bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic Silencing of Death Receptor 4 Mediates Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Resistance in Gliomas
Authors: Elias Agnes , Siegelin Markus D. , Steinmüller Albert , von Deimling Andreas , Lass Ulrike , Korn Bernhard , Mueller Wolf 
Published: August 2009

Abstract
Purpose: To identify and characterize epigenetically regulated genes able to predict sensitivity or resistance to currently tested chemotherapeutic agents in glioma therapy.
Experimental Design: We used methylation-sensitive BeadArray technology to identify novel epigenetically regulated genes associated with apoptosis and with potential therapeutic targets in glioma therapy. To elucidate the functional consequences of promoter methylation in the identified target death receptor 4 (DR4), we investigated tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–mediated and anti-DR4–mediated apoptosis in glioma cell lines (U373 and A172) with loss of DR4 and one glioma cell line (LN18) with robust DR4 expression.
Results: In human astrocytic tumors, we detected DR4 promoter hypermethylation in 60% (n = 5) of diffuse astrocytomas WHO grade 2, in 75% (n = 8) of anaplastic astrocytomas WHO grade 3, and in 70% of glioblastomas WHO grade 4 (n = 33). DR4 is a cell surface protein restricted to glioma cells and is targeted by TRAIL. Glioma cell lines U373 and A172 harbored heavily methylated DR4 promoters, and 5-aza-2-deoxycytidine–mediated demethylation reconstituted DR4 expression in these cell lines. Functional knockdown of DR4 by DR4-specific small interfering RNA in TRAIL-sensitive glioma cell line LN18 significantly mitigated apoptosis induced by an agonistic anti-DR4 antibody. 5-Aza-2-deoxycytidine–mediated demethylation resulted in a functional reconstitution of DR4 on the cell surface of TRAIL-resistant glioma cell line U373 and sensitized U373 to TRAIL-mediated apoptosis. Suppression of DR4 by small interfering RNA in demethylated U373 successfully reestablished the TRAIL-resistant phenotype of U373.
Conclusions: DR4 promoter methylation is frequent in human astrocytic gliomas, and epigenetic silencing of DR4 mediates resistance to TRAIL/DR4-based glioma therapies. (Clin Cancer Res 2009;15(17):5457–65)
Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis
Authors: Carriero Maria Vincenza , Longanesi-Cattani Immacolata , Bifulco Katia , Maglio Ornella , Lista Liliana , Barbieri Antonio , Votta Giuseppina , Masucci Maria Teresa , Arra Claudio , Franco Renato , De Rosa Mario , Stoppelli Maria Patrizia , Pavone Vincenzo 
Published: August 2009

AbstractThe urokinase-type plasminogen activator receptor (uPAR) plays a central role in sustaining the malignant phenotype and promoting tumor metastasis. The Ser88-Arg-Ser-Arg-Tyr92 is the minimum chemotactic sequence of uPAR required to induce the same intracellular signaling as its ligand uPA. Here, we describe the generation of new peptide inhibitors of cell migration and invasion derived from SRSRY by a drug design approach. Ac-Arg-Glu-Arg-Phe-NH2 (i.e., RERF), which adopts a turned structure in solution, was selected for its ability to potently prevent SRSRY-directed cell migration. Fluorescein-RERF associates with very high affinity to RBL-2H3 rat basophilic leukemia cells expressing the human formyl peptide receptor (FPR). Accordingly, femtomolar concentrations of RERF prevent agonist-dependent internalization of FPR and inhibit N-formyl-Met-Leu-Phe–dependent migration in a dose-dependent manner. In the absence of FPR, fluorescein-RERF binds to cell surface at picomolar concentrations in an αv integrin–dependent manner. The involvement of vitronectin receptor is further supported by the findings that 100 pmol/L RERF selectively inhibits vitronectin-dependent RBL-2H3 cell migration and prevents SRSRY-triggered uPAR/αv association. Furthermore, RERF reduces the speed of wound closure and the extent of Matrigel invasion by human fibrosarcoma HT1080 cells without affecting cell proliferation. Finally, a 3- to 5-fold reduction of lung metastasis number and size in nude mice following i.v. injection of green fluorescent protein–expressing HT1080 cells in the presence of 3.32 mg/kg RERF is observed. Our findings indicate that RERF effectively prevents malignant cell invasion in vivo with no signs of toxicity and may represent a promising prototype drug for anticancer therapy. [Mol Cancer Ther 2009;8(9):2708–17]
Multiangular Polarized Characteristics of Optically Thin Cirrus in the Visible and Near-Infrared Spectral Region
Authors: Cheng T. H. , Gu X. F. , Chen L. F. , Yu T. , Tian G. L. 
Published: August 2009

AbstractOptically thin cirrus play a key role in the earth’s radiation budget and global climate change. Their radiative effects depend critically on the thin cirrus optical and microphysical properties. In this paper, inhomogeneous hexagonal monocrystals (IHMs), which consist of a pure hexagon with spherical air bubble or aerosol inclusions, are applied to calculate the single-scattering properties of individual ice crystals. The multiangular polarized characteristics of optically thin cirrus for the 0.865- and 1.38-μm spectral bands are simulated on the basis of an adding–doubling radiative transfer program. The sensitivity of total and polarized reflectance at the top of the atmosphere (TOA) to different aerosol, cirrus, and surface parameters is studied. A new sensitivity index is introduced to further quantify the sensitivity study. The TOA polarized reflectance measured by the Polarization and Directionality of the Earth’s Reflectance (POLDER) instruments is compared to simulated TOA total and polarized reflectance. The test results are reasonable, although small deviations caused by the change of aerosol properties and thin cirrus optical thickness do exist. Finally, on the basis of the sensitivity study, a conceptual approach is suggested to simultaneously retrieve thin cirrus clouds’ optical thickness, ice particle shape, and the underlying aerosol optical thickness using the TOA total and polarized reflectance of the 0.865- and 1.38-μm spectral bands measured at multiple viewing angles.
A Density Current Parameterization Coupled with Emanuel’s Convection Scheme. Part I: The Models
Authors: Grandpeix Jean-Yves , Lafore Jean-Philippe 
Published: August 2009

AbstractThe aim of the present series of papers is to develop a density current parameterization for global circulation models. This first paper is devoted to the presentation of this new wake parameterization coupled with Emanuel’s convective scheme. The model represents a population of identical circular cold pools (the wakes) with vertical frontiers. The wakes are cooled by the precipitating downdrafts while the outside area is warmed by the subsidence induced by the saturated drafts. The budget equations for mass, energy, and water yield evolution equations for the prognostic variables (the vertical profiles of the temperature and humidity differences between the wakes and their exterior). They also provide additional terms for the equations of the mean variables. The driving terms of the wake equations are the differential heating and drying due to convective drafts. The action of the convection on the wakes is implemented by splitting the convective tendency and attributing the effect of the precipitating downdrafts to the wake region and the effect of the saturated drafts to their exterior. Conversely, the action of the wakes on convection is implemented by introducing two new variables representing the convergence at the leading edge of the wakes. The available lifting energy (ALE) determines the triggers of deep convection: convection occurs when ALE exceeds the convective inhibition. The available lifting power (ALP) determines the intensity of convection; it is equal to the power input into the system by the collapse of the wakes. The ALE/ALP closure, together with the splitting of the convective heating and drying, implements the full coupling between wake and convection. The coupled wake–convection scheme thus created makes it possible to represent the moist convective processes more realistically, to prepare the coupling of convection with boundary layer and orographic processes, and to consider simulating the propagation of convective systems.
Assessing the Skill of Precipitation and Temperature Seasonal Forecasts in Spain: Windows of Opportunity Related to ENSO Events
Authors: Frías M. D. , Herrera S. , Cofiño A. S. , Gutiérrez J. M. 
Published: August 2009

Abstract
The skill of state-of-the-art operational seasonal forecast models in extratropical latitudes is assessed using a multimodel ensemble from the Development of a European Multimodel Ensemble System for Seasonal-to-Interannual Prediction (DEMETER) project. In particular, probabilistic forecasts of surface precipitation and maximum temperature in Spain are analyzed using a high-resolution observation gridded dataset (Spain02). To this aim, a simple statistical test based on the observed and predicted tercile anomalies is used. First, the whole period 1960–2000 is considered and it is shown that the only significant skill is found for dry events in autumn. Then, the influence of ENSO events as a potential source of conditional predictability is studied and the validation to strong La Niña or El Niño periods is restricted. Skillful seasonal predictions are found in partial agreement with the observed teleconnections derived from the historical records. On the one hand, predictability is found in spring related to El Niño events for dry events over the south and the Mediterranean coast and for hot events in the southeast areas. In contrast, La Niña drives predictability in winter for dry events over the western part and for hot events in summer over the south and the Mediterranean coast.
This study considers both the direct model outputs and the postprocessed predictions obtained using a statistical downscaling method based on analogs. In general, the use of the downscaling method outperforms the direct output for precipitation, whereas in the case of the temperature no improvement is obtained.
Characteristics and Variability of Storm Tracks in the North Pacific, Bering Sea, and Alaska*
Authors: Mesquita Micheld S. , Atkinson David E. , Hodges Kevin I. 
Published: August 2009

Abstract
The North Pacific and Bering Sea regions represent loci of cyclogenesis and storm track activity. In this paper climatological properties of extratropical storms in the North Pacific/Bering Sea are presented based upon aggregate statistics of individual storm tracks calculated by means of a feature-tracking algorithm run using NCEP–NCAR reanalysis data from 1948/49 to 2008, provided by the NOAA/Earth System Research Laboratory and the Cooperative Institute for Research in Environmental Sciences, Climate Diagnostics Center. Storm identification is based on the 850-hPa relative vorticity field (ζ) instead of the often-used mean sea level pressure; ζ is a prognostic field, a good indicator of synoptic-scale dynamics, and is directly related to the wind speed. Emphasis extends beyond winter to provide detailed consideration of all seasons.
Results show that the interseasonal variability is not as large during the spring and autumn seasons. Most of the storm variables—genesis, intensity, track density—exhibited a maxima pattern that was oriented along a zonal axis. From season to season this axis underwent a north–south shift and, in some cases, a rotation to the northeast. This was determined to be a result of zonal heating variations and midtropospheric moisture patterns. Barotropic processes have an influence in shaping the downstream end of storm tracks and, together with the blocking influence of the coastal orography of northwest North America, result in high lysis concentrations, effectively making the Gulf of Alaska the “graveyard” of Pacific storms. Summer storms tended to be longest in duration. Temporal trends tended to be weak over the study area. SST did not emerge as a major cyclogenesis control in the Gulf of Alaska.
Interhemispheric Influence of the Atlantic Warm Pool on the Southeastern Pacific
Authors: Wang Chunzai , Lee Sang-Ki , Mechoso Carlos R. 
Published: August 2009

Abstract
The Atlantic warm pool (AWP) is a large body of warm water comprising the Gulf of Mexico, Caribbean Sea, and western tropical North Atlantic. The AWP can vary on seasonal, interannual, and multidecadal time scales. The maximum AWP size is in the boreal late summer and early fall, with the largest extent in the year being about 3 times the smallest one. The AWP alternates with the Amazon basin in South America as the seasonal heating source for circulations of the Hadley and Walker type in the Western Hemisphere. During the boreal summer/fall, a strong Hadley-type circulation is established, with ascending motion over the AWP and subsidence over the southeastern tropical Pacific. This is accompanied by equatorward flow in the lower troposphere over the southeastern tropical Pacific, as dynamically required by the Sverdrup vorticity balance.
It is shown by analyses of observational data and NCAR community atmospheric model simulations that an anomalously large (small) AWP during the boreal summer/fall results in a strengthening (weakening) of the Hadley-type circulation with enhanced descent (ascent) over the southeastern tropical Pacific. It is further demonstrated—by using a simple two-level model linearized about a specified background mean state—that the interhemispheric connection between the AWP and the southeastern tropical Pacific depends on the configuration of the background mean zonal winds in the Southern Hemisphere.
The Atlantic Meridional Mode and Its Coupled Variability with the Guinea Dome
Authors: Doi Takeshi , Tozuka Tomoki , Yamagata Toshio 
Published: August 2009

Abstract
Using an ocean–atmosphere coupled general circulation model, air–sea interaction processes associated with the Atlantic meridional mode are investigated from a new viewpoint of its link with the Guinea Dome in the northern tropical Atlantic. The subsurface thermal oceanic dome develops off Dakar from late spring to late fall owing to wind-induced Ekman upwelling. Its seasonal evolution is due to surface wind variations associated with the northward migration of the intertropical convergence zone (ITCZ). Since the upwelling cools the mixed layer in the Guinea Dome region during summer, it is very important to reproduce its variability in order to simulate the sea surface temperature (SST) there.
During the preconditioning phase of the positive (negative) Atlantic meridional mode, the dome is anomalously weak (strong) and the mixed layer is anomalously deep (shallow) there in late fall. This condition reduces (enhances) the sensitivity of the mixed layer temperature to the climatological atmospheric cooling. As a result, the positive (negative) SST anomaly appears there in early winter. Then, it develops in the following spring through the wind–evaporation–SST (WES) positive feedback associated with the anomalous northward (southward) migration of the ITCZ. This, in turn, leads to the stronger (weaker) Ekman upwelling and colder (warmer) subsurface temperature in the dome region during summer. It plays an important role on the decay of the warm (cold) SST anomaly through entrainment as a negative feedback. Therefore, simulating this interesting air–sea interaction in the Guinea Dome region is critical in improving prediction skill for the Atlantic meridional mode.
Improving rehabilitation treatment in a local setting: a case study of prosthetic rehabilitation
Authors: van Twillert Sacha , Postema Klaas , Geertzen Jan HB , Hemminga Titia , Lettinga Ant T 
Published: August 2009

Objective: To contribute to the discussion on the research—practice gap by illustrating obstacles and opportunities that arise in an evidence-informed improvement process of prosthetic rehabilitation in a local setting. Setting: Dutch rehabilitation centre. Presupposition: The improvement process was considered as a two-way translation process rather than a unidirectional process of knowledge transfer between science and practice. Method: Case study and participatory research methods comprising documentary analysis, treatment observations, individual and focus groups interviews, and literature studies. A qualitative software program (Atlas-ti) was used to triangulate the collected data. Results: The main concern of local practitioners was identified to be the post-discharge decline in functional capacity in elderly amputees. This was related to a predominantly biomedical and biomechanical approach, and accompanying traditional therapist—patient interactions. The content and underpinnings of prosthetic treatments were scarcely specified in either the scientific literature or the local setting. Generic principles and practices from other fields were useful for treatment innovation for post-discharge problems, such as task- and context-specific training and self-management education. A circuit training focused on motor learning and a problem-solving training focused on social learning were developed by integrating amputation-specific knowledge. Conclusion: Improving rehabilitation practice with the use of available evidence is a heterogeneous and multifaceted scientific enterprise. Such an enterprise requires as much self-reflexivity from researchers as from practitioners.
A prospective study of positive adjustment to lower limb amputation
Authors: Unwin Jennifer , Kacperek Lynn , Clarke Chris 
Published: August 2009

Objective: To examine prospectively the influence of demographic, amputation and psychosocial variables on positive psychological adjustment outcomes for lower limb amputees. Design: A quantitative questionnaire study with two time points: at the beginning of rehabilitation and at six-month follow-up. Multiple regression analyses were used to determine the contribution of demographic/amputation factors versus psychosocial factors to adjustment outcomes. Setting: A regional outpatient specialist mobility and rehabilitation centre in the UK. Subjects: Participants were recruited as a consecutive sample of new referrals with lower limb amputation. Main measures: Age, gender, level and cause of amputation were recorded. The following measures were used: Hope Scale, Multidimensional Scale of Perceived Social Support (MSPSS), Trinity Amputation and Prosthetic Experiences Scale (TAPES) pain subscale initially and the Positive and Negative Affect Scale (PANAS) and full TAPES at six-month follow up. The measures were administered by two specialist nurses. Results: Ninety-nine patients provided data at both time points. Hope at the beginning of rehabilitation was related to positive mood (P<0.001) and hope and social support were related to general adjustment (P<0.01, P<0.001) at follow-up. Demographic and amputation factors were not related to psychological adjustment outcomes in this study. Conclusions: The findings demonstrate prospectively the importance of psychosocial variables in the prediction of positive adjustment to lower limb amputation.
Cognitive performance, symptoms and counter-regulation during hypoglycaemia in patients with type 1 diabetes and high or low renin-angiotensin system activity
Authors: Høi-Hansen Thomas , Pedersen-Bjergaard Ulrik , Andersen Rikke Due , Kristensen Peter Lommer , Thomsen Carsten , Kjær Troels , Høgenhaven Hans , Smed Annelise , Holst Jens Juul , Dela Flemming , Boomsma Frans , Thorsteinsson Birger 
Published: August 2009

Introduction. High basal renin-angiotensin system (RAS) activity is associated with increased risk of severe hypoglycaemia in type 1 diabetes. We tested whether this might be explained by more pronounced cognitive dysfunction during hypoglycaemia in patients with high RAS activity than in patients with low RAS activity. Materials and methods. Nine patients with type 1 diabetes and high and nine with low RAS activity were subjected to hypoglycaemia and euglycaemia in a cross-over study using an intravenous insulin infusion protocol. Cognitive function, electroencephalography, auditory evoked potentials and hypoglycaemic symptoms were recorded. Results. At a hypoglycaemic nadir of 2.2 (SD 0.3) mmol/L the high RAS group displayed significant deterioration in cognitive performance during hypoglycaemia in the three most complex reaction time tasks. In the low RAS group, hypoglycaemia led to cognitive dysfunction in only one reaction time task. The high RAS group reported lower symptom scores during hypoglycaemia than the low RAS group, suggesting poorer hypoglycaemia awareness. Conclusion. High RAS activity is associated with increased cognitive dysfunction and blunted symptoms during mild hypoglycaemia compared to low RAS activity. This may explain why high RAS activity is a risk factor for severe hypoglycaemia in type 1 diabetes.
Association of angiotensin-converting enzyme intron 16 insertion/deletion polymorphism with history of foetal loss
Authors: Bukreeva Larisa , Grigorov Alexander , Kiesewetter Holger , Hoppe Berthold 
Published: August 2009

Introduction. The angiotensin-converting enzyme (ACE) intron 16 insertion/deletion (I/D) polymorphism is associated with ACE activity and has been discussed as a risk factor for pre-eclampsia. Disturbances of uteroplacental circulation are involved in the pathogenesis of pre-eclampsia. In this study, we tested whether the ACE I/D genotype is associated with history of foetal loss (FL) or uteroplacental dysfunction (UPD). Patients and methods. ACE I/D genotype was determined in 312 women presenting with a history of FL and 112 women admitted because of UPD. The association of the ACE I/D genotype with FL or UPD was assessed in a case-control study using 527 patients with diagnoses other than FL or UPD. To exclude potential biases due to associations of this genotype with other diagnoses, we additionally performed a case-control study using 553 healthy controls. Results. ACE I/D genotype was significantly associated with history of FL in both case-control studies (patient controls: odds ratio 1.52, p<0.02; healthy controls: odds ratio 1.48, p=0.02). There was no evidence for allele-dose dependency. No association of the ACE I/D genotype with UPD could be detected. Conclusions. The ACE I/D genotype exhibits a statistically significant association with a history of FL. These results corroborate an involvement of the renin-angiotensin system in pregnancy complications.
Natural nanoclays: applications and future trends – a Chilean perspective
Authors: Calabi Floody M. , Theng B. K. G. , Reyes P. , Mora M. L. 
Published: August 2009

AbstractBecause of their large potential for agricultural, industrial and medicinal applications, nanomaterials have been the focus of much research during the past few decades. Nanoclays are natural nanomaterials that occur in the clay fraction of soil, among which montmorillonite and allophane are the most important species. Montmorillonite is a crystalline hydrous phyllosilicate (layer silicate). Organically-modified montmorillonites or ‘organoclays’, formed by intercalation of quaternary ammonium cations, have long been used as rheological modifiers and additives in paints, inks, greases and cosmetics and as carriers and delivery systems for the controlled release of drugs. Perhaps the largest single usage of organoclays over recent years has been in the manufacture of polymer-clay nanocomposites. These organic–inorganic hybrid materials show superior mechanical, thermal and gas-barrier properties. Organoclays are also useful in pollution control and water treatment. Allophane is a non-crystalline aluminosilicate derived from the weathering of volcanic ash. A large proportion of the agricultural land in Chile is covered by volcanic soils,the clay fraction of which is dominated by allophane. Consisting of nanosize (3.5–5.0 nm) hollow spherules, allophane is a suitable support material for enzyme immobilization. Allophane is also effective at adsorbing phenolic compounds and colour from kraft mill effluents and phosphate from water and wastewater.