bluuebunny/crossref_metadata_2025 huggingface dataset:
Due Process and Fair Trial Rights at the Special Court: How the Desire for Accountability Outweighed the Demands of Justice at the Special Court for Sierra Leone
Authors: JORDASH WAYNE , MARTIN SCOTT
Published: July 2010

It was recognized that it was critical to the process of national reconciliation and the maintenance of peace in Sierra Leone that the Special Court for Sierra Leone (SCSL) be a strong and credible court operating in accordance with international standards of justice, fairness, and due process of law. This article assesses the fulfilment of this mandate through an examination of the fairness of the RUF trial as illustrated through two issues: the interpretation of the accused's right to be informed of the nature and cause of the charges and the approach taken by the Trial Chamber and the Appeals Chamber in assessing the evidential links between the accused and the crimes pursuant to the joint criminal enterprise (JCE) mode of liability. First, the article discusses the decisions that led to the omission of 250 charges from the indictment and their introduction into the trial through late evidential disclosures after the commencement of the prosecution case. Second, the article examines the way in which the charges, in a majority of cases, were found to be part of a common criminal purpose without a sufficient nexus being established to the accused or any member of the alleged JCE. The article concludes that the judicial approach to these issues abandoned the safeguards contained in the jurisprudence developed at the International Criminal Tribunal for the former Yugoslavia and the International Criminal Tribunal for Rwanda, giving rise to a trial that failed to adhere to international standards of justice, fairness, and due process, leading to manifestly unjust convictions.
Emergence of dengue virus type 4 (genotype I) in India
Authors: DASH P. K. , SHARMA S. , SRIVASTAVA A. , SANTHOSH S. R. , PARIDA M. M. , NEERAJA M. , SUBBALAXMI M. V. S. , LAKSHMI V. , RAO P. V. L.
Published: July 2010

Dengue is an emerging arboviral disease and currently poses the greatest arboviral threat to human health. In recent decades, there has been a substantial increase in dengue outbreaks in many parts of the world including India. We performed an in-depth investigation of a major dengue outbreak in Andhra Pradesh, southern India in 2007 by serology, virus isolation, RT–PCR and genotyping. The results revealed an unusual emergence of dengue virus type 4 (DENV-4) along with the prevailing DENV-3. Phylogenetic analysis based on complete envelope gene of 182 globally diverse DENV-4 isolates demonstrated the involvement of a unique clade of genotype I of DENV-4 in the outbreak. This study also demonstrated a clear shift in the dominant serotype from DENV-3 to DENV-4 in India. This is the first report regarding the molecular characterization of Indian isolates of DENV-4, which has the potential to be involved in future outbreaks.
Hierarchical Consequentialism
Authors: SEGEV RE'EM
Published: July 2010

The article considers a hierarchical theory that combines concern for two values: individual well-being – as a fundamental, first-order value – and (distributive) fairness – as a high-order value whose exclusive function is to complete the value of individual well-being by resolving internal clashes within it that occur in interpersonal conflicts. The argument for this unique conception of high-order fairness is that fairness is morally significant in itself only regardingwhat matters– individual well-being – andwhen it matters– in interpersonal conflicts in which constitutive aspects of individual well-being clash. Consequently, the proposed theory is not exposed to the claim that fairness comes at the expense of welfare. This theory is considered within a consequential framework, based on the standard version and, alternatively, on a novel interpretation of consequentialism. Thus, it refutes the claim that consequentialism does not take the distinction between persons seriously.
Seasonal and growth stage changes in lipid and fatty acid composition in the multigeneration copepodDrepanopus pectinatusfrom Iles Kerguelen
Authors: Mayzaud P. , Lacombre S. , Boutoute M.
Published: July 2010

Changes in adult weight, lipid and fatty acid composition per lipid class were studied over a complete seasonal cycle inDrepanopus pectinatusBrady. This copepod displayed a strong seasonality in adult individual weight and total lipid content. Stages C3 to adult from a summer cohort were compared in terms of lipid and fatty acid structure. Changes in lipid content were related to wax esters and polar lipids (PL) while triacylglycerols (TAG) and cholesterol remained minor constituents except at the end of winter. Changes in fatty acid composition of different lipid classes showed that food limitation in winter was high enough to affect 22:6n-3 (DHA) content in PL, and provoke accumulation of maximal percentages of bacterial marker as branched acids. Composition of TAG followed closely the changes in trophic interactions as diatom and flagellate markers dominated in spring and summer while bacterial and detritus particle markers dominated in late winter. The composition of wax esters followed the same seasonal succession but with a lower level of turn over time and shifted characteristics (bacterial markers) from winter to spring individuals when compared to TAG. Ontogenetic changes showed high triacylglycerols content in younger C3 stages and increasing wax esters with increasing developmental stages. Fatty acid composition of PL showed low percentages of EPA and DHA in stage C3, and recovery of high levels of DHA for stage C4 or 20:5n-3 (EPA) at stage C5. The same trend was observed for 18:4n-3. The reverse pattern was noted for the n-6 polyunsaturated acids (PUFA) suggesting a greater requirement in younger stages. Fatty acid partitioning between neutral and PL suggested essential fatty acids selective incorporation from neutral classes into membrane lipids.
CAPITALIZING R&D EXPENDITURES
Authors: Diewert W. Erwin , Huang Ning
Published: July 2010

The next international version of the System of National Accounts will recommend that R&D (Research and Development) expenditures be capitalized instead of being immediately expensed as in the present System of National Accounts 1993. An R&D project creates a new technology, which in principle does not depreciate like a reproducible asset. A new technology is, however, subject to obsolescence, which acts in a manner that is somewhat similar to depreciation. The paper looks at the net benefits of an R&D project in the context of a very simple intertemporal general equilibrium model and suggests that R&D expenditures be amortized using the matching principle that has been developed in the accounting literature to match the fixed costs of a project to a stream of future benefits. Of particular interest is the evaluation of the net benefits of a publicly funded project where the results are made freely available to the public.
Influence of Blue Light on the Leaf Morphoanatomy ofIn Vitro Kalanchoe pinnata(Lamarck) Persoon (Crassulaceae)
Authors: Leal-Costa Marcos Vinicius , Nascimento Luana Beatriz dos Santos , Moreira Nattacha dos Santos , Reinert Fernanda , Costa Sônia Soares , Lage Celso Luiz Salgueiro , Tavares Eliana Schwartz
Published: July 2010

Kalanchoe pinnata(Lamarck) Persoon (Crassulaceae) (air plant, miracle leaf) is popularly used to treat gastrointestinal disorders and wounds. Recently, the species was tested to treat cutaneous leishmaniasis with successful results. This medicinal activity was associated with the phenolic fraction of the plant. Blue light induces biosynthesis of phenolic compounds and many changes in anatomical characteristics. We studied the effects of supplementary blue light on the leaf morphology ofin vitro K. pinnata. Plants cultured under white light (W plants) only and white light plus blue light (WB plants) show petioles with plain-convex section, amphistomatic leaf blades with simple epidermis, homogeneous mesophyll with densely packed cells, and a single collateral vascular bundle in the midrib. W plants have longer branches, a larger number of nodes per branch, and smaller leaves, whereas WB plant leaves have a thicker upper epidermis and mesophyll. Leaf fresh weight and leaf dry weight were similar in both treatments. Phenolic idioblasts were observed in the plants supplemented with blue light, suggesting that blue light plays an important role in the biosynthesis of phenolic compounds inK. pinnata.
Atom Scale Characterization of the Near Apex Region of an Atomic Force Microscope Tip
Authors: Tourek Christopher J. , Sundararajan Sriram
Published: July 2010

Three-dimensional atom probe tomography (APT) is successfully used to analyze the near-apex regions of an atomic force microscope (AFM) tip. Atom scale material structure and chemistry from APT analysis for standard silicon AFM tips and silicon AFM tips coated with a thin film of Cu is presented. Comparison of the thin film data with that observed using transmission electron microscopy indicates that APT can be reliably used to investigate the material structure and chemistry of the apex of an AFM tip at near atomic scales.
HERMENEUTICS AND THE NEW FORMENLEHRE: AN INTERPRETATION OF HAYDN'S ‘OXFORD’ SYMPHONY, FIRST MOVEMENT
Authors: RILEY MATTHEW
Published: July 2010

This article establishes a dialogue between twenty-first-century music theory and historical modes of enquiry, adapting the new Formenlehre (Caplin, Hepokoski/Darcy) to serve a historically oriented hermeneutics. An analytical case study of the first movement of Haydn's Symphony No. 92 (1789) traces the changing functional meanings of the opening ‘caesura prolongation phrase’. The substance of the exposition consists largely of things functionally ‘before-the-beginning’ and ‘after-the-end’, while the recapitulation follows a logic of suspense and surprise, keeping the listener continually guessing. The analysis calls into question Hepokoski and Darcy's restriction of the mode of signification of sonata-form movements to the narration of human action. The primary mode of signification of the recapitulation is indexical: it stands as the effect of a human cause. This account matches late eighteenth-century concepts of ‘genius’.
Graphene production goes industrial
Authors: Wilson Mark
Published: July 2010

A method that efficiently produces rectangular films of graphene nearly a meter in diameter may chart a course to commercialization.
Enhanced magnetic moment in ErMnO3 by copper doping and negative magnetocapacitance effect
Authors: Liu P , Cheng Z X , Du Y , Wang X L
Published: July 2010

Single phase ErCu
x
Mn1−x
O3(0 ⩽ x ⩽ 0.1) compounds were prepared by the standard solid-state reaction. The doping effects on the crystal structure, magnetic properties and dielectric properties were systematically studied. X-ray diffraction patterns show that all samples are single phase and crystallized in a hexagonal structure belonging to the P63
cm space group. Rietveld refinement indicates that the
a
lattice parameter increases and the
c
lattice parameter decreases with increasing Cu concentration. The magnetic moments of the doped samples are enhanced, which is due to modification of the frustrated spin arrangement by the superexchange interaction between Cu2+ ions and Mn3+ ions. The specific heat capacity data show a peak at the antiferromagnetic transition temperature, which decreases from 77 K for x = 0 to 61 K for x = 0.1. The samples become more conductive upon doping, which is responsible for the increase in the dielectric constant. A large negative magnetocapacitance effect was observed in paramagnetic-state ErCu0.05Mn0.95O3 at 300 K.
Improving the interfacial structure of nanocomposite magnets on an atomic scale
Authors: Guo Defeng , Li Wei , Li Xiaohong , Chen Yan , Sato Kiminori , Zhang Xiangyi
Published: July 2010

We succeeded in improving the interfacial structure of α-Fe/Nd2Fe14B type nanocomposite magnets on an atomic scale using an intergranular amorphous phase. An enrichment of Fe atoms surrounding vacancy-type interfacial free volumes in the magnets is experimentally evidenced by positron lifetime measurements combined with a coincident Doppler broadening measurement of the positron–electron annihilation photons, whereas the interfacial free volumes in the common nanocomposite magnets are dominantly surrounded by non-magnetic Nd atoms. This study provides an experimental approach to enhance magnetic coupling between the hard and soft phases and thus is of considerable interest for the development of nanocomposite magnets.
Dual-role plasma absorption probe to study the effects of sheath thickness on the measurement of electron density
Authors: Li Bin , Li Hong , Chen Zhipeng , Xie Jinlin , Liu Wandong
Published: July 2010

A sensitive plasma absorption probe (PAP) is reported for measuring electron density in processing plasmas. The sheath formed around the probe tip is important for the resonance of surface waves. For determining the absolute electron density from the absorption frequency of the sensitive PAP, a proper value of sheath thickness relative to the Debye length is required to be assigned in the data processing. In this paper, a dual-role PAP has been proposed to study the effects of sheath thickness on the measurement of electron density. It is used as a Langmuir probe and a sensitive PAP simultaneously. Based on these two functions, the sheath thickness is calibrated before the measurement of electron density. The calibrated value is assigned in the data processing to replace the fitting coefficient used in the previous work. Therefore, the measurement error caused by an inaccurately assigned sheath thickness can be minimized effectively. Because of the bi-functional characteristic, the dual-role PAP is an independent diagnostic tool.
Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology
Authors: Delport Wayne , Poon Art F. Y. , Frost Simon D. W. , Kosakovsky Pond Sergei L.
Published: July 2010

Summary: Datamonkey is a popular web-based suite of phylogenetic analysis tools for use in evolutionary biology. Since the original release in 2005, we have expanded the analysis options to include recently developed algorithmic methods for recombination detection, evolutionary fingerprinting of genes, codon model selection, co-evolution between sites, identification of sites, which rapidly escape host-immune pressure and HIV-1 subtype assignment. The traditional selection tools have also been augmented to include recent developments in the field. Here, we summarize the analyses options currently available on Datamonkey, and provide guidelines for their use in evolutionary biology.

Availability and documentation:  http://www.datamonkey.org

Contact:  spond@ucsd.edu
Prediction of Specific Japanese Sponge Cake Volume Using Pasting Properties of Flour
Authors: Nakamura Kazuhiro , Taniguchi Yoshinori , Taira Masato , Ito Hiroyuki
Published: July 2010

In Japanese soft wheat (Triticum aestivum L.) breeding programs, protein content (PC), and specific surface area (SSA) of flour have been used as important factors for the baking quality of Japanese sponge cake. We proposed batter pasting viscosity (BPV) as a parameter to predict the baking quality of Japanese sponge cake. BPV was measured using a Rapid Visco‐Analyser (RVA) with a modified heating profile. Twenty soft wheat samples from the 2006‐07 season and 22 from the 2007‐08 season, including Japanese soft wheat cultivars, advanced breeders' lines, and Western White (WW) imported from the United States, were milled and evaluated for solvent retention capacity (SRC) values of four solvents, batter pasting properties, flour pasting properties, PC, SSA, and specific cake volume (SCV) to investigate their relationships. BPV was the most strongly correlated of the parameters to SCV (r = –0.90, P < 0.001). Stepwise multiple regression analysis selected BPV and minimum viscosity (MV) of flour pasting as significant independent variables to predict SCV (corrected R2 = 0.848). The variability in BPV related to cake batter expansion was highly explained by PC and sucrose SRC (corrected R2 = 0.854, P < 0.001). MV was correlated to SSA (r = 0.56, P < 0.001) and might be related to the prevention of sponge cake shrinkage during baking.
Turnip mosaic virus (TuMV) Is Able to Use Alleles of Both eIF4E and eIF(iso)4E from Multiple Loci of the Diploid Brassica rapa
Authors: Jenner Carol E. , Nellist Charlotte F. , Barker Guy C. , Walsh John A.
Published: July 2010

Three copies of eIF4E and three copies of eIF(iso)4E have been identified and sequenced from a Turnip mosaic virus (TuMV)-susceptible, inbred, diploid Brassica rapa line, R-o-18. One of the copies of eIF4E lacked exons 2 and 3 and appeared to be a pseudogene. The two other copies of eIF4E and two of the three copies of eIF(iso)4E were isolated from a bacterial artificial chromosome library of R-o-18. Using an Arabidopsis line (Col-0::dSpm) with a transposon knock-out of the eIF(iso)4E gene which resulted in a change from complete susceptibility to complete resistance to TuMV, complementation experiments were carried out with the two versions of eIF4E and the two versions of eIF(iso)4E. When transformed into Col-0::dSpm, all four Brassica transgenes complemented the Arabidopsis eIF(iso)4E knock-out, conferring susceptibility to both mechanical and aphid challenge with TuMV. One of the copies of eIF4E did not appear to support viral replication as successfully as the other copy of eIF4E or the two copies of eIF(iso)4E. The results show that TuMV can use both eIF4E and eIF(iso)4E from B. rapa for replication and, for the first time, that a virus can use eIF4E and eIF(iso)4E from multiple loci of a single host plant.
The Reemergence and Management of Currant Cane Dieback in the Northeastern United States
Authors: Singer Stacy D. , Cox Kerik D.
Published: July 2010

Currant cane dieback, caused by the fungus Botryosphaeria ribis (syn. Neofusicoccum ribis), devastated currant production in the northeastern United States approximately a century ago. Later epidemics of this disease were halted by bans on the planting of Ribes spp. to control white pine blister rust, but since regulations restricting the planting of currants were removed in the 1980s and 1990s, currant cane dieback has reemerged in the northeastern United States. In this study, we obtained fungal isolates from diseased canes at four production operations in New York and Connecticut. We confirmed the isolates as N. ribis on the basis of morphology and ribosomal DNA sequence analysis, and verified pathogenicity through inoculation of healthy currant bushes. Furthermore, field trials to study the effects of cultivar, pruning of symptomatic canes, and fungicide applications were conducted over 2 years. Differences in Ribes cultivar susceptibility to N. ribis were demonstrated, with a pink fruiting cultivar (Pink Champagne) having lower levels of dieback compared to two red cultivars (Rovada and Jonkheer van Tets) and one white cultivar (Blanka) evaluated. While there were no consistent reductions in cane dieback incidence over both years and for all cultivars when pruning or fungicide treatments (copper hydroxide and sulfur applications) were used alone, fungicide treatment combined with pruning resulted in significant (P < 0.05) reductions (>80%) in the incidence of dieback compared to bushes not treated with fungicide or pruned.
High degree of genetic diversity of non-polio enteroviruses identified in Georgia by environmental and clinical surveillance, 2002–2005
Authors: Khetsuriani N. , Kutateladze T. , Zangaladze E. , Shutkova T. , Peñaranda S. , Nix W. A. , Pallansch M. A. , Oberste M. S.
Published: July 2010

Enterovirus surveillance data are useful for establishing temporal and geographical patterns of circulation and for virus characterization to determine phylogenetic relationships between strains. Almost no information is available on circulating enteroviruses in Georgia and the surrounding region. To describe enterovirus circulation in Georgia, determine relationships with previously characterized strains and assess the role of environmental and clinical enterovirus surveillance, this study analysed a total of 112 non-polio enterovirus isolates identified during 2002–2005 from sewage and human stool samples. Viruses were isolated in cell culture using standard methods and typed by partial sequencing of the VP1 gene. A total of 20 different non-polio enterovirus serotypes were identified over the 4-year period. The most commonly detected enteroviruses included echovirus (E) 6 (21 isolates; 18.8 %), E20, E3 and E7 (11 isolates each; 9.8 %), E11, coxsackievirus (CV) B4 and CVB5 (seven isolates each; 6.3 %), and E13, E19 and E30 (six isolates each; 5.4 %). Phylogenetic analysis showed that many serotypes were represented by more than one genetic lineage. The present study showed a very high degree of enterovirus diversity in Georgia and demonstrated the added value of environmental enterovirus surveillance, particularly in settings with limited clinical surveillance. Several serotypes would not have been detected without having both clinical and environmental surveillance in place. Several serotypes detected in Georgia were among those rarely reported in the USA and Europe (e.g. E3, E20 and E19). As the emergence of new genetic lineages of enterovirus in a particular area is often associated with large-scale outbreaks, continued monitoring of enterovirus strains by both environmental and clinical surveillance and genetic characterization should be encouraged.
The shift from a response strategy to object-in-place strategy during learning is accompanied by a matching shift in neural firing correlates in the hippocampus
Authors: Lee Inah , Kim Jangjin
Published: July 2010

Hippocampal-dependent tasks often involve specific associations among stimuli (including egocentric information), and such tasks are therefore prone to interference from irrelevant task strategies before a correct strategy is found. Using an object-place paired-associate task, we investigated changes in neural firing patterns in the hippocampus in association with a shift in strategy during learning. We used an object-place paired-associate task in which a pair of objects was presented in two different arms of a radial maze. Each object was associated with reward only in one of the arms, thus requiring the rats to consider both object identity and its location in the maze. Hippocampal neurons recorded in CA1 displayed a dynamic transition in their firing patterns during the acquisition of the task across days, and this corresponded to a shift in strategy manifested in behavioral data. Specifically, before the rats learned the task, they chose an object that maintained a particular egocentric relationship with their body (response strategy) irrespective of the object identity. However, as the animal acquired the task, it chose an object according to both its identity and the associated location in the maze (object-in-place strategy). We report that CA1 neurons in the hippocampus changed their prospective firing correlates according to the dominant strategy (i.e., response versus object-in-place strategy) employed at a given stage of learning. The results suggest that neural firing pattern in the hippocampus is heavily influenced by the task demand hypothesized by the animal and the firing pattern changes flexibly as the perceived task demand changes.
Proper Levels of the Arabidopsis Cohesion Establishment Factor CTF7 Are Essential for Embryo and Megagametophyte, But Not Endosperm, Development
Authors: Jiang Ling , Yuan Li , Xia Ming , Makaroff Christopher A.
Published: July 2010

CTF7 is an essential gene in yeast that is required for the formation of sister chromatid cohesion. While recent studies have provided insights into how sister chromatid cohesion is established, less is known about how specifically CTF7 facilitates the formation of cohesion, and essentially nothing is known about how sister chromatid cohesion is established in plants. In this report, we describe the isolation and characterization of CTF7 from Arabidopsis (Arabidopsis thaliana). Arabidopsis CTF7 is similar to Saccharomyces cerevisiae CTF7 in that it lacks an amino-terminal extension, exhibits acetyltransferase activity, and can complement a yeast ctf7 temperature-sensitive mutation. CTF7 transcripts are found throughout the plant, with the highest levels present in buds. Seeds containing T-DNA insertions in CTF7 exhibit mitotic defects in the zygote. Interestingly, the endosperm developed normally in ctf7 seeds, suggesting that CTF7 is not essential for mitosis in endosperm nuclei. Minor defects were observed in female gametophytes of ctf7+/2 plants, and plants that overexpress CTF7 exhibited female gametophyte lethality. Pollen development appeared normal in both CTF7 knockout and overexpression plants. Therefore, proper levels of CTF7 are critical for female gametophyte and embryo development but not for the establishment of mitotic cohesion during microgametogenesis or during endosperm development.
Vernalization-Mediated VIN3 Induction Overcomes the LIKE-HETEROCHROMATIN PROTEIN1/POLYCOMB REPRESSION COMPLEX2-Mediated Epigenetic Repression
Authors: Kim Dong-Hwan , Zografos Brett R. , Sung Sibum
Published: July 2010

VERNALIZATION INSENSITIVE3 (VIN3) induction by vernalization is one of the earliest events in the vernalization response of Arabidopsis (Arabidopsis thaliana). However, the mechanism responsible for vernalization-mediated VIN3 induction is poorly understood. Here, we show that the constitutive repression of VIN3 in the absence of the cold is due to multiple repressive components, including a transposable element-derived sequence, LIKE-HETEROCHROMATIN PROTEIN1 and POLYCOMB REPRESSION COMPLEX2. Furthermore, the full extent of VIN3 induction by vernalization requires activating complex components, including EARLY FLOWERING7 and EARLY FLOWERING IN SHORT DAYS. In addition, we observed dynamic changes in the histone modifications present at VIN3 chromatin during the course of vernalization. Our results show that the induction of VIN3 includes dynamic changes at the level of chromatin triggered by long-term cold exposure.
Genome‐wide analysis of phenylpropanoid defence pathways
Authors: NAOUMKINA MARINA A. , ZHAO QIAO , GALLEGO‐GIRALDO LINA , DAI XINBIN , ZHAO PATRICK X. , DIXON RICHARD A.
Published: July 2010

Phenylpropanoids can function as preformed and inducible antimicrobial compounds, as well as signal molecules, in plant–microbe interactions. Since we last reviewed the field 8 years ago, there has been a huge increase in our understanding of the genes of phenylpropanoid biosynthesis and their regulation, brought about largely by advances in genome technology, from whole‐genome sequencing to massively parallel gene expression profiling. Here, we present an overview of the biosynthesis and roles of phenylpropanoids in plant defence, together with an analysis of confirmed and predicted phenylpropanoid pathway genes in the sequenced genomes of 11 plant species. Examples are provided of phylogenetic and expression clustering analyses, and the large body of underlying genomic data is provided through a website accessible from the article.
Synergistic and persistent effect of T‐cell immunotherapy with anti‐CD19 or anti‐CD38 chimeric receptor in conjunction with rituximab on B‐cell non‐Hodgkin lymphoma
Authors: Mihara Keichiro , Yanagihara Kazuyoshi , Takigahira Misato , Kitanaka Akira , Imai Chihaya , Bhattacharyya Joyeeta , Kubo Takanori , Takei Yoshifumi , Yasunaga Shin’ichiro , Takihara Yoshihiro , Kimura Akiro
Published: July 2010

Using artificial receptors, it is possible to redirect the specificity of immune cells to tumour‐associated antigens, which is expected to provide a useful strategy for cancer immunotherapy. Given that B‐cell non‐Hodgkin lymphoma (B‐NHL) cells invariably express CD19 and CD38, these antigens may be suitable molecular candidates for such immunotherapy. We transduced human peripheral T cells or a T‐cell line with either anti‐CD19‐chimeric receptor (CAR) or anti‐CD38‐CAR, which contained an anti‐CD19 or anti‐CD38 antibody‐derived single‐chain variable domain respectively. Retroviral transduction led to anti‐CD19‐CAR or anti‐CD38‐CAR expression in T cells with high efficiency (>60%). The T cell line, Hut78, when transduced with anti‐CD19‐CAR or anti‐CD38‐CAR, exerted strong cytotoxicity against the B‐NHL cell lines, HT and RL, and lymphoma cells isolated from patients. Interestingly, use of both CARs had an additive cytotoxic effect on HT cells in vitro. In conjunction with rituximab, human peripheral T cells expressing either anti‐CD19‐CAR or anti‐CD38‐CAR enhanced cytotoxicity against HT‐luciferase cells in xenografted mice. Moreover, the synergistic tumour‐suppressing activity was persistent in vivo for over 2 months. These results provide a powerful rationale for clinical testing of the combination of rituximab with autologous T cells carrying either CAR on aggressive or relapsed B‐NHLs.
Application of genomics for risk stratification of childhood acute lymphoblastic leukaemia: from bench to bedside?
Authors: Izraeli Shai
Published: July 2010

The remarkable progress in the treatment of childhood acute lymphoblastic leukaemia (ALL) has been based on the adjustment of therapy to subgroups of leukaemia stratified by their prognostic implications. Here, the contribution of the last decade of advanced genomic research on the clinical management of childhood ALL is examined. The application of genomics for routine diagnosis of ALL is feasible but depends on commercial development of appropriate certified platforms. The discovery of several novel high‐risk markers, such as deletions in IKZF1 might be integrated into clinical protocols in the near future. Several novel targets for therapy have been identified and have led to phase I/II therapeutic trials. This and any future progress depends on the maintenance of high quality bio‐banks including biological material and clinical data of each patient enrolled on a prospective clinical protocol.
Plasma levels of advanced glycation end products are associated with haemolysis‐related organ complications in sickle cell patients
Authors: Nur Erfan , Brandjes Dees P. , Schnog John‐John B. , Otten Hans‐Martin , Fijnvandraat Karin , Schalkwijk Casper G. , Biemond Bart J. ,   the CURAMA Study Group
Published: July 2010

Oxidative stress plays an important role in the pathophysiology of sickle cell disease (SCD). Plasma levels of advanced glycation end products (AGEs) are increased under oxidative conditions and are associated with disease severity in diabetes and inflammatory diseases. We investigated whether AGEs are increased in sickle cell patients and whether they are associated with SCD‐related complications. Plasma levels of the AGEs pentosidine, Nε‐(carboxymethyl)lysine (CML) and Nε‐(carboxyethyl)lysine (CEL) were measured using single‐column high performance liquid chromatography with fluorescence detection (pentosidine) and ultra performance liquid chromatography‐tandem mass spectrometry (CML and CEL). Plasma levels of pentosidine and CML were increased in HbSS/HbSβ0‐thalassaemia (n = 60) and HbSC/HbSβ+‐thalassaemia (n = 42) patients during steady state as compared to healthy HbAA controls (n = 30) without increments during painful crisis. CEL levels were comparable between all groups. Pentosidine and CML levels correlated significantly to haemolytic rate during the clinically asymptomatic state while pentosidine was significantly related to the number of haemolysis‐related organ complications. The increased plasma AGE levels in sickle cell patients and their association with haemolysis and haemolysis‐related complications suggest AGEs might be implicated in the pathophysiology of the haemolytic phenotype of SCD. Measurement of AGEs might be useful in predicting organ complications in SCD.
CD200R1 regulates the severity of arthritis but has minimal impact on the adaptive immune response
Authors: Šimelyte E , Alzabin S , Boudakov I , Williams R
Published: July 2010

CD200R1 is a member of the immunoglobulin supergene family that is thought to play an inhibitory role in immunity. Previous studies have established the anti-arthritic effect of CD200Fc, an agonist of CD200R1. However, the physiological role played by CD200R1 in arthritis remains to be established. The aims of this study are to assess the contribution of endogenous CD200R1 in regulating the severity of arthritis and to determine its role in shaping the immune response to type II collagen within the context of collagen-induced arthritis, an animal model of rheumatoid arthritis. Arthritis was induced in DBA/1 mice by immunization with type II collagen and the kinetics of expression of CD200R1 and CD200 were monitored by quantitative reverse transcription–polymerase chain reaction. Next, a comparison was made between CD200R1−/− and wild-type mice in terms of the progression of collagen-induced arthritis, as well as the B and T cell responses to type II collagen. The expression of both CD200R1 and CD200 was increased after immunization and reached maximal levels at the height of the inflammatory response. In addition, the severity of arthritis was increased significantly in CD200R1−/− mice compared to wild-type mice. However, little or no differences were observed between CD200R1−/− and wild-type mice in terms of the T or B cell responses to type II collagen. It was concluded that the CD200R1/CD200 pathway is up-regulated in arthritis and plays a significant physiological role in regulating the severity of disease. In contrast, CD200R1 plays a minimal role in shaping the immune response to collagen in this model.
Non‐obese early onset diabetes mellitus in mutant cryptochrome1 transgenic mice
Authors: Okano Satoshi , Hayasaka Kiyoshi , Igarashi Masahiko , Iwai Harue , Togashi Yoshiyuki , Nakajima Osamu
Published: July 2010

Eur J Clin Invest 2010; 40 (11): 1011–1017

Background  An earlier report described that transgenic mice ubiquitously expressing cryptochrome1 (CRY1) with a mutation in cystein414 (CRY1‐AP Tg mice) display diabetes mellitus in addition to anomalous circadian behaviours. This study examined characteristic aspects of symptoms to clarify the diabetes type and pathogenesis.

Materials and methods  The body weights and blood glucose levels of CRY1‐AP Tg mice were measured for 7 weeks starting at 3 weeks after birth. Glucose tolerance test for the mice of various ages and insulin tolerance test at 6 weeks of age were conducted. Immunohistochemical analysis of islets was carried out for the mice of 19 and 40 weeks of age. Basal and glucose‐stimulated serum insulin levels of mice at 27 weeks were also measured.

Results  Three‐week‐old CRY1‐AP Tg mice, which showed mild retardation in growth, already displayed glucose intolerance. Hyperglycaemia progressed with age, without accompanying insulin resistance. Insulin‐stained areas in islets in CRY1‐AP Tg mice were smaller than that in wild‐type controls. Both basal and glucose‐stimulated secretion of insulin decreased in CRY1‐AP Tg mice.

Conclusion  The symptoms of diabetes in CRY1‐AP Tg mice turned out to be similar to those of maturity onset diabetes of the young (MODY) in humans in terms of early onset, non‐obesity and primary dysfunction of beta cells. The CRY1‐AP Tg mice might serve as an animal model of early onset insulin‐secretory defect of diabetes.
Item response modelling for clinical and laboratory testing
Authors: Cleophas Ton J. , Zwinderman Aeilko H.
Published: July 2010

Eur J Clin Invest 2010; 40 (10): 911–917

Background  Item response models using exponential modelling are more sensitive than classical linear methods for making predictions from psychological questionnaires.

Objective  To assess whether they can also be used for making predictions from quality of life questionnaires and clinical and laboratory diagnostic‐tests.

Methods  Of 1000 anginal patients assessed for quality of life and 1350 patients assessed for peripheral vascular disease with diagnostic laboratory tests, items response modelling was applied using the Latent Trait Analysis program ‐2 of Uebersax.

Results  The 32 different response patterns obtained from test batteries of five items produced 32 different quality of life scores ranging from 3·4% to 74·5% and 32 different levels of peripheral vascular disease ranging from 9·9% to 83·5% with overall mean scores, by definition, of 50%, whereas the classical method of analysis produced the discrete scores of only 0–5. The item response models produced an adequate fit for the data as demonstrated by chi‐square goodness of fit values/degrees of freedom of 0·86 and 0·64.

Conclusions  1 Quality of life assessments and diagnostic tests can be analysed through item response modelling, and provide more sensitivity than do classical linear models.

2 Item response modelling can change largely qualitative data into fairly accurate quantitative data, and can, even with limited sets of items, produce fairly accurate frequency distribution patterns of quality of life, severity of disease and other latent traits.
Source location using time‐reverse imaging
Authors: Artman Brad , Podladtchikov Igor , Witten Ben
Published: July 2010

We present the chain of time‐reverse modeling, image space wavefield decomposition and several imaging conditions as a migration‐like algorithm called time‐reverse imaging. The algorithm locates subsurface sources in passive seismic data and diffractors in active data. We use elastic propagators to capitalize on the full waveforms available in multicomponent data, although an acoustic example is presented as well. For the elastic case, we perform wavefield decomposition in the image domain with spatial derivatives to calculate P and S potentials. To locate sources, the time axis is collapsed by extracting the zero‐lag of auto and cross‐correlations to return images in physical space. The impulse response of the algorithm is very dependent on acquisition geometry and needs to be evaluated with point sources before processing field data. Band‐limited data processed with these techniques image the radiation pattern of the source rather than just the location. We present several imaging conditions but we imagine others could be designed to investigate specific hypotheses concerning the nature of the source mechanism. We illustrate the flexible technique with synthetic 2D passive data examples and surface acquisition geometry specifically designed to investigate tremor type signals that are not easily identified or interpreted in the time domain.
Dental management of a child with EEC syndrome
Authors: TANBOǦA ILKNUR , PINÇE SEZER , DÜZDAR LALE
Published: July 2010

Summary. The EEC syndrome is a condition characterized by ectrodactyly, ectodermal dysplasia and clefting of the lip and/or palate. Here we report a case of a boy with the EEC syndrome. The clinical and radiologic aspects of this condition, as well as the dental treatment, are reviewed.

La dysplasie ectodermique, l'ectrodactyle et la fente palatine et labiale sont caractéristiques d'un syndrôme. L'aspect clinique, radiologique et le traitement dentaire d'un patient atteint de ce syndrôme, sont étudiés dans cet article.

Das EEC Syndrom ist charakterisiert durch Ektrodaktylie, ektodermale Dysplasie und durch Lippenoder und Gaumenspalten. In diesem Bericht wird ein Fall mit EEC Syndrom beschrieben, die klinischen und röntgoloischen Aspekte dieses Syndromes, ebenso die zahnärztliche Behandlung dieses Falles.

El sindrome EEC (EDF) es una condición caracterizada por ectrodactilidad, displasia ectodérmica y fisura (hendidura) del labio y/o paladar. Se reporta un caso con el síndrome EEC y los aspectos clínicos y radiográficos de la condición así como el tratmiento odontológico realizado.
Classification and sequelae of arrested eruption of primary molars
Authors: KJÆR INGER , FINK‐JENSEN MERETE , ANDREASEN JENS OVE
Published: July 2010

Aim.  The aim of this study was to classify early arrested eruption of primary molars and to analyse and explain the sequelae for the surrounding alveolar bone and the succeeding premolar.

Design.  The position of the arrested primary molars in the mandible, the height of the local alveolar bone, and the morphology and location of the succeeding premolar were evaluated on radiographs from 29 children.

Results.  Four groups of arrest from mild to severe with regards to infra‐position were categorized (Groups I–IV). Mean ages at the time of referral decreased from Groups I (8 years, 10 months) to Group IV (5 years, 9 months).

Sequelae.  (i) Reduction of alveolar bone height (Groups I–III); (ii) delayed maturity of the succeeding premolar (two‐thirds of the cases); (iii) malformation of the succeeding premolar (mainly Groups III and IV); and (iv) ectopically located premolar occlusal to the retained molar (Group IV).

Conclusions.  The deeper in the alveolar process a primary molar is retained, the earlier the disturbance in the eruption has occurred, and the greater is the risk of the permanent tooth germ being malformed and malpositioned. It is estimated that the earliest occurrences of arrested eruption of primary molars supposedly occur before the age of 3.
Electrophysiological Characteristics of Gonadotrophin‐Releasing Hormone 1–3 Neurones: Insights From a Study of Fish Brains
Authors: Oka Y.
Published: July 2010

The vertebrate gonadotrophin‐releasing hormone (GnRH) neurones are considered to consist of one group of hypothalamic neuroendocrine and two groups of extrahypothalamic neuromodulatory GnRH neurones, and each group of neurones expresses different molecular species of GnRH peptide. Different GnRH peptides are produced by one of the three paralogous GnRH genes, gnrh1, gnrh2 and gnrh3, which are considered to have originated from gene duplications. All three GnRH systems are well developed in teleost brains. By taking advantage of this, and especially the use of GnRH‐green fluoresecent protein transgenic fish, the anatomical and electrophysiological properties of all three types of GnRH neurones can now be studied. The hypophysiotropic GnRH1 neurones in the preoptic area show episodic spontaneous electrical activities, whereas the extrahypothalamic GnRH2 neurones in the midbrain and GnRH3 neurones in the terminal nerve show regular intrinsic pacemaker activities. It is suggested that these different electrophysiological properties are related to their different functions (i.e. GnRH1 neurones act as hypophysiotropic neuroendocrine regulators and GnRH2 and GnRH3 neurones act as neuromodulators). The present review focuses on recent electrophysiological analyses of GnRH3 neurones, which have revealed the excitatory GABAergic and the inhibitory FMRFamide‐like peptidergic regulations acting upon them, as well as gap junctional electrotonic coupling.
Restoring ecological balance to the British mammal fauna
Authors: GORMAN MARTYN L.
Published: July 2010

The mammal fauna of the British Isles has seen major perturbations since the end of the last ice age, some natural and some anthropogenic. Today, 61 species of terrestrial mammals breed in the British Isles, but only 39 of them are native species, the rest have been introduced. Furthermore, 19 native species have disappeared from the fauna including all the large predators, lynx Lynx lynx, wolf Canis lupus and brown bear Ursus arctos.

Inevitably, these changes in species composition have been accompanied by major changes in community function including changes in patterns of energy flow through the mammalian community. For example, a high percentage of all the energy now flows through the introduced rabbit Oryctolagus cuniculus population and red deer Cervus elaphus, which, in the absence of natural predators, are living at extremely high densities.

Could the reintroduction of species help to reverse such changes in community structure and function? The successful return to the wild of species such as the Arabian oryx Oryx leucoryx and beaver Castor fiber has shown that reintroductions are certainly possible. However, the impact on community function of returned species is more difficult to evaluate.

This question is addressed in relation to the consequences for deer populations of any possible reintroduction of the wolf to Scotland. Based on what we know of wolves elsewhere, predictions are made about the likely demography and patterns of killing behaviour of introduced wolves. These values are then used to parameterize a Leslie matrix simulation of the impact of wolves on contemporary populations of red deer in Scotland. The simulations suggest very strongly that wolves are very unlikely to have any significant impact on the high‐density populations of deer now living in the Scottish landscape.
Leprosy in transplant recipients: report of a case after liver transplantation and review of the literature
Authors: Trindade M.A.B. , Palermo M.L. , Pagliari C. , Valente N. , Naafs B. , Massarollo P.C.B. , D'Albuquerque L.A.C. , Benard G.
Published: July 2010

M.A.B. Trindade, M. de Lourdes Palermo, C. Pagliari, N. Valente, B. Naafs, P.C.B. Massarollo, L.A.C. D'Albuquerque, G. Benard. Leprosy in transplant recipients: report of a case after liver transplantation and review of the literature. Transpl Infect Dis 2011: 13: 63–69. All rights reserved

Abstract: Leprosy still is an important public health problem in several parts of the world including Brazil. Unlike the diseases caused by other mycobacteria, the incidence and clinical presentation of leprosy seems little affected in immunosuppressed patients. We report the first case, to our knowledge, of a liver transplant patient who developed multi‐bacillary leprosy. The patient presented with papules and infiltrated plaques with loss of sensation suggestive of leprosy 3.5 years after living‐related liver transplantation for autoimmune hepatitis. A skin biopsy showing non‐caseating macrophagic granulomas, neuritis, and intact acid‐fast bacilli on Fite‐Faraco stain, confirmed the diagnosis of borderline lepromatous leprosy. The donor of the liver did not show any evidence of leprosy. During follow‐up, the patient presented 2 episodes of upgrading leprosy type I reactions, 1 mild before leprosy treatment, and 1 moderate 3 months after receiving standard multi‐drug treatment (rifampicin, clofazimine, and dapsone). These reactions were accompanied by increase in liver function tests, especially of canalicular enzymes. This reaction occurred despite the patient's triple immunosuppression regimen. The moderate reaction was successfully treated with further immunosuppression (prednisone, 0.5 mg/kg). Currently, the patient is asymptomatic, off leprosy medication, with routine liver transplant follow‐up. The dilemmas in diagnosis and management of such a case are discussed and the literature on leprosy in transplant recipients is reviewed.