res Treat 125:243-252, 2011) were used for comparisons with ADH. A well-characterized histochemical H-score was employed for quantitative assessment of aromatase in the various tissue studied. RESULTS: The H-score of aromatase staining was statistically significantly higher (p = 0.003) in the ADH epithelium than surrounding epithelial tissue. In order of H-score from highest to lowest were ADH, issue surrounding ADH, dense normal and non-dense normal breast tissues. The levels of aromatase in a subset of women with ADH who went on to develop breast cancer were not higher than in women who did not. CONCLUSIONS: We suggest from these studies that overexpression of aromatase in breast tissue and its resultant increase in estradiol levels may contribute to the later development of breast cancer in women with ADH.

How molecular is the chemisorptive bond?

Trends in adsorption energies as a function of transition metal differ for adsorbates that are attached atop a surface atom or are adsorbed onto a high coordination site. When adsorption onto early and late transition metals is compared variation in relative bond energies of adsorbates attached to different sites is large. A theoretical understanding is provided based on the analysis of the electronic structure of the respective chemical bonds. The electronic structure analysis is based on partial density of states (PDOS) and bond order overlap population densities from crystal orbital Hamiltonian population (COHP) calculations available from DFT electronic structure computations. This is complemented by calculations of Bader charge densities and electron density topology properties. Variation of the respective bond energies depends on the symmetry of the molecular orbitals that form the chemical bond. The key electronic structure parameters are the position of the Fermi level in the bonding or antibonding molecular orbital partial density of states region of the chemical bond and chemical bond polarity. These are very different for adsorbates adsorbed onto the same transition metal surface, but which have different coordination with surface metal atoms. The adsorption energies and the respective electronic structures of adatoms H, C and O and molecular fragments CHx (x = 1-3) are compared with those of the analogous molecules that contain a single transition metal atom. When adsorbed atop, trends in bond energies are remarkably similar to those of the corresponding molecules. The difference in bond energies of adsorbates and transition metal molecules, i.e. the embedding energy, is shown to consist of three contributions: quenching of the sometimes high molecular spin states, weakening of the adsorbate-surface interaction energy and weakening of the metal-metal atom bond energies next to the adsorbate. Conventional scaling rules of the interaction energies of adsorbed CHx (0 < x ≤ 3) fragments are satisfied only for adsorbates in high coordination sites. For the early transition metals a breaking of this rule is found for C and CH or N and NH when adsorbed atop a transition metal surface or when they are part of a transition metal molecule. The M-C bond energy is found to be only stronger than that of the M-CH bond as long as the Fermi level or the HOMO is located in the antibonding molecular orbital partial density of states of the chemical bond.

Treatment of symptoms of the menopause: an Endocrine Society Clinical Practice Guideline

OBJECTIVE: The objective of this document is to generate a practice guideline for the management and treatment of symptoms of the menopause. PARTICIPANTS: The Treatment of Symptoms of the Menopause Task Force included six experts, a methodologist, and a medical writer, all appointed by The Endocrine Society. EVIDENCE: The Task Force developed this evidenced-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned three systematic reviews of published data and considered several other existing meta-analyses and trials. CONSENSUS PROCESS: Multiple e-mail communications, conference calls, and one face-to-face meeting determined consensus. Committees of The Endocrine Society, representatives from endorsing societies, and members of The Endocrine Society reviewed and commented on the drafts of the guidelines. The Australasian Menopause Society, the British Menopause Society, European Menopause and Andropause Society, the European Society of Endocrinology, and the International Menopause Society (co-sponsors of the guideline) reviewed and commented on the draft. CONCLUSIONS: Menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms and other symptoms of the climacteric. Benefits may exceed risks for the majority of symptomatic postmenopausal women who are under age 60 or under 10 years since the onset of menopause. Health care professionals should individualize therapy based on clinical factors and patient preference. They should screen women before initiating MHT for cardiovascular and breast cancer risk and recommend the most appropriate therapy depending on risk/benefit considerations. Current evidence does not justify the use of MHT to prevent coronary heart disease, breast cancer, or dementia. Other options are available for those with vasomotor symptoms who prefer not to use MHT or who have contraindications because these patients should not use MHT. Low-dose vaginal estrogen and ospemifene provide effective therapy for the genitourinary syndrome of menopause, and vaginal moisturizers and lubricants are available for those not choosing hormonal therapy. All postmenopausal women should embrace appropriate lifestyle measures.

Vaginal administration of estradiol: effects of dose, preparation and timing on plasma estradiol levels.

CONTEXT: The use of systemic estrogens for the treatment of menopausal symptoms has declined by approximately 80% following the initial publication of the Women's Health Initiative in 2002. Current attention focuses on vaginal estrogen as a local therapeutic means to achieve control of symptoms due to vulvovaginal atrophy without increasing plasma estradiol levels. A key issue is whether or not vaginally administered estrogens are absorbed and produce systemic effects. EVIDENCE ACQUISITION: Medline and PubMed were searched for relevant English-language articles using pertinent key words. The bibliographies of the pertinent articles were then read to identify further relevant articles. EVIDENCE SYNTHESIS: Several confounding factors influenced the data analysis including: (1) estradiol assay sensitivity and specificity; (2) acute versus chronic absorption; (3) delivery systems, doses, timing, and formulation; and (4) effect of atrophic versus mature vaginal mucosa on absorption. Each preparation was associated with acute estradiol absorption with peaks at approximately 8 h and return to baseline at 12 h. Low-dose vaginal estrogen, arbitrarily defined as the 7.5-µg vaginal ring and 10-µg tablet, increased plasma estradiol levels during chronic administration but not above the normal range of ≤ 20 pg/ml. Surprisingly, these increments were associated with systemic effects to lower plasma levels of low density lipoprotein cholesterol and bone resorption rates. Intermediate doses (i.e. 25 µg estradiol or 0.3 mg conjugated equine estrogen) resulted in plasma estradiol levels approaching or exceeding 20 pg/ml. The higher doses (50-2000 µg estradiol or 0.625-2.5 mg conjugated equine estrogen) resulted in premenopausal levels of estrogen. CONCLUSIONS: Low-dose vaginal estrogen appears to be an effective strategy for managing women whose symptoms result from vulvovaginal atrophy. These regimens limit but do not completely eliminate systemic absorption. Low-doses regimens should be preferred clinically to intermediate- or high-dose methods.

Mechanism and microkinetics of the Fischer-Tropsch reaction.

The increasing availability of quantum-chemical data on surface reaction intermediates invites one to revisit unresolved mechanistic issues in heterogeneous catalysis. One such issue of particular current interest is the molecular basis of the Fischer-Tropsch reaction. Here we review current molecular understanding of this reaction that converts synthesis gas into longer hydrocarbons where we especially elucidate recent progress due to the contributions of computational catalysis. This perspective highlights the theoretical approach to heterogeneous catalysis that aims for kinetic prediction from quantum-chemical first principle data. Discussion of the Fischer-Tropsch reaction from this point of view is interesting because of the several mechanistic options available for this reaction. There are many proposals on the nature of the monomeric single C atom containing intermediate that is inserted into the growing hydrocarbon chain as well as on the nature of the growing hydrocarbon chain itself. Two dominant conflicting mechanistic proposals of the Fischer-Tropsch reaction that will be especially compared are the carbide mechanism and the CO insertion mechanism, which involve cleavage of the C-O bond of CO before incorporation of a CHx species into the growing hydrocarbon chain (the carbide mechanism) or after incorporation into the growing hydrocarbon chain (the CO insertion mechanism). The choice of a particular mechanism has important kinetic consequences. Since it is based on molecular information it also affects the structure sensitivity of this particular reaction and hence influences the choice of catalyst composition. We will show how quantum-chemical information on the relative stability of relevant reaction intermediates and estimates of the rate constants of corresponding elementary surface reactions provides a firm foundation to the kinetic analysis of such reactions and allows one to discriminate between the different mechanistic options. The paper will be concluded with a short perspective section dealing with the needs for future research. Many of the current key questions on the physical chemistry as well as computational study of heterogeneous catalysis relate to particular topics for further research on the fundamental aspects of Fischer-Tropsch catalysis.

Oncology in midlife and beyond.

The onset of the menopause is often a time when women's concerns can act as a powerful trigger to encourage healthy modifications in lifestyle which will maintain, or improve, their general health. This document aims to help women to understand their potential risks, to encourage them to find proactive preventive strategies by modifying some of their attitudes, and to use health resources (when available) to be screened. Cancer is an important cause of death but not the primary cause of mortality. Cardio/circulatory diseases represent 35-40% of causes of death in most developed countries and 20-25% of women will die from cancers in Western Europe, Australasia, high-income North America, high-income Asia Pacific, East Asia and Southern Latin America. Breast cancer, lung cancer and colorectal cancer are prevalent in most regions of the world. Cervical cancer remains a hallmark of low access to health care. Preventive strategies (decreasing smoking and alcohol consumption, losing weight, eating a healthy diet and undertaking physical activity) and implementation of screening could help to significantly decrease the incidence of and mortality from cancer. The mortality/incidence ratio is higher in developing countries compared to high-income regions as well as in subgroups of populations in developed countries with lower socioeconomic levels. Implementation of better diagnostic methods and management of cancer according to the local resources will help to decrease the mortality rate in developing countries, and effort has to be made to decrease social inequities and improve access to health care for low-income groups. In conclusion, cancer incidence is increasing as a consequence of longer life expectancy all over the world. National health programs are mandatory to implement screening and to improve individual management. Finally, educating women so that they are aware of ways to improve their general health, to minimize their own risk factors and to identify signs of change in their own health which may be markers of impending cancer will help to reduce the burden of disease and improve the prognosis for tumors detected at an earlier stage.

Metabolic effects of oral versus transdermal 17ß-estradiol (E2): a randomized clinical trial in girls with Turner syndrome.

CONTEXT: The long-term effects of pure 17ß-estradiol (E2) depending on route of administration have not been well characterized. OBJECTIVE: Our objective was to assess metabolic effects of oral vs transdermal (TD) 17ß-E2 replacement using estrogen concentration-based dosing in girls with Turner syndrome (TS). PATIENTS: Forty girls with TS, mean age 16.7 ± 1.7 years, were recruited. DESIGN: Subjects were randomized to 17ß-E2 orally or TD. Doses were titrated using mean E2 concentrations of normally menstruating girls as therapeutic target. E2, estrone (E1), and E1 sulfate (E1S) were measured by liquid chromatography tandem mass spectrometry and a recombinant cell bioassay; metabolites were measured, and dual-energy x-ray absorptiometry scan and indirect calorimetry were performed. MAIN OUTCOME: Changes in body composition and lipid oxidation were evaluated. RESULTS: E2 concentrations were titrated to normal range in both groups; mean oral dose was 2 mg, and TD dose was 0.1 mg. After 6 and 12 months, fat-free mass and percent fat mass, bone mineral density accrual, lipid oxidation, and resting energy expenditure rates were similar between groups. IGF-1 concentrations were lower on oral 17ß-E2, but suppression of gonadotropins was comparable with no significant changes in lipids, glucose, osteocalcin, or highly sensitive C-reactive protein between groups. However, E1, E1S, SHBG, and bioestrogen concentrations were significantly higher in the oral group. CONCLUSIONS: When E2 concentrations are titrated to the normal range, the route of delivery of 17ß-E2 does not affect differentially body composition, lipid oxidation, and lipid concentrations in hypogonadal girls with TS. However, total estrogen exposure (E1, E1S, and total bioestrogen) is significantly higher after oral 17ß-E2. TD 17ß-E2 results in a more physiological estrogen milieu than oral 17ß-E2 administration in girls with TS.

Hormone therapy and breast cancer risk 10 years after the WHI.

Ten years after the publication of the first Women's Health Initiative (WHI) report, a substantial decrease in hormone replacement therapy (HRT) has been observed world-wide. Fear of developing breast cancer represents one of the reasons for an important shift toward alternatives for treatment of menopause symptoms or abstention from therapy altogether. Many publications in the scientific and lay press have emphasized the magnitude of the relative risk of breast cancer but have not focused on excess or attributable risk. Since the original report of the WHI study, new information has been published on risk factors for breast cancer related to hormone therapy use. Accordingly, we believe it important to review current data and examine excess rather than relative or absolute risk. A balanced perspective on excess risk determined from existing data suggests that the benefits of HRT for quality of life can outweigh the risks in management of a large number of postmenopausal women. In addition, alternative strategies for relief of menopausal symptoms are not as effective as HRT in treating the climacteric symptoms.

Ethylene epoxidation catalyzed by chlorine-promoted silver oxide.

It is demonstrated that, on a silver oxide surface, direct formation of ethylene oxide (EO) through the reaction between gas phase ethylene and surface oxygen is possible. The direct reaction channel produces EO selectively without competing with acetaldehyde (AA) formation. The oxometallacycle (OMC) forms on an oxygen vacant surface and reduces EO selectivity. Cl adsorption removes these surface vacant sites and hence prevents the formation of the OMC intermediate.

Clinical review: Effect of endocrine therapies on bone in breast cancer patients.

CONTEXT: Two common strategies are used to treat estrogen receptor-positive breast cancer in women: tamoxifen to inhibit estrogen action, and aromatase inhibitors (AIs) to block estrogen biosynthesis. Recent data suggest that AIs are more effective than tamoxifen in the adjuvant and advanced disease settings and are now being more commonly used. Tamoxifen, as a selective estrogen receptor modulator, exerts estrogenic effects to preserve bone, whereas the AIs profoundly lower estrogen levels and cause bone loss. Recent comparative studies of these agents provide extensive data on fracture rates, bone mineral density, and markers of bone formation and resorption. OBJECTIVE: The aim of the study was to review the mechanistic effects of estrogen on bone and clinical data regarding bone density, bone turnover markers, and fracture rates in women with breast cancer taking tamoxifen or AIs. EVIDENCE ACQUISITION AND SYNTHESIS: Data presented reflect a review of the literature and data integration from the perspective of the author's knowledge of the field. RESULTS: Tamoxifen increases bone density and reduces fractures in postmenopausal women with breast cancer, whereas AIs increase rate of fracture, accelerate loss of bone mineral density, and enhance levels of markers of bone formation and resorption. Bisphosphonates and denosumab counteract the effects of the AIs on bone. Guidelines for management of AI-induced bone loss are available from several sources, but a simple algorithm guides decision making most effectively. CONCLUSIONS: Endocrine therapy for postmenopausal women with breast cancer exerts substantial effects on bone, and guidelines are available to assist in the management of bone-related problems.

On the nature of dense CO adlayers on fcc(100) surfaces: a kinetic Monte Carlo study.

We present a kinetic Monte Carlo lattice gas model including top and bridge sites on a square lattice, with pairwise lateral interactions between the adsorbates. In addition to the pairwise lateral interactions we include an additional interaction: an adsorbate is forbidden to adsorb on a bridge site formed by two surface atoms when both surface atoms are already forming a bond with an adsorbate. This model is used to reproduce the low and high coverage adsorption behaviour of CO on Pt(100) and Rh(100). The parameter set used to simulate CO on Pt(100) produces the c(2 x 2)-2t ordered structure at 0.50 ML coverage, a one-dimensionally ordered structure similar to the experimentally observed (3 square root(2) x square root(2)) - 2t + 2b structure at 0.67 ML coverage, the c(4 x 2)-4t + 2b ordered structure at 0.75 ML coverage, and the recently reported c(6 x 2)-6t + 4b ordered structure at 0.83 ML coverage. The (5 square root(2) x square root(2)) ordered structure at 0.60 ML coverage is not reproduced by our model. The parameter set used to simulate CO on Rh(100) produces the c(2 x 2)-2t ordered structure at 0.50 ML coverage, a one-dimensionally ordered structure similar to the experimentally observed (4 square root(2) x square root(2)) - 2t + 4b structure at 0.75 ML coverage, and the c(6 x 2)-6t + 4b ordered structure at 0.83 ML coverage. Additionally, the simulated change of top and bridge site occupation as a function of coverage matches the trend in experimental vibrational peak intensities.

Vesicle deformation by draining: geometrical and topological shape changes.

A variety of factors, including changes in temperature or osmotic pressure, can trigger morphological transitions of vesicles. Upon osmotic upshift, water diffuses across the membrane in response to the osmotic difference, resulting in a decreased vesicle volume to membrane area ratio and, consequently, a different shape. In this paper, we study the vesicle deformations on osmotic deflation using coarse grained molecular dynamics simulations. Simple deflation of a spontaneously formed spherical vesicle results in oblate ellipsoid and discous vesicles. However, when the hydration of the lipids in the outer membrane leaflet is increased, which can be the result of a changed pH or ion concentration, prolate ellipsoid, pear-shaped and budded vesicles are formed. Under certain conditions the deflation even results in vesicle fission. The simulations also show that vesicles formed by a bilayer to vesicle transition are, although spontaneously formed, not immediately stress-free. Instead, the membrane is stretched during the final stage of the transition and only reaches equilibrium once the excess interior water has diffused across the membrane. This suggests the presence of residual membrane stress immediately after vesicle closure in experimental vesicle formation and is especially important for MD simulations of vesicles where the time scale to reach equilibrium is out of reach.

History of aromatase: saga of an important biological mediator and therapeutic target.

Aromatase is the enzyme that catalyzes the conversion of androgens to estrogens. Initial studies of its enzymatic activity and function took place in an environment focused on estrogen as a component of the birth control pill. At an early stage, investigators recognized that inhibition of this enzyme could have major practical applications for treatment of hormone-dependent breast cancer, alterations of ovarian and endometrial function, and treatment of benign disorders such as gynecomastia. Two general approaches ultimately led to the development of potent and selective aromatase inhibitors. One targeted the enzyme using analogs of natural steroidal substrates to work out the relationships between structure and function. The other approach initially sought to block adrenal function as a treatment for breast cancer but led to the serendipitous finding that a nonsteroidal P450 steroidogenesis inhibitor, aminoglutethimide, served as a potent but nonselective aromatase inhibitor. Proof of the therapeutic concept of aromatase inhibition involved a variety of studies with aminoglutethimide and the selective steroidal inhibitor, formestane. The requirement for even more potent and selective inhibitors led to intensive molecular studies to identify the structure of aromatase, to development of high-sensitivity estrogen assays, and to "mega" clinical trials of the third-generation aromatase inhibitors, letrozole, anastrozole, and exemestane, which are now in clinical use in breast cancer. During these studies, unexpected findings led investigators to appreciate the important role of estrogens in males as well as in females and in multiple organs, particularly the bone and brain. These studies identified the important regulatory properties of aromatase acting in an autocrine, paracrine, intracrine, neurocrine, and juxtacrine fashion and the organ-specific enhancers and promoters controlling its transcription. The saga of these studies of aromatase and the ultimate utilization of inhibitors as highly effective treatments of breast cancer and for use in reproductive disorders serves as the basis for this first Endocrine Reviews history manuscript.

Interaction of graphene with FCC-Co(111).

One of the possible catalyst deactivation mechanisms in the Fischer-Tropsch synthesis is carbon deposition in the form of a graphene overlayer. Currently no information is available on the nature of the interaction of these layers with the surface. The adsorption of graphene on the FCC-Co(111) surface was therefore studied. A chemical interaction between the graphene sheet and the cobalt surface was observed as evidenced by the partial DOS and Bader charge analysis. The adsorption energy was found to be small when normalized per carbon atom, but becoming large for extended graphene sheets. Graphene removal from the surface via lifting or sliding was considered. The energy barrier for sliding a graphene sheet is lower than the barrier for lifting, but the energy barriers become significant when placed into the context of realistic catalytic surfaces in the nanometer range.

Catalytic ammonia oxidation on platinum: mechanism and catalyst restructuring at high and low pressure.

Catalytic ammonia oxidation over platinum has been studied experimentally from UHV up to atmospheric pressure with polycrystalline Pt and with the Pt single crystal orientations (533), (443), (865), and (100). Density functional theory (DFT) calculations explored the reaction pathways on Pt(111) and Pt(211). It was shown, both in theory and experimentally, that ammonia is activated by adsorbed oxygen, i.e. by O(ad) or by OH(ad). In situ XPS up to 1 mbar showed the existence of NH(x)(x= 0,1,2,3) intermediates on Pt(533). Based on a mechanism of ammonia activation via the interaction with O(ad)/OH(ad) a detailed and a simplified mathematical model were formulated which reproduced the experimental data semiquantitatively. From transient experiments in vacuum performed in a transient analysis of products (TAP) reactor it was concluded that N(2)O is formed by recombination of two NO(ad) species and by a reaction between NO(ad) and NH(x,ad)(x= 0,1,2) fragments. Reaction-induced morphological changes were studied with polycrystalline Pt in the mbar range and with stepped Pt single crystals as model systems in the range 10(-5)-10(-1) mbar.

Lipid-based mechanisms for vesicle fission.

Shape transformations and topological changes of lipid vesicles, such as fusion, budding, and fission, have important chemical physical and biological significance. In this paper, we study the fission process of lipid vesicles. Two distinct routes are considered that are both based on an asymmetry of the lipid distribution within the membrane. This asymmetry consists of a nonuniform distribution of two types of lipids. In the first mechanism, the two types of lipids are equally distributed over both leaflets of the membrane. Phase separation of the lipids within both leaflets, however, results in the formation of rafts, which form buds that can split off. In the second mechanism, the asymmetry consists of a difference in composition between the two monolayers of the membrane. This difference in composition yields a spontaneous curvature, reshaping the vesicle into a dumbbell such that it can split. Both pathways are studied with molecular dynamics simulations using a coarse-grained lipid model. For each of the pathways, the conditions required to obtain complete fission are investigated, and it is shown that for the second pathway, much smaller differences between the lipids are needed to obtain fission than for the first pathway. Furthermore, the lipid composition of the resulting split vesicles is shown to be completely different for both pathways, and essential differences between the fission pathway and the pathway of the inverse process, i.e., fusion, are shown to exist.