Melting of Polydisperse Hard Disks

The melting of a polydisperse hard disk system is investigated by Monte Carlo simulations in the semigrand canonical ensemble. This is done in the context of possible continuous melting by a dislocation unbinding mechanism, as an extension of the 2D hard disk melting problem. We find that while there is pronounced fractionation in polydispersity, the apparent density-polydispersity gap does not increase in width, contrary to 3D polydisperse hard spheres. The point where the Young's modulus is low enough for the dislocation unbinding to occur moves with the apparent melting point, but stays within the density gap, just like for the monodisperse hard disk system. Additionally, we find that throughout the accessible polydispersity range, the bound dislocation-pair concentration is high enough to affect the dislocation unbinding melting as predicted by Kosterlitz, Thouless, Halperin, Nelson and Young.Comment: 6 pages, 6 figure

Methods to split cognitive task data for estimating split-half reliability: A comprehensive review and systematic assessment

Estimating the reliability of cognitive task datasets is commonly done via split-half methods. We review four methods that differ in how the trials are split into parts: a first-second half split, an odd-even trial split, a permutated split, and a Monte Carlo-based split. Additionally, each splitting method could be combined with stratification by task design. These methods are reviewed in terms of the degree to which they are confounded with four effects that may occur in cognitive tasks: effects of time, task design, trial sampling, and non-linear scoring. Based on the theoretical review, we recommend Monte Carlo splitting (possibly in combination with stratification by task design) as being the most robust method with respect to the four confounds considered. Next, we estimated the reliabilities of the main outcome variables from four cognitive task datasets, each (typically) scored with a different non-linear algorithm, by systematically applying each splitting method. Differences between methods were interpreted in terms of confounding effects inflating or attenuating reliability estimates. For three task datasets, our findings were consistent with our model of confounding effects. Evidence for confounding effects was strong for time and task design and weak for non-linear scoring. When confounding effects occurred, they attenuated reliability estimates. For one task dataset, findings were inconsistent with our model but they may offer indicators for assessing whether a split-half reliability estimate is appropriate. Additionally, we make suggestions on further research of reliability estimation, supported by a compendium R package that implements each of the splitting methods reviewed here

Clinical radiography education across Europe

Purpose: To establish a picture of clinical education models within radiography programmes across Europe by surveying higher education institutions registered as affiliate members of the European Federation of Radiography Societies (EFRS). Method: An online survey was developed to ascertain data on: practical training, supervisory arrangements, placement logistics, quality assurance processes, and the assessment of clinical competencies. Responses were identifiable in terms of educational institution and country. All educational institutions who were affiliate members at the time of the study were invited to participate (n=46). Descriptive and thematic analyses are reported. Results: A response rate of 82.6% (n=38) was achieved from educational institutions representing 21 countries. Over half of responding institutions (n=21) allocated in excess of 60 European Credit Transfer and Accumulation System (ECTS) credits to practical training. In nearly three-quarters of clinical placements there was a dedicated clinical practice supervisor in place; two-thirds of these were employed directly by the hospital. Clinical practice supervisors were typically state registered radiographers, who had a number of years of clinical experience and had received specific training for the role. Typical responsibilities included monitoring student progress, providing feedback and completing paperwork, this did however vary between respondents. In almost all institutions there were support systems in place for clinical placement supervisors within their roles. Conclusions: Similarities exist in the provision of clinical radiography education across Europe. Clinical placements are a core component of radiography education and are supported by experienced clinical practice supervisors. Mechanisms are in place for the selection, training and support of clinical practice supervisors. Professional societies should work collaboratively to establish guidelines for effective clinical placements

Islands of conformational stability for Filopodia

Filopodia are long, thin protrusions formed when bundles of fibers grow outwardly from a cell surface while remaining closed in a membrane tube. We study the subtle issue of the mechanical stability of such filopodia and how this depends on the deformation of the membrane that arises when the fiber bundle adopts a helical configuration. We calculate the ground state conformation of such filopodia, taking into account the steric interaction between the membrane and the enclosed semiflexible fiber bundle. For typical filopodia we find that a minimum number of fibers is required for filopodium stability. Our calculation elucidates how experimentally observed filopodia can obviate the classical Euler buckling condition and remain stable up to several tens of . We briefly discuss how experimental observation of the results obtained in this work for the helical-like deformations of enclosing membrane tubes in filopodia could possibly be observed in the acrosomal reactions of the sea cucumber Thyone, and the horseshoe crab Limulus. Any realistic future theories for filopodium stability are likely to rely on an accurate treatment of such steric effects, as analysed in this work

Critical role of metals in biochemical properties of xylose isomerase

Improving the activity of xylose isomerase (XI) is highly desired for achieving efficient fermentation of xylose in lignocellulosic biomass using XI-expressing S. cerevisiae. XI is a metalloenzyme which requires two bivalent metals for its catalytic activity. The enzyme from Piromyces sp. E2 (PirXI)[1],[2] is activated with various metal ions including Mg2+, Mn2+, Ca2+, Co2+, Zn2+ and Fe2+. The biochemical properties of PirXI are dependent on the types of its metal cofactors. Moreover, the enzyme shows different affinities towards these metals. Characterization of these properties is critical for understanding the enzyme behavior in vivo and to further adapt the enzyme to the cytosolic metal environment. Recently, we have shown that altered intracellular metal composition can improve anaerobic growth of a xylose-fermenting strain by enhancing the activity of PirXI[3]. Furthermore, our current study on PirXI and other studies on different XIs have shown that it is also possible to change the metal preferences of the enzyme[4]. A PirXI variant with a single amino acid substitution in the proximity of the metal binding residues showed significant changes in metal preference compared to the wild-type PirXI. Further exploration on metal specificity of PirXI is necessary to optimize the in vivo enzyme activity. References: 1.Kuyper M, Harhangi HR, Stave AK, Winkler AA, Jetten MS, de Laat WT, den Ridder JJ, Op den Camp HJ, van Dijken JP, Pronk JT, FEMS Yeast Research 4 (2003) 69-78 2.van Maris AJ, Winkler AA, Kuyper M, de Laat WT, van Dijken JP, Pronk JT, Adv Biochem Engin/Biotechnol (2007) 108: 179–204 3.Verhoeven MD, Lee M, Kamoen L, van den Broek M, Janssen DB, Daran JG, van Maris AJA, Pronk JT, Sci. Rep (2017) 7, 46155 4.van Tilbeurgh H, Jenkins J, Chiadmi M, Janin J, Wodak SJ, Mrabet NT, Lambeir AM, Biochemistry (1992) 31: 5467-547

The Granulin/Epithelin Precursor Abrogates the Requirement for the Insulin-like Growth Factor 1 Receptor for Growth in Vitro

3T3 cells null for the type 1 insulin-like growth factor receptor are refractory to stimulation by a variety of purified growth factors that are known to be required for the stimulation of other 3T3 cells. However, these cells, known as R- cells, grow in serum-supplemented medium and also in media conditioned by certain cell lines. We report here the purification of a growth factor that stimulates DNA synthesis (and growth) of R- cells. The growth factor, purified to homogeneity by SDS-polyacrylamide gel electrophoresis, was identified as the granulin/epithelin precursor by an accurate determination of the masses of endoproteinase Lys-C peptides using matrix-assisted laser desorption ionization mass spectrometry, followed by a data base search. The granulin/epithelin precursor is a little known growth factor, secreted by a variety of epithelial and hemopoietic cells. It is at present the only purified growth factor that can stimulate the growth of mouse embryo fibroblasts null for the type 1 insulin-like growth factor receptor

Exploring the conformational dynamics of alanine dipeptide in solution subjected to an external electric field: A nonequilibrium molecular dynamics simulation

In this paper, we investigate the conformational dynamics of alanine dipeptide under an external electric field by nonequilibrium molecular dynamics simulation. We consider the case of a constant and of an oscillatory field. In this context we propose a procedure to implement the temperature control, which removes the irrelevant thermal effects of the field. For the constant field different time-scales are identified in the conformational, dipole moment, and orientational dynamics. Moreover, we prove that the solvent structure only marginally changes when the external field is switched on. In the case of oscillatory field, the conformational changes are shown to be as strong as in the previous case, and non-trivial nonequilibrium circular paths in the conformation space are revealed by calculating the integrated net probability fluxes.Comment: 23 pages, 12 figure

Phase I study on docetaxel and ifosfamide in patients with advanced solid tumours.

Docetaxel and ifosfamide have shown significant activity against a variety of solid tumours. This prompted a phase I trial on the combination of these drugs. This phase I study was performed to assess the feasibility of the combination, to determine the maximum tolerated dose (MTD) and the side effects, and to propose a safe schedule for further phase II studies. A total of 34 patients with a histologically confirmed solid tumour, who were not pretreated with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-h infusion followed by ifosfamide as a 24-h infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg m(-2) and ifosfamide doses from 2.5 to 5.0 g m(-2). Granulocytopenia grade 3 and 4 were common (89%), short lasting and ifosfamide dose dependent. Febrile neutropenia and sepsis occurred in 17% and 2% of courses respectively. Non-haematological toxicities were mild to moderate and included alopecia, nausea, vomiting, mucositis, diarrhoea, sensory neuropathy, skin and nail toxicity and oedema. There did not appear to be any pharmacokinetic interaction between docetaxel and ifosfamide. One complete response (CR) (soft tissue sarcoma) and two partial responses (PRs) were documented. A dose of 75 mg m(-2) of docetaxel combined with 5.0 g m(-2) ifosfamide appeared to be manageable. Schedule A was advocated for further treatment

Lattice-switch Monte Carlo

We present a Monte Carlo method for the direct evaluation of the difference between the free energies of two crystal structures. The method is built on a lattice-switch transformation that maps a configuration of one structure onto a candidate configuration of the other by `switching' one set of lattice vectors for the other, while keeping the displacements with respect to the lattice sites constant. The sampling of the displacement configurations is biased, multicanonically, to favor paths leading to `gateway' arrangements for which the Monte Carlo switch to the candidate configuration will be accepted. The configurations of both structures can then be efficiently sampled in a single process, and the difference between their free energies evaluated from their measured probabilities. We explore and exploit the method in the context of extensive studies of systems of hard spheres. We show that the efficiency of the method is controlled by the extent to which the switch conserves correlated microstructure. We also show how, microscopically, the procedure works: the system finds gateway arrangements which fulfill the sampling bias intelligently. We establish, with high precision, the differences between the free energies of the two close packed structures (fcc and hcp) in both the constant density and the constant pressure ensembles.Comment: 34 pages, 9 figures, RevTeX. To appear in Phys. Rev.