The surface science of quasicrystals

The surfaces of quasicrystals have been extensively studied since about 1990. In this paper we review work on the structure and morphology of clean surfaces, and their electronic and phonon structure. We also describe progress in adsorption and epitaxy studies. The paper is illustrated throughout with examples from the literature. We offer some reflections on the wider impact of this body of work and anticipate areas for future development. (Some figures in this article are in colour only in the electronic version

Suicide nanoplasmids coding for ribosome-inactivating proteins

Conventional eukaryotic expression plasmids contain a DNA backbone that is dispensable for the cellular expression of the transgene. In order to reduce the vector size, minicircle DNA technology was introduced. A drawback of the minicircle technology are considerable production costs. Nanoplasmids are a relatively new class of mini-DNA constructs that are of tremendous potential for pharmaceutical applications. In this study we have designed novel suicide nanoplasmid constructs coding for plant derived ribosome-inactivating proteins. The suicide-nanoplasmids were formulated with a targeted K(16)-lysine domain, analyzed for size, and characterized by electron microscopy. The anti-proliferative activity of the suicide-nanoplasmids was investigated in vitro by real time microscopy and the expression kinetic was determined using an enhanced green fluorescent protein nanoplasmid variant. In an aggressive in vivo neuroblastoma tumor model, treated mice showed a reduced tumor growth whereby the therapy was well tolerated

Structure of metal site in azurin, met 121 mutants of azurin, and stellacyanin investigated by 111m Cd Perturbed Angular Correlation (PAC)

The geometries of the metal sites in cadmium-substituted azurins have been investigated by Cd-111m perturbed angular correlation (PAC), The study includes wild type azurin as well as Met(121) mutants of azurin, where methionine has been substituted by Ala, Asn, Asp, Gin, Glu, and Leu.The nuclear quadrupole interaction of wild type azurin analyzed in the angular overlap model is well described as coordination of His(46), His(117), and Cys(112) and cannot be described by coordination of Met(121) and/or Gly(45).For most of the mutants, there exist two coordination geometries of the cadmium ion, With the exception of the Gau and Asp mutants, one of the conformations is similar to the wild type conformation. The other coordination geometries are either best described by a coordinating water molecule close to the original methionine position or by coordination by the substituting amino acid, These experiments show that even though the methionine does not coordinate it plays an important role for the geometry of the metal site.The nuclear quadrupole interaction of stellacyanin was also measured, The value resembles the most prominent nuclear quadrupole interaction of the Met(121) --> Gin mutant of Alcaligenes denitrificans azurin, indicating that the structures of the two metal sites are similar.Macromolecular Biochemistr

Studies of colossal magnetoresistive oxides with radioactive isotopes

We propose to study Colossal Magnetoresistive (CMR) oxides with several nuclear techniques, which use radioactive elements at ISOLDE. Our aim is to provide local and element selective information on some of the doping mechanisms that rule electronic interactions and magnetoresistance, in a complementary way to the use of conventional characterisation techniques. Three main topics are proposed: \\ \\ a) Studies of local [charge and] structural modifications in antiferromagnetic LaMnO$_{3+ \delta}$ and La$_{1-x}$R$_{x}$MnO$_{3}$ with R=Ca and Cd, doped ferromagnetic systems with competing interactions: - research on the lattice site and electronic characterisation of the doping element. \\ \\ b) Studies of self doped La$_{x}$R$_{1-x}$MnO$_{3+\delta}$ systems, with oxygen and cation non-stoichiometry: -learning the role of defects in the optimisation of magnetoresistive properties. \\ \\ c) Probing the disorder and quenched random field effects in the vicinity of the charge or orbital Ordered/Ferromagnetic phase instability: - Investigating the local environment of ions at the Mn site, which trigger the ferromagnetic phase. Our approach to study these problems, combines complementary techniques such as Perturbed Angular Correlation, Emission Channeling and Electrical/Magnetic Measurements in pellets, single crystals and high quality thin films of CMR oxides doped with radioactive isotopes. Preliminary results obtained in La Cd MnO$_{3+x}$ pellets and thin films implanted with $^{111m}$Cd are also presented

Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells

Chemotherapy in patients with inoperable or advanced breast cancer inevitably results in low-dose exposure of tumor-cell subset and senescence. Metabolically active senescent cells secrete multiple tumor promoting factors making their elimination a therapeutic priority. Viscum album is one of the most widely used alternative anti-cancer medicines facilitating chemotherapy tolerance of breast cancer patients. The aim of this study was to model and investigate how Viscum album extracts execute additive anti-tumor activity with low-dose Dox using ER + MCF7 breast cancer cells. We report that cotreatment of MCF7 with Viscum album and Dox abrogates G2/M cycle arrest replacing senescence with intrinsic apoptotic program. Mechanistically, this switch was associated with down-regulation of p21, p53/p73 as well as Erk1/2 and p38 activation. Our findings, therefore, identify a novel mechanistic axis of additive antitumor activity of Viscum album and low dose-Dox. In conclusion, ER + breast cancer patients may benefit from addition of Viscum album to low-dose Dox chemotherapy due to suppression of cancer cell senescence and induction of apoptosis

The Political Economy of Failure: The Euro as an International Currency

How do international currencies get established and consolidated? What domestic and international political foundations support an international currency? And what kinds of macro-economic flows enable an international currency? In this essay we consider these perennial questions of modern IPE scholarship in reverse order to ask whether the euro could ever have become, or seek to become, a true international currency rivalling the US dollar, used not only for passive foreign exchange reserves but also as a major commercial currency outside the EU. We argue that the EU lacks the will, the ideas and the capacity to promote the euro into the status of an international currency. In this article, we concentrate on this final issue of capacity, as the will and ideas issues have already been well explored. Capacity is an issue coeval with, if not prior to, the first two issues. The EU's current institutional arrangements and its economic geography create macro-economic consequences that diminish the euro's capacity to operate as a top currency. These conflicts go beyond the well-recognized issue that the euro-zone is not an optimum currency area. Examining the euro's debilities sheds light not only on the euro's (in)capacity to rival the dollar as an international currency, but also on the future of both the euro and the dollar in the aftermath of the euro-zone crisis

Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: The OPTIPARK open-label study

BACKGROUND: The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. METHODS: OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). RESULTS: Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. CONCLUSIONS: Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. TRIAL REGISTRATION: Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research

<p>Abstract</p> <p>Background</p> <p><it>Viscum album </it>L. extracts (VAE, European mistletoe) are a widely used medicinal plant extract in gynaecological and breast-cancer treatment.</p> <p>Methods</p> <p>Systematic review to evaluate clinical studies and preclinical research on the therapeutic effectiveness and biological effects of VAE on gynaecological and breast cancer. Search of databases, reference lists and expert consultations. Criteria-based assessment of methodological study quality.</p> <p>Results</p> <p>19 randomized (RCT), 16 non-randomized (non-RCT) controlled studies, and 11 single-arm cohort studies were identified that investigated VAE treatment of breast or gynaecological cancer. They included 2420, 6399 and 1130 patients respectively. 8 RCTs and 8 non-RCTs were embedded in the same large epidemiological cohort study. 9 RCTs and 13 non-RCTs assessed survival; 12 reported a statistically significant benefit, the others either a trend or no difference. 3 RCTs and 6 non-RCTs assessed tumour behaviour (remission or time to relapse); 3 reported statistically significant benefit, the others either a trend, no difference or mixed results. Quality of life (QoL) and tolerability of chemotherapy, radiotherapy or surgery was assessed in 15 RCTs and 9 non-RCTs. 21 reported a statistically significant positive result, the others either a trend, no difference, or mixed results. Methodological quality of the studies differed substantially; some had major limitations, especially RCTs on survival and tumour behaviour had very small sample sizes. Some recent studies, however, especially on QoL were reasonably well conducted. Single-arm cohort studies investigated tumour behaviour, QoL, pharmacokinetics and safety of VAE. Tumour remission was observed after high dosage and local application. VAE application was well tolerated. 34 animal experiments investigated VAE and isolated or recombinant compounds in various breast and gynaecological cancer models in mice and rats. VAE showed increase of survival and tumour remission especially in mice, while application in rats as well as application of VAE compounds had mixed results. <it>In vitro </it>VAE and its compounds have strong cytotoxic effects on cancer cells.</p> <p>Conclusion</p> <p>VAE shows some positive effects in breast and gynaecological cancer. More research into clinical efficacy is warranted.</p

Transverse momentum spectra of charged particles in proton-proton collisions at s=900\sqrt{s} = 900 GeV with ALICE at the LHC

The inclusive charged particle transverse momentum distribution is measured in proton-proton collisions at $\sqrt{s} = 900$ GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region $(|\eta|<0.8)$ over the transverse momentum range $0.15<p_{\rm T}<10$ GeV/$c$. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for $|\eta|<0.8$ is $\left<p_{\rm T}\right>_{\rm INEL}=0.483\pm0.001$ (stat.) $\pm0.007$ (syst.) GeV/$c$ and \left_{\rm NSD}=0.489\pm0.001 (stat.) $\pm0.007$ (syst.) GeV/$c$, respectively. The data exhibit a slightly larger $\left<p_{\rm T}\right>$ than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.Comment: 20 pages, 8 figures, 2 tables, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/390