bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental investigation of the electron energy distribution function (EEDF) by Thomson scattering and optical emission spectroscopy
Authors: Carbone E A D , Hübner S , Jimenez-Diaz M , Palomares J M , Iordanova E , Graef W A A D , Gamero A. , van der Mullen J J A M
Published: November 2012

The electron temperature of an argon surface wave discharge generated by a surfatron plasma at intermediate pressures is measured by optical emission spectroscopy (OES) and Thomson scattering (TS). The OES method, namely absolute line intensity (ALI) measurements gives an electron temperature which is found to be (more or less) constant along the plasma column. TS, on the other hand, shows a different behaviour; the electron temperature is not constant but rises in the direction of the wave propagation. In the pressure range of this study, it is theoretically known that deviations from Maxwell equilibrium are expected towards the end of the plasma column. In this paper, we propose a combination of methods to probe the electron energy distribution function (EEDF) in this relatively high-pressure regime. The ALI method combined with a collisional–radiative model allows one to measure the effective (Maxwellian) creation temperature of the plasma while TS measures the mean electron energy of the EEDF.

The differences between the two temperature methods can be explained by the changes in the form of the EEDF along the plasma column. A strong correlation is found with decreasing ionization degree for different pressures. Numerical calculations of the EEDF with a Boltzmann solver are used to investigate the departure from a Maxwellian EEDF. The relatively higher electron temperature found by TS compared with the ALI measurements is finally quantitatively correlated with the departure from a Maxwellian EEDF with a depleted tail.
Debris mitigation power of various buffer gases for CO2 laser produced tin plasmas
Authors: Wu Tao , Wang Xinbing , Lu Hong , Lu Peixiang
Published: November 2012

Debris mitigation using an ambient gas is the easiest way for laser-produced plasma extreme ultraviolet light source. The debris mitigation power of hydrogen, helium and argon buffer gases against CO2 laser produced tin plasma plumes was quantitatively estimated by means of the visualization imaging system as well as the optical emission spectroscopy technique. The debris mitigation power of hydrogen buffer gas was assessed under ambient pressure ranging from 30 to 104 Pa. The debris mitigation power of the hydrogen buffer gas was determined as 150 eV mm−1 for energetic particles of 400 eV under a pressure of 104 Pa, which remained as high as 40 eV mm−1 at a pressure of 100 Pa. The maximum stopping power and collision scattering cross section of argon were measured to be almost three times larger in comparison with hydrogen and one and a half times larger than helium atmosphere at a pressure of 2000 Pa. Time-resolved optical emission spectroscopy showed that thermalizing collisions were responsible for slowing down the fast energetic ions and atoms towards a thermal equilibrium.
Nanomechanical properties of pure and doped Ta2O5 and the effect of microwave irradiation
Authors: Atanassova E , Lytvyn P , Dub S N , Konakova R V , Mitin V F , Spassov D
Published: November 2012

The nanomechanical properties of pure and doped Ta2O5 films (100 nm) on Si, and the effect of short time (10 s) microwave irradiation are studied by nanoindentation testing. The local mechanical parameters as determined by the force measuring ability of atomic force microscopy are compared with the data from both the Oliver–Pharr nanoindentation technique and the continuous stiffness measurements. The impact of the dopant type (Hf and Al) on the surface morphology, elastic modulus and hardness of the films is determined. The results reveal an increase in elastic modulus and hardness after the doping. The irradiation produces a little lower values of mechanical parameters. The results are discussed in juxtaposition with the established previously strong effect of irradiation on the electrical properties of Ta2O5-based stacks. From device perspective point of view Hf-doped Ta2O5 is noteworthy for micro-electro-mechanical system applications.
The RNA-binding protein Y14 inhibits mRNA decapping and modulates processing body formation
Authors: Chuang Tzu-Wei , Chang Wei-Lun , Lee Kuo-Ming , Tarn Woan-Yuh
Published: November 2012

The exon-junction complex (EJC) deposited on a newly spliced mRNA plays an important role in subsequent mRNA metabolic events. Here we show that an EJC core heterodimer, Y14/Magoh, specifically associates with mRNA-degradation factors, including the mRNA-decapping complex and exoribonucleases, whereas another core factor, eIF4AIII/MLN51, does not. We also demonstrate that Y14 interacts directly with the decapping factor Dcp2 and the 5′ cap structure of mRNAs via different but overlapping domains and that Y14 inhibits the mRNA-decapping activity of Dcp2 in vitro. Accordingly, overexpression of Y14 prolongs the half-life of a reporter mRNA. Therefore Y14 may function independently of the EJC in preventing mRNA decapping and decay. Furthermore, we observe that depletion of Y14 disrupts the formation of processing bodies, whereas overexpression of a phosphomimetic Y14 considerably increases the number of processing bodies, perhaps by sequestering the mRNA-degradation factors. In conclusion, this report provides unprecedented evidence for a role of Y14 in regulating mRNA degradation and processing body formation and reinforces the influence of phosphorylation of Y14 on its activity in postsplicing mRNA metabolism.
Endoplasmic spreading requires coalescence of vimentin intermediate filaments at force-bearing adhesions
Authors: Lynch Christopher D. , Lazar Andre M. , Iskratsch Thomas , Zhang Xian , Sheetz Michael P.
Published: November 2012

For cells to develop long-range forces and carry materials to the periphery, the microtubule and organelle-rich region at the center of the cell—the endoplasm—needs to extend to near the cell edge. Depletion of the actin cross-linking protein filamin A (FlnA) causes a collapse of the endoplasm into a sphere around the nucleus of fibroblasts and disruption of matrix adhesions, indicating that FlnA is involved in endoplasmic spreading and adhesion growth. Here, we report that treatment with the calpain inhibitor N-[N-(N-acetyl-l-leucyl)-l-leucyl]-l-norleucine (ALLN) restores endoplasmic spreading as well as focal adhesion (FA) growth on fibronectin-coated surfaces in a Fln-depleted background. Addback of calpain-uncleavable talin, not full-length talin, achieves a similar effect in Fln-depleted cells and indicates a crucial role for talin in endoplasmic spreading. Because FA maturation involves the vimentin intermediate filament (vIF) network, we also examined the role of vIFs in endoplasmic spreading. Wild-type cells expressing a vimentin variant incapable of polymerization exhibit deficient endoplasmic spreading as well as defects in FA growth. ALLN treatment restores FA growth despite the lack of vIFs but does not restore endoplasmic spreading, implying that vIFs are essential for endoplasm spreading. Consistent with that hypothesis, vIFs are always displaced from adhesions when the endoplasm does not spread. In Fln-depleted cells, vIFs extend beyond adhesions, nearly to the cell edge. Finally, inhibiting myosin II–mediated contraction blocks endoplasmic spreading and adhesion growth. Thus we propose a model in which myosin II–mediated forces and coalescence of vIFs at mature FAs are required for endoplasmic spreading.
West Nile virus NS2A protein facilitates virus-induced apoptosis independently of interferon response
Authors: Melian Ezequiel Balmori , Edmonds Judith H. , Nagasaki Tomoko Kim , Hinzman Edward , Floden Nadia , Khromykh Alexander A.
Published: November 2012

The flavivirus NS2A protein is a small, multifunctional protein, involved in replication, virion formation and regulation of the innate immune response. Using the Kunjin strain of West Nile virus (WNVKUN) we previously demonstrated that a single amino acid change from alanine to proline at position 30 of the NS2A protein (A30P) reduced viral cytopathicity in cells and virulence in mice. To further investigate functions of the NS2A protein we have substituted alanine at position 30 with different amino acids (A30 mutants) in a WNVKUN infectious clone. The virulence of mutant viruses in wild-type (WT) and IRF3/IRF7 double-knockout mice was influenced by the amino acid change and ranged from high to low in the order of WT>A30L>A30E>A30P/A30G. Moreover, infection of beta interferon (IFN-β)-deficient Vero cells with A30P virus showed less pronounced chromosomal DNA degradation and lower percentage of cells with positive TUNEL labelling than in WT virus infection, indicating a role for the WT NS2A protein in IFN-independent apoptotic cell death.
Addition of a single N-glycan to street rabies virus glycoprotein enhances virus production
Authors: Yamada Kentaro , Noguchi Kazuko , Nonaka Daichi , Morita Muneshin , Yasuda Aiko , Kawazato Hiroaki , Nishizono Akira
Published: November 2012

Most street rabies virus G proteins have twoN-glycosylation sites, i.e. Asn37and Asn319, whereas additional sites are found in fixed (laboratory adapted) viruses. In this study, we performed a pseudotyped virus assay using G-deficient rabies virus and demonstrated that single-N-glycan additions to the G protein of street rabies virus strain 1088, which are found in adapted strains, enhanced virus production in neural and non-neural cell lines, while additions to Asn194or Asn247enhanced production greatly. Moreover, we found thatN-glycan additions at Asn194or Asn247facilitated the production of cell-associated virus. In contrast, deletion of the sequon at Asn37reduced viral production, while a deletion at Asn319resulted in extensive loss of production. Furthermore, G proteins lacking anN-glycan at Asn319failed to fold into their correct structure and lost their fusion activity, indicating that Asn319N-glycosylation is important for the functional expression of street virus G proteins.
Clinical Outcome and Fusion Rates after the First 30 Extreme Lateral Interbody Fusions
Authors: Malham Gregory M. , Ellis Ngaire J. , Parker Rhiannon M. , Seex Kevin A.
Published: November 2012

Introduction. The lateral transpsoas approach for lumbar interbody fusion (XLIF) is gaining popularity. Studies examining a surgeon's early experience are rare. We aim to report treatment, complication, clinical, and radiographic outcomes in an early series of patients.Methods. Prospective data from the first thirty patients treated with XLIF by a single surgeon was reviewed. Outcome measures included pain, disability, and quality of life assessment. Radiographic assessment of fusion was performed by computed tomography.Results. Average follow-up was 11.5 months, operative time was 60 minutes per level and blood loss was 50 mL. Complications were observed: clinical subsidence, cage breakage upon insertion, new postoperative motor deficit and bowel injury. Approach side-effects were radiographic subsidence and anterior thigh sensory changes. Two patients required reoperation; microforaminotomy and pedicle screw fixation respectively. VAS back and leg pain decreased 63% and 56%, respectively. ODI improved 41.2% with 51.3% and 8.1% improvements in PCS and MCS. Complete fusion (last follow-up) was observed in 85%.Conclusion. The XLIF approach provides superior treatment, clinical outcomes and fusion rates compared to conventional surgical approaches with lowered complication rates. Mentor supervision for early cases and strict adherence to the surgical technique including neuromonitoring is essential.
Economic-Oriented Stochastic Optimization in Advanced Process Control of Chemical Processes
Authors: Dobos László , Király András , Abonyi János
Published: November 2012

Finding the optimal operating region of chemical processes is an inevitable step toward improving economic performance. Usually the optimal operating region is situated close to process constraints related to product quality or process safety requirements. Higher profit can be realized only by assuring a relatively low frequency of violation of these constraints. A multilevel stochastic optimization framework is proposed to determine the optimal setpoint values of control loops with respect to predetermined risk levels, uncertainties, and costs of violation of process constraints. The proposed framework is realized as direct search-type optimization of Monte-Carlo simulation of the controlled process. The concept is illustrated throughout by a well-known benchmark problem related to the control of a linear dynamical system and the model predictive control of a more complex nonlinear polymerization process.
Network Completion Using Dynamic Programming and Least-Squares Fitting
Authors: Nakajima Natsu , Tamura Takeyuki , Yamanishi Yoshihiro , Horimoto Katsuhisa , Akutsu Tatsuya
Published: November 2012

We consider the problem of network completion, which is to make the minimum amount of modifications to a given network so that the resulting network is most consistent with the observed data. We employ here a certain type of differential equations as gene regulation rules in a genetic network, gene expression time series data as observed data, and deletions and additions of edges as basic modification operations. In addition, we assume that the numbers of deleted and added edges are specified. For this problem, we present a novel method using dynamic programming and least-squares fitting and show that it outputs a network with the minimum sum squared error in polynomial time if the maximum indegree of the network is bounded by a constant. We also perform computational experiments using both artificially generated and real gene expression time series data.
DNA methyltransferase3A as a molecular switch mediating the neural tube-to-neural crest fate transition
Authors: Hu Na , Strobl-Mazzulla Pablo , Sauka-Spengler Tatjana , Bronner Marianne E.
Published: November 2012

Here, we explore whether silencing via promoter DNA methylation plays a role in neural versus neural crest cell lineage decisions. We show that DNA methyltransferase3A (DNMT3A) promotes neural crest specification by directly mediating repression of neural genes likeSox2andSox3.DNMT3Ais expressed in the neural plate border, and its knockdown causes ectopicSox2 and Sox3expression at the expense of neural crest markers. In vivo chromatin immunoprecipitation of neural folds demonstrates that DNMT3A specifically associates with CpG islands in theSox2andSox3promoter regions, resulting in their repression by methylation. Thus, DNMT3A functions as a molecular switch, repressing neural to favor neural crest cell fate.
Biology of PIWI-interacting RNAs: new insights into biogenesis and function inside and outside of germlines
Authors: Ishizu Hirotsugu , Siomi Haruhiko , Siomi Mikiko C.
Published: November 2012

PIWI-interacting RNAs (piRNAs) are endogenous small noncoding RNAs that act as guardians of the genome, protecting it from invasive transposable elements in the germline. Animals lacking piRNA functions show defects in gametogenesis and exhibit sterility. Their descendants are also predisposed to inheriting mutations. Thus, the piRNA pathway has evolved to repress transposons post-transcriptionally and/or transcriptionally. A growing number of studies on piRNAs have investigated piRNA-mediated gene silencing, including piRNA biogenesis. However, piRNAs remain the most enigmatic among all of the silencing-inducing small RNAs because of their complexity and uniqueness. Although piRNAs have been previously suggested to be germline-specific, recent studies have shown that piRNAs also play crucial roles in nongonadal cells. Furthermore, piRNAs have also recently been shown to have roles in multigenerational epigenetic phenomena in worms. The purpose of this review is to highlight new piRNA factors and novel insights in the piRNA world.
Sample Processing Considerations for Detecting Copy Number Changes in Formalin-Fixed, Paraffin-Embedded Tissues
Authors: Jacobs Sharoni
Published: November 2012

The Whole Genome Sampling Analysis (WGSA) assay in combination with Affymetrix GeneChip Mapping Arrays is used for copy number analysis of high-quality DNA samples (i.e., samples that have been collected from blood, fresh or frozen tissue, or cell lines). Formalin-fixed, paraffin-embedded (FFPE) samples, however, represent the most prevalent form of archived clinical samples, but they provide additional challenges for molecular assays. FFPE processing usually results in the degradation of FFPE DNA and in the contamination and chemical modification of these DNA samples. Because of these issues, FFPE DNA is not suitable for all molecular assays designed for high-quality DNA samples. Strategies recommended for processing FFPE DNA samples through WGSA and to the Mapping arrays are described here.
The Best Laid Plans: Analyzing Courtship Defects inDrosophila
Authors: Goodwin Stephen F. , O'Dell Kevin M.C.
Published: November 2012

Courtship can be defined as behavioral interactions between males and females, the evolutionary objective of which is copulation and the ultimate perpetuation of the species. This protocol allows determination of two aspects of courtship inDrosophila:to assess whether there is a deficiency in mating frequency and, if this is the case, to resolve the nature of the specific problem. The first part of the approach provides a simple, objective, high-throughput strategy that is ideal for determining whether a specific strain has any courtship defect. Any strain that mates at a frequency comparable to that of wild-type flies must be considered reasonably fit in an evolutionary sense. If a specific strain has an abnormal mating frequency, we are then interested in determining whether there is a specific courtship defect, as described in the second half of the protocol. This requires direct live observation or digital recording of courtship.
Objective-Type Total Internal Reflection Microscopy (Excitation) for Single-Molecule FRET
Authors: Joo Chirlmin , Ha Taekjip
Published: November 2012

Single-molecule (sm) fluorescence detection is a powerful method for studying biological events without time and population averaging. Förster (fluorescence) resonance energy transfer (FRET) is a spectroscopic technique in which the efficiency of energy transfer from donor to acceptor molecules is used to determine distances between molecules in the 30–80 Å range. Structural changes in biological molecules or relative motion between two interacting molecules can be detected by a change in FRET. A variant of smFRET is based on total internal reflection (TIR) microscopy, which can be set up in two ways, either using an oil-immersion (objective-type) or a water-immersion (prism-type) lens. This protocol describes objective-type TIR microscopy (excitation), including setup of the laser beam and epifluorescence microscopy, and conversion of the latter into TIR.
In Vitro Transcription of Labeled RNA: Synthesis, Capping, and Substitution
Authors: Nilsen Timothy W. , Rio Donald C.
Published: November 2012

All in vitro RNA transcription reactions involve the use of common components: a template, phage RNA polymerase, and ribonucleoside triphosphates (rNTPs). The concentration of rNTPs is a crucial variable that is manipulated to determine the specific activities of labeled RNAs. This protocol describes methods used to synthesize RNAs of low specific activity (trace labeled), medium specific activity, and high specific activity. Also described is how the same principles that determine the level of incorporation of labeled rNTPs are applicable to the synthesis of transcripts containing modified nucleotides, including 5′ cap and internal (body) modifications such as biotinylated uridine, 4-thiouridine, and phosphorothiotated nucleotides. Careful attention to detail in setting up the transcription reaction will permit the synthesis of any number of “designer RNAs.”
Lymphangiography of the Mouse Tail
Authors: Jain Rakesh K. , Munn Lance L. , Fukumura Dai
Published: November 2012

The lymphatic system is an important route for metastasis of cancer cells. Lymphatic microvessels have been studied by adapting lymphangiography to the mouse tail. In this technique, a high-molecular-weight fluorescently labeled tracer is injected into the interstitial compartment of the tail tissue. The tracer migrates to the local lymphatic vessels and fills the network, allowing visualization. By implanting a tumor in the tail, the structure and function of the lymphatics at the tumor periphery can be monitored. This protocol describes a method for injecting tumor cells into a mouse tail and for microlymphangiography.
Lymphangiography of the Mouse Ear
Authors: Jain Rakesh K. , Munn Lance L. , Fukumura Dai
Published: November 2012

The lymphatic system is an important route for metastasis of cancer cells. Lymphatic microvessels have been studied by adapting lymphangiography to the mouse ear. In this technique, a high-molecular-weight fluorescently labeled tracer is injected into the interstitial compartment of the ear chamber. The tracer migrates to the local lymphatic vessels and fills the network, allowing visualization. Lymphangiography with Evan's blue dye or fluorescein isothiocyanate (FITC)-dextran reveals a dense auricular network of lymphatic capillaries, draining to a larger vessel at the ear base and subsequently to the exposed superficial cervical lymph node.
Removing rRNA from Deproteinized, Phenol-Extracted Total RNA by Enzymatic Digestion
Authors: Nilsen Timothy W.
Published: November 2012

Ribosomal RNAs (28S, 18S, 5.8S, and 5S rRNAs) comprise the vast majority of total cellular RNAs (>95%). When other RNAs are to be analyzed, it is very advantageous to remove the rRNA species. The best way to eliminate rRNA “contamination” is to pellet subunits before deproteinization. When this is not possible, certain RNAs can be separated from bulk rRNA after extraction. This protocol describes enzymatic digestion to remove rRNAs from deproteinized, phenol-extracted total RNA.
CLIP (Cross-Linking and Immunoprecipitation) Identification of RNAs Bound by a Specific Protein
Authors: Darnell Robert B.
Published: November 2012

Guilt by association remains a powerful argument for assigning function in biological processes: Proteins that bind a specific RNA are strongly implicated in modulating the fate and action of that RNA. Detecting such associations is a major goal in understanding RNA function. The cross-linking and immunoprecipitation (CLIP) method described here allows assignments of RNA-binding proteins to their RNA targets by using ultraviolet (UV) cross-linking to covalently capture close (near-covalent bond distances) association of RNA with protein, followed by immunopurification of the protein partner with extraction and subsequent characterization of the RNA partner sequence(s). Pools of target sequences can be captured and their genomic origins are studied so that regulatory and other functional relationships between the protein and its RNA targets can be inferred. The advantage of this protocol is that it captures only intimately associated RNAs and proteins, and so is expected to be highly specific. Some investigators report capturing cross-links between rRNA and nonribosomal proteins in cases where ribosomes are not efficiently cleared from the lysate before immunopurification of the target protein, so the limits of specificity for the method are yet to be fully explored. Its main disadvantages are its many steps and that it may fail to work for all proteins or capture all legitimate targets of any given protein if the necessary chemical groups are not optimally arranged for photocross-linking in the complex. However, properly performed, this method should provide many useful insights into the nature of the RNA ligands for an RNA-binding protein of interest.
Imaging Intracellular Signaling Using Two-Photon Fluorescent Lifetime Imaging Microscopy
Authors: Yasuda Ryohei
Published: November 2012

The recent development of Förster resonance energy transfer (FRET) sensors and FRET imaging techniques permits visualization of the dynamics of intracellular signaling events with high spatiotemporal resolution. In particular, fluorescence lifetime imaging in combination with two-photon laser-scanning microscopy (two-photon fluorescence lifetime imaging microscopy [2pFLIM]) is a powerful tool to monitor signaling events in small subcellular compartments in thick tissue. This article provides practical guidelines for quantitative imaging of intracellular signaling using 2pFLIM.
Safety and efficacy of four steroid‐minimization protocols in liver transplant recipients: 3‐year follow‐up in a single center
Authors: Hu An Bin , Wu Lin Wei , Tai Qiang , Zhu Xiao Feng , He Xiao Shun
Published: November 2012

Objective

To evaluate the safety and efficacy of steroid‐minimization therapy in liver transplantation (LT) recipients with hepatitis B virus‐related diseases in China.

Methods

From March 2000 to June 2007, 502 adult LT recipients, mostly with hepatitis B (HBV)‐related diseases, were enrolled in our study. Four study groups were setup according to the steroid‐minimization protocols: tacrolimus (TAC) with 6 months steroids withdrawal (6M SW), TAC with 3 months SW (3M SW), TAC with 14 days SW (14d SW), and TAC with basiliximab induction and steroids avoidance (Bas SA). All patients were followed up for at least 36 months after LT.

Results

There were no significant differences in the overall 3‐year survival rates of the patients and graft, and chronic rejection among the four groups (P = 0.092, P = 0.113 and P = 0.684, respectively). There was also no difference in acute rejection within 12 months after LT (P = 0.514). The 3‐year recurrence rates of HBV infection and hepatocellular carcinoma (HCC) after LT were significantly different among all the groups (lowest in TAC/Bas SA group; P = 0.037 and P = 0.029, respectively). The overall incidence of infection was significantly higher in the 6M SW group (62.2% vs 56.1% in 3M SW, 30.5% in 14d SW, 20.5% in Bas SA; P < 0.01). By the end of the 3‐year follow‐up, more than 90% of the surviving patients could safely receive TAC monotherapy.

Conclusion

Bas SA immunosuppressive protocol can be achieved safely in LT and reduce HBV infection and HCC recurrence and side effects of steroids after LT.
Specificity of archaeal caspase activity in the extreme halophile Haloferax volcanii
Authors: Seth‐Pasricha Mansha , Bidle Kelly A. , Bidle Kay D.
Published: November 2012

Caspase‐like proteases are key initiators and executioners of programmed cell death (PCD), which is initiated by environmental stimuli and manifests in organisms ranging from unicellular microbes to higher eukaryotes. Archaea had been absent from the caspase inheritance discussion due to a lack of gene homologues. We recently demonstrated extremely high, basal caspase‐like catalytic activity in the model haloarcheon, Haloferax volcanii, which was linked to the cellular stress response and was widespread among diverse Archaea. Here, we rigorously tested the catalytic specificity of the observed archaeal caspase‐like activities using hydrolytic assays with a diverse suite of protease substrates and inhibitors compared with known model serine and cysteine proteases (trypsin, cathepsin, papain, and human caspase‐8). Our experiments demonstrate that exponentially growing H. volcanii possesses a highly specific caspase‐like activity that most closely resembles caspase‐4, is preferentially inhibited by the pan‐caspase inhibitor, zVAD‐FMK, and has no cross‐reactivity with other known protease families. Our findings firmly root the extremely high levels of caspase‐like activity as the dominant proteolytic activity in this extreme haloarcheaon, thereby providing further support for housekeeping functions in Haloarchaea. Given the deep archaeal roots of eukaryotes, we suggest that this activity served as a foundation for stress pathways in higher organisms.
Gray matter volume alterations related to trait dissociation in PTSD and traumatized controls
Authors: Nardo D. , Högberg G. , Lanius R. A. , Jacobsson H. , Jonsson C. , Hällström T. , Pagani M.
Published: November 2012

Objective

This study used voxel‐based morphometry (VBM) to investigate brain structural alterations related to trait dissociation and its relationship with post‐traumatic stress disorder (PTSD).

Method

Thirty‐two subjects either developing (N = 15) or non‐developing (N = 17) PTSD underwent MRI scanning and were assessed with the Dissociative Experience Scale (DES), subscales for pathological (DES‐T) and non‐pathological trait (DES‐A) dissociation, and other clinical measures. Gray matter volume (GMV) was analyzed using VBM as implemented in SPM. PTSD and non‐PTSD subjects were compared to assess brain alterations related to PTSD pathology, whereas correlation analyses between dissociation measures and GMV were performed on the whole sample (N = 32), irrespective of PTSD diagnosis, to identify alterations related to trait dissociation.

Results

As compared to traumatized controls, PTSD subjects showed reduced GMV in the prefrontal cortex, hippocampus and lingual gyrus. Correlations with dissociation measures (DES, DES‐T, and DES‐A) consistently showed increased GMV in the medial and lateral prefrontal, orbitofrontal, parahippocampal, temporal polar, and inferior parietal cortices.

Conclusion

PTSD and dissociation seem to be associated with opposite volumetric patterns in the prefrontal cortex. Trait dissociation appears to involve increased GMV in prefrontal, paralimbic, and parietal cortices, with negligible differences between pathological and non‐pathological dissociation.
Limited niche differentiation within remarkable co‐occurrences of congeneric species:Monomoriumants in theAustralian seasonal tropics
Authors: ANDERSEN ALAN N. , ARNAN XAVIER , SPARKS KATHRYN
Published: November 2012

Niche theory predicts that few closely related species can co‐occur because such species tend to be ecologically similar and niche differentiation is required to avoid competitive exclusion. We analyse the co‐occurrence of a remarkable 10–15 species of the ant genusMonomoriumoccurring within single 10 × 10 m plots in a tropical savanna of northernAustralia. Most of the species are undescribed, so we use genetic analysis to validate our species demarcations. We document nest dispersion patterns, and investigate differentiation in the three primary niche dimensions: space, time and food. We also examine species differences in competitive abilities, by describing rates of foraging activity, foraging ranges, worker aggression, and levels of behavioural dominance. Analyses of nest and forager distributions showed very limited evidence of spatial segregation within plots. The great majority of species foraged either exclusively or primarily during daylight hours. Body size and isotopic analyses indicated very limited dietary differentiation. Such limited niche partitioning occurred despite the species differing markedly in their competitive abilities as measured by rates of resource discovery, recruitment and monopolization. Our findings defy the traditional assumption that multiple closely related and ecologically similar species of highly interactive taxa cannot co‐occur. It seems very likely that species coexistence in our study system is determined to a very large degree by stochastic processes relating to dispersal and establishment, as predicted by neutral theory. However, neutral theory assumes competitive equivalence, whereas we found very marked differences in the competitive abilities of our co‐occurring species. We suggest that competitive exclusion is prevented by the modular nature of ant colonies, with competition limiting colony performance but not preventing occurrence. We conclude that other factors that allow species persistence, and not just competitive equivalence, can allow dispersal and establishment processes to drive species coexistence.
Reoperation and patient satisfaction after the Mobility total ankle arthroplasty
Authors: Summers Johanne Carly , Bedi Harvinder S.
Published: November 2012

Background

The purpose of the present study was to report on the frequency of reoperation, failure and patient satisfaction after the Mobility total ankle arthroplasty.

Methods

Sixty‐two consecutive primary total ankle arthroplasties in 60 patients were performed with the use of the DePuy Mobility total ankle system between February 2006 and January 2009. Fifty‐eight ankles in 56 patients were followed up between 14 and 49 months (mean: 32 months).

Results

Eighteen ankles (31%) underwent an initial reoperation at a mean time of 14 months after primary total ankle arthroplasty. Only three ankles (17%) had improved symptoms after initial reoperation. Eight of these 18 ankles (44%) underwent a second reoperation. A total of seven ankles (12%) had been revised. Overall, 67% were satisfied, and 79% stated that they would undergo the same operation again.

Discussion

This study on a third‐generation total ankle arthroplasty reported a relatively high rate of reoperation. There was a significant increase in the reported failure when using re‐operation rather than component revision as the end point. This may be one of the inherent limitations in Joint Registry data that only include component revision.
Outcome of extremely low gestational age newborns after introduction of a revised protocol to assist preterm infants in their transition to extrauterine life
Authors: Mehler Katrin , Grimme Judith , Abele Julia , Huenseler Christoph , Roth Bernhard , Kribs Angela
Published: November 2012

Aim:  To evaluate the outcome of a cohort of extremely low gestational age newborn infants (ELGAN) below 26‐week gestation who were treated following a revised, gentle delivery room protocol to assist them in the transition and adaptation to extrauterine life.

Methods:  A cohort of infants with a gestational age (GA) below 26 weeks (study group; n = 164) was treated according to a revised delivery room protocol. The protocol included an optimized prenatal management, strict use of continuous positive airway pressure (CPAP), avoiding mechanical ventilation and early administration of surfactant without intubation. The parameters management of respiratory distress syndrome, survival, neonatal morbidity and neurodevelopmental outcome were compared with a historical control group (n = 44).

Results:  Seventy‐four per cent of the study group infants were initially treated with CPAP and surfactant administration without intubation. In comparison with the control group, significantly less children were intubated in the delivery room (24% vs. 41%) and needed mechanical ventilation (51% vs. 72%; both p < 0.05). Furthermore, compared with the historical control overall mortality (20% vs. 39%), rate of bronchopulmonary dysplasia (18% vs. 37%) and IVH > II° (10% vs. 33%) in survivors were significantly lower during the observational period (all p < 0.05). Neurodevelopmental outcome was normal in 70% of examined study group infants.

Conclusions:  A revised delivery room management protocol was applied safely to infants with a GA below 26 completed weeks with improved rates of survival and morbidity.
Evaluating Helping Babies Breathe: training for healthcare workers at hospitals in Rwanda
Authors: Musafili Aimable , Essén Birgitta , Baribwira Cyprien , Rukundo Alphonse , Persson Lars‐Åke
Published: November 2012

Aim

To evaluate the educational effectiveness of the Helping Babies Breathe programme.

Methods

Knowledge of trainees from two district hospitals and one tertiary referral hospital was evaluated before and after training in 2010. A postcourse practical skills evaluation was performed on a Neonatalie Newborn Simulator. Participants underwent a re‐evaluation after 3 months.

Results

One hundred eighteen trainees completed the course. The percentages of correct answers on a written test significantly increased from 77 ± 15% to 91 ± 9% (p < 0.01) after training. The mean score obtained on a postcourse skill evaluation was 89 ± 9%; 64% of the trainees achieved passing scores. Retesting 3 months later showed that knowledge remained at the same level, while practical skills decreased to 83 ± 16%, and the pass rate dropped significantly to 43% (p < 0.01).

Conclusion

Healthcare workers who participate in a Helping Babies Breathe programme can significantly improve their knowledge. While such knowledge is retained for at least 3 months, skills dropped to unsatisfactory levels in that period of time, indicating the need for retraining in the interim or the acquisition of practical experience by such healthcare workers.
TV viewing and obesity among Norwegian children: the importance of parental education
Authors: Kristiansen Hege , Júlíusson Pétur B , Eide Geir E , Roelants Mathieu , Bjerknes Robert
Published: November 2012

Aim

To analyse the effect of lifestyle factors on the prevalence of overweight and obesity in 6–15‐year‐old Norwegian children.

Methods

Questionnaire data on lifestyle factors (sedentary behaviour, activity and eating habits) and prevalence numbers of overweight and obesity based on measured height and weight were analysed using multinomial logistic regression in a sample of 2281 children included in the Bergen Growth Study.

Results

More screen time increased the risk of overweight (odds ratio (OR): 1.25; p = 0.02) and obesity (OR: 1.12; p = 0.02) as did the presence of a TV in the child's bedroom (OR: 1.26 (overweight), OR: 1.81 (obese); p = 0.04). The obese children reported less sugar intake than the not overweight children (OR: 0.58; p = 0.01). Higher parental education was associated with less screen time (p = 0.02), lower frequency of TV in the child's bedroom (p = 0.001), more sports (p = 0.005), as well as eating more fruit and vegetables, less sweets, soft drinks and fast food, and more regular meals (for all, p < 0.03).

Conclusion

Indicators of sedentary lifestyle, such as screen time and the presence of a TV in the child's bedroom, were associated with overweight and obesity in Norwegian schoolchildren. Higher parental education was generally associated with less obesogenic lifestyle.
Testing the Pediatric Cardiac Quality of Life Inventory in the United Kingdom
Authors: Wray Jo , Franklin Rodney , Brown Kate , Cassedy Amy , Marino Bradley S
Published: November 2012

Aim

To establish the validity and reliability of the Pediatric Cardiac Quality of Life Inventory (PCQLI) for children with heart disease in the United Kingdom.

Methods

Three paediatric cardiac centres recruited patients aged 8–18 years with heart disease. Patient–parent pairs completed a disease‐specific paediatric cardiac quality of life measure (PCQLI), a generic quality of life measure (PedsQL4.0) and behaviour and self‐perception questionnaires. Validity was assessed by correlation of PCQLI scores with heart disease severity, medical care utilization, and PedsQL, behaviour and self‐perception scores, and by correlation of patient and parent PCQLI scores. Reliability was evaluated by administering the PCQLI at two time points.

Results

The study was completed by 771 patient–parent pairs. Validity was confirmed by the association of lower total PCQLI scores with more complex heart disease and a greater number of hospitalizations and cardiac surgeries (all p < 0.001); moderate to good correlations between patient and parent scores (0.50–0.68); and fair to good correlations between scores for the PCQLI and PedsQL4.0 (0.67–0.77), self‐perception (0.42–0.49) and behaviour measures (0.18–0.62). Test–retest reliability correlations were high (0.72–0.90).

Conclusion

The PCQLI is a reliable and valid disease‐specific quality‐of‐life measure for children with heart disease in the United Kingdom.
Transient receptor potential channels in bladder function
Authors: Avelino A. , Charrua A. , Frias B. , Cruz C. , Boudes M. , de Ridder D. , Cruz F.
Published: November 2012

The transient receptor potential (TRP) superfamily of cationic ion channels includes proteins involved in the transduction of several physical and chemical stimuli to finely tune physiological functions. In the urinary bladder, they are highly expressed in, but not restricted to, primary afferent neurons. The urothelium and some interstitial cells also express several TRP channels. In this review, we describe the expression and the known roles of some members of TRP subfamilies, namely TRPV, TRPM and TRPA, in the urinary bladder. The therapeutic interest of modulating the activity of TRP channels to treat bladder dysfunctions is also discussed.
Histology of the venom gland of Trachinus draco (Actinopterygii, Trachinidae)
Authors: Portillo Strempel Andrés , Herrera Ceballos Enrique
Published: November 2012

The structure of the venom gland of Trachinus draco was studied by histological techniques using light microscopy. New structures in the large glandular cells were detected, including concentric cytoplasmic laminae, basal vesicles, silver nitrate staining cytoplasmic granules, and a high affinity for wheat‐germ agglutinin lectin in the cytoplasm of mature large glandular cells.We also describe morphologic changes of the venom gland during thermal test. At low temperatures, the large glandular cells and their nuclei become enlarged, whereas at high temperatures the large glandular cells are smaller and their nuclei irregular in shape. Similarly, samples from fish captured during two opposite seasons showed differences in their nuclei, which were smaller in summer than winter. The larger growth of supporting cells at low temperatures, together with their aggregation during conditions of stress and their vacuoles secretion, suggest that supporting cells could be played several roles.
Clopidogrel variability: role of plasma protein binding alterations
Authors: Ganesan Shobana , Williams Craig , Maslen Cheryl L. , Cherala Ganesh
Published: November 2012

Aim

The large inter‐individual variability in clopidogrel response is attributed to pharmacokinetics. Although, it has been used since the late 1990s the pharmacokinetic fate of clopidogrel and its metabolites are poorly explained. The variable response to clopidogrel is believed to be multi‐factorial, caused both by genetic and non‐genetic factors. In this study, we examined whether the inactive metabolite can alter the plasma protein binding of the active metabolite, thus explaining the large inter‐individual variability associated with clopidogrel response.

Methods

Female subjects (n = 28) with stable coronary disease who were not taking clopidogrel were recruited. Serial blood samples were collected following 300 mg oral dose of clopidogrel, plasma was isolated and quantified for total and free concentrations of active and inactive metabolites. Inhibition of platelet aggregation was measured using the phosphorylated vasodilator stimulated phosphoprotein (VASP) assay.

Results

A significant correlation was observed between VASP and both free (r = 0.49, P < 0.05) and total (r = 0.49, P < 0.05) concentrations of the active metabolite. Surprisingly, we observed a significant correlation with both free (r = 0.42, P < 0.05) and total (r = 0.67, P < 0.001) concentrations of the inactive metabolite as well. Free fractions of the active metabolite rose with increasing protein binding of the inactive metabolite (P < 0.05).

Conclusions

The above in vivo data suggest that the inactive metabolite displaces the active metabolite from binding sites. Thus, the inactive metabolite might increase the free concentration of the active metabolite leading to enhanced inhibition of platelet aggregation. The plasma protein binding mechanism would offer an additional therapeutic strategy to optimize clopidogrel pharmacotherapy.
The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of inhaled fluticasone furoate and vilanterol trifenatate in healthy subjects
Authors: Kempsford Rodger , Allen Ann , Bal Joanne , Rubin David , Tombs Lee
Published: November 2012

Aim

To investigate the effects of the cytochrome P450 3A4 (CYP3A4) inhibitor ketoconazole on the pharmacokinetics (PK) and pharmacodynamics of fluticasone furoate (FF) and vilanterol trifenatate (VI).

Methods

Two double‐blind, randomized, placebo‐controlled, two‐way crossover studies in healthy subjects. In study 1, subjects received single doses of ketoconazole (400 mg) or placebo on days 1–6, with a single dose of inhaled VI (25 μg) on day 5. Pharmacodynamic and PK data were obtained up to 48 h following the VI dose. In study 2, subjects received once daily ketoconazole (400 mg) or placebo for 11 days, with FF/VI (200/25 μg) for the final 7 days. Pharmacodynamic and PK data were obtained up to 48 h following the day 11 dose.

Results

In study 1, there was no effect of co‐administration of ketoconazole and VI on pharmacodynamic or PK parameters. In study 2, co‐administration of ketoconazole and FF/VI had no effect on 0–4 h maximal heart rate or minimal blood potassium {treatment difference [90% confidence interval (CI)] –0.6 beats min–1 (−5.8, 4.5) and 0.04 mmol l−1 (−0.03, 0.11), respectively}, whilst there was a 27% decrease in 24 h weighted mean serum cortisol [treatment ratio (90% CI) 0.73 (0.62, 0.86)]. Co‐administration of ketoconazole increased [percentage change (90% CI)] FF area under the curve (0‐24) and maximal plasma concentration by 36% (16, 59) and 33% (12, 58), respectively, and VI area under the curve (0–t′) and maximal plasma concentration by 65% (38, 97) and 22% (8, 38), respectively.

Conclusion

Co‐administration of FF/VI or VI with ketoconazole resulted in a less than twofold increase in systemic exposure to FF and VI. There was no increase in β‐agonist systemic pharmacodynamic effects, while serum cortisol was decreased by 27%. Co‐administration of FF/VI with strong CYP3A4 inhibitors has the potential to increase systemic exposure to both fluticasone furoate and vilanterol, which could lead to an increase in the potential for adverse reactions.
Correlation of aldo‐ketoreductase (AKR) 1C3 genetic variant with doxorubicin pharmacodynamics in Asian breast cancer patients
Authors: Voon Pei Jye , Yap Hui Ling , Ma Cho‐Yee‐Thu , Lu Fan , Wong Andrea L. A. , Sapari Nur Sabrina , Soong Richie , Soh Thomas I. P. , Goh Boon‐Cher , Lee How‐Sung , Lee Soo‐Chin
Published: November 2012

Aims

Aldo‐ketoreductases have been implicated in the metabolism of doxorubicin. We sought to assess the influence of AKR1C3 genetic variants on doxorubicin metabolism.

Methods

We sequenced AKR1C3 exon 5 and genotyped seven functional single nucleotide polymorphisms in CBR3, ABCB1 and SLC22A16 involved in doxorubicin pharmacology in 151 Asian breast cancer patients treated with doxorubicin‐containing chemotherapy, and correlated these genotypes with doxorubicin pharmacokinetics and pharmacodynamics.

Results

Two previously reported AKR1C3 intronic variants, IVS4–212 C>G and IVS4+218 G>A, were detected. The AKR1C3 IVS4–212 GG genotype was associated with significantly lower cycle 1 day 15 leucocyte (mean leucocytes 2.49 ± 1.57 × 109 vs. 3.85 ± 3.42 × 109 l−1, P = 0.007) and neutrophil counts (mean neutrophils 0.70 ± 1.01 × 109 vs. 1.56 ± 2.80 × 109 l−1, P = 0.008) and significant improvement of progression‐free survival [PFS, mean PFS 49.0 (95% confidence interval 42.2–55.8) vs. 31.0 (95% confidence interval 20.7–41.2) months, P = 0.017] and overall survival [OS; mean OS 64.4 (95% confidence interval 58.3–70.5) vs. 46.3 (95% confidence interval 35.1–57.5) months, P = 0.006] compared with those carrying at least one C allele. There was no significant association between AKR1C3 IVS4–212 C>G and doxorubicin pharmacokinetics. Of the other seven single nucleotide polymorphisms genotyped, CBR3 G11A correlated with doxorubicinol area under the concentration–time curve and OS, ABCB1 G2677T/A correlated with doxorubicin clearance and platelet toxicity, while ABCB1 IVS26+59 T>G correlated with OS. The AKR1C3 IVS4–212 C<G genotype remained significantly correlated with both PFS and OS on multivariate analysis with clinical prognosticators.

Conclusions

The AKR1C3 IVS4–212 GG genotype was associated with greater haematological toxicity and longer progression‐free survival and overall survival after doxorubicin‐based therapy, suggesting potential interaction of this variant with doxorubicin metabolism.