bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased amyloidogenic processing of transgenic human APP in X11-like deficient mouse brain
Authors: Kondo Maho , Shiono Maki , Itoh Genzo , Takei Norio , Matsushima Takahide , Maeda Masahiro , Taru Hidenori , Hata Saori , Yamamoto Tohru , Saito Yuhki , Suzuki Toshiharu
Published: September 2010

Background

X11-family proteins, including X11, X11-like (X11L) and X11-like 2 (X11L2), bind to the cytoplasmic domain of amyloid β-protein precursor (APP) and regulate APP metabolism. Both X11 and X11L are expressed specifically in brain, while X11L2 is expressed ubiquitously. X11L is predominantly expressed in excitatory neurons, in contrast to X11, which is strongly expressed in inhibitory neurons. In vivo gene-knockout studies targeting X11, X11L, or both, and studies of X11 or X11L transgenic mice have reported that X11-family proteins suppress the amyloidogenic processing of endogenous mouse APP and ectopic human APP with one exception: knockout of X11, X11L or X11L2 has been found to suppress amyloidogenic metabolism in transgenic mice overexpressing the human Swedish mutant APP (APPswe) and the mutant human PS1, which lacks exon 9 (PS1dE9). Therefore, the data on X11-family protein function in transgenic human APP metabolism in vivo are inconsistent.

Results

To confirm the interaction of X11L with human APP ectopically expressed in mouse brain, we examined the amyloidogenic metabolism of human APP in two lines of human APP transgenic mice generated to also lack X11L. In agreement with previous reports from our lab and others, we found that the amyloidogenic metabolism of human APP increased in the absence of X11L.

Conclusion

X11L appears to aid in the suppression of amyloidogenic processing of human APP in brain in vivo, as has been demonstrated by previous studies using several human APP transgenic lines with various genetic backgrounds. X11L appears to regulate human APP in a manner similar to that seen in endogenous mouse APP metabolism.
A rare mitochondrial disorder: Leigh syndrome - a case report
Authors: Shrikhande Dhananjay Y , Kalakoti Piyush , Syed MM Aarif , Ahya Kunal , Singh Gurmeet
Published: September 2010

Leigh syndrome is a rare progressive neurodegenerative, mitochondrial disorder of childhood with only a few cases documented from India. The clinical presentation of Leigh syndrome is highly variable. However, in most cases it presents as a progressive neurological disease with motor and intellectual developmental delay and signs and symptoms of brain stem and/or basal ganglia involvement. Raised lactate levels in blood and/or cerebrospinal fluid is noted. It is the neuroimaging, mainly the Magnetic Resonance Imaging showing characteristic symmetrical necrotic lesions in the basal ganglia and/or brain stem that leads to the diagnosis. Here, we report a case of 7 months old female child presenting to us with status epilepticus, delayed developmental milestones and regression of the achieved milestones suspected to be a case of neurodegenerative disorder, which on MRI was diagnosed as Leigh syndrome.
Large-scale data integration framework provides a comprehensive view on glioblastoma multiforme
Authors: Ovaska Kristian , Laakso Marko , Haapa-Paananen Saija , Louhimo Riku , Chen Ping , Aittomäki Viljami , Valo Erkka , Núñez-Fontarnau Javier , Rantanen Ville , Karinen Sirkku , Nousiainen Kari , Lahesmaa-Korpinen Anna-Maria , Miettinen Minna , Saarinen Lilli , Kohonen Pekka , Wu Jianmin , Westermarck Jukka , Hautaniemi Sampsa
Published: September 2010

Background

Coordinated efforts to collect large-scale data sets provide a basis for systems level understanding of complex diseases. In order to translate these fragmented and heterogeneous data sets into knowledge and medical benefits, advanced computational methods for data analysis, integration and visualization are needed.

Methods

We introduce a novel data integration framework, Anduril, for translating fragmented large-scale data into testable predictions. The Anduril framework allows rapid integration of heterogeneous data with state-of-the-art computational methods and existing knowledge in bio-databases. Anduril automatically generates thorough summary reports and a website that shows the most relevant features of each gene at a glance, allows sorting of data based on different parameters, and provides direct links to more detailed data on genes, transcripts or genomic regions. Anduril is open-source; all methods and documentation are freely available.

Results

We have integrated multidimensional molecular and clinical data from 338 subjects having glioblastoma multiforme, one of the deadliest and most poorly understood cancers, using Anduril. The central objective of our approach is to identify genetic loci and genes that have significant survival effect. Our results suggest several novel genetic alterations linked to glioblastoma multiforme progression and, more specifically, reveal Moesin as a novel glioblastoma multiforme-associated gene that has a strong survival effect and whose depletion in vitro significantly inhibited cell proliferation. All analysis results are available as a comprehensive website.

Conclusions

Our results demonstrate that integrated analysis and visualization of multidimensional and heterogeneous data by Anduril enables drawing conclusions on functional consequences of large-scale molecular data. Many of the identified genetic loci and genes having significant survival effect have not been reported earlier in the context of glioblastoma multiforme. Thus, in addition to generally applicable novel methodology, our results provide several glioblastoma multiforme candidate genes for further studies.

Anduril is available at http://csbi.ltdk.helsinki.fi/anduril/

The glioblastoma multiforme analysis results are available at http://csbi.ltdk.helsinki.fi/anduril/tcga-gbm/
Seismic wave attenuation and dispersion resulting from wave-induced flow in porous rocks — A review
Authors: Müller Tobias M. , Gurevich Boris , Lebedev Maxim
Published: September 2010

One major cause of elastic wave attenuation in heterogeneous porous media is wave-induced flow of the pore fluid between heterogeneities of various scales. It is believed that for frequencies below [Formula: see text], the most important cause is the wave-induced flow between mesoscopic inhomogeneities, which are large compared with the typical individual pore size but small compared to the wavelength. Various laboratory experiments in some natural porous materials provide evidence for the presence of centimeter-scale mesoscopic heterogeneities. Laboratory and field measurements of seismic attenuation in fluid-saturated rocks provide indications of the role of the wave-induced flow. Signatures of wave-induced flow include the frequency and saturation dependence of P-wave attenuation and its associated velocity dispersion, frequency-dependent shear-wave splitting, and attenuation anisotropy. During the last four decades, numerous models for attenuation and velocity dispersion from wave-induced flow have been developed with varying degrees of rigor and complexity. These models can be categorized roughly into three groups ac-cording to their underlying theoretical framework. The first group of models is based on Biot’s theory of poroelasticity. The second group is based on elastodynamic theory where local fluid flow is incorporated through an additional hydrodynamic equation. Another group of models is derived using the theory of viscoelasticity. Though all models predict attenuation and velocity dispersion typical for a relaxation process, there exist differences that can be related to the type of disorder (periodic, random, space dimension) and to the way the local flow is incorporated. The differences manifest themselves in different asymptotic scaling laws for attenuation and in different expressions for characteristic frequencies. In recent years, some theoretical models of wave-induced fluid flow have been validated numerically, using finite-difference, finite-element, and reflectivity algorithms applied to Biot’s equations of poroelasticity. Application of theoretical models to real seismic data requires further studies using broadband laboratory and field measurements of attenuation and dispersion for different rocks as well as development of more robust methods for estimating dissipation attributes from field data.
Computational poroelasticity — A review
Authors: Carcione José M. , Morency Christina , Santos Juan E.
Published: September 2010

Computational physics has become an essential research and interpretation tool in many fields. Particularly in reservoir geophysics, ultrasonic and seismic modeling in porous media is used to study the properties of rocks and to characterize the seismic response of geologic formations. We provide a review of the most common numerical methods used to solve the partial differential equations describing wave propagation in fluid-saturated rocks, i.e., finite-difference, pseudospectral, and finite-element methods, including the spectral-element technique. The modeling is based on Biot-type theories of dynamic poroelasticity, which constitute a general framework to describe the physics of wave propagation. We explain the various techniques and discuss numerical implementation aspects for application to seismic modeling and rock physics, as, for instance, the role of the Biot diffusion wave as a loss mechanism and interface waves in porous media.
Petroleum reservoir characterization using downhole microseismic monitoring
Authors: Maxwell S. C. , Rutledge J. , Jones R. , Fehler M.
Published: September 2010

Imaging of microseismic data is the process by which we use information about the source locations, timing, and mechanisms of the induced seismic events to make inferences about the structure of a petroleum reservoir or the changes that accompany injections into or production from the reservoir. A few key projects were instrumental in the development of downhole microseismic imaging. Most recent microseismic projects involve imaging hydraulic-fracture stimulations, which has grown into a widespread fracture diagnostic technology. This growth in the application of the technology is attributed to the success of imaging the fracture complexity of the Barnett Shale in the Fort Worth basin, Texas, and the commercial value of the information obtained to improvecompletions and ultimately production in the field. The use of commercial imaging in the Barnett is traced back to earlier investigations to prove the technology with the Cotton Valley imaging project and earlier experiments at the M-Site in the Piceance basin, Colorado. Perhaps the earliest example of microseismic imaging using data from downhole recording was a hydraulic fracture monitored in 1974, also in the Piceance basin. However, early work is also documented where investigators focused on identifying microseismic trace characteristics without attempting to locate the microseismic sources. Applications of microseismic reservoir monitoring can be tracked from current steam-injection imaging, deformation associated with reservoir compaction in the Yibal field in Oman and the Ekofisk and Valhall fields in the North Sea, and production-induced activity in Kentucky, U.S.A.
Seismic anisotropy in exploration and reservoir characterization: An overview
Authors: Tsvankin Ilya , Gaiser James , Grechka Vladimir , van der Baan Mirko , Thomsen Leon
Published: September 2010

Recent advances in parameter estimation and seismic processing have allowed incorporation of anisotropic models into a wide range of seismic methods. In particular, vertical and tilted transverse isotropy are currently treated as an integral part of velocity fields employed in prestack depth migration algorithms, especially those based on the wave equation. We briefly review the state of the art in modeling, processing, and inversion of seismic data for anisotropic media. Topics include optimal parameterization, body-wave modeling methods, P-wave velocity analysis and imaging, processing in the [Formula: see text] domain, anisotropy estimation from vertical-seismic-profiling (VSP) surveys, moveout inversion of wide-azimuth data, amplitude-variation-with-offset (AVO) analysis, processing and applications of shear and mode-converted waves, and fracture characterization. When outlining future trends in anisotropy studies, we emphasize that continued progress in data-acquisition technology is likely to spur transition from transverse isotropy to lower anisotropic symmetries (e.g., orthorhombic). Further development of inversion and processing methods for such realistic anisotropic models should facilitate effective application of anisotropy parameters in lithology discrimination, fracture detection, and time-lapse seismology.
Electromagnetic geophysics: Notes from the past and the road ahead
Authors: Zhdanov Michael S.
Published: September 2010

During the last century, electrical geophysics has been transformed from a simple resistivity method to a modern technology that uses complex data-acquisition systems and high-performance computers for enhanced data modeling and interpretation. Not only the methods and equipment have changed but also our ideas about the geoelectrical models used for interpretation have been modified tremendously. This paper describes the evolution of the conceptual and technical foundations of EM methods. It outlines a framework for further development, which should focus on multitransmitter and multireceiver surveys, analogous to seismic data-acquisition systems. Important potential topics of future research efforts are in the areas of multidimensional modeling and inversion, including a new approach to the formulation and understanding of EM fields based on flux and voltage representation, which corresponds well to geophysical experiments involving the measurement of voltage and flux of electric and magnetic fields.
Recent advances in optimized geophysical survey design
Authors: Maurer Hansruedi , Curtis Andrew , Boerner David E.
Published: September 2010

Survey design ultimately dictates the quality of subsurface information provided by practical implementations of geophysical methods. It is therefore critical to design experimental procedures that cost effectively produce those data that maximize the desired information. This review cites recent advances in statistical experimental design techniques applied in the earth sciences. Examples from geoelectrical, crosswell and surface seismic, and microseismic monitoring methods are included. Using overdetermined 1D and 2D geoelectrical examples, a minor subset of judiciously chosen measurements provides a large percentage of the information content theoretically offered by the geoelectrical method. In contrast, an underdetermined 2D seismic traveltime tomography design study indicates that the information content increases almost linearly with the amount of traveltime data (source-receiver pairs) considered until the underdeterminancy is reduced substantially. An experimental design study of frequency-domain seismic-waveform inversion experiments reveals that a few optimally chosen frequencies offer as much subsurface information as the full bandwidth. A nonlinear experimental design for a seismic amplitude-versus-angle survey identifies those incidence angles most important for characterizing a reservoir. A nonlinear design example shows that designing microseismic monitoring surveys based on array aperture is a poor strategy that almost certainly leads to suboptimal designs.
A Paleontology Primer for Oncologists
Authors: Provenzano Anthony
Published: September 2010

Just as a blazing meteor wiped out large dinosaurs, health care reform may eliminate solo practitioners.
Clinical Research Site Infrastructure and Efficiency
Authors: Baer Allison R. , Bridges Kerry Dune , O'Dwyer Mary , Ostroff Joy , Yasko Joyce
Published: September 2010

Increasing efficiency in the clinical trials development process ensures a vibrant clinical trials system that makes best use of resources, and keeps pace with scientific discoveries in the field of cancer research.
National Practice Benchmark: 2010 Report on 2009 Data
Authors: Towle Elaine L. , Barr Thomas R.
Published: September 2010

Results from this survey indicate an overall lowering of the cost of practice operations, even as cost of drugs continues to rise; and an overall increase in service delivery efficiency.
Rac controls PIP5K localisation and PtdIns(4,5)P2 synthesis, which modulates vinculin localisation and neurite dynamics
Authors: Halstead Jonathan R. , Savaskan Nicolai E. , van den Bout Iman , Van Horck Francis , Hajdo-Milasinovic Amra , Snell Mireille , Keune Willem-Jan , ten Klooster Jean-Paul , Hordijk Peter L. , Divecha Nullin
Published: September 2010

In N1E-115 cells, neurite retraction induced by neurite remodelling factors such as lysophosphatidic acid, sphingosine 1-phosphate and semaphorin 3A require the activity of phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks). PIP5Ks synthesise the phosphoinositide lipid second messenger phosphatidylinositol(4,5)bisphosphate [PtdIns(4,5)P2], and overexpression of active PIP5K is sufficient to induce neurite retraction in both N1E-115 cells and cerebellar granule neurones. However, how PIP5Ks are regulated or how they induce neurite retraction is not well defined. Here, we show that neurite retraction induced by PIP5Kβ is dependent on its interaction with the low molecular weight G protein Rac. We identified the interaction site between PIP5Kβ and Rac1 and generated a point mutant of PIP5Kβ that no longer interacts with endogenous Rac. Using this mutant, we show that Rac controls the plasma membrane localisation of PIP5Kβ and thereby the localised synthesis of PtdIns(4,5)P2 required to induce neurite retraction. Mutation of this residue in other PIP5K isoforms also attenuates their ability to induce neurite retraction and to localise at the membrane. To clarify how increased levels of PtdIns(4,5)P2 induce neurite retraction, we show that mutants of vinculin that are unable to interact with PtdIns(4,5)P2, attenuate PIP5K- and LPA-induced neurite retraction. Our findings support a role for PtdIns(4,5)P2 synthesis in the regulation of vinculin localisation at focal complexes and ultimately in the regulation of neurite dynamics.
Negative regulation ofDrosophilaJAK–STAT signalling by endocytic trafficking
Authors: Vidal Oscar Marino , Stec Wojciech , Bausek Nina , Smythe Elizabeth , Zeidler Martin P.
Published: September 2010

Appropriate regulation of signal transduction pathways is essential for normal development and is often disrupted in disease. Therefore, many regulatory mechanisms and feedback loops have evolved to ensure appropriate signalling. One mechanism previously suggested to modulate a range of signal transduction pathways involves the internalisation and destruction of transmembrane receptors by the endocytic trafficking machinery. Strikingly, a recent report has suggested that the endocytic trafficking of the Drosophila JAK–STAT pathway receptor Domeless (Dome) does not act to downregulate pathway activity, but rather is necessary for in vivo signalling. Here, we examine this relationship to address the interaction of Drosophila JAK–STAT pathway signalling and endocytic trafficking. We show that Dome is trafficked through clathrin-mediated endocytosis and a directed RNAi screen identified several components of the endocytic machinery as negative regulators of pathway signalling. We demonstrate that Dome signals both from the plasma membrane and internalised vesicles and show, using knockdown experiments, that endocytic components negatively regulate JAK–STAT signalling in vivo. As such, disruption in endocytic trafficking represents a potent negative regulator of the disease relevant JAK–STAT signalling cascade.
Evaluation of the Thermofluid Performance of an Automotive Engine Cooling-Fan System Motor
Authors: Savory E , Martinuzzi R J , Ryval J , Li Z , Blissitt M
Published: September 2010

Experimental tests and computational fluid dynamics (CFD) simulations using the commercial code FLUENT were carried out to investigate the effects of the fan support hub geometry on the component heat transfer and cooling air flow through a simplified model of an electric motor for an automotive cooling-fan system, since little is known about the thermofluid dynamics of such machines. It has been found that the presence of radial ribs on the fan hub has a significant effect on drawing cooling air through the motor, particularly at lower air flowrates, regardless of the rotational speed. In addition, the rotational speed, hub diameter, fin height, and rib width are important parameters for inducing flow inside the hub while the tip gap and hub depth are not as influential. Increasing the number of ribs or fins has little impact on the performance of the hub. Good agreement was found between the experimental and predicted temperatures from heat transfer simulations of the motor for representative underhood environmental conditions. The present work shows that a valuable CFD tool can be developed to predict the temperature distribution inside the motor and offers a guide to the methodology whereby design modifications may be made to improve motor performance for a given application.
Estimating the effect of the vehicle model year on crash and injury involvement
Authors: Cooper P J , Osborn J , Meckle W
Published: September 2010

The study was designed to investigate the effect of the model year on crashes and injuries, where the latter were of the mild to moderate variety, independent of other driver or vehicle factors and travel exposure. Previous research on vehicle safety design has focused on fatal or serious injuries but, for traffic safety evaluations in smaller jurisdictions and over limited time frames, a more numerous-outcome variable must be used.

The study was conducted with over 32 000 driver–vehicle combinations. Binary logistic regression was employed to estimate the effects of the model year ranges on injuries and driving exposure, while controlling the other factors. A salutory effect of increasing the model year on the injury risk was found but this was countered by the increased travel associated with the newer vehicles.
Emission Comparison of Light-Duty in-Use Flexible-Fuel Vehicles Fuelled with Gasoline and Compressed Natural Gas Based on the ECE 15 Driving Cycle
Authors: Zhang C-H , Xie Y-L , Wang F-S , Ma Z-Y , Qi D-H , Qiu Z-W
Published: September 2010

This paper presents an exhaust emission comparison for light-duty in-use compressed natural gas (CNG)-gasoline flexible-fuel vehicles under the ECE 15 driving cycle protocol. The aim of this study is to provide a scientific basis for determining the level of emissions reduction for gasoline vehicles fuelled with CNG. The emission characteristics of gasoline and CNG under the ECE 15 driving cycle are experimentally measured and parabolic fits to the data are performed to obtain the relationship between CO, HC, and NO x emission levels and vehicle mileage. As the mileage exceeds 200 000 km, changes in the level of emissions gradually begin to become apparent. When the mileage exceeds 300 000 km, the level of emission of pollutants increases dramatically. Compared to the emission levels measured for gasoline, the values for CNG are, averagely, reduced 30.34 per cent for CO, 15.30 per cent for HC, and 7.22 per cent for NO x, respectively. No obvious differences in the emission level at a given mileage can be found for the three vehicle types used in this study.
Oxidative Stability of Biodiesel Fuel
Authors: Bannister C D , Chuck C J , Bounds M , Hawley J G
Published: September 2010

Biodiesel, the fatty acid alkyl esters derived from vegetable oils, animal fats, or waste cooking oils, is an alternative to diesel fuel. One of the major technical issues with the use of biodiesel is its susceptibility to oxidation. Oxidation of biodiesel is a complex process which involves a number of mechanisms producing an array of chemical components such as aldehydes, acids, ketones, and oligomeric compounds. These components in turn increase the viscosity and deposits in the fuel beyond acceptable levels. A variety of factors affect the level of these decomposition products as well as the rate of formation and decay. These factors include the temperature, presence of light, catalytic metals in the fuel system, sump oil, or storage containers, type of biodiesel, fatty acid profile, blend level, other contaminants, and presence of antioxidants. This paper examines the relevant factors influencing the biodiesel oxidative stability, the methods used to analyse and test biodiesel oxidation, as well as the effect that oxidation has on the fuel's properties.
Finite Element Modelling of a Hybrid III Dummy and Material Identification for Validation
Authors: Yi S-I , Mohan P K , Kan C-D , Park G-J
Published: September 2010

Anthropomorphic test devices (ATDs) are used to predict the human injury risk in a crash test. The Hybrid III crash test dummy is a standard ATD used for measuring the occupant safety in a frontal impact test. Since a real crash test using a vehicle is expensive, computer simulation using the finite element method (FEM) is widely used. Therefore, a detailed and robust finite element (FE) dummy model is required to acquire more precise occupant injury data and more accurate behaviour of a dummy during the crash. This research proposes the process of modelling and validation of an FE model of a Hybrid III crash test dummy, and a high-fidelity FE model of the Hybrid III dummy is developed on the basis of the proposed process. The proposed process consists of two phases. First, the FE model is constructed on the basis of the reverse engineering technique. Second, the material identification process is performed for validation of the constructed FE model of the Hybrid III crash test dummy. A certification test for each part of the physical dummy model and also computer simulation of the constructed FE model are performed. The material identification process is carried out by an optimization process to minimize the difference between the physical test results and the computer simulation results. The utilized optimization algorithm is the successive response surface method (SRSM).
Efficient tether dynamic model formulation using recursive rigid-body dynamics
Authors: Hembree B , Slegers N
Published: September 2010

A computationally efficient discrete model for low-strain tethers used in many engineering applications is developed without the use of elastic elements. The tether is modelled using N links, with each link treated as a body of revolution where it is assumed the tether spin is negligible to the dynamics, resulting in each link having only two degrees of freedom. A recursive algorithm is developed for the dynamic equations, with the solution procedure being an order N method requiring only a 2×2 matrix inversion, resulting in approximately half the computations of the general recursive algorithm. A comparison between the proposed efficient recursive rigid-body model and a lumped point mass model shows that the absence of stiff elastic elements eliminates high-frequency axial vibrations that appear in many lumped point mass tether models. The absence of high-frequency axial vibration facilitates numerical integration of the equations, providing further improvement in computational speed.
Semantic data model in multibody system simulation
Authors: Kortelainen J , Mikkola A
Published: September 2010

This article introduces an approach for using a semantic data model and knowledge representation technologies in the data management of multibody system simulation. This is accomplished by developing a semantic ontology for multibody system modelling. As an example of semantic ontology modelling, the introduced approach is applied to a simple double-pendulum model. The purpose of the example is to demonstrate that multibody system simulation data can be expressed using semantic data representation. In addition, semantic data representation enables a general and straightforward application integration solution for design tools and other information systems typically involved in the industrial product design process. It is also important to note that this approach enables knowledge of the domain of interest to be stored together with the modelling data. By including rules and constraints with the data and applying a semantic reasoning methodology, the apparent intelligence of the stored data is increased.
Noncanonical cytoplasmic processing of viral microRNAs
Authors: Shapiro Jillian S. , Varble Andrew , Pham Alissa M. , tenOever Benjamin R.
Published: September 2010

Cellular utilization of RNA interference (RNAi) as a mechanism to combat virus infection is thought to be restricted to plants and invertebrates. In vertebrates, antiviral defenses are largely dependent on interferons (IFNs), with the use of small RNAs restricted to microRNA (miRNA)–mediated targeting of host transcripts. Here we demonstrate that incorporation of a primary miRNA into a cytoplasmic virus results in the formation of a Dicer-dependent, DGCR8-independent, mature miRNA capable of conferring RNAi-like activity. Processing of the viral mirtron-like product (virtron) is indistinguishable from endogenous miRNA maturation and elicits post-transcriptional gene silencing, albeit at a reduced level. Furthermore, virtrons impose Dicer-dependent, microprocessor-independent, and IFN-independent interference on virus replication in a sequence-specific manner. Taken together, these results suggest the existence of a noncanonical, small-RNA-based activity capable of processing cytoplasmic hairpins and perhaps contributing to the cell's antiviral arsenal.
Cardiology: Treatment of Systolic Heart Failure in the Elderly: An Evidence-Based Review
Authors: Arif Sally A , Mergenhagen Karl A , O Diaz Del Carpio Roberto , Ho Christopher
Published: September 2010

Objective:

To review relevant literature supporting the use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics, digoxin, aldosterone antagonists, and vasodilators in the management of heart failure in an elderly patient population aged ≥65 years.

Data Sources:

PubMed, EMBASE, and MEDLINE searches (January 1960–April 2010) were utilized to identify primary literature using the key terms heart failure, treatment, and elderly. Additionally, reference citations from publications identified were utilized, as well as the American College of Cardiology/American Heart Association (ACC/AHA) Guidelines for the Diagnosis and Management of Chronic Heart Failure in the Adult.

Study Selection and Data Extraction:

Primary and tertiary literature, including subgroup analyses, published in English and relating to the use of pharmacotherapy in the treatment of systolic heart failure in the elderly was reviewed.

Data Synthesis:

The aging of the US population is creating a higher prevalence of systolic heart failure in the elderly. Most clinical trials have established the mortality and morbidity benefit of pharmacotherapy in heart failure in nonelderly patients; however, the current ACC/AHA guidelines do not clearly delineate this benefit in persons ≥65 years of age.

Conclusions:

Clinical trial data, based on limited numbers of individuals aged ≥65 years, suggest that use of β-blockers, ACE inhibitors, ARBs, aldosterone antagonists, and vasodilators (hydralazine/nitrates) have similar mortality benefit to that observed in younger patients. As supported in the ACC/AHA guidelines, these agents should be prescribed with clinical judgment to all elderly patients, with close monitoring for adverse events. Future clinical trials with greater inclusion of patients ≥65 years will help to elucidate the magnitude of benefits of optimal pharmacotherapy on mortality and morbidity rates in this population.
Retrospective Analysis of the Consequences of Acid Suppressive Therapy on Ketoconazole Efficacy in Advanced Castration-Resistant Prostate Cancer
Authors: Keisner Sidney V , Shah Sachin R , Jean Gary W , Gressett Ussery Sarah M , Dowell Jonathan E
Published: September 2010

Background:

The area under the curve of a single ketoconazole dose has been shown to decrease significantly when administered with acid suppressive therapy. No published studies have examined the clinical impact of concurrent ketoconazole and acid suppressive therapy in patients with castration-resistant prostate cancer (CRPC).

Objective:

To evaluate the effect of acid suppressive therapy on prostate-specific antigen (PSA) response rate in CRPC patients receiving ketoconazole.

Methods:

This retrospective study evaluated CRPC patients treated with ketoconazole 3 times daily between January 1, 1999, and September 30, 2009. Patients included in the analysis had failed androgen deprivation therapy, and were subsequently initiated on ketoconazole. Response (PSA decline ≥50% maintained ≥4 weeks) was evaluated in patients receiving ketoconazole with (group 1 [G1]) or without (group 2 [G2]) concurrent acid suppressive therapy.

Results:

Thirty patients (G1: 11 patients; G2: 19 patients) were included in the analysis. Mean age in G1 and G2 was 71.8 and 69.6 years, respectively. Most patients had received prior therapy with an antiandrogen (90.9% G1; 100% G2) and fewer patients received antiandrogen withdrawal therapy (27.3% G1; 21.1% G2). Median baseline PSA was 109.4 (G1) and 86.9 ng/mL (G2) (p = 0.55). Median duration of ketoconazole was 7.2 months in G1 and 5.8 months in G2 (p = 0.09). Ketoconazole adherence was 82% (G1) and 100% (G2). Median duration of concurrent acid suppressive therapy was 3.8 months (range 2.0–20.4) in G1. PSA response (72.7% and 47.4%; p = 0.26) and time to PSA response (1.2 vs 0.9 mo; p = 0.53) were statistically similar between G1 and G2, respectively. Median progression free survival was higher in G1 (11.5 vs 6.9 months in G2; p = 0.047).

Conclusions:

Use of concurrent acid suppressive therapy and ketoconazole in CRPC patients did not decrease PSA response rate, and progression free survival was unexpectedly higher compared with the non–acid suppressive therapy group. Larger studies are needed to verify the clinical impact of acid suppressive therapy in combination with ketoconazole.
Metallic materials for biomedical applications: Laboratory and clinical studies
Authors: Milošev Ingrid
Published: September 2010

Prolongation of the average life expectancy and an active lifestyle in old age are related to the constant increase in the number of joint diseases that eventually require a surgical procedure. The diseased joint is replaced with a joint prosthesis, the functionality of the joint is recovered, and pain is reduced. In the last decade, the number of joint replacement operations has increased several times over and is expected to increase further. In order to enable patients to have a painless and active lifestyle, it is necessary to develop materials that are long-lasting in vivo. Metallic biomaterials must exhibit high corrosion and wear resistance. In vitro research on materials under simulated physiological conditions is presented. These experiments are complemented by examples from clinical practice performed in collaboration with orthopedic surgeons. Morphological and chemical changes in the material during the course of in vivo performance are related to processes of wear and corrosion. The local and systemic consequences of these processes in the human body are presented.
Proliferating Private-Label Portfolios: How Introducing Economy and Premium Private Labels Influences Brand Choice
Authors: Geyskens Inge , Gielens Katrijn , Gijsbrechts Els
Published: September 2010

Three-tiered private-label (PL) portfolio strategies (low-quality tier: economy PLs, mid-quality tier: standard PLs, and top-quality tier: premium PLs) are gaining interest around the world. Drawing on the context-effects literature, the authors postulate how the introduction of economy and premium PLs may affect the choice of mainstream-quality and premium-quality national brands (NBs) and the choice of the retailer's existing PL offering. The authors use the natural experiment offered by Asda's and Sainsbury's introduction of economy and premium PL tiers in the corn flakes and canned soup categories in the United Kingdom to test their framework. Using brand choice models that accommodate context (compromise, similarity, and attraction) effects, the authors find that both economy and premium PLs cannibalize incumbent PLs. Economy PL introductions benefit mainstream-quality NBs because these NBs become a compromise or middle option in terms of quality in the retailer's assortment. The effects of premium PL introductions on premium-quality NBs are mixed: Their share improves in two of four cases but decreases in the other two cases.
The “Right” Consumers for Better Concepts: Identifying Consumers High in Emergent Nature to Develop New Product Concepts
Authors: Hoffman Donna L. , Kopalle Praveen K. , Novak Thomas P.
Published: September 2010

While much research has emphasized improving current new product concept techniques, little work has focused on trait-based approaches that specify which consumers are the “right” ones to use in the new product development process, particularly in the consumer goods industry. The authors propose that the right consumers to use possess what they call an “emergent nature,” defined as the unique capability to imagine or envision how concepts might be developed so that they will be successful in the mainstream marketplace. The authors draw on research on personality theory and information-processing styles to support their conceptualization and develop and validate a highly reliable scale to measure emergent nature (Study 1). In subsequent multipart studies, they show in both group (Studies 2a–2c) and individual (Studies 3a and 3b) settings across two distinct product categories that consumers high in emergent nature are able to develop product concepts that mainstream consumers find significantly more appealing and useful than concepts developed by typical, lead user, or even innovative consumers.
Asymmetric Social Interactions in Physician Prescription Behavior: The Role of Opinion Leaders
Authors: Nair Harikesh S. , Manchanda Puneet , Bhatia Tulikaa
Published: September 2010

The authors quantify the impact of social interactions and peer effects in the context of physicians’ prescription choices. Using detailed individual-level prescription data, along with self-reported social network information, the authors document that physician prescription behavior is significantly influenced by the behavior of research-active specialists, or “opinion leaders,” in the physician's reference group. The authors leverage a natural experiment in the category: New guidelines released about the therapeutic nature of the focal drug generated conditions in which physicians were more likely to be influenced by the behavior of specialist physicians in their network. The authors (1) find important, statistically significant peer effects that are robust across model specifications; (2) document asymmetries in response to marketing activity across nominators and opinion leaders; (3) measure the incremental value to firms of directing targeted sales force activity to these opinion leaders; and (4) present estimates of the social multiplier of detailing in this category.
Shaping Customer Satisfaction through Self-Awareness Cues
Authors: Pham Michel Tuan , Goukens Caroline , Lehmann Donald R. , Stuart Jennifer Ames
Published: September 2010

Six studies show that subtle contextual cues that increase customers’ self-awareness can be used to influence their satisfaction with service providers (while holding the objective service delivery constant). Self-awareness cues tend to increase customers’ satisfaction when the outcome of a service interaction is unfavorable, but they tend to decrease customers’ satisfaction when the outcome of the interaction is favorable. This is because higher self-awareness increases customers’ tendency to attribute outcomes to themselves rather than to the provider. Self-awareness can even influence satisfaction with service interactions that occurred far in the past. The authors demonstrate these effects across a variety of lab and field settings with different simulated retail experiences and with different real-life service interactions, including college courses, meals taken at a university cafeteria, and items purchased at an actual clothing store. The results further show that attempts to shape customers’ satisfaction by means of self-awareness are more likely to be effective when there is substantial customer responsibility for the outcome; when customers’ responsibility is limited, such attempts may backfire.
The Orientation-Matching Hypothesis: An Emotion-Specificity Approach to Affect Regulation
Authors: Labroo Aparna A. , Rucker Derek D.
Published: September 2010

This article proposes that merely considering outcomes associated with a positive approach emotion (e.g., happiness) can regulate negative emotions that evoke an approach orientation (e.g., sadness, anger). In contrast, outcomes associated with a positive avoidance emotion (e.g., calmness) best regulate negative emotions that evoke an avoidance orientation (e.g., anxiety, embarrassment). Although such orientation-matched (versus mismatched) positive outcomes might not address the problem that caused the negative emotion, they automatically signal a reduced need for affect regulation specific to the evoked orientation. Thus, orientation matching results in emotional benefit, increases preferences toward matched outcomes, and frees resources for subsequent tasks.
An Assessment of Chronic Regulatory Focus Measures
Authors: Haws Kelly L. , Dholakia Utpal M. , Bearden William O.
Published: September 2010

Prior consumer research has demonstrated the ability of promotion and prevention regulatory orientations to moderate a variety of consumer and marketing phenomena but also has used several different methods to measure chronic regulatory focus. This article assesses five chronic regulatory focus measures using the criteria of theoretical coverage, internal consistency, homogeneity, stability, and predictive ability. The results reveal a lack of convergence among the measures and variation in their performance along these criteria. The authors provide specific guidance for choosing a particular measure in regulatory focus research and suggest a composite measure.
Case Study of Mechanical Control of Condensation in Exterior Walls
Authors: Morgan Christopher M. , McGowan Linda M. , Flick Loren D.
Published: September 2010

An electronics manufacturing facility in Colorado was constructed with typical commercial steel framing containing fiberglass batt insulation with foil-facing as the vapor retarder. A large portion of the facility required constant positive space pressurization and an indoor relative humidity (RH) of 48 % RH at 21°C (70°F). Due to a lack of containment of the moist interior air, condensation formed in the exterior walls, in the roofing, on the window and door systems, and on the skylights of the facility, particularly along the north and east elevations of the building, which resulted in significant damage to the wall components and the inability of the HVAC system to remain properly balanced. The as-constructed exterior wall systems were evaluated for performance relative to the existing building mechanical system. It was determined that the as-designed and as-constructed exterior wall assemblies and components could not perform satisfactorily under the necessary indoor environmental requirements. Options were explored to improve the performance of the exterior wall assemblies and related details. Due to a number of constraints, it was decided that constructing new walls inside the as-constructed exterior walls and windows, thereby creating an “interstitial” space to separate the exterior walls from the interior building space for their full height and mechanically supplying warm, dry air to this interstitial space, was the desired method to correct the condensation problems that were occurring. These repairs have proven to be effective. This paper discusses the original design and construction, the method of evaluation of the condensation problems that occurred, and the design and results of the implemented repairs.
A Role for Protein Kinase C-Dependent Upregulation of Adrenomedullin in the Development of Morphine Tolerance in Male Rats
Authors: Hong Yanguo , Wang Dongmei , Chabot Jean-Guy , Ma Weiya , Chen Peiwen , Quirion Rémi
Published: September 2010

Adrenomedullin (AM) belongs to calcitonin gene-related peptide (CGRP) family and is a pronociceptive mediator. This study investigated whether AM plays a role in the development of tolerance to morphine-induced analgesia. Repetitive intrathecal injection of morphine increased the expression of AM-like immunoreactivity (AM-IR) in the spinal dorsal horn and dorsal root ganglion (DRG) neurons. Ganglion explant culture study showed that this upregulation of AM-IR was μ-opioid receptor dependent through the use of another agonist, fentanyl, and a selective antagonist, CTAP (d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2). The coadministration of the selective AM receptor antagonist AM22-52markedly attenuated the development of morphine tolerance, associated thermal hyperalgesia, and increase in AM-IR. A likely autocrine mechanism is supported by the finding that AM-IR is colocalized with AM receptor components in DRG neurons. Furthermore, opiate-induced increase in AM content was blocked by protein kinase C (PKC) inhibitors, whereas a PKC activator increased AM synthesis and release. A treatment with AM22-52also inhibited increases in the expression of CGRP-IR in the spinal cord and DRGs as well as in culture ganglion explants, whereas exposure to CGRP failed to alter AM content. Together, these results reveal that a sustained opiate treatment induces an upregulation of AM through the activation of μ-opioid receptors and the PKC signaling pathway. This phenomenon contributes to the development of tolerance to the antinociceptive effects of opiates at least partially via the upregulation of CGRP. Targeting AM and its receptors should be considered as a novel approach to preserve the analgesic potency of opiates during their chronic use.
The Role of the Primary Visual Cortex in Perceptual Suppression of Salient Visual Stimuli
Authors: Keliris Georgios A. , Logothetis Nikos K. , Tolias Andreas S.
Published: September 2010

The role of primary visual cortex (area V1) in subjective perception has intrigued students of vision for decades. Specifically, the extent to which the activity of different types of cells (monocular versus binocular) and electrophysiological signals (i.e., local field potentials versus spiking activity) reflect perception is still debated. To address these questions we recorded from area V1 of the macaque using tetrodes during the paradigm of binocular flash suppression, where incongruent images presented dichoptically compete for perceptual dominance. We found that the activity of a minority (20%) of neurons reflect the perceived visual stimulus and these cells exhibited perceptual modulations substantially weaker compared with their sensory modulation induced by congruent stimuli. Importantly, perceptual modulations were found equally often for monocular and binocular cells, demonstrating that perceptual competition in V1 involves mechanisms across both types of neurons. The power of the local field potential (LFP) also showed moderate perceptual modulations with similar percentages of sites showing significant effects across frequency bands (18–22%). The possibility remains that perception may be strongly reflected in more elaborate aspects of activity in V1 circuits (e.g., specific neuronal subtypes) or perceptual states might have a modulatory role on more intricate aspects of V1 firing patterns (e.g., synchronization), not necessarily altering the firing rates of single cells or the LFP power dramatically.