bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscle metaboreflex control of ventricular contractility during dynamic exercise
Authors: Sala-Mercado Javier A. , Hammond Robert L. , Kim Jong-Kyung , Rossi Noreen F. , Stephenson Larry W. , O'Leary Donal S.
Published: September 2005

When oxygen delivery to active skeletal muscle is insufficient for the metabolic demands, afferent nerves within muscles are activated, which elicit reflex increases in heart rate (HR), cardiac output (CO), and arterial pressure (AP), termed the muscle metaboreflex (MMR). To what extent the increases in CO are the result of increased ventricular contractility is unclear. A widely accepted index of contractility is maximal left ventricular elastance ( Emax), the slope of the end-systolic pressure-volume relationship, such as during rapidly imposed reductions in preload. The objective of the present study was to determine whether MMR activation elicits increases in Emax. Experiments were performed using conscious dogs chronically instrumented to measure left ventricular pressure and volume at rest and during mild or moderate treadmill exercise with and without partial hindlimb ischemia to elicit MMR responses. At both workloads, MMR activation significantly increased CO, HR, AP, and maximum rate of change of left ventricular pressure. During both mild and moderate exercise, MMR activation increased Emax to 159.6 ± 8.83 and 155.8 ± 6.32% of the exercise value under free-flow conditions, respectively. We conclude that the increase of ventricular elastance associated with MMR activation indicates that a substantial increase in ventricular contractility contributes to the rise in CO during dynamic exercise.
Adenosine induces fibronectin expression in lung epithelial cells: implications for airway remodeling
Authors: Roman Jesse , Rivera Hilda N. , Roser-Page Susanne , Sitaraman Shanthi V. , Ritzenthaler Jeffrey D.
Published: September 2005

Adenosine is an extracellular nucleoside that is elevated in tissues during hypoxia and ischemia reperfusion and has been implicated in asthma and other lung disorders. There, adenosine is considered an important modulator of physiological functions and inflammation, but its effects on matrix expression and turnover during tissue remodeling are unknown. We examined the effects of adenosine on lung epithelial cells with particular attention to the expression of fibronectin, a matrix glycoprotein highly expressed in injured tissues that has been implicated in wound healing. In A549 lung epithelial cells, we found that adenosine induced expression of fibronectin mRNA and protein in a dose- and time-dependent manner and found that the stimulatory effect of adenosine was inhibited by specific adenosine receptor antagonists. Adenosine stimulation was associated with increased levels of intracellular cAMP and with phosphorylation and DNA binding of the cAMP response element binding protein (CREB), known for its ability to stimulate fibronectin gene transcription. To confirm the latter, A549 cells were transfected with a DNA construct containing the human fibronectin promoter connected to a luciferase reporter gene. Adenosine stimulated transcription of the gene, and this effect was blocked by inhibitors of protein kinase activation. Finally, we tested primary lung fibroblasts and primary alveolar epithelial type II cells and found increased fibronectin expression in response to adenosine. Overall, our observations suggest that adenosine might modulate tissue remodeling by stimulating fibronectin expression in lung epithelial cells through induction of purinergic receptor-mediated signals that target CREB phosphorylation and stimulate fibronectin gene transcription.
Ionic mechanism of forskolin-induced liquid secretion by porcine bronchi
Authors: Ballard Stephen T. , Trout Laura , Garrison Jennifer , Inglis Sarah K.
Published: September 2005

cAMP-elevating agents such as forskolin and vasoactive intestinal peptide induce liquid secretion by tracheobronchial submucosal glands. This pathway is thought to be CFTR dependent and thus defective in cystic fibrosis; however, the ionic mechanism that drives this secretion process is incompletely understood. To better define this mechanism, we studied the effects of ion transport inhibitors on the forskolin-induced liquid secretion response (Jv) of porcine distal bronchi. The forskolin-induced Jvwas driven by a combination of bumetanide-sensitive Cl−secretion and DIDS-sensitive HCO3−secretion. When Cl−secretion was inhibited with bumetanide, Na+/H+exchange-dependent HCO3−secretion was apparently induced to compensate for the loss of Cl−secretion. The forskolin-induced Jvwas significantly inhibited by the anion channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid, diphenylamine-2-carboxylate, and glibenclamide. We conclude that the forskolin-induced Jvshares many characteristics of cholinergically induced secretion except for the presence of a DIDS-sensitive component. Although the identity of the DIDS-sensitive component is unclear, we speculate that it represents a basolateral membrane Na+-HCO3−cotransporter or an Na+-dependent anion exchanger, which could account for transepithelial HCO3−secretion.
Role of phosphatidylinositol 3-kinase-γ in mediating lung neutrophil sequestration and vascular injury induced byE. colisepsis
Authors: Ong Evan , Gao Xiao-Pei , Predescu Dan , Broman Michael , Malik Asrar B.
Published: September 2005

We addressed the in vivo role of phosphatidylinositol 3-kinase-γ (PI3K-γ) in signaling the sequestration of polymorphonuclear leukocytes (PMNs) in lungs and in the mechanism of inflammatory lung vascular injury. We studied mice with deletion of the p110 catalytic subunit of PI3K-γ (PI3K-γ−/−mice). We measured lung tissue PMN sequestration, microvascular permeability, and edema formation after bacteremia induced by intraperitoneal Escherichia coli challenge. PMN infiltration into the lung interstitium in PI3K-γ−/−mice as assessed morphometrically was increased 100% over that in control mice within 1 h after bacterial challenge. PI3K-γ−/−mice also developed a greater increase in lung microvascular permeability after E. coli challenge, resulting in edema formation. The augmented lung tissue PMN sequestration in PI3K-γ−/−mice was associated with increased expression of the PMN adhesive proteins CD47 and β3-integrins. We observed increased association of CD47 and β3-integrins with the extracellular matrix protein vitronectin in lungs of PI3K-γ−/−mice after E. coli challenge. PMNs from these mice also showed increased β3-integrin expression and augmented β3-integrin-dependent PMN adhesion to vitronectin. These results point to a key role of PMN PI3K-γ in negatively regulating CD47 and β3-integrin expression in gram-negative sepsis. PI3K-γ activation in PMNs induced by E. coli may modulate the extent of lung tissue PMN sequestration secondary to CD47 and β3-integrin expression. Therefore, the level of PI3K-γ activation may be an important determinant of PMN-dependent lung vascular injury.
Ceramide decreases surfactant protein B gene expression via downregulation of TTF-1 DNA binding activity
Authors: Sparkman Loretta , Chandru Hemakumar , Boggaram Vijayakumar
Published: September 2005

Ceramide, a sphingolipid, is an important signaling molecule in the inflammatory response. Mediators of acute lung injury such as TNF-α, platelet-activating factor, and Fas/Apo ligand stimulate sphingomyelin hydrolysis to increase intracellular ceramide levels. Surfactant protein B (SP-B), a hydrophobic protein of pulmonary surfactant, is essential for surfactant function and lung stability. In this study we investigated the effects of ceramide on SP-B gene expression in H441 lung epithelial cells. Ceramide decreased SP-B mRNA levels in control and dexamethasone-treated cells after 24-h incubation and inhibition of SP-B mRNA was associated with inhibition of immunoreactive SP-B. In transient transfections assays, ceramide inhibited SP-B promoter activity, indicating that the inhibitory effects are exerted at the transcriptional level. Deletion mapping experiments showed that the ceramide-responsive region is located within the −233/−80-bp region of human SP-B promoter. Electrophoretic mobility shift and reporter assays showed that ceramide reduced the DNA binding activity and transactivation capability of thyroid transcription factor 1 (TTF-1/Nkx2.1), a key factor for SP-B promoter activity. Collectively these data showed that ceramide inhibits SP-B gene expression by reducing the DNA biding activity of TTF-1/Nkx2.1 transcription factor. Protein kinase C inhibitor bisindolylmaleimide and the protein tyrosine kinase inhibitor genistein partially reversed ceramide inhibition, indicating that protein kinases play important roles in the ceramide inhibition of SP-B gene expression. Chemical inhibitors of de novo ceramide synthesis and sphingomyelin hydrolysis had no effect on TNF-α inhibition of SP-B promoter activity and mRNA levels, suggesting that ceramide does not play a role in the inhibition.
siRNA-induced caveolin-1 knockdown in mice increases lung vascular permeability via the junctional pathway
Authors: Miyawaki-Shimizu Kayo , Predescu Dan , Shimizu Jun , Broman Michael , Predescu Sanda , Malik Asrar B.
Published: September 2005

Caveolin-1, the principal integral membrane protein of caveolae, has been implicated in regulating the structural integrity of caveolae, vesicular trafficking, and signal transduction. Although the functions of caveolin-1 are beginning to be explored in caveolin-1−/−mice, these results are confounded by unknown compensatory mechanisms and the development of pulmonary hypertension, cardiomyopathy, and lung fibrosis. To address the role of caveolin-1 in regulating lung vascular permeability, in the present study we used small interfering RNA (siRNA) to knock down caveolin-1 expression in mouse lung endothelia in vivo. Intravenous injection of siRNA against caveolin-1 mRNA incorporated in liposomes selectively reduced the expression of caveolin-1 by ∼90% within 96 h of injection compared with wild-type mice. We observed the concomitant disappearance of caveolae in lung vessel endothelia and dilated interendothelial junctions (IEJs) as well as increased lung vascular permeability to albumin via IEJs. The reduced caveolin-1 expression also resulted in increased plasma nitric oxide concentration. The nitric oxide synthase inhibitor l-NAME, in part, blocked the increased vascular albumin permeability. These morphological and functional effects of caveolin-1 knockdown were reversible within 168 h after siRNA injection, corresponding to the restoration of caveolin-1 expression. Thus our results demonstrate the essential requirement of caveolin-1 in mediating the formation of caveolae in endothelial cells in vivo and in negatively regulating IEJ permeability.
Carnitine/xenobiotics transporters in the human mammary gland epithelia, MCF12A
Authors: Kwok Bruce , Yamauchi Ariko , Rajesan Ratheishan , Chan Lillian , Dhillon Upinder , Gao Wen , Xu Haibo , Wang Bernice , Takahashi Shinichiro , Semple John , Tamai Ikumi , Nezu Jun-Ichi , Tsuji Akira , Harper Patricia , Ito Shinya
Published: September 2005

The barrier function of the human mammary gland collapses if challenged with cationic drugs, causing their accumulation in milk. However, underlying molecular mechanisms are not well understood. To gain insight into the mechanism, we characterized transport of organic cations in the MCF12A human mammary gland epithelial cells, using carnitine and tetraethylammonium (TEA) as representative nutrient and xenobiotics probes, respectively. Our results show that the mammary gland cells express mRNA and proteins of human (h) novel organic cation transporters (OCTN) 1 and hOCTN2 (a Na+-dependent carnitine carrier with Na+-independent xenobiotics transport function), which belong to the solute carrier superfamily (SLC) of transporters. Other SLC OCTs such as hOCT1 and extraneuronal monoamine transporter (EMT)/hOCT3 are also expressed at mRNA levels, but hOCT2 was undetectable. We further showed mRNA expression of ATB0+(an amino acid transporter with a Na+/Cl−-dependent carnitine transport activity), and Fly-like putative transporter 2/OCT6 (a splice variant of carnitine transporter 2: a testis-specific Na+-dependent carnitine transporter). TEA uptake was pH dependent. Carnitine uptake was dependent on Na+, and partly on Cl−, compatible with hOCTN2 and ATB0+function. Modeling analyses predicted multiplicity of the uptake mechanisms with the high-affinity systems characterized by Kmof 5.1 μM for carnitine and 1.6 mM for TEA, apparently similar to the reported hOCTN2 parameter for carnitine, and that of EMT/hOCT3 for TEA. Verapamil, cimetidine, carbamazepine, quinidine, and desipramine inhibited the carnitine uptake but required supratherapeutic concentrations, suggesting robustness of the carnitine uptake systems against xenobiotic challenge. Our findings suggest functional roles of a network of multiple SLC organic cation/nutrient transporters in human mammary gland drug transfer.
Effects of mandibular advancement on brain activation during inspiratory loading in healthy subjects: a functional magnetic resonance imaging study
Authors: Hashimoto Koji , Ono Takashi , Honda Ei-ichi , Maeda Keiko , Shinagawa Hideo , Tsuiki Satoru , Hiyama Shigetoshi , Kurabayashi Tohru , Ohyama Kimie
Published: September 2005

Oral appliances have been a popular treatment option for subjects with obstructive sleep apnea. However, little information is available on how brain activation induced by respiratory challenge is modulated by mandibular advancement with these appliances. We hypothesized that the brain activation caused by respiratory stress may be alleviated by mandibular advancement. Respiratory stress was induced in 12 healthy subjects by resistive inspiratory loading. The effects of mandibular advancement during resistive inspiratory loading were assessed subjectively by using a visual analog scale. These effects were also evaluated objectively by using blood oxygenation level-dependent functional magnetic resonance imaging. The score for the visual analog scale significantly decreased with mandibular advancement. Cortical deactivation, in association with mandibular advancement, was localized to several specific regions, including the left cingulate gyrus and the bilateral prefrontal cortexes. These regions are known to be involved in respiratory control. Our results suggest that mandibular advancement with an oral appliance appears to be useful for reducing respiratory stress, based on both subjective and neuronal criteria.
Physical inactivity amplifies the sensitivity of skeletal muscle to the lipid-induced downregulation of lipoprotein lipase activity
Authors: Zderic Theodore W. , Hamilton Marc T.
Published: September 2005

Physical inactivity is a risk factor for lipoprotein disorders and the metabolic syndrome. Physical inactivity has a powerful effect on suppressing lipoprotein lipase (LPL) activity in skeletal muscle, the rate-limiting enzyme for hydrolysis of triglyceride (TG)-rich lipoproteins. We tested the ability of several compounds to prevent the decrease in LPL. The present study minimized standing and ordinary light nonexercise movements in rats to compare the effects of inactivity and nonexercise activity thermogenesis (NEAT) on LPL activity. The key new insight was that the typically quick decrease in LPL activity of oxidative muscle caused by physical inactivity was prevented by nicotinic acid (NA), whereas inhibitors of TNF-α, inducible nitric oxide synthase, and NF-κB had no such effect. NA was administered at a dose known to acutely impede the appearance of plasma TG from the liver and free fatty acids from adipose tissue, and it was effective at intentionally lowering plasma lipid concentrations to the same level in active and inactive groups. As measured from heparin-releasable LPL activity, LPL in the microvasculature of the most oxidative muscles was ∼90% lower in the inactive group compared with controls, and this suppression was completely blocked by NA. In contrast to inactivity, NA did not raise muscle LPL in ambulatory controls, whereas a large exogenous fat delivery did decrease LPL activity. In vitro control studies revealed that NA did not have a direct effect on skeletal muscle LPL activity. In conclusion, physical inactivity amplifies the ability of plasma lipids to suppress muscle LPL activity. The light ambulatory contractions responsible for NEAT are sufficient for mitigating these deleterious effects.
Transfer of Endothelial Progenitor and Bone Marrow Cells Influences Atherosclerotic Plaque Size and Composition in Apolipoprotein E Knockout Mice
Authors: George Jacob , Afek Arnon , Abashidze Anastasia , Shmilovich Haim , Deutsch Varda , Kopolovich Juri , Miller Hylton , Keren Gad
Published: September 2005

Objectives—

Recent clinical trials use cell therapy with bone marrow (BM) cells or endothelial progenitor cells (EPCs) for ischemic syndromes. We explored the effect of BM cell– or spleen cell–derived EPC transfer on plaque size and stability markers in the apolipoprotein E knockout (apoE KO) mouse model.

Methods and Results—

ApoE KO mice aged 10 weeks served as recipients. Labeled BM cells and spleen cell–derived EPCs from age-matched apoE KO mice were injected intravenously to 2 groups of recipient mice each. Additional mice served as controls receiving saline. Both protocols were repeated 3 times at 2 weekly intervals. On killing, plaque size and character were studied, lipid profile analyzed, and serum and aortic cytokines assayed. Spleen cell–derived cells contained a significantly larger number of endothelial cell precursors. Labeled EPCs and BM cells were found abundantly in the spleens, yet also in the lesions of the recipient mice. Aortic sinus lesion size was significantly increased in mice receiving BM cells (n=10) in the EPC-treated group (n=10) compared with controls (n=10; a 54% and a 34% increase in aortic sinus plaque area, respectively). Mice receiving EPCs exhibited plaques with larger lipid cores and thinner fibrous caps and a higher number of infiltrating CD3 cells. RT-PCR analysis of aortas revealed reduced expression of mRNA for interleukin-10 (IL-10) in both cell transfer groups. Higher serum concentrations of IL-6 and monocyte chemoattractant protein-1 were found in sera from BM recipients, whereas lower IL-10 levels were found in mice transfused with spleen-derived EPCs.

Conclusions—

Transfer of BM cells and EPCs may result in an increase in atherosclerotic lesion size, whereas EPC transfer could also potentially influence plaque stability.
Delayed In Vivo Catabolism of Intermediate-Density Lipoprotein and Low-Density Lipoprotein in Hemodialysis Patients as Potential Cause of Premature Atherosclerosis
Authors: Ikewaki Katsunori , Schaefer Juergen R. , Frischmann Michael E. , Okubo Keio , Hosoya Tatsuo , Mochizuki Seibu , Dieplinger Benjamin , Trenkwalder Evi , Schweer Horst , Kronenberg Florian , Koenig Paul , Dieplinger Hans
Published: September 2005

Objective—Premature cardiovascular disease is the leading cause of death in patients with end-stage renal disease treated by hemodialysis (HD). Low-density lipoprotein (LDL) levels are not generally increased in HD patients, but their LDL metabolism is still poorly understood. We therefore investigated the in vivo metabolism of apoB-containing lipoproteins in two different ethnic populations of HD patients and controls.

Methods and Results—We performed stable isotope kinetic studies using a primed constant infusion of deuterated leucine in 12 HD patients and 13 healthy controls. Tracer/tracee ratio of apoB was determined by means of gas chromatography/mass spectrometry, and the modeling program SAAMII was used to estimate the fractional catabolic rate (FCR) of apoB. Mean LDL-apoB plasma concentrations were almost identical in both groups (HD: 95±30 mg/dL, controls: 91±40 mg/dL), whereas LDL-apoB FCR was 50% lower in HD patients as compared with controls (0.22±0.12 days−1versus 0.46±0.20 days−1,P=0.001) with concomitantly decreased production rates of LDL. Compared with controls, intermediate-density lipoprotein (IDL)-apoB FCR was 65% lower (2.87±1.02 days−1versus 8.89±4.94 days−1,P=0.014), accompanied by 1.5-fold higher IDL-apoB levels in HD. Very low-density lipoprotein metabolism was similar in both study groups.

Conclusions—In vivo catabolism of LDL and IDL is severely impaired in HD patients but misleadingly masked by normal plasma cholesterol levels. The resulting markedly prolonged residence times of both IDL and LDL particles might thus significantly contribute to the well-documented high risk for premature cardiovascular disease in HD patients.
Cyclin-Dependent Kinase Inhibitor p27
Kip1
, But Not p21
WAF1/Cip1
, Is Required for Inhibition of Hypoxia-Induced Pulmonary Hypertension and Remodeling by Heparin in Mice
Authors: Yu Lunyin , Quinn Deborah A. , Garg Hari G. , Hales Charles A.
Published: September 2005

Heparin has growth inhibitory effects on pulmonary artery smooth muscle cell (PASMC) in vitro and in vivo. However, the mechanism has not been fully defined. In this study, we investigated the role of cyclin-dependent kinase inhibitors, p21
WAF1/cip1
(p21) and p27
Kip1
(p27), in the inhibitory effect of heparin on PASMC proliferation in vitro and on hypoxia-induced pulmonary hypertension in vivo using p21 and p27-null mice. In vitro, loss of the p27 gene negated the inhibitory effect of heparin on PASMC proliferation, but p21 was not critical for this inhibition. In vivo, heparin significantly inhibited the development of hypoxia-induced pulmonary hypertension and remodeling, as evidenced by decreased right ventricular systolic pressure, ratio of right ventricular weight to left ventricle plus septum weight, and percent wall thickness of pulmonary artery, in p21
+/+
, p21
−/−
, p27
+/+
, and p27
+/−
, but not in p27
−/−
mice. We also observed that hypoxia decreased p27 expression significantly in mouse lung, which was restored by heparin. Heparin inhibited Ki67 proliferative index in terminal bronchial vessel walls in p27
+/+
and p27
+/−
, but not in p27
−/−
mice exposed to hypoxia. Therefore, we conclude that the cyclin-dependent kinase inhibitor p27, but not p21, is required for the inhibition of hypoxic pulmonary vascular remodeling by heparin.
Eloquent Bodies: Rituals in the Contexts of Alleviating Suffering
Authors: Hornborg Anne-Christine
Published: September 2005

It seems that the revitalization of traditional rituals has been an effective way of developing a new embodiment and identity. The ability of the Canadian Mi'kmaq Indians to rework the cultural body, historically imposed on them by the dominant society, opens the way to weeding out destructive patterns unconsciously or consciously embedded historically in their bodies. The ritual opens up opportunities to explore new habitus and to employ the body in a domain shared with like-minded peers so as to facilitate new ways of approaching the world. The rituals thus provide redemptive opportunities for bodies that have been disempowered by hegemonic contexts, and simultaneously offer social affirmation of the new way of being in the world.
What Controls the Mean Depth of the PBL?
Authors: Medeiros Brian , Hall Alex , Stevens Bjorn
Published: September 2005

The depth of the planetary boundary layer (PBL) is a climatologically important quantity that has received little attention on regional to global scales. Here a 10-yr climatology of PBL depth from the University of California, Los Angeles (UCLA) atmospheric GCM is analyzed using the PBL mass budget. Based on the dominant physical processes, several PBL regimes are identified. These regimes tend to exhibit large-scale geographic organization. Locally generated buoyancy fluxes and static stability control PBL depth nearly everywhere, though convective mass flux has a large influence at tropical marine locations. Virtually all geographical variability in PBL depth can be linearly related to these quantities. While dry convective boundary layers dominate over land, stratocumulus-topped boundary layers are most common over ocean. This division of regimes leads to a dramatic land–sea contrast in PBL depth. Diurnal effects keep mean PBL depth over land shallow despite large daytime surface fluxes. The contrast arises because the large daily exchange of heat and mass between the PBL and free atmosphere over land is not present over the ocean, where mixing is accomplished by turbulent entrainment. Consistent treatment of remnant air from the deep, daytime PBL is necessary for proper representation of this diurnal behavior over land. Many locations exhibit seasonal shifts in PBL regime related to changes in PBL clouds. These shifts are controlled by seasonal variations in buoyancy flux and static stability.
Did the ECMWF Seasonal Forecast Model Outperform Statistical ENSO Forecast Models over the Last 15 Years?
Authors: Jan van Oldenborgh Geert , Balmaseda Magdalena A. , Ferranti Laura , Stockdale Timothy N. , Anderson David L. T.
Published: September 2005

The European Centre for Medium-Range Weather Forecasts (ECMWF) has made seasonal forecasts since 1997 with ensembles of a coupled ocean–atmosphere model, System-1 (S1). In January 2002, a new version, System-2 (S2), was introduced. For the calibration of these models, hindcasts have been performed starting in 1987, so that 15 yr of hindcasts and forecasts are now available for verification.

Seasonal predictability is to a large extent due to the El Niño–Southern Oscillation (ENSO) climate oscillations. ENSO predictions of the ECMWF models are compared with those of statistical models, some of which are used operationally. The relative skill depends strongly on the season. The dynamical models are better at forecasting the onset of El Niño or La Niña in boreal spring to summer. The statistical models are comparable at predicting the evolution of an event in boreal fall and winter.
The Statistics and Structure of Subseasonal Midlatitude Variability in NASA GSFC GCMs
Authors: Robinson Dennis P. , Black Robert X.
Published: September 2005

A comprehensive analysis of midlatitude intraseasonal variability in extended integrations of NASA GSFC general circulation models (GCMs) is conducted. This is approached by performing detailed intercomparisons of the representation of the storm tracks and anomalous weather regimes occurring during wintertime in the Atmospheric Model Intercomparison Project (AMIP)-type simulations of both the NASA–NCAR and a version of the Aries model used in NASA’s Seasonal-to-Interannual Prediction Project (NSIPP) model. The model-simulated statistics, three-dimensional structure, and dynamical characteristics of these phenomena are diagnosed and directly compared to parallel observational analyses derived from NCEP–NCAR reanalyses.

A qualitatively good representation of the vertical structure of intraseasonal eddy kinetic energy (EKE) is provided by both models with maximum values of EKE occurring near 300 hPa. The main model shortcoming is an underestimation of EKE in the upper troposphere, especially for synoptic eddies in the NSIPP model. Nonetheless, both models provide a reasonable representation of the three-dimensional structure and dynamical characteristics of synoptic eddies. Discrepancies in the storm-track structures simulated by the models include an anomalous local minimum over the eastern Pacific basin. However, both GCMs faithfully reproduce the observed Pacific midwinter storm-track suppression. Interestingly, the NSIPP model also produces a midwinter suppression feature over the Atlantic storm track in association with the anomalously strong upper-level jet stream simulated by NSIPP in this region.

The regional distribution of anomalous weather regime events is well simulated by the models. However, substantial structural differences exist between observed and simulated events over the North Pacific region. In comparison to observations, model events are horizontally more isotropic, have stronger westward vertical tilts, and are more strongly driven by baroclinic dynamics. The structure and dynamics of anomalous weather regimes occurring over the North Atlantic region are qualitatively better represented by the models. The authors suggest that model deficiencies in representing the zonally asymmetric climatological-mean flow field (particularly the magnitude and structure of the Pacific and Atlantic jet streams) help contribute to model shortcomings in (i) the strength and seasonal variability of the storm tracks and (ii) dynamical distinctions in the maintenance of large-scale weather regimes.
Asymmetry between El Niño and La Niña in a Global Coupled GCM with an Eddy-Permitting Ocean Resolution
Authors: Dong Buwen
Published: September 2005

Observations show the asymmetric nature of El Niño and La Niña sea surface temperature (SST) anomalies. Warm events are often stronger than cold events. This asymmetric behavior is an important feature that can be used to validate coupled models to test their ability to represent the climate system. The asymmetry of El Niño and La Niña SST anomalies has been investigated in a simulation of the Hadley Centre eddy-permitting coupled general circulation model. It is found that the asymmetric behavior is captured by the model with SST anomalies associated with strong El Niño events being greater than those associated with strong La Niña events. The pattern of the SST asymmetry also bears some similar characteristics to those based on observations despite the deficiency that SST anomalies associated with both El Niño and La Niña extend too far westward in the model.

Through a heat budget analysis of the ocean mixed layer, it is shown that nonlinear dynamic heating (NDH) is important in generating intense El Niño and the SST asymmetry between El Niño and La Niña events, especially in the eastern tropical Pacific Ocean. This nonlinear dynamic heating enhances the amplitude of El Niño and reduces the amplitude of La Niña, and therefore leads to the asymmetry between El Niño and La Niña events, with El Niño being stronger. However, the skewness and asymmetry in the model are relatively weak, being consistent with a relatively weak nonlinear dynamical heating. It is also shown that the eastward-propagating feature of subsurface anomalies provides a favorable phase relationship between temperature and current anomalies that results in strong nonlinear dynamical heating that tends to produce stronger El Niños. In addition, in the model simulation, the nonlinear nature of zonal wind stress anomalies between El Niño and La Niña events also plays an important role in the central tropical Pacific. These different mechanisms work constructively to determine the asymmetry between El Niño and La Niña events in the model, and they are similar to those proposed in recent studies based on observations. The ability of the model to simulate this asymmetric feature is encouraging and offers hope to the challenge of predicting the amplitude of strong El Niño events.
Seasonal Surface Air Temperature and Precipitation in the FSU Climate Model Coupled to the CLM2
Authors: Shin D. W. , Cocke S. , LaRow T. E. , O’Brien James J.
Published: September 2005

The current Florida State University (FSU) climate model is upgraded by coupling the National Center for Atmospheric Research (NCAR) Community Land Model Version 2 (CLM2) as its land component in order to make a better simulation of surface air temperature and precipitation on the seasonal time scale, which is important for crop model application. Climatological and seasonal simulations with the FSU climate model coupled to the CLM2 (hereafter FSUCLM) are compared to those of the control (the FSU model with the original simple land surface treatment). The current version of the FSU model is known to have a cold bias in the temperature field and a wet bias in precipitation. The implementation of FSUCLM has reduced or eliminated this bias due to reduced latent heat flux and increased sensible heat flux. The role of the land model in seasonal simulations is shown to be more important during summertime than wintertime. An additional experiment that assimilates atmospheric forcings produces improved land-model initial conditions, which in turn reduces the biases further. The impact of various deep convective parameterizations is examined as well to further assess model performance. The land scheme plays a more important role than the convective scheme in simulations of surface air temperature. However, each convective scheme shows its own advantage over different geophysical locations in precipitation simulations.
ENSO Suppression due to Weakening of the North Atlantic Thermohaline Circulation*
Authors: Timmermann A. , An S-I. , Krebs U. , Goosse H.
Published: September 2005

Changes of the North Atlantic thermohaline circulation (THC) excite wave patterns that readjust the thermocline globally. This paper examines the impact of a freshwater-induced THC shutdown on the depth of the Pacific thermocline and its subsequent modification of the El Niño–Southern Oscillation (ENSO) variability using an intermediate-complexity global coupled atmosphere–ocean–sea ice model and an intermediate ENSO model, respectively. It is shown by performing a numerical eigenanalysis and transient simulations that a THC shutdown in the North Atlantic goes along with reduced ENSO variability because of a deepening of the zonal mean tropical Pacific thermocline. A transient simulation also exhibits abrupt changes of ENSO behavior, depending on the rate of THC change. The global oceanic wave adjustment mechanism is shown to play a key role also on multidecadal time scales. Simulated multidecadal global sea surface temperature (SST) patterns show a large degree of similarity with previous climate reconstructions, suggesting that the observed pan-oceanic variability on these time scales is brought about by oceanic waves and by atmospheric teleconnections.
Treatment of Anterior Cruciate Ligament Injuries, Part I
Authors: Beynnon Bruce D. , Johnson Robert J. , Abate Joseph A. , Fleming Braden C. , Nichols Claude E.
Published: September 2005

Anterior cruciate ligament injuries are common among athletes. Although the true natural history remains unclear, anterior cruciate ligament injuries are functionally disabling; they predispose the knee to subsequent injuries and the early onset of osteoarthritis. This article, the first in a 2-part series, was initiated with the use of the PubMed database and a comprehensive search of articles that appeared between January 1994 to the present, using the keywords anterior cruciate ligament. A total of 3810 citations were identified and reviewed to determine the current state of knowledge about the treatment of these injuries. Articles pertaining to the biomechanical behavior of the anterior cruciate ligament, the prevalence of anterior cruciate ligament injury, the natural history of the anterior cruciate ligament–deficient knee, injuries associated with anterior cruciate ligament disruption, risk factors for anterior cruciate ligament injury, indications for treatment of anterior cruciate ligament injuries, and nonoperative and operative treatments were obtained, reviewed, and served as the basis for part I. Part II, to be presented in another issue of this journal, includes technical aspects of anterior cruciate ligament surgery, bone tunnel widening, graft healing, rehabilitation after reconstruction, and the effect of sex, age, and activity level on the outcome of surgery. Our approach was to build on prior reviews and to provide an overview of the literature for each of the before-mentioned areas of study by summarizing the highest level of scientific evidence available. For the areas that required a descriptive approach to research, we focused on the prospective studies that were available; for the areas that required an experimental approach, we focused on the prospective, randomized controlled trials and, when necessary, the highest level of evidence available. We were surprised to learn that considerable advances have been made during the past decade regarding the treatment of this devastating injury.
Study on Stiffness of Stitched Laminates
Authors: Gui Liang-Jin , Fan Zi-Jie , Li Zheng-Neng
Published: September 2005

An analytical model was developed to determine the effective elastic constants of stitched laminae. The effects of stitch parameters on effective elastic constants were analyzed by considering the nonuniformity and in-plan fiber waviness induced by stitching. Based on the model, the constitutive relationship of stitched laminates was presented and the effects of stitch parameters on stiffness of stitched laminates were investigated. Tension and compression tests were conducted to validate the predictions. The experimental results were in good agreement with predictions based on the analytical model.
The Effect of Environment on Tensile Properties of Stitched and Unstitched Laminates (with a Hole)
Authors: Chen Gang , Cheng Xiaoquan , Li Zhengneng , Kou Changhe
Published: September 2005

Tensile tests are conducted on stitched and unstitched uniweave T300/QY9512 laminates (with a hole) in hygrothermal environment and normal environment. It is shown that in a normal environment stitching reduces the tensile strength of laminates and does not significantly alter the open-hole tensile strength. The hygrothermal environment has a beneficial effect on the tensile strength of laminates and open-hole laminates, especially of stitched specimens. It is also noted that stitching direction has no effect on the tensile properties.
Thermoelastic Stresses in Composite Beams with Functionally Graded Layer
Authors: Nirmala K. , Upadhyay P. C. , Prucz J. , Loyns D.
Published: September 2005

Analytical expressions have been derived for the thermoelastic stresses in a threelayered composite beam system having a middle layer of functionally graded material (FGM). Continuous gradation of volume fraction in the FGM layer is taken in the form of the mth power of the coordinate axes in the thickness direction of the beam. Using a single algorithm, solutions for the beams with continuous gradation in the FGM layer of linear, quadratic, or cubic nature, can be obtained just by changing the value of ‘ m’. A numerical scheme of discretizing the continuous FGM layer (in sublayers) and treating the beam as a discretely graded structure has also been discussed. Appropriate expressions for the solution have been derived for the power law gradation (mth power) of the FGM layer. A discretized FGM layer scheme has been shown to give results practically matching with the results obtained analytically.
Origin of quartz cores in tourmaline from Roche Rock, SW England
Authors: Müller A. , Williamson B. J. , Smith M.
Published: September 2005

The nature and mode of origin of quartz-cored tourmalines (QCT) are studied from hydrothermal quartz veins within massive quartz-tourmaline (MQT) rocks at Roche, SW England. The QCT are annular, have blue maximum absorption colour and occur together with tourmalines with brown cores rimmed by blue tourmaline. Where the quartz core is not continuous throughout the length of the QCT crystals, the tourmaline core has brown maximum absorption colour, similar to tourmalines without quartz cores. Both the blue and brown tourmalines are schorl, but are compositionally distinct showing different Fe/(Mg + Ti) ratios and Ca concentrations. Fluid inclusion data indicate quartz precipitation from a moderate salinity (∼20–25 wt.% NaCl eq.) brine which periodically boiled following pressure drops within the vein system. The QCT show rheomorphic and lobate textures on their inner margins indicating selective dissolution of their brown, relative Mg-, Ti- and Ca-rich tourmaline cores and replacement with quartz. This presents a problem in terms of the nature of the fluid responsible for such selective dissolution because tourmaline is generally highly resistant under the normal range of hydrothermal fluid conditions. It is proposed that the relatively high concentrations of Ti, Mg and Ca in the brown tourmaline caused significant lattice strain, which together with an increase in pH, and probably Al, in the boiling hydrothermal fluid caused the brown cores to become unstable compared with the Fe-rich blue tourmaline rims.
Exsolution and hydration of pyroxenes from partially serpentinized harzburgites
Authors: Viti C. , Mellini M. , Rumori C.
Published: September 2005

Ortho- and clinopyroxenes within partially-hydrated harzburgites from Elba and Val di Cecina (Italy) show lamellar exsolution textures and variable replacement by biopyriboles, talc-chlorite-serpentine mixed layers and serpentine. Chemical and geothermometric data suggest that the pyroxenes crystallized at 1240–1051°C, followed by subsolidus exsolution at slightly lower T (1145–1025°C for clinopyroxene lamellae + orthopyroxene matrix pairs and a 1033–982°C range for orthopyroxene lamellae + clinopyroxene matrix pairs).

Investigation by transmission electron microscopy of exsolved enstatite and augite reveals a multistage hydration process. The first stage (highest T, probably in the amphibole stability field) leads to the formation of biopyribole lamellae within exsolved augite, leaving the enstatite matrix unaffected. The second stage (~500–300°C) corresponds to the topotactic replacement of enstatite by layer silicates (talc + chlorite + serpentine, with (001)layer silicates parallel to (100)enstatite). Enstatite is also replaced by randomly oriented, poorly crystalline serpentine. The last hydration stage (<300°C) corresponds to the disappearence of augite and recrystallization of serpentine, leading to completely hydrated bastites with random lizardite lamellae, polygonal serpentine and minor chrysotile.
Microdiamonds, their classification and tectonic implications for the host eclogites from the Dabie and Su-Lu regions in central eastern China
Authors: Xu Shutong , Liu Yican , Chen Guanbao , Ji Shouyuan , Ni Pei , Xiao Wanshen
Published: September 2005

We have found >10 in situ microdiamonds in thin sections of eclogites from the Dabie and Su-Lu regions of central eastern China since the first occurrence of microdiamond in eclogites from the Dabie Mountains (DMT) reported in 1992. The microdiamonds are found not only in the central part but also in the northern part of the DMT. Several free crystals have been recovered from the crushed eclogites from the central DMT. Most in situ microdiamonds are inclusions in garnets but a few larger ones are intergranular. Most of the diamondiferous eclogites in the central part of the DMT are associated with coesite. Most importantly, the observation of microdiamonds in northern Dabie lead us to question the supposition that this is a low-P metamorphic terrane. All the diamondiferous eclogites from both the north and central DMT are of continental affinity as demonstrated by their negative εNd values. Therefore, both the north and central eclogite belts in the DMT are considered to be from the deep subducted terrane. Five in situ microdiamonds and two free crystals are first reported in this paper. The dimensions of the in situ microdiamonds are 30–180 µm and the free crystals are up to 400–700 mm across. All the microdiamonds are confirmed as such by Raman spectroscopy. The results of an infrared spectroscopic investigation on two larger free crystals and two in situ microdiamonds show that all the microdiamonds from both the Dabie and Su-Lu regions are mixed types IaA and IaB diamonds and there is no indication of any synthetic microdiamonds in our samples because such synthetic microdiamonds are always rich in type Ib.
Sudden blastic transformation in patients with chronic myeloid leukemia treated with imatinib mesylate
Authors: Jabbour Elias , Kantarjian Hagop , O'Brien Susan , Rios Mary Beth , Abruzzo Lynne , Verstovsek Srdan , Garcia-Manero Guillermo , Cortes Jorge
Published: September 2005

Sudden blastic transformation (SBT) has been reported in 0.5% to 2.5% of patients treated with interferon-α (IFN-α) during the first 3 years of therapy. Imatinib is now standard therapy for patients with chronic myeloid leukemia in chronic phase. We investigated the occurrence of SBT among patients treated with imatinib. Among 541 patients treated with imatinib in chronic phase, 23 developed blast phase, which was of sudden onset (ie, occurring in patients previously in complete cytogenetic remission) in 4 patients (17%; 0.7% of the total), 2 lymphoid and 2 myeloid. Patients with SBT were found to have low-risk features more often at the time of presentation and had achieved optimal response with imatinib. Three of the 4 patients underwent allogeneic stem cell transplantation and achieved a molecular remission. SBT is still a rare event, probably less common than that observed with IFN-α therapy. Continuous monitoring of patients treated with imatinib is mandatory.
A soluble tissue factor-annexin V chimeric protein has both procoagulant and anticoagulant properties
Authors: Huang Xin , Ding Wei-Qun , Vaught Joshua L. , Wolf Roman F. , Morrissey James H. , Harrison Roger G. , Lind Stuart E.
Published: September 2005

Tissue factor (TF) initiates blood coagulation, but its expression in the vascular space requires a finite period of time. We hypothesized that targeting exogenous tissue factor to sites of vascular injury could lead to accelerated hemostasis. Since phosphatidylserine (PS) is exposed on activated cells at sites of vascular injury, we cloned the cDNA for a chimeric protein consisting of the extracellular domain of TF (called soluble TF or sTF) and annexin V, a human PS-binding protein. Both the sTF and annexin V domains had ligand-binding activities consistent with their native counterparts, and the chimera accelerated factor X activation by factor VIIa. The chimera exhibited biphasic effects upon blood coagulation. At low concentrations it accelerated blood coagulation, while at higher concentrations it acted as an anticoagulant. The chimera accelerated coagulation in the presence of either unfractionated or low-molecular-weight heparins more potently than factor VIIa and shortened the bleeding time of mice treated with enoxaparin. The sTF-annexin V chimera is a targeted procoagulant protein that may be useful in accelerating thrombin generation where PS is exposed to the vasculature, such as may occur at sites of vascular injury or within the vasculature of tumors.
Dicistronic MLV-retroviral vectors transduce neural precursors in vivoand co-express two genes in their differentiated neuronal progeny
Authors: Derrington Edmund A , López-Lastra Marcelo , Darlix Jean-Luc
Published: September 2005

Dicistronic MLV-based retroviral vectors, in which two IRESes independently initiate the translation of two proteins from a single RNA, have been shown to direct co-expression of proteins in several cell culture systems. Here we report that these dicistronic retroviral vectors can drive co-expression of two gene products in brain cells in vivo. Injection of retroviral vector producer cells leads to the transduction of proliferating precursors in the external granular layer of the cerebellum and throughout the ventricular regions. Differentiated neurons co-expressing both transgenes were observed in the cerebellum and in lower numbers in distant brain regions such as the cortex. Thus, we describe an eukaryotic dicistronic vector system that is capable of transducing mouse neural precursors in vivo and maintaining the expression of genes after cell differentiation.