bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac resynchronization therapy in patients with heart failure and conduction abnormalities other than left bundle‐branch block: Analysis of the multicenter insync randomized clinical evaluation (MIRACLE)
Authors: Aranda Juan M. , Conti Jamie B. , Johnson James W. , Petersen‐Stejskal Susan , Curtis Anne B.
Published: June 2007

Background:Cardiac resynchronization therapy (CRT) has been proposed as a treatment for patients with congestive heart failure (CHF) and prolonged QRS durations. Previous studies have predominantly included patients with left bundle‐branch block (LBBB). The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) investigators assessed the efficacy of CRT in patients with CHF with QRS durations > 130 ms and found that CRT lead to improvement in several measures of functional capacity and exercise tolerance.

Hypothesis:We designed this retrospective study to determine whether patients with CHF who have conduction abnormalities other than LBBB also respond favorably to CRT.

Methods:We divided patients enrolled in the MIRACLE trial into three subgroups according to conduction abnormality ‐ LBBB, right bundle‐branch block (RBBB), and nonspecific interventricular conduction delay (IVCD) ‐ and compared the response among and within these groups to CRT or no CRT at baseline and 6‐months' follow‐up.

Results:We found 313 patients with LBBB, 43 with RBBB, and 35 with IVCD. When they received CRT, significant improvement was achieved in functional class (p = 0.001) by patients with RBBB, and in quality of life (p = 0.038) by patients with IVCD. Patients in the RBBB and IVCD groups showed improvement in exercise time and peak oxygen consumption after CRT. Most patients with RBBB (82%) also had either left anterior fascicular block or left posterior fascicular block.

Conclusions:Patients with CHF with RBBB and IVCD do benefit from CRT. Improvement with CRT in patients with RBBB may be due to concomitant left‐sided conduction abnormalities. Further subgroup analyses of other CRT trials are necessary to validate these results.
Markers of myocardial reperfusion as predictors of left ventricular function recovery in acute myocardial infarction treated with primary angioplasty
Authors: Bellandi Francesco , Leoncini Mario , Maioli Mauro , Toso Anna , Gallopin Michela , Dabizzi Roberto Piero
Published: June 2007

Background:Myocardial blush grade (MBG), corrected TIMI frame count (cTFC), and ST‐segment reduction are indices of myocardial reperfusion.

Hypothesis:We evaluated their predictive value for left ventricular (LV) function recovery by gated single‐photon emission computed tomography (SPECT) after acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI).

Methods:In 40 patients with AMI, gated SPECT was performed at admission and repeated 7 and 30 days after PCI. Left ventricular function recovery was defined as an increase ≥ 10 points in SPECT LV ejection fraction from baseline to 1 month. The MBG, cTFC, and ST‐segment elevation index 1 h after PCI were determined to evaluate reperfusion.

Results:Twenty‐four patients (Group 1) had LV function recovery and 16 (Group 2) did not. A significant correlation was found between LV function recovery and MBG (r = 0.66; p=0.0001), and ST‐segment elevation index at 1 h(r=−0.55; p = 0.0001), but not with cTFC. Univariate predictors of LV function recovery were MBG (p = 0.0003) and ST‐segment elevation index 1 h after intervention (p = 0.0026), but not cTFC. In a multivariate analysis, MBG was the only predictor of LV function recovery. Myocardial blush grade ≥ 2 and ST‐segment elevation index reduction had the same accuracy (88%) for predicting LV function recovery. Lower accuracy (75%) was shown by fast cTFC (< 23 frames). Myocardial blush grade ≥ 2 showed the better negative likelihood ratio, and ST‐segment elevation index reduction had the higher positive likelihood ratio in predicting LV function recovery.

Conclusions:Myocardial blush grade was the best parameter for prediction of LV function recovery: MBG ≥ 2 and ST‐segment elevation index reduction showed good accuracy in predicting LV function recovery. The cTFC failed to be a significant predictor.
Long‐term effects of acute pulmonary embolism on echocardiographic doppler indices and functional capacity
Authors: Ciurzyński M. , Kurzyna M. , Bochowicz A. , Lichodziejewska B. , Liszewska‐Pfejfer D. , Pruszczyk P. , Torbicki A.
Published: June 2007

Background and hypothesis:Hemodynamic and functional consequences of acute pulmonary embolism (APE) are believed to be reversible with antithrombotic treatment. To verify this hypothesis, we reassessed our patients at least 1 year after an episode of APE.

Methods:We compared echo Doppler indices and 6‐min walking test parameters (6‐MWT) of 36 patients (13 men, 23 women, age 66 ± 11 years), studied on average 3.1 ± 2.2 years after an acute episode of pharmacologically treated massive or submassive APE, with data of 30 age‐matched subjects (12 men, 18 women, age 67 ± 12 years).

Results:At least 1 year after APE, right ventricular (RV) diameter remained increased in patients compared with controls (27 ± 2 vs. 23 ± 2 mm, p < 0.001). Also, acceleration time of pulmonary ejection (AcT) was markedly shorter (97 ± 19 vs. 123 ± 19 ms, p < 0.001) and the diameter of the pulmonary trunk was significantly larger in patients than in controls (21 ± 2.6 vs. 18 ± 2.2, p < 0.001). Although the mean value of the tri‐cuspid valve peak systolic gradient (TVPG) in the APE group at follow‐up was similar to that in controls, TVPG > 30 mmHg was recorded in three patients with APE (8.3%). There was no difference in the distance of 6‐MWT between both groups; however, the mean desaturation after 6‐MWT was higher in the APE group than in controls (3.04 ± 2.08 vs. 1.45 ± 0.69%, p = 0.0005).

Conclusions:Pharmacologic treatment of acute pulmonary embolism does not prevent mild persistent changes in morphology and function of the cardiovascular system. Despite normalization of pulmonary artery systolic pressure and similar exercise capacity, survivors of APE present signs suggesting RV dysfunction and/or its disturbed coupling to the pulmonary arterial bed, as well as ventilation to perfusion mismatch at exertion persisting long after the acute embolic episode.
Tissue factor activities of streptozotocin induced diabetic rat tissues and the effect of peanut consumption
Authors: Emekli‐Alturfan Ebru , Kasikci Emel , Yarat Aysen
Published: June 2007

Background

Tissue factor (TF) is considered to be a major regulator of normal haemostasis and thrombosis. Circulating TF activity is suggested to be associated with diabetes mellitus. Various tissues and body fluids have TF activity. The aim of the present study was to investigate the TF activity of streptozotocin (STZ) induced diabetic rat tissues. Peanut consumption is reported to be associated with decreased risk of type 2 diabetes. Therefore, the effect of peanut consumption on the TF activity of STZ induced diabetic rat tissues, and haemostatic parameters such as protrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen levels were determined.

Methods

Twenty‐four Wistar rats were divided into 3 groups of 8 rats each as control, STZ‐induced diabetic and diabetic + peanut group. Twelve weeks later, TF activity of liver, kidney, spleen, heart, kidney, lung, pancreas and aorta and haemostatic parameters were determined.

Results

In the diabetic group, TF activities of liver, kidney and spleen increased (p < 0.01) whereas the TF activity of brain decreased (p < 0.01) compared to the control group. Peanut consumption in the diabetic group decreased the TF activity of spleen and aorta (p < 0.01; p < 0.05). Haemostatic parameters did not change significantly in the groups.

Conclusion

Elevated TF activity in diabetic rat tissues, may contribute to the increased risk of atherothrombotic disease that accompanies the diabetic complications whereas the decreased brain TF activity may be due to a different haemostatic mechanism to protect this vital organ from the diabetic status. The decreased TF activity of peanut given diabetic rat tissues might protect these tissues from the risk of thrombosis. Copyright © 2007 John Wiley & Sons, Ltd.
ISEE: Internet‐based Simulation for Earthquake Engineering—Part II: The application protocol approach
Authors: Wang Kung‐Juin , Tsai Keh‐Chyuan , Wang Shiang‐Jung , Cheng Wei‐Choung , Yang Yuan‐Sen
Published: June 2007

This paper develops new techniques for integrating a number of different structural laboratories together through the Internet in order to jointly conduct a single structural experiment. A computer‐networking platform, called Platform for Networked Structural Experiments (PNSE), was developed to achieve this goal. PNSE runs directly on top of the Transmission Control Protocol/Internet Protocol (TCP/IP). It is a multi‐client system consisting of a number of client programs, which include one command
generation program and a number of facility control programs, connected to a server program via TCP point‐to‐point connections across the Internet. An associated application protocol, called Networked Structural Experiment Protocol (NSEP), was developed to work with the PNSE. In addition to communication rules, the NSEP defines general experimental information, significant laboratory events, commands and signals, as well as obligated behaviours of all PNSE programs. Both domestic and transnational pseudo‐dynamic (PSD) tests were performed to verify the validity and efficiency of the PNSE. Test results showed that on the PNSE: signals were correctly transmitted; significant laboratory events were promptly reflected; and data transmission was remarkably efficient, with the round‐trip time (RTT) between Taiwan and the United States less than 0.1701 s. The characteristic of environment independency was also demonstrated through the successful collaboration of different facility control programs running on different operating systems. Copyright © 2007 John Wiley & Sons, Ltd.
Material order‐independent interface reconstruction using power diagrams
Authors: Schofield Samuel P. , Garimella Rao V. , Francois Marianne M. , Loubère Raphaël
Published: June 2007

We have developed a new, multi‐material, piecewise linear interface reconstruction method that correctly locates the position of each material in the mesh cell and matches the required volume fractions with no material ordering required. This is different from other volume tracking interface reconstruction methods in which an improper material ordering may result in materials being incorrectly located within the cell. The new method utilizes a type of weighted Voronoi diagram, known as a power diagram, to reconstruct the interface from approximate material locations derived either from a particle model or quadrature formula. It works on structured and general polygonal grids, for an arbitrary number of materials and can be naturally extended to three dimensions. Published in 2007 by John Wiley & Sons, Ltd.
On the effects of a compressible viscous lubricant on the load‐bearing capacity of a journal bearing
Authors: Bollada P. C. , Phillips T. N.
Published: June 2007

A compressible viscous isothermal model is presented for studying journal‐bearing lubrication. The viscosity in the model thickens with increasing density. The governing equations are written in terms of velocity, the natural logarithm of the density and the kinematic extra‐stress tensor. A semi‐Làgrangian treatment of the material derivatives is combined with a spectral element discretization in space. The roles of the speed of sound and the eccentricity ratio on the load‐bearing capacity of the journal bearing are investigated. Compressibility is shown to enhance the load‐bearing capacity and this effect is amplified as the eccentricity ratio approaches unity. It is shown that for speeds of sound in the region of those of multigrade oils, the dominant component of the force on the journal acts along the line joining the centres of the bearing and journal and in the direction away from the narrow gap. Copyright © 2007 John Wiley & Sons, Ltd.
Instability of the separated shear layer in flow past a cylinder: Forced excitation
Authors: Mittal Sanjay
Published: June 2007

The receptivity of the separated shear layer for Re = 300 flow past a cylinder is investigated by forced excitation via an unsteady inflow. In order to isolate the shear layer instability, a numerical experiment is set up that suppresses the primary wake instability. Computations are carried out for one half of the cylinder, in two dimensions. The flow past half a cylinder with steady inflow is found to be stable for Re = 300. However, an inlet flow with pulsatile perturbations, of amplitude 1% of the mean, results in the excitation of the shear layer mode. The frequency of the perturbation of the inlet flow determines the frequency associated with the shear layer vortices. For a certain range of forced frequencies the recirculation region undergoes a low‐frequency longitudinal contraction and expansion. An attempt is made to relate this instability to a global mode of the wake determined from a linear stability analysis. Interestingly, this phenomenon disappears when the outflow boundary of the computational domain is shifted sufficiently downstream. This study demonstrates the need of carefully investigating the effect of the location of outflow
boundaries if the computational results indicate the presence of low‐frequency fluctuations. The effect of Re and amplitude of unsteadiness at the inlet are also presented. All computations have been carried out using a stabilized finite element formulation of the incompressible flow equations. Copyright © 2007 John Wiley & Sons, Ltd.
Optimisation of Manufacturing Parameters for an Ni–Ag Fuel Cell Electrode
Authors: Pishbin M. H. , Mohammadi A. R. , Nasri M.
Published: June 2007

The aim of this research is to optimise manufacturing parameters for a fuel cell electrode. The combination of nickel oxide, silver oxide and ammonium bicarbonate powders is used to produce the electrode. The main role of silver element is to increase the activity in the electrode. Ni–Ag electrode can be used in fuel cells as positive and negative electrodes. All powders are mixed in the benzene solution by a magnetic mixer and then compressed to form green electrode. The range of pressure in this step is between 40 and 160 MPa. The green electrode is sintered in hydrogen atmosphere through a tube furnace and then cooled to 200 °C under argon atmosphere. The range of sintering temperature and time is 500–800 °C and 10–60 min, respectively. Also, silver oxide and ammonium bicarbonate percentages are varied from 20 to 65 and 15 to 35%, respectively. All parameters including composition, pressure, sintering temperature and time are changed during electrode fabrication to achieve optimised properties in the electrode. So, it is necessary to perform several tests measuring porosity, surface area, density, weight loss, mechanical strength, shrinkage, exchange current density and metallographic photos.

The optimum conditions of the electrode production resulting from this investigation include compacting pressure 60 MPa, sintering temperature 560 °C, sintering time 15 min, silver oxide percentage 50% and ammonium bicarbonate percentage 27%.
Long‐term site formation processes at the natural springs Nadaouiyeh and Hummal in the El Kowm Oasis, Central Syria
Authors: Tensorer Jean‐Marie Le , Jagher Reto , Rentzel Philippe , Hauck Thomas , Ismail‐Meyer Kristin , Pümpin Christine , Wojtczak Dorota
Published: June 2007

The El Kowm oasis in the desert steppe of Central Syria is one of the oldest settlement centers in the Middle East and is significant worldwide for its great density of Paleolithic sites. About 180 open‐air sites dating between about one million and 10,000 years ago testify that humans regularly resided at or near the springs. The region represents a unique archive where the long‐term cultural history and the development of the landscape can be observed. The sites of Nadaouiyeh and Hummal are the main focus of our research. Geoarchaeological studies on both sites have defined the formation of different sediment types, such as limnic, littoral, and terrestrial deposits. Those sediments provide evidence of eolian processes, but also post‐depositional transformations like the precipitation of silica or pedogenesis. Additional archaeological layers give answers concerning the depositional environment, anthropogenic influence, and post‐sedimentary changes. © 2007 Wiley Periodicals, Inc.
The correlation between Hamra and the Paleolithic on the Coastal Plain of the Southern Levant
Authors: Laukhin Stanislav A. , Ranov Vadim A. , Volgina Valerya A.
Published: June 2007

Fieldwork and literature studies indicate that Paleolithic sites of the coastal plain in the Southern Levant were connected with climatic changes and transgressive‐regressive cycles of the Mediterranean Sea. The presence of archaeological sites corresponds with periods of regressions, during which hamra (a local variety of red soils) formed and was subsequently reworked by slope processes. When the hamra was inundated by shallow lakes, people could settle on the lake shores. Six types of connections have been documented between Paleolithic sites and hamra pedocomplexes. © 2007 Wiley Periodicals, Inc.
The impact of geology and geomorphology on cave and rockshelter archaeological site formation, preservation, and distribution in the Zagros mountains of Iran
Authors: Heydari Saman
Published: June 2007

This paper is a first attempt to explore the impact of geological and geomorphological settings on formation processes of shelter sites in the karstic Zagros Mountains of Iran. In general, the Zagros Mountains can be divided geologically and geomorphologically into two main zones, highland and folded, which are located parallel to each other and run from the northeast to the southwest in western Iran. Both the geological and geomorphological zones have implications for the formation processes of archaeological deposits at shelter sites. These environmental differences also influence the preservation of archaeological deposits at these types of sites. It is suggested that apart from site formation and post‐depositional processes, the local geological and geomorphological structure might also have had some influence on the distribution of prehistoric sites in the region. © 2007 Wiley Periodicals, Inc.
Advantages and limitations of thermoluminescence dating of heated flint from Paleolithic sites
Authors: Richter Daniel
Published: June 2007

Thermoluminescence (TL) dating is now widely used in the age determination of Paleolithic sites. Although the basic principle of TL‐dating is simple, the underlying assumptions are not trivial. One major source of error is the external dose rate, which contributes to a varying degree to the denominator of the age formula and thus has a varying influence on the dating result. The intention of this paper is to enable the user to evaluate TL age determinations of heated flint. The parameters used for age determination and some of their relationships are discussed. It is shown that the reliability of TL results of heated flint depends on the proportion of the various dose‐rate parameters and that these are important for the evaluation of ages. The limitations of the method as well as the advantages are discussed. TL‐dating results for two Near Eastern Paleolithic sites (Rosh Ein Mor and Jerf al‐Ajla) are discussed as examples. © 2007 Wiley Periodicals, Inc.
Transcriptional regulation of scar gene expression in primary astrocytes
Authors: Gris Paul , Tighe Allyson , Levin David , Sharma Rahul , Brown Arthur
Published: June 2007

The failure of the adult injured spinal cord to support axonal regeneration is in part attributed to the glial scar. Reactive astrocytes constitute a major cellular component of the glial scar and are heterogeneous with respect to the extracellular matrix proteins that they secrete. Astrocytes may produce antiregenerative molecules such as chondroitin sulphate proteoglycans (CSPGs) or proregenerative molecules such as laminin and fibronectin. While many different CSPGs are expressed after spinal cord injury (SCI) they all rely on the same enzymes, xylosyltransferase‐I and ‐II (XT‐I, XT‐II) and chondroitin 4‐sulfotransferase (C4ST) to add the repulsive chondroitin sulfate side chains to their core proteins. We show that XT‐I, XT‐II, and C4ST are part of a CSPG biosynthetic gene (CBG) battery. Using primary astrocyte cultures and quantitative PCR we demonstrate that TGFβ2, PDGF, and IL‐6 induce the expression of CBGs, laminin and fibronectin by several‐fold. We further show that over‐expression of the transcription factor SOX9 also strongly induces the expression of CBGs but does not increase the expression of laminin or fibronectin. Correspondingly, SOX9 knock‐down in primary astrocytes causes a decrease in CBG and an increase in laminin and fibronectin mRNA levels. Finally, we show that the in vivo expression profiles of TGFβ2, PDGF, IL‐6, and SOX9 are consistent with their potential roles in differentially regulating CBGs, laminin and fibronectin gene expression in the injured spinal cord. This work suggests that SOX9 levels may be pivotal in determining the balance of pro‐ and anti‐regenerative extracellular matrix molecules produced by astrocytes. © 2007 Wiley‐Liss, Inc.
Correlation between motor and phosphene thresholds: A transcranial magnetic stimulation study
Authors: Deblieck Choi , Thompson Benjamin , Iacoboni Marco , Wu Allan D.
Published: June 2007

Transcranial magnetic stimulation (TMS) has become a common tool for the brain mapping of a wide variety of cognitive functions. Because TMS over cortical regions of interest other than motor cortex often does not produce easily observable effects, the ability to calibrate TMS intensity for stimulation over nonmotor regions can be problematic. Previous studies reported no correlation between motor thresholds (MT) over the motor cortex and phosphene thresholds (PT) over the visual cortex. However, different thresholding methods, lighting, and eye‐closure conditions were used to determine MT and PT. We investigated the correlation between resting MT (rMT), active MT (aMT), and PT in 27 dark‐adapted healthy volunteers. All thresholds were measured with eyes‐open in the dark and determined by gradually reducing stimulation intensity downward. All subjects had aMT and rMT; 21 subjects had measurable PT. rMT was 70.4% ± 9.8% (mean ± SD of maximum stimulator output); aMT was 61.1% ± 7.9%; PT was 82.2% ± 10.1%. A significant positive correlation was found between aMT and PT (r = 0.53; P = 0.014) with a trend toward correlation between rMT and PT (r = 0.43; P = 0.052). Our results suggest that sensitivity to TMS over visual and motor cortices may be correlated under similar thresholding procedures. They also provide a rationale for the use of easily obtained aMT to calibrate TMS intensities in brain mapping studies that employ TMS in cortical regions besides motor cortex. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
A comparison of brain activation patterns during covert and overt paced auditory serial addition test tasks
Authors: Forn Cristina , Ventura‐Campos Noelia , Belenguer Antonio , Belloch Vicente , Parcet Maria Antònia , Ávila César
Published: June 2007

The Paced Auditory Serial Addition test (PASAT) is a sensitive task for evaluating cognitive impairment in patients with diffuse brain disorders, such as multiple sclerosis patients. Brain areas involved in this task have been investigated in diverse fMRI studies using different methodologies to control the subjects' responses during scanning. Here, we examined the possible differences between overt and covert responses during the PASAT task in 13 volunteers. Results showed similar activations in parietal and frontal brain areas during both versions of the task. The contrast between the two conditions (overt and covert) indicated that differences in these two methodologies were minimal. Unlike the covert condition, the overt version of the task obtained significant activations in the left superior and inferior frontal gyrus, bilateral occipital cortex, caudate nucleus and cerebellum. As expected, no significant overactivations were observed in the covert when compared with the overt condition. Discussion focuses on the lower cost of using verbal responses to monitor performance during the PASAT task, which might be generalisable to other frontal lobe tasks requiring discrete responses. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Developmental differences in white matter architecture between boys and girls
Authors: Schmithorst Vincent J. , Holland Scott K. , Dardzinski Bernard J.
Published: June 2007

Previous studies have found developmental differences between males and females in brain structure. During childhood and adolescence, relative white matter volume increases faster in boys than in girls. Sex differences in the development of white matter microstructure were investigated in a cohort of normal children ages 5–18 in a cross‐sectional diffusion tensor imaging (DTI) study. Greater fractional anisotropy (FA) in boys was shown in associative white matter regions (including the frontal lobes), while greater FA in girls was shown in the splenium of the corpus callosum. Greater mean diffusivity (MD) in boys was shown in the corticospinal tract and in frontal white matter in the right hemisphere; greater MD in girls was shown in occipito‐parietal regions and the most superior aspect of the corticospinal tract in the right hemisphere. Significant sex–age interactions on FA and MD were also shown. Girls displayed a greater rate of fiber density increase with age when compared with boys in associative regions (reflected in MD values). However, girls displayed a trend toward increased organization with age (reflected in FA values) only in the right hemisphere, while boys displayed this trend only in the left hemisphere. These results indicate differing developmental trajectories in white matter for boys and girls and the importance of taking sex into account in developmental DTI studies. The results also may have implications for the study of the relationship of brain architecture with intelligence. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Atorvastatin lowers portal pressure in cirrhotic rats by inhibition of RhoA/Rho-kinase and activation of endothelial nitric oxide synthase
Authors: Trebicka Jonel , Hennenberg Martin , Laleman Wim , Shelest Nataliya , Biecker Erwin , Schepke Michael , Nevens Frederik , Sauerbruch Tilman , Heller Jörg
Published: June 2007

In cirrhosis, increased RhoA/Rho-kinase signaling and decreased nitric oxide (NO) availability contribute to increased intrahepatic resistance and portal hypertension. Hepatic stellate cells (HSCs) regulate intrahepatic resistance. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) inhibit synthesis of isoprenoids, which are necessary for membrane translocation and activation of small GTPases like RhoA and Ras. Activated RhoA leads to Rho-kinase activation and NO synthase inhibition. We therefore investigated the effects of atorvastatin in cirrhotic rats and isolated HSCs. Rats with secondary biliary cirrhosis (bile duct ligation, BDL) were treated with atorvastatin (15 mg/kg per day for 7 days) or remained untreated. Hemodynamic parameters were determinedin vivo(colored microspheres). Intrahepatic resistance was investigated inin situperfused livers. Expression and phosphorylation of proteins were analyzed by RT-PCR and immunoblots. Three-dimensional stress-relaxed collagen lattice contractions of HSCs were performed after incubation with atorvastatin. Atorvastatin reduced portal pressure without affecting mean arterial pressurein vivo. This was associated with a reduction in intrahepatic resistance and reduced responsiveness ofin situ–perfused cirrhotic livers to methoxamine. Furthermore, atorvastatin reduced the contraction of activated HSCs in a 3-dimensional stress-relaxed collagen lattice. In cirrhotic livers, atorvastatin significantly decreased Rho-kinase activity (moesin phosphorylation) without affecting expression of RhoA, Rho-kinase and Ras. In activated HSCs, atorvastatin inhibited the membrane association of RhoA and Ras. Furthermore, in BDL rats, atorvastatin significantly increased hepatic endothelial nitric oxide synthase (eNOS) mRNA and protein levels, phospho-eNOS, nitrite/nitrate, and the activity of the NO effector protein kinase G (PKG).Conclusion:In cirrhotic rats, atorvastatin inhibits hepatic RhoA/Rho-kinase signaling and activates the NO/PKG-pathway. This lowers intrahepatic resistance, resulting in decreased portal pressure. Statins might represent a therapeutic option for portal hypertension in cirrhosis. (HEPATOLOGY 2007;46:242–253.)
Posterior parahippocampal place learning in H.M.
Authors: Bohbot Véronique D. , Corkin Suzanne
Published: June 2007

In a previous experiment with patients who had undergone unilateral temporal thermocoagulation lesions to alleviate intractable epilepsy, we demonstrated that the right parahippocampal cortex was critical for the performance of a spatial memory task (Bohbot et al. (1998) Neuropsychologia 36:1217–1238). Based on this evidence, we predicted that H.M., whose caudal parahippocampal cortex was structurally intact (Corkin et al. (1997) J Neurosci 17:3964–3979), would be able to learn the spatial memory task. This task was designed to be a human analogue of the Morris water maze in that it measured participants' ability to learn the location of a target, which was an invisible weight sensor placed under a carpet (Bohbot et al. (1998) Neuropsychologia 36:1217–1238). H.M. was first tested with the sensor under a small carpet (162 cm × 150 cm). Then, interspersed with the first sensor location, he was tested with the sensor in a second location, covered by a larger carpet (250 cm × 210 cm). He found the second target location in a direct path on only 10% of the trials. In contrast, when tested on the first sensor location, he walked directly toward the center of the testing area in 19/35 trials and from there found the sensor in a direct path on 15 of the 19 trials (80%). The number of direct hits at the first target location was significantly greater than chance (P< 0.0005). An analysis of H.M.'s paths showed that they were characteristic of fast learning, and that he did not rely on egocentric, short‐term, or working memory strategies to learn the task. H.M's ability to locate the sensor is remarkable given his severe amnesia and his inability to explicitly recollect the testing episode. These findings underscore the role of the parahippocampal cortex in spatial memory. © 2007 Wiley‐Liss, Inc.
Cohesiveness of spatial and directional representations recorded from neural ensembles in the anterior thalamus, parasubiculum, medial entorhinal cortex, and hippocampus
Authors: Hargreaves Eric L. , Yoganarasimha D. , Knierim James J.
Published: June 2007

Anatomical and physiological evidence suggests that hippocampal place cells derive their spatial firing properties from the medial entorhinal cortex (MEC) and other parahippocampal areas that send spatial and directional input to the MEC. MEC neurons fire in a precise, geometric pattern, forming a hexagonal grid that tessellates the surface of environments. Similar to place cells and head direction cells, the orientation of grid cell firing patterns can be controlled by visual landmarks, but the cells maintain their firing patterns even in the dark. Place cells and head direction cells can also completely decouple from external landmarks in the light, but it is not known whether the MEC and parahippocampal regions exhibit similar properties or are more explicitly tied to external landmarks. We recorded neurons in the MEC, parasubiculum, and CA1 and head direction cells of the anterior thalamus as the rat's internal direction sense was pitted against a salient visual landmark by slowly rotating the rat in a covered bucket while counter‐rotating the visual cue. In different sessions, spatial firing rate maps and head direction tuning curves either rotated their preferred firing locations/directions by the same amount as the bucket rotation or maintained their preferences in the external laboratory framework. In few cases, the firing preferences rotated with the cue card. When cells from different regions were recorded simultaneously, the dominant response in one area almost always matched the response of the other areas. Although dominant responses were consistent throughout the recording regions, CA1 ensembles exhibited a greater degree of response heterogeneity than other regions, which nearly all exhibited internally consistent responses. Thus, the parahippocampal and MEC input to the hippocampus can be controlled by the animal's internal direction sense (presumably reflected in the firing of head direction cells) and become completely decoupled from external sensory input, yet maintain internal coherence with each other and in general with the place cell system of the hippocampus. © 2007 Wiley‐Liss, Inc.
Hippocampal and neocortical interactions during context discrimination: Electrophysiological evidence from the rat
Authors: Mizumori Sheri J.Y. , Smith David M. , Puryear Corey B.
Published: June 2007

There is substantial evidence that hippocampus plays an important role in the processing of contextual information. Its specific role, however, remains unclear. One possibility is that single hippocampal neurons represent context information so that local circuits can construct representations of the current context, and the context that is expected based on past experience. Population codes derived from input by multiple local circuits may then engage match–mismatch algorithms that compare current and expected context information to determine the extent to which an expected context has changed. The results of such match–mismatch comparisons can be used to discriminate contexts. When context changes are detected, efferent messages may be passed on to connected neocortical areas so that informed “decisions” regarding future behavioral and cognitive strategies can be made. Here, a brief review describes evidence that a primary consequence of hippocampal processing is the discrimination of meaningful contexts. Then, the functional significance of neocortical circuits that likely receive hippocampal output messages are described in terms of their contribution to the control of ongoing behavioral and cognitive strategy, especially during active navigation. It is clear from this systems view that studies of spatial navigation continue to provide researchers with an excellent model of hippocampal–neocortical interactions during learning. © 2007 Wiley‐Liss, Inc.
Space and context in the temporal cortex
Authors: Bilkey David K.
Published: June 2007

The hippocampus has a critical role in certain kinds of spatial memory processes. Hippocampal “place” cells, fire selectively when an animal is in a particular location within the environment. It is thought that this activity underlies a representation of the environment that can be used for memory‐based spatial navigation. But how is this representation constructed and how is it “read”? A simple mechanism, based on place field density across an environment, is described that could allow hippocampal representations to be “read” by other brain regions for the purpose of navigation. The possible influence of activity in neighboring brain regions such as the perirhinal cortex, and pre‐ and para‐subiculum on the construction of the hippocampal spatial representation is then discussed. © 2007 Wiley‐Liss, Inc.
An oscillatory interference model of grid cell firing
Authors: Burgess Neil , Barry Caswell , O'Keefe John
Published: June 2007

We expand upon our proposal that the oscillatory interference mechanism proposed for the phase precession effect in place cells underlies the grid‐like firing pattern of dorsomedial entorhinal grid cells (O'Keefe and Burgess (2005) Hippocampus 15:853–866). The original one‐dimensional interference model is generalized to an appropriate two‐dimensional mechanism. Specifically, dendritic subunits of layer II medial entorhinal stellate cells provide multiple linear interference patterns along different directions, with their product determining the firing of the cell. Connection of appropriate speed‐ and direction‐ dependent inputs onto dendritic subunits could result from an unsupervised learning rule which maximizes postsynaptic firing (e.g. competitive learning). These inputs cause the intrinsic oscillation of subunit membrane potential to increase above theta frequency by an amount proportional to the animal's speed of running in the “preferred” direction. The phase difference between this oscillation and a somatic input at theta‐frequency essentially integrates velocity so that the interference of the two oscillations reflects distance traveled in the preferred direction. The overall grid pattern is maintained in environmental location by phase reset of the grid cell by place cells receiving sensory input from the environment, and environmental boundaries in particular. We also outline possible variations on the basic model, including the generation of grid‐like firing via the interaction of multiple cells rather than via multiple dendritic subunits. Predictions of the interference model are given for the frequency composition of EEG power spectra and temporal autocorrelograms of grid cell firing as functions of the speed and direction of running and the novelty of the environment. © 2007 Wiley‐Liss, Inc.
Cingulate cortex projections to the parahippocampal region and hippocampal formation in the rat
Authors: Jones Bethany F. , Witter Menno P.
Published: June 2007

In the present study we aimed to determine the topographical and laminar characteristics of cingulate projections to the parahippocampal region and hippocampal formation in the rat, using the anterograde tracers Phaseolus vulgaris‐leucoagglutinin and biotinylated dextranamine. The results show that all areas of the cingulate cortex project extensively to the parahippocampal region but not to the hippocampal formation. Rostral cingulate areas (infralimbic‐, prelimbic cortices, rostral 1/3 of the dorsal anterior cingulate cortex) primarily project to the perirhinal and lateral entorhinal cortices. Projections from the remaining cingulate areas preferentially target the postrhinal and medial entorhinal cortices as well as the presubiculum and parasubiculum. At a more detailed level the projections show differences in topographical specificities according to their site of origin within the cingulate cortex suggesting the functional contribution of cingulate areas may differ at an individual level. This organization of the cingulate‐parahippocampal projections relates to the overall organization of postulated parallel parahippocampal‐hippocampal processing streams mediated through the lateral and medial entorhinal cortex respectively. The mid‐rostrocaudal part of the dorsal anterior cingulate cortex appears to be connected to both networks as well as to rostral and caudal parts of the cingulate cortex. This region may therefore responsible for integrating information across these specific networks. © 2007 Wiley‐Liss, Inc.
Optimal operation of reservoirs for downstream water quality control using linked simulation optimization
Authors: Dhar Anirban , Datta Bithin
Published: June 2007

A methodology is developed for optimal operation of reservoirs to control water quality requirements at downstream locations. The physicochemical processes involved are incorporated using a numerical simulation model. This simulation model is then linked externally with an optimization algorithm. This linked simulation–optimization‐based methodology is used to obtain optimal reservoir operation policy. An elitist genetic algorithm is used as the optimization algorithm. This elitist‐genetic‐algorithm‐based linked simulation–optimization model is capable of evolving short‐term optimal operation strategies for controlling water quality downstream of a reservoir. The performance of the methodology developed is evaluated for an illustrative example problem. Different plausible scenarios of management are considered. The operation policies obtained are tested by simulating the resulting pollutant concentrations downstream of the reservoir. These performance evaluations consider various scenarios of inflow, permissible concentration limits, and a number of management periods. These evaluations establish the potential applicability of the developed methodology for optimal control of water quality downstream of a reservoir. Copyright © 2007 John Wiley & Sons, Ltd.
ADAMTSL3/punctin‐2, a gene frequently mutated in colorectal tumors, is widely expressed in normal and malignant epithelial cells, vascular endothelial cells and other cell types, and its mRNA is reduced in colon cancer
Authors: Koo Bon‐Hun , Hurskainen Tiina , Mielke Katrina , Aung Phyu Phyu , Casey Graham , Autio‐Harmainen Helena , Apte Suneel S.
Published: June 2007

ADAMTSL3/punctin‐2 is a secreted glycoprotein that resembles the ADAMTS proteases. Recently, identification of frequent ADAMTSL3 mutations in colorectal cancer suggested it might have a regulatory role in cellular homeostasis in colorectal epithelium or in pathways to colorectal malignancy. Here, we used in situ hybridization to validate ADAMTSL3 antibodies for IHC of a variety of normal and malignant tissues, including colon cancer. Quantitative real‐time PCR (RTQ‐PCR) was used to compare mRNA expression levels in colon carcinoma (n = 10) and adjacent normal colon. ADAMTSL3 is expressed in epithelial cells of the colon, fallopian tube, skin, breast, prostate, epididymis, liver, pancreatic islets and bile ducts, as well as by vascular endothelial cells, smooth muscle cells, fibroblasts, cortical and ganglionic neurons and cardiac myocytes. Malignant epithelial cells in colon cancer, as well as breast, prostate, renal and skin tumors expressed ADAMTSL3. Normal colon showed stronger immunostaining of surface than basal crypt epithelium and staining of a variety of cells within the lamina propria and submucosa. Colon carcinomas demonstrated weaker staining in tumor cells than normal colon epithelium and weak stromal staining. RTQ‐PCR comparison of ADAMTSL3 mRNA in colon carcinoma and adjacent normal colon demonstrated a statistically significant reduction in the tumors, possibly reflecting their decreased stromal content and lack of complete differentiation of tumor samples. The major findings of these studies are that ADAMTSL3 is expressed in numerous tissues, suggesting a broader regulatory role than in colorectal epithelium alone, and that colorectal cancer has both structural mutations as well as decreased expression of ADAMTSL3. © 2007 Wiley‐Liss, Inc.
Mammary cancer resistance and precocious mammary differentiation in the WKY rat: Identification of 2 quantitative trait loci
Authors: Lella Virginie , Stieber Daniel , Rivière Michèle , Szpirer Josiane , Szpirer Claude
Published: June 2007

The COP and WKY rat strains are resistant to mammary cancer. It has shown previously that upon chemical carcinogen treatment, COP females exhibit mammary preneoplastic lesions which disappear within a few weeks. We show here that in similar conditions, WKY females do not exhibit any visible preneoplastic lesions. WKY females are characterized by precocious mammary tissue differentiation, including active expression of the beta‐casein gene in young virgin females. This trait might be critical in resistance to mammary carcinogenesis of WKY rats. To test this hypothesis, we took advantage of 2 congenic strains that contain a limited chromosome segment of WKY origin, derived either from chromosome 5 or from chromosome 18, introgressed in the susceptible genetic background (SPRD‐Cu3). Each of these congenic strains has been shown to be partially resistant to chemically induced mammary carcinogenesis (reduction in tumour multiplicity with respect to the susceptible SPRD‐Cu3 rats). We show here that these 2 congenic strains also exhibit precocious mammary differentiation, though to a lower extent than the WKY females. The conclusion of this study is thus 2‐fold: (i) eradication of preneoplastic lesions is not a general phenomenon in mammary cancer resistance; (ii) the same segment of rat chromosomes 5 or 18 that controls mammary cancer resistance also contains a quantitative trait locus imposing precocious mammary differentiation. These 2 traits are thus associated, supporting the hypothesis that there might be a cause‐effect relationship between precocious mammary differentiation and cancer resistance. © 2007 Wiley‐Liss, Inc.
Binding of endostatin to human ovarian cancer cells inhibits cell attachment
Authors: Yokoyama Yumi , Ramakrishnan S.
Published: June 2007

Endostatin, a C‐terminal fragment of collagen type XVIII, is one of the well‐characterized endogenous inhibitors of angiogenesis. Endostatin is known to bind integrin α5β1, which is upregulated on tumor endothelium. Most of the ovarian cancer cells express significant amounts of α5β1 integrin, which is important for ovarian cancer cells to attach to the peritoneal wall. Therefore we investigated whether endostatin could directly bind ovarian cancer cells and inhibit tumor cell attachment to extracellular matrix. Binding of endostatin to ovarian cancer cells was characterized by preincubation with function blocking antibodies to integrin subunits. These studies showed that ovarian cancer cell attachment to fibronectin‐coated wells can be inhibited by α5β1 integrin specific antibodies as well as endostatin. Downregulation of integrin α5 and β1 by siRNA abrogated the binding of OVCAR5 and human umbilical vein endothelial cell to endostatin. Although endostatin treatment did not affect ovarian cancer cell migration, treated cells failed to attach mouse peritoneal wall preparations. These studies suggest an extra‐antiangiogenic role for endostatin, which can be used prevent peritoneal attachment and dissemination of ovarian cancer cells. © 2007 Wiley‐Liss, Inc.
An evaluation of the life cycle effects of minimum pensions on retirement behavior
Authors: Jiménez‐Martín Sergi , Sánchez Martín Alfonso R.
Published: June 2007

In this paper we explore the effects of the minimum pension program on welfare and retirement in Spain. This is done with a stylized life cycle model which provides a convenient analytical characterization of optimal behavior. We use data from the Spanish Social Security to estimate the behavioral parameters of the model and then simulate the changes induced by the minimum pension in aggregate retirement patterns. The impact is substantial: there is a threefold increase in retirement at 60 (the age of first entitlement) with respect to the economy without minimum pensions, and total early retirement (before or at 60) is almost 50% larger. Copyright © 2007 John Wiley & Sons, Ltd.