bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of clinically meaningful complex interventions – The contribution of qualitative research
Authors: Ludvigsen Mette Spliid , Meyer Gabriele , Hall Elisabeth , Fegran Liv , Aagaard Hanne , Uhrenfeldt Lisbeth
Published: June 2013

The debate about the “right” methods and designs for nursing research is on-going. According to international surveys, studies on the effectiveness and safety of nursing interventions are rare. Since nursing practice deals daily with interventions, nurses ostensibly expose hospital patients and nursing home residents frequently to unproven therapeutic and preventive nursing interventions. Nursing interventions are predominately of a complex nature, consisting of several components depending on and interacting with each other and their complex contextual factors. Thus, evaluation studies are often challenging and need especially careful development, ambitious designs and systematic evaluations. The UK Medical Research Council (MRC) has proposed a framework, where qualitative and quantitative research rely on each other in order to develop theory-based complex interventions, prepare and conduct their optimal delivery, explain how the interventions work and which conditions contributed in case they did not work. The present essay outlines the points where qualitative research contributes towards the development and evaluation of complex interventions. First, the UK MRC framework is introduced, and secondly it is illustrated where qualitative research should necessarily be located using examples from a handful of qualitative studies. Future clinically meaningful and implementable nursing interventions should best be developed by research groups with both excellent qualitative and quantitative research skills.
Space for Thought
Authors: Quartier Vincent , Antonietti Jean-Philippe , Franck Laure , Iglesias Carlos
Published: June 2013

Aim: The psychoanalytic theories of Bion, Anzieu, Berger, and Gibello postulate that the development of thinking depends upon the formation of a psychic space. This thinking space has its origin in the body and in our interpersonal relations. This study aims to validate this psychodynamic hypothesis. Method: A group of 8- to 14-year-old children participated in this research. The presence of a thinking space was operationalized by the Barrier and Penetration scores on the Rorschach’s Fisher and Cleveland scales, and intellectual efficiency was measured using a short version of the WISC-IV. Results: Results show that extreme scores on the Barrier and Penetration variables predict a lower intellectual level than average scores on the same variables. Conclusion: The development of thinking and personality are undoubtedly linked and the Barrier and Penetration variables are useful measures when evaluating the development of a space for thought.
Rorschach-CS Scores of Six Groups of Patients
Authors: Berghout Caspar C. , Zevalkink Jolien , Pieters Abraham N. J. , Meyer Gregory J.
Published: June 2013

In this study we used a quasiexperimental, cross-sectional design with six cohorts differing in phase of treatment (pretreatment, posttreatment, 2-year posttreatment) and treatment type (psychoanalysis and psychoanalytic psychotherapy) and investigated scores on 39 Rorschach-CS variables. The total sample consisted of 176 participants from four mental health care organizations in The Netherlands. We first examined pretreatment differences between patients entering psychoanalysis and patients entering psychoanalytic psychotherapy. The two treatment groups did not seem to differ substantially before treatment, with the exception of the level of ideational problems. Next, we studied the outcome of psychoanalysis and psychoanalytic psychotherapy by comparing the Rorschach-CS scores of the six groups of patients. In general, we found significant differences between pretreatment and posttreatment on a relatively small number of Rorschach-CS variables. More pre/post differences were found between the psychoanalytic psychotherapy groups than between the psychoanalysis groups. More research is needed to examine whether analyzing clusters of variables might reveal other results.
Two‐dimensional spreading scheme employing 2D orthogonal variable spreading factor codes for orthogonal frequency and code division multiplexing systems
Authors: Puri Parul , Singh Neetu
Published: June 2013

Future 4G systems require transmission of richer multimedia services which inevitably implies an increase in data rate. Orthogonal frequency and code division multiplexing (OFCDM) technique has shown promising results in achieving a high data rate while simultaneously combating multipath fading. OFCDM is an amalgamation of orthogonal frequency division multiplexing and two‐dimensional (2D) spreading. 2D spreading helps to achieve diversity gains in both time and frequency domains. The present OFCDM systems employ 1D orthogonal variable spreading factor (OVSF) codes to achieve the required 2D spreading in code multiplexed channels. However, 2D OVSF codes have better correlation properties in comparison to 1D OVSF codes. Motivated by this principle, the authors propose a spreading scheme for OFCDM systems using 2D OVSF codes. The spreading scheme is designed to increase the system throughput and reduce multi‐code interference. Here, the authors study the OFCDM system performance using the proposed spreading scheme in a multipath fast fading channel with varying spreading factors in both time and frequency domains. The results are compared with the existing OFCDM systems using 1D OVSF codes.
Finding sub‐optimum signature matrices for overloaded code division multiple access systems
Authors: Khoozani Mohsen Heidari , Marvasti Farokh , Azghani Masoumeh , Ghassemian Mona
Published: June 2013

The objective of this study is to design sub‐optimal signature matrices for binary inputs for an overloaded code division multiple access (CDMA) system as developed by this author group. In this study, the authors propose to use the sum capacity, the bit error rate and distance criteria as objective functions for signature matrix optimisation. Three optimisation techniques, the genetic algorithm, the particle swarm optimisation and the conjugate gradient (CG) are exploited in this work. Since the optimisation computational complexity increases by matrix dimensions, it is practically impossible to directly optimise the large signature matrices. In order to address this problem, a method is proposed to enlarge small‐scale signature matrices. It is also proved that the sum channel capacity of the enlarged matrix is scaled by its enlargement factor. The results indicate that this proposed signature matrices provide higher sum capacity than the commonly used signature matrices. The authors also address that this matrices are applicable for highly overloaded CDMA systems.
Outage probability analysis of an amplify‐and‐forward cooperative communication system with multi‐path channels and max–min relay selection
Authors: Eddaghel Masoud M. , Mannai Usama N. , Chen Gaojie J. , Chambers Jonathon A.
Published: June 2013

The authors perform an outage probability analysis of a cooperative communication system which transmits over multi‐path channels with best single, or best two relay pair selection and amplify‐and‐forward two‐hop relaying. The probability density function of the multi‐path links is modelled in the time domain with an Erlang distribution function. The analytical expressions for the probability density function and cumulative density function of the end‐to‐end signal‐to‐noise ratio are obtained for an arbitrary number of relay nodes and multi‐path channel lengths of 2 and 3 with best single and best two relay pair selection from N available relays; from which outage probabilities are calculated. The spatial and temporal cooperative diversity of the network is then analysed. Finally, the theoretical results are compared with simulations to confirm the validity of the analysis, and the advantage of two relay selection is verified through bit error rate evaluation.
Performance analysis for multiple‐input multiple‐output‐maximum ratio transmission systems with channel estimation error, feedback delay and co‐channel interference
Authors: Chu Thi My Chinh , Duong Trung Q. , Zepernick Hans‐Jürgen
Published: June 2013

In this study, the authors analyse the impact of channel estimation error (CEE), feedback delay (FD), and co‐channel interference (CCI) on the performance of multiple‐input multiple‐output (MIMO) systems deploying maximum ratio transmission (MRT). In particular, the authors derive closed‐form expressions for the ergodic capacity and the symbol error rate (SER) as well as the outage probability (OP). In addition, to reveal the effect of CEE, FD and CCI on the MIMO‐MRT system, the authors adopt more simplified and tractable formulas in terms of asymptotic expressions for the ergodic capacity, SER and OP. The analysis shows that the system performance is degraded considerably under imperfect transmission conditions such as CEE, FD and CCI. However, the authors can compensate part of this degradation by deploying MRT transmission with a large number of antennas at the transmitter and receiver. Finally, the selected examples exhibit consistency between analytical results and Monte Carlo simulations.
Correlated four-component EPR g-tensors for doublet molecules
Authors: Vad Mads S. , Pedersen Morten N. , Nørager Anette , Jensen Hans Jørgen Aa.
Published: June 2013

The first correlated ab initio four-component calculations of electron paramagnetic resonance (EPR) g-tensors for doublet radicals are reported. We have implemented a first-order degenerate perturbation theory approach based on the four-component Dirac-Coulomb Hamiltonian and fully relativistic configuration interaction wave functions in the DIRAC program package. We find that the correlation effects on the g-tensors can be sufficiently well described with manageable basis sets of triple-zeta quality and manageable configuration spaces. The new fully relativistic EPR module in DIRAC should be useful for benchmarking density functional theory approaches, however, with future optimization of the code we believe it will also be useful for applications.
Sensitivity analysis and optimization of thin-film thermoelectric coolers
Authors: Harsha Choday Sri , Roy Kaushik
Published: June 2013

The cooling performance of a thermoelectric (TE) material is dependent on the figure-of-merit (ZT = S2σT/κ), where S is the Seebeck coefficient, σ and κ are the electrical and thermal conductivities, respectively. The standard definition of ZT assigns equal importance to power factor (S2σ) and thermal conductivity. In this paper, we analyze the relative importance of each thermoelectric parameter on the cooling performance using the mathematical framework of sensitivity analysis. In addition, the impact of the electrical/thermal contact parasitics on bulk and superlattice Bi2Te3 is also investigated. In the presence of significant contact parasitics, we find that the carrier concentration that results in best cooling is lower than that of the highest ZT. We also establish the level of contact parasitics that are needed such that their impact on TE cooling is negligible.
Orientating layers with adjustable pretilt angles for liquid crystals deposited by a linear atmospheric pressure plasma source
Authors: Jian Shih-Jie , Kou Chwung-Shan , Hwang Jennchang , Lee Chein-Dhau , Lin Wei-Cheng
Published: June 2013

A method for controlling the pretilt angles of liquid crystals (LC) was developed. Hexamethyldisiloxane polymer films were first deposited on indium tin oxide coated glass plates using a linear atmospheric pressure plasma source. The films were subsequently treated with the rubbing method for LC alignment. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy measurements were used to characterize the film composition, which could be varied to control the surface energy by adjusting the monomer feed rate and input power. The results of LC alignment experiments showed that the pretilt angle continuously increased from 0° to 90° with decreasing film surface energy.
Structural and energetic determinants of co-translational folding
Authors: Krobath Heinrich , Shakhnovich Eugene I. , Faísca Patrícia F. N.
Published: June 2013

We performed extensive lattice Monte Carlo simulations of ribosome-bound stalled nascent chains (RNCs) to explore the relative roles of native topology and non-native interactions in co-translational folding of small proteins. We found that the formation of a substantial part of the native structure generally occurs towards the end of protein synthesis. However, multi-domain structures, which are rich in local interactions, are able to develop gradually during chain elongation, while those with proximate chain termini require full protein synthesis to fold. A detailed assessment of the conformational ensembles populated by RNCs with different lengths reveals that the directionality of protein synthesis has a fine-tuning effect on the probability to populate low-energy conformations. In particular, if the participation of non-native interactions in folding energetics is mild, the formation of native-like conformations is majorly determined by the properties of the contact map around the tethering terminus. Likewise, a pair of RNCs differing by only 1-2 residues can populate structurally well-resolved low energy conformations with significantly different probabilities. An interesting structural feature of these low-energy conformations is that, irrespective of native structure, their non-native interactions are always long-ranged and marginally stabilizing. A comparison between the conformational spectra of RNCs and chain fragments folding freely in the bulk reveals drastic changes amongst the two set-ups depending on the native structure. Furthermore, they also show that the ribosome may enhance (up to 20%) the population of low energy conformations for chains folding to native structures dominated by local interactions. In contrast, a RNC folding to a non-local topology is forced to remain largely unstructured but can attain low energy conformations in bulk.
Magnetic structure and magnetodielectric effect of YFe0.5Cr0.5O3
Authors: Nair Vidhya G. , Das A. , Subramanian V. , Santhosh P. N.
Published: June 2013

X-ray diffraction studies reveal Pnma space group for YFe0.5Cr0.5O3. The Neel temperature for YFe0.5Cr0.5O3 is found to be ∼275 K using temperature dependence of magnetization and neutron diffraction studies. The variation of magnetization with applied magnetic field shows a hysteresis loop at 20 K, which depicts a weak ferromagnetic behavior. Rietveld refinement of the neutron diffraction data divulge a canted antiferromagnetic structure (Γ4 = GzFyAx) for YFe0.5Cr0.5O3. Dielectric measurement depicts a relaxor like transition (peak at ∼507 K for 10 kHz) for YFe0.5Cr0.5O3. An anomaly in the magnetization curve around this transition temperature points the possibility of magnetodielectric effect in YFe0.5Cr0.5O3. Non-Debye type relaxation is observed with activation energy of 0.40 eV at low temperature and 1.01 eV at high temperature. At high temperatures, oxygen ion vacancies are found to contribute to the conduction process in addition to polaron hopping.
Subcritical crack growth in SiNx thin-film barriers studied by electro-mechanical two-point bending
Authors: Guan Qingling , Laven Jozua , Bouten Piet C. P. , de With Gijsbertus
Published: June 2013

Mechanical failure resulting from subcritical crack growth in the SiNx inorganic barrier layer applied on a flexible multilayer structure was studied by an electro-mechanical two-point bending method. A 10 nm conducting tin-doped indium oxide layer was sputtered as an electrical probe to monitor the subcritical crack growth in the 150 nm dielectric SiNx layer carried by a polyethylene naphthalate substrate. In the electro-mechanical two-point bending test, dynamic and static loads were applied to investigate the crack propagation in the barrier layer. As consequence of using two loading modes, the characteristic failure strain and failure time could be determined. The failure probability distribution of strain and lifetime under each loading condition was described by Weibull statistics. In this study, results from the tests in dynamic and static loading modes were linked by a power law description to determine the critical failure over a range of conditions. The fatigue parameter n from the power law reduces greatly from 70 to 31 upon correcting for internal strain. The testing method and analysis tool as described in the paper can be used to understand the limit of thin-film barriers in terms of their mechanical properties.
Atomic scale investigation of a PbTiO3/SrRuO3/DyScO3 heterostructure
Authors: Egoavil R. , Tan H. , Verbeeck J. , Bals S. , Smith B. , Kuiper B. , Rijnders G. , Koster G. , Van Tendeloo G.
Published: June 2013

An epitaxial PbTiO3 thin film grown on self-organized crystalline SrRuO3 nanowires deposited on a DyScO3 substrate with ordered DyO and ScO2 chemical terminations is investigated by transmission electron microscopy. In this PbTiO3/SrRuO3/DyScO3 heterostructure, the SrRuO3 nanowires are assumed to grow on only one type of substrate termination. Here, we report on the structure, morphology, and chemical composition analysis of this heterostructure. Electron energy loss spectroscopy reveals the exact termination sequence in this complex structure. The energy loss near-edge structure of the Ti–L2,3, Sc–L2,3, and O K edges shows intrinsic interfacial electronic reconstruction. Furthermore, PbTiO3 domain walls are observed to start at the end of the nanowires resulting in atomic steps on the film surface.
In-situ synchrotron x-ray transmission microscopy of the sintering of multilayers
Authors: Yan Zilin , Guillon Olivier , Martin Christophe L. , Wang Steve , Lee Chul-Seung , Bouvard Didier
Published: June 2013

This letter reports on in-situ characterization of the high temperature sintering of multilayer ceramic capacitors by high-resolution synchrotron x-ray imaging. Microstructural evolution was obtained in real time by a continuous recording of 2-dimensional radiographs. Anisotropic strains were measured for different layers. Quantification of defects was conducted with 3-dimensional nano-computed tomography. These in-situ observations prove that electrode discontinuities occur at the early stage of sintering and originate from initial heterogeneities linked to the particulate nature of the starting powders.
Tunable gold-chitosan nanocomposites by local field engineering
Authors: Cazacu Ana , Curecheriu Lavinia , Neagu Alexandra , Padurariu Leontin , Cernescu Adrian , Lisiecki Isabelle , Mitoseriu Liliana
Published: June 2013

A method to control the permittivity and tunability in composite materials formed by conductive nanoparticles embedded in a flexible nonlinear dielectric matrix is proposed. The local field distributions in composite structures were determined and the field-induced permittivity was estimated for different volume fraction of conductive particles. The predicted tunability behavior agrees well with the observed trends obtained for gold nanoparticles embedded in chitosan matrix. The paper demonstrates the concept of engineered local fields in nanocomposites by using metallic nanoparticles as fillers in polymer matrix for tailoring the permittivity and tunability values.
Synthesis of vertically grown N,N′-dioctyl-3,4,9,10-perylenedicarboximide nanostructure for photovoltaic application
Authors: Pradhan S. , Dhar A.
Published: June 2013

We report here the formation of vertical N,N′-dioctyl-3,4,9,10-perylenedicarboximide (PTCDI-C8) nanostructure with simple chemical treatment over thermally evaporated thin film of PTCDI-C8. Here, we have used PTCDI-C8 nanostructures as an electron accepting material and a conjugated polymer as an electron donor material in the solar cell device. The study shows that the utilization of nanostructure over bilayer architecture gives better performance. The higher donor/acceptor effective interface and its effect on the device performance are realized with the nanostructured PTCDI-C8 layer.
Manipulation at a distance: Atomic-scale observation of ballistic electron transport in single layer graphene
Authors: Yang H. , Mayne A. J. , Cejas C. , Dujardin G. , Kuk Y.
Published: June 2013

We present scanning tunneling microscopy manipulation experiments on epitaxial graphene and the carbon buffer layer grown on hexagonal silicon carbide. Low voltage pulses applied to the graphene layer with the microscope tip induce nonlocal modifications of a bare carbon buffer region 10 nm away. The graphene itself is not affected. This is direct evidence for ballistic hot electrons propagating along the graphene layer to the graphene edge. High energy states in the graphene band structure (Van Hove Singularities) may explain both the electron transport and the coupling of the graphene edge to the adjacent bare carbon buffer region.
Synthesis, CMC Determination, and Outer Sphere Electron Transfer Reaction of the Surfactant–Complex Ion, cis-[Co(en)2(4CNP)(DA)]3+ with [Fe(CN)6]4– in Micelles, β-cyclodextrin, and Liposome (Dipalmidoylphosphotidylcholine) Vesicles
Authors: Nagaraj Karuppiah , Arunachalam Sankaralingam
Published: June 2013

The surfactant cobalt(iii) complex, cis-[Co(en)2(4CNP)(DA)](ClO4)3, en = ethylenediamine, 4CNP = 4-cyanopyridine, DA = dodecylamine, was synthesized and characterized by physico-chemical and spectroscopic methods. The critical micelle concentration value of this complex was obtained from the conductivity measurements at different temperatures to evaluate, ΔGm0, ΔHm0, and ΔSm0. The kinetics of outer sphere electron transfer reaction of this complex with Fe(CN)64– ion in micelles, β-cyclodextrin as well as in liposome vesicles media were studied. The rate constant increases with increase in the concentration of micelles but decreases in presence of β-cyclodextrin, which is a good structure breaker of micelles. In liposome vesicles media the rate constant is different at below and above phase transition temperature. The results have been explained based on the hydrophobic effect, the presence of pyridine ligand containing 4-cyano substituent and the reactants with opposite charge.
Many-body Spin Interactions in Semiconductor Quantum Wires
Authors: Reilly D. J. , Pfeiffer L. N. , Facer G. R. , West K. W. , Dzurak A. S. , Kane B. E. , Clarke R. G. , Stiles P. J. , O'Brien J. L. , Lumpkin N. E.
Published: June 2013

Zero length quantum wires (or point contacts) exhibit unexplained conductance
structure close to 0.7 � 2e
2 /h in the absence of an
applied magnetic field. We have studied the density- and temperature-dependent
conductance of ultra-low-disorder GaAs/AlGaAs quantum wires with nominal
lengths l=0 and 2�m,
fabricated from structures free of the disorder associated with modulation
doping. In a direct comparision we observe structure near 0.7 �
2e 2 /h
for l = 0, whereas thel
= 2�m wires show structure evolving with
increasing electron density to 0.5 � 2e
2 /h in
zero magnetic field, the value expected for an ideal
spin-split sub-band. Our results suggest the dominant mechanism through which
electrons interact can be strongly affected by the length of the 1D region.
The Distribution of Dislocations in Linear Arrays
Authors: Head AK , Louat N
Published: June 2013

An approximate method is given for finding the equilibrium distribution of arrays of dislocations. The analysis is based on the assumption that an array of discrete dislocations may be replaced by a continuous distribution of smeared dislocation. The solutions of a number of problems of physical interest are investigated, including some in which dislocations of opposite sign are involved.
Plasma Emission Processes in a Magnetoactive Plasma
Authors: Melrose DB , Sy WN
Published: June 2013

Plasma emission (i.e. emission at about the plasma frequency and twice this frequency) is treated taking into account the effects of the magnetic field on the electron plasma waves, on the conversion processes, and on the escaping radiation. The expected degrees of polarization of the fundamental and second harmonic are calculated in the weak field limit. The results are used to estimate the magnetic field strength B at the 80 MHz level from the observed polarization of type III bursts; the result B < 0�04 G is smaller than previous estimates. The possible importance of electron-cyclotron waves in an application to type I bursts is noted.
The Transformation Properties of the Energy?Momentum Tensor for Dispersive Waves
Authors: Melrose DB
Published: June 2013

A covariant formulation of wave dispersion is extended to include dissipation and hence to identify the energy-momentum tensor for dispersive waves. The resulting form is equivalent to that obtained from an averaged-Lagrangian approach. The transformation properties of the wave energy-momentum tensor are discussed. The appearance of unacceptable negative wave energies in frames moving at greater than the phase speed of the waves may be avoided by choosing a physically equivalent second branch of the solution of the dispersion equation in such frames. A quantum mechanical description of dispersive waves as a collection of wave quanta with energy liw and momentum lik is compatible with the form of the energy-momentum tensor discussed here. The quantum description also involves the occupation number which plays the role of the distribution function of the wave quanta. The classical counterpart of the occupation number is defined, shown to be an invariant and shown to obey an equation which may be interpreted directly as a transfer equation for a distribution of wave quanta.
Additional Rigidly Rotating Solutions in the String Model of Hadrons
Authors: Burden CJ , Tassie LJ
Published: June 2013

Solutions to the relativistic string equation are found which correspond to rigid body rotation about the z-axis with azimuthal velocity greater than the velocity of light. If the solutions lie entirely in the x-y plane they are rotating epicycloids, complimentary to the hypocycloid solutions found previously. The use of a general solution to the string equation in terms of two arbitrary world-lines with null tangents provides an alternative derivation of the rigidly rotating solutions.
Induced Parity Violation in Odd Dimensions
Authors: Delbourgo R , Waites AB
Published: June 2013

One of the interesting features about field theories in odd dimensions is the induction of parity-violating terms and well-defined finite topological actions via quantum loops if a fermion mass term is originally present and conversely. Aspects of this issue are illustrated for electrodynamics in 2+ 1 and 4+ 1 dimensions.
Condom use errors among sexually unfaithful and consensually nonmonogamous individuals
Authors: Conley Terri D. , Moors Amy C. , Ziegler Ali , Matsick Jes L. , Rubin Jennifer D.
Published: June 2013

This research involved comparisons of the condom use behaviours of people who are in monogamous relationships but who have engaged in extradyadic sex (i.e. committed infidelity) to those who are in consensually nonmonogamous (CNM) relationships. Consensual nonmonogamy is the practice of openly having multiple sexual or romantic partners simultaneously, with the full knowledge and consent of all participating partners. Participants in CNM relationships used condoms more correctly in their last instance of intercourse than those who were committing infidelity.
Effective peer education in HIV: defining factors that maximise success
Authors: Lambert Steven M. , Debattista Joseph , Bodiroza Aleksandar , Martin Jack , Staunton Shaun , Walker Rebecca
Published: June 2013

Background
Peer education is considered an effective health promotion and education strategy, particularly to populations traditionally resistant to conventional forms of health information dissemination. This has made it very applicable to HIV education and prevention, where those who are affected or at risk are often amongst the most vulnerable in society. However, there still remains uncertainty as to the reasons for its effectiveness, what constitutes an effective methodology and why a consistent methodology can often result in widely variable outcomes. Method: Between 2008 and 2010, three separate reviews of peer education were undertaken across more than 30 countries in three distinct geographical regions across the globe. The reviews sought to identify determinants of the strengths and weaknesses inherent in approaches to peer education, particularly targeting young people and the most at-risk populations. Results: By assessing the implementation of peer education programs across a variety of social environments, it was possible to develop a contextual understanding for peer education’s effectiveness and provide a picture of the social, cultural, political, legal and geographic enablers and disablers to effective peer education. Several factors were significant contributors to program success, not as strategies of methodology, but as elements of the social, cultural, political and organisational context in which peer education was situated. Conclusion: Contextual elements create environments supportive of peer education. Consequently, adherence to a methodology or strategy without proper regard to its situational context rarely contributes to effective peer education.
Marsupial immunology bounding ahead
Authors: Belov Katherine , Miller Robert D. , Old Julie M. , Young Lauren J.
Published: June 2013

Marsupial immune responses were previously touted as ‘primitive’ but we now know that the marsupial immune system is complex and on par with that of eutherian mammals. In this manuscript we review the field of marsupial immunology, focusing on basic anatomy, developmental immunology, immunogenetics and evolution. We concentrate on advances to our understanding of marsupial immune gene architecture, made possible by the recent sequencing of the opossum, tammar wallaby and Tasmanian devil genomes. Characterisation of immune gene sequences now paves the way for the development of immunological assays that will allow us to more accurately study health and disease in marsupials.
Targeting of the MNK–eIF4E axis in blast crisis chronic myeloid leukemia inhibits leukemia stem cell function
Authors: Lim Sharon , Saw Tzuen Yih , Zhang Min , Janes Matthew R. , Nacro Kassoum , Hill Jeffrey , Lim An Qi , Chang Chia-Tien , Fruman David A. , Rizzieri David A. , Tan Soo Yong , Fan Hung , Chuah Charles T. H. , Ong S. Tiong
Published: June 2013

Significance

Cancer stem cells (CSCs) frequently acquire the ability to self-renew and persist in their hosts by coopting normal stem cell programs. Blast crisis (BC) chronic myeloid leukemia is a prototypic example, as the acquired activation of β-catenin signaling that enables BC CSC function is also important in normal hematopoietic stem cell maintenance. In identifying eIF4E phosphorylation by the MNK kinases as a necessary step in β-catenin activation in BC CSCs, but not normal hematopoietic stem cells, we define a therapeutic target in BC. Our studies suggest that clinical trials with MNK kinase inhibitors are warranted in BC chronic myeloid leukemia.
Expression of murine Unc93b1 is up-regulated by interferon and estrogen signaling: implications for sex bias in the development of autoimmunity
Authors: Panchanathan Ravichandran , Liu Hongzhu , Choubey Divaker
Published: June 2013

The endoplasmic reticulum transmembrane protein, Unc93b1, is essential for trafficking of endosomal TLRs from the endoplasmic reticulum to endosomes. A genetic defect in the human UNC93B1 gene is associated with immunodeficiency. However, systemic lupus erythematosus (SLE) patients express increased levels of the UNC93B1 protein in B cells. Because SLE in patients and certain mouse models exhibits a sex bias and increased serum levels of type I interferons in patients are associated with the disease activity, we investigated whether the female sex hormone estrogen (E2) or type I interferon signaling could up-regulate the expression of the murine Unc93b1 gene. We found that steady-state levels of Unc93b1 mRNA and protein were measurably higher in immune cells (CD3+, B220+, CD11b+ and CD11c+) isolated from C57BL/6 (B6) females than age-matched males. Moreover, treatment of CD11b+ and B220+ cells with E2 or interferons (IFN-α, IFN-β or IFN-γ) significantly increased the levels of Unc93b1 mRNA and protein. Accordingly, a deficiency of estrogen receptor-α or STAT1 expression in immune cells decreased the expression levels of the Unc93b1 protein. Interestingly, levels of Unc93b1 protein were appreciably higher in B6.Nba2 lupus-prone female mice compared with age-matched B6 females. Furthermore, increased expression of the interferon- and E2-inducible p202 protein in a murine macrophage cell line (RAW264.7) increased the levels of the Unc93b1 protein, whereas knockdown of p202 expression reduced the levels. To our knowledge, our observations demonstrate for the first time that activation of interferon and estrogen signaling in immune cells up-regulates the expression of murine Unc93b1.
Transcriptional and post-transcriptional regulation of IκB-ζ upon engagement of the BCR, TLRs and FcγR
Authors: Hanihara Fumito , Takahashi Yuta , Okuma Atsushi , Ohba Tomoyuki , Muta Tatsushi
Published: June 2013

IκB-ζ is a nuclear IκB protein robustly induced in macrophages and fibroblasts upon TLR or IL-1R stimulation. IκB-ζ associates with NF-κB in the cell nucleus and is essential for the induction of a subset of secondary response genes represented by IL-6. Here, we analyzed induction of IκB-ζ in mouse B cells and found that IκB-ζ is induced by BCR or TLR stimulation. Similar to TLR stimulation, BCR stimulation elicited NF-κB-mediated transcriptional activation and mRNA stabilization of IκB-ζ via a cis-element in IκB-ζ mRNA. Proteasome inhibitors inhibited transcriptional activation but not post-transcriptional activation, indicating independency of the two signals. Co-stimulation of the BCR and TLR9 or TLR7, but not TLR2/1, synergistically induced IκB-ζ. Co-engagement of inhibitory Fcγ receptor suppressed BCR-mediated IκB-ζ expression but not that induced by TLR stimulation alone or co-stimulation of TLR and the BCR. The PI3K inhibitor LY294002 inhibited BCR-mediated, but not TLR-mediated, induction of IκB-ζ, consistent with the role of PI3K in BCR signaling and its suppression by FcγR. Analysis of IκB-ζ-deficient B cells demonstrated that IκB-ζ was essential upon stimulation of BCR or TLR for the expression of several genes including IL-10 and CTLA4. IκB-ζ-deficient B cells exhibited impaired proliferation and enhanced up-regulation of CD86 following stimulation of TLR9, but not the BCR, indicating critical roles for IκB-ζ in TLR signaling in B cells. Strict regulatory mechanisms for the induction of IκB-ζ via multiple pathways and its essential function upon stimulation indicate that IκB-ζ plays an important role in B cells.
Differential regulation of marginal zone and follicular B cell responses by CD83
Authors: Uhde Melanie , Kuehl Svenja , Richardt Ulricke , Fleischer Bernhard , Osterloh Anke
Published: June 2013

Transgenic over-expression of CD83 on B cells leads to a reduced response to BCR engagement but to an enhanced secretion of IL-10 upon LPS stimulation. In this study, we analyzed the differential influence of CD83 on the stimulation of different B cell subsets via the BCR or TLR4. Neither wild type nor CD83 transgenic (CD83tg) B cells produced any IL-10 in response to BCR stimulation. BCR engagement led to reduced activation of LYN, SYK and ERK1/2 resulting in reduced numbers of proliferating cells in all CD83tg B cell subsets. Moreover, CD83tg follicular (FO) but not marginal zone (MZ) or transitional (TN) B cells showed significantly enhanced cell death. In contrast, LPS stimulation led to normal frequencies of proliferating CD83tg FO, MZ and TN B cells although TLR4 engagement did not rescue FO B cells from apoptosis. Furthermore, LPS stimulation led to high IL-10 production derived from CD83tg MZ B cells that reacted to LPS stimulation with enhanced ERK1/2 activation. Finally, we show that CD83 co-localizes with the BCR complex as well as with the LPS receptor complex suggesting that CD83 interacts with components of both signaling complexes. Taken together, the results of this study show that CD83 already inhibits the initiation of BCR signaling leading to insufficient activation signals in all B cells and reduced survival especially of FO B cells. On the other hand, CD83 supports TLR4-mediated IL-10 release exclusively in MZ B cells. Thus, CD83 differentially modulates FO and MZ B cell responses.
A deterministic model for the occurrence and dynamics of multiple mutations in hierarchically organized tissues
Authors: Werner Benjamin , Dingli David , Traulsen Arne
Published: June 2013

Cancers are rarely caused by single mutations, but often develop as a result of the combined effects of multiple mutations. For most cells, the number of possible cell divisions is limited because of various biological constraints, such as progressive telomere shortening, cell senescence cascades or a hierarchically organized tissue structure. Thus, the risk of accumulating cells carrying multiple mutations is low. Nonetheless, many diseases are based on the accumulation of such multiple mutations. We model a general, hierarchically organized tissue by a multi-compartment approach, allowing any number of mutations within a cell. We derive closed solutions for the deterministic clonal dynamics and the reproductive capacity of single clones. Our results hold for the average dynamics in a hierarchical tissue characterized by an arbitrary combination of proliferation parameters. We show that hierarchically organized tissues strongly suppress cells carrying multiple mutations and derive closed solutions for the expected size and diversity of clonal populations founded by a single mutant within the hierarchy. We discuss the example of childhood acute lymphoblastic leukaemia in detail and find good agreement between our predicted results and recently observed clonal diversities in patients. This result can contribute to the explanation of very diverse mutation profiles observed by whole genome sequencing of many different cancers.
Clocks for the city: circadian differences between forest and city songbirds
Authors: Dominoni D. M. , Helm B. , Lehmann M. , Dowse H. B. , Partecke J.
Published: June 2013

To keep pace with progressing urbanization organisms must cope with extensive habitat change. Anthropogenic light and noise have modified differences between day and night, and may thereby interfere with circadian clocks. Urbanized species, such as birds, are known to advance their activity to early morning and night hours. We hypothesized that such modified activity patterns are reflected by properties of the endogenous circadian clock. Using automatic radio-telemetry, we tested this idea by comparing activity patterns of free-living forest and city European blackbirds (
Turdus merula
). We then recaptured the same individuals and recorded their activity under constant conditions. City birds started their activity earlier and had faster but less robust circadian oscillation of locomotor activity than forest conspecifics. Circadian period length predicted start of activity in the field, and this relationship was mainly explained by fast-paced and early-rising city birds. Although based on only two populations, our findings point to links between city life, chronotype and circadian phenotype in songbirds, and potentially in other organisms that colonize urban habitats, and highlight that urban environments can significantly modify biologically important rhythms in wild organisms.
Giant lizards occupied herbivorous mammalian ecospace during the Paleogene greenhouse in Southeast Asia
Authors: Head Jason J. , Gunnell Gregg F. , Holroyd Patricia A. , Hutchison J. Howard , Ciochon Russell L.
Published: June 2013

Mammals dominate modern terrestrial herbivore ecosystems, whereas extant herbivorous reptiles are limited in diversity and body size. The evolution of reptile herbivory and its relationship to mammalian diversification is poorly understood with respect to climate and the roles of predation pressure and competition for food resources. Here, we describe a giant fossil acrodontan lizard recovered with a diverse mammal assemblage from the late middle Eocene Pondaung Formation of Myanmar, which provides a historical test of factors controlling body size in herbivorous squamates. We infer a predominately herbivorous feeding ecology for the new acrodontan based on dental anatomy, phylogenetic relationships and body size. Ranking body masses for Pondaung Formation vertebrates indicates that the lizard occupied a size niche among the larger herbivores and was larger than most carnivorous mammals. Paleotemperature estimates of Pondaung Formation environments based on the body size of the new lizard are approximately 2–5°C higher than modern. These results indicate that competitive exclusion and predation by mammals did not restrict body size evolution in these herbivorous squamates, and elevated temperatures relative to modern climates during the Paleogene greenhouse may have resulted in the evolution of gigantism through elevated poikilothermic metabolic rates and in response to increases in floral productivity.
Ecological variation in South American geophagine cichlids arose during an early burst of adaptive morphological and functional evolution
Authors: Arbour Jessica Hilary , López-Fernández Hernán
Published: June 2013

Diversity and disparity are unequally distributed both phylogenetically and geographically. This uneven distribution may be owing to differences in diversification rates between clades resulting from processes such as adaptive radiation. We examined the rate and distribution of evolution in feeding biomechanics in the extremely diverse and continentally distributed South American geophagine cichlids. Evolutionary patterns in multivariate functional morphospace were examined using a phylomorphospace approach, disparity-through-time analyses and by comparing Brownian motion (BM) and adaptive peak evolutionary models using maximum likelihood. The most species-rich and functionally disparate clade (CAS) expanded more efficiently in morphospace and evolved more rapidly compared with both BM expectations and its sister clade (GGD). Members of the CAS clade also exhibited an early burst in functional evolution that corresponds to the development of modern ecological roles and may have been related to the colonization of a novel adaptive peak characterized by fast oral jaw mechanics. Furthermore, reduced ecological opportunity following this early burst may have restricted functional evolution in the GGD clade, which is less species-rich and more ecologically specialized. Patterns of evolution in ecologically important functional traits are consistent with a pattern of adaptive radiation within the most diverse clade of Geophagini.
Outbreak of acute respiratory disease caused by human adenovirus type 7 in a military training camp in Shaanxi, China
Authors: Yu Pengbo , Ma Chaofeng , Nawaz Muhammad , Han Lei , Zhang Jianfang , Du Quanli , Zhang Lixia , Feng Qunling , Wang Jingjun , Xu Jiru
Published: June 2013

Outbreaks of ARD associated with HAdV have been reported in military populations in many countries. Here, we report an ARD outbreak caused by HAdV‐7 in a military training camp in Shaanxi Province, China, from February to March of 2012. Epidemic data and samples from the patients were collected, and viral nucleotides from samples and viral isolations were detected and sequenced. IgG and IgA antibodies against HAdV, and the neutralization antibodies against the viral strain isolated in this outbreak, were detected. Epidemiological study showed that all personnel affected were males with an average age of 19.1 years. Two peaks appeared on the epicurve and there was an 8‐day interval between peaks. Laboratory results of viral nucleotide detection carried out with clinical specimens were positive for HAdV (83.33%, 15/18). Further study through serum antibody assay, virus isolation and phylogenetic analysis showed that HAdV‐7 was the etiological agent responsible for the outbreak. IgA antibody began to appear on the 4th day after the onset and showed 100% positivity on the 8th day. The virus strain in the present outbreak was highly similar to the virus isolated in Hanzhong Shaanxi in 2009. We conclude that HAdV‐7 was the pathogen corresponding to the outbreak, and this is the first report of an ARD outbreak caused by HAdV‐7 in military persons in China. Vaccine development, as well as enhanced epidemiological and virological surveillance of HAdV infections in China should be emphasized.
Social network analysis of wild chimpanzees provides insights for predicting infectious disease risk
Authors: Rushmore Julie , Caillaud Damien , Matamba Leopold , Stumpf Rebecca M. , Borgatti Stephen P. , Altizer Sonia
Published: June 2013

Heterogeneity in host association patterns can alter pathogen transmission and strategies for control. Great apes are highly social and endangered animals that have experienced substantial population declines from directly transmitted pathogens; as such, network approaches to quantify contact heterogeneity could be crucially important for predicting infection probability and outbreak size following pathogen introduction, especially owing to challenges in collecting real‐time infection data for endangered wildlife.

We present here the first study using network analysis to quantify contact heterogeneity in wild apes, with applications for predicting community‐wide infectious disease risk. Specifically, within a wild chimpanzee community, we ask how associations between individuals vary over time, and we identify traits of highly connected individuals that might contribute disproportionately to pathogen spread.

We used field observations of behavioural encounters in a habituated wild chimpanzee community in Kibale National Park, Uganda to construct monthly party level (i.e. subgroup) and close‐contact (i.e. ≤5 m) association networks over a 9‐month period.

Network analysis revealed that networks were highly dynamic over time. In particular, oestrous events significantly increased pairwise party associations, suggesting that community‐wide disease outbreaks should be more likely to occur when many females are in oestrus.

Bayesian models and permutation tests identified traits of chimpanzees that were highly connected within the network. Individuals with large families (i.e. mothers and their juveniles) that range in the core of the community territory and to a lesser extent high‐ranking males were central to association networks, and thus represent the most important individuals to target for disease intervention strategies.

Overall, we show striking temporal variation in network structure and traits that predict association patterns in a wild chimpanzee community. These empirically‐derived networks can inform dynamic models of pathogen transmission and have practical applications for infectious disease management of endangered wildlife species.