bluuebunny/crossref_metadata_2025 huggingface dataset:
Involvement of Native TRPC3 Proteins in ATP-Dependent Expression of VCAM-1 and Monocyte Adherence in Coronary Artery Endothelial Cells
Authors: Smedlund Kathryn , Vazquez Guillermo
Published: September 2008

Background—

Vascular cell adhesion molecule-1 (VCAM-1) is critical in monocyte recruitment to the endothelium, a key event in development of atherosclerotic lesions. Stimulation of human coronary artery endothelial cells (HCAECs) with ATP positively modulates VCAM-1 expression and function through a mechanism involving Ca
2+
signaling. We here examined the role of Ca
2+
influx and native TRPC3 channels in that mechanism.

Methods and Results—

Omission of extracellular Ca
2+
or pretreatment of cells with channel blockers markedly reduced ATP-induced VCAM-1 and monocyte adhesion. Using a siRNA strategy and real-time fluorescence, we found that native TRPC3 proteins contribute to constitutive and ATP-regulated Ca
2+
influx. ATP-dependent upregulation of VCAM-1 was accompanied by an increase in basal cation entry and TRPC3 expression. Notably, TRPC3 knock-down resulted in a dramatic reduction of ATP-induced VCAM-1 and monocyte adhesion.

Conclusions—

These findings indicate that in HCAECs, native TRPC3 proteins form channels that contribute to constitutive and ATP-dependent Ca
2+
influx, and that TRPC3 expression and function are fundamental to support VCAM-1 expression and monocyte binding. This is the first evidence to date relating native TRPC3 proteins with regulated expression of cell adhesion molecules in coronary endothelium, and suggests a potential pathophysiological role of TRPC3 in coronary artery disease.
FRNK Expression Promotes Smooth Muscle Cell Maturation During Vascular Development and After Vascular Injury
Authors: Sayers Rebecca L. , Sundberg-Smith Liisa J. , Rojas Mauricio , Hayasaka Haruko , Parsons J. Thomas , Mack Christopher P. , Taylor Joan M.
Published: September 2008

Objective—

Smooth muscle cell (SMC) differentiation is a dynamic process that must be tightly regulated for proper vascular development and to control the onset of vascular disease. Our laboratory previously reported that a specific focal adhesion kinase (FAK) inhibitor termed FRNK (FAK Related Non-Kinase) is selectively expressed in large arterioles when SMCs are transitioning from a synthetic to contractile phenotype and that FRNK inhibits FAK-dependent SMC proliferation and migration. Herein, we sought to determine whether FRNK expression modulates SMC phenotypes in vivo.

Methods and Results—

We present evidence that FRNK
−/−
mice exhibit attenuated SM marker gene expression during postnatal vessel growth and after vascular injury. We also show that FRNK expression is regulated by transforming growth factor (TGF)-β and that forced expression of FRNK in cultured cells induces serum- and TGF-β–stimulated SM marker gene expression, whereas FRNK deletion or expression of a constitutively activated FAK variant attenuated SM gene transcription.

Conclusions—

These data highlight the possibility that extrinsic signals regulate the SMC gene profile, at least in part, by modulating the expression of FRNK and that tight regulation of FAK activity by FRNK is important for proper SMC differentiation during development and after vascular injury.
Termination of Cardiac Ca
2+
Sparks
Authors: Zima Aleksey V. , Picht Eckard , Bers Donald M. , Blatter Lothar A.
Published: September 2008

Ca
2+
release from cardiac sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) is regulated by dyadic cleft [Ca
2+
] and intra-SR free [Ca
2+
] ([Ca
2+
]
SR
). Robust SR Ca
2+
release termination is important for stable excitation–contraction coupling, and partial [Ca
2+
]
SR
depletion may contribute to release termination. Here, we investigated the regulation of SR Ca
2+
release termination of spontaneous local SR Ca
2+
release events (Ca
2+
sparks) by [Ca
2+
]
SR
, release flux, and intra-SR Ca
2+
diffusion. We simultaneously measured Ca
2+
sparks and Ca
2+
blinks (localized elementary [Ca
2+
]
SR
depletions) in permeabilized ventricular cardiomyocytes over a wide range of SR Ca
2+
loads and release fluxes. Sparks terminated via a [Ca
2+
]
SR
-dependent mechanism at a fixed [Ca
2+
]
SR
depletion threshold independent of the initial [Ca
2+
]
SR
and release flux. Ca
2+
blink recovery depended mainly on intra-SR Ca
2+
diffusion rather than SR Ca
2+
uptake. Therefore, the large variation in Ca
2+
blink recovery rates at different release sites occurred because of differences in the degree of release site interconnection within the SR network. When SR release flux was greatly reduced, long-lasting release events occurred from well-connected junctions. These junctions could sustain release because local SR Ca
2+
release and [Ca
2+
]
SR
refilling reached a balance, preventing [Ca
2+
]
SR
from depleting to the termination threshold. Prolonged release events eventually terminated at a steady [Ca
2+
]
SR
, indicative of a slower, [Ca
2+
]
SR
-independent termination mechanism. These results demonstrate that there is high variability in local SR connectivity but that SR Ca
2+
release terminates at a fixed [Ca
2+
]
SR
termination threshold. Thus, reliable SR Ca
2+
release termination depends on tight RyR regulation by [Ca
2+
]
SR
.
Patterns of Brain Arteriovenous Malformation Treatment
Authors: van Beijnum Janneke , Bhattacharya Jo J. , Counsell Carl E. , Papanastassiou Vakis , Ritchie Vaughn , Roberts Richard C. , Sellar Robin J. , Warlow Charles , Salman Rustam Al-Shahi
Published: September 2008

Background and Purpose—

The extent of variation in the interventional treatment of brain arteriovenous malformations (AVMs) is unknown, so we explored patterns of treatment at 4 neuroscience centers in one European country.

Methods—

We included every participant with an AVM in a prospective, population-based cohort study of adults aged ≥16 years residing in Scotland at the time of AVM diagnosis in 1999 to 2003.

Results—

Only 11 (5%) of the 229 adults were not managed at a neuroscience center. Adults who received interventional treatment were younger (median, 43 versus 54 years), more likely to have presented with hemorrhage (OR, 2.8; 95% CI, 1.6 to 4.9), and had smaller AVMs (median nidus diameter, 2 cm versus 3 cm;
P
=0.003) than those who did not. Adults seen at the 4 centers only differed in AVM Spetzler-Martin grade (
P
=0.04). The 4 centers did not differ in the proportion of adults with AVMs who received interventional treatment (
P
=0.16), but they differed in the Spetzler-Martin grade of the AVMs they treated (Grades III to IV,
P
=0.01) and the interventional treatments used (
P
=0.004). The 2 largest centers differed from each other in the likelihood of surgical resection (OR, 0.2; 95% CI, 0.1 to 0.6) and stereotactic radiosurgery (OR, 2.8; 95% CI, 1.3 to 6.1), and the choice of modality varied within some Spetzler-Martin grades.

Conclusions—

Patient characteristics and patterns of AVM interventional treatment differ between neuroscience centers in the same population necessitating careful consideration of these factors when comparing one hospital’s outcome with another.
Marks of Oppression: A Postcolonial Reading of Paul's Stigmata in Galatians 6:7
Authors: Barrier Jeremy
Published: September 2008

In this essay I examine Gal. 6.17 in hopes of recovering an interpretation of Paul that demonstrates Paul's self-identity as a slave. To be more specific, I investigate Gal. 6.11-17 in light of current studies in postcolonialism, in order to see the influences that the Roman Empire had upon Paul in regard to Paul's understanding of his stigmata ('marks'). The purpose of this article is (1) to evaluate the contemporary historical and social-scientific interpretations of the stigmata and argue for the importance of understanding these 'marks' in light of ancient rhetoric, (2) I will argue to situate this discussion within a postcolonial dialogue with a specific definition of postcolonialism that rejects overly simplistic 'dualistic' rubrics and investigates a text looking for domination/coordination/subordination relationships, (3) reconsider Paul's stigmata in light of the slavery metaphor by comparing Paul's stigmata to the ancient slave concept of basanos, and (4) offer a new interpretation of the stigmata as it reveals Paul's suppressed status as a colonized Jew looking for an alternative language to express his deep need for a master worthy of his loyalty. The results may be less than desirable, but I hope to both make people aware of the slave metaphor, and stimulate thought as to other meaningful metaphors that might be considered to understand Paul's relationship to Christ as it is conceived within a postcolonial optic.
Storm-Relative Helicity Revealed from Polarimetric Radar Measurements
Authors: Kumjian Matthew R. , Ryzhkov Alexander V.
Published: September 2008

The dual-polarization radar variables are especially sensitive to the microphysical processes of melting and size sorting of precipitation particles. In deep convective storms, polarimetric measurements of such processes can provide information about the airflow in and around the storm that may be used to elucidate storm behavior and evolution. Size sorting mechanisms include differential sedimentation, vertical transport, strong rotation, and wind shear. In particular, winds that veer with increasing height typical of supercell environments cause size sorting that is manifested as an enhancement of differential reflectivity (ZDR) along the right or inflow edge of the forward-flank downdraft precipitation echo, which has been called the ZDR arc signature. In some cases, this shear profile can be augmented by the storm inflow. It is argued that the magnitude of this enhancement is related to the low-level storm-relative environmental helicity (SRH) in the storm inflow.

To test this hypothesis, a simple numerical model is constructed that calculates trajectories for raindrops based on their individual sizes, which allows size sorting to occur. The modeling results indicate a strong positive correlation between the maximum ZDR in the arc signature and the low-level SRH, regardless of the initial drop size distribution aloft. Additional observational evidence in support of the conceptual model is presented. Potential changes in the ZDR arc signature as the supercell evolves and the low-level mesocyclone occludes are described.
How Well Do Atmospheric General Circulation Models Capture the Leading Modes of the Interannual Variability of the Asian–Australian Monsoon?
Authors: Zhou Tianjun , Wu Bo , Wang Bin
Published: September 2008

The authors evaluate the performances of 11 AGCMs that participated in the Atmospheric Model Intercomparison Project II (AMIP II) and that were run in an AGCM-alone way forced by historical sea surface temperature covering the period 1979–99 and their multimodel ensemble (MME) simulation of the interannual variability of the Asian–Australian monsoon (AAM). The authors explore to what extent these models can reproduce two observed major modes of AAM rainfall for the period 1979–99, which account for about 38% of the total interannual variances. It is shown that the MME SST-forced simulation of the seasonal rainfall anomalies reproduces the first two leading modes of variability with a skill that is comparable to the NCEP/Department of Energy Global Reanalysis 2 (NCEP-2) in terms of the spatial patterns and the corresponding temporal variations as well as their relationships with ENSO evolution. Both the biennial tendency and low-frequency components of the two leading modes are captured reasonably in MME. The skill of AMIP simulation is seasonally dependent. December–February (DJF) [July–August (JJA)] has the highest (lowest) skill. Over the extratropical western North Pacific and South China Sea, where ocean–atmosphere coupling may be critical for modeling the monsoon rainfall, the MME fails to demonstrate any skill in JJA, while the reanalysis has higher skills. The MME has deficiencies in simulating the seasonal phase of two anticyclones associated with the first mode, which are not in phase with ENSO forcing in observations but strictly match that of Niño-3.4 SST in MME. While the success of MME in capturing essential features of the first mode suggests the dominance of remote El Niño forcing in producing the predictable portion of AAM rainfall variability, the deficiency in capturing the seasonal phase implies the importance of local air–sea coupling effects. The first mode generally concurs with the turnabout of El Niño; meanwhile, the second mode is driven by La Niña at decaying stage. Multimodel intercomparison shows that there are good relationships between the simulated climatology and anomaly in terms of the degree of accuracy.
An Intercomparison of ERS-Scat and AMSR-E Soil Moisture Observations with Model Simulations over France
Authors: Rüdiger Christoph , Calvet Jean-Christophe , Gruhier Claire , Holmes Thomas R. H. , de Jeu Richard A. M. , Wagner Wolfgang
Published: September 2008

This paper presents a study undertaken in preparation of the work leading up to the assimilation of Soil Moisture and Ocean Salinity (SMOS) observations into the land surface model (LSM) Interaction Soil Biosphere Atmosphere (ISBA) at Météo-France. This study consists of an intercomparison experiment of different space-borne platforms providing surface soil moisture information [Advanced Microwave Scanning Radiometer for Earth Observing (AMSR-E) and European Remote Sensing Satellite Scatterometer (ERS-Scat)] with the reanalysis soil moisture predictions over France from the model suite of Système d’analyse fournissant des renseignements atmosphériques à la neige (SAFRAN), ISBA, and coupled model (MODCOU; SIM) of Météo-France for the years of 2003–05. Both modeled and remotely sensed data are initially validated against in situ observations obtained at the experimental soil moisture monitoring site Surface Monitoring of the Soil Reservoir Experiment (SMOSREX) in southwestern France. Two different AMSR-E soil moisture products are compared in the course of this study—the official AMSR-E product from the National Snow and Ice Data Center (NSIDC) and a new product developed at the Vrije Universiteit Amsterdam and NASA (VUA–NASA)—which were obtained using two different retrieval algorithms. This allows for an additional assessment of the different algorithms while using identical brightness temperature datasets. This study shows that a good correlation generally exists between AMSR-E (VUA–NASA), ERS-Scat, and SIM for low altitudes and low-to-moderate vegetation covers (1.5–3 kg m−2 vegetation water content), with a reduction in the correlation in mountainous regions. It also shows that the AMSR-E (NSIDC) soil moisture product has significant differences when compared to the other datasets.
Anticyclonic Eddies in the Alaskan Stream
Authors: Ueno Hiromichi , Sato Kanako , Freeland Howard J. , Crawford William R. , Onishi Hiroji , Oka Eitarou , Suga Toshio
Published: September 2008

Anticyclonic eddies propagating southwestward in the Alaskan Stream (AS) were investigated through analysis of altimetry data from satellite observations during 1992–2006 and hydrographic data from profiling float observations during 2001–06. Fifteen long-lived eddies were identified and categorized based on their area of first appearance. Three eddies were present at the beginning of the satellite observations; another three formed in the eastern Gulf of Alaska off Sitka, Alaska; and four were first detected at the head of the Gulf of Alaska near Yakutat, Alaska. The other five eddies formed along the AS between 157° and 169°W, and were named AS eddies. While the eddies that formed in the Gulf of Alaska mainly decayed before exiting the Gulf of Alaska, the AS eddies mostly crossed the 180° meridian and reached the western subarctic gyre. Four of five AS eddies formed under negative or weakly positive wind stress curls, which possibly caused AS separation from the coast. Comparison of eddy propagation speeds in the AS with the bottom slope showed that eddies propagated faster over steeper slopes, although eddy speeds were slower than those predicted by the topographic planetary wave dispersion relation. An AS eddy was observed by profiling floats in the western subarctic gyre after it detached from the AS. Intermediate-layer water near the eddy center had low potential vorticity compared with the surrounding water, suggesting that AS eddies provided the western subarctic gyre with water just south of the Aleutian Islands.
Dynamics of the Wind-Driven Sea Level Variation around Antarctica
Authors: Kusahara Kazuya , Ohshima Kay I.
Published: September 2008

Coastal sea level variation around Antarctica is characterized by a coherent (circumpolarly in-phase) fluctuation, correlated with the Antarctic Oscillation (AAO). This study addresses the dynamics of the wind-driven sea level variation around Antarctica. A realistic barotropic numerical model reproduced well the observed sea level around Antarctica. From numerical model experiments, the authors demonstrate that the forcing responsible for the coastal sea level is the wind stress at the coastal boundary. Both the dominant coherent signal and westward propagating signals are identified in the model, and these signals are trapped over the shelf and slope around Antarctica. As a mechanism of these trapped signals, the authors consider analytical solutions of the oceanic response to alongshore wind stress over the shelf and slope in the circumpolar domain. In these solutions, besides the shelf wave mode, a wavenumber-zero mode appears and characterizes the coastal dynamics around Antarctica. At periods from 10 to 200 days, the coherent sea level can be explained quantitatively by the solution of this wavenumber-zero mode with a 5–10-day damping time scale. The spectral peaks of the westward propagating signals can be explained by the resonance of the shelf wave mode. The wavenumber-zero mode can respond to the wavenumber-zero forcing at any frequency and the degree of response increases with decreasing frequency. In addition, the wavenumber-zero component of wind stress, corresponding to the AAO variation, is a dominant forcing. Therefore, the coherent sea level variation around Antarctica is preferably generated and becomes a dominant feature in the circumpolar domain, particularly at lower frequencies.
Comparison of Methods Used to Generate Probabilistic Quantitative Precipitation Forecasts over South America
Authors: Ruiz Juan , Saulo Celeste , Kalnay Eugenia
Published: September 2008

In this work, the quality of several probabilistic quantitative precipitation forecasts (PQPFs) is examined. The analysis is focused over South America during a 2-month period in the warm season. Several ways of generating and calibrating the PQPFs have been tested, using different ensemble systems and single-model runs. Two alternative calibration techniques (static and dynamic) have been tested.

To take into account different precipitation regimes, PQPF performance has been evaluated over two regions: the northern part of South America, characterized by a tropical regime, and the southern part, where synoptic-scale forcing is stronger. The results support the adoption of such area separation, since differences in the precipitation regimes produce significant differences in PQPF performance.

The more skillful PQPFs are the ones obtained after calibration. PQPFs derived from the ensemble mean also show higher skill and better reliability than those derived from the single ensemble members. The performance of the PQPFs derived from both ensemble systems is similar over the southern part of the region; however, over the northern part the superensemble approach seems to achieve better results in both reliability and skill.

Finally, the impact of using Climate Prediction Center morphing technique (CMORPH) estimates to calibrate the precipitation forecast has been explored since the more extensive coverage of this dataset would allow its use over areas where the rain gauge coverage is insufficient. Results suggest that systematic biases present in the CMORPH estimates produce only a slight degradation of the resulting PQPF.
Pharmacotherapy of Juvenile Idiopathic Arthritis
Authors: Bell Edward A.
Published: September 2008

Juvenile idiopathic arthritis is the most common rheumatic disorder of childhood, and is defined as arthritis beginning prior to the age of 16 years, lasting more than 6 weeks, with an unknown cause. Seven subtypes of juvenile idiopathic arthritis have recently been categorized and named. These subtypes differ broadly in the number of affected joints and the presence of systemic illness. Although many children with juvenile idiopathic arthritis may achieve remission prior to entering adulthood, many others will continue to have debilitating disease into adulthood. Pharmacotherapy plays a major role in the treatment of juvenile idiopathic arthritis. Nonsteroidal anti-inflammatory drugs and corticosteroids can be beneficial for many children and are used as initial therapy. Methotrexate may offer benefits to children unresponsive to these initial agents. Studies evaluating the use of several biologic agents and immunosuppressants have recently been published, and the role of these drugs for children with juvenile idiopathic arthritis is being assessed. Major clinical trials and pediatric implications are reviewed.
Osteoarthritis: An Update on Data Currently Reshaping Practice
Authors: Epstein Benjamin J. , Taylor James R.
Published: September 2008

Osteoarthritis is common, has considerable health consequences, and will affect increasing numbers of persons in coming years. Nonpharmacological interventions are of paramount importance in achieving adequate symptom control. Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) play a pivotal role in osteoarthritis pharmacotherapy. Acetaminophen, due to its safety profile, should be adequately trialed before resorting to NSAIDs. NSAIDs and celecoxib, a selective inhibitor of cyclooxygenase-2, should be selected thoughtfully so as to balance the likelihood of treatment success with gastrointestinal bleeding and cardiovascular events. Celecoxib may be used when the risk for gastrointestinal bleeding is high and the risk of cardiovascular events low. Otherwise, NSAIDs, usually naproxen, should be paired with a gastroprotective agent. Topical NSAIDs, including a recently approved diclofenac patch and gel, may also be useful when systemic exposure is undesirable. The role of glucosamine and chondroitin is controversial and the data conflicting. Other modalities, such as tramadol, opioids, and viscosupplementation should be tailored to the patient and clinical situation. Appropriate deployment of agents in the osteoarthritis armamentarium can maximize efficacy and safety thereby improving the disease burden for patients.
The Social Security Surplus and Public Saving
Authors: Hungerford Thomas L.
Published: September 2008

The U.S. net national saving rate reached a postwar peak of 12.3 percent in 1965 and has since trended downward to 1.2 percent in 2007. Consequently, many analysts claim that saving is too low. Since 1983, the Social Security program has been in surplus, and the trust funds have been building up to pay for the retirement benefits for the baby boom cohort. Several recent studies have concluded that the increases in the trust funds have been more than offset by reductions in surpluses elsewhere in the federal budget. These studies therefore conclude that public saving has fallen as a result of the trust fund buildup since the mid-1980s. This study reexamines this issue. In the results, the authors cannot find evidence that the trust fund surpluses have had an impact on the rest of the federal budget.
Effects of welding parameters on tensile strength of weld metal in flux cored arc welding
Authors: Bang K.-S. , Jung D.-H. , Park C. , Chang W.-S.
Published: September 2008

Effects of welding parameters such as welding current, voltage and travel speed on the tensile strength of weld metal in flux cored arc welding were studied. The results were interpreted in terms of chemical composition and microstructural change in the weld metal. When heat input was increased to 2˙1 kJ mm–1 by increasing welding current, the tensile strength of the weld metal increased. However, the tensile strength of the weld metal decreased when heat input was increased from 2˙1 to 4˙5 kJ mm–1 by reducing travel speed or by increasing voltage. It showed that when heat input is higher than 2˙1 kJ mm–1 the decrease in tensile strength was related with the microstructural change. However, when heat input is lower than 2˙1 kJ mm–1 the increase in tensile strength was hardly related with the microstructural change. As Pcm value in the weld metal increases in the heat input up to 2˙1 kJ mm–1, it is believed that Pcm value has more powerful effect than microstructure in the heat input range. It showed that variation of the welding parameter resulted in different recoveries of the alloying elements in the wire. The recoveries increased with an increase in welding current and/or travel speed, but they decreased with an increase in voltage. The effects of welding parameters on the recoveries were rationalised with the time available for the reaction with oxygen during welding.
Double sided arc welding of AA5182 aluminium alloy sheet
Authors: Kwon Y. , Weckman D. C.
Published: September 2008

The feasibility and merits of using the double sided arc welding (DSAW) process for making square welds in 1˙2 mm thick AA5182-O aluminium sheets in the butt-joint configuration for applications such as tailor welded blanks (TWB) has been studied. Full penetration, conduction mode DSAW welds were made using a balanced square wave AC, constant current power supply at welding speeds of 30 to 40 mm s–1 when using 2˙1 kW welding power and between 40 and 60 mm s–1 when using 3˙4 kW welding power. There was good cathodic cleaning of the oxide on both sides of the sheet and the weld bead quality and properties were excellent. All welds exhibited a columnar to equiaxed grain transition with up to 40% equiaxed grain area. The DSAW process was found to be capable of producing welds of equal or better quality and at comparable welding speeds to those produced using more traditional welding processes for TWB applications.
Metal vapour behaviour in thermal plasma of gas tungsten arcs during welding
Authors: Yamamoto K. , Tanaka M. , Tashiro S. , Nakata K. , Yamazaki K. , Yamamoto E. , Suzuki K. , Murphy A. B.
Published: September 2008

A gas tungsten arc in helium and argon was modelled taking into account the contamination of the plasma by metal vapour from the weld pool. The whole region of gas tungsten arc atmosphere including the tungsten cathode, arc plasma and weld pool was treated using a unified numerical model. A viscosity approximation was used to express the diffusion coefficient in terms of viscosity of shielding gas and metal vapour. The transient two-dimensional distributions of the temperature, velocity of plasma flow and iron vapour concentration were predicted, together with the weld penetration as a function of time for a 150 A arc current at the atmospheric pressure, both for helium and argon welding gases.

It was shown that the thermal plasma in gas tungsten arcs is influenced by iron vapour from the weld pool surface and that the concentration of iron vapour in plasma is dependent on the temperature of the weld pool.
Analytical thermal model of conduction mode double sided arc welding
Authors: Kwon Y. , Weckman D. C.
Published: September 2008

An analytical thermal model of conduction mode double sided arc welding (DSAW) has been derived and used to predict the weld pool dimensions and shapes and temperatures within 2˙5 and 1˙15 mm thick AA5182 Al alloy sheets as functions of the primary DSAW parameters. Separate Gaussian distributed arc heat sources from a plasma arc welding and gas tungsten arc welding torch were assumed to act on the top and bottom surfaces of the sheets. There was excellent correlation between observed and predicted DSAW weld pool dimensions and shapes provided that suitable values for arc efficiencies and distribution coefficients for the two separate arcs were used in the model. The model is capable of predicting weld pool dimensions and shapes of both full and partial penetration conduction mode DSAW welds made in Al alloy sheet, the welding speed at which there is a transition from full to partial penetration welding and the speed above which no melting occurs.
Role of hypoxia-inducible factor 1alpha in the integrity of articular cartilage in murine knee joints
Authors: Gelse Kolja , Pfander David , Obier Simon , Knaup Karl X , Wiesener Michael , Hennig Friedrich F , Swoboda Bernd
Published: September 2008

Introduction

Chondrocytes have to withstand considerable hypoxic conditions within the avascular articular cartilage. The present study investigated the effects of inhibiting or stabilizing hypoxia-inducible factor (HIF)-1α by 2-methoxyestradiol or dimethyloxaloylglycine on the progression of osteoarthritis in murine knee joints.

Methods

2-Methoxyestradiol was injected six times over a period of 2 weeks into the left knee joint of Balb/C mice. Joints were assessed by histochemical and immunohistochemical methods, 3 weeks and 12 weeks following the first injection. Dimethyloxaloylglycine, an inhibitor of HIF-degrading prolyl-hydroxylases, was injected into the left knee joints of STR/ORT mice once a week over the entire period of 12 weeks. Right knee joints that received a saline solution served as controls. In addition, the effects of dimethyloxaloylglycine on HIF-1 target gene expression and on collagen metabolism were analyzed in vitro.

Results

Injection of 2-methoxyestradiol led to osteoarthritic changes in the treated knee joints of Balb/C mice. The first signs of osteophyte formation were observed in the knee joints after 3 weeks, followed by progressive destruction of the articular cartilage at 12 weeks that was not, however, accompanied by inflammatory reactions. Injection of dimethyloxaloylglycine could not prevent severe osteoarthritis that spontaneously developed in the knee joints of STR/ORT mice. In chondrocyte cultures, administration of dimethyloxaloylglycine resulted in an upregulation of Sox9 expression. Such a stimulatory effect was not observed, however, for the expression of type II collagen, which might be the indirect consequence of intracellular collagen retention observed by immunofluorescence or of increased expression of IL-1β and IL-6.

Conclusions

Induction of osteoarthritis by 2-methoxyestradiol demonstrates the importance of HIF-1 in maintaining the integrity of hypoxic articular cartilage. Stabilization of HIF-1 by dimethyloxaloylglycine, however, was not of therapeutic value, since this nonselective prolyl-hydroxylase inhibitor also interferes with proper collagen metabolism and induces the expression of catabolic cytokines
Principles of Safe Practice Using an Oncology EHR System for Chemotherapy Ordering, Preparation, and Administration, Part 2 of 2
Authors: Shulman Lawrence N. , Miller Robert S. , Ambinder Edward P. , Yu Peter Paul , Cox John V.
Published: September 2008

Integrating electronic health records into the oncology office, while taking into consideration the principles of electronic health record usage, is a great way to improve the chemotherapy ordering and administration process.
Office-Based Intraperitoneal Chemotherapy for Ovarian Cancer
Authors: Robinson William R. , Coberly Cathy , Beyer Julie , Lewis April , Ballard Carrie
Published: September 2008

The challenges and opportunities when implementing an office-based intraperitoneal chemotherapy program.
Refocusing the Debate: Evidence-Based Clinical Cancer Research Versus Marketplace Reality
Authors: Markman Maurie
Published: September 2008

The continued development and licensing of modestly beneficial high-priced treatments, and the potential for widening disparities in cancer care, warrant a renewed focus on how we measure and define benefits and cost.
Glucose Controls Cytosolic Ca2+ and Insulin Secretion in Mouse Islets Lacking Adenosine Triphosphate-Sensitive K+ Channels Owing to a Knockout of the Pore-Forming Subunit Kir6.2
Authors: Ravier Magalie A. , Nenquin Myriam , Miki Takashi , Seino Susumu , Henquin Jean-Claude
Published: September 2008

Glucose-induced insulin secretion is classically attributed to the cooperation of an ATP-sensitive potassium (KATP) channel-dependent Ca2+ influx with a subsequent increase of the cytosolic free Ca2+ concentration ([Ca2+]c) (triggering pathway) and a KATP channel-independent augmentation of secretion without further increase of [Ca2+]c (amplifying pathway). Here, we characterized the effects of glucose in β-cells lacking KATP channels because of a knockout (KO) of the pore-forming subunit Kir6.2. Islets from 1-yr and 2-wk-old Kir6.2KO mice were used freshly after isolation and after 18 h culture to measure glucose effects on [Ca2+]c and insulin secretion. Kir6.2KO islets were insensitive to diazoxide and tolbutamide. In fresh adult Kir6.2KO islets, basal [Ca2+]c and insulin secretion were marginally elevated, and high glucose increased [Ca2+]c only transiently, so that the secretory response was minimal (10% of controls) despite a functioning amplifying pathway (evidenced in 30 mm KCl). Culture in 10 mm glucose increased basal secretion and considerably improved glucose-induced insulin secretion (200% of controls), unexpectedly because of an increase in [Ca2+]c with modulation of [Ca2+]c oscillations. Similar results were obtained in 2-wk-old Kir6.2KO islets. Under selected conditions, high glucose evoked biphasic increases in [Ca2+]c and insulin secretion, by inducing KATP channel-independent depolarization and Ca2+ influx via voltage-dependent Ca2+ channels. In conclusion, Kir6.2KO β-cells down-regulate insulin secretion by maintaining low [Ca2+]c, but culture reveals a glucose-responsive phenotype mainly by increasing [Ca2+]c. The results support models implicating a KATP channel-independent amplifying pathway in glucose-induced insulin secretion, and show that KATP channels are not the only possible transducers of metabolic effects on the triggering Ca2+ signal.

Glucose can stimulate insulin secretion from beta cells by increasing Ca2+ influx, cytosolic Ca2+ concentration, and Ca2+ action independently of ATP-sensitive K channels.
Novel Expression of Type 1 Corticotropin-Releasing Hormone Receptor in Multiple Endocrine Cell Types in the Murine Anterior Pituitary
Authors: Westphal Nicole J. , Evans Ryan T. , Seasholtz Audrey F.
Published: September 2008

The CRH family of ligands signals via two distinct receptors, CRH-R1 and CRH-R2. Previous studies localized CRH-R1 and CRH-R2 to a subset of anterior pituitary corticotropes and gonadotropes, respectively. However, numerous studies have indicated that stress and CRH activity can alter the secretion of multiple anterior pituitary hormones, suggesting a broader expression of the CRH receptors in pituitary. To examine this hypothesis, the in vivo expression of CRH-R1 and CRH-R2 mRNA was further characterized in adult mouse pituitary. Quantitative RT-PCR analysis demonstrated that CRH-R1 mRNA is greater than 100-fold more abundant than CRH-R2 mRNA in male and female mouse pituitaries. Dual in situ hybridization analysis identified cell-specific CRH-R1 expression in the anterior pituitary. At least half of the CRH-R1-positive cells expressed proopiomelanocortin-mRNA (50% in females; 70% in males). In females, a significant percentage of the cells expressing CRH-R1 also expressed transcript for prolactin (40%), LHβ (10%), or TSH (3%), all novel sites of CRH-R1 expression. Similarly in males, a percentage of CRH-R1-positive cells expressed prolactin (12%), LHβ (13%), and TSH (5%). RT-PCR studies with immortalized murine anterior pituitary cell lines showed CRH-R1 and/or CRH-R2 expression in corticotropes (AtT-20 cells), gonadotropes (αT3-1 and LβT2 cells), and thyrotropes (αTSH cells). Whereas CRH-R1 expression in corticotropes is well established, the presence of CRH-R1 mRNA in a subset of lactotropes, gonadotropes, and thyrotropes establishes these cell types as novel sites of murine CRH-R1 expression and highlights the pituitary as an important site of interaction between the hypothalamus-pituitary-adrenal and multiple endocrine axes.

Corticotropin-releasing hormone receptor 1 mRNA is detected in multiple mouse anterior pituitary cell types, including corticotropes, lactotropes, and gonadotropes, in a sexually dimorphic pattern.
Argonaute-2 Expression Is Regulated by Epidermal Growth Factor Receptor and Mitogen-Activated Protein Kinase Signaling and Correlates with a Transformed Phenotype in Breast Cancer Cells
Authors: Adams Brian D. , Claffey Kevin P. , White Bruce A.
Published: September 2008

Argonaute (Ago) 2 is the catalytic engine of mammalian RNA interference, but little is known concerning the regulation of Ago2 by cell-signaling pathways. In this study we show that expression of Ago2, but not Ago1, Ago3, or Ago4, is elevated in estrogen receptor (ER) α-negative (ERα−) vs. ERα-positive (ERα+) breast cancer cell lines, and in ERα− breast tumors. In MCF-7 cells the low level of Ago2 was found to be dependent upon active ERα/estrogen signaling. Interestingly, the high expression of Ago2 in ERα− cells was severely blunted by inhibition of the epidermal growth factor (EGF) receptor/MAPK signaling pathway, using either a pharmacological MAPK kinase inhibitor, U0126, or a small interfering RNA directed against EGF receptor. Half-life studies using cycloheximide indicated that EGF enhanced, whereas U0126 decreased, Ago2 protein stability. Furthermore, a proteosome inhibitor, MG132, blocked Ago2 protein turnover. The functional consequences of elevated Ago2 levels were examined by stable transfection of ERα+ MCF-7 cells with full-length and truncated forms of Ago2. The full-length Ago2 transfectants displayed enhanced proliferation, reduced cell-cell adhesion, and increased migratory ability, as shown by proliferation, homotypic aggregation, and wound healing assays, respectively. Overexpression of full-length Ago2, but not truncated forms of Ago2 or an empty vector control, reduced the levels of E-cadherin, β-catenin, and β-actin, as well as enhanced endogenous miR-206 activity. These data indicate that Ago2 is regulated at both the transcriptional and posttranslational level, and also implicate Ago2 and enhanced micro-RNA activity in the tumorigenic progression of breast cancer cell lines.

Argonaute-2 is elevated in ERα- breast cancer cells due to epidermal growth factor receptor/MAPK signaling, and overexpression of this gene induces a more transformed phenotype in ERα+ MCF-7 cells.
Target Gene-Specific Regulation of Androgen Receptor Activity by p42/p44 Mitogen-Activated Protein Kinase
Authors: Agoulnik Irina U. , Bingman William E. , Nakka Manjula , Li Wei , Wang Qianben , Liu X. Shirley , Brown Myles , Nancy L. Nancy L.
Published: September 2008

Evidence that the androgen receptor (AR) is not only important in androgen-dependent prostate cancer, but also continues to play a role in tumors that become resistant to androgen deprivation therapies, highlights the need to find alternate means to block AR activity. AR, a hormone-activated transcription factor, and its coactivators are phosphoproteins. Thus, we sought to determine whether inhibition of specific cell signaling pathways would reduce AR function. We found that short-term inhibition of p42/p44 MAPK activity either by a MAPK kinase inhibitor, U0126, or by depletion of kinase with small interfering RNA caused target gene-specific reductions in AR activity. AR enhances histone H3 acetylation of target genes that are sensitive to U0126 including prostate-specific antigen and TMPRSS2, but does not increase histone H3 acetylation of the U0126-resistant PMEPA1 gene. Thus, although AR induces transcription of many target genes, the molecular changes induced by AR at the chromatin level are target gene specific. Long-term treatment (24–48 h) with U0126 causes a G1 cell cycle arrest and reduces AR expression both through a decrease in AR mRNA and a reduction in AR protein stability. Thus, treatments that reduce p42/p44 MAPK activity in prostate cancer have the potential to reduce AR activity through a reduction in expression levels as well as by target gene-selective inhibition of AR function.
The Expression of GPIHBP1, an Endothelial Cell Binding Site for Lipoprotein Lipase and Chylomicrons, Is Induced by Peroxisome Proliferator-Activated Receptor-γ
Authors: Davies Brandon S. J. , Waki Hironori , Beigneux Anne P. , Farber Emily , Weinstein Michael M. , Wilpitz Damien C. , Tai Li-Jung , Evans Ronald M. , Fong Loren G. , Tontonoz Peter , Young Stephen G.
Published: September 2008

Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), a protein in the lymphocyte antigen 6 (Ly-6) family, plays a key role in the lipolytic processing of triglyceride-rich lipoproteins. GPIHBP1 binds lipoprotein lipase and chylomicrons and is expressed along the luminal surface of microvascular endothelial cells. Lipolysis is known to be regulated by metabolic factors and is controlled at multiple levels, including the number of LPL binding sites on capillaries. Here, we tested the possibility that GPIHBP1 expression could be regulated by dietary perturbations and by peroxisome proliferator-activated receptors (PPARs). Gpihbp1 transcript levels in the heart and in brown and white adipose tissue increased with fasting and returned toward baseline after refeeding. A PPARγ agonist increased Gpihbp1 expression in adipose tissue, heart, and skeletal muscle, whereas PPARα and PPARδ agonists had no effect. Gpihbp1 was expressed in endothelial cells of embryoid bodies generated from mouse embryonic stem cells, and Gpihbp1 expression in embryoid bodies was up-regulated by a PPARγ agonist. Sequences upstream from exon 1 of Gpihbp1 contain a strong PPAR binding site, and that site exhibited activity in a luciferase reporter assay. Gpihbp1 transcript levels in brown and white adipose tissue were lower in endothelial cell PPARγ knockout mice than in littermate control mice, suggesting that PPARγ regulates Gpihbp1 expression in vivo. We conclude that GPIHBP1 is regulated by dietary factors and by PPARγ.
Axl and Tyro3 Modulate Female Reproduction by Influencing Gonadotropin-Releasing Hormone Neuron Survival and Migration
Authors: Pierce Angela , Bliesner Brian , Xu Mei , Nielsen-Preiss Sheila , Lemke Greg , Tobet Stuart , Wierman Margaret E.
Published: September 2008

GnRH neurons must undergo a complex and precise pattern of neuronal migration to appropriately target their projections to the median eminence to trigger gonadotropin secretion and thereby control reproduction. Using NLT GnRH cells as a model of early GnRH neuronal development, we identified the potential importance of Axl and Tyro3, members of the TAM (Tyro3, Axl, and Mer) family of receptor tyrosine kinases in GnRH neuronal cell survival and migration. Silencing studies evaluated the role of Tyro3 and Axl in NLT GnRH neuronal cells and suggest that both play a role in Gas6 stimulation of GnRH neuronal survival and migration. Analysis of mice null for both Axl and Tyro3 showed normal onset of vaginal opening but delayed first estrus and persistently abnormal estrous cyclicity compared with wild-type controls. Analysis of GnRH neuronal numbers and positioning in the adult revealed a total loss of 24% of the neuronal network that was more striking (34%) when considered within specific anatomical compartments, with the largest deficit surrounding the organum vasculosum of the lamina terminalis. Analysis of GnRH neurons during embryogenesis identified a striking loss of immunoreactive cells within the context of the ventral forebrain compartment (36%) and not more rostrally. Studies using caspase 3 cleavage as a marker of apoptosis showed that Axl−/−, Tyro3−/− double-knockout mice had increased cell death in the nose and dorsal forebrain, supporting the underlying mechanism of cell loss. Together these data suggest that Axl and Tyro3 mediate the survival and appropriate targeting of GnRH neurons to the ventral forebrain, thereby contributing to normal reproductive function and cyclicity in the female.
Genetic substitution of Cdk1 by Cdk2 leads to embryonic lethality and loss of meiotic function of Cdk2
Authors: Satyanarayana Ande , Berthet Cyril , Lopez-Molina Javier , Coppola Vincenzo , Tessarollo Lino , Kaldis Philipp
Published: September 2008

It was believed that Cdk2-cyclin E complexes are essential to drive cells through the G1-S phase transition. However, it was discovered recently that the mitotic kinase Cdk1 (Cdc2a) compensates for the loss of Cdk2. In the present study, we tested whether Cdk2 can compensate for the loss of Cdk1. We generated a knockin mouse in which the Cdk2 cDNA was knocked into the Cdk1 locus (Cdk1Cdk2KI). Substitution of both copies of Cdk1 by Cdk2 led to early embryonic lethality,even though Cdk2 was expressed from the Cdk1 locus. In addition, we generated Cdk2-/-Cdk1+/Cdk2KI mice in which one copy of Cdk2 and one copy of Cdk1 were expressed from the Cdk1 locus and the Cdk2 gene was deleted from the endogenous Cdk2 locus. We found that both male and female Cdk2-/-Cdk1+/Cdk2KI mice were sterile, similar to Cdk2-/- mice, even though they expressed the Cdk2 protein from the Cdk1 locus in testes. The translocational and cell cycle properties of knockin Cdk2 in Cdk2-/-Cdk1+/Cdk2KI cells were comparable to those of endogenous Cdk2, but we detected premature transcriptional activation of Cdk1during liver regeneration in the absence of Cdk2. This study provides evidence of the molecular differences between Cdk2 and Cdk1 and highlights that the timing of transcriptional activation and the genetic locus play important roles in determining the function of Cdk proteins in vivo.
A Detailed Study of Low-Frequency Noise Complaints
Authors: Pedersen Christian Sejer , Møller Henrik , Waye Kerstin Persson
Published: September 2008

From 203 cases of low-frequency complaints a random selection of twenty-one cases were investigated. The main aim was to answer the question whether the annoyance is caused by an external physical sound or by a perceived but physically non-existing sound, i.e. low-frequency tinnitus. Noise recordings were made in the homes of the complainants, and the complainants were exposed to these in blind test listening experiments. Furthermore, the low-frequency hearing function of the complainants was investigated, and characteristics of the annoying sound were matched. The results showed that some of the complainants are annoyed by a physical sound (20–180 Hz), while others suffer from low-frequency tinnitus (perceived frequency 40–100 Hz). Physical sound at frequencies below 20 Hz (infrasound) is not responsible for the annoyance -or at all audible – in any of the investigated cases, and none of the complainants has extraordinary hearing sensitivity at low frequencies. For comparable cases of low-frequency noise complaints in general, it is anticipated that physical sound is responsible in a substantial part of the cases, while low-frequency tinnitus is responsible in another substantial part of the cases.
The Removal of Fe(III) Ions by Adsorption onto Zeolite Columns
Authors: Ostroski Indianara C. , Barros Maria A.S.D. , Silva Edson A. , Dantas João H. , Arroyo Pedro A. , Lima Oswaldo C. Motta
Published: September 2008

The uptake capacity of Fe(III) ions by NaY zeolite was investigated in this work. Column experiments were undertaken on continuous systems at 30°C, pH = 3.5, employing a flow rate of 2 m l/min and an average particle size of 0.180 mm. The dynamic system exhibited a distinct ion-exchange mechanism which generated a favourable isotherm with an Fe(III) ion uptake of 2.16 mequiv/g. A mathematical model was also applied to represent the dynamics of the sorption process. The dynamic isotherm was successfully modelled by the Langmuir equation while the mathematical model gave a good description of the experimental dynamic data for feed concentrations ranging from 0.2 mequiv/ l to 3.5 mequiv/ l. The ion-exchange kinetics for Fe(III) ions were studied using the first-, second-order and Langmuir kinetic models.