bluuebunny/crossref_metadata_2025 huggingface dataset:
Ordering the suggestions of a spellchecker without using context
Authors: MITTON ROGER
Published: August 2008

Having located a misspelling, a spellchecker generally offers some suggestions for the intended word. Even without using context, a spellchecker can draw on various types of information in ordering its suggestions. A series of experiments is described, beginning with a basic corrector that implements a well-known algorithm for reversing single simple errors, and making successive enhancements to take account of substring matches, pronunciation, known error patterns, syllable structure and word frequency. The improvement in the ordering produced by each enhancement is measured on a large corpus of misspellings. The final version is tested on other corpora against a widely used commercial spellchecker and a research prototype.
GROWTH AND INEQUALITY: MODEL EVALUATION BASED ON AN ESTIMATION-CALIBRATION STRATEGY
Authors: Jeong Hyeok , Townsend Robert M.
Published: August 2008

This paper evaluates two well-known models of growth with inequality that have explicit micro underpinnings related to household choice. With incomplete markets or transactions costs, wealth can constrain investment in business and the choice of occupation and also constrain the timing of entry into the formal financial sector. Using the Thai Socio-Economic Survey (SES), we estimate the distribution of wealth and the key parameters that best fit cross-sectional data on household choices and wealth. We then simulate the model economies for two decades at the estimated initial wealth distribution and analyze whether the model economies at those micro-fit parameter estimates can explain the observed macro and sectoral aspects of income growth and inequality change. Both models capture important features of Thai reality. Anomalies and comparisons across the two distinct models yield specific suggestions for improved research on the micro foundations of growth and inequality.
The role of the ‘on treatment’ review radiographer: what are the requirements?
Authors: Lees Laura
Published: August 2008

Purpose: The aims of this study were to describe the scope of practice of the radiotherapy ’on treatment’ review radiographer. This included trying to gain an insight in to what knowledge, skills and characteristics are needed to operate in this role extension and to establish whether the role requires skills in areas of patient care and support which are beyond the generic training of a treatment floor therapy radiographer.

Method: A qualitative grounded theory methodology was employed using semi-structured interviews with ’on treatment’ review radiographers from three different departments. The departments were selected to maximise the amount of data collected, consequently they were chosen due to the differences in the way their review service was set up. This ranged from full time, to team led, to part time review. Using coding and constant comparative analysis based on grounded theory, categories were developed describing attributes of the role.

Results: The scope of practice and challenges of the role varied slightly between the departments. The core categories needed to operate in the role were identified as knowledge, listening skills and characteristics with sub categories of self-reflection, interpersonal skills and attitudes.

Conclusions: To be a review radiographer requires advanced knowledge at Masters level, with well developed listening and interpersonal skills and enjoyment of the people side of the profession. These skills need to be regularly practised, updated and reflected upon. The requirements for further training needs are noted and recommendations for further research are identified along with the limitations of this research. The role appears to require knowledge and skills in areas of patient care and support, which are above the level of practice of a treatment floor therapy radiographer.
Differentiation and Tourism Destination Development: Small Business Success in a Close-Knit Community
Authors: Tinsley Ross , Lynch Paul A.
Published: August 2008

This paper considers small tourism business relations within a rural tourism destination. They are examined within the context of small business (predominantly hospitality-based) networks and their contribution to destination development. A cultural understanding of relations is presented through a qualitative research framework. Findings highlight the concept of differentiation at individual, business community and destinations levels. This ideal is discussed as a means for maintaining harmony within the business and wider social community through social network norms, which are reinforced at all levels of society.
Quench echoes
Authors: Nagel Sidney R. , Grest Gary S. , Rahman Aneesur
Published: August 2008

When we try to understand atomic motion in amorphous solids, we face a complicated problem in classical mechanics. What is the relationship between the motion of one atom and that of every other? Without a periodic crystal lattice to simplify the calculations, we must look for other properties that make things tractable. A phenomenon recently observed in computer models of many-body systems may give us such a simplification, at least in the calculation of a number of dynamical properties of glassy solids. This phenomenon, the “quench echo,” appears as a brief but dramatic drop in the temperature of a theoretical solid sometime after it has experienced two abrupt quenches of its kinetic energy, as we will see later in detail.
American physics and the origins of electrical engineering
Authors: Rosenberg Robert
Published: August 2008

At the same time that electricity was transforming American society in the last half of the 19th century, it was transforming the study of physics. During this period, electricity bridged the existing gap between pure science and useful applications, between thinkers and doers, scholars and tinkers, as no other technology had done before. It brought home to Americans the contributions of science to everyday life. It also quickened the pace of physics research in university classrooms and industrial laboratories.
Discovery of the Z0 at CERN also yields anomalous events
Authors: Lubkin Gloria B.
Published: August 2008

Once the W particle was reported in January, it was almost inevitable that the Z0 particle would eventually be found, provided that both the CERN collider and the two detector groups worked long and hard enough. The discovery of Z0, the neutral intermediate vector boson, was announced on 1 June; the UA1 group said it found five Z0 events. The 270-GeV protons colliding with 270-GeV antiprotons had produced four events in which the Z0 decayed into an electron-positron pair and one in which the Z0 decayed into a μ+μ− pair. On 15 July, the UA2 group also reported finding the Z0.
Coherent sources of extreme uv
Authors: Schwarzschild Bertram M.
Published: August 2008

Light sources in the extreme ultraviolet wavelength regime—from 104 nanometers down to the start of the x-ray region at about 10 nm—are of particular interest for molecular spectroscopy and solid-state surface studies. But this xuv domain poses special difficulties. The beams must be propagated in vacuum, but at these wavelengths there are no longer any solid materials available for vacuum windows or the harmonic generation of xuv light from longer wavelength sources. Crystalline lithium flouride, the last of the solids to maintain its transparency in the ultraviolet, becomes completely opaque at 104 nm. Beams of xuv can of course be generated by synchrotron light sources, but their usefulness is limited: The synchrotron beams do not provide coherent xuv light. Their spectral brightness (power per unit wavelength interval) is at present marginal for high-resolution molecular spectroscopy. Furthermore, synchrotron beams are available only at large storage-ring facilities; they cannot be brought into the experimenter's home laboratory.
Second heavy-fermion superconductor
Authors: Schwarzschild Bertram M.
Published: August 2008

The recent demonstration of superconductivity in uranium beryllide (UBe13) by an ETH–Los Alamos collaboration provides us the second example of an exotic and potentially instructive new class of materials, the “heavy-fermion superconductors.” Four years ago, Frank Steglich and his colleagues at Darmstadt and Cologne reported the discovery of the first of these unconventional and somewhat puzzling new superconductors—CeCu2Si2. The unearthing of UBe13 is important not only because it shows that CeCu2Si2 is not a unique abberation. Until recently, investigations of CeCu2Si2 have been plagued by the difficulty of fabricating stoichiometrically clean, reproducible samples of this material; different samples were giving distressingly different results. With the advent of UBe13, where one does not have this metallurgical problem, and with new techniques for making crystalline CeCu2Si2 samples of high quality, one now has two sources of reliable data on the heavy-fermion superconductors.
Doing physics with microcomputers
Authors: Bak Per
Published: August 2008

In the past year or so, the sale of microcomputers has increased from a few thousand to millions a year. Today, you can walk into a toy store and buy a computer for a few hundred dollars. Most micros are probably used for recreation, and until recently they have not been taken very seriously by scientists.
Roads to chaos
Authors: Kadanoff Leo P.
Published: August 2008

Hydrodynamic systems often show an extremely complicated and apparently erratic flow pattern of the sort shown in figure 1. These turbulent flows are so highly time-dependent that local measurements of any quantity that describes the flow—one component of the velocity, say—would show a very chaotic behavior. However, there is also an underlying regularity in which the motion can be analyzed (see figure 1 again) as a series of large swirls containing smaller swirls, and so forth. One approach to understanding this turbulence is to ask how it arises. If one puts a body in a stream of a fluid—for example, a piece of a bridge sitting in the stream of a river—then for very low speeds (figure 2a) the fluid flows in a regular and time-independent fashion, what is called laminar flow. As the speed is increased (figure 2b), the motion gains swirls but remains time-independent. Then, as the velocity increases still further, the swirls may break away and start moving downstream. This induces a time-dependent flow pattern—as viewed from the bridge. The velocity measured at a point downstream from the bridge gains a periodic time-dependence like that shown in figure 2c. The parameter that characterizes these changes in the flow pattern is the dimensionless Reynolds number ℛ which is the product of the velocity and density times a characteristic length (the size of the bridge pier, for example) divided by the viscosity. As ℛ is increased still further, the swirls begin to induce irregular internal swirls as in the flow pattern of figure 2d. In this case, there is a partially periodic and partially irregular velocity history (see the second column of figure 2d). Raise ℛ still further and a very complex velocity field is induced, and the v(t) looks completely chaotic as in figure 2e. The flow shown in figure 1 has this character.
The nuclear arsenals of the US and USSR
Authors: Levi Barbara G.
Published: August 2008

In the course of the nuclear arms race, both the US and the Soviet Union have filled their arsenals with tens of thousands of nuclear warheads and with thousands of vehicles to deliver those warheads. The nuclear weapons now deployed vary in size and design from sub-kiloton artillery shells to 20-megaton warheads, and their delivery vehicles include land- and sea-based ballistic missiles as well as long-range aircraft and the new cruise missiles. Not only have the numbers and types of nuclear weapons grown, so, too, have their capabilities. The newer ballistic missiles are tipped with multiple reentry vehicles. They have longer ranges, greater accuracies, and increasingly sophisticated guidance systems. These weapons are further augmented by ever-more-able systems for land, air and sea defense and for command, communication and control. These many dimensions of the US and Soviet nuclear arsenals require that one assess their respective strengths on a multiparameter scale. Even then, any inherently quantitative comparison is incomplete, for it ignores the equally important, qualitative features of the arsenals where, in fact, much of the recent development has occurred.
pp
¯
collision yield intermediate boson at 80 GeV. as predicted
Authors: Lubkin Gloria B.
Published: August 2008

In January the UA1 collaboration working at the new CERN proton–antiproton collider announced the discovery of the charged intermediate vector boson, or W. The electroweak theory unifying the weak and electromagnetic interactions, for which Sheldon Glashow, Abdus Salam and Steven Weinberg received the 1979 Nobel prize in physics, requires the existence of three massive intermediate bosons, or weakons, with spin 1—the Z0, the W+ and W−, to mediate the electroweak interaction.
New stable meson has fifth quark flavor
Authors: Schwarzschild Bertram M.
Published: August 2008

Although the list of known mesons is long, the few that are stable against hadronic and electromagnetic decay form a rather exclusive club. Until recently, the catalogue of mesons stable against all but weak decay included only the π+, K+, K0, D+, D0, F+ and their antiparticles. The stability of these particles attests to the conservation of their various quark flavors (up, down, strange and charmed). Only the weak interaction can transmute a quark of one flavor to another.
High-energy physics
Authors: Creutz Michael
Published: August 2008

Particle physicists have long been conspicuous consumers of computer time. Today's complex experiments generate prodigious quantities of raw data that require hours of cpu time to be reduced to a form comprehensible to human colleagues. As figure 1 shows, a multitude of computer cathode-ray screens often dominates the control room of a modern detector. The practicing high-energy experimentalist inevitably acquires an office cluttered with tapes and computer printouts, confering on the owner the image of a computer “hacker.”
Effects of the Modifiable Areal Unit Problem on the Delineation of Traffic Analysis Zones
Authors: Viegas José Manuel , Martinez L Miguel , Silva Elisabete A
Published: August 2008

Transportation analysis is typically thought of as one kind of spatial analysis. A major point of departure in understanding problems in transportation analysis is the recognition that spatial analysis has some limitations associated with the discretization of space. Among them, modifiable areal units and boundary problems are directly or indirectly related to transportation planning and analysis through the design of traffic analysis zones (TAZs). The modifiable boundary and the scale issues should all be given specific attention during the specification of a TAZ because of the effects these factors exert on statistical and mathematical properties of spatial patterns (ie the modifiable areal unit problem—MAUP). The results obtained from the study of spatial data are not independent of the scale, and the aggregation effects are implicit in the choice of zonal boundaries. The delineation of zonal boundaries of TAZs has a direct impact on the reality and accuracy of the results obtained from transportation forecasting models. In this paper the MAUP effects on the TAZ definition and the transportation demand models are measured and analyzed using different grids (in size and in origin location). This analysis was developed by building an application integrated in commercial GIS software and by using a case study (Lisbon Metropolitan Area) to test its implementabiity and performance. The results reveal the conflict between statistical and geographic precision, and their relationship with the loss of information in the traffic assignment step of the transportation planning models.
PTEN-deficient cancers depend on PIK3CB
Authors: Wee Susan , Wiederschain Dmitri , Maira Sauveur-Michel , Loo Alice , Miller Christine , deBeaumont Rosalie , Stegmeier Frank , Yao Yung-Mae , Lengauer Christoph
Published: August 2008

Deregulation of the PI3K signaling pathway is observed in many human cancers and occurs most frequently through loss of PTEN phosphatase tumor suppressor function or through somatic activating mutations in the Class IA PI3K,
PIK3CA
. Tumors harboring activated p110α, the protein product of
PIK3CA
, require p110α activity for growth and survival and hence are expected to be responsive to inhibitors of its lipid kinase activity. Whether PTEN-deficient cancers similarly depend on p110α activity to sustain activation of the PI3K pathway has been unclear. In this study, we used a single-vector lentiviral inducible shRNA system to selectively inactivate the three Class IA PI3Ks,
PIK3CA
,
PIK3CB
, and
PIK3CD
, to determine which PI3K isoforms are responsible for driving the abnormal proliferation of PTEN-deficient cancers. Down-regulation of
PIK3CA
in colorectal cancer cells harboring mutations in
PIK3CA
inhibited downstream PI3K signaling and cell growth. Surprisingly,
PIK3CA
depletion affected neither PI3K signaling nor cell growth in 3 PTEN-deficient cancer cell lines. In contrast, down-regulation of the
PIK3CB
isoform, which encodes p110β, resulted in pathway inactivation and subsequent inhibition of growth in both cell-based and
in vivo
settings. This essential function of
PIK3CB
in PTEN-deficient cancer cells required its lipid kinase activity. Our findings demonstrate that although p110α activation is required to sustain the proliferation of established
PIK3CA
-mutant tumors, PTEN-deficient tumors are dependent instead on p110β signaling. This unexpected finding demonstrates the need to tailor therapeutic approaches to the genetic basis of PI3K pathway activation to achieve optimal treatment response.
The supramolecular organization of self-assembling chlorosomal bacteriochlorophyll
c
,
d
, or
e
mimics
Authors: Jochum Tobias , Reddy Chilla Malla , Eichhöfer Andreas , Buth Gernot , Szmytkowski Jȩdrzej , Kalt Heinz , Moss David , Balaban Teodor Silviu
Published: August 2008

Bacteriochlorophylls (BChls)
c
,
d
, and
e
are the main light-harvesting pigments of green photosynthetic bacteria that self-assemble into nanostructures within the chlorosomes forming the most efficient antennas of photosynthetic organisms. All previous models of the chlorosomal antennae, which are quite controversially discussed because no single crystals could be grown so far from these organelles, involve a strong hydrogen-bonding interaction between the 3
1
hydroxyl group and the 13
1
carbonyl group. We have synthesized different self-assemblies of BChl
c
mimics having the same functional groups as the natural counterparts, that is, a hydroxyethyl substituent, a carbonyl group and a divalent metal atom ligated by a tetrapyrrole. These artificial BChl mimics have been shown by single crystal x-ray diffraction to form extended stacks that are packed by hydrophobic interactions and in the absence of hydrogen bonding. Time-resolved photoluminescence proves the ordered nature of the self-assembled stacks. FT-IR spectra show that on self-assembly the carbonyl frequency is shifted by ≈30 cm
−1
to lower wavenumbers. From the FT-IR data we can infer the proximal interactions between the BChls in the chlorosomes consistent with a single crystal x-ray structure that shows a weak electrostatic interaction between carbonyl groups and the central zinc atom.
Differential loss of embryonic globin genes during the radiation of placental mammals
Authors: Opazo Juan C. , Hoffmann Federico G. , Storz Jay F.
Published: August 2008

The differential gain and loss of genes from homologous gene families represents an important source of functional variation among the genomes of different species. Differences in gene content between species are primarily attributable to lineage-specific gene gains via duplication and lineage-specific losses via deletion or inactivation. Here, we use a comparative genomic approach to investigate this process of gene turnover in the β-globin gene family of placental mammals. By analyzing genomic sequence data from representatives of each of the main superordinal clades of placental mammals, we were able to reconstruct pathways of gene family evolution during the basal radiation of this physiologically and morphologically diverse vertebrate group. Our analysis revealed that an initial expansion of the nonadult portion of the β-globin gene cluster in the ancestor of placental mammals was followed by the differential loss and retention of ancestral gene lineages, thereby generating variation in the complement of embryonic globin genes among contemporary species. The sorting of ε-, γ-, and η-globin gene lineages among the basal clades of placental mammals has produced species differences in the functional types of hemoglobin isoforms that can be synthesized during the course of embryonic development.
Discordant on/off switching of gene expression in myocytes during cardiac hypertrophy
in vivo
Authors: Pandya Kumar , Cowhig John , Brackhan Joe , Kim Hyung Suk , Hagaman John , Rojas Mauricio , Carter Charles W. , Mao Lan , Rockman Howard A. , Maeda Nobuyo , Smithies Oliver
Published: August 2008

To determine whether the expression of cardiac genes changes in a graded manner or by on/off switching when cardiac myocytes change genetic programs in living animals, we have studied two indicator genes that change their expression oppositely in mouse binucleate ventricular cardiomyocytes during development and in response to cardiac hypertrophy. One is a single-copy transgene controlled by an α-myosin heavy chain (aMHC) promoter and coding for CFP. The other is the endogenous β-myosin heavy chain (bMHC) gene modified to code for a YFP–bMHC fusion protein. Using high-resolution confocal microscopy, we determined the expression of the two indicator genes in individual cardiomyocytes perinatally and after inducing cardiac hypertrophy by transverse aortic constriction. Our results provide strong evidence that the cardiac genes respond by switching their expression in an on/off rather than graded manner, and that responding genes within a single cell and within the two nuclei of cardiomyocytes do not necessarily switch concordantly.
Cross-regulatory protein–protein interactions between Hox and Pax transcription factors
Authors: Plaza Serge , Prince Frederic , Adachi Yoshitsugu , Punzo Claudio , Cribbs David L. , Gehring Walter J.
Published: August 2008

Homeotic
Hox
selector genes encode highly conserved transcriptional regulators involved in the differentiation of multicellular organisms. Ectopic expression of the Antennapedia (ANTP) homeodomain protein in
Drosophila
imaginal discs induces distinct phenotypes, including an antenna-to-leg transformation and eye reduction. We have proposed that the eye loss phenotype is a consequence of a negative posttranslational control mechanism because of direct protein–protein interactions between ANTP and Eyeless (EY). In the present work, we analyzed the effect of various ANTP homeodomain mutations for their interaction with EY and for head development. Contrasting with the eye loss phenotype, we provide evidence that the antenna-to-leg transformation involves ANTP DNA-binding activity. In a complementary genetic screen performed in yeast, we isolated mutations located in the N terminus of the ANTP homeodomain that inhibit direct interactions with EY without abolishing DNA binding
in vitro
and
in vivo
. In a bimolecular fluorescence complementation assay, we detected the ANTP–EY interaction
in vivo
, these interactions occurring through the paired domain and/or the homeodomain of EY. These results demonstrate that the homeodomain supports multiple molecular regulatory functions in addition to protein–DNA and protein–RNA interactions; it is also involved in protein–protein interactions.
B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients
Authors: Gavanescu Irina , Benoist Christophe , Mathis Diane
Published: August 2008

Autoimmune regulator (Aire)-deficient mice and humans have circulating autoantibodies against a multitude of organs and multiorgan autoinflammatory infiltrates. It is not known to what extent autoantibodies or their source, B lymphocytes, are required for disease onset or progression. We show in this research that B cells must be present for Aire-deficient mice to develop fulminant infiltrates. We found no evidence that autoantibodies were directly pathogenic; rather, B cells appeared to play a critical early role in T cell priming or expansion. A therapeutic reagent directed against B cells, Rituximab, induced remission of the autoimmune disease in Aire-deficient mice, raising the hope of applying it to human patients with autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).
Return To Oz
Authors: Mortimer John
Published: August 2008

John Mortimer took on the most infamous obscenity cases of the 1970s. He talks to Index about defending the editors of Oz magazine
Reality of Extremes
Authors: Malik Sabin
Published: August 2008

The government’s agenda for tackling extremism is missing its target audience, says Sabin Malik. It’s time to start listening
Big Chill
Authors: Watson Richard
Published: August 2008

Current legislation places journalists in an impossible position, writes Richard Watson
Drawing the Line
Authors: McNulty Tony
Published: August 2008

Government does not outlaw thought, says Tony McNulty, only actions
(2R,3aR,4S,7R,7aS,9R,10aR,11S,14R,14aS)-rel-3a,4,7,7a,10a,11,14,14a-Octahydro-4,14:7,11-diepoxy-2,9-propanonaphtho[1,2-f:5,6-f′]diisoindole-1,3,8,10-tetrone (9CI): a cyclophane derived from naphtho[1,2-c:5,6-c]difuran
Authors: Thibault Michelle E. , Parvez Masood , Dibble Peter W.
Published: August 2008

The title compound, C25H18N2O6, is a naphthalenophane styled in the manner of Warrener's alicyclic cyclophanes or molecular racks wherein a trimethylene tether is perfectly staggered between the two N atoms such that the central methylene H atoms point toward the naphthalene π-system. The dihedral angle between the mean planes of the two benzene rings is 7.61 (7)°.
Natural perovskite: (CaII
0.95 (1)CeIII
0.011 (2)NaI
0.010 (4))(FeIII
0.022 (2)TiIV
0.98 (1))O3
Authors: Gravina Érica G. , Ayala José D. , Fernandes Nelson G.
Published: August 2008

A natural sample of perovskite (calcium caesium sodium iron titanium oxide) from the Tapira Alkaline Complex in southeastern Brazil was found by electron microprobe analysis to have the chemical formula (Ca2+
0.95 (1)Ce3+
0.011 (2)Na+
0.010 (4))(Fe3+
0.022 (2)Ti4+
0.98 (1))O2−
3 and by IR spectroscopy to be an anhydrous mineral. Oxygen anions are arranged around Ti4+ in an almost perfect octahedron and around Ca2+ in a distorted 12-fold polyhedron.
Poly[[tetraaqua(μ6-2,2′-diiodobiphenyl-4,4′,5,5′-tetracarboxylato)dizinc(II)] dihydrate]
Authors: Wang Yan , Li Yue-Qin , Shen Ying-Zhong
Published: August 2008

In the title compound, {[Zn2(C16H4I2O8)(H2O)4]·2H2O}
n
, two crystallographically independent ZnII atoms are each located on a twofold rotation axis. Both ZnII atoms are in distorted octahedral coordination geometries: one is coordinated by six O atoms from four carboxylate groups, while the other is coordinated by two carboxylate groups and four water molecules. The tetracarboxylate ligand molecules connect the ZnII atoms, completing a three-dimensional metal–organic framework. O—H...O hydrogen bonds link the metal–organic framework with the uncoordinated water molecules.
(E)-3-(2,3-Dimethoxyphenyl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one
Authors: Escobar Carlos A. , Vega Andrés , Sicker Dieter , Ibañez Andrés
Published: August 2008

The molecular conformation of the title compound, C18H18O5, is stabilized by a strong intramolecular hydrogen bond between the hydroxyl and carbonyl groups. The C=C double bond displays an E configuration while the carbonyl group shows an S-cis configuration relative to the double bond. The dihedral angle between the two rings is 15.0 (1)°.
(3S,4S,5S)-4-Hydroxy-3-methyl-5-[(2S,3R)-3-methylpent-4-en-2-yl]-4,5-dihydrofuran-2(3H)-one
Authors: Gille Annika , Schürmann Markus , Preut Hans , Hiersemann Martin
Published: August 2008

The title compound, C11H18O3, was synthesized to prove the relative configuration of the corresponding acyclic C1—C8 stereopentade. Molecules are linked via O—H...O hydrogen bonds, forming a chain along the b axis.
catena-Poly[[aqua(pyrazino[2,3-f][1,10]phenanthroline-κ2
N
8,N
9)cobalt(II)]-μ-pyrazine-2,3-dicarboxylato-κ3
N
1
O
2:O
3]
Authors: Xu Zhan-Lin , Li Xiu-Ying , Che Guang-Bo , Lu Lu , Xu Chun-Hui
Published: August 2008

In the title compound, [Co(C6H2N2O4)(C14H8N4)(H2O)]
n
, the Co atom is bonded to one N,N′-bidentate pyrazino[2,3-f][1,10]phenanthroline (Pyphen) ligand, one N,O-bidentate pyrazine-2,3-dicarboxylate (PZDC) dianion and one water molecule in a distorted octahedral mer-CoN3O3 geometry. The CoII atoms are bridged by the PZDC dianions, forming an infinite one-dimensional chain running along the b axis. Adjacent chains pack together through π–π stacking interactions [centroid–centroid separations = 3.498 (4) and 3.528 (4) Å], and O—H...O and O—H...N hydrogen bonds involving the water molecule complete the structure.
2-[2-Chloro-5-(trifluoromethyl)phenyl]hexahydropyrimidine monohydrate
Authors: Fun Hoong-Kun , Kia Reza
Published: August 2008

The molecule of the title compound, C11H12ClF3N2·H2O, is a substituted hexahydropyrimidine. There are two crystallographically independent molecules (A and B) and two water molecules in the asymmetric unit of the title compound. Intermolecular C—H...Cl (× 2), C—H...F, and C—H...N (× 2) hydrogen bonds generate S(5) ring motifs. The dihedral angle between the two benzene rings is 8.17 (11)°. The F atoms in molecule B are disordered over four positions with refined site-occupancies of ca 0.35/0.19/0.29/0.17 for the four components. In the crystal structure, molecules are arranged into one-dimensional extended chains along the c axis and are further stacked along the a axis by directed four-membered O—H...O—H interactions, forming two-dimensional networks parallel to the ac plane. The short distances between the centroids of the benzene rings (3.8002–3.8327 Å) indicate the existence of π–π interactions. In addition, the crystal structure is further stabilized by N—H...O, O—H...N (× 4), N—H...Cl and C—H...O (× 2) hydrogen-bonding interactions.
9-(4-Fluorophenyl)-3,3,6,6-tetramethyl-10-p-tolyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione
Authors: Tang Ziqiang , Liu Changning , Wu Shanshan , Hao Wenjuan
Published: August 2008

The title compound, C30H32FNO2, was synthesized by the reaction of dimedone with 4-fluorobenzaldehyde and p-toluidine in water. The dihydropyridine and both of the cyclohexenone rings are not planar and have flattened boat conformations. The dihedral angle between the planar aromatic rings is 15.33 (3)°. In the crystal structure, intermolecular C—H...O hydrogen bonds link the molecules into centrosymmetric dimers.
2,5-Dibromoterephthalic acid dihydrate
Authors: Song Guang-Liang , Liu Shan , Liu Hua-Jun , Zeng Tao , Zhu Hong-Jun
Published: August 2008

The asymmetric unit of the title compound, C8H4Br2O4·2H2O, contains one half-molecule of 2,5-dibromoterephthalic acid (DBTA) and one water molecule. The DBTA molecule is centrosymmetric. In the crystal structure, intermolecular O—H...O hydrogen bonds link the molecules, forming a three-dimensional framework.
S-Benzylthiouronium 4-anilinobenzenesulfonate
Authors: Fun Hoong-Kun , Chantrapromma Suchada , D'Silva E. Deepak , Patil P. S. , Dharmaprakash S. M.
Published: August 2008

In the title compound, C8H11N2S+·C12H10NO3S−, the NH group of the S-benzylthiuronium is protonated and the interplanar angle between the phenyl ring and the CH2—S=C(NH2)2 unit is 47.44 (10)°. In the 4-anilinobenzenesulfonate anion, the interplanar angle between the two rings is 44.07 (8)°. In the crystal structure, anions are linked into chains along the c-axis direction by N—H...O hydrogen bonds, while additional N—H...O interactions link the cations to the anions in chains along the b-axis direction. These chains are further interconnected into a two-dimensional network parallel to the bc plane by C—H...O interactions. C—H...π contacts are also observed.
2,6-Diaminopyridinium bis(4-hydroxypyridine-2,6-dicarboxylato-κ3
O
2,N,O
6)chromate(III) dihydrate
Authors: Aghabozorg Hossein , Roshan Leila , Firoozi Najmeh , Ghadermazi Mohammad , Bagheri Sara
Published: August 2008

The reaction of chromium(III) nitrate hexahydrate, pyridine-2,6-diamine and 4-hydroxypyridine-2,6-dicarboxylic acid in a 1:2:2 molar ratio in aqueous solution resulted in the formation of the title compound, (C5H8N3)[Cr(C7H3NO5)2]·2H2O or (pydaH)[Cr(hypydc)2]·2H2O (where pyda is pyridine-2,6-diamine and hypydcH2 is 4-hydroxypyridine-2,6-dicarboxylic acid). Each CrIII atom is hexacoordinated by four O and two N atoms from two (hypydc)2− fragments, which act as tridentate ligands, in a distorted octahedral geometry. The O—Cr—O—C torsion angles between the two planes of the (hypydc)2− fragments [−99.81 (17) and 97.77 (17)°] indicate that these two units are almost perpendicular to one another. In the crystal structure, extensive O—H...O, N—H...O and C—H...O hydrogen bonds with D...A distances ranging from 2.560 (2) to 3.279 (3) Å, ion pairing, C—O...π [O...π = 3.166 (2) Å] and π–π stacking interactions between (hypydc)2− and (pydaH)+ rings [with a centroid–centroid distance of 3.3353 (14) Å] contribute to the formation of a three-dimensional supramolecular structure.
Bis(3-bromomethyl-2-methoxy-1-naphthyl)methane
Authors: Luo Jie-Wei , Zhou Li , He Rui , Wang Gui-Yu , Qin Da-Bin
Published: August 2008

The title compound, C25H22Br2O2, crystallizes with two molecules in the asymmetric unit. In each independent molecule, the two naphthalene ring systems are nearly perpendicular to one another, with dihedral angles of 85.6 (1) and 86.2 (1)°. The crystal structure is stabilized by C—H...π interactions, and inter- and intramolecular C—H...O and C—H...Br hydrogen bonds.
Population pharmacokinetics of oral diclofenac for acute pain in children
Authors: Standing Joseph F. , Howard Richard F. , Johnson Atholl , Savage Imogen , Wong Ian C. K.
Published: August 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Diclofenac is an effective oral analgesic for acute postoperative pain. In adults 25 mg is half as effective as 50 mg, but 50 mg and 100 mg are similarly effective (ceiling effect). Diclofenac has linear pharmacokinetics in this range.

• Diclofenac is frequently used ‘off‐label’ in children for acute pain but optimum dosing is unclear (dosing of diclofenac in clinical paediatric studies ranges from 0.5–2.5 mg kg−1). There is currently no licensed oral paediatric formulation of diclofenac.

WHAT THIS STUDY ADDS

• Using a new diclofenac oral suspension, a dose of 1 mg kg−1 in children aged 1 to 12 years gives a similar exposure to 50 mg in adults; paediatric patients are unlikely to benefit from higher doses.

AIMS

To develop a population pharmacokinetic model for a new diclofenac suspension (50 mg 5 ml−1) in adult volunteers and paediatric patients, and recommend a dose for acute pain in children.

METHODS

Blood samples were drawn at the start and end of surgery, and on removal of the venous cannula from 70 children (aged 1 to 12 years, weight 9 to 37 kg) who received a preoperative oral 1 mg kg−1 dose; these were pooled with rich (14 post‐dose samples) data from 30 adult volunteers. Population pharmacokinetic modelling was undertaken with NONMEM. The optimum adult dose of diclofenac for acute pain is 50 mg. Simulation from the final model was performed to predict a paediatric dose to achieve a similar AUC to 50 mg in adults.

RESULTS

A total of 558 serum diclofenac concentrations from 100 subjects was used in the pooled analysis. A single disposition compartment model with first order elimination and dual absorption compartments was used. The estimates of CL/F and VD/F were 53.98 l h−1 70 kg−1 and 4.84 l 70 kg−1 respectively. Allometric size models appeared to predict adequately changes in CL and VD with age. Of the simulated doses investigated, 1 mg kg−1 gave paediatric AUC(0,12 h) to adult 50 mg AUC(0,12 h) ratios of 1.00, 1.08 and 1.18 for ages 1–3, 4–6 and 7–12 years respectively.

CONCLUSIONS

This study has shown 1 mg kg−1 diclofenac to produce similar exposure in children aged 1 to 12 years as 50 mg in adults, and is acceptable for clinical practice; patients are unlikely to obtain further benefit from higher doses.
Public awareness and views on unlicensed use of medicines in children
Authors: Mukattash T. L. , Millership J. S. , Collier P. S. , McElnay J. C.
Published: August 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• There is increasing concern about the use of those medicines in children which have not been fully studied and licensed for childhood use. Such use is not uncommon, due in large part to a lack of availability of fully licensed products and formulations that are suitable for children.

• There is little published information on the views of the public on this important area of paediatric care.

WHAT THIS STUDY ADDS

• A survey of 1000 members of the public in Northern Ireland indicated that such use of medicines in children is not well known.

• However, when informed about this practice, the majority believed that it would compromise safety and increase the likelihood of adverse effects. They also believed that parents/guardians should be told if their child was prescribed a medicine that had not been fully tested in children.

• Participants in the survey indicated that they would be reluctant to involve their child in a clinical trial to help with the licensing process unless the child was suffering from a life‐threatening illness.

AIMS

To explore awareness and views of the general public on unlicensed use of medicines in children and on the participation of children in clinical trials.

METHODS

Members of the public completed a questionnaire survey administered by face‐to‐face interview in public areas in N. Ireland. The main outcome measures were the views on unlicensed use of medicines in children and on clinical trials in children.

RESULTS

One thousand participants (59.2% female) took part; 610 were parents. Most participants (86%) had no previous knowledge about unlicensed use of medicines in children. Being a parent did not influence this nor did being a parent of a child who suffered from a health problem (P > 0.05). Most participants (92%) felt that parents should be told about unlicensed use of medicines, with the doctor most frequently selected as the person who should inform parents. At the outset, only 1.8% of participants felt that the use of medicines in children was unsafe. However, having been informed about unlicensed use of medicines, this proportion increased dramatically (62.4%; P < 0.001). Views on whether participants would enter a child of their own into a clinical trial varied according to the health status of the child (P < 0.05) i.e. a child in good health (3.9%) vs a child with a life‐threatening condition (41.9%).

CONCLUSIONS

There is limited public knowledge of unlicensed use of medicines in children and a general reluctance to involve children in clinical trials unless the child to be involved has a life‐threatening condition.
Predictive factors for generalized seizures after deliberate citalopram overdose
Authors: Waring W. Stephen , Gray Julie A. , Graham Ann
Published: August 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Citalopram is a common means of self‐poisoning in young adults.

• Generalized seizures are a recognised complication after selective serotonin reuptake inhibitor overdose (including citalopram overdose).

WHAT THIS STUDY ADDS

• The minimum stated citalopram dose associated with seizures in the absence of co‐ingested drugs was 400 mg.

• Co‐ingestion of a tricyclic antidepressant or venlafaxine confers a 15‐fold increased risk of seizures.

AIMS

Seizures are a recognized complication of citalopram overdose. The present study sought to establish risk factors for seizures in this high‐risk patient group, including stated dose ingested, co‐ingested drugs or ethanol, and electrolyte disturbances.

METHODS

A retrospective casenote review was carried out of patients who attended the Emergency Department due to citalopram overdose between January 2000 and July 2007 inclusive. Stepwise logistic regression analysis considered age, gender, stated citalopram dose, acute ethanol consumption, co‐ingested drugs, administration of activated charcoal, and hyponatraemia.

RESULTS

There were 241 patients (177 women), and the median (interquartile range) stated citalopram dose was 300 mg (200 to 600 mg). Generalized seizures occurred in 18 patients (7.5%). Logistic regression analysis found co‐ingested tricyclic antidepressants or venlafaxine predicted seizures with odds ratio = 15 (95% confidence interval 3, 75). In the absence of co‐ingested drugs, the minimum citalopram dose associated with seizures was 400 mg. Odds ratio for seizures = 1.1 (95% confidence interval 1.0, 1.2) for every 100 mg increment in citalopram dose. Seizures were associated with a greater need for invasive ventilatory support, higher creatine kinase activity, and prolonged hospital stay.

CONCLUSIONS

Generalized seizures are an important manifestation of citalopram toxicity, and cannot be explained solely by electrolyte disturbances or co‐ingestion of other drugs or ethanol. The strongest predictors of seizures in this patient series were ingestion of high citalopram dosages and co‐ingestion of drugs capable of lowering seizure threshold.
Involvement of human ORC and TRF2 in pre‐replication complex assembly at telomeres
Authors: Tatsumi Yasutoshi , Ezura Kai , Yoshida Kazumasa , Yugawa Takashi , Narisawa‐Saito Mako , Kiyono Tohru , Ohta Satoshi , Obuse Chikashi , Fujita Masatoshi
Published: August 2008

The origin recognition complex (ORC) binds to replication origins to regulate the cell cycle‐dependent assembly of pre‐replication complexes (pre‐RCs). We have found a novel link between pre‐RC assembly regulation and telomere homeostasis in human cells. Biochemical analyses showed that human ORC binds to TRF2, a telomere sequence‐binding protein that protects telomeres and functions in telomere length homeostasis, via the ORC1 subunit. Immunostaining further revealed that ORC and TRF2 partially co‐localize in nuclei, whereas chromatin immunoprecipitation analyses confirmed that pre‐RCs are assembled at telomeres in a cell cycle‐dependent manner. Over‐expression of TRF2 stimulated ORC and MCM binding to chromatin and RNAi‐directed TRF2 silencing resulted in reduced ORC binding and pre‐RC assembly at telomeres. As expected from previous reports, TRF2 silencing induced telomere elongation. Interestingly, ORC1 silencing by RNAi weakened the TRF2 binding as well as the pre‐RC assembly at telomeres, suggesting that ORC and TRF2 interact with each other to achieve stable binding. Furthermore, ORC1 silencing also resulted in modest telomere elongation. These data suggest that ORC might be involved in telomere homeostasis in human cells.
Prophylaxis in von Willebrand disease
Authors: BERNTORP E.
Published: August 2008

Summary.  This paper reviews current issues regarding short‐term (i.e. for surgery and invasive procedures) and long‐term (i.e. regular infusions to prevent bleeding on a permanent or temporary basis) prophylaxis treatment using replacement concentrates for patients with von Willebrand disease (VWD) who do not respond satisfactorily to desmopressin. The standard treatment of these patients is with factor concentrates containing von Willebrand factor (VWF) and factor VIII (FVIII). When dosing these concentrates, the broad variations in content and quality of VWF as well as the FVIII content in the products should be considered. Peri‐operative management strategies will depend on the VWD subtype, baseline VWF and FVIII levels, and size of procedure. FVIII level and VWF ristocetin cofactor activity may both be used to determine concentrate potency and to monitor treatment. Long‐term prophylaxis, which has become a state‐of‐the‐art approach in haemophilia, is not very common in VWD. However, more recent data suggest that a substantial number of VWD patients could benefit from prophylactic treatment with VWF‐containing concentrates. For example, 35 Swedish VWD patients who required prophylaxis (mainly because of nose/mouth bleeds and joint bleeds) showed a substantial overall reduction in bleeding episodes and there were no signs of arthropathy in children who began prophylaxis before the age of 5 years since initiation of treatment with Haemate® P/Humate‐P®. Studies of prophylaxis in VWD are urgently needed to develop evidence‐based guidelines for this approach; the VWD International Prophylaxis study, for example, has commenced by the VWD Prophylaxis Network.
Pathogen safety of plasma‐derived products – Haemate® P/Humate‐P®
Authors: GRÖNER A.
Published: August 2008

Summary.  Plasma‐derived factor VIII (FVIII) and von Willebrand Factor (VWF)/FVIII concentrates have been successfully used to treat haemophilia since the late 1960s. These products are derived from pools of plasma donations that may contain viral contaminants – including hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) – and may therefore present a transmission risk to recipients. To ensure the safety of Haemate® P/Humate‐P®, a plasma‐derived VWF/FVIII concentrate, donors of plasma are carefully selected and all donations are screened for viral antigens (HBV), virus‐specific antibodies (HIV‐1/2, HCV) and genomic material [hepatitis A virus, HBV, HCV, HIV‐1 and high titres of human parvovirus B19 (B19V)]. As a quality control measure, plasma pools for fractionation are only released for further processing when non‐reactivity has been demonstrated in serological and genome amplification assays. The manufacturing process for plasma‐derived products, especially the fundamental procedure of pasteurization, is effective in inactivating and/or removing a wide variety of viruses that may potentially be present despite the screening process. This has been demonstrated in virus validation studies using a range of different viruses. New emerging infectious agents, including prions, which potentially pose a threat to recipients of plasma derivatives, are also the subject of safety evaluations. The multiple precautionary measures that are inherent in the overall production process of Haemate P/Humate‐P have resulted in an excellent safety record, documented during 25 years of clinical use, and will help to maintain the high safety margin in the future.
Transsplenic portal catheterization combined with a jugular double‐lumen catheter for pharmacokinetic and presystemic metabolization studies in pigs
Authors: GASTHUYS F. , DE BOEVER S. , SCHAUVLIEGE S. , REYNS T. , LEVET T. , CORNILLIE P. , CASTELEYN C. , DE BACKER P. , CROUBELS S.
Published: August 2008

The reliability of a silicone double‐lumen catheter implanted into the external jugular vein and tunnelled towards the neck region was investigated in eight pigs. Surgery was uneventful without interference with the normal homoeostasis during 8 days. After injection of amoxicillin/clavulanic acid through the distal port of the catheter, analysis of drug components in the simultaneous blood samples obtained by the proximal port and a Venoject®system were comparable in one pig. Histological control of the catheterized jugular veins pointed to an acceptable tissue reaction while bacteriological examination of the tip of the catheters was negative in only three animals. A moulding of the intestinal veins was made in a pig cadaver to determine the optimal length of insertion of a silicone portal catheter from the splenic vein towards the portal vein. Surgery was straightforward in four pigs whereby the catheter was exteriorized towards the back region. No complications were encountered during and after surgery for 9 days. The technique of a double‐lumen catheter placed into the jugular vein and a transsplenic portal catheter is a useful tool for the study of the pharmacokinetics and also the first‐pass effect of drugs in experimental pigs.