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We compare the strategy found by the optimal control theory in a complex molecular system according to the active subspace coupled to the field. The model is the isomerization during a Cope rearrangement of Thiele's ester that is the most stable dimer obtained by the dimerization of methyl-cyclopentadienenylcarboxylate. The crudest partitioning consists in retaining in the active space only the reaction coordinate, coupled to a dissipative bath of harmonic oscillators which are not coupled to the field. The control then fights against dissipation by accelerating the passage across the transition region which is very wide and flat in a Cope reaction. This mechanism has been observed in our previous simulations [Chenel et al., J. Phys. Chem. A 116, 11273 (2012)]. We compare here, the response of the control field when the reaction path is coupled to a second active mode. Constraints on the integrated intensity and on the maximum amplitude of the fields are imposed limiting the control landscape. Then, optimum field from one-dimensional simulation cannot provide a very high yield. Better guess fields based on the two-dimensional model allow the control to exploit different mechanisms providing a high control yield. By coupling the reaction surface to a bath, we confirm the link between the robustness of the field against dissipation and the time spent in the delocalized states above the transition barrier. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a severe multi-organ disease with interstitial lung disease (ILD) being the major cause of death. While targeted therapies are emerging, biomarkers for sub-stratifying patients based on individual profiles are lacking. Herein, we investigated how levels of serum metabolites correlated with different stages of SSc and SSc-ILD. Serum samples of patients with SSc without ILD, stable and progressive SSc-ILD as well as of healthy controls (HC) were analysed using liquid targeted tandem mass spectrometry. The best discriminating profile consisted of 4 amino acids (AA) and 3 purine metabolites. l-tyrosine, l-tryptophan, and 1-methyl-adenosine distinguished HC from SSc patients. l-leucine, l-isoleucine, xanthosine, and adenosine monophosphate differentiated between progressing and stable SSc-ILD. In SSc-ILD, both, l-leucine and xanthosine negatively correlated with changes in FVC% predicted. Additionally, xanthosine was negatively correlated with changes in DLco% predicted and positively with the prognostic GAP index. Validation of l-leucine and l-isoleucine by an enzymatic assay confirmed both the sub-stratification of SSc-ILD patients and correlation with lung function and prognosis score. Serum metabolites may have potential as biomarkers for discriminating SSc patients based on the presence and severity of ILD. Confirmation in larger cohorts will be needed to appreciate their value for routine clinical care. [ABSTRACT FROM AUTHOR]

The ultrafast geometrical rearrangement dynamics of NO doped cryogenic Ne matrices after femtosecond laser pulse excitation is studied using a quantum dynamical approach based on a multi-dimensional shell model, with the shell radii being the dynamical variables. The Ne-NO interaction being only weakly anisotropic allows the model to account for the main dynamical features of the rare gas solid. Employing quantum wave packet propagation within the time dependent Hartree approximation, both, the static deformation of the solid due to the impurity and the dynamical response after femtosecond excitation, are analysed. The photoinduced dynamics of the surrounding rare gas atoms is found to be a complex high-dimensional process. The approach allows to consider realistic time-dependent femtosecond pulses and the effect of the pulse duration is clearly shown. Finally, using the pulse parameters of previous experiments, pump-probe signals are calculated and found to be in good agreement with experimental results, allowing for a clear analysis of the ultrafast mechanism of the energy transfer into the solid. [ABSTRACT FROM AUTHOR]

The relation between laser pulses serving the purpose of controlling elementary molecular processes and the instantaneous dynamics of the perturbed system is investigated. The application of the conditions assuring a controlled change of the expectation value of an observable directly links the internal motion to the external perturbation. Several numerical applications document that the derived control fields are efficient and can be interpreted clearly on physical grounds. [ABSTRACT FROM AUTHOR]

The process of decoherence of vibrational states of I2 in a dense helium environment is studied theoretically using the mixed quantum/classical method based on the Bohmian formulation of quantum mechanics [E. Gindensperger, C. Meier, and J. A. Beswick, J. Chem. Phys. 113, 9369 (2000)]. Specifically, the revival of vibrational wave packets is a quantum phenomena which depends sensitively on the coherence between the vibrational states excited by an ultrafast laser pulse. Its detection by a pump-probe setup as a function of rare gas pressure forms a very accurate way of detecting vibrational dephasing. Vibrational revivals of I2 in high pressure rare gas environments have been observed experimentally, and the very good agreement with the simulated spectra confirms that the method can accurately describe decoherence processes of quantum systems in interaction with an environment. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

We apply the mixed quantum/classical method based on the Bohmian formulation of quantum mechanics [E. Gindensperger, C. Meier, and J. A. Beswick, J. Chem. Phys. 113, 9369 (2000)] to the case of rotational diffractive surface scattering of a diatomic molecule. The rotation as well as the normal translational degree of freedom are treated classically while the two parallel degrees of freedom that account for the diffraction are treated quantum mechanically. The effects of treating some degrees of freedom classically are discussed in detail by comparing our novel approximate method to quantum wave packet results obtained by the multiconfiguration time-dependent Hartree method. [ABSTRACT FROM AUTHOR]

We apply the MQCB (mixed quantum/classical mechanics based on Bohmian trajectories) [E. Gindensperger, C. Meier, and J. A. Beswick, J. Chem. Phys. 113, 9369 (2000)] to the case where the quantum degree of freedom contains both bound and continuum states. The quantum degree of freedom is treated by a wave packet that is propagated on a spatial grid with a Hamiltonian that depends parametrically on the classical degrees of freedom, while the classical degrees of freedom themselves are coupled to the wave function via quantum trajectories. The method is applied to a simple model of a light particle colliding with a heavy (classical) particle absorbed on a surface, which has been used by other authors to develop methods to combine quantum degrees of freedom including continuum states with classical mechanics. The results are compared to the Ehrenfest mean-field method as well as to full quantum results. © 2002 American Institute of Physics. [ABSTRACT FROM AUTHOR]

We calculate resonance energies, wave functions, and widths by propagating wave packets on a grid. A collinear model of a symmetric triatomic molecule is studied and the results are compared to those obtained from a time-independent complex scaling calculation. [ABSTRACT FROM AUTHOR]

Investigates the photoelectron distributions obtained from the two-photon pump/probe ionization of sodium[sub 2]. Study of the dynamics by time-delayed ionization caused by a chirped femtosecond laser pulse; Sensitivity of the photoelectron spectra to the choice of the chirp; Identification of the outward motion of the wave packet.

Investigates time-resolved negative-ion-to-neutral-to-positive-ion pump-probe spectroscopy where the dynamics of wave packets in a neutral molecule produced by photodetachment from the negative ion is probed by time-delayed photoionization. Photoionization signals; Numerical evaluation of the signals.

The expression of amino acid transporters in small intestine epithelia of human newborns has not been studied yet. It is further not known whether the maturation of imino acid (proline) transport is delayed as in the kidney proximal tubule. The possibility to obtain small intestinal tissue from patients undergoing surgery for jejunal or ileal atresia during their first days after birth was used to address these questions. As control, adult terminal ileum tissue was sampled during routine endoscopies. Gene expression of luminal imino and amino acid transporter SIT1 (SLC6A20) was approximately threefold lower in newborns versus adults. mRNA levels of all other luminal and basolateral amino acid transporters and accessory proteins tested were similar in newborn mucosa compared with adults. At the protein level, the major luminal neutral amino acid transporter B0AT1 (SLC6A19) and its accessory protein angiotensin-converting enzyme 2 were shown by immunofluorescence to be expressed similarly in newborns and in adults. SIT1 protein was not detectable in the small intestine of human newborns, in contrast to adults. The morphology of newborn intestinal mucosa proximal and distal to the obstruction was generally normal, but a decreased proliferation rate was visualized distally of the atresia by lower levels of the mitosis marker Ki-67. The mRNA level of the 13 tested amino acid transporters and accessory proteins was nonetheless similar, suggesting that the intestinal obstruction and interruption of amniotic fluid passage through the small intestinal lumen did not affect amino acid transporter expression. NEW & NOTEWORTHY System IMINO transporter SIT1 is not expressed in the small intestine of human newborns. This new finding resembles the situation in the proximal kidney tubule leading to iminoglycinuria. Lack of amniotic fluid passage in small intestinal atresia does not affect amino acid transporter expression distal to intestinal occlusion. [ABSTRACT FROM AUTHOR]

A model framework is presented to predict the current-voltage (I-U) characteristics and hence the electrical performance of a solid oxide fuel cell (SOFC) repeat unit, i.e., a planar SOFC with adjacent current collector plates. The model uses as input residence times obtained from 3D CFD data for the fuel flowing through the anodic gas channels of a current collector plate. These residence times are then used by an electrochemical model to predict the fuel conversion along different flow paths for various electrical loads. This way, the overall (I-U) behaviour of the repeat unit follows from combining the fuel conversion rates (and respective electrical currents) for the individual flow paths. Since we use a Lagrangian reference frame for the electrochemical model, for a given electrical load, only a simple timeintegration of a first-order ODE is required. Therefore, this modelling approach is very efficient and well suited for extensive parameter studies, e. g., to optimise the fuel residence times with respect to the electrical performance of the repeat unit. To ensure its reliability, the model has been validated by comparison with both experimental data and other (I-U) models. [ABSTRACT FROM AUTHOR]

Presents information on a study which determined the implantation-induced intermixing depth profile for ions by photoluminescence measurements on samples containing quantum wells. Application of focused ion beam implantation method; Effect of intermixing to the direction of depth dependence of energy.

Spatial covariance in the simulated temperature evolution over the past millennium has been reported to exceed that of multiproxy-based reconstructions. Here we use tree ring-based temperature reconstructions and state-of-the-art climate model simulations to assess temporal changes in Northern Hemisphere intercontinental temperature covariance during the last 1000 years. Tree ring-only approaches reveal stronger agreement with model simulations compared to multiproxy networks. Although simulated temperatures exhibit a substantial spread among individual models, intercontinental temperature coherency is mainly driven by the cooling of large volcanic eruptions in 1257, 1452, 1600, and 1815 Common Era. The coherence of these synchronizing events appears to be elevated in several climate simulations relative to their own unforced covariance baselines and in comparison to the proxy reconstructions. This suggests that some models likely overestimate the amplitude of abrupt summer cooling in response to volcanic eruptions, particularly at larger spatial scales. [ABSTRACT FROM AUTHOR]

The non-Markovianity of the electron transfer in an oligothiophene-fullerene heterojunction described by a spin-boson model is analyzed using the time dependent decoherence canonical rates and the volume of accessible states in the Bloch sphere. The dynamical map of the reduced electronic system is computed by the hierarchical equations of motion methodology (HEOM) providing an exact dynamics. Transitory witness of non-Markovianity is linked to the bath dynamics analyzed from the HEOM auxiliary matrices. The signature of the collective bath mode detected from HEOM in each electronic state is compared with predictions of the effective mode extracted from the spectral density. We show that including this main reaction coordinate in a one-dimensional vibronic system coupled to a residual bath satisfactorily describes the electron transfer by a simple Markovian Redfield equation. Non-Markovianity is computed for three inter fragment distances and compared with a priori criterion based on the system and bath characteristic timescales. [ABSTRACT FROM AUTHOR]

p73 is the older sibling of p53 and mimics most of its tumor-suppressor functions. Through alternative promoter usage and splicing, the TP73 gene generates more than two dozen isoforms of which N-terminal truncated DNp73 variants have a decisive role in cancer pathogenesis as they outweigh the positive effects of full-length TAp73 and p53 in acting as a barrier to tumor development. Beyond the prevailing view that DNp73 predominantly counteract cell cycle arrest and apoptosis, latest progress indicates that these isoforms acquire novel functions in epithelial-to-mesenchymal transition, metastasis and therapy resistance. New insight into the mechanisms underlying this behavior reinforced the expectation that DNp73 variants contribute to aggressive cellular traits through both loss of wild-type tumor-suppressor activity and gain-of-function, suggesting an equally important role in cancer progression as mutant p53. In this review, we describe the novel properties of DNp73 in the invasion metastasis cascade and outline the comprehensive p73 regulatome with an emphasis on molecular processes putting TAp73 out of action in advanced tumors. These intriguing insights provoke a new understanding of the acquisition of aggressive traits by cancer cells and may help to set novel therapies for a broad range of metastatic tumors. [ABSTRACT FROM AUTHOR]

The incidence of acute aortic syndrome is low, but the spontaneous course is often life-threatening. Adequate ECG-gated imaging is fundamental within the diagnostic workup. We here report a case of a 53-year-old man presenting with atypical chest pain, slight increase of D dimers at admission, and extended diameter of the ascending aorta accompanied by mild aortic regurgitation. Interpretation of an initial contrast-enhanced computed tomography was false negative due to inadequate gating and motion artifacts, thereby judging a tiny contrast signal in the left anterior quadrant of the ascending aorta as a pseudointimal flap. By hazard, cardiac magnetic resonance imaging demonstrated an ulcer-like lesion superior to the aortic root, leading to aortic surgery at the last moment. As sensitivity of imaging is not 100%, this example underlines that second imaging studies might be necessary if the first imaging is negative, but the clinical suspicion still remains high. [ABSTRACT FROM AUTHOR]

Tissue engineering of an anterior cruciate ligament (ACL) implant with functional enthesis requires site-directed seeding of different cell types on the same scaffold. Therefore, we studied the suitability of self-assembled three-dimensional spheroids generated by lapine ACL ligament fibroblasts for directed scaffold colonization. The spheroids were characterized in vitro during 14 days in static and 7 days in dynamic culture. Size maintenance of self-assembled spheroids, the vitality, the morphology and the expression pattern of the cells were monitored. Additionally, we analyzed the total sulfated glycosaminoglycan, collagen contents and the expression of the ligament components type I collagen, decorin and tenascin C on protein and for COL1A1, DCN and TNMD on gene level in the spheroids. Subsequently, the cell colonization of polylactide-co-caprolactone [P(LA-CL)] and polydioxanone (PDS) polymer scaffolds was assessed in response to a directed, spheroid-based seeding technique. ACL cells were able to self-assemble spheroids and survive over 14 days. The spheroids decreased in size but not in cellularity depending on the culture time and maintained or even increased their differentiation state. The area of P[LA-CL] scaffolds, colonized after 14 days by the cells of one spheroid, was in average 4.57 ± 2.3 mm. Scaffolds consisting of the polymer P[LA-CL] were more suitable for colonization by spheroids than PDS embroideries. We conclude that ACL cell spheroids are suitable as site-directed seeding strategy for scaffolds in ACL tissue engineering approaches and recommend the use of freshly assembled spheroids for scaffold colonization, due to their balanced proliferation and differentiation. [ABSTRACT FROM AUTHOR]

Invasive parasites are of great global concern. Understanding the factors influencing the spread of invading pest species is a first step in developing effective countermeasures. Growing empirical evidence suggests that spread rates are essentially influenced by spatiotemporal dynamics of host–parasite interactions, yet approaches modelling spread rate have typically assumed static environmental conditions. We analysed invasion history of the deer ked (Lipoptena cervi) in Finland with a diffusion–reaction model, which assumed either the movement rate, the population growth rate, or both rates may depend on spatial and temporal distribution of moose (Alces alces), the main host of deer ked. We fitted the model to the data in a Bayesian framework, and used the Bayesian information criterion to show that accounting for the variation in local moose density improved the model's ability to describe the pattern of the invasion. The highest ranked model predicted higher movement rate and growth rate of deer ked with increasing moose density. Our results suggest that the historic increase in host density has facilitated the spread of the deer ked. Our approach illustrates how information about the ecology of an invasive species can be extracted from the spatial pattern of spread even with rather limited data. [ABSTRACT FROM PUBLISHER]

Summary: Based on this double-blind, placebo-controlled study, ibandronate has no beneficial effect on clinical and radiological outcome in patients with spontaneous osteonecrosis of the knee over and above anti-inflammatory medication. Introduction: Observational studies suggest beneficial effects of bisphosphonates in spontaneous osteonecrosis (ON) of the knee. We investigated whether ibandronate would improve clinical and radiological outcome in newly diagnosed ON. Methods: In this randomized, double-blind, placebo-controlled trial, 30 patients (mean age, 57.3 ± 10.7 years) with ON of the knee were assigned to receive either ibandronate (cumulative dose, 13.5 mg) or placebo intravenously (divided into five doses 12 weeks). All subjects received additional treatment with oral diclofenac (70 mg) and supplementation with calcium carbonate (500 mg) and vitamin D (400 IU) to be taken daily for 12 weeks. Patients were followed for 48 weeks. The primary outcome was the change in pain score after 12 weeks. Secondary endpoints included changes in pain score, mobility, and radiological outcome (MRI) after 48 weeks. Results: At baseline, both treatment groups (IBN, n = 14; placebo, n = 16) were comparable in relation to pain score and radiological grading (bone marrow edema, ON). After 12 weeks, mean pain score was reduced in both ibandronate- (mean change, −2.98; 95 % CI, −4.34 to −1.62) and placebo- (−3.59; 95 % CI, −5.07 to −2.12) treated subjects (between-group comparison adjusted for age, sex, and osteonecrosis type, p = ns). Except for significant decrease in bone resorption marker (CTX) in ibandronate-treated subjects ( p < 0.01), adjusted mean changes in all functional and radiological outcome measures were comparable between treatment groups after 24 and 48 weeks. Conclusions: In patients with spontaneous osteonecrosis of the knee, bisphosphonate treatment (i.e., IV ibandronate) has no beneficial effect over and above anti-inflammatory medication. [ABSTRACT FROM AUTHOR]

We present a detailed theoretical analysis of biexciton state generation in InAs-GaAs quantum dots by strong, chirped laser pulses. Specifically, we derive an accurate analytical expression, which not only provides a clear physical picture of the process, but also allows identifications of laser parameter regimes where efficient biexciton generation should be possible, even at temperatures up to 80 K. The results are confirmed by numerical simulations, in very good agreement with the model proposed. A clear choice of parameters is proposed, which might pave the way towards the optimal design of high-fidelity sources of entangled photon pairs based on individual quantum dots. [ABSTRACT FROM AUTHOR]

The microscopic structure of light-activated paramagnetic conduction band tail states and their participation in spin-dependent hopping transport is studied in a microcrystalline silicon thin-film solar cell. Application of X- and S-band electrically detected magnetic resonance (EDMR) experiments in combination with numerical simulations of Rabi oscillations indicates that the spin-dependent process takes place between two neighbouring band tail states. For sufficiently high microwave (mw) power, two Rabi frequencies Ω1and Ω2= 2Ω1show up in the coherent EDMR signals. An analysis of their relative contributions to the Rabi traces suggests that theg-values of both spin partners are not correlated for the majority of the EDMR-active pairs. A small fraction of doublet pairs with similarg-values may explain the appearance of a larger Ω2contribution than predicted by the simulations. [ABSTRACT FROM PUBLISHER]

We present the enhancement of frequency doubled and tripled light in zinc oxide (ZnO) by utilizing arrays of Mie-resonant dielectric nanoantennas. The cylindrical antennas exhibit resonances at the fundamental excitation wavelength, enabling strong localization of light and redistribution of the electric field inside the structures. Linear transmission spectroscopy reveals the resonant behavior of the fabricated nanoantennas and confirms the performed theoretical simulations. Nonlinear spectroscopic measurements show direct dependency between the resonant behavior and the amplification of nonlinear signals. Comparing the unpatterned ZnO thin films with the dielectric nanostructures shows a maximum enhancement by factors of about 22 for SHG and 7 for THG from resonant excitations of the nanoantennas. [ABSTRACT FROM AUTHOR]

Motivated by recent experimental results, we present a detailed account of adiabatic population transfer in InGaAs/GaAs quantum dots by strong chirped laser pulses. Specifically, numerical simulations in very good agreement with experimental results allow for a clear physical picture of this process. An analytical expression is developed, which is used to analyze the strong-field adiabatic population transfer in the presence of the phonon environment. Optimal pulse parameters to achieve robust population transfer at temperatures as high as 80 K are identified and are confirmed by numerical simulations. [ABSTRACT FROM AUTHOR]

Abstract: Photoexcitation of NO embedded in rare gas matrices triggers a shock-wave like radial perturbation of the surrounding rare gas atoms. In this Letter, we present quantum dynamical studies of this process, based on a radial shell model. The high-dimensional quantum dynamics is preformed with the multi-configuration time dependent Hartree (MCTDH) method. By comparison with time-dependent Hartree (TDH) results, we study the effects of dynamical correlations. Their inclusion modifies the high-dimensional wavefunction, however, mean values are well described within the TDH ansatz. Finally, pump–probe signals are simulated and shown to lead to small but measurable effects when including the correlations. [Copyright &y& Elsevier]

At discharge of a 72 year old epileptic patient from the hospital, the clinician prescribed the switch from Orfiril® to Lamictal®. The general practitioner misinterpreted the confusing medication list and made handwritten changes. Later on, family members of the patient observed a discrepancy between the handwritten comments of the general practitioner and the medication list of the clinician. The medication could be re-evaluated in cooperation with the hospital pharmacy and the general practitioner. An early interdisciplinary collaboration would help improving patient safety. [ABSTRACT FROM AUTHOR]

At discharge of a 72 year old epileptic patient from the hospital, the clinician prescribed the switch from Orfiril® to Lamictal®. The general practitioner misinterpreted the confusing medication list and made handwritten changes. Later on, family members of the patient observed a discrepancy between the handwritten comments of the general practitioner and the medication list of the clinician. The medication could be re-evaluated in cooperation with the hospital pharmacy and the general practitioner. An early interdisciplinary collaboration would help improving patient safety. [ABSTRACT FROM AUTHOR]

This paper reviews the experiences and learnings derived from the European Foundation for Management Development's programme accreditation teChnology-Enhanced Learning (EFMD CEL) programme accreditation. The EFMD CEL quality framework is briefly described, and an overview of the programmes that have pursued accreditation is presented. Subsequently, the evaluation results for the programmes having undergone accreditation/re-accreditation are analysed. This analysis moves from a more aggregated view to a more detailed view, and observations are related to relevant findings in the literature. Also, the key issues and recommendations identified by the auditors for further development of the programmes reviewed are discussed, as are the evaluation results for three programmes that have undergone re-accreditation. Key findings are the following: (1) the quality criteria at the core of the EFMD CEL quality framework are applicable for diverse programmes; (2) the programmes receive differentiated evaluations on the different quality dimensions and quality criteria; (3) auditors' ideas for improvement and recommendations most commonly pertain to the quality dimensions 'Pedagogy' and 'Organization/Culture'; (4) noticeable quality improvements are indeed initiated through the EFDM CEL audit and accreditation process; and (5) quality management is not a one-way street, and slippage with regard to some quality criteria may be observed in re-accreditation results. [ABSTRACT FROM AUTHOR]

Leukemic blasts overexpress immunogenic antigens, so-called leukemia-associated antigens like the receptor for hyaluronan acidmediatedmotility (RHAMM). Persistent RHAMMexpression and decreasing CD8+ T-cell responses to RHAMMin the framework of allogeneic stem cell transplantation or chemotherapy alone might indicate the immune escape of leukemia cells. In the present study, we analyzed the expression of RHAMM in 48 patients suffering from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Furthermore, we correlated transcripts with the clinical course of the disease before and after treatment. Realtime quantitative reverse transcriptase polymerase chain reaction was performed fromRNA of peripheral blood mononuclear cells. T cell responses against RHAMMwere assessed by tetramer staining (flow cytometry) and enzyme-linked immunospot (ELISPOT) assays. Results were correlated with the clinical outcome of patients. The results of the present study showed that almost 60% of the patients were RHAMM positive; specific T-cells recognizing RHAMM could be detected, but they were nonfunctional in terms of interferon gamma or granzyme B release as demonstrated by ELISPOT assays. Immunotherapies like peptide vaccination or adoptive transfer of RHAMM-specific T cells might improve the immune response and the outcome of AML/MDS patients. [ABSTRACT FROM AUTHOR]

Fracture is a major contributor to human morbidity and mortality, especially in the elderly. It has been discussed in the literature that conditions associated with decreased stomach acidity may lead to a decrease in intestinal calcium absorption and, consequently, to an increased fracture risk. In recent years, several observational studies reported a slightly increased fracture risk in association with the use of proton pump inhibitors (PPIs) and/or histamine H(2) receptor antagonists. It was the objective of this review to critically assess the available evidence linking PPI use to an increased fracture risk. A MEDLINE and EMBASE search from 1960 to June 2010 was performed to identify the relevant articles using predefined search terms. Because (i) there is no proven mechanism, (ii) the reported magnitude of the risk elevation associated with the use of PPIs was only weak, and (iii) the likelihood of residual confounding despite adjustment for known co-morbidities and drug use cannot be ruled out, we conclude that the currently available literature does not support the notion that the use of PPIs is causally related to a materially increased fracture risk in humans. [ABSTRACT FROM AUTHOR]

Abstract: The non-Markovian master equation is applied to the calculation of reaction rates. Starting from the flux-side correlation function form, we treat both the thermal and real time evolution consistently within second order perturbation theory in the system–bath coupling. It is shown that the non-Markovian dynamics enter formally not only in the time propagation but also in the expressions for the initial system–bath correlations. We show that these initial correlations can have a significant effect on the reaction rate. The method presented, although approximate, is an effective way to calculate reaction rates for weakly coupled systems over a wide range of temperatures. As such it provides a complementary approach to the exact treatment based on the ML-MCTDH method of Craig et al. , which serves as reference in this work. [Copyright &y& Elsevier]

Osteoporosis is a generalized disease of bone that increases the fracture risk. Among the multiple factors involved in osteoporosis, some, but not all, are related to bone mass. Although bone mineral density (BMD) measurement is specific for detecting high-risk individuals, it misses a notable proportion of individuals who have clinical or epidemiological risk factors for osteoporotic fractures. Therefore, composite scores that rely both on BMD and on validated clinical risk factors have been developed. The Fracture Risk Assessment Tool (FRAX) was designed to predict the 10-year probabilities of sustaining a major osteoporotic fractures or a hip fracture. The cutoff value beyond which treatment should be initiated needs to be determined, based not only on clinical criteria, but also on economic considerations. [ABSTRACT FROM AUTHOR]

Abstract: We investigate the laser induced population transfer between electronic states of molecules which are subject to additional perturbations by an environment. In a former paper [S. Gräfe, M. Erdmann, V. Engel, Phys. Rev. A 72 (2005) 013404] it was shown that within the formalism of Local Control Theory, laser fields can be constructed which are able to selectively transfer population from the electronic ground to a target excited electronic state. Here, we address the question in how far the efficiency of the control process is influenced by additional perturbations. Therefore, we employ a stochastic Schrödinger equation including a fluctuation-term in the Hamiltonian. [Copyright &y& Elsevier]

The insulin-sensitizing thiazolidinediones (commonly known as glitazones) are an important and widely prescribed class of antidiabetic agents. Glitazones exert their action through activation of proliferator-activated receptor gamma (PPAR-gamma) nuclear transcription factor and are effective drugs to achieve glycaemic control in patients with type 2 diabetes mellitus. Recent rapidly growing evidence suggests that glitazone use is associated with accelerated bone loss and an increased risk of fracture. This review aims to evaluate the current knowledge of adverse effects of glitazone therapy on the skeleton. Articles in English, Spanish, German and French published up until April 2009 are included. Results from preclinical studies have demonstrated that activation of PPAR-gamma inhibits bone formation by primarily diverting mesenchymal stem cells to the adipocytic rather than to the osteogenic lineage, and that glitazones may increase bone resorption by stimulating osteoclasts. Numerous studies in humans have demonstrated decreased bone turnover, accelerated bone loss and impaired bone mineral density both in healthy volunteers and in patients with type 2 diabetes. Furthermore, results from recent large, randomized controlled trials and from observational studies provided evidence for an increased fracture risk for glitazone users, mostly for women, but possibly also for men. As a consequence of these observations, clinicians should carefully assess the fracture risk in patients with type 2 diabetes before starting therapy with glitazones. [ABSTRACT FROM AUTHOR]

Objective: Lactic acidosis has been associated with use of metformin. Hypoglycemia is a major concern using sulfonylureas. The aim of this study was to compare the risk of lactic acidosis and hypoglycemia among patients with type 2 diabetes using oral antidiabetes drugs.Research Design and Methods: This study is a nested case-control analysis using the U.K.-based General Practice Research Database to identify patients with type 2 diabetes who used oral antidiabetes drugs. Within the study population, all incident cases of lactic acidosis and hypoglycemia were identified, and hypoglycemia case subjects were matched to up to four control patients based on age, sex, practice, and calendar time.Results: Among the study population of 50,048 type 2 diabetic subjects, six cases of lactic acidosis during current use of oral antidiabetes drugs were identified, yielding a crude incidence rate of 3.3 cases per 100,000 person-years among metformin users and 4.8 cases per 100,000 person-years among users of sulfonylureas. Relevant comorbidities known as risk factors for lactic acidosis could be identified in all case subjects. A total of 2,025 case subjects with hypoglycemia and 7,278 matched control subjects were identified. Use of sulfonylureas was associated with a materially elevated risk of hypoglycemia. The adjusted odds ratio for current use of sulfonylureas was 2.79 (95% CI 2.23-3.50) compared with current metformin use.Conclusions: Lactic acidosis during current use of oral antidiabetes drugs was very rare and was associated with concurrent comorbidity. Hypoglycemic episodes were substantially more common among sulfonylurea users than among users of metformin. [ABSTRACT FROM AUTHOR]

As schools in South Africa become increasingly multicultural, pressure is being put on them to meet the needs of all learners. The South African Schools Act, No 84 of 1996, affirms the recognition of all forms of diversity in public schools. It seems clear from media reports, however, that diversity in schools is not readily accepted and that teachers are largely held accountable for racial prejudice in schools. This raises the question whether teachers fully understand multicultural education as a means to adequately manage diversity in schools. Against this background, a project was undertaken to establish what student teachers' understanding of multicultural education is, and what they regard as the most important aims of multicultural education. Data were obtained by the use of semi-structured questions serving as a self-report instrument. The data collected were consolidated and categorised into themes. It became clear from the data that most respondents showed a seriously deficient conception of the nature, aims and material manifestations of multicultural education. It is therefore recommended that teacher education programmes should be scrutinised to ascertain whether they are providing the right kind of knowledge content to prepare student teachers to function competently in multicultural schools. [ABSTRACT FROM AUTHOR]

The synthesis of phosphoramidites of C8-modified 2 '-deoxyadenosine with carcinogenic arylamines p-anisidine and 4-aminobiphenyl is described. Two different methods were studied related to the glycon and base protection groups. [ABSTRACT FROM AUTHOR]

Self-assembled InAs quantum dots can be controllably charged with a defined number of electrons per dot. We report on conductivity measurements of AlxGa1-xAs/GaAs heterostructures, where such quantum dots are embedded in the direct vicinity of a two-dimensional electron gas (2DEG). We demonstrate the controlled enhancement of the scattering rate in the 2DEG induced by charging the quantum dots with additional electrons. The resulting transport lifetimes are in good agreement with theoretical values for Coulomb scattering in two dimensions. [ABSTRACT FROM AUTHOR]

Abstract: Pronucleotides represent a promising tool to improve the biological activity of nucleoside analogs in antiviral and cancer chemotherapy. The cycloSal-approach is one of several conceptually different pronucleotide systems. This approach can be applied to various nucleoside analogs. A salicyl alcohol as a cyclic bifunctional masking unit is used, and shown to afford a chemically driven release of the particular nucleotide from the lipophilic phosphate triester precursor molecule. A conceptual extension of the cycloSal-approach results in the design of “lock-in”-cycloSal-derivatives. The cycloSal-approach is not restricted to the delivery of bioactive nucleotides but also useful for the intracellular delivery of hexose-1-phosphates. [Copyright &y& Elsevier]

2-Chloro-2 ′-deoxyadenosine (CdA, cladribine) is a nucleoside analogue (NA) used for the treatment of lymphoproliferative disorders. Phosphorylation of the drug to CdAMP by deoxycytidine kinase (dCK) and its subsequent conversion to CdATP is essential for its efficacy. DCK deficiency is a common mechanism of resistance to NA, which could be overcome by the pronucleotide approach. The latter consists of using the nucleoside monophosphate conjugated to a lipophilic group enabling CdAMP to enter the cells by passive diffusion. In this study, we show that cycloSaligenyl-2-chloro-2 ′-deoxyadenosine monophosphate (cycloSal-CdAMP) is 10-fold more potent that CdA in a dCK-deficient lymphoma cell line. These results suggest that the use of cycloSal-nucleotides could be a strategy to counteract resistance caused by dCK deficiency. [ABSTRACT FROM AUTHOR]

Abstract: Because variola virus might be used as a pathogen in biological attacks, there is an urgent need to provide effective antiviral drugs for the treatment of orthopoxvirus infections. Thus, the aim of the present study was to test the antiviral activity of 3 pro-nucleotides of the acyclic nucleoside analogues aciclovir (ACV), 3 of penciclovir (PCV) and 38 of the cyclic nucleoside analogue brivudin (BVDU), on the basis of cycloSaligenyl-nucleoside monophosphate approach against vaccinia virus and cowpox virus in vitro. In further experiments, 13 synthetic humic acid-like polymers, so-called polyhydroxycarboxylates, were examined. Antiviral screening was performed by means of the plaque reduction assay and for quantification of the cytotoxicity of the test compounds the XTT-based tetrazolium reduction assay EZ4U was used. As result, three cycloSal-monophosphate derivatives of ACV proved to be potent inhibitors of both vaccinia virus and cowpox virus replication in vitro. Among the tested monophosphate derivatives of cycloSal-PCV and cycloSal-BVDU, selected substances showed a promising antiviral activity against vaccinia virus and cowpox virus. For the polyanionic compounds, no relevant antiviral activity was detected. In conclusion, by the delivery of nucleoside monophosphates from neutral, membrane-permeable prodrugs on the basis of the cycloSaligenyl-nucleotide concept, different ACV, PCV and BVDU derivatives can act as potent and selective inhibitors of orthopoxvirus replication. However, most of the cycloSal-monophosphate derivatives of BVDU had a higher cytotoxicity than their parent nucleosides. [Copyright &y& Elsevier]

Enantiomerically pure carbocyclic 2′-deoxy-3′-azidothymidine monophosphate (AZTMP) and carba -2′deoxy-3′-thiocyanatothymidine monophosphate were synthesized to study their behavior toward their phosphorylation by thymidylate kinase. The nucleotides were synthesized starting from the parent nucleosides by an alkaline hydrolysis of the corresponding cyclo Sal-phosphate triesters. [ABSTRACT FROM AUTHOR]

C8-Arylamine-dG adducts were converted into their corresponding 5′- O -DMTr-3′- O -phosphoramidite-C8-arylamine-dG derivatives. These compounds were used for the automated synthesis of site-specifically modified oligonucleotides. The oligonucleotides were studied for their CD properties, T m values, and their effects on primer extension assays using human DNA-polymerase β. [ABSTRACT FROM AUTHOR]

In this Letter we present the results from a calculation of the full electroweak one-loop corrections for γZ vector-boson pair production at hadron colliders. The cases of proton–antiproton as well as proton–proton collisions, at the Tevatron and the LHC, respectively, are considered. Results are presented for the distribution of the γZ invariant mass and for the transverse momentum of the final-state photon. The higher-order electroweak effects are numerically significant, in particular for probing possible anomalous gauge-boson couplings. [Copyright &y& Elsevier]

We use frequency-dependent capacitance–voltage spectroscopy to study the dynamic charging of self-assembled InAs quantum dots. With increasing frequency, the AC charging becomes suppressed, beginning with the low-energy states. By applying an in-plane magnetic field, we generate an additional magnetic confinement that alters the tunneling barrier and hence the charging dynamics. In traveling through the potential barrier, the electrons acquire an additional momentum k0, proportional to the magnetic field B. As the tunneling is enhanced, when k0 matches the maximum of the electronic wave function Ψ (in momentum representation), we are able to map out the shape of Ψ by varying B. [Copyright &y& Elsevier]