Real-space observation of surface structuring induced by ultra-fast-laser illumination far below the melting threshold.

Intense short laser pulses are an intriguing tool for tailoring surface properties via ultra-fast melting of the surface layer of an irradiated target. Despite extensive studies on the interaction of femto-second laser interaction with matter, the initial steps of the morphological changes are not yet fully understood. Here, we reveal that substantial surface structure changes occur at energy densities far below the melting threshold. By using low-temperature scanning tunneling microscopy we resolve atomic-scale changes, i.e. the creation of nanosized adatom and vacancy clusters. The two cluster types have distinct non-linear fluence-dependencies. A theoretical analysis reveals their creation and motion to be non-thermal in nature. The formation of these atomistic changes, individually resolved here for the first time, recast our understanding of how surfaces respond to low-intensity ultra-short laser illumination. A visualization and control of the initial morphological changes upon laser illumination are not only of fundamental interest, but pave the way for the designing material properties through surface structuring.

Improving the Functional Control of Aged Ferroelectrics Using Insights from Atomistic Modeling.

We provide a fundamental insight into the microscopic mechanisms of the aging processes. Using large-scale molecular dynamics simulations of the prototypical ferroelectric material PbTiO_{3}, we demonstrate that the experimentally observed aging phenomena can be reproduced from intrinsic interactions of defect dipoles related to dopant-vacancy associates, even in the absence of extrinsic effects. We show that variation of the dopant concentration modifies the material's hysteretic response. We identify a universal method to reduce loss and tune the electromechanical properties of inexpensive ceramics for efficient technologies.

Deformation twinning and the role of amino acids and magnesium in calcite hardness from molecular simulation.

We employ classical molecular dynamics to calculate elastic properties and to model the nucleation and propagation of deformation twins in calcite, both as a pure crystal and with magnesium and aspartate inclusions. The twinning is induced by applying uniaxial strain to the crystal and relaxing all stress components except the uniaxial component. A detailed analysis of the atomistic processes reveal that the twinning mechanism involves small displacements of the Ca ions and cooperative rotations of the CO3 ions. The volume of the twinned region expands under increased uniaxial strain via the propagation of steps along the twin boundaries. The energy cost of the twin boundaries is compensated by the reduced hydrostatic stress and strain energy. The presence of biogenic impurities is shown to decrease the strain required to induce twin formation in calcite and, thus, the yield stress. This increased propensity for twinning provides a possible explanation for the increased hardness and penetration resistance observed experimentally in biominerals.

Electronic effects in high-energy radiation damage in tungsten.

Although the effects of the electronic excitations during high-energy radiation damage processes are not currently understood, it is shown that their role in the interaction of radiation with matter is important. We perform molecular dynamics simulations of high-energy collision cascades in bcc-tungsten using the coupled two-temperature molecular dynamics (2T-MD) model that incorporates both the effects of electronic stopping and electron-phonon interaction. We compare the combination of these effects on the induced damage with only the effect of electronic stopping, and conclude in several novel insights. In the 2T-MD model, the electron-phonon coupling results in less damage production in the molten region and in faster relaxation of the damage at short times. These two effects lead to a significantly smaller amount of the final damage at longer times.

The effect of surface topography on the micellisation of hexadecyltrimethylammonium chloride at the silicon-aqueous interface.

Amphiphilic aggregation at solid-liquid interfaces can generate mesostructured micelles that can serve as soft templates. In this study we have simulated the self-assembly of hexadecyltrimethylammonium chloride (C16TAC) surfactants at the Si(1 0 0)- and Si(1 1 1)-aqueous interfaces. The surfactants are found to form semicylindrical micelles on Si(1 0 0) but hemispherical micelles on Si(1 1 1). This difference in micelle structure is shown to be a consequence of the starkly different surface topographies that result from the reconstruction of the two silicon surfaces, and reveals that micelle structure can be governed by epitaxial matching even with non-polar substrates.

Electronic effects in high-energy radiation damage in iron.

Electronic effects have been shown to be important in high-energy radiation damage processes where a high electronic temperature is expected, yet their effects are not currently understood. Here, we perform molecular dynamics simulations of high-energy collision cascades in α-iron using a coupled two-temperature molecular dynamics (2T-MD) model that incorporates both the effects of electronic stopping and electron-phonon interaction. We subsequently compare it with the model employing electronic stopping only, and find several interesting novel insights. The 2T-MD results in both decreased damage production in the thermal spike and faster relaxation of the damage at short times. Notably, the 2T-MD model gives a similar amount of final damage at longer times, which we interpret to be the result of two competing effects: a smaller amount of short-time damage and a shorter time available for damage recovery.

Sexual dysfunction related to psychotropic drugs: a critical review. Part III: mood stabilizers and anxiolytic drugs.

INTRODUCTION: Sexual dysfunction is a potential side effect of mood stabilizers and anxiolytic drugs: this article presents a critical review of the current literature. Although many studies have been published on sexual side effects of psychopharmacological treatment, only a minority relate to mood stabilizers and anxiolytic drugs. Most of these studies are not methodologically robust, few are RCTs and most did not use a validated rating scale to evaluate sexual functioning. In addition, many of the studies on sexual dysfunction associated with mood stabilizers and anxiolytic drugs are limited by other methodological flaws. While there is evidence to suggest that mood stabilizers, with some exceptions, negatively affect sexual functioning, there is still insufficient evidence to draw any clear conclusions about the effects of anxiolytic drugs on sexual function. There is some weak evidence to indicate that switching from enzyme-inducing to non-enzyme-inducing anticonvulsant drugs, could be clinically useful. Some researchers recommend that sexual dysfunction in patients taking antiepileptic drugs should in general be treated according to standard guidelines for the management of sexual dysfunction, since reliable data on special populations is not available. However, specific approaches may be useful, but cannot yet be recommended until further validating research has been conducted. We did not find evidence supporting the use of any specific treatment strategy for sexual dysfunction associated with anxiolytic treatment. METHODS: This study was conducted in 2013 using the paper and electronic resources of the library of the Azienda Provinciale per i Servizi Sanitari (APSS) in Trento, Italy (http://atoz.ebsco.com/Titles/2793). The library has access to a wide range of databases including DYNAMED, MEDLINE Full Text, CINAHL Plus Full Text, The Cochrane Library, Micromedex healthcare series, BMJ Clinical Evidence. The full list of available journals can be viewed at http://atoz.ebsco.com/Titles/2793, or at the APSS web site (http://www.apss.tn.it). In completing this review, a literature search was conducted using the key words "anxiolytic drugs", "mood stabilizers", "benzodiazepines", "psychotrophic drugs", "sexual dysfunction", "sexual side effects", "treatment-emergent sexual dysfunction". All resulting listed articles were reviewed. DISCUSSION: This review includes studies that investigated the relationship between mood stabilizer and anxiolytic drug treatment and sexual dysfunction. The purpose was to identify possible intervention strategies for sexual dysfunction related to these drugs.

The nature of high-energy radiation damage in iron.

Understanding and predicting a material's performance in response to high-energy radiation damage, as well as designing future materials to be used in intense radiation environments, requires knowledge of the structure, morphology and amount of radiation-induced structural changes. We report the results of molecular dynamics simulations of high-energy radiation damage in iron in the range 0.2-0.5 MeV. We analyze and quantify the nature of collision cascades both at the global and the local scale. We observe three distinct types of damage production and relaxation, including reversible deformation around the cascade due to elastic expansion, irreversible structural damage due to ballistic displacements and smaller reversible deformation due to the shock wave. We find that the structure of high-energy collision cascades becomes increasingly continuous as opposed to showing sub-cascade branching as reported previously. At the local length scale, we find large defect clusters and novel small vacancy and interstitial clusters. These features form the basis for physical models aimed at understanding the effects of high-energy radiation damage in structural materials.

Charge localization on the hexa-interstitial cluster in MgO.

Density functional theory was used to study the effects of charge localization on the structure and mobility of the highly mobile hexa-interstitial cluster in MgO. It was found that the relative stability of the configurations changed as charge was localized, with the higher energy intermediate configuration of the neutral cluster becoming the lowest energy configuration for the doubly charged cluster. The singly charged cluster was found to have the lowest migration barrier, with a barrier of 0.18 eV. The high mobility of the singly charged hexa-interstitial cluster could have a significant effect on microstructure evolution following radiation damage, while the detailed properties will be sensitive to the level of doping in the material.

Cosmetic applications of sclerotherapy.

The aim of this study was to broaden practitioner perspectives regarding the scope, safety, and efficacy of sclerotherapy for cosmetically unattractive veins and other conditions involving a variety of anatomical sites. The author wrote a review of results obtained following cosmetic sclerotherapy for both veins and in other applications is presented. This study involves hundreds of patients treated in a private phlebology practice spanning 33 years along with a brief review of pertinent literature. Since treatment of dilated veins involving the dorsa of the hands and face are rarely discussed, and widely performed, their treatment will be emphasized. The largely historical usefulness of sclerotherapy for other applications is also reviewed. As with lower extremity veins there was a great deal of both regional and patient-to-patient variability in terms of sensitivity to sclerosants and response to treatment. However, sclerotherapy carried out for cosmetic purposes has routinely produced satisfactory results for various applications and in a multiplicity of locations. Potentially serious complications and treatment failures were rare in properly selected patients. Patient satisfaction with a few exceptions was uniformly high. The addition of cosmetic sclerotherapy to an established phlebology practice can be a rewarding and highly satisfactory application of this versatile technique. Both treatment site, lesion type and the cosmetic nature of this therapy affects every aspect of treatment; legal, ethical, and procedural. Experience suggests that each area and type of lesion treated exhibits predictable patterns of response and risks. Vein treatment outcomes varying with anatomical site may reflect: 1) evolutionarily adaptive processes which have produced veins specialized for specific environments; 2) differences in patterns of cytokine recruitment and apoptotic processes. It should also be noted that potential complications reflect area specific patterns of venous anastomoses, nerves, vital structures, and the complexities of arterial architecture.

Fusion power: a challenge for materials science.

The selection and design of materials that will withstand the extreme conditions of a fusion power plant has been described as one of the greatest materials science challenges in history. The high particle flux, high thermal load, thermal mechanical stress and the production of transmutation elements combine to produce a uniquely hostile environment. In this paper, the materials favoured for the diverse roles in a fusion power plant are discussed, along with the experimental and modelling techniques that are used to advance the understanding of radiation damage in materials. Areas where further research is necessary are highlighted.

Metadynamics simulations of calcite crystallization on self-assembled monolayers.

We show that recent developments in the application of metadynamics methods to direct simulations of crystallization make it possible to predict the orientation of crystals grown on self-assembled monolayers. In contrast to previous studies, the method allows for dynamic treatment of the organic component and the inclusion of explicit surface water without the need for computationally intensive interfacial energy calculations or prior knowledge of the interfacial structure. The method is applied to calcite crystallization on carboxylate terminated alkanethiols arrayed on Au (111). We demonstrate that a dynamic treatment of the monolayer is sufficient to reproduce the experimental results without the need to impose epitaxial constraints on the system. We also observe an odd-even effect in the variation of selectivity with organic chain length, reproducing experimentally observed orientations in both cases. Analysis of the ordering process in our simulations suggests a cycle of mutual control in which both the organic and mineral components induce complementary local order across the interface, leading to the formation of a critical crystalline region. The influence of pH, together with some factors that might affect the range of applicability of our method, is discussed.

Making tracks: electronic excitation roles in forming swift heavy ion tracks.

Swift heavy ions cause material modification along their tracks, changes primarily due to their very dense electronic excitation. The available data for threshold stopping powers indicate two main classes of materials. Group I, with threshold stopping powers above about 10 keV nm(-1), includes some metals, crystalline semiconductors and a few insulators. Group II, with lower thresholds, comprises many insulators, amorphous materials and high T(c) oxide superconductors. We show that the systematic differences in behaviour result from different coupling of the dense excited electrons, holes and excitons to atomic (ionic) motions, and the consequent lattice relaxation. The coupling strength of excitons and charge carriers with the lattice is crucial. For group II, the mechanism appears to be the self-trapped exciton model of Itoh and Stoneham (1998 Nucl. Instrum. Methods Phys. Res. B 146 362): the local structural changes occur roughly when the exciton concentration exceeds the number of lattice sites. In materials of group I, excitons are not self-trapped and structural change requires excitation of a substantial fraction of bonding electrons, which induces spontaneous lattice expansion within a few hundred femtoseconds, as recently observed by laser-induced time-resolved x-ray diffraction of semiconductors. Our analysis addresses a number of experimental results, such as track morphology, the efficiency of track registration and the ratios of the threshold stopping power of various materials.

Influence of supramammary lymph node extract on in vitro cell proliferation.

OBJECTIVES: Experiments were conducted to evaluate whether or not bovine supramammary lymph node extract (LNE) could support cell proliferation when it was substituted for bovine growth serum (BGS) in cell culture media. MATERIALS AND METHODS: Two different preparations of LNE were tested. The first yielded protein concentration of 3 mg/mL and the second contained 27 mg/mL protein. Three cell lines (MDA-MB-435, MAC-T and 1C6) were used in serum starvation assays to evaluate LNE. Cell proliferation assays were used to determine growth stimulation in the presence of LNE, and short-term or rapid adaptation cultures were evaluated for LNE effects on cell survival. RESULTS: Heat-inactivated preparation 1 supported cell proliferation as well as or better (12-39%) than BGS following 2 days of serum starvation in culture. The second lymph node preparation provided a stimulatory effect (263-702% greater than BGS across all cell lines) following serum starvation at 2.7 and 5.4 mg/mL protein supplementation. A gradual adaptation process with lymph node supplementation into media maintained cell population growth on a short-term basis. However, once cells were trypsinized or scraped and re-seeded into 2.7 mg/mL LNE protein containing media, cells were unable to re-adhere, leaving them detached, and eventually appearing to be dead. CONCLUSIONS: Substitution of BGS with LNE protein dramatically stimulated cells to proliferate, but did not allow for rapid cell population growth adaptation in vitro.

The ovulatory gonadotrophin surge stimulates cyclooxygenase expression and prostaglandin production by the monkey follicle.

Follicular prostaglandin concentrations increase following the gonadotrophin surge in domestic animals and rodents approximately 10 h before follicle rupture, suggesting a unifying role for prostaglandins in the timing of ovulation. However, little is known about prostaglandin production by the primate ovulatory follicle. In this study, adult female macaques received gonadotrophins to promote follicular development. Granulosa cells, follicular fluid, and ovaries were collected before (0 h) and 12, 24 or 36 h after administration of the ovulatory stimulus, human chorionic gonadotrophin (HCG). Cyclooxygenase (COX) isoform expression was assessed by reverse transcription-polymerase chain reaction and immunocytochemistry and follicular prostaglandin production was determined by enzyme immunoassay. COX-2 mRNA expression in granulosa cells was low at 0 h, rose 50-fold by 12 h, and remained elevated through to 36 h. COX-2 immunostaining was present in granulosa cells after, but not before, exposure to HCG. COX-1 mRNA levels did not change during the periovulatory interval, and COX-1 immunostaining of granulosa cells was not detected. Follicular fluid prostaglandin (PG) E (2) and PGF (2alpha) concentrations were low through to 24 h but increased 100-fold at 36 h. The elevated follicular prostaglandin concentrations 4-16 h before the expected time of ovulation support the hypothesis that the time between the LH surge and increased follicular prostaglandins determines the length of the periovulatory period. Differences between the localization and timing of COX-2 expression in monkey versus non-primate follicles suggest that the pattern of COX-2 expression and activity has aspects unique to primates.

Identification of an ovarian voltage-activated Na+-channel type: hints to involvement in luteolysis.

An endocrine type of voltage-activated sodium channel (eNaCh) was identified in the human ovary and human luteinized granulosa cells (GC). Whole-cell patch-clamp studies showed that the eNaCh in GC is functional and tetrodotoxin (TTX) sensitive. The luteotrophic hormone human CG (hCG) was found to decrease the peak amplitude of the sodium current within seconds. Treatment with hCG for 24-48 h suppressed not only eNaCh mRNA levels, but also mean Na+ peak currents and resting membrane potentials. An unexpected role for eNaChs in regulating cell morphology and function was indicated after pharmacological modulation of presumed eNaCh steady-state activity in GC cultures for 24-48 h using TTX (NaCh blocker) and veratridine (NaCh activator). TTX preserved a highly differentiated cellular phenotype. Veratridine not only increased the number of secondary lysosomes but also led to a significantly reduced progesterone production. Importantly, endocrine cells of the nonhuman primate corpus luteum (CL), which represent in vivo counterparts of luteinized GC, also contain eNaCh mRNA. Although the mechanism of channel activity under physiological conditions is not clear, it may include persistent Na+ currents. As observed in GC in culture, abundant secondary lysosomes were particularly evident in the regressing CL, suggesting a functional link between eNaCh activity and this form of cellular regression in vivo. Our results identify eNaCh in ovarian endocrine cells and demonstrate that their expression is under the inhibitory control of hCG. Activation of eNaChs in luteal cells, due to loss of gonadotropin support, may initiate a cascade of events leading to decreased CL function, a process that involves lysosomal activation and autophagy. These results imply that ovarian eNaChs are involved in the physiological demise of the temporary endocrine organ CL in the primate ovary during the menstrual cycle. Because commonly used drugs, including phenytoin, target NaChs, these results may be of clinical relevance.

Expression of estrogen receptor alpha and beta in the rhesus monkey corpus luteum during the menstrual cycle: regulation by luteinizing hormone and progesterone.

There are conflicting reports on the presence or absence of estrogen receptor (ER) in the primate corpus luteum, and the discovery of a second type of estrogen receptor, ERbeta, adds an additional level of complexity. To reevaluate ER expression in the primate luteal tissue, we used semiquantitative RT-PCR based assays and Western blotting to assess ERalpha and beta messenger RNA (mRNA) and protein levels in corpora lutea (n = 3/stage) obtained from adult female rhesus monkeys at early (days 3-5), mid (days 6-8), mid-late (days 10-12), and late (days 14-16) luteal phase of the natural menstrual cycle. ERalpha mRNA levels did not vary across the stages of the luteal phase, and ERalpha protein was not consistently detected in luteal tissues. However, ERbeta mRNA and protein levels were detectable in early and mid luteal phases and increased (P < 0.05) to peak levels at mid-late luteal phase before declining by late luteal phase. To determine if ERbeta mRNA expression in the corpus luteum is regulated by LH, monkeys received the GnRH antagonist antide either alone or with 3 daily injections of LH to simulate pulsatile LH release. Treatment with antide alone or concomitant LH administration did not alter luteal ERbeta mRNA levels. When monkeys also received the 3beta-hydroxysteroid dehydrogenase inhibitor trilostane to reduce luteal progesterone production, luteal ERbeta mRNA levels were 3-fold higher (P < 0.05) than in monkeys receiving antide + LH only. Replacement of progestin activity with R5020 reduced luteal ERbeta mRNA levels to those seen in animals receiving antide + LH. Thus, there is dynamic ERbeta expression in the primate corpus luteum during the menstrual cycle, consistent with a role for estrogen in the regulation of primate luteal function and life span via a receptor (ERbeta)-mediated pathway. Increased ERbeta expression in the progestin-depleted corpus luteum during LH exposure suggests that the relative progestin deprivation experienced by the corpus luteum between LH pulses may enhance luteal sensitivity to estrogens during the late luteal phase of the menstrual cycle.

D1-Receptor, DARPP-32, and PP-1 in the primate corpus luteum and luteinized granulosa cells: evidence for phosphorylation of DARPP-32 by dopamine and human chorionic gonadotropin.

The multifunctional phosphoprotein "dopamine and cAMP-related phosphoprotein, M(r) 32,000" (DARPP-32), which is able to act as an intracellular third messenger, was previously found to be present in human luteinized granulosa cells (GCs) and human ovary. DARPP-32 phosphorylation in GCs was increased by dopamine (DA) acting via a DA-1 receptors (D1-R). In the present study, we examined whether the major endocrine signaling molecule for GCs, LH/human CG (hCG), could also affect DARPP-32 phosphorylation. Immunoprecipitation studies showed that hCG, as well as DA, increased phosphorylation of DARPP-32 at threonine residues within 10 min, indicating that the signal transduction pathways of a hormone and a neurotransmitter involve DARPP-32 in GCs. Phosphorylated DARPP-32 is known to inhibit a cellular phosphatase (PP-1), which was also found to be expressed by GCs. Using RT-PCR and sequence analyses we showed that DARPP-32, PP-1, and D1-R genes were not restricted to cultured luteinized GCs, but were expressed in vivo, in the corpus luteum (CL) of the rhesus monkey throughout its entire life span. Whereas hCG increased steroid production in monkey luteinized GCs and in isolated luteal cells, DA failed to affect basal or hCG-stimulated progesterone production. This indicates that, unlike the LH/hCG receptor, the D1-R is not directly linked to steroid production. Although the precise role of D1-R in the CL remains to be shown, the presence of D1-R, DARPP-32, and its target PP-1 in this endocrine tissue, as well as the phosphorylation of DARPP-32 by a gonadotropin and by DA in luteinized GCs, indicate that the signal transduction pathways of the neurotransmitter DA and the gonadotropin hCG/LH involve DARPP-32. The PP-1 inhibitor DARPP-32 may, thus, be a third messenger used by both DA and hCG/LH to exert common regulatory influences on the cells of the CL.

Market model fails: linkages between health policy and performance outcomes in western industrial countries.

In recent years, political discourse has sung the merits of the market model as a panacea for escalating health expenditures. While selected market mechanisms may be useful to control spending, there are reasons to question full-scale use of this model to shape health policy. Using the experiences of seven western industrialized countries, the argument developed in this article is that the market model's own assumptions cannot be upheld because ethical, sociological, and political factors underlying health policy make its application impossible. Specifically, a competitive equilibrium does not exist; sale of health care goods and services do not conform to the rules of marketability; and non-increasing returns are not demonstrable. A discussion of health outcome performance and spending data points out the need to attend to equity distributional concerns, state commitment to the health care access, and the extent and breadth of input into health care decision-making as other factors that should be considered.

The role of sclerotherapy in abnormal varicose hand veins.

Large, tortuous veins involving the dorsa of the hands often become more prominent with the passage of time and are a common source of patient dissatisfaction. The objective was to evaluate the results of sclerotherapy in the management of unsightly varicose veins of the dorsum of the hand. From January of 1987 to August of 1998, 100 healthy, ambulatory female patients with a mean age of 56.5 years (range, 35 to 78 years) underwent sclerotherapy treatment for abnormally dilated veins on the dorsum of the hands. Patients were divided into two groups: group A consisted of 20 patients treated with 0.5% sodium tetradecyl sulfate (Sotradecol Elkins-Sin, Inc., Cherry Hill, N.J.) or 1.5% polidocanol (Aethoxysklerol Kreussler, Chemische-Fabrik, Wiesbaden, Germany). Group B consisted of 80 patients treated with 3% polidocanol. Postsclerotherapy compression was utilized in all cases. Failure was observed in 16 patients (80 percent) in group A. Successful elimination of varicose veins was obtained in 76 of 80 patients (95 percent) in group B. The diameter of treated vessels ranged from 1 to 6 mm (mean, 3 mm). Adverse events observed included pain, ecchymosis, various degrees of edema, and thrombosis of the treated veins. One patient (1 percent) developed transient neuropraxia of the superficial branch of the radial nerve following treatment of vessels located on the thenar web. Eleven of the 76 patients (14.5 percent) treated successfully with higher concentration developed microscopic neovascularization (matting). In conclusion, (1) low concentrations of sclerosing agents were associated with a high incidence of failure (80 percent); (2) the use of higher concentrations of polidocanol (3%) produced good results in 95 percent of treated patients; (3) adverse events common to sclerotherapy were observed in 90 percent of the treated patients-there were no serious adverse events; and (4) when appropriate sclerosant concentrations were employed, compression sclerotherapy proved to be an effective method of treatment for varicose veins involving the dorsum of the hand.