bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Vascular Endothelial Growth Factor Genetic Variability in Cancer
Authors: Schneider Bryan P. , Radovich Milan , Miller Kathy D.
Published: August 2009

Angiogenesis is a hallmark of tumor pathogenesis. Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis and its inhibition has become a successful approach to antitumor therapy across tumor types. The VEGF gene is highly polymorphic with multiple common single nucleotide polymorphisms (SNPs) in the promoter, 5′ untranslated region and 3′ untranslated region. There is evidence that these SNPs in the regulatory regions can affect VEGF expression. In vitro and in vivo data show that genetic variability affects the activity and expression of VEGF. Case-control and cohort studies suggest that genetic variability may affect risk and outcome of a variety of disease states that are tightly regulated by angiogenesis. Recently, genetic variability in VEGF has been studied as a potential predictive biomarker for bevacizumab. The VEGF-1154 AA and -2578 AA genotypes predicted an improved median overall survival, whereas the VEGF-634 CC and -1498 TT genotypes predicted protection from grade 3-4 hypertension in the pivotal trial, E2100. If validated, these finding could help direct which subgroup of patients should receive bevacizumab. (Clin Cancer Res 2009;15(17):5297–302)
Cyclin D1 Splice Variants: Polymorphism, Risk, and Isoform-Specific Regulation in Prostate Cancer
Authors: Comstock Clay E.S. , Augello Michael A. , Benito Ruth Pe , Karch Jason , Tran Thai H. , Utama Fransiscus E. , Tindall Elizabeth A. , Wang Ying , Burd Craig J. , Groh Eric M. , Hoang Hoa N. , Giles Graham G. , Severi Gianluca , Hayes Vanessa M. , Henderson Brian E. , Le Marchand Loic , Kolonel Laurence N. , Haiman Christopher A. , Baffa Raffaele , Gomella Leonard G. , Knudsen Erik S. , Rui Hallgeir , Henshall Susan M. , Sutherland Robert L. , Knudsen Karen E.
Published: August 2009

Purpose: Alternative CCND1 splicing results in cyclin D1b, which has specialized, protumorigenic functions in prostate not shared by the cyclin D1a (full length) isoform. Here, the frequency, tumor relevance, and mechanisms controlling cyclin D1b were challenged.

Experimental Design: First, relative expression of both cyclin D1 isoforms was determined in prostate adenocarcinomas. Second, relevance of the androgen axis was determined. Third, minigenes were created to interrogate the role of the G/A870 polymorphism (within the splice site), and findings were validated in primary tissue. Fourth, the effect of G/A870 on cancer risk was assessed in two large case-control studies.

Results: Cyclin D1b is induced in tumors, and a significant subset expressed this isoform in the absence of detectable cyclin D1a. Accordingly, the isoforms showed noncorrelated expression patterns, and hormone status did not alter splicing. Whereas G/A870 was not independently predictive of cancer risk, A870 predisposed for transcript-b production in cells and in normal prostate. The influence of A870 on overall transcript-b levels was relieved in tumors, indicating that aberrations in tumorigenesis likely alter the influence of the polymorphism.

Conclusions: These studies reveal that cyclin D1b is specifically elevated in prostate tumorigenesis. Cyclin D1b expression patterns are distinct from that observed with cyclin D1a. The A870 allele predisposes for transcript-b production in a context-specific manner. Although A870 does not independently predict cancer risk, tumor cells can bypass the influence of the polymorphism. These findings have major implications for the analyses of D-cyclin function in the prostate and provide the foundation for future studies directed at identifying potential modifiers of the G/A870 polymorphism. (Clin Cancer Res 2009;15(17):5338–49)
Complexity of CEBPA Dysregulation in Human Acute Myeloid Leukemia
Authors: Pabst Thomas , Mueller Beatrice U.
Published: August 2009

The transcription factor CCAAT enhancer binding protein alpha (CEBPA) is crucial for normal development of granulocytes. Various mechanisms have been identified how CEBPA function is dysregulated in patients with acute myeloid leukemia (AML). In particular, dominant-negative mutations located either at the N- or the C terminus of the CEBPA gene are observed in roughly 10% of AML patients, either in the combination on separate alleles or as sole mutation. Clinically significant complexity exists among AML with CEBPA mutations, and patients with double CEBPA mutations seem to have a more favorable course of the disease than patients with a single mutation. In addition, myeloid precursor cells of healthy carriers with a single germ-line CEBPA mutation evolve to overt AML by acquiring a second sporadic CEBPA mutation. This review summarizes recent reports on dysregulation of CEBPA function at various levels in human AML and therapeutic concepts targeting correction of CEBPA activity. The currently available data are persuasive evidence that impaired CEBPA function contributes directly to the development of AML, whereas restoring CEBPA function represents a promising target for novel therapeutic strategies in AML. (Clin Cancer Res 2009;15(17):5303–7)
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

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

The 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]
Technique of Mobile Bony Island for Cochlear Implantation in Children
Authors: Jian-Jun Sun , Yang Liu , Sheng Lin Yong , Wei Yuan
Published: August 2009

The technique of mobile bony island is designed to form a buffering platform for the receiver/stimulator device of cochlear implant. It is especially suitable for young children, in whom the skull is thin and the protrusion of the device would otherwise be significant. This technique was used in 6 cases with an age range from 2 to 12 years old. After the inverted U-shaped postauricular incision and the elevation of the skin/periosteal flap were carried out, the mobile island of bone was drilled in the temporo-parieto-occipital region with a fine diamond burr. This thin island of bone lies on the dura with its edge 0.8–1.0 mm apart from the surrounding bone. The receiver/stimulator device MED-EL COMBI 40+ was positioned on the floating bony seat, and could be recessed 1.5–2.5 mm under slight pressure. This ‘floating island of a bony seat’ could reduce the protrusion of the device and provide a degree of protection from trauma.
Acute Vision Loss after Intravitreal Injection of Bevacizumab (Avastin) Associated with Ocular Ischemic Syndrome
Authors: Huang Zei-Lun , Lin Kung-Hung , Lee Yuan-Chieh , Sheu Min-Muh , Tsai Rong-Kung
Published: August 2009

Aim: To report a patient with diabetic rubeosis who suffered from acute retinal ischemic change and stroke after intravitreal injection of bevacizumab. Methods: A 55-year-old man had diabetes with unilateral rubeosis and macular edema. Three days after receiving intravitreal injection of bevacizumab (1.25 mg in 0.1 ml), he developed acute vision loss and change of consciousness. A complete ocular examination, fluorescein angiography, carotid artery Doppler sonography and brain magnetic resonance imaging were performed. Results: Best corrected visual acuity before injection was 6/60 in the left eye. He had underlying left carotid artery stenosis combined with bilateral preproliferative diabetic retinopathy. Three days after intravitreal injection of bevacizumab, acute ocular ischemic syndrome occurred. He also suffered from acute stroke, and brain magnetic resonance angiography showed total left internal carotid artery occlusion. The final visual acuity was no light perception in the left eye and 3/6 in the right eye. Conclusions: Patients receiving intravitreal injections of bevacizumab should be evaluated for potential systemic risk factors such as carotid insufficiency, coagulopathy and poorly controlled diabetes mellitus. Acute ocular ischemic change may be associated with intravitreal injection of bevacizumab in patients with vascular compromised diabetic retinopathy and/or underlying stenosis of the carotid artery.
Persistence of Neuropsychological Testing Deficits in Mild Cognitive Impairment
Authors: Teng Edmond , Tingus Kathleen D. , Lu Po H. , Cummings Jeffrey L.
Published: August 2009

Background: The significant variability across studies of mild cognitive impairment (MCI) in rates of progression to Alzheimer’s disease (AD) and reversion to normal cognition may be due to differences in specific neuropsychological tests and thresholds used to define MCI. Methods: We assessed 115 subjects with amnestic (AMN) or non-amnestic (NON) MCI on a standardized neuropsychological battery at baseline and after a mean follow-up of 16.4 months to determine the prevalence and persistence of deficits identified with specific tests. Results: The prevalence of impaired performance varied widely across tests. Deficits were more persistent in the AMN group than in the NON group. Baseline deficits in Visual Reproduction II and the California Verbal Learning Test were the best predictors of persistent memory impairment. Subjects who at baseline were impaired on multiple memory tests or had poorer overall memory performance were more likely to exhibit persistent memory deficits. Conclusions: The use of different neuropsychological tests and thresholds to diagnose MCI identified subsets of subjects with different rates of persistence of cognitive impairment. Standardization of the operational definition of cognitive impairment in MCI may result in more consistent predictions of progression to AD.
Inhibitory Effect of the New Orally Active CCR4 Antagonist K327 on CCR4+CD4+ T Cell Migration into the Lung of Mice with Ovalbumin-Induced Lung Allergic Inflammation
Authors: Sato Takashi , Komai Masato , Iwase Miho , Kobayashi Katsuya , Tahara Harunobu , Ohshima Etsuo , Arai Hitoshi , Miki Ichiro
Published: August 2009

CC chemokine receptor 4 (CCR4) is expressed on Th2 cells, found in inflamed tissues of allergic diseases, and is therefore suspected to be involved in the pathogenesis of allergic diseases by controlling Th2 cell migration into inflamed tissues. The aim of the present study was to investigate the inhibitory effect of a selective CCR4 antagonist, K327 [6-cyclopropancarbonyl-4-(2,4-dichlorobenzylamino)-2-(4-[2-(piperidin-1-yl)ethyl] piperazin-1-yl)-7,8-dihydro-5H-pyrido (4,3-d)pyrimidine], on the recruitment of CCR4+CD4+ T cells to the airway of mice with ovalbumin-induced allergic airway inflammation. K327 was administered to mice in which CCR4+CD4+ T cell accumulation was elicited by multiple inhalations of aerosolized ovalbumin. K327 significantly and dose-dependently inhibited the recruitment of CCR4+CD4+ T cells with an ID50 value of 44 mg/kg, p.o. twice daily. The antiasthmatic potential of K327 was also demonstrated by the fact that K327 suppressed the elevation of Th2 cytokines and airway eosinophilia. These results indicate that CCR4 antagonists can control in vivo migration of Th2 cells which express CCR4 and, presumably, serve as a new class of therapeutic agent for allergy.
An Epidemiologic Study on Aging and Dysphagia in the Acute Care Hospitalized Population: 2000–2007
Authors: Leder Steven B. , Suiter Debra M.
Published: August 2009

Objectives: To describe total and yearly demographic trends relative to aging, dysphagia referral rates and oral feeding status in hospitalized patients from 2000 through 2007. Methods: We evaluated a prospective, consecutive, referred sample of 4,038 hospitalized patients in an urban, tertiary, acute care teaching hospital. Dysphagia referral rates are described according to year, age (decade), sex, admitting diagnostic category, results of dysphagia evaluations and oral feeding status. Diagnosis of dysphagia and feeding status were assessed objectively with fiberoptic endoscopic evaluation of swallowing. Results: Dysphagia referral rates doubled between 2000 and 2007, with increases of 20% per year and increases in all decades from 2002 through 2007. Over 70% of dysphagia referrals were for older patients of 60 years and above, and over 42% of these were old old patients over 80 years. Referrals for 80 to 89-year-old patients almost doubled and for patients over 90 years more than tripled between 2000 and 2007. Of older patients over 60 years, 62.3% (1,771/2,843) did not exhibit dysphagia, 18.0% (513/2,843) benefited from specific diet modifications to reduce aspiration risk and 19.7% (559/2,843) were made nil-by-mouth due to severe dysphagia and aspiration. Conclusions: From 2000 to 2007, dysphagia referrals across all ages increased by 20% each year, with more referrals for older (70.4%) than younger patients (29.6%). Referrals almost doubled for 80 to 89-year-old patients and more than tripled for patients over 90 years. This increase will necessitate additional trained dysphagia specialists at least through 2050 and probably longer.
Images in Gerontology: A Case Report
Authors: Coudroy R. , Debouverie O. , Poupet J.Y. , Roblot P. , Paccalin M.
Published: August 2009

Left ventricular aneurysm can complicate acute myocardial infarction. Clinical and electrocardiogram features are not specific. We describe a case with asymptomatic left ventricular aneurysm diagnosed by computerized-tomography angiography.
Direct Cleavage, Proteasomal Degradation and Sequestration: Three Mechanisms of Viral Subversion of Type I Interferon Responses
Authors: McInerney Gerald M. , Karlsson Hedestam Gunilla B.
Published: August 2009

The host type I interferon (IFN) system is central in antiviral defence and represents one of the greatest obstacles for a virus to overcome in order to establish a productive infection. Viruses have evolved many different mechanisms to repress the effects of the type I IFN system. For example, a number of viruses encode viral proteases, which can directly cleave and inactivate key components of the type I IFN induction and signalling pathway. Others recruit the ubiquitin proteasome system to destabilise proteins that are important for IFN responses. There are also many known viral proteins, which bind to and sequester proteins of the type I IFN system in an inactive state. Here, we review each of these different mechanisms of viral escape from the type I IFN response with examples from a range of viruses.
Differences in Pulmonary Function Based on Height Prediction Obtained by Using Alternative Measures
Authors: Sancho-Chust José N. , Chiner Eusebi , Camarasa Ana , Senent Cristina
Published: August 2009

Background: Standing height is an independent variable used to predict pulmonary function; however, some patients are not able to stand. Objectives: The objectives of this study were to compare predicted pulmonary function values obtained by using various alternative measures to estimate height, analyse the values’ reproducibility and evaluate their agreement. Methods: Standing height, knee height, ulna length, demi-span and arm span were measured in 100 subjects who were able to stand. Five groups of values were generated for predicted FVC and FEV1 based on measured standing height and the height estimated using each alternative measure. Results: The differences found between the height estimated using the different measures and measured standing height were statistically significant. The reproducibility was excellent; however, agreement was poor and all the measures tended to overestimate the predicted values based on standing height although this tendency was less marked in the case of knee height. Conclusions: The use of alternative measures to predict height introduces a certain degree of error in predicted pulmonary function and this error should be quantified. Knee height is the measure that shows the greatest agreement and, thus, could be used in patients who are unable to stand.
Protein Kinase A-Dependent Biophysical Phenotype for V227F-KCNJ2 Mutation in Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Vega Amanda L. , Tester David J. , Ackerman Michael J. , Makielski Jonathan C.
Published: August 2009

Background—

KCNJ2
encodes Kir2.1, a pore-forming subunit of the cardiac inward rectifier current, I
K1
.
KCNJ2
mutations are associated with Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia. The aim of this study was to characterize the biophysical and cellular phenotype of a
KCNJ2
missense mutation, V227F, found in a patient with catecholaminergic polymorphic ventricular tachycardia.

Methods and Results—

Kir2.1-wild-type (WT) and V227F channels were expressed individually and together in Cos-1 cells to measure I
K1
by voltage clamp. Unlike typical Andersen-Tawil syndrome-associated
KCNJ2
mutations, which show dominant negative loss of function, Kir2.1WT+V227F coexpression yielded I
K1
indistinguishable from Kir2.1-WT under basal conditions. To simulate catecholamine activity, a protein kinase A (PKA)-stimulating cocktail composed of forskolin and 3-isobutyl-1-methylxanthine was used to increase PKA activity. This PKA-simulated catecholaminergic stimulation caused marked reduction of outward I
K1
compared with Kir2.1-WT. PKA-induced reduction in I
K1
was eliminated by mutating the phosphorylation site at serine 425 (S425N).

Conclusions—

Heteromeric Kir2.1-V227F and WT channels showed an unusual latent loss of function biophysical phenotype that depended on PKA-dependent Kir2.1 phosphorylation. This biophysical phenotype, distinct from typical Andersen-Tawil syndrome mutations, suggests a specific mechanism for PKA-dependent I
K1
dysfunction for this
KCNJ2
mutation, which correlates with adrenergic conditions underlying the clinical arrhythmia.
Left Ventricular Septal and Left Ventricular Apical Pacing Chronically Maintain Cardiac Contractile Coordination, Pump Function and Efficiency
Authors: Mills Robert W. , Cornelussen Richard N. , Mulligan Lawrence J. , Strik Marc , Rademakers Leonard M. , Skadsberg Nicholas D. , van Hunnik Arne , Kuiper Marion , Lampert Anniek , Delhaas Tammo , Prinzen Frits W.
Published: August 2009

Background—

Conventional right ventricular (RV) apex pacing can lead to adverse clinical outcome associated with asynchronous activation and reduced left ventricular (LV) pump function. We investigated to what extent alternate RV (septum) and LV (septum, apex) pacing sites improve LV electric activation, mechanics, hemodynamic performance, and efficiency over 4 months of pacing.

Methods and Results—

After AV nodal ablation, mongrel dogs were randomized to receive 16 weeks of VDD pacing at the RV apex, RV septum, LV apex, or LV septum (transventricular septal approach). Electric activation maps (combined epicardial contact and endocardial noncontact) showed that RV apical and RV septal pacing induced significantly greater electric desynchronization than LV apical and LV septal pacing. RV apex and RV septal pacing also significantly increased mechanical dyssynchrony, discoordination (MRI tagging) and blood flow redistribution (microspheres) and reduced LV contractility, relaxation, and myocardial efficiency (stroke work/myocardial oxygen consumption). In contrast, LV apical and LV septal pacing did not significantly alter these parameters as compared with the values during intrinsic conduction. At 16 weeks, acute intrasubject comparison showed that single-site LV apical and LV septal pacing generally resulted in similar or better contractility, relaxation, and efficiency as compared with acute biventricular pacing.

Conclusions—

Acute and chronic LV apical and LV septal pacing maintain regional cardiac mechanics, contractility, relaxation, and efficiency near native levels, whereas RV apical or RV septal pacing diminish these variables. Acute LV apical and LV septal pacing tend to maintain or improve contractility and efficiency compared with biventricular pacing.
Would Achieving Healthy People 2010’s Targets Reduce Both Population Levels and Social Disparities in Heart Disease?
Authors: Alvarado Beatriz E. , Harper Sam , Platt Robert W. , Smith George Davey , Lynch John
Published: August 2009

Background—

The US Healthy People 2010 (HP2010) agenda set targets for major risk factors for coronary heart disease (CHD). However, the potential impact of achieving those risk factor reductions on both population levels and social disparities in CHD has not been quantified.

Methods and Results—

Data on 10-year risk of CHD (from the First National Health and Nutrition Examination Epidemiological Follow-Up study 1971 to 1982), prevalence of major CHD risk factors (from the National Health and Nutrition Examination Survey 2003 to 2004), and HP2010 targets for CHD risk factors (reduction of smoking rate to 12%, hypertension to 14%, high cholesterol levels to 17%, diabetes to 2.5%, and obesity to 15%) were used to estimate effects of different scenarios on population levels and social disparities in CHD. Over a 10-year period, the largest relative reductions in population levels of CHD (20.0% in men; 23.9% in women) would be achieved if all social groups met the HP2010 targets. CHD disparities would be most reduced if the less educated (absolute disparities reduced by 66.1% in men; 56.3% in women) and the low income group (absolute disparities reduced by 93.7% in men; 94.3% in women) achieved the targets before the most advantaged. These reductions are larger than those expected if targets were achieved overall for the population but relative social group differences in risk factors remained, or under leveling-up approaches in which the least advantaged achieved the current levels of risk factors of the most advantaged.

Conclusions—

Interventions to reduce CHD risk factors to HP2010 targets that focus on all social groups would produce the best overall scenario for both population levels and disparities in CHD.
Performance and Efficiency of Memetic Pittsburgh Learning Classifier Systems
Authors: Bacardit Jaume , Krasnogor Natalio
Published: August 2009

In this paper we empirically evaluate several local search (LS) mechanisms that heuristically edit classification rules and rule sets to improve their performance. Two kinds of operators are studied, (1) rule-wise operators, which edit individual rules, and (2) a rule set-wise operator, which takes the rules from N parents (N ≥ 2) to generate a new offspring, selecting the minimum subset of candidate rules that obtains maximum training accuracy. Moreover, various ways of integrating these operators within the evolutionary cycle of learning classifier systems are studied. The combinations of LS operators and policies are integrated in a Pittsburgh approach framework that we call MPLCS for memetic Pittsburgh learning classifier system. MPLCS is systematically evaluated using various metrics. Several datasets were employed with the objective of identifying which combination of operators and policies scale well, are robust to noise, generate compact solutions, and use the least amount of computational resources to solve the problems.
Locating and Characterizing the Stationary Points of the Extended Rosenbrock Function
Authors: Kok Schalk , Sandrock Carl
Published: August 2009

Two variants of the extended Rosenbrock function are analyzed in order to find the stationary points. The first variant is shown to possess a single stationary point, the global minimum. The second variant has numerous stationary points for high dimensionality. A previously proposed method is shown to be numerically intractable, requiring arbitrary precision computation in many cases to enumerate candidate solutions. Instead, a standard Newtonian method with multi-start is applied to locate stationary points. The relative magnitude of the negative and positive eigenvalues of the Hessian is also computed, in order to characterize the saddle points. For dimensions up to 100, only two local minimizers are found, but many saddle points exist. Two saddle points with a single negative eigenvalue exist for high dimensionality, which may appear as “near” local minima. The remaining saddle points we found have a predictable form, and a method is proposed to estimate their number. Monte Carlo simulation indicates that it is unlikely to escape these saddle points using uniform random search. A standard particle swarm algorithm also struggles to improve upon a saddle point contained within the initial population.
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

Optically 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

The 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

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

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

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

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.
How other people shape our careers: A typology drawn from career narratives
Authors: Bosley Sara L.C. , Arnold John , Cohen Laurie
Published: August 2009

From a constructionist perspective, we examine how non-managerial employees make sense of the part played by other people in shaping their careers. Taking as our starting point the methodological limitations of existing research into career shapers and arguing for a perspective that starts with actors’ situated understandings, we use a life story method to develop a new typology of career shapers. Grounded in our data, we distinguish and contrast the shaper categories of adviser, informant, witness, gatekeeper and intermediary in terms of their perceived impact on individuals, including their career aspirations, career enactment, and their career world-view and career self-concept. At the level of practice, locating themselves within this framework will enable line managers, human resources staff and professional careers advisers to be explicit about the career support they can offer, and to identify other potentially valuable career shapers.
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.
Identification of Contact Parameters from Stiff Multi-point Contact Robotic Operations
Authors: Verscheure Diederik , Sharf Inna , Bruyninckx Herman , Swevers Jan , De Schutter Joris
Published: August 2009

Computer simulations play an important role in the design and validation of constrained robotic operations. The fidelity of these simulations, however, depends on the specification of contact dynamics parameters, which often need to be determined experimentally. In this paper we investigate the identification of contact parameters from complex stiff multi-point contact scenarios encountered in typical robotic operations using a recently developed least-squares-based method. This method is extended to deal with geometric uncertainties by employing a non-linear separable least-squares formulation. The latter is solved using a variable projection method, and allows simultaneous identification of contact parameters and geometric uncertainties. The conditions for observability of geometric uncertainties are derived and a regularized formulation is proposed in case the identification of geometric uncertainties is ill-conditioned. The applicability of the original method and the benefits of the extended method with identification of geometric uncertainties for the identification of the contact parameters are illustrated by means of experimental data measured with the Special Purpose Dexterous Manipulator (SPDM) Task Verification Facility (STVF) manipulator at the Canadian Space Agency (CSA).
Transferring Post-Secondary Schools
Authors: Gallander Wintre Maxine , Morgan Ashley S.
Published: August 2009

The present study is an empirical investigation of the experience of students transferring from one post-secondary institution to another. Positioned within several theories, most notably emerging adulthood theory, the findings imply that transferring schools represents a positive growth experience for the student who recognizes an inappropriate match with the first institution attended. In telephone interviews, students who had transferred to a large, ethnically diverse, commuter university were asked about their perceived adjustment pre- and post-transfer, their perceived control over the transfer decision, and their transfer experiences. The results indicate that transfer students are engaging in a mature decision-making process. Transfer students perceived a better fit and improved adjustment at their new university, suggesting that transferring institutions was a beneficial decision.
Exploring Gen Y Responses to an Apparel Brand’s Use of Cause-Related Marketing Does Message Matter When It Comes to Support for the Breast Cancer Cause?
Authors: Hyllegard Karen H. , Paff Ogle Jennifer , Yan Ruoh-Nan , Attmann Julianne
Published: August 2009

This study explored Gen Y’s responses to cause-related marketing (CRM) in apparel advertising. Data were collected from 349 Gen Y consumers to examine the influence of CRM on attitudes and purchase intentions toward an apparel brand. Attitude toward the brand was predicted by awareness of the apparel brand, perception of CRM, evaluation of the advertisement, involvement in the breast cancer cause, and gender. The theory of reasoned action was used to predict Gen Y’s purchase intentions and the utility of the classic model was compared to that of an extended model that included variables external to the theory. In the classic model, purchase intention was predicted by attitude toward the brand and subjective norm. In the extended model, purchase intention was predicted by attitude toward the brand, subjective norm, awareness of the apparel brand, evaluation of the advertisement, and involvement in the breast cancer cause. A calculated F-ratio indicated that the extended model provided additional explanatory power.