311 research outputs found
Optimization of beam parameters and iodine quantification in dual-energy contrast enhanced digital breast tomosynthesis
International audienc
Non-pharmacological factors that determine drug use and addiction
Based on their pharmacological properties, psychoactive drugs are supposed to take control of the natural reward system to finally drive compulsory drug seeking and consumption. However, psychoactive drugs are not used in an arbitrary way as pure pharmacological reinforcement would suggest, but rather in a highly specific manner depending on non-pharmacological factors. While pharmacological effects of psychoactive drugs are well studied, neurobiological mechanisms of non-pharmacological factors are less well understood. Here we review the emerging neurobiological mechanisms beyond pharmacological reinforcement which determine drug effects and use frequency. Important progress was made on the understanding of how the character of an environment and social stress determine drug self-administration. This is expanded by new evidence on how behavioral alternatives and opportunities for drug instrumentalization generate different patterns of drug choice. Emerging evidence suggests that the neurobiology of non-pharmacological factors strongly determines pharmacological and behavioral drug action and may, thus, give rise for an expanded system’s approach of psychoactive drug use and addiction
Self-consistency and Symmetry in d-dimensions
Bethe approximation is shown to violate Bravais lattices translational
invariance. A new scheme is then presented which goes over the one-site Weiss
model yet preserving initial lattice symmetry. A mapping to a one-dimensional
finite closed chain in an external field is obtained. Lattice topology
determines the chain size. Using recent results in percolation, lattice
connectivity between chains is argued to be where is the
coordination number and is the space dimension. A new self-consistent
mean-field equation of state is derived. Critical temperatures are thus
calculated for a large variety of lattices and dimensions. Results are within a
few percent of exact estimates. Moreover onset of phase transitions is found to
occur in the range . For the Ising hypercube it yields the Golden
number limit .Comment: 16 pages, latex, Phys. Rev. B (in press
Dose reduction of epoetin-alpha in the prevention of chemotherapy-induced anaemia
Introduction: Anaemia during chemotherapy is often left untreated. Erythropoiesis-stimulating agents are frequently used to treat overt anaemia. Their prophylactic use, however, remains controversial and raises concerns about cost-effectiveness. Therefore, we assessed the efficacy of a dose-reduction schedule in anaemia prophylaxis. Materials and methods: The study included patients with untreated solid tumours about to receive platinum-based chemotherapy and had haemoglobin (Hb) levels ≥11g/dL. Epoetin-α was administered at a dose level of 3 × 10,000U weekly as soon as Hb descended to < 13g/dL. Dose reductions to 3 × 4,000U and 3 × 2,000U weekly were planned in 4-week intervals if Hb stabilised in the range of 11-13g/dL. Upon ascending to ≥13g/dL, epoetin was discontinued. Iron supplements of 100mg intravenous doses were given weekly. Of 37 patients who enrolled, 33 could be evaluated. Results and discussion: Their median Hb level was 13.7 (10.9-16.2) g/dL at baseline and descended to 11.0 (7.4-13.8) g/dL by the end of chemotherapy. Anaemia (Hb < 10g/dL) was prevented in 24 patients (73%). The mean dose requirement for epoetin-α was 3 × 5,866U per week per patient, representing a dose reduction of 41%. Treatment failed in nine patients (27%), in part due to epoetin-α resistance in four (12%) and blood transfusion in three (9%) patients. Conclusion: Dose reduction was as effective as fixed doses in anaemia prophylaxis but reduced the amount of prescribed epoetin substantiall
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Laccase-Enzyme Treated Flax Fibre for Use in Natural Fibre Epoxy Composites
Natural fibres have a high potential as reinforcement of polymer matrices, as they combine a high specific strength and modulus with sustainable production and reasonable prices. Modifying the fibre surface is a common method to increase the adhesion and thereby enhance the mechanical properties of composites. In this study, a novel sustainable surface treatment is presented: the fungal enzyme laccase was utilised with the aim of covalently binding the coupling agent dopamine to flax fibre surfaces. The goal is to improve the interfacial strength towards an epoxy matrix. SEM and AFM micrographs showed that the modification changes the surface morphology, indicating a deposition of dopamine on the surface. Fibre tensile tests, which were performed to check whether the fibre structure was damaged during the treatment, showed that no decrease in tensile strength or modulus occurred. Single fibre pullout tests showed a 30% increase in interfacial shear strength (IFSS) due to the laccase-mediated bonding of the coupling agent dopamine. These results demonstrate that a laccase + dopamine treatment modifies flax fibres sustainably and increases the interfacial strength towards epoxy
Atom gravimeters and gravitational redshift
In a recent paper, H. Mueller, A. Peters and S. Chu [A precision measurement
of the gravitational redshift by the interference of matter waves, Nature 463,
926-929 (2010)] argued that atom interferometry experiments published a decade
ago did in fact measure the gravitational redshift on the quantum clock
operating at the very high Compton frequency associated with the rest mass of
the Caesium atom. In the present Communication we show that this interpretation
is incorrect.Comment: 2 pages, Brief Communication appeared in Nature (2 September 2010
Synthesis and structure-activity relationships of cerebroside analogues as substrates of cerebroside sulphotransferase and discovery of a competitive inhibitor
Metachromatic leukodystrophy (MLD) is a rare genetic disease characterised by a dysfunction of the enzyme arylsulphatase A leading to the lysosomal accumulation of cerebroside sulphate (sulphatide) causing subsequent demyelination in patients. The enzyme galactosylceramide (cerebroside) sulphotransferase (CST) catalyses the transfer of a sulphate group from 3 '-phosphoadenosine-5'-phosphosulphate (PAPS) to cerebrosides producing sulphatides. Substrate reduction therapy for arylsulphatase A by inhibition of CST was proposed as a promising therapeutic approach. To identify competitive CST inhibitors, we synthesised and investigated analogues of the substrate galactosylceramide with variations at the anomeric position, the acyl substituent and the carbohydrate moiety, and investigated their structure-activity relationships. While most of the compounds behaved as substrates, alpha-galactosylceramide16was identified as the first competitive CST inhibitor. Compound16can serve as a new lead structure for the development of drugs for the treatment of this devastating disease, MLD, for which small molecule therapeutics are currently not available
Oscillations and temporal signalling in cells
ArXiv pre-print: http://arxiv.org/abs/q-bio/0703047.-- Final full-text version of the paper available at: http://dx.doi.org/10.1088/1478-3975/4/2/R01.PMID: 17664651The development of new techniques to quantitatively measure gene expression in cells has shed light on a number of systems that display oscillations in protein concentration. Here we review the different mechanisms which can produce oscillations in gene expression or protein concentration using a framework of simple mathematical models. We focus on three eukaryotic genetic regulatory networks which show ultradian oscillations, with a time period of the order of hours, and involve, respectively, proteins important for development (Hes1), apoptosis (p53) and immune response (NF-κB). We argue that underlying all three is a common design consisting of a negative feedback loop with time delay which is responsible for the oscillatory behaviour.SK, MHJ and KS acknowledge support from the Danish National Research Foundation and Villum Kann Rasmussen Foundation. GT acknowledges support from the FIRB 2003 program of the
Italian Ministry for University and Scientific Research
SoK: Why Johnny Can't Fix PGP Standardization
Pretty Good Privacy (PGP) has long been the primary IETF standard for
encrypting email, but suffers from widespread usability and security problems
that have limited its adoption. As time has marched on, the underlying
cryptographic protocol has fallen out of date insofar as PGP is unauthenticated
on a per message basis and compresses before encryption. There have been an
increasing number of attacks on the increasingly outdated primitives and
complex clients used by the PGP eco-system. However, attempts to update the
OpenPGP standard have failed at the IETF except for adding modern cryptographic
primitives. Outside of official standardization, Autocrypt is a "bottom-up"
community attempt to fix PGP, but still falls victim to attacks on PGP
involving authentication. The core reason for the inability to "fix" PGP is the
lack of a simple AEAD interface which in turn requires a decentralized public
key infrastructure to work with email. Yet even if standards like MLS replace
PGP, the deployment of a decentralized PKI remains an open issue
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