bluuebunny/crossref_metadata_2025 huggingface dataset:
Sonography's Expansion Into Space
Authors: Cole Kendell
Published: October 2008

In 2001, the National Aeronautics and Space Administration (NASA) integrated a sonography machine into the Health Research Facility on the International Space Station. With longer missions in space and a possible trip to Mars, NASA decided the International Space Station needed more diagnostic capabilities. A ground-to-space two-way communication system was set up between the astronauts and the radiologists at Mission Control. A series of studies was conducted to ensure the operating astronauts could produce diagnostic images under remote guidance. Some of the remotely guided studies included ocular examinations, the Focused Assessment with Sonography for Trauma scan, and musculoskeletal examinations.
Cross-sectional indentation technique for thick film interfacial adhesion characterisation
Authors: Lee C. Y. , Dupeux M. , Tuan W. H.
Published: October 2008

The adhesion strength of ceramic/metal interface plays an important role on the reliability of many engineering components. In the present study, the cross-sectional indentation technique is used to determine the interface adhesion of a thick silver film on barium titanate substrate. The test introduces a Vickers micro-indentation at the brittle substrate close to its interface; a small substrate chip is produced to push the thick film laterally and delaminate it from the substrate. The average strength value for the Ag/BaTiO3 interface varies from 2 to 4 J m–2. This is close to the value obtained using a blister technique.
Influence of background gas atmosphere on formation of Cr2O3 thin films prepared by pulsed laser deposition
Authors: Balakrishnan G. , Kuppusami P. , Sairam T. N. , Rao R. V. Subba , Mohandas E. , Sastikumar D.
Published: October 2008

Cr2O3 thin films deposited on Si (100) and glass substrates by pulsed laser deposition using Cr3C2 target were investigated. The films were deposited at base pressure (4 × 10−5 mbar) and at different gas atmospheres, such as argon and methane. X-ray diffraction and X-ray photoelectron spectroscopy studies of the films showed only Cr2O3 phase formation irrespective of the background gas environment during deposition. The films deposited on Si (100) substrates contain nanocrystallites with the size varying in the range 24–72 nm, while that on glass substrates contain crystallites of size varying from 19–56 nm. The ultraviolet visible spectroscopy studies showed that the films are transparent in the visible region. The band gap of the deposited films were calculated using Tauc plot and it was found to exhibit direct band gap in the range 3·10–3·60 eV. The band gap was minimum (3·10 eV) with the argon gas atmosphere, while it is 3·60 eV in methane atmosphere.
Optimisation of anodising electrolyte for magnesium alloy AZ31 and characteristics of anodic film
Authors: Wang H. M. , Chen Z. H. , Cheng Y. L.
Published: October 2008

An environmentally friendly anodising electrolyte for the corrosion protection of magnesium alloy AZ31 was optimised using orthogonal experimental design of four factors with three levels. Electrochemical tests were conducted to determine the corrosion resistance of anodic film. The microstructure and phase composition of the optimised film were characterised by scanning electron microscope and X-ray diffraction respectively. The results show that the optimised electrolyte is composed of 60 g L−1 potassium hydroxide, 20 g L−1 sodium silicate, 30 g L−1 sodium tetraborate and 10 g L−1 sodium phosphate. The significance of electrolyte factors affecting the corrosion resistance of anodic film can be ranked as sodium phosphate>sodium silicate>sodium tetraborate>potassium hydroxide. The optimised film is porous like the basic film, but it is more compact and therefore more corrosion resistant than the basic film. The optimised film is mainly composed of MgO, Mg2SiO4 and MgP4O11.
Structural, mechanical and corrosion properties of NbN films deposited using dc and pulsed dc reactive magnetron sputtering
Authors: Arslan E.
Published: October 2008

NbN thin films were deposited onto silicon wafer and M2 tool steel substrates using dc and pulsed dc reactive magnetron sputtering at 1·5, 2·5 and 3·5 A of target currents. The films were characterised using X-ray diffraction, scanning electron microscopy, microhardness, scratch adhesion tester and potentiodynamic polarisation techniques. The analysis revealed that the structural characteristics, mechanical and corrosion properties of NbN films depend on both deposition mode and target current. With increase in target current, all the films exhibited better structural, mechanical and corrosion properties for both modes. The results indicated that NbN films deposited using pulsed dc magnetron sputtering consistently outperform those deposited using dc magnetron sputtering.
Microstructure characterisation and wear properties of arc sprayed NiB containing amorphous coatings
Authors: Fu B.-Y. , He D.-Y. , Zhao L.-D. , Li X.-Y.
Published: October 2008

Two kinds of cored wires were used to deposit coatings containing amorphous phase and nanocrystalline grains by arc spraying. The microstructure characteristics of the coatings were conducted by scanning electron microscopy (SEM), transmission electron microscopy (TEM), electron probe micro-analyzer (EPMA) and X-ray diffraction (XRD). The microstructures of the both coatings had lamellar morphologies. Both coatings consisted of Fe rich matrix and several kinds of borides. The Fe rich matrix had a majority amorphous phase regions with a fraction of nanocrystalline grains. The coatings’ microhardness values for NiB coating is 950 HV(100 g) and for NiB–Cr3C2 coating is 1090 HV(100 g). Compared with the reference sample of Q235 steel, the coatings showed a much higher wear resistance, and the relative wear resistance of the NiB coating is 10 times while the NiB–Cr3C2 coating is 13·3 times higher than that of Q235 steel.
Thermal spray coating of abradable Ni based composite
Authors: Batra U.
Published: October 2008

Abradable clearance control coatings of compressor and turbine casing of aircraft engines are designed to wear in performance to the opposing blade tip or other moving parts. In the present work the mild steel surface has been coated with KNA (boron nitride, nickel, silicon and carbon) using thermal spray coating technique. The feed rate of the coating material has been optimised or the required hardness of 15 to 25 kg mm−2. The coating has been characterised for porosity, coating thickness, adhesion strength, deposit efficiency and hardness in order to analyse the performance of the coating. Scanning electron microscopy has been carried out to observe the microstructure of the coating and distribution of boron nitride particles.
Comparison of chromium coatings and electrochemical behaviour with direct current and pulse current deposition in trivalent chromium formate urea bath as alternative to conventional Cr coatings
Authors: Mohan S , Saravanan G , Renganathan N G
Published: October 2008

Alternative process to hexavalent chromium (Cr) plating, substitute materials and new designs are urgently needed owing to the requirement of ‘clean’ manufacture. Trivalent Cr coatings with thickness of 29·7 μm, Hardness (HV 1131) and acceptable quality that can be used for wear resistance as well as corrosion resistance purposes were produced successfully in the present work. The results show that the coatings exhibited crack free surface and amorphous/microcrystalline structure. The effect of direct current (DC) and pulse current (PC) on the thickness, hardness and current efficiencies were compared with DC and PC deposition. The Cr coatings were characterised by scanning electron microscope, atomic force microscopy and X-ray diffraction. The morphology of Cr deposits obtained in the formate urea electrolyte is a typical nodular and fine grained structure. As regards to the electrochemical behaviour, the deposited Cr by PC and DC coatings exhibited better corrosion resistance than the mild steel. Therefore, the electroplated Cr coatings are environmentally acceptable to replace the conventional Cr coatings.
Effect of TiAlN PVD coatings on corrosion performance of WC–6%Co
Authors: Gil L. E. , Liscano S. , Goudeau P. , Bourhis E. Le , Puchi-Cabrera E. S. , Staia M. H.
Published: October 2008

The present study has been carried out to evaluate the corrosion performance of three different (Ti1–xAlx)N/TiN multilayers coatings commercially deposited on WC–Co inserts. Two of these coatings were nanostructured, and all of them presented different Ti/Al atomic ratios varying from 2 : 3 up to 7 : 3 and were deposited by employing a commercial physical vapour deposition cathodic arc process. X-ray diffraction analysis indicated that the grain size for both the TiAlN and TiN layers in the coatings architecture, varied between approximately 9 to 14 nm. The corrosion performance was evaluated in a 3 wt-%NaCl solution using both open circuit potential and potentiodynamic polarisation measurements. Scanning electron microscopy and energy dispersive spectroscopy surface characterisation before and after corrosion testing allowed the determination that all the coatings under study show a corrosion current density of approximately one order of magnitude smaller than the uncoated substrate, indicating thus their beneficial effect from the corrosion protection viewpoint.
A retroviral mutagenesis screen reveals strong cooperation between Bcl11a overexpression and loss of the Nf1 tumor suppressor gene
Authors: Yin Bin , Delwel Ruud , Valk Peter J. , Wallace Margaret R. , Loh Mignon L. , Shannon Kevin M. , Largaespada David A.
Published: October 2008

NF1 inactivation occurs in specific human cancers, including juvenile myelomonocytic leukemia, an aggressive myeloproliferative disorder of childhood. However, evidence suggests that Nf1 loss alone does not cause leukemia. We therefore hypothesized that inactivation of the Nf1 tumor suppressor gene requires cooperating mutations to cause acute leukemia. To search for candidate genes that cooperate with Nf1 deficiency in leukemogenesis, we performed a forward genetic screen using retroviral insertion mutagenesis in Nf1 mutant mice. We identified 43 common proviral insertion sites that contain candidate genes involved in leukemogenesis. One of these genes, Bcl11a, confers a growth advantage in cultured Nf1 mutant hematopoietic cells and causes early onset of leukemia of either myeloid or lymphoid lineage in mice when expressed in Nf1-deficient bone marrow. Bcl11a-expressing cells display compromised p21Cip1 induction, suggesting that Bcl11a's oncogenic effects are mediated, in part, through suppression of p21Cip1. Importantly, Bcl11a is expressed in human chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia samples. A subset of AML patients, who had poor outcomes, of 16 clusters, displayed high levels of BCL11A in leukemic cells. These findings suggest that deregulated Bcl11a cooperates with Nf1 in leukemogenesis, and a therapeutic strategy targeting the BCL11A pathway may prove beneficial in the treatment of leukemia.
Urokinase mediates endothelial cell survival via induction of the X-linked inhibitor of apoptosis protein
Authors: Prager Gerald W. , Mihaly Judit , Brunner Patrick M. , Koshelnick Yuri , Hoyer-Hansen Gunilla , Binder Bernd R.
Published: October 2008

Urokinase-type plasminogen activator (uPA) additionally elicits a whole array of pro-angiogenic responses, such as differentiation, proliferation, and migration. In this study, we demonstrate that in endothelial cells uPA also protects against apoptosis by transcriptional up-regulation and partially by mRNA stabilization of inhibitor of apoptosis proteins, most prominently the X-linked inhibitor of apoptosis protein (XIAP). The antiapoptotic activity of uPA was dependent on its protease activity, the presence of uPA receptor (uPAR) and low-density lipoprotein receptor-related protein (LRP), but independent of the phosphatidylinositol 3 (PI3) kinase pathway, whereas vascular endothelial growth factor (VEGF)–induced antiapoptosis was PI3 kinase dependent. uPA-induced cell survival involved phosphorylation of p21-activated kinase 1 (Pak1) and the IκB kinase α that leads to nuclear factor κB (NF-κB) p52 activation. Indeed, blocking NF-κB activation by using specific NF-κB inhibitors abolished uPA-induced cell survival as it blocked uPA-induced XIAP up-regulation. Furthermore, down-regulating XIAP expression by small interfering RNA (siRNA) significantly reduced uPA-dependent endothelial cell survival. This mechanism is also important for VEGF-induced antiapoptosis because VEGF-dependent up-regulation of XIAP was found defective in uPA−/− endothelial cells. This led us to conclude that uPA is part of a novel NF-κB–dependent cell survival pathway.
Evidence for the significant role of immunoglobulin light chains in antigen recognition and selection in chronic lymphocytic leukemia
Authors: Hadzidimitriou Anastasia , Darzentas Nikos , Murray Fiona , Smilevska Tanja , Arvaniti Eleni , Tresoldi Cristina , Tsaftaris Athanasios , Laoutaris Nikolaos , Anagnostopoulos Achilles , Davi Frederic , Ghia Paolo , Rosenquist Richard , Stamatopoulos Kostas , Belessi Chrysoula
Published: October 2008

We analyzed somatic hypermutation (SHM) patterns and secondary rearrangements involving the immunoglobulin (IG) light chain (LC) gene loci in 725 patients with chronic lymphocytic leukemia (CLL). Important differences regarding mutational load and targeting were identified in groups of sequences defined by IGKV/IGLV gene usage and/or K/LCDR3 features. Recurrent amino acid (AA) changes in the IGKV/IGLV sequences were observed in subsets of CLL cases with stereotyped B-cell receptors (BCRs), especially those expressing IGHV3-21/IGLV3-21 and IGHV4-34/IGKV2-30 BCRs. Comparison with CLL LC sequences carrying heterogeneous K/LCDR3s or non-CLL LC sequences revealed that distinct amino acid changes appear to be “CLL-biased.” Finally, a significant proportion of CLL cases with monotypic LC expression were found to carry multiple potentially functional LC rearrangements, alluding to active, (auto)antigen-driven receptor editing. In conclusion, SHM targeting in CLL LCs is just as precise and, likely, functionally driven as in heavy chains. Secondary LC gene rearrangements and subset-biased mutations in CLL LC genes are strong indications that LCs are crucial in shaping the specificity of leukemic BCRs, in association with defined heavy chains. Therefore, CLL is characterized not only by stereotyped HCDR3 and heavy chains but, rather, by stereotyped BCRs involving both chains, which generate distinctive antigen-binding grooves.
Notch signaling is required for proliferation but not for differentiation at a well-defined β-selection checkpoint during human T-cell development
Authors: Taghon Tom , Van de Walle Inge , De Smet Greet , De Smedt Magda , Leclercq Georges , Vandekerckhove Bart , Plum Jean
Published: October 2008

Notch signaling is absolutely required for β-selection during mouse T-cell development, both for differentiation and proliferation. In this report, we investigated whether Notch has an equally important role during human T-cell development. We show that human CD34+ thymocytes can differentiate into CD4+CD8β+ double positive (DP) thymocytes in the absence of Notch signaling. While these DP cells phenotypically resemble human β-selected cells, they lack a T-cell receptor (TCR)–β chain. Therefore, we characterized the β-selection checkpoint in human T-cell development, using CD28 as a differential marker at the immature single positive CD4+CD3−CD8α− stage. Through intracellular TCR-β staining and gene expression analysis, we show that CD4+CD3−CD8α−CD28+ thymocytes have passed the β-selection checkpoint, in contrast to CD4+CD3−CD8α−CD28− cells. These CD4+CD3−CD8α−CD28+ thymocytes can efficiently differentiate into CD3+TCRαβ+ human T cells in the absence of Notch signaling. Importantly, preselection CD4+CD3−CD8α−CD28− thymocytes can also differentiate into CD3+TCRαβ+ human T cells without Notch activation when provided with a rearranged TCR-β chain. Proliferation of human thymocytes, however, is clearly Notch-dependent. Thus, we have characterized the β-selection checkpoint during human T-cell development and show that human thymocytes require Notch signaling for proliferation but not for differentiation at this stage of development.
Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia
Authors: Bougie Daniel W. , Birenbaum Jessica , Rasmussen Mark , Poncz Mortimer , Aster Richard H.
Published: October 2008

Drug-induced immune thrombocytopenia (DITP) is caused by drug-dependent antibodies (DDAbs) that are nonreactive in themselves but bind tightly to specific platelet membrane glycoproteins (GP) when soluble drug is present at pharmacologic concentrations. This reaction takes place without covalent linkage of drug to the target, indicating that drug does not function as a classical hapten to promote antibody binding. Studies to define other mechanism(s) responsible for this interaction have been frustrated by the polyclonal nature of human DDAbs and limited quantities of antibody usually available. We produced 2 monoclonal antibodies (mAbs), 314.1 and 314.3, from a mouse immunized with purified human GPIIb/IIIa and quinine that recognize the N terminus of the GPIIb β propeller domain only when soluble quinine is present. Both monoclonals closely mimic the behavior of antibodies from patients with quinine-induced immune thrombo-cytopenia in their reactions at various concentrations of quinine and quinine congeners. Sequencing studies showed that the 2 mAbs are closely related structurally and that mAb 314.3 probably evolved from mAb 314.1 in the course of the immune response. These monoclonal reagents are the first of their kind and should facilitate studies to define the molecular basis for drug-dependent antibody binding and platelet destruction in DITP.
Normalization of Illumina Infinium whole-genome SNP data improves copy number estimates and allelic intensity ratios
Authors: Staaf Johan , Vallon-Christersson Johan , Lindgren David , Juliusson Gunnar , Rosenquist Richard , Höglund Mattias , Borg Åke , Ringnér Markus
Published: October 2008

Background

Illumina Infinium whole genome genotyping (WGG) arrays are increasingly being applied in cancer genomics to study gene copy number alterations and allele-specific aberrations such as loss-of-heterozygosity (LOH). Methods developed for normalization of WGG arrays have mostly focused on diploid, normal samples. However, for cancer samples genomic aberrations may confound normalization and data interpretation. Therefore, we examined the effects of the conventionally used normalization method for Illumina Infinium arrays when applied to cancer samples.

Results

We demonstrate an asymmetry in the detection of the two alleles for each SNP, which deleteriously influences both allelic proportions and copy number estimates. The asymmetry is caused by a remaining bias between the two dyes used in the Infinium II assay after using the normalization method in Illumina's proprietary software (BeadStudio). We propose a quantile normalization strategy for correction of this dye bias. We tested the normalization strategy using 535 individual hybridizations from 10 data sets from the analysis of cancer genomes and normal blood samples generated on Illumina Infinium II 300 k version 1 and 2, 370 k and 550 k BeadChips. We show that the proposed normalization strategy successfully removes asymmetry in estimates of both allelic proportions and copy numbers. Additionally, the normalization strategy reduces the technical variation for copy number estimates while retaining the response to copy number alterations.

Conclusion

The proposed normalization strategy represents a valuable tool that improves the quality of data obtained from Illumina Infinium arrays, in particular when used for LOH and copy number variation studies.
Domain-specific regulation of foxP2 CNS expression by lef1
Authors: Bonkowsky Joshua L , Wang Xu , Fujimoto Esther , Lee Ji Eun , Chien Chi-Bin , Dorsky Richard I
Published: October 2008

Background

FOXP2 is a forkhead transcription factor critical for normal development of language in humans, but little is known of its broader function and regulation during central nervous system (CNS) development. We report here that lef1, a member of the Lef/Tcf family of transcription factors activated by Wnt signaling, regulates foxP2 during embryogenesis, and we isolate novel foxP2 enhancers which are lef1-dependent.

Results

Loss, knock down, or inhibition of lef1 led to loss of foxP2 expression. We isolated DNA fragments from the foxP2 genomic region that function as enhancers to drive GFP expression in the CNS during development, including in the telencephalon, diencephalon, eye, tectum, and hindbrain. Three of these enhancers, foxP2-enhancerA.1, foxP2-enhancerB, and foxP2-enhancerD, contain putative Lef1 binding sites, and are regulated by lef1. However, two other genomic fragments containing Lef1 sites failed to function in vivo as enhancers. Chromatin immunoprecipitation confirmed that Lef1 binds to sites in foxP2-enhancerA.1 and foxP2-enhancerB.

Conclusion

This work shows that lef1 is necessary for expression of foxP2 in the tectum, mid-hindbrain boundary, and hindbrain during CNS development, and is the first insight into the upstream regulation of foxP2 during development. We also demonstrate that in silico prediction of potential lef1 binding sites poorly predicts their ability to function in vivo as enhancers. The foxP2 enhancers we identified will allow dissection of foxP2's role during CNS development.
Matching curated genome databases: a non trivial task
Authors: Descorps-Declère Stéphane , Barba Matthieu , Labedan Bernard
Published: October 2008

Background

Curated databases of completely sequenced genomes have been designed independently at the NCBI (RefSeq) and EBI (Genome Reviews) to cope with non-standard annotation found in the version of the sequenced genome that has been published by databanks GenBank/EMBL/DDBJ. These curation attempts were expected to review the annotations and to improve their pertinence when using them to annotate newly released genome sequences by homology to previously annotated genomes. However, we observed that such an uncoordinated effort has two unwanted consequences. First, it is not trivial to map the protein identifiers of the same sequence in both databases. Secondly, the two reannotated versions of the same genome differ at the level of their structural annotation.

Results

Here, we propose CorBank, a program devised to provide cross-referencing protein identifiers no matter what the level of identity is found between their matching sequences. Approximately 98% of the 1,983,258 amino acid sequences are matching, allowing instantaneous retrieval of their respective cross-references. CorBank further allows detecting any differences between the independently curated versions of the same genome. We found that the RefSeq and Genome Reviews versions are perfectly matching for only 50 of the 641 complete genomes we have analyzed. In all other cases there are differences occurring at the level of the coding sequence (CDS), and/or in the total number of CDS in the respective version of the same genome.

CorBank is freely accessible at http://www.corbank.u-psud.fr. The CorBank site contains also updated publication of the exhaustive results obtained by comparing RefSeq and Genome Reviews versions of each genome. Accordingly, this web site allows easy search of cross-references between RefSeq, Genome Reviews, and UniProt, for either a single CDS or a whole replicon.

Conclusion

CorBank is very efficient in rapid detection of the numerous differences existing between RefSeq and Genome Reviews versions of the same curated genome. Although such differences are acceptable as reflecting different views, we suggest that curators of both genome databases could help reducing further divergence by agreeing on a minimal dialogue and attempting to publish the point of view of the other database whenever it is technically possible.
Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection
Authors: Idh Jonna , Westman Anna , Elias Daniel , Moges Feleke , Getachew Assefa , Gelaw Aschalew , Sundqvist Tommy , Forslund Tony , Alemu Addis , Ayele Belete , Diro Ermias , Melese Endalkachew , Wondmikun Yared , Britton Sven , Stendahl Olle , Schön Thomas
Published: October 2008

Background

Nitric oxide (NO) is essential for host defense in rodents, but the role of NO during tuberculosis (TB) in man remains controversial. However, earlier observations that arginine supplementation facilitates anti-TB treatment, supports the hypothesis that NO is important in the host defense against TB. Local production of NO measured in fractional exhaled air (FeNO) in TB patients with and without HIV co-infection has not been reported previously. Thus, our aim was to investigate levels of FeNO in relation to clinical symptoms and urinary NO metabolites (uNO).

Methods

In a cross sectional study, FeNO and uNO were measured and clinical symptoms, chest x-ray, together with serum levels of arginine, tumor necrosis factor alpha (TNF-alpha) and interleukin 12 (IL-12) were evaluated in sputum smear positive TB patients (HIV+/TB, n = 36, HIV-/TB, n = 59), their household contacts (n = 17) and blood donors (n = 46) from Gondar University Hospital, Ethiopia.

Results

The proportion of HIV-/TB patients with an increased FeNO level (> 25 ppb) was significantly higher as compared to HIV+/TB patients, but HIV+/TB patients had significantly higher uNO than HIV-/TB patients. HIV+ and HIV-/TB patients both had lower levels of FeNO compared to blood donors and household contacts. The highest levels of both uNO and FeNO were found in household contacts. Less advanced findings on chest x-ray, as well as higher sedimentation rate were observed in HIV+/TB patients as compared to HIV-/TB patients. However, no significant correlation was found between FeNO and uNO, chest x-ray grading, clinical symptoms, TNF-alpha, IL-12, arginine levels or sedimentation rate.

Conclusion

In both HIV negative and HIV co infected TB patients, low levels of exhaled NO compared to blood donors and household were observed. Future studies are needed to confirm whether low levels of exhaled NO could be a risk factor in acquiring TB and the relative importance of NO in human TB.
The clinicopathological and prognostic impact of 14-3-3 sigma expression on vulvar squamous cell carcinomas
Authors: Wang Zhihui , Tropè Claes G , Suo Zhenhe , Trøen Gunhild , Yang Guanrui , Nesland Jahn M , Holm Ruth
Published: October 2008

Background

14-3-3 sigma (σ) promotes G2/M cell cycle arrest by sequestering cyclin B1-CDC2 complex in cytoplasm. Down-regulation of 14-3-3σ, which has been demonstrated in various carcinomas, may contribute to malignant transformation. However, the exact role of 14-3-3σ in the pathogenesis of vulvar carcinoma is not fully characterized, and the prognostic impact of 14-3-3σ protein expression is still unknown.

Methods

We investigated the 14-3-3σ expression in a series of 302 vulvar squamous cell carcinomas using immunohistochemistry and its associations with clinicopathological factors and clinical outcome.

Results

In cytoplasm, nucleus and cytoplasm/nucleus of vulvar carcinomas high 14-3-3σ protein expression was found in 72%, 59% and 75% of the carcinomas, respectively, and low levels in 28%, 41% and 25% of the cases, respectively. High level of 14-3-3σ in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to large tumor diameter (p = 0.001, p = 0.002 and p = 0.001, respectively) and deep invasion (p = 0.01, p = 0.001 and p = 0.007, respectively). Variations of 14-3-3σ protein expression were not associated to disease-specific survival.

Conclusion

Our results indicate that 14-3-3σ may be involved in the development of a subset of vulvar squamous cell carcinomas by down-regulation of 14-3-3σ protein. Neither cytoplasmic nor nuclear level of 14-3-3σ expression was associated with prognosis.
Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants: carrot study
Authors: Westerbeek Elisabeth AM , van Elburg Ruurd M , Berg Anemone van den , Berg Jolice van den , Twisk Jos WR , Fetter Willem PF , Lafeber Harrie N
Published: October 2008

Background

Prevention of serious infections in preterm infants is a challenge, since prematurity and low birth weight often requires many interventions and high utility of devices. Furthermore, the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system. In combination with delayed intestinal bacterial colonisation compared with term infants, this may increase the risk for serious infections. Acidic and neutral oligosaccharides play an important role in the development of the immune system, intestinal bacterial colonisation and functional integrity of the gut. This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity (primary outcome), immune response to immunizations, feeding tolerance and short-term and long-term outcome in preterm infants. In addition, an attempt is made to elucidate the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut.

Methods/Design

In a double-blind placebo controlled randomised trial, 120 preterm infants (gestational age <32 weeks and/or birth weight <1500 gram) are randomly allocated to receive enteral acidic and neutral oligosaccharides supplementation (20%/80%) or placebo supplementation (maltodextrin) between day 3 and 30 of life. Primary outcome is infectious morbidity (defined as the incidence of serious infections). The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations, plasma cytokine concentrations, faecal Calprotectin and IL-8. The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance, intestinal permeability, intestinal viscosity, and determining intestinal microflora. Furthermore, short-term and long-term outcome are evaluated.

Discussion

Especially preterm infants, who are at increased risk for serious infections, may benefit from supplementation of prebiotics. Most studies with prebiotics only focus on the colonisation of the intestinal microflora. However, the pathways how prebiotics may influence the immune system are not yet fully understood. Studying the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants. The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system. Increased insight in the effects of prebiotics on the developing immune system may help to decrease the (infectious) morbidity and mortality in preterm infants.

Trial registration

Current Controlled Trials ISRCTN16211826.
Isolated metastatic extremity liposarcoma to the liver, an uncommon and transient finding
Authors: Garces Christopher A , Reith John D , Grobmyer Stephen R , Hochwald Steven N
Published: October 2008

Background

Extremity liposarcomas can metastasize to different areas of the body but have rarely been demonstrated to metastasize to the liver. Due to the unusual occurrence of isolated metastatic extremity liposarcoma to the liver, the optimal treatment of this condition is unknown.

Case presentation

Less than one year after resection of a myxoid/round cell liposarcoma of the left lateral calf, a 61-year-old male presented with a CT scan showing a 2 cm low-density lesion in the right lobe of the liver. The lesion tripled in size over the next few months. An extensive evaluation revealed isolated disease to the liver. The lesion was surgically removed with a right hepatic lobectomy and the pathology was consistent with metastatic myxoid/round cell liposarcoma.

Conclusion

Although extremity liposarcoma rarely metastasizes solely to the liver, the best chance at cure is with complete resection. Unfortunately, cure rates are very low in the setting of metastatic disease. As expected, the patient experienced progression of disease at sites outside of the liver 5 months after the liver resection.
Flexible Two-Phase studies for rare exposures: Feasibility, planning and efficiency issues of a new variant
Authors: Wild Pascal , Andrieu Nadine , Goldstein Alisa M , Schill Walter
Published: October 2008

The two-phase design consists of an initial (Phase One) study with known disease status and inexpensive covariate information. Within this initial study one selects a subsample on which to collect detailed covariate data. Two-phase studies have been shown to be efficient compared to standard case-control designs. However, potential problems arise if one cannot assure minimum sample sizes in the rarest categories or if recontact of subjects is difficult.

In the case of a rare exposure with an inexpensive proxy, the authors propose the flexible two-phase design for which there is a single time of contact, at which a decision about full covariate ascertainment is made based on the proxy. Subjects are screened until the desired numbers of cases and controls have been selected for full data collection. Strategies for optimizing the cost/efficiency of this design and corresponding software are presented. The design is applied to two examples from occupational and genetic epidemiology. By ensuring minimum numbers for the rarest disease-covariate combination(s), we obtain considerable efficiency gains over standard two-phase studies with an improved practical feasibility.

The flexible two-phase design may be the design of choice in the case of well targeted studies of the effect of rare exposures with an inexpensive proxy.
Questions on causality and responsibility arising from an outbreak of Pseudomonas aeruginosa infections in Norway
Authors: Iversen Bjørn G , Hofmann Bjørn , Aavitsland Preben
Published: October 2008

In 2002, Norway experienced a large outbreak of Pseudomonas aeruginosa infections in hospitals with 231 confirmed cases. This fuelled intense public and professional debates on what were the causes and who were responsible. In epidemiology, other sciences, in philosophy and in law there is a long tradition of discussing the concept of causality. We use this outbreak as a case; apply various theories of causality from different disciplines to discuss the roles and responsibilities of some of the parties involved. Mackie's concept of INUS conditions, Hill's nine viewpoints to study association for claiming causation, deterministic and probabilistic ways of reasoning, all shed light on the issues of causality in this outbreak. Moreover, applying legal theories of causation (counterfactual reasoning and the "but-for" test and the NESS test) proved especially useful, but the case also illustrated the weaknesses of the various theories of causation.

We conclude that many factors contributed to causing the outbreak, but that contamination of a medical device in the production facility was the major necessary condition. The reuse of the medical device in hospitals contributed primarily to the size of the outbreak. The unintended error by its producer – and to a minor extent by the hospital practice – was mainly due to non-application of relevant knowledge and skills, and appears to constitute professional negligence. Due to criminal procedure laws and other factors outside the discourse of causality, no one was criminally charged for the outbreak which caused much suffering and shortening the life of at least 34 people.
Protocol of an expertise based randomized trial comparing surgical Venae Sectio versus radiological Puncture of Vena Subclavia for insertion of Totally Implantable Access Port in oncological patients
Authors: Knebel Philip , Fischer Lars , Cremonese Eva , Lopez-Benitez Ruben , Stampfl Ulrike , Radeleff Boris , Kauczor Hans-Ulrich , Büchler Markus W , Seiler Christoph M
Published: October 2008

Background

Totally Implantable Access Ports (TIAP) are being extensively used world-wide and can be expected to gain further importance with the introduction of new neoadjuvant and adjuvant treatments in oncology. Two different techniques for the implantation can be selected: A direct puncture of a central vein and the utilization of a Seldinger device or the surgical Venae sectio. It is still unclear which technique has the optimal benefit/risk ratio for the patient.

Design

A single-center, expertise based randomized, controlled superiority trial to compare two different TIAP implantation techniques. 100 patients will be included and randomized pre-operatively. All patients aged 18 years or older scheduled for primary elective implantation of a TIAP under local anesthesia who signed the informed consent will be included. The primary endpoint is the primary success rate of the randomized technique. Control Intervention: Venae Sectio will be employed to insert a TIAP by a surgeon; Experimental intervention: Punction of V. Subclavia will be used to place a TIAP by a radiologist. Duration of study: Approximately 10 months, follow up time: 90 days.

Organisation/Responsibility

The PORTAS 2 – Trial will be conducted in accordance with the protocol and in compliance with the moral, ethical, and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and Good Clinical Practice (GCP). The Center of Clinical Trials at the Department of Surgery, University Hospital Heidelberg is responsible for design and conduct of the trial including randomization and documentation of patients' data. Data management and statistical analysis will be performed by the independent Institute for Medical Biometry and Informatics (IMBI), University of Heidelberg.

Trial Registration

The trial is registered at ClinicalTrials.gov (NCT00600444).
Mucinous breast carcinoma presenting as Paget's disease of the nipple in a man: A case report
Authors: Peschos Dimitrios , Tsanou Elena , Dallas Pavlos , Charalabopoulos Konstantinos , Kanaris Christos , Batistatou Anna
Published: October 2008

Introduction

Male breast cancer is rare compared to its female counterpart representing less than 1% of cancer in men. Moreover, mucinous carcinoma of the male breast is an extremely rare histological subtype of malignancy. Paget's disease of the nipple is rarely observed in males.

Case report

Herein, we describe a unique case of an 86 years old man with mucinous breast cancer presenting as Paget's disease of the nipple. According to the immunohistochemical evaluation the neoplastic cells were positive for estrogen (ER) and progesterone receptors (PR).

Conclusion

To our best knowledge this is the first case of mucinous male breast cancer presenting as Paget's disease of the nipple.
Selective segregation of DNA strands persists in long label retaining mammary cells during pregnancy
Authors: Booth Brian W , Boulanger Corinne A , Smith Gilbert H
Published: October 2008

Introduction

During pregnancy the mammary epithelial compartment undergoes extreme proliferation and differentiation, facilitated by stem/progenitor cells. Mouse mammary epithelium in nonpregnant mice contains long label-retaining epithelial cells (LREC) that divide asymmetrically and retain their template DNA strands. The role of LREC during alveogenesis has not been determined.

Methods

We performed immunohistochemistry and autoradiography on murine mammary glands that had been labeled with 5-bromodeoxyuridine (5BrdU) during allometric ductal growth to investigate the co-expression of DNA label retention and estrogen receptor-α or progesterone receptor during pregnancy. A second DNA label ([3H]-thymidine) was administered during pregnancy to identify label-retaining cells (LRC), which subsequently enter the cell cycle. Use of this methodology allowed us to investigate the co-localization of 5BrdU with smooth muscle actin, CD31, cytokeratin, and desmin in periductal or peri-acinar LRC in mammary tissue from pregnant mice subsequent to a long chase period in order to identify LRC.

Results

Estrogen receptor-α positive and progesterone receptor positive cells represented approximately 30% to 40% of the LREC, which is under 1.0% of the epithelial subpopulation. Pregnancy altered the percentage of LREC expressing estrogen receptor-α. LRC situated in periductal or peri-acinar positions throughout the gland do not express epithelial, endothelial, or myoepithelial markers, and these undefined LRCs persist throughout pregnancy. Additionally, new cycling LREC ([3H]-thymidine retaining) appear during alveologenesis, and LRC found in other tissue types (for example, endothelium and nerve) within the mammary fat pad become double labeled during pregnancy, which indicates that they may also divide asymmetrically.

Conclusions

Our findings support the premise that there is a subpopulation of LREC in the mouse mammary gland that persists during alveologenesis. These cells react to hormonal cues during pregnancy and enter the cell cycle while continuing to retain, selectively, their original template DNA. In addition, nonepithelial LRC are found in periductal or peri-acinar positions. These LRC also enter the cell cycle during pregnancy. During alveologenesis, newly created label-retaining ([3H]-thymidine) epithelial cells appear within the expanding alveoli and continue to cycle and retain their original template DNA ([3H]-thymidine) strands, as determined by a second pulse of 5BrdU.
Age-dependent, polyclonal hyperactivation of T cells is reduced in TNF-negativegld/gldmice
Authors: Wiede Florian , Roomberg Alicia , Cretney Erika , Lechner Anja , Fromm Phillip , Wren Leia , Smyth Mark J , Körner Heinrich
Published: October 2008

The generalized lymphoproliferative disorder (gld) mouse strain is characterized by severe splenomegaly/lymphadenopathy, the production of autoimmune antibodies, and the appearance of CD4/CD8-negative T cells. An additional TNF deficiency of gld/gld mice attenuates the course of the disorder through a yet-unknown mechanism. In this study, we could demonstrate that the reduced splenomegaly and lymphadenopathy in B6.gld/gld.TNF−/− mice were correlated with a decreased peripheral T cell proliferation rate and a delayed polyclonal activation. A comparative analysis of naïve T cells and memory/effector T cells showed an age-dependent difference in the T cell activation pattern in the spleen of B6.gld/gld and B6.gld/gld.TNF−/− mice. T cells from B6.gld/gld.TNF−/− spleens and lymph nodes showed significantly higher levels of CCR7 and CD62 ligand on their surface compared with B6.gld/gld mice when mice of the same age were compared. Additionally, we found an increased titer of the Th1 cytokine IFN-γ in the serum of B6.gld/gld mice, whereas the concentration of IFN-γ was markedly reduced in the serum of B6.gld/gld.TNF−/− mice. These findings support the hypothesis that increased T cell activation and proliferation in the presence of TNF contribute to the exacerbation of the gld syndrome.
Direct observations of the kinetics of migrating T cells suggest active retention by endothelial cells with continual bidirectional migration
Authors: McGettrick Helen M , Hunter Kirsty , Moss Paul A , Buckley Christopher D , Rainger G Ed , Nash Gerard B
Published: October 2008

The kinetics and regulatory mechanisms of T cell migration through the endothelium have not been fully defined. In experimental, filter-based assays in vitro, transmigration of lymphocytes takes hours, compared with minutes, in vivo. We cultured endothelial cell (EC) monolayers on filters, solid substrates, or collagen gels and treated them with TNF-α, IFN-γ, or both prior to analysis of lymphocyte migration in the presence or absence of flow. PBL, CD4+ cells, or CD8+ cells took many hours to migrate through EC-filter constructs for all cytokine treatments. However, direct microscopic observations of EC filters, which had been mounted in a flow chamber, showed that PBL crossed the endothelial monolayer in minutes and were highly motile in the subendothelial space. Migration through EC was also observed on clear plastic, with or without flow. After a brief settling without flow, PBL and isolated CD3+ or CD4+ cells crossed EC in minutes, but the numbers of migrated cells varied little with time. Close observation revealed that lymphocytes migrated back and forth continuously across endothelium. Under flow, migration kinetics and the proportions migrating back and forth were altered little. On collagen gels, PBL again crossed EC in minutes and migrated back and forth but showed little penetration of the gel over hours. In contrast, neutrophils migrated efficiently through EC and into gels. These observations suggest a novel model for lymphoid migration in which EC support migration but retain lymphocytes (as opposed to neutrophils), and additional signal(s) are required for onward migration.
Comparison of AIRGrav and GT-1A airborne gravimeters for research applications
Authors: Studinger Michael , Bell Robin , Frearson Nick
Published: October 2008

Airborne gravimetry has played a vital role in contributing to our knowledge of the subglacial environment in polar regions. Previous programs have produced extensive gravity data sets in Antarctica, but the resolution and accuracy of the data have been limited. We have evaluated the relative performance and suitability of two different airborne gravimeters for research applications from flight tests over the Canadian Rocky Mountains near Calgary. Survey design, mission profiles, and demands on the performance of an airborne gravimeter are different for the remote polar environment than for most commercial exploration surveys. Both systems, the AIRGrav and GT-1A, can produce higher-resolution data with improved flight efficiency than can the BGM-3 and LaCoste & Romberg gravimeters used in Antarctica. The AIRGrav and GT-1A systems are capable of draped flying of airborne gravity, allowing new applications for polar use. Both systems could provide the academic community with a significant increase in accuracy and horizontal resolution to enable major advances in understanding the subglacial environment. Compared to the GT-1A system, the AIRGrav system has a lower noise level and higher accuracy, and it is less sensitive to changing flight conditions — in particular, vertical accelerations during turbulent flights.