bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma disc decompression compared with fluoroscopy-guided transforaminal epidural steroid injections for symptomatic contained lumbar disc herniation: a prospective, randomized, controlled trial
Authors: Gerszten Peter C. , Smuck Matthew , Rathmell James P. , Simopoulos Thomas T. , Bhagia Sarjoo M. , Mocek Christopher K. , Crabtree Tami , Bloch Daniel A.
Published: March 2010

Object

Patients with radiculopathy, with or without back pain, often do not respond to conservative care and may be considered for epidural steroid injection therapy or a disc decompression procedure. Plasma disc decompression (PDD) using the Coblation SpineWand device is a percutaneous, minimally invasive interventional procedure. The purpose of this study was to evaluate clinical outcomes with PDD as compared with standard care using fluoroscopy-guided transforaminal epidural steroid injection (TFESI) over the course of 2 years.

Methods

This was a multicenter randomized controlled clinical study. Ninety patients (18–66 years old) who had sciatica (visual analog scale score ≥50) associated with a single-level lumbar contained disc herniation were enrolled. In all cases, their condition was refractory to initial conservative care and 1 epidural steroid injection had failed. Participants were randomly assigned to receive either PDD (46 patients) or TFESI (44 patients, up to 2 injections).

Results

The patients in the PDD Group had significantly greater reduction in leg pain scores and significantly improved Oswestry Disability Index and 36-Item Short Form Health Survey ([SF-36], physical function, bodily pain, social function, and physical components summary) scores than those in the TFESI Group. During the 2-year follow-up, 25 (56%) of the patients in the PDD Group and 11 (28%) of those in the TFESI Group remained free from having a secondary procedure following the study procedure (log-rank p = 0.02). A significantly higher percentage of patients in the PDD Group showed minimum clinically important change in scores for leg and back pain and SF-36 scores that exceeded literature-based minimum clinically important changes. Procedure-related adverse events, including injection site pain, increased leg or back pain, weakness, and lightheadedness, were observed in 5 patients in the PDD Group (7 events) and 7 in the TFESI Group (14 events).

Conclusions

In study patients who had radicular pain associated with a contained lumbar disc herniation, those patients treated with PDD had significantly reduced pain and better quality of life scores than those treated using repeated TFESI. In addition, significantly more PDD patients than TFESI patients avoided having to undergo a secondary procedure during the 2-year study follow-up.
Activated Carbon Modified with Copper for Adsorption of Propanethiol
Authors: Moreno-Piraján Juan Carlos , Tirano Joaquín , Salamanca Brisa , Giraldo Liliana
Published: March 2010

Activated carbons were characterized texturally and chemically before and after treatment, using surface area determination in the BET model, Boehm titration, TPR, DRX and immersion calorimetry. The adsorption capacity and the kinetics of sulphur compound removal were determined by gas chromatography. It was established that the propanethiol retention capacity is dependent on the number of oxygenated groups generated on the activated carbon surface and that activated carbon modified with CuO at 0.25 M shows the highest retention of propanethiol. Additionally is proposed a mechanism of decomposition of propenothiol with carbon-copper system.
Aza-27-crown-9 Amino Acid
Authors: Späth Andreas , König Burkhard
Published: March 2010

A luminescent aza-27-crown-9 ether amino acid was prepared by a three-step reaction sequence. The compound signals ammonium ion binding by an increase in emission intensity.
Catalytic Asymmetric Nitro-Mannich Reactions with a Yb/K Heterobimetallic Catalyst
Authors: Nitabaru Tatsuya , Kumagai Naoya , Shibasaki Masakatsu
Published: March 2010

A catalytic asymmetric nitro-Mannich (aza-Henry) reaction with rare earth metal/alkali metal heterobimetallic catalysts is described. A Yb/K heterobimetallic catalyst assembled by an amide-based ligand promoted the asymmetric nitro-Mannich reaction to afford enantioenriched anti-b-nitroamines in up to 86% ee. Facile reduction of the nitro functionality allowed for efficient access to optically active 1,2-diamines.
Synthesis of syn-γ-Amino-β-hydroxyphosphonates by Reduction of β-Ketophosphonates Derived from L-Proline and L-Serine
Authors: Ordóñez Mario , Lagunas-Rivera Selene , Hernández-Núñez Emanuel , Labastida-Galván Victoria
Published: March 2010

The reduction of γ-N-benzylamino-β-ketophosphonates 6 and 10, readily available from L-proline and L-serine, respectively, can be carried out in high diastereoselectivity with catecholborane (CB) in THF at -78 ºC to produce the syn-γ-N-benzylamino-β-hydroxyphosphonates 11 and 13 as a single detectable diastereoisomer, under non-chelation or Felkin-Anh model control.
Reductive Heck Reactions of N-Methyl-substituted Tricyclic Imides
Authors: Goksu Gokce , Ocal Nuket , Kaufmann Dieter E.
Published: March 2010

The palladium-catalyzed hydroarylation of N-methyl-substituted tricyclic imides was studied in order to find a new stereoselective access to a series of new exo-aryl(hetaryl)-substituted tricyclic N-methylimides.
Wide Dynamic Range CMOS Potentiostat for Amperometric Chemical Sensor
Authors: Wang Wei-Song , Kuo Wei-Ting , Huang Hong-Yi , Luo Ching-Hsing
Published: March 2010

Presented is a single-ended potentiostat topology with a new interface connection between sensor electrodes and potentiostat circuit to avoid deviation of cell voltage and linearly convert the cell current into voltage signal. Additionally, due to the increased harmonic distortion quantity when detecting low-level sensor current, the performance of potentiostat linearity which causes the detectable current and dynamic range to be limited is relatively decreased. Thus, to alleviate these irregularities, a fully-differential potentiostat is designed with a wide output voltage swing compared to single-ended potentiostat. Two proposed potentiostats were implemented using TSMC 0.18-μm CMOS process for biomedical application. Measurement results show that the fully differential potentiostat performs relatively better in terms of linearity when measuring current from 500 ºpA to 10 uA. Besides, the dynamic range value can reach a value of 86 dB.
Study of Sodium Ion Selective Electrodes and Differential Structures with Anodized Indium Tin Oxide
Authors: Lin Jyh-Ling , Hsu Hsiang-Yi
Published: March 2010

The objective of this work is the study and characterization of anodized indium tin oxide (anodized-ITO) as a sodium ion selective electrode and differential structures including a sodium-selective-membrane/anodized-ITO as sensor 1, an anodized-ITO membrane as the contrast sensor 2, and an ITO as the reference electrode. Anodized-ITO was fabricated by anodic oxidation at room temperature, a low cost and simple manufacture process that makes it easy to control the variation in film resistance. The anodized-ITO based on EGFET structure has good linear pH sensitivity, approximately 54.44 mV/pH from pH 2 to pH 12. The proposed sodium electrodes prepared by PVC-COOH, DOS embedding colloid, and complex Na-TFBD and ionophore B12C4, show good sensitivity at 52.48 mV/decade for 10−4 M to 1 M, and 29.96 mV/decade for 10−7 M to 10−4 M. The sodium sensitivity of the differential sodium-sensing device is 58.65 mV/decade between 10−4 M and 1 M, with a corresponding linearity of 0.998; and 19.17 mV/decade between 10−5 M and 10−4 M.
Renewable Energy Use in Smallholder Farming Systems: A Case Study in Tafresh Township of Iran
Authors: Fami Hossein Shabanali , Ghasemi Javad , Malekipoor Rahil , Rashidi Parinaz , Nazari Saeede , Mirzaee Arezoo
Published: March 2010

This study was conducted to investigate use of renewable energy and materials in smallholder farming system of the Tafresh township of Iran. The population of the study consisted of 2,400 small farmers working in the smallholder farming systems of the area, in which 133 people were selected as sample using Cochran formula and simple random sampling technique. In order to gather the information, a questionnaire was developed for the study and validated by the judgment of the experts in agricultural development and extension. The reliability of the main scales of the questionnaire was examined by Cronbach Alpha coefficients, which ranged from 0.7 to 0.93, indicating the tool of study is reliable. The findings revealed that the majority of the respondents use renewable energy and materials directly in its traditional forms without enabling technologies, and they lack the access to renewable technologies to improve the efficiency of energy use. They preferred fossil energy for many activities due to its lower cost and ease of access. The overall conclusion is that there are potentials and capacities for using renewable energies and materials in the farming systems of the Tafresh township. The government has to support and encourage the adoption of renewable technologies and abandon fossil fuels wherever possible.
Identification of a Unique Population of Tissue-Memory CD4+ T Cells in the Airways after Influenza Infection That Is Dependent on the Integrin VLA-1
Authors: Chapman Timothy J. , Topham David J.
Published: March 2010

During the immune response to influenza infection, activated T cells are distributed to both lymphoid and extralymphoid tissues, including the infected airways where direct recognition of viral Ag-bearing cells takes place. The collagen-binding α1β1 integrin VLA-1 is essential for the development of memory CD8+ T cells in the airways, and although expressed by some CD4+ T cells, its significance has not been demonstrated. We investigated the role of VLA-1 on virus-specific CD4+ T cells during and after primary or secondary influenza infection of mice. The proportion of CD4+ cells expressing CD49a (α1 integrin) was low in all tissues sampled during primary infection but increased in the airways after viral clearance. Furthermore, during the first 24 h of a secondary influenza challenge, the majority of IFN-γ–secreting effector CD4+ T cells from the airways was in the CD49a+ population. Airway CD49a+CD4+ cells also expressed reduced markers of apoptosis compared with CD49a− cells, and fewer memory or effector CD4+ cells could be recovered from airways of α1−/− mice, although lymphoid tissues appeared unaffected. These data suggest VLA-1 expression defines a population of tissue memory CD4+ T cells that act as rapid effectors upon reinfection, and VLA-1 expression is integral to their accumulation in the airways.
Cutting Edge: A Critical Role for the G Protein-Coupled Receptor mFPR2 in Airway Inflammation and Immune Responses
Authors: Chen Keqiang , Le Yingying , Liu Ying , Gong Wanghua , Ying Guoguang , Huang Jian , Yoshimura Teizo , Tessarollo Lino , Wang Ji Ming
Published: March 2010

The formylpeptide receptor-like 1, now officially termed FPR2, in human and its mouse homolog mFPR2 mediate leukocyte migration in response to agonists associated with inflammation and immune responses. To clarify the in vivo role of the receptor, we generated mice deficient in mFPR2. mFPR2−/− mice showed markedly reduced severity in OVA/alum-induced allergic airway inflammation. This was associated with diminished recruitment of CD11c+ dendritic cells into the airway mucosa and secondary lymphoid organs, as well as reduced production of Type 2 cytokines and Igs. We also found that the bronchoalveolar lavage fluid from wild type mice with airway inflammation contained mFPR2 agonist activity. This study reveals a critical role for mFPR2 in the progression of allergic airway inflammation and immune responses.
Activation of Tolerogenic Dendritic Cells in the Tumor Draining Lymph Nodes by CD8+ T Cells Engineered to Express CD40 Ligand
Authors: Higham Eileen M. , Wittrup K. Dane , Chen Jianzhu
Published: March 2010

Tolerogenic dendritic cells in the tumor microenvironment can inhibit the generation and maintenance of robust antitumor T cell responses. In this study, we investigated the effects of local delivery of CD40L by tumor-reactive CD8+ T cells on dendritic cell activation and antitumor T cell responses in the TRAMP model. To increase the immunostimulatory signal, CD40L was engineered, by deleting the majority of the cytoplasmic domain, to increase its levels of expression and duration on the surface of CD8+ T cells. Tumor-reactive CD8+ T cells expressing the truncated form of CD40L stimulated maturation of dendritic cells in vitro and in the prostate draining lymph nodes in vivo. Following dendritic cell maturation, a significantly higher fraction of adoptively transferred, tumor-reactive (reporter) CD8+ T cells was stimulated to express IFN-γ and infiltrate the prostate tissue. The antitumor CD8+ T cell response was further enhanced if TRAMP mice were also immunized with a tumor-specific Ag. These findings demonstrate that augmented T cell responses can be achieved by engineering tumor-reactive T cells to deliver stimulatory signals to dendritic cells in the tumor microenvironment.
Febrile-Range Hyperthermia Augments Lipopolysaccharide-Induced Lung Injury by a Mechanism of Enhanced Alveolar Epithelial Apoptosis
Authors: Lipke Anne B. , Matute-Bello Gustavo , Herrero Raquel , Kurahashi Kiyoyasu , Wong Venus A. , Mongovin Stephen M. , Martin Thomas R.
Published: March 2010

Fever is common in critically ill patients and is associated with worse clinical outcomes, including increased intensive care unit mortality. In animal models, febrile-range hyperthermia (FRH) worsens acute lung injury, but the mechanisms by which this occurs remain uncertain. We hypothesized that FRH augments the response of the alveolar epithelium to TNF-α receptor family signaling. We found that FRH augmented LPS-induced lung injury and increased LPS-induced mortality in mice. At 24 h, animals exposed to hyperthermia and LPS had significant increases in alveolar permeability without changes in inflammatory cells in bronchoalveolar lavage fluid or lung tissue as compared with animals exposed to LPS alone. The increase in alveolar permeability was associated with an increase in alveolar epithelial apoptosis and was attenuated by caspase inhibition with zVAD.fmk. At 48 h, the animals exposed to hyperthermia and LPS had an enhanced lung inflammatory response. In murine lung epithelial cell lines (MLE-15, LA-4) and in primary type II alveolar epithelial cells, FRH enhanced apoptosis in response to TNF-α but not Fas ligand. The increase in apoptosis was caspase-8 dependent and associated with suppression of NF-κB activity. The FRH-associated NF-κB suppression was not associated with persistence of IκB-α, suggesting that FRH-mediated suppression of NF-κB occurs by means other than alteration of IκB-α kinetics. These data show for the first time that FRH promotes lung injury in part by increasing lung epithelial apoptosis. The enhanced apoptotic response might relate to FRH-mediated suppression of NF-κB activity in the alveolar epithelium with a resultant increase in susceptibility to TNF-α–mediated cell death.
Cutting Edge: Mast Cells Express IL-17A in Rheumatoid Arthritis Synovium
Authors: Hueber Axel J. , Asquith Darren L. , Miller Ashley M. , Reilly Jim , Kerr Shauna , Leipe Jan , Melendez Alirio J. , McInnes Iain B.
Published: March 2010

The proinflammatory cytokine IL-17A is considered a crucial player in rheumatoid arthritis (RA) pathogenesis. In experimental models of autoimmune arthritis, it has been suggested that the cellular source of IL-17A is CD4+ T cells (Th17 cells). However, little is known about the source of IL-17 in human inflamed RA tissue. We explored the cellular sources of IL-17A in human RA synovium. Surprisingly, only a small proportion of IL-17–expressing cells were T cells, and these were CCR6 negative. Unexpectedly, the majority of IL-17A expression colocalized within mast cells. Furthermore, we demonstrated in vitro that mast cells produced RORC-dependent IL-17A upon stimulation with TNF-α, IgG complexes, C5a, and LPS. These data are consistent with a crucial role for IL-17A in RA pathogenesis but suggest that in addition to T cells innate immune pathways particularly mediated via mast cells may be an important component of the effector IL-17A response.
Extraovarian Granulosa Cell Tumor of Mesentery: A Case Report
Authors: Naniwadekar Manjiri R. , Patil N. J.
Published: March 2010

Extraovarian granulosa cell tumor (GCT) is a very uncommon tumor, assumed to arise from the ectopic gonadal tissue along the embryonal route of the genital ridge. A 54 years old female patient presented with a mass and acute pain in abdomen. Exploratory laparatomy revealed hemoperitoneum with a large mesenteric mass measuring 13 × 12 cm in size, showing extensive areas of haemorrhages. Histopathological examination of the excised mass showed features of adult-type GCT. As the patient had a history of hysterectomy with bilateral salpingo-oophorectomy 10 years ago for ‘‘leiomyoma’’ with no evidence of GCT of the ovary in the histopathology report, a diagnosis of extraovarian GCT was made. A diagnosis of extraovarian GCT should be carried out after excluding any previous history of GCT of the ovary. Tumor rupture with haemoperitoneum is a well-known complication of GCT. Extraovarian GCT is a rare tumor with only 10 cases reported in literature. The case is presented for its rarity.
Derivation of Vasculature from Embryonic Stem Cells
Authors: Lindquist Jeffrey N. , Cheresh David A. , Snyder Evan Y.
Published: March 2010

The formation of the multicellular vascular system is critical to the growth, development, and viability of an organism, and many embryonic lethal mouse knockouts are due to vascular defects. Unfortunately, the complex nature, and many cell types involved in vasculogenesis and angiogenesis has stymied in vitro models of vascular formation. This unit describes a system that allows human embryonic stem cells to differentiate and spontaneously form vascular networks via both vasculogenesis and angiogenesis in the context of the three germ layers. Curr. Protoc. Stem Cell Biol. 12:1F.9.1‐1F.9.6. © 2010 by John Wiley & Sons, Inc.
Convergence depth control for interior point methods
Authors: Chen Weifeng , Shao Zhijiang , Wang Kexin , Chen Xi , Biegler Lorenz T.
Published: March 2010

For practical applications, optimization algorithms may converge to the optimal solution unreasonably slowly because of factors such as the poor scaling, ill‐conditioning, errors in calculation, and so on. Most improvements during the optimization procedure are made within a small part of the total computation time. To relieve the heavy computational burden, it is necessary to balance the calculation accuracy and computation cost. The traditional termination criteria based on the Karush‐Kuhn‐Tucker conditions cannot appropriately meet this requirement. Convergence depth control (CDC) strategy for Reduced Hessian Successive Quadratic Programming (RSQP) was presented as an alternative measure in a previous study. This work incorporates interior point methods with the modified CDC strategy, which was tested through AMPL interface and Aspen Open Solvers interface. Related properties are proved. © 2010 American Institute of Chemical Engineers AIChE J, 2010
Constant number Monte Carlo simulation of population balances with multiple growth mechanisms
Authors: Khalili Samira , Lin Yulan , Armaou Antonios , Matsoukas Themis
Published: March 2010

We present a complete simulation scheme for particulate processes based on the constant number Monte Carlo methodology. Specifically, the proposed scheme can be applied towards the solution of population balances that include nucleation, coagulation and surface deposition, coupled to chemical reactions. The synthesis of titania (TiO2) by flame oxidation of TiCl4 is employed as a comparison basis of the relative advantages and weaknesses of Monte Carlo against more classical numerical approaches. © 2010 American Institute of Chemical Engineers AIChE J, 2010
Ceria in catalysis: From automotive applications to the water–gas shift reaction
Authors: Gorte Raymond J.
Published: March 2010

Ceria is a crucial component of automotive catalysts, where its ability to be reduced and re‐oxidized provides oxygen storage capacity. Because of these redox properties, ceria can greatly enhance catalytic activities for a number of important reactions when it is used as a support for transition metals. For reactions that use steam as an oxidant (e.g., the water–gas‐shift reaction and steam reforming of hydrocarbons), rates for ceria‐supported metals can be several orders of magnitude higher than that for ceria or the transition metal alone. Because the redox properties of ceria are strongly dependent on treatment history and the presence of additives, there are significant opportunities for modifying catalysts based on ceria to further improve their performance. This article will review some of the contributions from my laboratory on understanding and using ceria in these applications. © 2010 American Institute of Chemical Engineers AIChE J, 2010
A method for computing the partial derivatives of experimental data
Authors: Yeow Y. Leong , Isac Jordan , Khalid Fathullah A. , Leong Yee‐Kwong , Lubansky A. S.
Published: March 2010

This article describes a procedure for obtaining the partial derivatives of experimental data that depend on two independent variables. The starting equation is an ill‐posed integral equation of the first kind. Tikhonov regularization is used to keep noise amplification under control. Implementation of the computation steps is described and the performance of the procedure is demonstrated by four practical examples. © 2010 American Institute of Chemical Engineers AIChE J, 2010
Role of operating conditions in determining droplet size and viscosity of tackifier emulsions formed via phase inversion
Authors: Song Daoyun , Zhang Wu , Gupta Rakesh K. , Melby Earl G.
Published: March 2010

Water‐based pressure‐sensitive adhesives are formulated by combining a polymer latex with a tackifier emulsion. The latter is an oil‐in‐water emulsion made by the process of phase inversion. The phase inversion itself is carried out in a stirred tank fitted with a heating jacket by progressively adding water to a water‐in‐oil emulsion. The point of onset of phase inversion and the characteristics of the emulsion that is formed depend on process conditions; these include temperature, rate of water addition, and agitation speed. The role of these operating conditions is elucidated here. Increasing temperature delayed the onset of phase inversion slightly, but it did not affect emulsion particle size, provided it remained below a critical value. Agitation speed had to be increased upon increasing the water flow rate to prevent increasing the particle size. Finally, the point of onset of phase inversion could be predicted reasonably well using a model available in the literature. © 2010 American Institute of Chemical Engineers AIChE J, 57: 96–106, 2011
Decomposition kinetics and recycle of binary hydrogen‐tetrahydrofuran clathrate hydrate
Authors: Yoshioka Hiroki , Ota Masaki , Sato Yoshiyuki , Watanabe Masaru , Inomata Hiroshi , Smith Richard L. , Peters Cor J.
Published: March 2010

Decomposition kinetics and recycle of hydrogen–tetrahydrofuran (H2–THF) clathrate hydrates were investigated with a pressure decay method at temperatures from 265.1 to 273.2 K, at initial pressures from 3.1 to 8.0 MPa, and at stoichiometric THF hydrate concentrations for particle sizes between 250 and 1000 μm. The decomposition was modeled as a two‐step process consisting of H2 diffusion in the hydrate phase and desorption from the hydrate cage. The adsorption process occurred at roughly two to three times faster than the desorption process, whereas the diffusion process during formation was slightly higher (ca. 20%) than that during decomposition. Successive formation and decomposition cycles showed that occupancy seemed to decrease only slightly with cycling and that there were no large changes in hydrate structure due to cycling. Results provide evidence that the formation and decomposition of H2 clathrate hydrates occur reversibly and that H2 clathrate hydrates can be recycled with pressure. © 2010 American Institute of Chemical Engineers AIChE J, 2011
Architectonic Subdivisions of Neocortex in the Galago (Otolemur garnetti)
Authors: Wong Peiyan , Kaas Jon H.
Published: March 2010

In the present study, galago brains were sectioned in the coronal, sagittal, or horizontal planes, and sections were processed with several different histochemical and immunohistochemical procedures to reveal the architectonic characteristics of the various cortical areas. The histochemical methods used included the traditional Nissl, cytochrome oxidase, and myelin stains, as well as a zinc stain, which reveals free ionic zinc in the axon terminals of neurons. Immunohistochemical methods include parvalbumin (PV) and calbindin (CB), both calcium‐binding proteins, and the vesicle glutamate transporter 2 (VGluT2). These different procedures revealed similar boundaries between areas, which suggests that functionally relevant borders were being detected. These results allowed a more precise demarcation of previously identified areas. As thalamocortical terminations lack free ionic zinc, primary cortical areas were most clearly revealed by the zinc stain, because of the poor zinc staining of layer 4. Area 17 was especially prominent, as the broad layer 4 was nearly free of zinc stain. However, this feature was less pronounced in the primary auditory and somatosensory cortex. As VGluT2 is expressed in thalamocortical terminations, layer 4 of primary sensory areas was darkly stained for VGluT2. Primary motor cortex had reduced VGluT2 staining, and increased zinc‐enriched terminations in the poorly developed granular layer 4 compared to the adjacent primary somatosensory area. The middle temporal visual (MT) showed increased PV and VGluT2 staining compared to the surrounding cortical areas. The resulting architectonic maps of cortical areas in galagos can usefully guide future studies of cortical organizations and functions. Anat Rec, 2010.© 2010 Wiley‐Liss, Inc.
Immunocytochemical Studies of Adhesion Molecules on Mouse UNK Cells and Their Extracellular Matrix Ligands During Mouse Pregnancy
Authors: Zavan Bruno , Paffaro Andréa Mollica Amarante , Joazeiro Paulo Pinto , Yamada Áureo Tatsumi , Paffaro Valdemar Antonio
Published: March 2010

Uterine natural killer (uNK) cells are the dominant lymphocytes of pregnant mammals' uterus. Studies have identified four differentiation stage of mouse uNK cells based on Dolichos biflorus lectin cytochemistry, and their distribution showed preferential domain in the uterus through out the pregnancy. This work was done to investigate the expression of α5, α6, and β7 integrins on uNK cells and their ligands distribution. Section of mouse uterus from sixth to seventeenth gestational days were submitted to immunocytochemistry and positive reactions for α5, α6, and β7 integrins were found on uNK from eighth to tenth gestational days but not after twelfth gestational days. Fibronectin reactions were seemed from sixth to tenth gestational days around uNK from the myometrium and endometrium close to the myometrium. No reaction for fibronectin was seen in the decidualized and nondecidualized endometrium near the placenta. Laminin reaction was seen just in the antimesometrial side. β7 integrin seems to be the active receptor to bind with VCAM‐1 or MAdCAM‐1 of endothelial cells, promoting the uNK cross through the vessels. The absence of laminin in an uNK domain suggests these cells are not dependent of laminin and α6 integrin for their establishment. However, fibronectin seems to support uNK migration, proliferation, differentiation, and survival in the uterus by binding with α5 integrin. The loss of α5 integrin ligation by the down regulation of fibronectin could inhibits these events and further studies are need to investigate whether unligated α5 can actively and initiate apoptosis, maybe in a caspase 8‐dependent way that has been called integrin‐mediated death. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Effect of oleocanthal and its derivatives on inflammatory response induced by lipopolysaccharide in a murine chondrocyte cell line
Authors: Iacono Anna , Gómez Rodolfo , Sperry Jeffrey , Conde Javier , Bianco Giuseppe , Meli Rosaria , Gómez‐Reino Juan J. , Smith Amos B. , Gualillo Oreste
Published: March 2010

Objective

In joint diseases, cartilage homeostasis is disrupted by mechanisms that are driven by combinations of biologic factors that vary according to the disease process. In osteoarthritis (OA), biomechanical stimuli predominate, with up‐regulation of both catabolic and anabolic factors. Likewise, OA progression is characterized by increased nitric oxide (NO) production, which has been associated with cartilage degradation. Given the relevance of cartilage degenerative diseases in our society, the development of a novel pharmacologic intervention is a critically important public health goal. Recently, oleocanthal isolated from extra virgin olive oil was found to display nonsteroidal antiinflammatory drug activity similar to that of ibuprofen, a drug widely used in the therapeutic management of joint inflammatory diseases. We undertook this study to evaluate the effect of oleocanthal and its derivatives on the modulation of NO production in chondrocytes.

Methods

Cultured ATDC‐5 chondrocytes were tested with different doses of oleocanthal and its derivatives. Cell viability was evaluated using the MTT assay. Nitrite accumulation was determined in culture supernatant using the Griess reaction. Inducible NO synthase (NOS2) protein expression was examined using Western blotting analysis.

Results

Oleocanthal and its derivatives decreased lipopolysaccharide‐induced NOS2 synthesis in chondrocytes without significantly affecting cell viability at lower concentrations. Among the derivatives we examined, derivative 231 was the most interesting, since its inhibitory effect on NOS2 was devoid of cytotoxicity even at higher concentrations.

Conclusion

This class of molecules shows potential as a therapeutic weapon for the treatment of inflammatory degenerative joint diseases.
Autocitrullination of human peptidyl arginine deiminase type 4 regulates protein citrullination during cell activation
Authors: Andrade Felipe , Darrah Erika , Gucek Marjan , Cole Robert N. , Rosen Antony , Zhu Xiaoming
Published: March 2010

Objective

To address mechanisms that control the activity of human peptidyl arginine deiminase type 4 (PAD‐4).

Methods

PAD‐4 autocitrullination was determined by anti–modified citrulline immunoblotting, using purified recombinant and endogenous PAD‐4 from activated human primary neutrophils and cell lines expressing PAD‐4. The citrullination sites in PAD‐4 were determined by mass spectrometry. Mechanisms of autocitrullination‐induced inactivation and the functional consequences of autocitrullination in PAD‐4 polymorphic variants were addressed using purified components and cell lines expressing PAD‐4 wild‐type, PAD‐4 mutant, and PAD‐4 polymorphic variants relevant to rheumatoid arthritis (RA).

Results

PAD‐4 is autocitrullinated in vitro and during activation of primary cells and cell lines expressing PAD‐4. Interestingly, this modification inactivated the function of the enzyme. The efficiency of inactivation differed among genetically defined PAD‐4 variants relevant to RA. PAD‐4 was citrullinated at 10 sites, which are clustered into 3 distinct regions, including a cluster of arginines around the active site cleft where Arg‐372 and ‐374 were identified as the potential autocitrullination targets that inactivate the enzyme. Autocitrullination also modified the structure of PAD‐4, abrogating its recognition by multiple rabbit antibodies, but augmenting its recognition by human anti–PAD‐4 autoantibodies.

Conclusion

Our findings suggest that autocitrullination regulates the production of citrullinated proteins during cell activation, and that this is affected by structural polymorphisms in PAD‐4. Autocitrullination also influences PAD‐4 structure and immune response.
Indagator: Investigating perceived gratifications of an application that blends mobile content sharing with gameplay
Authors: Lee Chei Sian , Goh Dion Hoe‐Lian , Chua Alton Y. K. , Ang Rebecca P.
Published: March 2010

The confluence of mobile content sharing and pervasive gaming yields new opportunities for developing novel applications on mobile devices. Yet, studies on users' attitudes and behaviors related to mobile gaming, content‐sharing, and retrieval activities (referred to simply as content sharing and gaming) have been lacking. For this reason, the objectives of this article are three‐fold. One, it introduces Indagator, an application that incorporates multiplayer, pervasive gaming elements into mobile content‐sharing activities. Two, it seeks to uncover the motivations for content sharing within a game‐based environment. Three, it aims to identify types of users who are motivated to use Indagator for content sharing. Informed by the uses and gratifications paradigm, a survey was designed and administered to 203 undergraduate and graduate students from two large universities. The findings revealed that perceived gratification factors, such as information discovery, entertainment, information quality, socialization, and relationship maintenance, demographic variables, such as basic familiarity with features of mobile communication devices, and IT‐related backgrounds were significant in predicting intention to use mobile sharing and gaming applications such as Indagator. However, age, gender, and the personal status gratification factor were nonsignificant predictors. This article concludes by presenting the implications, limitations, and future research directions.
Limit process of stationary TASEP near the characteristic line
Authors: Baik Jinho , Ferrari Patrik L. , Péché Sandrine
Published: March 2010

The totally asymmetric simple exclusion process (TASEP) on\input amssym ${\Bbb Z}$ with the Bernoulli‐ρ measure as an initial condition, 0 < ρ < 1, is stationary. It is known that along the characteristic line, the current fluctuates at an order of t1/3. The limiting distribution has also been obtained explicitly. In this paper we determine the limiting multipoint distribution of the current fluctuations moving away from the characteristics by the order t2/3. The main tool is the analysis of a related directed last percolation model. We also discuss the process limit in tandem queues in equilibrium. © 2010 Wiley Periodicals, Inc.
Long‐term consequences of Sox9 depletion on inner ear development
Authors: Park Byung‐Yong , Saint‐Jeannet Jean‐Pierre
Published: March 2010

The transcription factor Sox9 has been implicated in inner ear formation in several species. To investigate the long‐term consequences of Sox9 depletion on inner ear development we analyzed the inner ear architecture of Sox9‐depleted Xenopus tadpoles generated by injection of increasing amounts of Sox9 morpholino antisense oligonucleotides. We found that Sox9‐depletion resulted in major defects in the development of vestibular structures, semicircular canals and utricle, while the ventrally located saccule was less severely affected in these embryos. Consistent with this phenotype, we observed a specific loss of the dorsal expression of Wnt3a expression in the otic vesicle of Sox9 morphants, associated with an increase in cell death and a reduction in cell proliferation in the region of the presumptive otic epithelium. We propose that, in addition to its early role in placode specification, Sox9 is also required for the maintenance of progenitors in the otic epithelium. Developmental Dynamics 239:1102–1112, 2010. © 2010 Wiley‐Liss, Inc.
Zinc signals promote IL‐2‐dependent proliferation of T cells
Authors: Kaltenberg Jennifer , Plum Laura M. , Ober‐Blöbaum Julia L. , Hönscheid Andrea , Rink Lothar , Haase Hajo
Published: March 2010

Zinc signals, i.e. a change of the intracellular concentration of free zinc ions in response to receptor stimulation, are involved in signal transduction in several immune cells. Here, the role of zinc signals in T‐cell activation by IL‐2 was investigated in the murine cytotoxic T‐cell line CTLL‐2 and in primary human T cells. Measurements with the fluorescent dyes FluoZin‐3 and Zinquin showed that zinc is released from lysosomes into the cytosol in response to stimulation of the IL‐2‐receptor. Activation of the ERK‐pathway was blocked by chelation of free zinc with N,N,N′,N′‐tetrakis‐2(pyridyl‐methyl)ethylenediamine, whereas zinc was not required for STAT5 phosphorylation. In addition, the key signaling molecules MEK and ERK were activated in response to elevated free intracellular zinc, induced by incubation with zinc and the ionophore pyrithione. Downstream of ERK activation, ERK‐specific gene expression of c‐fos and IL‐2‐induced proliferation was found to depend on zinc. Further experiments indicated that inhibition of MEK and ERK‐dephosphorylating protein phosphatases is the molecular mechanism for the influence of zinc on this pathway. In conclusion, an increase of cytoplasmic free zinc is required for IL‐2‐induced ERK signaling and proliferation of T cells.
The NK receptor KLRG1 is dispensable for virus‐induced NK and CD8+ T‐cell differentiation and function in vivo
Authors: Gründemann Carsten , Schwartzkopff Sabrina , Koschella Marie , Schweier Oliver , Peters Christoph , Voehringer David , Pircher Hanspeter
Published: March 2010

The killer cell lectin‐like receptor G1 (KLRG1) is expressed by NK and T‐cell subsets and recognizes members of the classical cadherin family. KLRG1 is widely used as a lymphocyte differentiation marker in both humans and mice but the physiological role of KLRG1 in vivo is still unclear. Here, we generated KLRG1‐deficient mice by homologous recombination and used several infection models for their characterization. The results revealed that KLRG1 deficiency did not affect development and function of NK cells examined under various conditions. KLRG1 was also dispensable for normal CD8+ T‐cell differentiation and function after viral infections. Thus, KLRG1 is a marker for distinct NK and T‐cell differentiation stages but it does not play a deterministic role in the generation and functional characteristics of these lymphocyte subsets. In addition, we demonstrate that E‐cadherin expressed by K562 target cells inhibited NK‐cell reactivity in transgenic mice over‐expressing KLRG1 but not in KLRG1‐deficient or WT mice. Hence, the inhibitory potential of KLRG1 in mice is rather weak and strong activation signals during viral infections may override the inhibitory signal in vivo.
CCL21 is sufficient to mediate DC migration, maturation and function in the absence of CCL19
Authors: Britschgi Mirjam R. , Favre Stéphanie , Luther Sanjiv A.
Published: March 2010

Mice deficient in CCR7 signals show severe defects in lymphoid tissue architecture and immune response. These defects are due to impaired attraction of CCR7+ DC and CCR7+ T cells into the T zones of secondary lymphoid organs and altered DC maturation. It is currently unclear which CCR7 ligand mediates these processes in vivo as CCL19 and CCL21 show an overlapping expression pattern and blocking experiments have given contradictory results. In this study, we addressed this question using CCL19‐deficient mice expressing various levels of CCL21. Complete deficiency of CCL19 and CCL21 but not CCL19 alone was found to be associated with abnormal frequencies and localization of DC in naïve LN. Similarly, CCL19 was not required for DC migration from the skin, full DC maturation and efficient T‐cell priming. Our findings suggest that CCL21 is the critical CCR7 ligand regulating DC homeostasis and function in vivo with CCL19 being redundant for these processes.
The controversial relationship between NLRP3, alum, danger signals and the next‐generation adjuvants
Authors: Spreafico Roberto , Ricciardi‐Castagnoli Paola , Mortellaro Alessandra
Published: March 2010

Alum has been the only adjuvant licensed for human vaccines for decades and is still widely used, but its mechanism of action remains obscure. Recently, the NLRP3 inflammasome has been linked to the immunostimulatory properties of alum and other particulate adjuvants, although it is disputed to what degree NLRP3 is genuinely essential in vivo. Meanwhile, researchers are testing adjuvants harnessing both the infectious/non‐infectious‐discriminating TLR and the danger‐sensing NLRP3 inflammasome pathways. Could this be the basis of a long‐needed rationale in the design of adjuvants?
Pyroptosis – a cell death modality of its kind?
Authors: Kepp Oliver , Galluzzi Lorenzo , Zitvogel Laurence , Kroemer Guido
Published: March 2010

The term “pyroptosis” was originally introduced to describe a particular form of cell death in macrophages, which is induced by bacterial infection, is accompanied by caspase‐1 activation and hence leads to the release of pyrogenic interleukins; however, it is still controversial whether pyroptosis – which can also be triggered by non‐bacterial pathological stimuli – truly represents a cell death modality on its own or whether it constitutes a special case of apoptosis or necrosis.
Signaling by ROS drives inflammasome activation
Authors: Martinon Fabio
Published: March 2010

Inflammasomes are innate immune signaling pathways that sense pathogens and injury to direct the proteolytic maturation of inflammatory cytokines such as IL‐1β and IL‐18. Among inflammasomes, the NLRP3/NALP3 inflammasome is the most studied. However, little is known on the molecular mechanisms that mediate its assembly and activation. Recent findings suggest that ROS are produced by NLRP3/NALP3 activators and are essential secondary messengers signaling NLRP3/NALP3 inflammasome activation.
The role of inflammasomes in the immunostimulatory effects of particulate vaccine adjuvants
Authors: Harris James , Sharp Fiona A. , Lavelle Ed C.
Published: March 2010

Adjuvants are essential for enhancing and directing immunity to vaccine antigens. Most adjuvants in clinical use are particulates, but how they drive innate and adaptive immune responses is unclear. A major recent advance was the demonstration that particulate adjuvants promote activation of the NLRP3 inflammasome. The mechanisms underlying this activation have been partly resolved and the role of NLRP3 in particulate adjuvant‐induced adaptive immunity is currently the subject of intense interest.
Inflammasomes as microbial sensors
Authors: Franchi Luigi , Muñoz‐Planillo Raul , Reimer Thornik , Eigenbrod Tatjana , Núñez Gabriel
Published: March 2010

Members of the Nod‐like receptor family and the adaptor ASC assemble into multiprotein platforms, termed inflammasomes, to mediate the activation of caspase‐1 and subsequent secretion of IL‐1β and IL‐18. Recent studies have identified microbial and endogenous molecules as well as possible mechanisms involved in inflammasome activation.
Critical functions of priming and lysosomal damage for NLRP3 activation
Authors: Hornung Veit , Latz Eicke
Published: March 2010

Inflammasomes are cytosolic multi‐protein complexes that form in response to infectious or injurious challenges. Inflammasomes control the activity of caspase‐1, which is essential for the maturation and release of IL‐1β family cytokines. The NLRP1, IPAF and AIM2 inflammasomes recognize specific substances, while the NLRP3 inflammasome responds to many structurally and chemically diverse triggers. Here, we discuss the critical roles of priming and lysosomal damage in NLRP3 inflammasome activation.
Sterile inflammatory responses mediated by the NLRP3 inflammasome
Authors: Cassel Suzanne L. , Sutterwala Fayyaz S.
Published: March 2010

Through pattern recognition receptors the innate immune system detects disruption of the normal function of the organism and initiates responses directed at correcting these derangements. Cellular damage from microbial or non‐microbial insults causes the activation of nucleotide‐binding domain leucine‐rich repeat containing receptors in multiprotein complexes called inflammasomes. Here we discuss the role of the NLRP3 inflammasome in the recognition of cellular damage and the initiation of sterile inflammatory responses.
NOD‐like receptor (NLR) signaling beyond the inflammasome
Authors: Shaw Patrick J. , Lamkanfi Mohamed , Kanneganti Thirumala‐Devi
Published: March 2010

Recent years have witnessed a marked progress in our knowledge of NOD‐like receptors (NLR), intracellular sensors with central roles in innate and adaptive immunity. A majority of the research has focused on caspase‐1 inflammasomes. However, several members of the mammalian NLR family exert important roles in immunity beyond inflammasome signaling. Here we highlight the emerging roles of several of these NLR.
Loss of DNAM‐1 contributes to CD8+ T‐cell exhaustion in chronic HIV‐1 infection
Authors: Cella Marina , Presti Rachel , Vermi William , Lavender Kerry , Turnbull Emma , Ochsenbauer‐Jambor Christina , Kappes John C. , Ferrari Guido , Kessels Lisa , Williams Ian ,   CHAVI Clinical Core B, McMichael Andrew J. , Haynes Barton F. , Borrow Persephone , Colonna Marco ,   the NIAID Center for HIV/AIDS Vaccine Immunology
Published: March 2010

The hallmark of chronic viral infections is a progressive exhaustion of antigen‐specific CD8+ T cells that leads to persisting viral replication. It is generally believed that exhaustion is a consequence of the accumulation of multiple inhibitory receptors on CD8+ T cells that makes them dysfunctional. Here, we show that during human chronic HIV‐1 infection, a CD8+ T‐cell positive costimulatory pathway mediated by DNAX‐activating molecule‐1 is also disrupted. Thus, DNAX‐activating molecule‐1 downregulation on CD8+ T cells aggravates the impairment of CTL effector function in chronic HIV‐1 infection.
IL‐1: Discoveries, controversies and future directions
Authors: Dinarello Charles A.
Published: March 2010

Although there has been a great amount of progress in the 25 years since the first reporting of the cDNA for IL‐1α and IL‐1β, the history of IL‐1 goes back to the early 1940s. In fact, the entire field of inflammatory cytokines, TLR and the innate immune response can be found in the story of IL‐1. This Viewpoint follows the steps from the identification of the fever‐inducing activities of “soluble factors” produced by endotoxin‐stimulated leukocytes through to the discovery of cryopyrin and the caspase‐1 inflammasome and on to the clinical benefits of anti‐IL‐1β‐based therapeutics. It also discusses some of the current controversies regarding the activation of the inflammasome. The future of novel anti‐inflammatory agents to combat chronic inflammation is based, in part, on the diseases that are uniquely responsive to anti‐IL‐1β, which is surely a reason to celebrate the 25th anniversary of the cloning of IL‐1α and IL‐1β.
Cover Picture: Eur. J. Immunol. 3/10
Authors: Meng Guangxun , Strober Warren
Published: March 2010

The cover picture features the hallmark set of scales representing the balancing of opinions in our Viewpoint series, with the cells representing the various immune components affected by altered inflammasome activation. The schematic is taken from the article by Meng and Strober (pp. 649–653), which examines the role of Nlrp3 mutations in murine models of autoinflammatory diseases.