bluuebunny/crossref_metadata_2025 huggingface dataset:
The 1,4-benzodiazepine Ro5-4864 (4-chlorodiazepam) suppresses multiple pro-inflammatory mast cell effector functions
Authors: Yousefi Omid Sascha , Wilhelm Thomas , Maschke-Neuß Karin , Kuhny Marcel , Martin Christian , Molderings Gerhard J , Kratz Felix , Hildenbrand Bernd , Huber Michael
Published: February 2013

Activation of mast cells (MCs) can be achieved by the high-affinity receptor for IgE (FcεRI) as well as by additional receptors such as the lipopolysaccharide (LPS) receptor and the receptor tyrosine kinase Kit (stem cell factor [SCF] receptor). Thus, pharmacological interventions which stabilize MCs in response to different receptors would be preferable in diseases with pathological systemic MC activation such as systemic mastocytosis. 1,4-Benzodiazepines (BDZs) have been reported to suppress MC effector functions. In the present study, our aim was to analyze molecularly the effects of BDZs on MC activation by comparison of the effects of the two BDZs Ro5-4864 and clonazepam, which markedly differ in their affinities for the archetypical BDZ recognition sites, i.e., the GABAAreceptor and TSPO (previously termed peripheral-type BDZ receptor). Ro5-4864 is a selective agonist at TSPO, whereas clonazepam is a selective agonist at the GABAAreceptor. Ro5-4864 suppressed pro-inflammatory MC effector functions in response to antigen (Ag) (degranulation/cytokine production) and LPS and SCF (cytokine production), whereas clonazepam was inactive. Signaling pathway analyses revealed inhibitory effects of Ro5-4864 on Ag-triggered production of reactive oxygen species, calcium mobilization and activation of different downstream kinases. The initial activation of Src family kinases was attenuated by Ro5-4864 offering a molecular explanation for the observed impacts on various downstream signaling elements. In conclusion, BDZs structurally related to Ro5-4864 might serve as multifunctional MC stabilizers without the sedative effect of GABAAreceptor-interacting BDZs.
Primary idiopathic silent chylopericardium
Authors: Kwon Jong Bum , Choi Si Young , Kim Chi Kyung , Park Chan Beom
Published: February 2013

Chylopericardium usually occurs secondary to trauma, cardiothoracic surgery, radiation therapy, or neoplasm of the mediastinum. Idiopathic chylopericardium is extremely rare. We report a case of primary chylopericardium in a 79-year-old male patient. Although pericardial window and thoracic duct ligation are the treatment of choice, the patient has been doing well for six months since video-assisted thoracoscopic pericardial window.
The carotenoid lutein enhances matrix metalloproteinase-9 production and phagocytosis through intracellular ROS generation and ERK1/2, p38 MAPK, and RARβ activation in murine macrophages
Authors: Lo Huey-Ming , Chen Chih-Li , Yang Chuen-Mao , Wu Pi-Hui , Tsou Chih-Jen , Chiang Kai-Wen , Wu Wen-Bin
Published: February 2013

Carotenoid lutein causes MMP-9 release that participates in macrophage phagocytosis.

Early studies have demonstrated the ability of dietary carotenoids to enhance immune response, but the mechanism underlying their influence on macrophage activity remains unclear. Here, we investigated the effects of carotenoids on macrophage activity. Carotenoids, including lutein and lycopene, enhanced MMP-9 activity in RAW264.7 macrophages. Lutein was chosen as a representative and analyzed further in this study. It increased the synthesis, activity, and release of MMP-9 in murine RAW264.7 and primary-cultured peritoneal macrophages. MMP-9 induction by lutein was through the transcriptional regulation of mmp-9. It was blunted by the MAPK inhibitors targeting ERK1/2 and p38 MAPK, the reagents that inhibit free radical signaling, and the inhibitors and siRNA targeting RARβ. Moreover, lutein induced Nox activation and intracellular ROS production at an early stage of treatment. This carotenoid also caused ERK1/2 and p38 MAPK activation, RARβ expression, and RAR interaction with its responsive element in the promoter region. These findings suggest the involvement of ROS, MAPKs, and RARβ activation in lutein-driven MMP-9 expression and release. Interestingly, lutein enhanced the phagocytic activity of macrophages, and the secreted MMP-9 appeared to be involved in this process. In summary, we provide evidence here for the first time that the carotenoid lutein induces intracellular ROS generation and MAPK and RARβ activation in macrophages, leading to an increase in MMP-9 release and macrophage phagocytosis. Our results demonstrate that lutein exerts an immunomodulatory effect on macrophages.
The Use of Stochastic Optimization in Ground Motion Prediction
Authors: Segou Margaret , Voulgaris Nicholas
Published: February 2013

In recent years stochastic optimization has become popular in modeling highly complex natural systems as opposed to traditional approaches, such as regression analysis. This paper tests the efficiency of regression analysis over mathematical optimization by evaluating the performance of stochastic (genetic algorithms, simulated annealing) and deterministic algorithms (nonlinear least squares, pattern search) in solving minimization problems. Qualitative and quantitative comparison of these solvers reveals that the implementation of genetic algorithms with initial population development, using Latin Hypercube sampling, outperformed other algorithms. Using the aforementioned solver, ground motion prediction equations are derived for the estimation of horizontal peak ground acceleration, velocity, and 5% damped spectral acceleration ordinates at discrete period estimators between 0.05 s and 2 s. Ground motion for stiff and soft soil sites is amplified by a constant factor with respect to rock site. These strong motion prediction equations are proposed for application in the range M4.5–M6.6 and for distances up to 150 km.
Simulation of Reinforced Concrete Frames with Nonductile Beam-Column Joints
Authors: Park Sangjoon , Mosalam Khalid M.
Published: February 2013

The accurate prediction of shear strength and flexibility of beam-column joints without transverse reinforcement is essential to assess the seismic performance of nonductile reinforced concrete (RC) buildings characterized by having such unreinforced beam-column joints. In this study, a multilinear backbone curve to represent the moment-rotation relationship of an unreinforced corner beam-column joint is proposed. The modeling parameters of the backbone curve are estimated based on experimental results of four corner joint specimens recently tested by the authors. Furthermore, the proposed backbone curve is modified to be applicable to interior and roof beam-column joints. These backbone curves are validated by accurate reproduction of the force-drift responses of the four corner joint specimens and eight other exterior and interior joint specimens from literature. Using these backbone curves, nonlinear dynamic analyses are performed on three hypothetical building frames. The analytical results demonstrate the importance of joint flexibility for seismic assessment of nonductile RC buildings.
Seismic Performance Assessment of Unreinforced Masonry Buildings with a Hybrid Modeling Approach
Authors: Aldemir Alper , Altuğ Erberik M. , Demirel I. Ozan , Sucuoğlu HalÛk
Published: February 2013

This study proposes a hybrid modeling approach for the seismic performance assessment of unreinforced masonry buildings. The method combines finite-element and equivalent-frame approaches such that more powerful features of each approach are utilized. The finite-element approach is used to model the masonry components of different geometrical and material characteristics with a high level of accuracy. Then this numerically simulated database is used in the analytical modeling of masonry buildings with equivalent beams and columns instead of spandrels and piers. Thus it becomes possible to model a masonry building as a frame structure that can simply be analyzed in order to capture the global behavior. The method has been verified by comparing the analytical results with the previous experimental findings. The last part of the study is devoted to the implementation of the method to an existing masonry building that was damaged during a severe earthquake.
Estimating Economic Losses from Earthquakes Using an Empirical Approach
Authors: Jaiswal Kishor , Wald David J.
Published: February 2013

We extended the U.S. Geological Survey's Prompt Assessment of Global Earthquakes for Response (PAGER) empirical fatality estimation methodology proposed by Jaiswal et al. (2009) to rapidly estimate economic losses after significant earthquakes worldwide. The requisite model inputs are shaking intensity estimates made by the ShakeMap system, the spatial distribution of population available from the LandScan database, modern and historic country or sub-country population and Gross Domestic Product (GDP) data, and economic loss data from Munich Re's historical earthquakes catalog. We developed a strategy to approximately scale GDP-based economic exposure for historical and recent earthquakes in order to estimate economic losses. The process consists of using a country-specific multiplicative factor to accommodate the disparity between economic exposure and the annual per capita GDP, and it has proven successful in hindcast-ing past losses. Although loss, population, shaking estimates, and economic data used in the calibration process are uncertain, approximate ranges of losses can be estimated for the primary purpose of gauging the overall scope of the disaster and coordinating response. The proposed methodology is both indirect and approximate and is thus best suited as a rapid loss estimation model for applications like the PAGER system.
Application of Supplemental Damping Characteristics to Response Spectrum Analyses of Nonproportionally Damped Multistory Asymmetric-Plan Buildings
Authors: Lin Jui-Liang , Tsai Keh-Chyuan
Published: February 2013

For practicing engineers, knowledge of the characteristics of supplemental damping in buildings is essential to understand the resultant effects of added damping. Characterizing the overall system parameters representing the amount and the plan-wise distribution of the supplemental damping in a single-story asymmetrical building is straightforward. However, this becomes a difficult task for multistory asymmetrical buildings. For this reason, this paper first develops the effective one-story building (EOSB), which retains the characteristics of the two dominant vibration modes of the original nonproportionally damped multistory asymmetrical building. By using the EOSB, it becomes convenient to characterize the supplemental damping in the original multistory asymmetrical building. The effectiveness of this approach is verified by using three numerical examples, which include one one-story, three eight-story, and one 20-story asymmetrical buildings. Next, the relationships between the roof displacements of the original building and those of the EOSB are established. This enables the application of the response spectra constructed from the EOSBs to estimate the peak roof displacements of the original multistory asymmetrical building.
The F-BAR protein Cip4/Toca-1 antagonizes the formin Diaphanous in membrane stabilization and compartmentalization
Authors: Yan Shuling , Lv Zhiyi , Winterhoff Moritz , Wenzl Christian , Zobel Thomas , Faix Jan , Bogdan Sven , Großhans Jörg
Published: February 2013

During Drosophila embryogenesis the first epithelium with defined cortical compartments is established during cellularization. Actin polymerization is required for the separation of lateral and basal domains as well as suppression of tubular extensions in the basal domain. The actin nucleator mediating this function is unknown. We found that the formin diaphanous (dia) is required for establishing and maintaining distinct lateral and basal domains during cellularization. In dia mutant embryos lateral marker proteins, such as Discs-large (Dlg) and Armadillo/beta-Catenin (Arm) spread into the basal compartment. Furthermore, high-resolution and live-imaging analysis of dia mutant embryos revealed an increased number of membrane extensions and endocytic activity at the basal domain, indicating a suppressing function of dia on membrane invaginations. Dia function may be based on an antagonistic interaction with the F-BAR protein Cip4/Toca-1, a known activator of the WASP/WAVE-Arp2/3 pathway. Dia and Cip4 physically and functionally interact and overexpression of Cip4 phenocopies dia loss-of-function. In vitro, Cip4 inhibits mainly actin nucleation by Dia. Thus, our data support a model in which linear actin filaments induced by Dia stabilize cortical compartmentalization by antagonizing WASP/WAVE-Arp2/3 induced membrane turnover.
Numerical Study of Impact Forces on Railway Sleepers under Wheel Flat
Authors: Bian J. , Gu Y.T. , Murray M.
Published: February 2013

Wheel-rail interaction is one of the most important research topics in railway engineering. It includes track vibration, track impact response and safety of the track. Track structure failures caused by impact forces can lead to significant economic loss for track owners through damage to rails and to the sleepers beneath. The wheel-rail impact forces occur because of imperfections on the wheels or rails such as wheel flats, irregular wheel profile, rail corrugation and differences in the height of rails connected at a welded joint. The vehicle speed and static wheel load are important factors of the track design, because they are related to the impact forces under wheel-rail defects. In this paper, a 3-Dimensional finite element model for the study of wheel flat impact is developed by use of the FEA software package ANSYS. The effects of the wheel flat to impact force on sleepers with various speeds and static wheel loads under a critical wheel flat size are investigated. It has found that both wheel-rail impact force and impact force on sleeper induced by wheel flat are varying nonlinearly by increasing the vehicle speed; both impact forces are nonlinearly and monotonically increasing by increasing the static wheel load. The relationships between both of impact forces induced by wheel flat and vehicles speed or static load are important to the track engineers to improve the design and maintenance methods in railway industry.
Suppressing Influence of Measurement Noise on Vibration-Based Damage Detection Involving Higher-Order Derivatives
Authors: Xu Hao , Cheng Li , Su Zhongqing
Published: February 2013

Aimed at minimizing the influence of measurement noise on the precision and robustness of vibration-based damage detection (particularly for those approaches involving higher-order derivatives of vibration signals), three independent noise reduction strategies were proposed, including low-pass wavenumber filtering (LWF), adjustment of measurement density (AMD), and hybrid data fusion. Residing on a spectrum analysis, LWF suppresses the noise influence by filtering the measurement noise out of a specific wavenumber domain whilst remaining damage-associated signal features only. AMD is based on an inherent correlation between the degree of noise influence and the density of measurement points. By selecting an optimal AMD, the effect of measurement noise on detection precision can be alleviated. The hybrid data fusion amalgamates signal features acquired under different measurement conditions, giving prominence to the salient features in common ( i.e., those pertaining to damage) whereas suppressing less salient features in individuals ( e.g., measurement noise and uncertainties). Three proposed noise reduction techniques were validated respectively in simulation, and then applied experimentally to the detection of damage in a plate-like structure under a noisy measurement condition. Satisfactory noise suppression was achieved, demonstrating the effectiveness of the proposed noise reduction strategies for vibration-based damage detection.
Differences in microRNA detection levels are technology and sequence dependent
Authors: Leshkowitz Dena , Horn-Saban Shirley , Parmet Yisrael , Feldmesser Ester
Published: February 2013

Identification and quantification of small RNAs are challenging because of their short length, high sequence similarities within microRNA (miRNA) families, and the existence of miRNA isoforms and O-methyl 3′ modifications. In this study, the detection performance of three high-throughput commercial platforms, Agilent and Affymetrix microarrays and Illumina next-generation sequencing, was systematically and comprehensively compared. The ability to detect miRNAs was shown to depend strongly on the platform and on miRNA modifications and sequence. Using synthetic transcripts, including mature, precursor, and O-methyl-modified miRNAs spiked into human RNA, a large intensity variation in all spiked-in miRNAs and a reduced capacity in detecting O-methyl-modified miRNAs were observed between the tested platforms. In addition, endogenous human miRNA expression levels were assessed across the platforms. Detected miRNA expression levels were not consistent between platforms. Although biases in miRNA detection were previously described, here the end-point result, i.e., detection intensity, of these biases was investigated on multiple platforms in a controlled fashion. A detailed exploration of a large number of attributes, including base composition, sequence structure, and isoform miRNA attributes, suggests their impact on miRNA expression detection level. This study provides a basis for understanding the attributes that should be considered to adjust platform-dependent detection biases.
Axonally Synthesized β-Actin and GAP-43 Proteins Support Distinct Modes of Axonal Growth
Authors: Donnelly Christopher J. , Park Michael , Spillane Mirela , Yoo Soonmoon , Pacheco Almudena , Gomes Cynthia , Vuppalanchi Deepika , McDonald Marguerite , Kim Hak Hee , Merianda Tanuja T. , Gallo Gianluca , Twiss Jeffery L.
Published: February 2013

Increasing evidence points to the importance of local protein synthesis for axonal growth and responses to axotomy, yet there is little insight into the functions of individual locally synthesized proteins. We recently showed that expression of a reporter mRNA with the axonally localizing β-actin mRNA 3′UTR competes with endogenous β-actin and GAP-43 mRNAs for binding to ZBP1 and axonal localization in adult sensory neurons (Donnelly et al., 2011). Here, we show that the 3′UTR of GAP-43 mRNA can deplete axons of endogenous β-actin mRNA. We took advantage of this 3′UTR competition to address the functions of axonally synthesized β-actin and GAP-43 proteins. In cultured rat neurons, increasing axonal synthesis of β-actin protein while decreasing axonal synthesis of GAP-43 protein resulted in short highly branched axons. Decreasing axonal synthesis of β-actin protein while increasing axonal synthesis of GAP-43 protein resulted in long axons with few branches. siRNA-mediated depletion of overall GAP-43 mRNA from dorsal root ganglia (DRGs) decreased the length of axons, while overall depletion of β-actin mRNA from DRGs decreased the number of axon branches. These deficits in axon growth could be rescued by transfecting with siRNA-resistant constructs encoding β-actin or GAP-43 proteins, but only if the mRNAs were targeted for axonal transport. Finally,in ovoelectroporation of axonally targeted GAP-43 mRNA increased length and axonally targeted β-actin mRNA increased branching of sensory axons growing into the chick spinal cord. These studies indicate that axonal translation of β-actin mRNA supports axon branching and axonal translation of GAP-43 mRNA supports elongating growth.
Reputational Priors Magnify Striatal Responses to Violations of Trust
Authors: Fouragnan Elsa , Chierchia Gabriele , Greiner Susanne , Neveu Remi , Avesani Paolo , Coricelli Giorgio
Published: February 2013

Humans learn to trust each other by evaluating the outcomes of repeated interpersonal interactions. However, available prior information on the reputation of traders may alter the way outcomes affect learning. Our functional magnetic resonance imaging study is the first to allow the direct comparison of interaction-based and prior-based learning. Twenty participants played repeated trust games with anonymous counterparts. We manipulated two experimental conditions: whether or not reputational priors were provided, and whether counterparts were generally trustworthy or untrustworthy. When no prior information is available our results are consistent with previous studies in showing that striatal activation patterns correlate with behaviorally estimated reinforcement learning measures. However, our study additionally shows that this correlation is disrupted when reputational priors on counterparts are provided. Indeed participants continue to rely on priors even when experience sheds doubt on their accuracy. Notably, violations of trust from a cooperative counterpart elicited stronger caudate deactivations when priors were available than when they were not. However, tolerance to such violations appeared to be mediated by prior-enhanced connectivity between the caudate nucleus and ventrolateral prefrontal cortex, which anticorrelated with retaliation rates. Moreover, on top of affecting learning mechanisms, priors also clearly oriented initial decisions to trust, reflected in medial prefrontal cortex activity.
Neuronal d-Serine and Glycine Release Via the Asc-1 Transporter Regulates NMDA Receptor-Dependent Synaptic Activity
Authors: Rosenberg Dina , Artoul Samar , Segal Adi C. , Kolodney Goren , Radzishevsky Inna , Dikopoltsev Elena , Foltyn Veronika N. , Inoue Ran , Mori Hisashi , Billard Jean-Marie , Wolosker Herman
Published: February 2013

d-Serine and glycine are coagonists of NMDA receptors (NMDARs), but their relative contributions for several NMDAR-dependent processes are unclear. We now report that the alanine–serine–cysteine transporter-1 (Asc-1) mediates release of bothd-serine and glycine from neurons, and, in turn, this modulates NMDAR synaptic activity. Asc-1 antiporter activity is enhanced byd-isoleucine (d-Ile), which releasesd-serine and glycine from Asc-1-transfected cells, primary neuronal cultures, and hippocampal slices.d-Ile has no effect on astrocytes, which do not express Asc-1. We show thatd-Ile enhances the long-term potentiation (LTP) in rat and mouse hippocampal CA1 by stimulating Asc-1-mediated endogenousd-serine release.d-Ile effects on synaptic plasticity are abolished by enzymatically depletingd-serine or by using serine racemase knock-out (SR-KO) mice, confirming its specificity and supporting the notion that LTP depends mostly ond-serine release. Conversely, our data also disclose a role of glycine in activating synaptic NMDARs. Although acute enzymatic depletion ofd-serine also drastically decreases the isolated NMDAR synaptic potentials, these responses are still enhanced byd-Ile. Furthermore, NMDAR synaptic potentials are preserved in SR-KO mice and are also enhanced byd-Ile, indicating that glycine overlaps withd-serine binding at synaptic NMDARs. Altogether, our results disclose a novel role of Asc-1 in regulating NMDAR-dependent synaptic activity by mediating concurrent non-vesicular release ofd-serine and glycine. Our data also highlight an important role of neuron-derivedd-serine and glycine, indicating that astrocyticd-serine is not solely responsible for activating synaptic NMDARs.
Transcription of the Immediate-Early GeneArcin CA1 of the Hippocampus Reveals Activity Differences along the Proximodistal Axis That Are Attenuated by Advanced Age
Authors: Hartzell Andrea L. , Burke Sara N. , Hoang Lan T. , Lister James P. , Rodriguez Crystal N. , Barnes Carol A.
Published: February 2013

The CA1 region of the hippocampus receives distinct patterns of afferent input to distal (near subiculum) and proximal (near CA2) zones. Specifically, distal CA1 receives a direct projection from cells in the lateral entorhinal cortex that are sensitive to objects, whereas proximal CA1 is innervated by cells in the medial entorhinal cortex that are responsive to space. This suggests that neurons in different areas along the proximodistal axis of CA1 of the hippocampus will be functionally distinct. The current experiment investigated this possibility by monitoring behavior-induced cell activity across the CA1 axis usingArcmRNA imaging methods that compared adult and old rats in two conditions: (1) exploration of the same environment containing the same objects twice (AA) or (2) exploration of two different environments that contained identical objects (AB). The hypothesis was that CA1 place cells should show field remapping in the condition in which environments were changed, but the extent of remapping was expected to differ between proximal and distal regions and between age groups. In fact, neurons in the proximal region of CA1 in adult animals exhibited a greater degree of remapping than did distal CA1 cells when the environment changed, suggesting that cells receiving input from the medial entorhinal cortex are more sensitive to spatial context. However, in old rats, there were no differences in remapping across the proximodistal CA1 axis. Together, these data suggest that distal and proximal CA1 may be functionally distinct and differentially vulnerable to normative aging processes.
Hyperthyroidism causes cardiac dysfunction by mitochondrial impairment and energy depletion
Authors: Maity Sangeeta , Kar Dipak , De Kakali , Chander Vivek , Bandyopadhyay Arun
Published: February 2013

This study elucidates the role of metabolic remodeling in cardiac dysfunction induced by hyperthyroidism. Cardiac hypertrophy, structural remodeling, and expression of the genes associated with fatty acid metabolism were examined in rats treated with triiodothyronine (T3) alone (8 μg/100 g body weight (BW), i.p.) for 15 days or along with a peroxisome proliferator-activated receptor alpha agonist bezafibrate (Bzf; 30 μg/100 g BW, oral) and were found to improve in the Bzf co-treated condition. Ultrastructure of mitochondria was damaged in T3-treated rat heart, which was prevented by Bzf co-administration. Hyperthyroidism-induced oxidative stress, reduction in cytochromecoxidase activity, and myocardial ATP concentration were also significantly checked by Bzf. Heart function studied at different time points during the course of T3treatment shows an initial improvement and then a gradual but progressive decline with time, which is prevented by Bzf co-treatment. In summary, the results demonstrate that hyperthyroidism inflicts structural and functional damage to mitochondria, leading to energy depletion and cardiac dysfunction.
Segregation and Diffusion of Sb Compared to as for Ultra-Shallow Implantation Into Silicon
Authors: Krüger D. , Zaumseil P. , Melnik V. , Kurps R. , Formanek P. , Bolze D.
Published: February 2013

We investigate diffusion and segregation of Sb and As after low energy implantation and annealing. Sb implantation profiles are significantly more stable against segregation for implantation energies higher than 5 keV compared to As. For ultra-shallow profiles and annealing temperatures above 850°C we demonstrate strong Sb and As segregation up to 1021 cm–3 in an interfacial layer less than 3 nm. In comparison to As antimony profiles show reduced tails mainly due to less sensitivity for excess Si self-interstitial effects generated both during implantation defect anneal and during deactivation of heavily n-doped regions by clustering.
Pedicled Lingual Flap to Provide Keratinized Tissue Regeneration Over Dental Implants: A Description of the Technique and a Case Report
Authors: Herford Alan S. , Tandon Rahul , Pivetti Luca , Cicciù Marco
Published: February 2013

The aim of this study is to report the efficacy of a lingual pedicle flap for soft tissue pre-prosthetic surgery in implant rehabilitation. While it has been demonstrated that keratinized gingiva is an important factor for implant success, there remains a dearth of case reports concerning the use of a lingual pedicle flap to achieve this desired outcome in such a large reconstructive effort. For this case report, the patient underwent an anterior mandibular resection of an ameloblastoma and subsequent reconstruction, resulting in soft tissue loss. To satisfy the patient's desires, both functionally and esthetically, a bilateral rotated pedicled lingual flap was performed to augment keratinized tissue on the anterior mandibular ridge. An additional vestibuloplasty with two collagen matrices was also performed, and an acrylic splint was then applied to achieve better stabilization. The primary outcome was to evaluate the efficacy of this technique, which, until now, was used only for exposed root coverage. The site demonstrated excellent healing over time, even resulting in an excess of healthy and pink soft tissue, which later had to be corrected with a small gingivectomy. Although the patient reported slight discomfort for a few days after surgery, she was nonetheless pleased both with her ability to function and her appearance. The results of this study show that the bilateral rotated pedicled lingual flap is a viable technique for the correction of soft tissue defects in implant dentistry, providing a good amount of keratinized gingiva.
Avaliando a capacidade de governo: reflexões sobre a experiência do prêmio "Municípios que Fazem Render Mais" (2010 e 2011)
Authors: Fonseca Francisco , Beltrão Ricardo Ernesto Vasquez , Prado Otávio
Published: February 2013

Este artigo analisa conceitualmente a experiência do Prêmio "Municípios que Fazem Render Mais", desenvolvido por pesquisadores do Centro de Estudos em Administração Pública e Governo da Fundação Getulio Vargas de São Paulo, em dois momentos: nos estados do Sul em 2010 e no estado de São Paulo em 2011. A partir do conceito de "triângulo de governo", desenvolvido por Carlos Matus em seu construto sobre o Planejamento Estratégico Situacional (PES), analisa-se especialmente a "capacidade de governo" - um dos vértices do triângulo - dos municípios inscritos no Prêmio. O artigo descreve os pressupostos que informam o Prêmio, assim como os critérios e a metodologia adotados, e reflete sobre as escolhas realizadas para premiar os municípios ao analisar os desafios que representa avaliar gestões municipais. Por fim, o artigo analisa especificamente os municípios paulistas, o que implica estabelecer parâmetros para a comparação de contextos e gestões bastante distintos.
Estudos transcriptômicos no contexto da conectividade perturbada em esquizofrenia
Authors: Schmitt Andrea , Reich-Erkelenz Daniela , Gebicke-Härter Peter , Falkai Peter
Published: February 2013

Esquizofrenia é uma severa doença neurobiológica com fatores genéticos e ambientais desempenhando um papel na fisiopatologia. Diversas regiões cerebrais têm sido implicadas no processo da doença e estão conectadas em complexos circuitos neuronais. Nos níveis molecular e celular, a conectividade afetada entre essas regiões, envolvendo mielinização disfuncional dos axônios neuronais, bem como as alterações no nível sináptico e metabolismo energético levando a distúrbios na plasticidade sináptica, são os maiores achados em estudos post-mortem. Estudos de microarranjos investigando a expressão gênica contribuíram para os achados de alterações em vias complexas em regiões cerebrais relevantes na esquizofrenia. Além disso, estudos utilizando microdissecção e captura a laser permitiram a investigação da expressão gênica em grupos específicos de neurônios. Entretanto, deve ser mantido em mente que em estudos post-mortem, confusos efeitos de medicação, qualidade de RNAm, bem como capacidade de mecanismos regenerativos neuroplásticos do cérebro em indivíduos com história de vida de esquizofrenia, podem influenciar o complexo padrão de alterações no nível molecular. Apesar dessas limitações, estudos transcriptômicos livres de hipóteses em tecido cerebral de pacientes esquizofrênicos oferecem uma possibilidade única para aprender mais sobre os mecanismos subjacentes, levando a novas ópticas da fisiopatologia da doença.
Estilos de pensamento em educação em enfermagem: a produção científica de três regiões do Brasil
Authors: Schveitzer Mariana Cabral , Backes Vânia Marli Schubert , Cutolo Luiz Roberto Agea , Viana Ligia de Oliveira
Published: February 2013

Este estudo objetivou identificar os Estilos de Pensamento dos Grupos de Pesquisa em Educação em Enfermagem de três regiões do Brasil. MÉTODO: Pesquisa do tipo descritiva, exploratório-analítica, em base documental, de natureza qualitativa. RESULTADOS: A Região Norte demonstrou um Estilo Libertador, caracterizado por uma postura pedagógica libertadora e dialógica. A Região Centro-Oeste apresentou um Estilo Tecnicista-Libertador, caracterizado por uma postura pedagógica intermediária, que mostra exceções à postura pedagógica tecnicista e a crescente valorização da postura pedagógica crítica. Na Região Nordeste, apareceu o Estilo Tecnicista-Libertador-Efetivo, caracterizado por discutir a implantação das Diretrizes Curriculares Nacionais para o curso de Enfermagem nos Projetos Políticos Pedagógicos das Instituições de Ensino. CONCLUSÃO: Os Estilos identificados estão em constante movimento, porém, nesse momento, identificar a pedagogia libertadora e a sua efetivação a partir das Diretrizes Curriculares é essencial para o desenvolvimento da Educação em Enfermagem e o seu reconhecimento.
Preventing Ensemble Collapse and Honoring Multipoint Geostatistics with the Subspace EnKF/EnS and Kernel PCA Parameterization
Authors: Sarma Pallav , Chen Wen H.
Published: February 2013

Although the EnKF has many advantages, such as ease of implementation and efficient uncertainty quantification, it suffers from a few key issues that limit its application to large-scale simulation models of real fields. Among these key issues is the well known problem of ensemble collapse, which is particularly evident for small ensembles. Further, EnKF is theoretically appropriate only if all ensemble members belong to the same multi-Gaussian random field. This is an important issue because for most real fields, we have more than one geological scenario, and ideally, we would like to obtain one or more history-matched models for each geological scenario. Similar issues also affect the ensemble smoother (EnS).

We propose a new variant of the EnKF, called the subspace EnKF, to alleviate both these issues. The basic idea behind the subspace EnKF is to constrain each ensemble member to a different subspace of the full space to which the ensemble members belong. This is done by applying a different parameterization to each ensemble member with appropriate modification of the EnKF formulation, such that the parameterization ensures that each ensemble member remains in the subspace to which it is constrained through any number of updates, thereby preventing collapse. Further, if each parameterization is so chosen as to honor different geostatistical properties, then these statistics will also be honored throughout the updates, thus retaining the geostatistical properties of each ensemble member though each update. The EnS can also be extended similarly with the subspace formulation.

We first formulate and demonstrate the validity of the subspace EnKF with the standard PCA parameterization. We further improve the subspace EnKF/EnS to honor multi-point geostatistics by extending the subspace formulation with kernel PCA. We have earlier demonstrated the use of the kernel PCA parameterization with gradient-based history matching for honoring multi-point geostatistics of non-Gaussian random fields. Kernel PCA parameterization can also be used with the EnKF/EnS, however KPCA further aggravates the ensemble collapse problem due to the much larger dimensionality of the feature space. As such, formulating the subspace EnKF/EnS with kernel PCA parameterization alleviates both the key problems of the traditional EnKF/EnS, namely ensemble collapse and inability to honor multi-point geostatistics. The procedure is demonstrated on two examples, one with a multi-Gaussian permeability field, one with a channel sand, and is shown to prevent ensemble collapse while also honoring geostatistical properties much better compared to the standard EnKF/EnS.
A Novel Mechanism by Which SDF-1β Protects Cardiac Cells From Palmitate-Induced Endoplasmic Reticulum Stress and Apoptosis via CXCR7 and AMPK/p38 MAPK-Mediated Interleukin-6 Generation
Authors: Zhao Yuguang , Tan Yi , Xi Shugang , Li Yunqian , Li Cai , Cui Jiuwei , Yan Xiaoqing , Li Xiaokun , Wang Guanjun , Li Wei , Cai Lu
Published: February 2013

We studied the protective effect of stromal cell-derived factor-1β (SDF-1β) on cardiac cells from lipotoxicity in vitro and diabetes in vivo. Exposure of cardiac cells to palmitate increased apoptosis by activating NADPH oxidase (NOX)–associated nitrosative stress and endoplasmic reticulum (ER) stress, which was abolished by pretreatment with SDF-1β via upregulation of AMP-activated protein kinase (AMPK)–mediated p38 mitogen-activated protein kinase (MAPK) phosphorylation and interleukin-6 (IL-6) production. The SDF-1β cardiac protection could be abolished by inhibition of AMPK, p38 MAPK, or IL-6. Activation of AMPK or addition of recombinant IL-6 recaptured a similar cardiac protection. SDF-1β receptor C-X-C chemokine receptor type 4 (CXCR4) antagonist AMD3100 or CXCR4 small interfering RNA could not, but CXCR7 small interfering RNA completely abolished SDF-1β’s protection from palmitate-induced apoptosis and activation of AMPK and p38 MAPK. Administration of SDF-1β to diabetic rats, induced by feeding a high-fat diet, followed by a small dose of streptozotocin, could significantly reduce cardiac apoptosis and increase AMPK phosphorylation along with prevention of diabetes-induced cardiac oxidative damage, inflammation, hypertrophy, and remodeling. These results showed that SDF-1β protects against palmitate-induced cardiac apoptosis, which is mediated by NOX-activated nitrosative damage and ER stress, via CXCR7, to activate AMPK/p38 MAPK–mediated IL-6 generation. The cardiac protection by SDF-1β from diabetes-induced oxidative damage, cell death, and remodeling was also associated with AMPK activation.
Targeting Pyruvate Carboxylase Reduces Gluconeogenesis and Adiposity and Improves Insulin Resistance
Authors: Kumashiro Naoki , Beddow Sara A. , Vatner Daniel F. , Majumdar Sachin K. , Cantley Jennifer L. , Guebre-Egziabher Fitsum , Fat Ioana , Guigni Blas , Jurczak Michael J. , Birkenfeld Andreas L. , Kahn Mario , Perler Bryce K. , Puchowicz Michelle A. , Manchem Vara Prasad , Bhanot Sanjay , Still Christopher D. , Gerhard Glenn S. , Petersen Kitt Falk , Cline Gary W. , Shulman Gerald I. , Samuel Varman T.
Published: February 2013

We measured the mRNA and protein expression of the key gluconeogenic enzymes in human liver biopsy specimens and found that only hepatic pyruvate carboxylase protein levels related strongly with glycemia. We assessed the role of pyruvate carboxylase in regulating glucose and lipid metabolism in rats through a loss-of-function approach using a specific antisense oligonucleotide (ASO) to decrease expression predominantly in liver and adipose tissue. Pyruvate carboxylase ASO reduced plasma glucose concentrations and the rate of endogenous glucose production in vivo. Interestingly, pyruvate carboxylase ASO also reduced adiposity, plasma lipid concentrations, and hepatic steatosis in high fat–fed rats and improved hepatic insulin sensitivity. Pyruvate carboxylase ASO had similar effects in Zucker Diabetic Fatty rats. Pyruvate carboxylase ASO did not alter de novo fatty acid synthesis, lipolysis, or hepatocyte fatty acid oxidation. In contrast, the lipid phenotype was attributed to a decrease in hepatic and adipose glycerol synthesis, which is important for fatty acid esterification when dietary fat is in excess. Tissue-specific inhibition of pyruvate carboxylase is a potential therapeutic approach for nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes.
Lack of Effectiveness of Hyperbaric Oxygen Therapy for the Treatment of Diabetic Foot Ulcer and the Prevention of Amputation
Authors: Margolis David J. , Gupta Jayanta , Hoffstad Ole , Papdopoulos Maryte , Glick Henry A. , Thom Stephen R. , Mitra Nandita
Published: February 2013

OBJECTIVE

Hyperbaric oxygen (HBO) is a device that is used to treat foot ulcers. The study goal was to compare the effectiveness of HBO with other conventional therapies administered in a wound care network for the treatment of a diabetic foot ulcer and prevention of lower-extremity amputation.

RESEARCH DESIGN AND METHODS

This was a longitudinal observational cohort study. To address treatment selection bias, we used propensity scores to determine the “propensity” that an individual was selected to receive HBO.

RESULTS

We studied 6,259 individuals with diabetes, adequate lower limb arterial perfusion, and foot ulcer extending through the dermis, representing 767,060 person-days of wound care. In the propensity score–adjusted models, individuals receiving HBO were less likely to have healing of their foot ulcer (hazard ratio 0.68 [95% CI 0.63–0.73]) and more likely to have an amputation (2.37 [1.84–3.04]). Additional analyses, including the use of an instrumental variable, were conducted to assess the robustness of our results to unmeasured confounding. HBO was not found to improve the likelihood that a wound might heal or to decrease the likelihood of amputation in any of these analyses.

CONCLUSIONS

Use of HBO neither improved the likelihood that a wound would heal nor prevented amputation in a cohort of patients defined by Centers for Medicare and Medicaid Services eligibility criteria. The usefulness of HBO in the treatment of diabetic foot ulcers needs to be reevaluated.
Proinsulin/Insulin Autoantibodies Measured With Electrochemiluminescent Assay Are the Earliest Indicator of Prediabetic Islet Autoimmunity
Authors: Yu Liping , Dong Fran , Miao Dongmei , Fouts Alexandra R. , Wenzlau Janet M. , Steck Andrea K.
Published: February 2013

OBJECTIVE

We evaluated a novel electrochemiluminescent assay for insulin/proinsulin autoantibodies (ECL-IAA) as a new marker of the onset of islet autoimmunity and as a predictor of type 1 diabetes.

RESEARCH DESIGN AND METHODS

The Diabetes Autoimmunity Study in the Young (DAISY) prospectively follows children at increased genetic risk for development of islet autoimmunity (defined as presence of autoantibodies to insulin, GAD65, IA-2, or zinc transporter 8 [ZnT8]) and type 1 diabetes (general population of children and first-degree relatives). Serial serum samples from subjects who progressed to type 1 diabetes and who had their first islet autoantibodies measured by age 18 months (N = 47) were tested using ECL-IAA.

RESULTS

Almost all prediabetic children tested positive for ECL-IAA (46 of 47, 98%) during follow-up. ECL-IAA was almost always the first autoantibody to appear (94% total; 21% very first [by itself]; 23% with only mIAA; 19% with another islet autoantibody [GAD or ZnT8]; and 30% with ≥2 other antibodies [mIAA, GAD, IA-2, or ZnT8]). Among the 46 subjects who were ECL-IAA positive, ECL-IAA antedated the onset of other islet autoantibodies by a mean of 2.3 years (range, 0.3–7.2 years). Both the age of appearance of autoantibody and IAA levels (but not GAD65, IA2, or ZnT8 levels) are major determinants of the age of diabetes onset.

CONCLUSIONS

This new ECL-IAA assay defines more precisely the onset of prediabetic autoimmunity and may help identify events triggering islet autoimmunity, as well as allow earlier intervention for type 1 diabetes. Nearly all young children progressing to diabetes are insulin autoantibody positive.
Frequency and chronological distribution of linear enamel hypoplasia (LEH) in the Late Neolithic and Early Bronze Age population from Żerniki Górne (Poland) – preliminary report
Authors: Tomczyk Jacek , Tomczyk-Gruca Maria , Zalewska Marta
Published: February 2013

Linear enamel hypoplasia (LEH) is treated as a nonspecific indicator of stress, but even so, many authors consider it the most reliable tool stress in anthropological research. Its analysis allows the reconstruction of health related to the socio-economic status of the group. This study documents and interprets patterns of LEH in Żerniki Górne (Poland), a settlement which was functional in the Late Neolithic and the Early Bronze Age. We examined two successive cultures: the Corded Ware Culture (CWC; 3200–2300BC) and the Trzciniec Culture (TC; 1500–1300BC).

In total, there were 1486 permanent teeth (124 adult individuals). The frequency of LEH in the examined cultures shows a small rising trend. In these series from Żernik Górne, males showed a higher occurrence of LEH (16.5%) than females (13.4%). The earliest LEH appeared at similar ages at about 2.0/2.2 years and the last LEH occurred at about 4.2 years of age in both cultures. However, it is worth noting that periods associated with physiological stress were more common but not very long (four months on average) in the CWC. Longer stress periods (nine months on average) were associated with the TC.
An introduction to the palaeoenvironmental reconstruction of the Bathonian (Middle Jurassic) ore-bearing clays at Gnaszyn, Kraków-Silesia Homocline, Poland
Authors: Gedl Przemysław , Kaim Andandrzej
Published: February 2013

Gedl. P. and Kaim, A. 2012. An introduction to the palaeoenvironmental reconstruction of the Bathonian (Middle Jurassic) ore-bearing clays at Gnaszyn, Kraków-Silesia Homocline, Poland. Acta Geologica Polonica, 62 (3), 267- 280. Warszawa.

This paper provides introductory data for multidisciplinary studies on palaeoenvironmental reconstructions of the Bathonian (Middle Jurassic) ore-bearing clays exposed at Gnaszyn, southern Poland. These dark-coloured fine-clastic deposits have been studied for micropalaeontology, sedimentology and geochemistry (published in separate papers within this volume). Brief outlines of the Middle Jurassic palaeogeography of the Polish epicontinental basin and the geology of the Kraków-Silesia Homocline are given. A description of the ore-bearing clays succession exposed in the clay-pit at Gnaszyn is provided, including locations of the sections studied, their ammonite biostratigraphy, brief lithology and macrofossil distribution. The sample positions collected for micropalaeontological and geochemical studies are specified.
Palaeoenvironmental significance of iron carbonate concretions from the Bathonian (Middle Jurassic) ore-bearing clays at Gnaszyn, Kraków-Silesia Homocline, Poland
Authors: Witkowska Magdalena
Published: February 2013

Witkowska, M. 2012. Palaeoenvironmental significance of iron carbonate concretions from the Bathonian (Middle Jurassic) ore-bearing clays at Gnaszyn, Krakow-Silesia Homocline, Poland. Acta Geologica Polonica, 62 (3), 307-324. Warszawa.

Iron carbonate concretion horizons are characteristic features of the Bathonian (Middle Jurassic) claystone-mudstone succession at Gnaszyn. They occur in single horizons, which generally represent the same genetic type. The siderite concretions are the main type of iron carbonate concretions at Gnaszyn; a second type is represented by phosphate-siderite concretions. On the basis of the fieldwork, and their petrographical and mineralogical characteristics, the genesis of the concretions and their palaeoenvironmental significance is discussed. The results of this study (based on the localization, mode of occurrence, mineralogy of iron carbonate concretions and also the textural relationship between the concretions and host sediment layers) suggest an early diagenetic origin of the concretions. The preferential occurrence of the concretion horizons in single layers in the ambient sediments was associated with particular conditions of their deposition and early diagenesis, favored by a slower sedimentation rate and more intense bioturbation, and related primarily to the greater availability of reactive iron ions. From the viewpoint of physicochemical conditions the horizons with iron carbonate concretions in the study area reflect the redox boundary between oxic/bioturbated and anoxic/non-bioturbated zones. The conditions favoring the formation of such horizons was possibly due to longer periods of diminished sedimentation rate when the redox boundary remained in the same position within the sediment.