2,310 research outputs found
A geometric characterization of c-optimal designs for heteroscedastic regression
No full textWe consider the common nonlinear regression model where the variance as well as the mean is a parametric function of the explanatory variables. The c-optimal design problem is investigated in the case when the parameters of both the mean and the variance function are of interest. A geometric characterization of c-optimal designs in this context is presented, which generalizes the classical result of Elfving (1952) for c-optimal designs. As in Elfving's famous characterization c-optimal designs can be described as representations of boundary points of a convex set. However, in the case where there appear parameters of interest in the variance, the structure of the Elfving set is different. Roughly speaking the Elfving set corresponding to a heteroscedastic regression model is the convex hull of a set of ellipsoids induced by the underlying model and indexed by the design space. The c-optimal designs are characterized as representations of the points where the line in direction of the vector c intersects the boundary of the new Elfving set. The theory is illustrated in several examples including pharmacokinetic models with random effects. --c-optimal design,heteroscedastic regression,Elfving's theorem,pharmacokinetic models,random effects,locally optimal design,geometric characterization
Peak Car and Beyond: The Fourth Era of Travel
No full textThere is emerging evidence that personal daily travel, particularly by car, has ceased to grow in the developed economies. This can be attributed to saturation of demand, given high levels of access and choice now widely available, together with constraints on higher speeds. We are therefore at a time of transition from an era of growth of per capita travel to an era of stability, in which the future factors determining the growth of total travel demand are demographic — population growth, increasing longevity, and urbanisation. The peak car phenomenon, which marks this transition, is seen in successful cities that attract a growing population whose travel needs are increasingly met by investment in rail-based transport, the revival of which is a characteristic of the new era
Mercer 5: A probable new globular cluster in the Galactic bulge
No full textWe present a detailed study of a dust-obscured Galactic star cluster Mercer 5 ([MCM2005b] 5) in an extremely crowded field in the Milky Way. Near-infrared (near-IR) photometry from United Kingdom Infrared Digital Sky Surveys (UKIDSS) and the Son of ISAAC on the New Technology Telescope (SofI/NTT), combined with near-IR spectroscopy also from SofI, indicates that it is almost certainly a Galactic globular cluster, located at the edge of the Galactic bulge. The cluster suffers ~9 mag of visual extinction, with strong evidence for an extinction gradient across the cluster. A simulation of the differential reddening in the cluster using empirical data from NGC 6539 (chosen because it had high signal-to-noise ratio data and low field star contamination) as a template mimics the observations extremely well. This simulation and other arguments are used to indicate that the most prominent clump of stars in the colour-magnitude diagrams is a horizontal branch clump. On this basis we conclude that the cluster is at a distance of ~5.5kpc and suffers from visual extinction ranging from ~8.5 to ~12.5 mag. Alternative explanations for its nature, such as a young cluster or an old open cluster, are much less likely, on the grounds of no visible main sequence or stars with IR excesses for the former and location versus lifetime arguments for the latter. © 2011 The Authors Monthly Notices of the Royal Astronomical Society © 2011 RAS
Preservice Teachers' Development of Effective Approaches to Text-based Discussion
No full textText-based discussion is a dialogic instructional practice to promote reading comprehension among students. To enact this practice, a teacher engages students in authentic conversation about text as students read it, to assist them in building understanding of text ideas as they are encountered. Text-based discussion has the potential to promote the development of both low-level and high-level comprehension skills among students, yet teachers need support in learning to enact it. Research has indicated that text-based discussion is not well-represented in classrooms today, likely because not many teachers have access to this support.
Recently, some teacher educators have focused on teaching preservice teachers (PSTs) to enact text-based discussions during teacher preparation programs, in an attempt to increase the presence of the practice in classrooms. Practice-based methods courses have been developed which attempt to provide preservice teachers with the knowledge and skill needed to enact text-based discussions successfully. This study investigated the ways in which six preservice teachers’ enactments of text-based discussion developed over the course of their one-year student teaching placements, after completing one such methods course in which they learned to enact the practice.
Data were collected at three time points during student teaching, and included transcripts of enactments of text-based discussion, lesson plans, interview transcripts, and assessments of lesson quality using the Instructional Quality Instrument (Junker et al., 2004). Analysis of the data suggested that the PSTs entered student teaching with the ability to enact text-based discussions with a moderate level of success, and that the quality of the discussions continued to improve over the course of the school year. The methods course seemed to support PSTs in learning to link student comments and press students for accuracy and reasoning. PSTs were more successful in eliciting student linking and recall of explicit text information than in eliciting elaborated responses from students; the participation structure enforced by the PST seemed to influence the extent to which students provided elaborated responses. This study supports the use of practice-based methods courses to teach PSTs to enact text-based discussions, and uncovers several areas that are in need of additional focus during these courses
Role of mutation in pseudomonas aeruginosa biofilm development.
No full textThe survival of bacteria in nature is greatly enhanced by their ability to grow within surface-associated communities called biofilms. Commonly, biofilms generate proliferations of bacterial cells, called microcolonies, which are highly recalcitrant, 3-dimensional foci of bacterial growth. Microcolony growth is initiated by only a subpopulation of bacteria within biofilms, but processes responsible for this differentiation remain poorly understood. Under conditions of crowding and intense competition between bacteria within biofilms, microevolutionary processes such as mutation selection may be important for growth; however their influence on microcolony-based biofilm growth and architecture have not previously been explored. To study mutation in-situ within biofilms, we transformed Pseudomonas aeruginosa cells with a green fluorescent protein gene containing a +1 frameshift mutation. Transformed P. aeruginosa cells were non-fluorescent until a mutation causing reversion to the wildtype sequence occurs. Fluorescence-inducing mutations were observed in microcolony structures, but not in other biofilm cells, or in planktonic cultures of P. aeruginosa cells. Thus microcolonies may represent important foci for mutation and evolution within biofilms. We calculated that microcolony-specific increases in mutation frequency were at least 100-fold compared with planktonically grown cultures. We also observed that mutator phenotypes can enhance microcolony-based growth of P. aeruginosa cells. For P. aeruginosa strains defective in DNA fidelity and error repair, we found that microcolony initiation and growth was enhanced with increased mutation frequency of the organism. We suggest that microcolony-based growth can involve mutation and subsequent selection of mutants better adapted to grow on surfaces within crowded-cell environments. This model for biofilm growth is analogous to mutation selection that occurs during neoplastic progression and tumor development, and may help to explain why structural and genetic heterogeneity are characteristic features of bacterial biofilm populations
Strengthening the capability approach : the foundations of the capability approach, with insights from two challenges
No full textThe Capability Approach was initially developed by Nobel laureate Amartya Sen, with the first basic articulation presented in his 1979 ‘Equality of What?’ Tanner Lecture. Since then, the approach has gained a huge amount of attention as a conceptual framework which offers a clear and insightful way to measure well-being and development. Most recently, the approach has been refined and extended by Martha Nussbaum to issues of disability, nationality, and species membership in political philosophy.
This project is about the foundations of the capability approach. More specifically, this project asks whether we can, and whether there are good reasons to, strengthen those foundations. The conclusions drawn here are that we ought to think seriously about the way that the capability approach develops as a theory that responds to real world challenges and change. More importantly, this project contends – in light of the challenges of future people and indigenous peoples – that there is good reason to think of new ways to ground the approach. This project takes up this challenge and grounds the approach in a modified version of Tim Mulgan’s approach to well-being. This project demonstrates that this alternative enriches the capability approach by providing us with a way of making sense of important problems, and with options for moving forward.
Overall, this project asks important questions about how the capability approach could evolve based on challenges that remain relatively under-explored in the current literature. This project contributes to this literature by demonstrating that we can and ought to strengthen the capability approach and its ability to understand, take on board, and resolve these challenges
Selective anticancer activity of a hexapeptide with sequence homology to a non-kinase domain of Cyclin Dependent Kinase 4
No full textBackground: cyclin-dependent kinases 2, 4 and 6 (Cdk2, Cdk4, Cdk6) are closely structurally homologous proteins which are classically understood to control the transition from the G1 to the S-phases of the cell cycle by combining with their appropriate cyclin D or cyclin E partners to form kinase-active holoenzymes. Deregulation of Cdk4 is widespread in human cancer, CDK4 gene knockout is highly protective against chemical and oncogene-mediated epithelial carcinogenesis, despite the continued presence of CDK2 and CDK6; and overexpresssion of Cdk4 promotes skin carcinogenesis. Surprisingly, however, Cdk4 kinase inhibitors have not yet fulfilled their expectation as 'blockbuster' anticancer agents. Resistance to inhibition of Cdk4 kinase in some cases could potentially be due to a non-kinase activity, as recently reported with epidermal growth factor receptor. Results: a search for a potential functional site of non-kinase activity present in Cdk4 but not Cdk2 or Cdk6 revealed a previously-unidentified loop on the outside of the C'-terminal non-kinase domain of Cdk4, containing a central amino-acid sequence, Pro-Arg-Gly-Pro-Arg-Pro (PRGPRP). An isolated hexapeptide with this sequence and its cyclic amphiphilic congeners are selectively lethal at high doses to a wide range of human cancer cell lines whilst sparing normal diploid keratinocytes and fibroblasts. Treated cancer cells do not exhibit the wide variability of dose response typically seen with other anticancer agents. Cancer cell killing by PRGPRP, in a cyclic amphiphilic cassette, requires cells to be in cycle but does not perturb cell cycle distribution and is accompanied by altered relative Cdk4/Cdk1 expression and selective decrease in ATP levels. Morphological features of apoptosis are absent and cancer cell death does not appear to involve autophagy. Conclusion: these findings suggest a potential new paradigm for the development of broad-spectrum cancer specific therapeutics with a companion diagnostic biomarker and a putative functional site for kinase-unrelated activities of Cdk4
Structure and redox kinetics of nickel(II) tetraazamacrocycles containing pendant carboxylate groups
No full textThe nickel(II) complex of the deprotonated pendant-arm macrocycle 5,12-dimethyl-7,14-diphenyl-1,4,8,11-tetraazacyclotetradecane-4,11-diace tate (L-2)(2-) has been structurally characterized by X-ray crystallography. The Ni(II)L-2 complex crystallizes in the monoclinic system, space group P2(1)/c, with a = 12.981(8), b = 16.474(6), c = 14.262(7) Angstrom and beta = 98.81(4)degrees. The complex shows a distorted cis-geometry about the metal centre, the macrocyclic ligand being folded about a N-Ni-N axis, with the pendant arms coordinated cis to one another. The Ni(II)L-1 (where (L-1)(2-) is meso-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane-4,11-di acetate) and Ni(II)L-2 complexes undergo reversible one-electron oxidation, with redox potentials of 0.717 and 0.766 V (vs. S.H.E.), respectively. Chemical oxidation of the complexes by peroxodisulfate obey overall second-order rate laws. Enthalpies and entropies of activation for Ni(II)L-1 are 38 +/- 3 kJ mol(1) and -106 +/- 9 J K-1 mol(1); and for Ni(II)L-2 the corresponding values are 41 +/- 5 kJ mol(1) and -126 +/- 15 J K-1 mol(1). Outer-sphere oxidation of Ni(II)L-1 by bis-(triazacyclononane)nickel(III) ([Ni(III)(tacn)(2)](3+)) has been studied, and a self-exchange rate constant for the [Ni(II)L-1](0/+) system has been estimated at 55 mol(1) dm(3) s(1).PT: J; CR: *MOL STRUCT CORP, 1997, TEXS WIND CRYST STRU ADMIRIAL G, DIRDIF 94 PROGRAM SY ASTRUC D, 1995, ELECT TRANSFER RADIC, P20 BANERJEE P, 1981, Z ANORG ALLG CHEM, V473, P224 BELSKY VK, 1993, POLYHEDRON, V12, P831 BERNHARD P, 1985, J AM CHEM SOC, V107, P312 BERNHARDT PV, 1990, COORDIN CHEM REV, V104, P297 BOSNICH B, 1965, INORG CHEM, V4, P1102 BU XH, 1995, J CHEM SOC DA, P2289 BURGESS J, 1966, J CHEM SOC A, P1772 CHARBONNIER F, 1998, TETRAHEDRON LETT, V39, P3481 CHEN LQ, 1993, CAN J CHEM, V71, P1805 COLLIN JP, 1987, J CHEM SOC CHEM COMM, P1075 COX JPL, 1989, J CHEM SOC CHEM COMM, P797 CURTIS NF, 1968, COORDIN CHEM REV, V3, P3 DAVIES PJ, 1996, INORG CHIM ACTA, V246, P1 GILMORE CJ, 1984, J APPL CRYSTALLOGR, V17, P42 GORE ES, 1973, INORG CHEM, V12, P1 GUPTA SS, 1981, INORG CHEM, V20, P454 HAINES RI, 1981, COORDIN CHEM REV, V39, P77 HAINES RI, 1992, CAN J CHEM, V70, P2785 HAINES RI, 1993, CAN J CHEM, V71, P976 HOLBA V, 1987, TRANSIT METAL CHEM, V12, P121 HOUSE DA, 1962, CHEM REV, V62, P185 JORDAN RB, 1998, REACTION MECH INORGA, P200 KIMURA E, 1985, J CHEM SOC CHEM COMM, P385 LAPPIN AG, 1988, ADV INORG CHEM, V32, P241 LEWIS NB, 1949, J CHEM SOC, P386 LI HL, 1989, INORG CHEM, V28, P863 MACARTNEY DH, 1983, INORG CHEM, V22, P3530 MARCUS RA, 1964, ANNU REV PHYS CHEM, V15, P155 MARCUS RA, 1985, BIOCHIM BIOPHYS ACTA, V811, P265 MCAULEY A, 1982, J CHEM SOC CHEM COMM, P274 MCAULEY A, 1984, INORG CHEM, V23, P1938 MCAULEY A, 1984, J CHEM SOC DA, P1501 MCAULEY A, 1993, CAN J CHEM, V71, P1792 MORPHY JR, 1989, J CHEM SOC CHEM COMM, P792 SHERRY AD, 1989, INORG CHEM, V28, P620 SPERANZINI RA, 1989, MATER PERFORMANCE, V28, P67 SUTIN N, 1983, PROG INORG CHEM, V30, P441 TACHIKAWA E, 1984, NUCL TECHNOL, V65, P138 TAIT M, 1978, INORG SYNTH, V18, P4 TOBE ML, 1999, INORGANIC REACTION M, P481 VOLAROVA O, 1986, COLLECT CZECH CHEM C, V51, P1049 WANG JF, 1989, INORG CHEM, V28, P3481 XU JD, 1986, INORG CHIM ACTA, V111, P61 XU JD, 1988, INORG CHEM, V27, P4651; NR: 47; TC: 6; J9: CAN J CHEM; PG: 9; GA: 399WASource type: Electronic(1
To Which Is Prefixed, An Account of the Life and Writings of the Author
No full textBy The late Adam Smith, LL. D. Fellow Of The Royal Societies Of London And Edinburgh, &c. &c.. To Which Is Prefixed, An Account of the Life and Writings of the Author / By Dugald Stewart, F.R.S.E.Bis auf das Impressum und das nur hier vorhandene Zwischentitelblatt für den "Account ..." satzgleich wie die Ausgabe von 1800, also mit hoher Wahrscheinlichkeit vom selben Drucker (Johann Jakob Thurneysen IV? Wilhelm Haas Sohn?) gedrucktZum Drucker: Germann scheint anzunehmen, dass das Werk von Johann Jakob Thurneysen IV gedruckt wurde (was eine Kooperation von Thurneysen u. Jakob Decker bedeuten würde); falls es sich beim "Editor of the Collection of English Classics" jedoch um Johann Lucas Legrand handeln sollte (und nicht um Thurneysen selbst?), könnte er auch aus Wilhelm Haas' (Sohn) Werkstatt stammen (die Zusammenarbeit von Thurneysen u. Legrand wurde 1791 beendet und Legrand liess danach bei Haas drucken)Keine eigene Nummer bei Germann (nur unter der Ausgabe von 1800, WV Nr. 96, erwähnt
Syllis mercedesae Lucas, Martín & Parapar, 2012, sp. nov.
No full textSyllis mercedesae sp. nov. Figures 5–6, Table 1 Type material: A total of 8 specimens were obtained from three DIVA-Artabria I samples. Sample AT- 1000, holotype (MNCN 16.01 / 12018) and 5 paratypes (MNCN 16.01 / 12021 - 25). Sample AT-600, 1 paratype, 11 /09/ 2002, 629– 631 m, nodules and stones, 43 º 53.457 ’N; 08º 48.461 ’W (MNCN 16.01 / 12019). Sample DRN-800, 1 paratype, 11 /09/ 2002, 827– 819 m, stones, 43 º 51.265 ’N; 08º 54.480 ’W (MNCN 16.01 / 12020). Diagnostic characters: Midbody parapodia with straight aciculae and moderately long spiniger-like chaetae having indistinct subdistal tooth and appearing almost unidentate. Description based on holotype: Body long, thin; holotype 15 mm long, 0.5 mm wide, 72 chaetigers; longest specimen 20 mm long, 1 mm wide, 94 chaetigers. Prostomium semicircular to pentagonal, with four eyes in trapezoidal arrangement, anterior eyes larger than posterior; apparently without eyespots (Figs. 5 A, B). Median antenna longer than prostomium and palps together, inserted between posterior eyes with 12–14 articles (Fig. 5 B); lateral antennae inserted near anterior margin of prostomium, similar in shape to median antenna, with 12 articles. Peristomium somewhat shorter than subsequent segments; dorsal tentacular cirri long, with 17–23 articles; ventral cirri shorter than dorsal ones with about 10 articles. First dorsal cirri longer than remaining ones (20–26 articles), then alternating short (11–12 articles) and long (17–18 articles), becoming progressively shorter and fusiform after proventricle, with 8–9 articles, at midbody to 7–8 articles in posterior-most cirri (Figs. 5 A–C). Anterior parapodia with 10–14 compound heterogomph chaetae; dorsal-most ones with relatively long blades (70 µm long) with short marginal spines, slightly bidentate (Fig. 6 A); remaining chaetae with shorter blades, decreasing progressively in length from dorsal (27–28 µm long) to ventral (22 µm long), with short marginal spines and distinct subdistal tooth (Fig. 6 B). Number of compound chaetae per parapodium progressively decreasing to 8 from midbody: 1–2 dorsal, with elongated blades (70 µm long), spiniger-like, bidentate, with subdistal tooth small, and short marginal spines (Figs. 6 D, E); remaining chaetae with marked dorsoventral gradation in blade length (from 40 to 20 µm), bidentate. Posterior parapodia with 8 compound chaetae, one with slightly elongated blade (44 µm long) and short marginal spines, bidentate, with subdistal tooth distinct (Fig. 6 G); remaining chaetae with shorter articles (27–28 µm to 19–20 µm long), with short marginal spines and distinct subdistal tooth (Fig 6 H). Dorsal simple capillary chaeta on posterior parapodia, bidentate, smooth (Fig. 6 I). Ventral simple chaeta on posterior parapodia, slender, bidentate, with subdistal tooth small, smooth (Fig. 6 J). Anterior parapodia with four aciculae, three of them thin, with straight, blunt tips; one with truncate tip (Fig. 6 C); then progressively decreasing to two at midbody (Fig. 6 F) and one in posterior parapodia, straight, acute distally, protruding from parapodial lobes (Fig. 6 K). Pygidium small, with two long anal cirri with 14 articles (Fig. 5 C). Pharynx long and slender, through about nine segments (Fig. 6 A); middorsal pharyngeal tooth located on anterior margin. Proventricle shorter than pharynx, through seven segments with about 27–28 muscle cell rows. Etymology: The species is named after Mercedes Lucas Rodríguez, sister of first author. Type locality: Continental slope off Ártabro Gulf (Galicia, NW Spain), on hard substrates (dead corals and stones), from 1091 to 1132 m deep. Remarks. Thirty two species of Syllis are currently known for the Iberian Peninsula (San Martín 2003; Del Pilar Ruso & San Martín 2012), none combining the presence of straight aciculae, protruding from parapodial lobes in posterior-most parapodia with the midbody moderately long spiniger-like chaetae with indistinct subdistal tooth, appearing almost unidentate. The new species resembles Syllis parapari San Martín and López, 2000 (San Martín & López 2000), but the pseudo-spiniger chaetae in Syllis mercedesae sp. nov. have shorter articles and indistinctly bidentate distal ends; the posterior dorsal and ventral simple chaetae are bidentate, smooth (with broad tip and spinulated in S. parapari); the dorsal cirri are somewhat thicker and less sharpened distally (more elongated and sharpened in S. parapari); and, finally, the 6–8 anterior aciculae differ in shape in both species. Syllis beneliahuae Campoy and Alquézar, 1982 (Campoy & Alquézar 1982) also resembles the new species in having falciger chaetae very similar in shape, but differs in the acicular shape (slender, acuminate in S. beneliahuae; straight, acute, protruding out of the parapodia in S. mercedesae sp. nov.) The spiniger-like chaetae of the new species are similar to those of Syllis rosea (Langerhans, 1879), but differs in their length and, also, in the shape of its posterior aciculae (broad, ending in right angle in S. rosea). Syllis cornuta Rathke, 1843 (species wrongly reported in the Iberian Peninsula) differs from S. mercedesae sp. nov. in having longer, slender dorsal cirri, as well as in some chaetal details. The differences among all these species in blade length of pseudospiniger chaetae, together with some other relevant characters are summarized in Table 1. Furthermore, no other species of the genus worldwide (Licher 1999) has the peculiar combination of characters of S. mercedesae sp. nov., allowing the description of a new species.Published as part of Lucas, Yolanda, Martín, Guillermo San & Parapar, Julio, 2012, Two new species of Syllidae (Annelida: Polychaeta) from DIVA-Artabria I project (cruise 2002) to deep areas off NW Spain, pp. 77-88 in Zootaxa 3589 on pages 83-86, DOI: 10.5281/zenodo.21048
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