bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA transcriptome profiles during swine skeletal muscle development
Authors: McDaneld Tara G , Smith Timothy PL , Doumit Matthew E , Miles Jeremy R , Coutinho Luiz L , Sonstegard Tad S , Matukumalli Lakshmi K , Nonneman Dan J , Wiedmann Ralph T
Published: February 2009

Background

MicroRNA (miR) are a class of small RNAs that regulate gene expression by inhibiting translation of protein encoding transcripts. To evaluate the role of miR in skeletal muscle of swine, global microRNA abundance was measured at specific developmental stages including proliferating satellite cells, three stages of fetal growth, day-old neonate, and the adult.

Results

Twelve potential novel miR were detected that did not match previously reported sequences. In addition, a number of miR previously reported to be expressed in mammalian muscle were detected, having a variety of abundance patterns through muscle development. Muscle-specific miR-206 was nearly absent in proliferating satellite cells in culture, but was the highest abundant miR at other time points evaluated. In addition, miR-1 was moderately abundant throughout developmental stages with highest abundance in the adult. In contrast, miR-133 was moderately abundant in adult muscle and either not detectable or lowly abundant throughout fetal and neonate development. Changes in abundance of ubiquitously expressed miR were also observed. MiR-432 abundance was highest at the earliest stage of fetal development tested (60 day-old fetus) and decreased throughout development to the adult. Conversely, miR-24 and miR-27 exhibited greatest abundance in proliferating satellite cells and the adult, while abundance of miR-368, miR-376, and miR-423-5p was greatest in the neonate.

Conclusion

These data present a complete set of transcriptome profiles to evaluate miR abundance at specific stages of skeletal muscle growth in swine. Identification of these miR provides an initial group of miR that may play a vital role in muscle development and growth.
Inducible expression of beta defensins by human respiratory epithelial cells exposed to Aspergillus fumigatusorganisms
Authors: Alekseeva Ludmila , Huet Dominique , Féménia Françoise , Mouyna Isabelle , Abdelouahab Mahdia , Cagna Adrien , Guerrier Daniel , Tichanné-Seltzer Virginie , Baeza-Squiban Armelle , Chermette René , Latgé Jean-Paul , Berkova Nadia
Published: February 2009

Background

Aspergillus fumigatus, a saprophytic mould, is responsible for life-threatening, invasive pulmonary diseases in immunocompromised hosts. The role of the airway epithelium involves a complex interaction with the inhaled pathogen. Antimicrobial peptides with direct antifungal and chemotactic activities may boost antifungal immune response.

Results

The inducible expression of defensins by human bronchial epithelial 16HBE cells and A549 pneumocyte cells exposed toA. fumigatuswas investigated. Using RT-PCR and real time PCR, we showed an activation of hBD2 and hBD9 defensin genes: the expression was higher in cells exposed to swollen conidia (SC), compared to resting conidia (RC) or hyphal fragments (HF). The kinetics of defensin expression was different for each one, evoking a putative distinct function for each investigated defensin. The decrease of defensin expression in the presence of heat-inactivated serum indicated a possible link between defensins and the proteins of the host complement system. The presence of defensin peptide hBD2 was revealed using immunofluorescence that showed a punctual cytoplasmic and perinuclear staining. Quantification of the cells stained with anti hBD2 antibody demonstrated that SC induced a greater number of cells that synthesized hBD2, compared to RC or HF. Labelling of the cells with anti-hBD-2 antibody showed a positive immunofluorescence signal around RC or SC in contrast to HF. This suggests co-localisation of hBD2 and digested conidia. The HBD2 level was highest in the supernatants of cells exposed to SC, as was determined by sandwich ELISA. Experiments using neutralising anti-interleukine-1β antibody reflect the autocrine mechanism of defensin expression induced by SC. Investigation of defensin expression at transcriptional and post-transcriptional levels demonstrated the requirement of transcription as well as new protein synthesis duringA. fumigatusdefensin induction. Finally, induced defensin expression in primary culture of human respiratory cells exposed toA. fumigatuspoints to the biological significance of described phenomena.

Conclusion

Our findings provide evidence that respiratory epithelium might play an important role in the immune response duringAspergillusinfection. Understanding the mechanisms of regulation of defensin expression may thus lead to new approaches that could enhance expression of antimicrobial peptides for potential therapeutic use during aspergillosis treatment.
Identification of two proteins that interact with the Erp virulence factor from Mycobacterium tuberculosis by using the bacterial two-hybrid system
Authors: Klepp Laura I , Soria Marcelo , Blanco Federico C , Bianco María V , Santangelo María P , Cataldi Angel A , Bigi Fabiana
Published: February 2009

Background

The exported repetitive protein (erp) gene encodes a secreted 36-kDa protein with a central domain containing several proline-glycine-leucine-threonine-serine (PGLTS) repeats. It has been demonstrated that erp is a virulence-associated factor since the disruption of this gene impairs the growth of Mycobacterium bovis and Mycobacterium tuberculosis in mice.

Results

In order to elucidate the function of Erp we searched for Erp-binding proteins from M. tuberculosis by using a bacterial two-hybrid system. Our results indicate that Erp interacts specifically with two putative membrane proteins, Rv1417 and Rv2617c. Further analysis revealed that the latter two interact with each other, indicating that Rv1417, Rv2617c and Erp are connected through multiple interactions. While Rv1417 is disseminated in several Actinomycetales genera, orthologues of Rv2617c are exclusively present in members of the M. tuberculosis complex (MTC). The central and amino-terminal regions of Erp were determined to be involved in the interaction with Rv1417 and Rv2627c. Erp forms from Mycobacterium smegmatis and Mycobacterium leprae were not able to interact with Rv2617c in two-hybrid assays. Immunolocalization experiments showed that Rv1417 and Rv2617c are found on the cell membrane and Erp on the bacterial cell wall. Finally, comparative genomics and expression studies revealed a possible role of Rv1417 in riboflavin metabolism.

Conclusion

We identified interactive partners of Erp, an M. tuberculosis protein involved in virulence, which will be the focus of future investigation to decipher the function of the Erp family protein.
Extremely short duration high intensity interval training substantially improves insulin action in young healthy males
Authors: Babraj John A , Vollaard Niels BJ , Keast Cameron , Guppy Fergus M , Cottrell Greg , Timmons James A
Published: February 2009

Background

Traditional high volume aerobic exercise training reduces cardiovascular and metabolic disease risk but involves a substantial time commitment. Extremely low volume high-intensity interval training (HIT) has recently been demonstrated to produce improvements to aerobic function, but it is unknown whether HIT has the capacity to improve insulin action and hence glycemic control.

Methods

Sixteen young men (age: 21 ± 2 y; BMI: 23.7 ± 3.1 kg·m-2; VO2peak: 48 ± 9 ml·kg-1·min-1) performed 2 weeks of supervised HIT comprising of a total of 15 min of exercise (6 sessions; 4–6 × 30-s cycle sprints per session). Aerobic performance (250-kJ self-paced cycling time trial), and glucose, insulin and NEFA responses to a 75-g oral glucose load (oral glucose tolerance test; OGTT) were determined before and after training.

Results

Following 2 weeks of HIT, the area under the plasma glucose, insulin and NEFA concentration-time curves were all reduced (12%, 37%, 26% respectively, all P < 0.001). Fasting plasma insulin and glucose concentrations remained unchanged, but there was a tendency for reduced fasting plasma NEFA concentrations post-training (pre: 350 ± 36 v post: 290 ± 39 μmol·l-1, P = 0.058). Insulin sensitivity, as measured by the Cederholm index, was improved by 23% (P < 0.01), while aerobic cycling performance improved by ~6% (P < 0.01).

Conclusion

The efficacy of a high intensity exercise protocol, involving only ~250 kcal of work each week, to substantially improve insulin action in young sedentary subjects is remarkable. This novel time-efficient training paradigm can be used as a strategy to reduce metabolic risk factors in young and middle aged sedentary populations who otherwise would not adhere to time consuming traditional aerobic exercise regimes.
The uterine expression of SEC63gene is up-regulated at implantation sites in association with the decidualization during the early pregnancy in mice
Authors: Su Ren-wei , Sun Zhao-gui , Zhao Yue-chao , Chen Qiu-ju , Yang Zeng-ming , Li Run-sheng , Wang Jian
Published: February 2009

Background

Sec63 is a key component of the protein translocation machinery in the mammalian endoplasmic reticulum (ER), and involved in the post-translation processing of secretory proteins. The aim of this study was to determine the expression pattern of SEC63 gene in mouse uterus during the early pregnancy.

Methods

Real-time quantitative PCR and Western blot analyses were used to evaluate the alteration in levels of uterine SEC63 gene expression during the peri-implantation period in mice. Further, both in situ hybridization and immunohistochemical analyses were performed to examine the spatial localization of SEC63 gene expression in mouse uterine tissues. The presence of Sec63 protein in human uterine tissue was also detected by immunohistochemical analysis. Statistical analysis was carried out using Tukey test.

Results

Uterine SEC63 gene expression was up-regulated and predominantly localized in mouse decidual cells during days 5–8 of pregnancy. More interestingly, Sec63 protein was also detected in human decidua of 10-week pregnancy, whereas was not observed in human endometrial tissues both at proliferative and secretory phases of menstrual cycle.

Conclusion

The pattern of SEC63 gene expression is consistent with a possible role for SEC63 in decidualization.
Enhanced Quantal Release of Excitatory Transmitter in Anterior Cingulate Cortex of Adult Mice with Chronic Pain
Authors: Toyoda Hiroki , Zhao Ming-Gao , Zhuo Min
Published: February 2009

The anterior cingulate cortex (ACC) is a forebrain structure that plays important roles in emotion, learning, memory and persistent pain. Our previous studies have demonstrated that the enhancement of excitatory synaptic transmission was induced by peripheral inflammation and nerve injury in ACC synapses. However, little information is available on their presynaptic mechanisms, since the source of the enhanced synaptic transmission could include the enhanced probability of neurotransmitter release at existing release sites and/or increases in the number of available vesicles. The present study aims to perform quantal analysis of excitatory synapses in the ACC with chronic pain to examine the source of these increases. The quantal analysis revealed that both probability of transmitter release and number of available vesicles were increased in a mouse model of peripheral inflammation, whereas only probability of transmitter release but not number of available vesicles was enhanced in a mouse model of neuropathic pain. In addition, we compared the miniature excitatory postsynaptic potentials (mEPSCs) in ACC synapses with those in other pain-related brain areas such as the amygdala and spinal cord. Interestingly, the rate and amplitude of mEPSCs in ACC synapses were significantly lower than those in the amygdala and spinal cord. Our studies provide strong evidences that chronic inflammatory pain increases both probability of transmitter release and number of available vesicles, whereas neuropathic pain increases only probability of transmitter release in the ACC synapses.
Modulation of Transient Receptor Potential Vanilloid 4-Mediated Membrane Currents and Synaptic Transmission by Protein Kinase C
Authors: Cao De-Shou , Yu Shuang-Quan , Premkumar Louis S
Published: February 2009

Background

Transient receptor potential Vanilloid (TRPV) receptors are involved in nociception and are expressed predominantly in sensory neurons. TRPV1, a non-selective cation channel has been extensively studied and is responsible for inflammatory thermal hypersensitivity. In this study, the expression and function of TRPV4 have been characterized and compared with those of TRPV1.

Results

Immunohistochemical studies revealed that both TRPV1 and TRPV4 were co-expressed in dorsal root ganglion (DRG) neuronal cell bodies and in the central terminals of laminae I and II of the spinal dorsal horn (DH). In Ca2+ fluorescence imaging and whole-cell patch-clamp experiments, TRPV1- and TRPV4-mediated responses were observed in a population of the same DRG neurons. Sensitization of TRPV1 has been shown to be involved in inflammatory pain conditions. Incubation with phorbol 12, 13-dibutyrate (PDBu), a PKC activator, resulted in a significant potentiation of TRPV4 currents in DRG neurons. In TRPV4 expressing HEK 293T cells, PDBu increased 4α-phorbol 12, 13-didecanoate (4α-PDD)-induced single-channel activity in cell-attached patches, which was abrogated by bisindolylmaleimide (BIM), a selective PKC inhibitor. TRPV4 is also expressed at the central terminals of sensory neurons. Activation of TRPV4 by 4α-PDD increased the frequency of miniature excitatory post synaptic currents (mEPSCs) in DRG-DH neuronal co-cultures. 4α-PDD-induced increase in the frequency of mEPSCs was further enhanced by PDBu. The expression of TRP channels has been shown in other areas of the CNS; application of 4α-PDD significantly increased the mEPSC frequency in cultured hippocampal neurons, which was further potentiated by PDBu, whereas, TRPV1 agonist capsaicin did not modulate synaptic transmission. Conclusion: These results indicate that TRPV4 and TRPV1 are co-expressed in certain DRG neurons and TRPV4 can be sensitized by PKC not only in DRG neuronal cell bodies, but also in the central sensory and non-sensory nerve terminals. Co-expression of TRPV1 and TRPV4 ion channels, their modulation of synaptic transmission and their sensitization by PKC may synergistically play a role in nociception.
An in vitrostudy investigating the survival and phenotype of mesenchymal stem cells following injection into nucleus pulposus tissue
Authors: Le Maitre Christine L , Baird Pauline , Freemont Anthony J , Hoyland Judith A
Published: February 2009

Introduction

The decreased disc height characteristic of intervertebral disc (IVD) degeneration has often been linked to low back pain, and thus regeneration strategies aimed at restoring the disc extracellular matrix and ultimately disc height have been proposed as potential treatments for IVD degeneration. One such therapy under investigation by a number of groups worldwide is the use of autologous mesenchymal stem cells (MSCs) to aid in the regeneration of the IVD extracellular matrix. To date, however, the optimum method of application of these cells for regeneration strategies for the IVD is unclear, and few studies have investigated the direct injection of MSCs alone into IVD tissues. In the present article, we investigated the survival and phenotype of human MSCs, sourced from aged individuals, following injection into nucleus pulposus (NP) tissue explant cultures.

Methods

Human MSCs extracted from bone marrow were expanded in monolayer culture and, after labelling with adenoviral vectors carrying the green fluorescent protein transcript, were injected into NP tissue explants (sourced from bovine caudal discs) and maintained in culture for 2, 7, 14 and 28 days post injection. Following fixation and paraffin embedding, cell viability was assessed using in situ hybridisation for polyA-mRNA and using immunohistochemistry for caspase 3. Immunohistochemistry/fluorescence for aggrecan, Sox-9 and types I, II and X collagen together with Alizarin red staining was employed to investigate the MSC phenotype and matrix formation.

Results

MSCs were identified in all injected tissue samples and cell viability was maintained for the 4 weeks investigated. MSCs displayed cellular staining for Sox-9, and displayed cellular and matrix staining for aggrecan and type II collagen that increased during culture. No type I collagen, type X collagen or Alizarin red staining was observed at any time point.

Conclusions

MSCs from older individuals differentiate spontaneously into chondrocyte-like NP cells upon insertion into NP tissue in vitro, and thus may not require additional stimulation or carrier to induce differentiation. This is a key finding, as such a strategy would minimise the level of external manipulation required prior to insertion into the patient, thus simplifying the treatment strategy and reducing costs.
Effects of interventional lung assist on haemodynamics and gas exchange in cardiopulmonary resuscitation: a prospective experimental study on animals with acute respiratory distress syndrome
Authors: Zick Günther , Schädler Dirk , Elke Gunnar , Pulletz Sven , Bein Berthold , Scholz Jens , Frerichs Inéz , Weiler Norbert
Published: February 2009

Introduction

Interventional lung assist (ILA), based on the use of a pumpless extracorporeal membrane oxygenator, facilitates carbon dioxide (CO2) elimination in acute respiratory distress syndrome (ARDS). It is unclear whether an ILA system should be clamped during cardiopulmonary resuscitation (CPR) in patients with ARDS or not. The aim of our study was to test the effects of an ILA on haemodynamics and gas exchange during CPR on animals with ARDS and to establish whether the ILA should be kept open or clamped under these circumstances.

Methods

The study was designed to be prospective and experimental. The experiments were performed on 12 anaesthetised and mechanically ventilated pigs (weighing 41 to 58 kg). One femoral artery and one femoral vein were cannulated and connected to an ILA. ARDS was induced by repeated bronchoalveolar lavage. An indwelling pacemaker was used to initiate ventricular fibrillation and chest compressions were immediately started and continued for 30 minutes. In six animals, the ILA was kept open and in the other six it was clamped.

Results

Systolic and mean arterial pressures did not differ significantly between the groups. With the ILA open mean ± standard deviation systolic blood pressures were 89 ± 26 mmHg at 5 minutes, 71 ± 28 mmHg at 10 minutes, 63 ± 33 mmHg at 20 minutes and 83 ± 23 mmHg at 30 minutes. The clamped ILA system resulted in systolic pressures of 77 ± 30 mmHg, 90 ± 23 mmHg, 72 ± 11 mmHg and 72 ± 22 mmHg, respectively. In the group with the ILA system open, arterial partial pressure of CO2 was significantly lower after 10, 20 and 30 minutes of CPR and arterial partial pressure of oxygen was higher 20 minutes after the onset of CPR (191 ± 140 mmHg versus 57 ± 14 mmHg). End-tidal partial pressure of CO2 decreased from 46 ± 23 Torr (ILA open) and 37 ± 9 Torr (ILA clamped) before intervention to 8 ± 5 Torr and 8 ± 10 Torr, respectively, in both groups after 30 minutes of CPR.

Conclusions

Our results indicate that in an animal model of ARDS, blood pressures were not impaired by keeping the ILA system open during CPR compared with the immediate clamping of the ILA with the onset of CPR. The effect of ILA on gas exchange implied a beneficial effect.
Critical porosity and elastic properties of microporous mixed carbonate-siliciclastic rocks
Authors: Fournier F. , Borgomano J.
Published: February 2009

By integrating elastic-property measurements and quantitative mineralogic and petrographic analyses of 45 mixed carbonate-siliciclastic samples from two wells drilled in Late Cretaceous rock of the South Provence Basin (southeast France), we can (1) identify and quantify the parameters controlling elastic properties; (2) demonstrate that micrite can be considered as a porous medium with a low critical porosity, averaging 18%; and (3) relate diagenetic transformations, pore-structure modifications, and elastic-property changes. Microporous carbonates with compact anhedral and euhedral microrhombic micrites display a steeper decrease in compressional and shear velocities with increasing porosity than do carbonate rocks with moldic, intergranular, or intercrystalline macroporosity. The low value of critical porosity estimated in micrites (18%), as well as the steep slopes of velocity-porosity relationships at low porosity, is believed to result from a pore-network geometry characterized by very flat, thin pores bounded by planar faces of micrite crystals. Cementation of microrhombic micrite steeply increases elastic moduli, whereas dissolution processes significantly increase porosity with low variations of elastic moduli. Thus, critical-porosity concepts can help describe and model elastic properties of micritic microporous carbonate.
True-amplitude Gaussian-beam migration
Authors: Gray Samuel H. , Bleistein Norman
Published: February 2009

Gaussian-beam depth migration and related beam migration methods can image multiple arrivals, so they provide an accurate, flexible alternative to conventional single-arrival Kirchhoff migration. Also, they are not subject to the steep-dip limitations of many (so-called wave-equation) methods that use a one-way wave equation in depth to downward-continue wavefields. Previous presentations of Gaussian-beam migration have emphasized its kinematic imaging capabilities without addressing its amplitude fidelity. We offer two true-amplitude versions of Gaussian-beam migration. The first version combines aspects of the classic derivation of prestack Gaussian-beam migration with recent results on true-amplitude wave-equation migration, yields an expression involving a crosscorrelation imaging condition. To provide amplitude-versus-angle (AVA) information, true-amplitude wave-equation migration requires postmigration mapping from lateral distance (between image location and source location) to subsurface opening angle. However, Gaussian-beam migration does not require postmigration mapping to provide AVA data. Instead, the amplitudes and directions of the Gaussian beams provide information that the migration can use to produce AVA gathers as part of the migration process. The second version of true-amplitude Gaussian-beam migration is an expression involving a deconvolution imaging condition, yielding amplitude-variation-with-offset (AVO) information on migrated shot-domain common-image gathers.
1D inversion of multicomponent, multifrequency marine CSEM data: Methodology and synthetic studies for resolving thin resistive layers
Authors: Key Kerry
Published: February 2009

Numerical methods for 1D forward modeling and inversion of marine controlled-source electromagnetic (CSEM) data are used to examine the inherent resolution of various acquisition configurations to thin resistive layers simulating offshore hydrocarbon reservoirs. Synthetic data studies indicate that jointly inverting frequencies of 0.1 and [Formula: see text] offers better resolution than inverting either frequency alone. Further increasing the bandwidth or density of frequencies does not produce a commensurate increase in resolution. An inline horizontal electric dipole is found to provide better resolution than either broadside or vertical electric dipoles. The horizontal electric and magnetic fields for any transmitter orientation have better resolution than vertical fields. Separate inversions of electric and magnetic fields perform equally well at recovering the reservoir, and there is no resolution improvement from jointly inverting both fields. Smooth inversion for a multiple resistive layer model detects the presence of all resistive layers, and shallow thin resistive layers do not impact the ability to image deeper resistive layers. The accuracy of the inverted models is improved substantially by including the boundary depths of resistive layers as a priori structure in the inversion. Including the seawater resistivity profile as fixed structure in the inversion is found to be essential for obtaining optimal resolution of subseafloor resistivity.
A signal comprising a basic cluster and an amphipathic α-helix interacts with lipids and is required for the transport of Ist2 to the yeast cortical ER
Authors: Maass Kiran , Fischer Marcel André , Seiler Markus , Temmerman Koen , Nickel Walter , Seedorf Matthias
Published: February 2009

The yeast integral membrane protein Ist2 is encoded by a bud-localised mRNA and accumulates at patch-like domains of the cell periphery, either at the cortical ER or at ER-associated domains of the plasma membrane. Transport of IST2 mRNA and local protein synthesis are not prerequisite for this localisation, indicating that Ist2 can travel through the general ER to membranes at the cell periphery. Here, we describe that the accumulation of Ist2 at the cortical ER requires a cytosolically exposed complex sorting signal that can interact with lipids at the yeast plasma membrane. Binding of the Ist2 sorting signal to lipids and rapid and efficient transport of Ist2 from perinuclear to cortical ER depend on a cluster of lysine residues, the formation of an amphipathic α-helix and a patch of hydrophobic side chains positioned at one side of the amphipathic α-helix. We suggest that a direct interaction of the Ist2 sorting signal with lipids at the plasma membrane places Ist2 at contact sites between cortical ER and plasma membrane. This provides a physical link of an integral membrane protein of the cortical ER with the plasma membrane and might allow direct transport of proteins from cortical ER to domains of the plasma membrane.
Yersinia enterocolitica differentially modulates RhoG activity in host cells
Authors: Roppenser Bernhard , Röder Anja , Hentschke Moritz , Ruckdeschel Klaus , Aepfelbacher Martin
Published: February 2009

Pathogenic bacteria of the genus Yersinia (Y. pestis, Y. enterocolitica and Y. pseudotuberculosis) have evolved numerous virulence factors (termed a stratagem) to manipulate the activity of Rho GTPases. Here, we show that Y. enterocolitica modulates RhoG, an upstream regulator of other Rho GTPases. At the contact site of virulent Y. enterocolitica and host cells, we could visualise spatiotemporally organised activation and deactivation of RhoG. On the one hand, the β1-integrin clustering protein Invasin on the bacterial surface was found to activate RhoG and this promoted cell invasion. On the other hand, active RhoG was downregulated by the type III secretion system effector YopE acting as a GTPase-activating protein (GAP). YopE localised to Golgi and endoplasmic reticulum, and this determined its specificity for RhoG and other selected Rho GTPases. RhoG and its downstream effector module Elmo/Dock180 controlled both Rac1 activation by Invasin and Rac1 deactivation by YopE. We propose that RhoG is a central target of the Yersinia stratagem and a major upstream regulator of Rac1 during different phases of the Yersinia infection cycle.
Akt promotes BMP2-mediated osteoblast differentiation and bone development
Authors: Mukherjee Aditi , Rotwein Peter
Published: February 2009

Signaling through the IGF-I receptor by locally synthesized IGF-I or IGF-II is crucial for normal skeletal development and for bone remodeling. Osteogenesis is primarily regulated by bone morphogenetic proteins (BMPs), which activate gene expression programs driven by bone-specific transcription factors. In a mesenchymal stem cell model of osteoblast commitment and differentiation controlled by BMP2, we show that an inhibitor of PI3-kinase or a dominant-negative Akt were as potent in preventing osteoblast differentiation as the IGF binding protein IGFBP5, whereas a Mek inhibitor was ineffective. Conversely, an adenovirus encoding an inducible-active Akt was able to overcome the blockade of differentiation caused by IGFBP5 or the PI3-kinase inhibitor, and could restore normal osteogenesis. Inhibition of PI3-kinase or Akt did not block BMP2-mediated signaling, because the Smad-responsive genes Sox9 and JunB were induced normally under all experimental conditions. When activated during different stages of osteoblast maturation, dominant-negative Akt prevented accumulation of bone-specific alkaline phosphatase and reduced mineralization, and more significantly inhibited the longitudinal growth of metatarsal bones in primary culture by interfering with both chondrocyte and osteoblast development and function. We conclude that an intact IGF-induced PI3-kinase–Akt signaling cascade is essential for BMP2-activated osteoblast differentiation and maturation, bone development and growth, and suggest that manipulation of this pathway could facilitate bone remodeling and fracture repair.
A mesh-independent Gurson—Tvergaard—Needleman damage model and its application in simulating ductile fracture behaviour
Authors: Samal M K , Seidenfuss M , Roos E , Dutta B K , Kushwaha H S
Published: February 2009

In this study, the classical Gurson—Tvergaard—Needleman (GTN) model has been extended to a non-local form using damage parameter ‘ d’ as a degree of freedom in the finite-element (FE) formulation. The evolution of the non-local damage is related to the actual void volume fraction ‘ f’ in ductile fracture using a diffusion type equation. The coupled mechanical equilibrium and damage diffusion equations have been discretized using the finite-element (FE) method. In order to demonstrate the mesh-independent nature of the new formulation, a standard fracture mechanics specimen (i.e. 1T compact tension) has been analysed using different mesh sizes near the crack tip and the results have been compared with those of the experiment. The effect of different GTN parameters on the fracture resistance behaviour of this specimen has been studied for the non-local model and these results have also been compared with those of the experiment.
LDP Lean Document Production—O.R.-Enhanced Productivity Improvements for the Printing Industry
Authors: Rai Sudhendu , Duke Charles B. , Lowe Vaughn , Quan-Trotter Cyndi , Scheermesser Thomas
Published: February 2009

Xerox has invented, tested, and implemented a novel class of operations-research-based productivity-improvement offerings, trademarked LDP Lean Document Production® solutions, for the $100 billion printing industry in the United States. These solutions, which Xerox has implemented in approximately 100 sites to date, have provided dramatic productivity and cost improvements for both print shops and document-manufacturing facilities, as measured by reductions of 20–40 percent in revenue-per-unit labor cost. They have generated approximately $200 million of incremental profit across the Xerox customer value chain since their initial introduction in 2000. The offerings have extended the use of operations research to small- and medium-sized print shops, while increasing the scope of its application to large document-production facilities.
US Environmental Protection Agency Uses Operations Research to Reduce Contamination Risks in Drinking Water
Authors: Murray Regan , Hart William E. , Phillips Cynthia A. , Berry Jonathan , Boman Erik G. , Carr Robert D. , Riesen Lee Ann , Watson Jean-Paul , Haxton Terra , Herrmann Jonathan G. , Janke Robert , Gray George , Taxon Thomas , Uber James G. , Morley Kevin M.
Published: February 2009

The US Environmental Protection Agency (EPA) is the lead federal agency for the security of drinking water in the United States. The agency is responsible for providing information and technical assistance to the more than 50,000 water utilities across the country. The distributed physical layout of drinking-water utilities makes them inherently vulnerable to contamination incidents caused by terrorists. To counter this threat, the EPA is using operations research to design, test, and deploy contamination warning systems (CWSs) that rapidly detect the presence of contaminants in drinking water. We developed a software tool to optimize the design process, published a decision-making process to assist utilities in applying the tool, pilot-tested the tool on nine large water utilities, and provided training and technical assistance to a larger group of utilities. We formed a collaborative team of industry, academia, and government to critique our approach and share CWS deployment experiences. Our work has demonstrated that a CWS is a cost-effective, timely, and capable method of detecting a broad range of contaminants. Widespread application of these new systems will significantly reduce the risks associated with catastrophic contamination incidents: the median estimated fatalities reduction for the nine utilities already studied is 48 percent; the corresponding economic-impact reduction is over $19 billion. Because of this operations research program, online monitoring programs, such as a CWS, are now the accepted technology for reducing contamination risks in drinking water.
Can we get sick if we want to? Children's and adults' recognition of intentionality in the origins of illness and injuries
Authors: Raman Lakshmi
Published: February 2009

The present set of studies examined the impact of intentionality (wanting/not wanting to get sick) on the transmission of contagious illness and injuries. Study 1 examined whether preschoolers and adults thought that a recipient of an illness is more likely to get sick if he/she wanted to. Studies 2, 2a, and 3 examined if the intentions of the transmitter would influence the transmission of illness to the recipient. Study 4 examined the influence of germs on intentionality. Both preschoolers and adults reasoned that the intentions of the recipient would play a significant role in the probability of contracting an illness but only adults reasoned that the recipient having knowledge of the transmitter's intentions would have an impact on illness. Moreover, preschoolers (but not adults) judged that biological contaminants such as germs would interact with the intentionality of the recipient to increase the chances of contracting an illness whereas adults reasoned that psychological states can have a direct influence on the manifestation of illness. These results suggest that preschoolers and adults entertain a highly sophisticated and selective process when assessing, the impact of psychological factors such as intentionality on biological processes such as the origins of illness.
Executive function in children with high and low attentional skills: Correspondences between behavioural and cognitive profiles
Authors: Scope Alison , Empson Janet , McHale Sue
Published: February 2009

Cognitive performance was compared between two groups of typically developing children, who had been observed and rated as differing significantly in their attentional skills at school. The participants were 24 8‐ and 9‐year‐old children scoring poorly relative to peers, on a classroom observation scale and teacher rating scale for attention, hyperactivity, and impulsivity [low‐attentional skills (LAS) group] and 24 sex‐ and age‐matched children scoring at a high level compared to peers [high‐attentional skills (HAS) group]. The two groups were compared on a series of cognitive tasks to assess executive function (EF). The LAS group performed within the typical range yet at a significantly lower level than the HAS group on the majority of the EF tasks administered, namely working memory and inhibition measures, even though there were no significant differences between the groups on a measure of intellectual ability. Working memory measures followed by measures of inhibition emerged as the best predictors of group membership. These findings provide empirical evidence that there are individual differences in attentional skills. Specifically, that there is a relationship between behavioural inattention, hyperactivity, and impulsivity and cognitive performance on working memory and inhibitory control tasks.
Genetic Influences on Type 2 Diabetes and Metabolic Syndrome Related Quantitative Traits in Mauritius
Authors: Jowett Jeremy B. , Diego Vincent P. , Kotea Navaratnam , Kowlessur Sudhir , Chitson Pierrot , Dyer Thomas D. , Zimmet Paul , Blangero John
Published: February 2009

Epidemiological studies report a high prevalence of type 2 diabetes and metabolic syndrome in the island nation of Mauritius. The Mauritius Family Study was initiated to examine heritable factors that contribute to these high rates of prevalence and consists of 400 individuals in 24 large extended multigenerational pedigrees. Anthropometric and biochemical measurements relating to the metabolic syndrome were undertaken in addition to family and lifestyle based information for each individual. Variance components methods were used to determine the heritability of the type 2 diabetes and metabolic syndrome related quantitative traits. The cohort was made up of 218 females (55%) and 182 males with 22% diagnosed with type 2 diabetes and a further 30% having impaired glucose tolerance or impaired fasting glucose. Notably BMI was not significantly increased in those with type 2 diabetes (P= .12), however a significant increase in waist circumference was observed in these groups (P= .02). The heritable proportion of trait variance was substantial and greater than values previously published for hip circumference, LDL and total cholesterol, diastolic and systolic blood pressure and serum creatinine. Height, weight and BMI heritabilities were all in the upper range of those previously reported. The phenotypic characteristics of the Mauritius family cohort are similar to those previously reported in the Mauritian population with a high observed prevalence rate of type 2 diabetes. A high heritability for key type 2 diabetes and metabolic syndrome related phenotypes (range 0.23 to 0.68), suggest the cohort will have utility in identifying genes that influence these quantitative traits.
Der Familienname als Nationalsymbol. Über den Untergang deutscher Familiennamen im Ungarn des 19. Jahrhunderts
Authors: Maitz Péter , Farkas Tamás
Published: February 2009

As a result of German-Hungarian societal bilingualism German family names had been present in multilingual 19th century Hungary for centuries. Magyarizations of family names in the second half of the 19th century mostly affected the German and Yiddish speech communities bearing German family names. This paper explores the causes and characteristics of this phenomenon by examining the social, psychological, and ideological factors influencing the use of family names. After giving the numerical description of family name changes, the authors examine the sociolinguistic background of family name use, focusing on the situation of ethnolinguistic communities whose members bore German family names. By analysing the semantic structure of family names, the authors present how and why these family names could become tools of linguistic nationalism in contemporary Hungary, generating the claim of changing foreign-sounding family names to Hungarian ones. The political and social background of family name changes as well as social stratification of the applicants are also examined. The authors describe the movement of family name Magyarizations as a behavioural pattern of middle-class people ready to accept social mobility and willing to take part in assimilation. The aesthetic, functional and linguistic principles found behind these family name changes are also discussed. After briefly presenting the history of German family names in 20th century Hungary, the authors deduce some basic theoretical and methodological conclusions.
High-Temperature, High-Shear Oil Viscosity: Measurement and Relationship to Engine Operation
Authors: Spearot JA
Published: February 2009

Description

8 papers summarize and review the state-of-the-art in making and interpreting oil viscosity measurements at high temperatures and shear rates.
Development of ASTM Standard Test Methods for Measuring Engine Oil Viscosity Using Rotational Viscometers at High-Temperature and High-Shear Rates
Authors: Rhodes RB
Published: February 2009

Two ASTM standards have been developed for the measurement of engine oil viscosity at high temperature (150°C) and high shear rate (106 s-1) using rotational viscometers. Both methods resulted from significant international participation at the working group level. One test method resulted from work done primarily within ASTM Committee D-2, Subcommittee 7, using the tapered bearing simulator. The other resulted from work done within the Co-ordinating European Council (CEC) using the Ravenfield viscometer, herein called the tapered plug viscometer. The chronological development of each standard is reviewed, and test method and precision are compared. Expansion of measurement capabilities are discussed with regard to the study of lubricant rheology and engine performance.
Development of an ASTM Standard Test Method for Measuring Engine Oil Viscosity Using Capillary Viscometers at High-Temperature and High-Shear Rates
Authors: Demko JM
Published: February 2009

The development of a standard ASTM test method for measuring engine oil viscosity at high temperature (150°C) and high rate of shear (106 S-1) is discussed. A review is provided of the ASTM interlaboratory program that incorporated several different viscometer designs to evaluate a single generalized procedure for viscosity determination. A statistical analysis for ASTM repeatability and reproducibility resulted in a level of precision that approached that of rotational high-temperature, high-shear viscometers. Excellent correlation between capillary viscometers and rotational instruments is also demonstrated. The method is applicable to existing high-temperature, high-shear viscosity requirements in the European Committee of Common Market Automobile Constructors (CCMC) specification as well as individual high-temperature, high-shear specifications established by original equipment manufacturers.
Co-ordinating European Council (CEC) Contribution to the Measurement of High-Temperature, High-Shear-Rate Viscosity and Its Relationship to Engine Operation
Authors: Vickars MA , Bates TW
Published: February 2009

Co-ordinating European Council (CEC) studies showed good agreement among results obtained with different types of high-shear viscometers. Curve-fitting procedures based on the Extended Cross Equation provided a means of comparing results from different viscometers and permitted the interpolation and extrapolation of viscosities to a standard temperature and shear rate, for example, 150°C and 106 s-1. These studies contributed significantly to the development of the first low-cost, commercial, rotational viscometer capable of measuring viscosity over appropriate temperature and shear rate ranges. Satisfactory precision was demonstrated, and international standard procedures were established for the Ravenfield viscometer. Engine studies showed strong linear correlations of high-temperature, high-shear (HTHS) viscosity with engine friction, engine-bearing oil flow, and fuel saving. Results of engine wear tests, however, did not appear to be viscosity dependent. Areas for future study, for example, measurement of bearing oil film thickness, are indicated, and the interaction of CEC with the European Committee of Common Market Automobile Constructors (CCMC), ASTM, and the Society of Automotive Engineers (SAE) is described.
Involvement of TRPC Channels in CCL2-Mediated Neuroprotection against Tat Toxicity
Authors: Yao Honghong , Peng Fuwang , Dhillon Navneet , Callen Shannon , Bokhari Sirosh , Stehno-Bittel Lisa , Ahmad S. Omar , Wang John Q. , Buch Shilpa
Published: February 2009

Chemokine (C-C motif) ligand 2 (CCL2), also known as monocyte chemoattractant protein-1, plays a critical role in leukocyte recruitment and activation. In the present study, we identify an additional role for CCL2 that of neuroprotection against HIV-1 transactivator protein (Tat) toxicity in rat primary midbrain neurons. Furthermore, we report the involvement of transient receptor potential canonical (TRPC) channels in CCL2-mediated neuroprotection. TRPC are Ca2+-permeable, nonselective cation channels with a variety of physiological functions. Blockage of TRPC channels resulted in suppression of both CCL2-mediated neuroprotection and intracellular Ca2+elevations. Parallel but distinct extracellular signal-regulated kinase (ERK)/cAMP response element-binding protein (CREB) and Akt/nuclear factor κB (NF-κB) pathways were involved in the CCL2-mediated neuroprotection. Blocking TRPC channels and specific downregulation of TRPC channels 1 and 5 resulted in suppression of CCL2-induced ERK/CREB activation but not Akt/NF-κB activation.In vivorelevance of these findings was further corroborated in wild-type and CCR2 knock-out mice. In the wild-type but not CCR2 knock-out mice, exogenous CCL2 exerted neuroprotection against intrastriatal injection of HIV-1 Tat. These findings clearly demonstrate a novel role of TRPC channels in the protection of neurons against Tat through the CCL2/CCR2 axis.
Developmental Regulation of Sensory Neurite Growth by the Tumor Necrosis Factor Superfamily Member LIGHT
Authors: Gavaldà Núria , Gutierrez Humberto , Davies Alun M.
Published: February 2009

In a PCR screen to identify novel cytokine candidates involved in neuronal development, we identified transcripts for the tumor necrosis factor superfamily member 14 (TNFSF14), generally known as LIGHT (lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells), together with its receptors, lymphotoxin-β receptor (LTβR) and TNF family receptor herpesvirus entry mediator (HVEM), in the experimentally tractable sensory neurons of the mouse nodose ganglion. Immunocytochemistry revealed coexpression of LIGHT and its receptors in all nodose ganglion neurons in neonates. Enhancing LIGHT signaling in these neurons by overexpressing LIGHT inhibited BDNF-promoted neurite growth during a narrow window of development in the immediate perinatal period without affecting neuronal survival. Overexpressing a LIGHT mutant that selectively activates HVEM, but not one that selectively activates LTβR, also inhibited BDNF-promoted growth, suggesting that neurite growth inhibition is mediated via HVEM. Blocking HVEM signaling by a function-blocking anti-HVEM antibody significantly enhanced neurite growth from nodose neurons grown both with and without BDNF. Likewise, neurons from LIGHT-deficient neonates exhibited significantly greater neurite growth than neurons from wild-type littermates in both the presence and absence of BDNF. LIGHT overexpression significantly inhibited NF-κB activity, while preventing LIGHT-induced NF-κB inhibition by overexpressing the p65 and p50 NF-κB subunits prevented LIGHT-mediated growth inhibition. Together, these findings show that LIGHT/HVEM signaling negatively regulates neurite growth from developing sensory neurons via NF-κB inhibition.