bluuebunny/crossref_metadata_2025 huggingface dataset:
The path to the high performance thermal building insulation materials and solutions of tomorrow
Authors: Jelle Bjørn Petter , Gustavsen Arild , Baetens Ruben
Published: July 2010

In today’s society there is an increased focus on various energy aspects. Buildings constitute a large part of the total energy consumption in the world. In this respect it is important to have the optimum heat balance in buildings. That is, in a cold climate one wants to have as well thermally insulated building envelopes as possible. However, even in cold climates there might often be relatively long periods of overheating in the buildings, for example, due to solar heat gains and excessive heat loads from miscellaneous indoor activities. In warm climates overheating is most often the case, for example, in office work spaces with large window glass facades and extensive use of electrical equipment. Insulation retrofit is among the most cost-effective measures, even more cost-effective than, for example, solar photovoltaics. The traditional thermal insulation materials of today have typically thermal conductivities between 33 and 40 mW/(mK). State-of-the-art thermal insulation includes vacuum insulation panels (VIPs) with conductivities between 3 and 4 mW/(mK) in fresh condition to typically 8 mW/(mK) after 25 years aging due to water vapor and air diffusion into the VIP core material, which has an open pore structure. Puncturing the VIP envelope causes an increase in the thermal conductivity to about 20 mW/(mK). The main emphasis of this work centers around the possibilities of inventing and developing innovative and robust highly thermal insulating materials. That is, within this work the objective is to go beyond VIPs and other current state-of-the-art technologies. New concepts are introduced, that is, advanced insulation materials (AIMs) as vacuum insulation materials (VIMs), gas insulation materials (GIMs), nano insulation materials (NIMs), and dynamic insulation materials (DIMs). These materials may have closed pore structures (VIMs and GIMs) or either open or closed pore structures (NIMs). The DIMs aim at controlling the material insulation properties, that is, solid state thermal conductivity, emissivity, and pore gas content. Fundamental theoretical studies aimed at developing an understanding of the basics of thermal conductance in solid state matter at an elementary and atomic level have been addressed. The ultimate goal of these studies is to develop tailor-made novel high performance thermal insulation materials and dynamic insulation materials, the latter one enabling to control and regulate the thermal conductivity in the materials themselves, that is from highly insulating to highly conducting. Furthermore, requirements of the future high performance thermal insulation materials and solutions have been proposed. At the moment, the NIM solution seems to represent the best high performance low conductivity thermal solution for the foreseeable future. If robust and practical DIMs can be manufactured, they have great potential due to their thermal insulation regulating abilities.
Therapy options in pulmonary alveolar proteinosis
Authors: Luisetti Maurizio , Kadija Zamir , Mariani Francesca , Rodi Giuseppe , Campo Ilaria , Trapnell Bruce C.
Published: July 2010

Pulmonary alveolar proteinosis is a rare condition characterized by the accumulation of lipoproteinaceous material within the airspaces, resulting in impaired gas transfer, and clinical manifestations ranging from asymptomatic to severe respiratory failure. To the best of the authors’ knowledge, there are only a few conditions whose natural history has been so dramatically changed by the influence of advances in basic science, clinical medicine, and translational research in therapeutic approaches. Whole-lung lavage is the current standard of care and it plays a critical role as a modifier factor of the natural history of proteinosis. That notwithstanding, the identification of autoantibodies neutralizing granulocyte-macrophage colony-stimulating factor in serum and lung of patients affected by the form of proteinosis previously referred to as idiopathic, has opened the way to novel therapeutic options, such as supplementation of exogenous granulocyte-macrophage colony-stimulating factor, or strategies aimed at reducing the levels of the autoantibodies. The aim of this paper is to provide an updated review of the current therapeutic approach to proteinosis.
A hydrothermal clay mineral assemblage at the Late Proterozoic unconformity in the Buenos Aires Complex – La Tinta Formation, Barker area, Tandilia Ranges (Argentina)
Authors: Martínez J. C. , Dristas J. A. , Massonne H.-J. , Theye T.
Published: July 2010

A general alteration pattern of two transitional clay mineral assemblages was determined by petrography and X-ray diffractometry studies at the Tandilia Late Proterozoic unconformity zone, around the Barker locality: (1) K-white mica + chlorite + calcite ± anatase-rutile ± secondary quartz (farther from the unconformity) and (2) pyrophyllite + K-white mica + Ti-rich hematite ± aluminium phosphate-sulphate minerals ± tourmaline ± anatase-rutile (closer to the unconformity). The local occurrence of Na in K-white micas and K-Na in pyrophyllite is described for the first time. Possible interlayering with intermediate K-Na mica and paragonite is indicated by detailed X-ray diffraction analyses. A negative Eu anomaly (Eu/Eu* = 0.24), strongly positive Eu anomaly (Eu/Eu* =11.7) and positive Ce anomaly characterized rapid changes from an unaltered basement to the most altered basement and sedimentary rocks at the unconformity. Aluminium phosphate-sulphate minerals dominate patterns of LREE. A model of hydrothermal alteration comparable to that of unconformity-related uranium deposits is presented.
Fluoroleakeite, NaNa2(Mg2Fe3+2Li)Si8O22F2, a new mineral of the amphibole group from the Verkhnee Espe deposit, Akjailyautas Mountains, Eastern Kazakhstan District, Kazakhstan: description and crystal structure
Authors: Cámara F. , Hawthorne F. C. , Ball N. A. , Bekenova G. , Stepanov A. V. , Kotel'nikov P. E.
Published: July 2010

Fluoroleakeite, NaNa2(Mg2Fe3+2Li)Si8O22F2 is a new mineral of the amphibole group from the Verkhnee Espe deposit, Akjailyautas mountains, eastern Kazakhstan district, Kazakhstan. The granites and their host rocks have been intensely reworked by post-magmatic and host-rock fluids, resulting in intense recrystallization, enrichment in F, Li and rare elements, and replacement of primary biotite and sodic-calcic amphiboles by Li-bearing riebeckite, aegirine, astrophyllite and other sodic minerals including fluoroleakeite. Crystals are prismatic parallel to [001] with {100} and {110} faces and cleavage surfaces, and the prism direction is terminated by irregular fractures. Grains are up to 3 mm long, and occur as isolated crystals, as small aggregates, and as inclusions in cámaraite. Crystals are black with a very pale grey to colourless streak. Fluoroleakeite is brittle, has a Mohs hardness of 6 and a splintery fracture; it is non-fluorescent with perfect {110} cleavage, no observable parting, and has a calculated density of 3.245 g cm–3. In plane-polarized light, it is pleochroic, X = pale grey-green, Y = medium grey, Z = grey-brown; X^a = 14.1° (in β obtuse), Y ‖ b, Z^c = 75.9° (in β acute). Fluoroleakeite is biaxial negative, α = 1.663(2), β = 1.673(2), γ = 1.680(2); 2Vobs = 80.9(6)°, 2Vcalc = 79.4°

Fluoro-leakeite is monoclinic, space group C2/m, a = 9.8927(3), b = 17.9257(6), c = 5.2969(2) Å, β = 103.990(1)°, V = 905.7(1) Å3, Z = 2. The strongest ten X-ray diffraction lines in the powder pattern are [d in Å(I)(hkl)]: 2.718(100)(151), 8.434(40)(110), 4.464(30)(021), 3.405(30)(131), 3.137(20)(310), 2.541(20)(), 2.166(20)(261), 2.325(15)(), 2.275(15)() and 2.806(10)(330). Analysis by a combination of electron microprobe and crystal-structure refinement gives SiO2 53.34, Al2O3 0.62, TiO2 1.27, V2O3 0.05, Fe2O3 15.10, FeO 6.00, MnO 2.04, ZnO 0.18, MgO 6.40, CaO 0.13, Na2O 9.08, K2O 1.98, Li2O 1.10, F 3.33, H2Ocalc 0.16, sum 99.39 wt.%. The formula unit, calculated on the basis of 23 O, is A(Na0.64K0.38)(Na1.98Ca0.02)(Li0.66Mg1.42Fe0.752+Mn0.262+Zn0.02Fe1.693+V0.013+Ti0.144+Al0.03) (Si7.93Al0.07)O22(F1.57OH0.16O0.27). Crystal-structure refinement shows Li to be completely ordered at the M(3) site. Fluoroleakeite, ideally NaNa2(Mg2Fe23+Li)Si8O22F2, is related to end-member leakeite, NaNa2(Mg2Fe23+Li)Si8O22(OH)2 by the substitution F → (OH).
Thermal behaviour of libethenite from room temperature up to dehydration
Authors: Zema M. , Tarantino S. C. , Callegari A. M.
Published: July 2010

The structural modifications with temperature of libethenite, Cu2(PO4)(OH), were determined by single-crystal X-ray diffraction up to dehydration and consequent decomposition of the crystal under investigation. In the temperature range 25–475°C, libethenite shows positive and linear expansion. The axial thermal expansion coefficients, determined over this temperature range, are: αa = 6.6(1)·10–6 K–1, αb = 1.21(2)·10–5 K–1, αc = 9.0(2)·10–6 K–1, αv = 2.78(3)·10–5 K–1. Axial expansion is then anisotropic with αa:αb:αc = 1:1.83:1.33.

Structure refinements of X-ray diffraction data collected at different temperatures allowed us to characterize the mechanisms by which the libethenite structure accommodates variations in temperature. Increasing temperature induces expansion of both Cu polyhedra and no significant variation of the PO4 tetrahedron, which acts as a rigid unit. Cu(1) octahedra expand mostly as a consequence of the increase of the axial bonds, and become more distorted. Starting from T = 500°C, precursor signs of incoming dehydration are visible: two adjacent OH groups approach each other and cause dramatic changes in the whole structure. Concomitantly, the libethenite crystal begins to deteriorate and, at T = 600°C, broad and weak diffraction effects of polycrystalline material are observed.
A protease-resistant PML-RARα has increased leukemogenic potential in a murine model of acute promyelocytic leukemia
Authors: Uy Geoffrey L. , Lane Andrew A. , Welch John S. , Grieselhuber Nicole R. , Payton Jacqueline E. , Ley Timothy J.
Published: July 2010

Previous studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves promyelocytic leukemia–retinoic acid receptor (PML-RAR)α (PR), the fusion protein that initiates acute promyelocytic leukemia (APL). Further, NE deficiency reduces the penetrance of APL in a murine model of this disease. We therefore predicted that NE-mediated PR cleavage might be important for its ability to initiate APL. To test this hypothesis, we generated a mouse expressing NE-resistant PR. These mice developed APL indistinguishable from wild-type PR, but with significantly reduced latency (median leukemia-free survival of 274 days vs 473 days for wild-type PR, P < .001). Resistance to proteolysis may increase the abundance of full-length PR protein in early myeloid cells, and our previous data suggested that noncleaved PR may be less toxic to early myeloid cells. Together, these effects appear to increase the leukemogenicity of NE-resistant PR, contrary to our previous prediction. We conclude that NE deficiency may reduce APL penetrance via indirect mechanisms that are still NE dependent.
Hematopoiesis in 3 dimensions: human and murine bone marrow architecture visualized by confocal microscopy
Authors: Takaku Tomoiku , Malide Daniela , Chen Jichun , Calado Rodrigo T. , Kajigaya Sachiko , Young Neal S.
Published: July 2010

In many animals, blood cell production occurs in the bone marrow. Hematopoiesis is complex, requiring self-renewing and pluripotent stem cells, differentiated progenitor and precursor cells, and supportive stroma, adipose tissue, vascular structures, and extracellular matrix. Although imaging is a vital tool in hematology research, the 3-dimensional architecture of the bone marrow tissue in situ remains largely uncharacterized. The major hindrance to imaging the intact marrow is the surrounding bone structures are almost impossible to cut/image through. We have overcome these obstacles and describe a method whereby whole-mounts of bone marrow tissue were immunostained and imaged in 3 dimensions by confocal fluorescence and reflection microscopy. We have successfully mapped by multicolor immunofluorescence the localization pattern of as many as 4 cell features simultaneously over large tiled views and to depths of approximately 150 μm. Three-dimensional images can be assessed qualitatively and quantitatively to appreciate the distribution of cell types and their interrelationships, with minimal perturbations of the tissue. We demonstrate its application to normal mouse and human marrow, to murine models of marrow failure, and to patients with aplastic anemia, myeloid, and lymphoid cell malignancies. The technique should be generally adaptable for basic laboratory investigation and for clinical diagnosis of hematologic diseases.
GeneBrowser 2: an application to explore and identify common biological traits in a set of genes
Authors: Arrais Joel P , Fernandes João , Pereira João , Oliveira José Luís
Published: July 2010

Background

The development of high-throughput laboratory techniques created a demand for computer-assisted result analysis tools. Many of these techniques return lists of genes whose interpretation requires finding relevant biological roles for the problem at hand. The required information is typically available in public databases, and usually, this information must be manually retrieved to complement the analysis. This process is a very time-consuming task that should be automated as much as possible.

Results

GeneBrowser is a web-based tool that, for a given list of genes, combines data from several public databases with visualisation and analysis methods to help identify the most relevant and common biological characteristics. The functionalities provided include the following: a central point with the most relevant biological information for each inserted gene; a list of the most related papers in PubMed and gene expression studies in ArrayExpress; and an extended approach to functional analysis applied to Gene Ontology, homologies, gene chromosomal localisation and pathways.

Conclusions

GeneBrowser provides a unique entry point to several visualisation and analysis methods, providing fast and easy analysis of a set of genes. GeneBrowser fills the gap between Web portals that analyse one gene at a time and functional analysis tools that are limited in scope and usually desktop-based.
Paralysis and delayed Z-disc formation in the Xenopus tropicalis unc45b mutant dicky ticker
Authors: Geach Timothy J , Zimmerman Lyle B
Published: July 2010

Background

The protein components of mature skeletal muscle have largely been characterized, but the mechanics and sequence of their assembly during normal development remain an active field of study. Chaperone proteins specific to sarcomeric myosins have been shown to be necessary in zebrafish and invertebrates for proper muscle assembly and function.

Results

The Xenopus tropicalis mutation dicky ticker results in disrupted skeletal muscle myofibrillogenesis, paralysis, and lack of heartbeat, and maps to a missense mutation in the muscle-specific chaperone unc45b. Unc45b is known to be required for folding the head domains of myosin heavy chains, and mutant embryos fail to incorporate muscle myosin into sarcomeres. Mutants also show delayed polymerization of α-actinin-rich Z-bodies into the Z-disks that flank the myosin-containing A-band.

Conclusions

The dicky ticker phenotype confirms that a requirement for myosin-specific chaperones is conserved in tetrapod sarcomerogenesis, and also suggests a novel role for myosin chaperone function in Z-body maturation.
High prevalence of antibodies against polyomavirus WU, polyomavirus KI, and human bocavirus in German blood donors
Authors: Neske Florian , Prifert Christiane , Scheiner Barbara , Ewald Moritz , Schubert Jörg , Opitz Andreas , Weissbrich Benedikt
Published: July 2010

Background

DNA of the polyomaviruses WU (WUPyV) and KI (KIPyV) and of human bocavirus (HBoV) has been detected with varying frequency in respiratory tract samples of children. However, only little is known about the humoral immune response against these viruses. Our aim was to establish virus-specific serological assays and to determine the prevalence of immunoglobulin G (IgG) against these three viruses in the general population.

Methods

The capsid proteins VP1 of WUPyV and KIPyV and VP2 of HBoV were cloned into baculovirus vectors and expressed in Sf9 insect cells. IgG antibodies against WUPyV VP1, KIPyV VP1, and HBoV VP2 were determined by immunofluorescence assays in 100 plasma samples of blood donors.

Results

The median age of the blood donors was 31 years (range 20 - 66 yrs), 52% were male. 89% of the samples were positive for WUPyV IgG (median age 31 yrs, 49.4% male), 67% were positive for KIPyV IgG (median age 32 yrs, 46.3% male), and 76% were positive for HBoV IgG (median age 32 yrs, 51.3% male). For WUPyV and HBoV, there were no significant differences of the seropositivity rates with respect to age groups or gender. For KIPyV, the seropositivity rate increased significantly from 59% in the age group 20 - 29 years to 100% in the age group > 50 years.

Conclusions

High prevalences of antibodies against WUPyV, KIPyV, and HBoV were found in plasma samples of healthy adults. The results indicate that primary infection with these viruses occurs during childhood or youth. For KIPyV, the seropositivity appears to increase further during adulthood.
Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins
Authors: Teutschbein Janka , Haydn Johannes M , Samans Birgit , Krause Michael , Eilers Martin , Schartl Manfred , Meierjohann Svenja
Published: July 2010

Background

Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase) triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation.

Methods

Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated.

Results

Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1), early growth response 1 (Egr1), osteopontin (Opn), insulin-like growth factor binding protein 3 (Igfbp3), dual-specificity phosphatase 4 (Dusp4), and tumor-associated antigen L6 (Taal6). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that FOSL1, OPN, IGFBP3, DUSP4, and TAAL6 also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration.

Conclusion

Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute new possible molecular players in melanoma development. Specifically, a role of FOSL1 in melanomagenic processes is demonstrated. These data are the basis for future detailed analyses of the investigated target genes.
The need for continued monitoring of antibiotic resistance patterns in clinical isolates of Staphylococcus aureus from London and Malta
Authors: Gould Simon WJ , Cuschieri Paul , Rollason Jess , Hilton Anthony C , Easmon Sue , Fielder Mark D
Published: July 2010

Background

Antibiotic resistance is an increasing problem in isolates of Staphylococcus aureus (S. aureus) worldwide. In 2001 The National Health Service in the UK introduced a mandatory bacteraemia surveillance scheme for the reporting of S. aureus and methicillin-resistant S. aureus (MRSA). This surveillance initiative reports on the percentage of isolates that are methicillin resistant. However, resistance to other antibiotics is not currently reported and therefore the scale of emerging resistance is currently unclear in the UK. In this study, multiple antibiotic resistance (MAR) profiles against fourteen antimicrobial drugs were investigated for 705 isolates of S. aureus collected from two European study sites in the UK (London) and Malta.

Results

All isolates were susceptible to linezolid, teicoplanin and vancomycin. Multiple antibiotic resistance profiles from both countries were determined, a total of forty-two and forty-five profiles were seen in the UK cohort (MRSA and MSSA respectively) and comparatively, sixty-two and fifty-two profiles were shown in the Maltese group. The largest MAR profile contained six antibiotics (penicillin G, methicillin, erythromycin, ciprofloxacin, clindamycin and clarithromycin) and was observed in the MRSA isolates in both the UK and Maltese cohorts.

Conclusion

The data presented here suggests that the monitoring of changing resistance profiles locally in maintaining treatment efficacy to resistant pathogens.
Evaluation of normalization methods for two-channel microRNA microarrays
Authors: Zhao Yingdong , Wang Ena , Liu Hui , Rotunno Melissa , Koshiol Jill , Marincola Francesco M , Landi Maria Teresa , McShane Lisa M
Published: July 2010

Background

MiR arrays distinguish themselves from gene expression arrays by their more limited number of probes, and the shorter and less flexible sequence in probe design. Robust data processing and analysis methods tailored to the unique characteristics of miR arrays are greatly needed. Assumptions underlying commonly used normalization methods for gene expression microarrays containing tens of thousands or more probes may not hold for miR microarrays. Findings from previous studies have sometimes been inconclusive or contradictory. Further studies to determine optimal normalization methods for miR microarrays are needed.

Methods

We evaluated many different normalization methods for data generated with a custom-made two channel miR microarray using two data sets that have technical replicates from several different cell lines. The impact of each normalization method was examined on both within miR error variance (between replicate arrays) and between miR variance to determine which normalization methods minimized differences between replicate samples while preserving differences between biologically distinct miRs.

Results

Lowess normalization generally did not perform as well as the other methods, and quantile normalization based on an invariant set showed the best performance in many cases unless restricted to a very small invariant set. Global median and global mean methods performed reasonably well in both data sets and have the advantage of computational simplicity.

Conclusions

Researchers need to consider carefully which assumptions underlying the different normalization methods appear most reasonable for their experimental setting and possibly consider more than one normalization approach to determine the sensitivity of their results to normalization method used.
Fitting additive Poisson models
Authors: Boshuizen Hendriek C , Feskens Edith JM
Published: July 2010

This paper describes how to fit an additive Poisson model using standard software. It is illustrated with SAS code, but can be similarly used for other software packages.
Self-assembly of virus-like particles of porcine circovirus type 2 capsid protein expressed from Escherichia coli
Authors: Yin Shuanghui , Sun Shiqi , Yang Shunli , Shang Youjun , Cai Xuepeng , Liu Xiangtao
Published: July 2010

Background

Porcine circovirus 2 (PCV2) is a serious problem to the swine industry and can lead to significant negative impacts on profitability of pork production. Syndrome associated with PCV2 is known as porcine circovirus closely associated with post-weaning multisystemic wasting syndrome (PMWS). The capsid (Cap) protein of PCV2 is a major candidate antigen for development of recombinant vaccine and serological diagnostic method. The recombinant Cap protein has the ability to self-assemble into virus-like particles (VLPs) in vitro, it is particularly opportunity to develop the PV2 VLPs vaccine in Escherichia coli,(E.coli ), because where the cost of the vaccine must be weighed against the value of the vaccinated pig, when it was to extend use the VLPs vaccine of PCV2.

Results

In this report, a highly soluble Cap-tag protein expressed in E.coli was constructed with a p-SMK expression vector with a fusion tag of small ubiquitin-like modifiers (SUMO). The recombinant Cap was purified using Ni2+ affinity resins, whereas the tag was used to remove the SUMO protease. Simultaneously, the whole native Cap protein was able to self-assemble into VLPs in vitro when viewed under an electron microscope. The Cap-like particles had a size and shape that resembled the authentic Cap. The result could also be applied in the large-scale production of VLPs of PCV2 and could be used as a diagnostic antigen or a potential VLP vaccine against PCV2 infection in pigs.

Conclusion

we have, for the first time, utilized the SUMO fusion motif to successfully express the entire authentic Cap protein of PCV2 in E. coli. After the cleavage of the fusion motif, the nCap protein has the ability to self-assemble into VLPs, which can be used as as a potential vaccine to protect pigs from PCV2-infection.
Polycyclic aromatic hydrocarbon components contribute to the mitochondria-antiapoptotic effect of fine particulate matter on human bronchial epithelial cells via the aryl hydrocarbon receptor
Authors: Ferecatu Ioana , Borot Marie-Caroline , Bossard Camille , Leroux Melanie , Boggetto Nicole , Marano Francelyne , Baeza-Squiban Armelle , Andreau Karine
Published: July 2010

Background

Nowadays, effects of fine particulate matter (PM2.5) are well-documented and related to oxidative stress and pro-inflammatory response. Nevertheless, epidemiological studies show that PM2.5exposure is correlated with an increase of pulmonary cancers and the remodeling of the airway epithelium involving the regulation of cell death processes. Here, we investigated the components of Parisian PM2.5involved in either the induction or the inhibition of cell death quantified by different parameters of apoptosis and delineated the mechanism underlying this effect.

Results

In this study, we showed that low levels of Parisian PM2.5are not cytotoxic for three different cell lines and primary cultures of human bronchial epithelial cells. Conversely, a 4 hour-pretreatment with PM2.5prevent mitochondria-driven apoptosis triggered by broad spectrum inducers (A23187, staurosporine and oligomycin) by reducing the mitochondrial transmembrane potential loss, the subsequent ROS production, phosphatidylserine externalization, plasma membrane permeabilization and typical morphological outcomes (cell size decrease, massive chromatin and nuclear condensation, formation of apoptotic bodies). The use of recombinant EGF and specific inhibitor led us to rule out the involvement of the classical EGFR signaling pathway as well as the proinflammatory cytokines secretion. Experiments performed with different compounds of PM2.5suggest that endotoxins as well as carbon black do not participate to the antiapoptotic effect of PM2.5. Instead, the water-soluble fraction, washed particles and organic compounds such as polycyclic aromatic hydrocarbons (PAH) could mimic this antiapoptotic activity. Finally, the activation or silencing of the aryl hydrocarbon receptor (AhR) showed that it is involved into the molecular mechanism of the antiapoptotic effect of PM2.5at the mitochondrial checkpoint of apoptosis.

Conclusions

The PM2.5-antiapoptotic effect in addition to the well-documented inflammatory response might explain the maintenance of a prolonged inflammation state induced after pollution exposure and might delay repair processes of injured tissues.
Inflammatory myofibroblastic tumor of the lung- a case report
Authors: Chen Chien-Kuang , Jan Chia-Ing , Tsai Jian-Shun , Huang Hsu-Chih , Chen Pin-Ru , Lin Yu-Sen , Chen Chih-Yi , Fang Hsin-Yuan
Published: July 2010

A 45-year-old man presented with a six-month history of progressive dyspnea with productive cough and wheezing. The patient was a heavy smoker and had a history of tongue cancer, hypertension, and asthma. Chest X-ray and computed tomography showed a mass lesion in the left hilar region and total collapse of the upper left lobe of the lung. Bronchoscopy revealed a whitish solid tumor obstructing the left upper lobe bronchus. Positron emission tomography showed increased tracer uptake in the lesion. A thoracoscopic lobectomy of the left upper lobe of the lung was performed. The final pathologic diagnosis was inflammatory myofibroblastic tumor.
Parameter inference for discretely observed stochastic kinetic models using stochastic gradient descent
Authors: Wang Yuanfeng , Christley Scott , Mjolsness Eric , Xie Xiaohui
Published: July 2010

Background

Stochastic effects can be important for the behavior of processes involving small population numbers, so the study of stochastic models has become an important topic in the burgeoning field of computational systems biology. However analysis techniques for stochastic models have tended to lag behind their deterministic cousins due to the heavier computational demands of the statistical approaches for fitting the models to experimental data. There is a continuing need for more effective and efficient algorithms. In this article we focus on the parameter inference problem for stochastic kinetic models of biochemical reactions given discrete time-course observations of either some or all of the molecular species.

Results

We propose an algorithm for inference of kinetic rate parameters based upon maximum likelihood using stochastic gradient descent (SGD). We derive a general formula for the gradient of the likelihood function given discrete time-course observations. The formula applies to any explicit functional form of the kinetic rate laws such as mass-action, Michaelis-Menten, etc. Our algorithm estimates the gradient of the likelihood function by reversible jump Markov chain Monte Carlo sampling (RJMCMC), and then gradient descent method is employed to obtain the maximum likelihood estimation of parameter values. Furthermore, we utilize flux balance analysis and show how to automatically construct reversible jump samplers for arbitrary biochemical reaction models. We provide RJMCMC sampling algorithms for both fully observed and partially observed time-course observation data. Our methods are illustrated with two examples: a birth-death model and an auto-regulatory gene network. We find good agreement of the inferred parameters with the actual parameters in both models.

Conclusions

The SGD method proposed in the paper presents a general framework of inferring parameters for stochastic kinetic models. The method is computationally efficient and is effective for both partially and fully observed systems. Automatic construction of reversible jump samplers and general formulation of the likelihood gradient function makes our method applicable to a wide range of stochastic models. Furthermore our derivations can be useful for other purposes such as using the gradient information for parametric sensitivity analysis or using the reversible jump samplers for full Bayesian inference. The software implementing the algorithms is publicly available at http://cbcl.ics.uci.edu/sgd
Parkinsonism secondary to metastatic lesions within the central nervous system: a case report
Authors: Hortelano Eduardo , Perea Christian , Uña Esther , Cebayos Amelia , Diezhandino Patricia , González Montserrat
Published: July 2010

Introduction

Colorectal cancer is one of the most common human diseases worldwide, and metastases are detected in approximately 20% of patients at diagnosis. Brain metastases occur in only 4% of cases, however, and usually present with hemiparesis or other motor or sensory symptoms. There have been only a few reports of parkinsonism secondary to a brain tumor-related mass effect.

Case presentation

We present an unusual case of parkinsonism secondary to multiple brain metastases. A 57-year-old Caucasian man had recently been diagnosed with primary carcinoma of the colon and had multiple metastases in the lungs and liver. He subsequently developed bilateral symmetrical parkinsonism, and multiple brain tumors were detected by computed tomography scanning. The condition of our patient deteriorated rapidly, and he became akinetic and dependent for all activities of daily living. He was followed up and treated at home by our palliative care unit team and died two weeks after the onset of his neurologic symptoms.

Conclusion

Although primary and secondary brain tumors are uncommon causes of parkinsonism, their clinical presentation may resemble that of idiopathic Parkinson's disease. An awareness of this rare differential diagnosis is therefore important in ensuring early diagnosis and treatment, thus improving prognosis and quality of life. A rapid progression in neurologic symptoms was observed in our patient, and clinicians should be alert to this atypical presentation of secondary parkinsonism.
A synthetic three-color scaffold for monitoring genetic regulation and noise
Authors: Cox Robert Sidney , Dunlop Mary J , Elowitz Michael B
Published: July 2010

Background

Current methods for analyzing the dynamics of natural regulatory networks, and quantifying synthetic circuit function, are limited by the lack of well-characterized genetic measurement tools. Fluorescent reporters have been used to measure dynamic gene expression, but recent attempts to monitor multiple genes simultaneously in single cells have not focused on independent, isolated measurements. Multiple reporters can be used to observe interactions between natural genes, or to facilitate the 'debugging' of biologically engineered genetic networks. Using three distinguishable reporter genes in a single cell can reveal information not obtainable from only one or two reporters. One application of multiple reporters is the use of genetic noise to reveal regulatory connections between genes. Experiments in both natural and synthetic systems would benefit from a well-characterized platform for expressing multiple reporter genes and synthetic network components.

Results

We describe such a plasmid-based platform for the design and optimization of synthetic gene networks, and for analysis of endogenous gene networks. This network scaffold consists of three distinguishable fluorescent reporter genes controlled by inducible promoters, with conveniently placed restriction sites to make modifications straightforward. We quantitatively characterize the scaffold in Escherichia coli with single-cell fluorescence imaging and time-lapse microscopy. The three spectrally distinct reporters allow independent monitoring of genetic regulation and analysis of genetic noise. As a novel application of this tool we show that the presence of genetic noise can reveal transcriptional co-regulation due to a hidden factor, and can distinguish constitutive from regulated gene expression.

Conclusion

We have constructed a general chassis where three promoters from natural genes or components of synthetic networks can be easily inserted and independently monitored on a single construct using optimized fluorescent protein reporters. We have quantitatively characterized the baseline behavior of the chassis so that it can be used to measure dynamic gene regulation and noise. Overall, the system will be useful both for analyzing natural genetic networks and assembling synthetic ones.
Positive end-expiratory pressure affects the value of intra-abdominal pressure in acute lung injury/acute respiratory distress syndrome patients: a pilot study
Authors: Verzilli Daniel , Constantin Jean-Michel , Sebbane Mustapha , Chanques Gérald , Jung Boris , Perrigault Pierre-François , Malbrain Manu , Jaber Samir
Published: July 2010

Introduction

To examine the effects of positive end-expiratory pressure (PEEP) on intra-abdominal pressure (IAP) in patients with acute lung injury (ALI).

Methods

Thirty sedated and mechanically ventilated patients with ALI or acute respiratory distress syndrome (ARDS) admitted to a sixteen-bed surgical medical ICU were included. All patients were studied with sequentially increasing PEEP (0, 6 and 12 cmH2O) during a PEEP-trial.

Results

Age was 55 ± 17 years, weight was 70 ± 17 kg, SAPS II was 44 ± 14 and PaO2/FIO2 was 192 ± 53 mmHg. The IAP was 12 ± 5 mmHg at PEEP 0 (zero end-expiratory pressure, ZEEP), 13 ± 5 mmHg at PEEP 6 and 15 ± 6 mmHg at PEEP 12 (P < 0.05 vs ZEEP). In the patients with intra-abdominal hypertension defined as IAP ≥ 12 mmHg (n = 15), IAP significantly increased from 15 ± 3 mmHg at ZEEP to 20 ± 3 mmHg at PEEP 12 (P < 0.01). Whereas in the patients with IAP < 12 mmHg (n = 15), IAP did not significantly change from ZEEP to PEEP 12 (8 ± 2 vs 10 ± 3 mmHg). In the 13 patients in whom cardiac output was measured, increase in PEEP from 0 to 12 cmH2O did not significantly change cardiac output, nor in the 8 out of 15 patients of the high-IAP group. The observed effects were similar in both ALI (n = 17) and ARDS (n = 13) patients.

Conclusions

PEEP is a contributing factor that impacts IAP values. It seems necessary to take into account the level of PEEP whilst interpreting IAP values in patients under mechanical ventilation.
Pex11pβ-mediated growth and division of mammalian peroxisomes follows a maturation pathway
Authors: Delille Hannah K. , Agricola Brigitte , Guimaraes Sofia C. , Borta Heike , Lüers Georg H. , Fransen Marc , Schrader Michael
Published: July 2010

Peroxisomes are ubiquitous subcellular organelles, which multiply by growth and division but can also form de novo via the endoplasmic reticulum. Growth and division of peroxisomes in mammalian cells involves elongation, membrane constriction and final fission. Dynamin-like protein (DLP1/Drp1) and its membrane adaptor Fis1 function in the later stages of peroxisome division, whereas the membrane peroxin Pex11pβ appears to act early in the process. We have discovered that a Pex11pβ-YFPm fusion protein can be used as a specific tool to further dissect peroxisomal growth and division. Pex11pβ-YFPm inhibited peroxisomal segmentation and division, but resulted in the formation of pre-peroxisomal membrane structures composed of globular domains and tubular extensions. Peroxisomal matrix and membrane proteins were targeted to distinct regions of the peroxisomal structures. Pex11pβ-mediated membrane formation was initiated at pre-existing peroxisomes, indicating that growth and division follows a multistep maturation pathway and that formation of mammalian peroxisomes is more complex than simple division of a pre-existing organelle. The implications of these findings on the mechanisms of peroxisome formation and membrane deformation are discussed.
Synthesized basement membranes direct the differentiation of mouse embryonic stem cells into pancreatic lineages
Authors: Higuchi Yuichiro , Shiraki Nobuaki , Yamane Keitaro , Qin Zeng , Mochitate Katsumi , Araki Kimi , Senokuchi Takafumi , Yamagata Kazuya , Hara Manami , Kume Kazuhiko , Kume Shoen
Published: July 2010

We previously reported that embryonic stem (ES) cells cultured on M15 cells, a mesoderm-derived supportive cell line, were efficiently differentiated towards an endodermal fate, finally adopting the specific lineages of various digestive organs such as the pancreas and liver. We show here that the endoderm-inducing activity of M15 cells is in part mediated through the extracellular matrices, and that laminin α5 is one of the crucial components. In an attempt to establish a feeder-free ES-cell procedure for pancreatic differentiation, we used a synthesized basement membrane (sBM) substratum using an HEK293 cell line stably expressing laminin-511. On the sBM, mouse ES or induced pluripotent stem (iPS) cells sequentially differentiated into the definitive endoderm, pancreatic progenitor cells, and then insulin-expressing pancreatic β-cells in vitro. Knockdown of ES cells with integrin β1 (Itgb1) reduces differentiation towards pancreatic cells. Heparan sulfate proteoglycan 2 (HSPG2) knockdown and heparitinase treatment synergistically decreased the number of Pdx1-expressing cells. These findings indicate that components of the basement membrane have an important role in the differentiation of definitive endoderm lineages. This novel procedure will be useful for the study of pancreatic differentiation of ES or iPS cells and the generation of potential sources of surrogate cells for regenerative medicine.
A p120-catenin–CK1ε complex regulates Wnt signaling
Authors: Casagolda David , del Valle-Pérez Beatriz , Valls Gabriela , Lugilde Ero , Vinyoles Meritxell , Casado-Vela Juan , Solanas Guiomar , Batlle Eduard , Reynolds Albert B. , Casal José Ignacio , de Herreros Antonio García , Duñach Mireia
Published: July 2010

p120-catenin is an E-cadherin-associated protein that modulates E-cadherin function and stability. We describe here that p120-catenin is required for Wnt pathway signaling. p120-catenin binds and is phosphorylated by CK1ε in response to Wnt3a. p120-catenin also associates to the Wnt co-receptor LRP5/6, an interaction mediated by E-cadherin, showing an unexpected physical link between adherens junctions and a Wnt receptor. Depletion of p120-catenin abolishes CK1ε binding to LRP5/6 and prevents CK1ε activation upon Wnt3a stimulation. Elimination of p120-catenin also inhibits early responses to Wnt, such as LRP5/6 and Dvl-2 phosphorylation and axin recruitment to the signalosome, as well as later effects, such as β-catenin stabilization. Moreover, since CK1ε is also required for E-cadherin phosphorylation, a modification that decreases the affinity for β-catenin, p120-catenin depletion prevents the increase in β-catenin transcriptional activity even in the absence of β-catenin degradation. Therefore, these results demonstrate a novel and crucial function of p120-catenin in Wnt signaling and unveil additional points of regulation by this factor of β-catenin transcriptional activity different of β-catenin stability.
New insights into the role of mitochondria in aging: mitochondrial dynamics and more
Authors: Seo Arnold Y. , Joseph Anna-Maria , Dutta Debapriya , Hwang Judy C. Y. , Aris John P. , Leeuwenburgh Christiaan
Published: July 2010

A decline in mitochondrial function plays a key role in the aging process and increases the incidence of age-related disorders. A deeper understanding of the intricate nature of mitochondrial dynamics, which is described as the balance between mitochondrial fusion and fission, has revealed that functional and structural alterations in mitochondrial morphology are important factors in several key pathologies associated with aging. Indeed, a recent wave of studies has demonstrated the pleiotropic role of fusion and fission proteins in numerous cellular processes, including mitochondrial metabolism, redox signaling, the maintenance of mitochondrial DNA and cell death. Additionally, mitochondrial fusion and fission, together with autophagy, have been proposed to form a quality-maintenance mechanism that facilitates the removal of damaged mitochondria from the cell, a process that is particularly important to forestall aging. Thus, dysfunctional regulation of mitochondrial dynamics might be one of the intrinsic causes of mitochondrial dysfunction, which contributes to oxidative stress and cell death during the aging process. In this Commentary, we discuss recent studies that have converged at a consensus regarding the involvement of mitochondrial dynamics in key cellular processes, and introduce a possible link between abnormal mitochondrial dynamics and aging.
Risk of Invasive Cervical Cancer and Cervical Intraepithelial Neoplasia Grade Iii in Central Italy by Area of Birth
Authors: Crocetti Emanuele , Manneschi Gianfranco , Visioli Carmen Beatriz , Zappa Marco
Published: July 2010

Objective

To evaluate cervical cancer incidence among women born in different countries but residing in Italy.

Setting

Women aged 25-59 from a central Italian population-based cancer registry.

Methods

Invasive and in situ cervical cancer incidence rates from 2000-2004 were calculated. Standardized incidence rates were based on the European standard population. Places of birth were categorized by nine different areas.

Results

Within the resident population aged 25-59, there were 148 invasive cervical cancers (17.6% in women born outside Italy) and 501 (14.2% in women born outside Italy) cervical intraepithelial neoplasia grade III (CIN III) diagnoses. The incidence of invasive cervical cancer for women born in ‘Central & South America and the Caribbean’ was 60.5 per 100,000 and in ‘Central and Eastern Europe’ it was 38.3, statistically significantly higher than for women born in Italy (9.5 per 100,000). The CIN III rate was 35.0 per 100,000 for women born in Italy. The ratio between standardized rates for CIN III and invasive cancers was around 4 for women born in Italy and the ‘extended European Union’, and around 6 for those born in ‘Asia’. It was 1.64 for women born in ‘Africa’, 1.31 in ‘Central & South America and the Caribbean’ and 0.69 for those born in ‘Eastern Europe’.

Conclusions

Women who reside in Italy but were born in ‘Central & South America and the Caribbean’ or in ‘Central and Eastern Europe’ are at high risk for invasive cervical cancer. These groups are less inclined to participate in screening, and appropriate preventive strategies should be planned accordingly.
A Fall-off in Cervical Screening Coverage of Younger Women in Developed Countries
Authors: Lancucki L , Fender M , Koukari A , Lynge E , Mai V , Mancini E , Onysko J , Ronco G , Tornberg S , Vessey M , Patnick J
Published: July 2010

Objectives

To analyse cervical screening coverage data by age over time in a number of developed countries throughout the world, with specific emphasis on trends for younger women and on age differentials between younger and older women.

Methods

Routinely collected cervical screening statistics and survey data were collected on the proportion of women who have undergone cervical screening with cytology in seven countries in the period 1995 to 2005.

Results

Data for the 25-29 age group were examined. Coverage fell in most countries, in three by more than 5 percentage points. In two countries while overall coverage rose in the period, the rise was not as steep in the youngest group of women. Data for each available 5-year age group for the different countries shows a similar gradient in most, regardless of the absolute level of coverage. Although the trend is not uniform in every country, it appears that generally the gap between coverage of younger women and coverage of older women increased, sometimes dramatically, between the mid-1990s and the mid-2000s.

Conclusions

There is a general trend in developed countries towards lower coverage in young women (25-29 years old). No common underlying cause has been clearly identified and there is a need for further studies to investigate the possible reasons for this phenomenon.
Eurocat Website Data on Prenatal Detection Rates of Congenital Anomalies
Authors: Garne Ester , Dolk Helen , Loane Maria , Eurocat Patricia A Boyd, On Behalf Of
Published: July 2010

The EUROCAT website www.eurocat-network.eu publishes prenatal detection rates for major congenital anomalies using data from European population-based congenital anomaly registers, covering 28% of the EU population as well as non-EU countries. Data are updated annually. This information can be useful for comparative purposes to clinicians and public health service managers involved in the antenatal care of pregnant women as well as those interested in perinatal epidemiology.