bluuebunny/crossref_metadata_2025 huggingface dataset:
The Case for the Use of PPARγ Agonists as an Adjunctive Therapy for Cerebral Malaria
Authors: Serghides Lena
Published: June 2011

Cerebral malaria is a severe complication ofPlasmodium falciparuminfection associated with high mortality even when highly effective antiparasitic therapy is used. Adjunctive therapies that modify the pathophysiological processes caused by malaria are a possible way to improve outcome. This review focuses on the utility of PPARγ agonists as an adjunctive therapy for the treatment of cerebral malaria. The current knowledge of PPARγ agonist use in malaria is summarized. Findings from experimental CNS injury and disease models that demonstrate the potential for PPARγ agonists as an adjunctive therapy for cerebral malaria are also discussed.
PD-1/PD-L1 Interactions Contribute to Functional T-Cell Impairment in Patients Who Relapse with Cancer After Allogeneic Stem Cell Transplantation
Authors: Norde Wieger J. , Maas Frans , Hobo Willemijn , Korman Alan , Quigley Michael , Kester Michel G.D. , Hebeda Konnie , Falkenburg J.H. Frederik , Schaap Nicolaas , de Witte Theo M. , van der Voort Robbert , Dolstra Harry
Published: June 2011

Tumor relapses remain a serious problem after allogeneic stem cell transplantation (alloSCT), despite the long-term persistence of minor histocompatibility antigen (MiHA)-specific memory CD8+ T cells specific for the tumor. We hypothesized that these memory T cells may lose their function over time in transplanted patients. Here, we offer functional and mechanistic support for this hypothesis, based on immune inhibition by programmed death-1 (PD-1) expressed on MiHA-specific CD8+ T cells and the associated role of the PD-1 ligand PD-L1 on myeloid leukemia cells, especially under inflammatory conditions. PD-L1 was highly upregulated on immature human leukemic progenitor cells, whereas costimulatory molecules such as CD80 and CD86 were not expressed. Thus, immature leukemic progenitor cells seemed to evade the immune system by inhibiting T-cell function via the PD-1/PD-L1 pathway. Blocking PD-1 signaling using human antibodies led to elevated proliferation and IFN-γ production of MiHA-specific T cells cocultured with PD-L1–expressing leukemia cells. Moreover, patients with relapsed leukemia after initial MiHA-specific T-cell responses displayed high PD-L1 expression on CD34+ leukemia cells and increased PD-1 levels on MiHA-specific CD8+ T cells. Importantly, blocking PD-1/PD-L1 interactions augment proliferation of MiHA-specific CD8+ memory T cells from relapsed patients. Taken together, our findings indicate that the PD-1/PD-L pathway can be hijacked as an immune escape mechanism in hematological malignancies. Furthermore, they suggest that blocking the PD-1 immune checkpoint offers an appealing immunotherapeutic strategy following alloSCT in patients with recurrent or relapsed disease. Cancer Res; 71(15); 5111–22. ©2011 AACR.
Enhanced Efficacy of IGF1R Inhibition in Pediatric Glioblastoma by Combinatorial Targeting of PDGFRα/β
Authors: Bielen Aleksandra , Perryman Lara , Box Gary M. , Valenti Melanie , de Haven Brandon Alexis , Martins Vanessa , Jury Alexa , Popov Sergey , Gowan Sharon , Jeay Sebastien , Raynaud Florence I. , Hofmann Francesco , Hargrave Darren , Eccles Suzanne A. , Jones Chris
Published: June 2011

Pediatric glioblastoma (pGBM), although rare, is one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. We have identified IGF1R to be a potential therapeutic target in pGBM due to gene amplification and high levels of IGF2 expression in some tumor samples, as well as constitutive receptor activation in pGBM cell lines. To evaluate the therapeutic potential of strategies targeting the receptor, we have carried out in vitro and in vivo preclinical studies using the specific IGF1R inhibitor NVP-AEW541. A modest inhibitory effect was seen in vitro, with GI50 values of 5 to 6 μmol/L, and concurrent inhibition of receptor phosphorylation. Specific targeting of IGF1R with short interfering RNA decreased cell viability, diminished downstream signaling through phosphoinositide 3-kinase (PI3K), and induced G1 arrest, effects mimicked by NVP-AEW541, both in the absence and presence of IGF2. Hallmarks of PI3K inhibition were observed after treatment with NVP-AEW541 by expression profiling and Western blot analysis. Phospho–receptor tyrosine kinase (RTK) arrays showed phosphorylation of platelet-derived growth factor receptor (PDGFR) α/β in pGBM cells, suggesting coactivation of an alternative RTK pathway. Treatment of KNS42 with the PDGFR inhibitor imatinib showed additional effects targeting the mitogen-activated protein kinase pathway, and cotreatment of the PDGFR inhibitor imatinib with NVP-AEW541 resulted in a highly synergistic interaction in vitro and increased efficacy after 14 days therapy in vivo compared with either agent alone. These data provide evidence that inhibition of IGF1R, in combination with other targeted agents, may be a useful and novel therapeutic strategy in pGBM. Mol Cancer Ther; 10(8); 1407–18. ©2011 AACR.
Association of Interleukin-1β Gene Polymorphism and Peritonitis in Uremic Patients Undergoing Peritoneal Dialysis
Authors: Shu Kuo-Hsiung , Chuang Ya-Wen , Huang Shih-Ting , Cheng Chi-Hung , Wu Ming-Ju , Chen Cheng-Hsu , Yu Tung-Min
Published: June 2011

Objective: Interleukin-1 (IL-1) is involved in the disease process of peritonitis. We hypothesize that IL-1 gene polymorphism may have an impact on the occurrence of peritonitis in uremic patients undergoing peritoneal dialysis (PD). Methods: Uremic patients were recruited for the study of IL-1β (–511) C/T gene polymorphism in 2002. These patients were then prospectively followed up to monitor their peritoneal membrane characteristics, biochemical parameters, occurrence of peritonitis and patient as well as PD technique survival. Results: A total of 74 patients were enrolled in the study. During follow-up, at least one episode of peritonitis occurred in 36 patients. Compared with patients without peritonitis, the carriage of C allele in IL-1β gene polymorphism (C/C and C/T genotypes) was significantly associated with the occurrence of peritonitis (p = 0.013). This was further confirmed in the multivariate logistic regression analysis (odds ratio 8.18, p = 0.017). Conclusion: Carriers of C allele were associated with an increased risk of peritonitis.
Distribution of Volumes of Individual Glomeruli in Kidneys at Autopsy: Association with Physical and Clinical Characteristics and with Ethnic Group
Authors: Hoy Wendy E. , Hughson Michael D. , Diouf Boucar , Zimanyi Monika , Samuel Terence , McNamara Bridgette J. , Douglas-Denton Rebecca N. , Holden Libby , Mott Susan A. , Bertram John F.
Published: June 2011

We have demonstrated considerable variability in the volumes of different glomeruli in given individuals (individual glomerular volume: IGV) in a stereologic study of kidneys at forensic autopsy performed to investigate sudden or unexpected death in people without manifest kidney disease. We review some important associations of IGV by subject characteristics and by ethnic groups. IGVs were measured by the Cavalieri method in 30 glomeruli in each of 111 adult males who belonged to 4 ethnic groups, i.e. US Whites, African-Americans, Africans from Senegal, and Australian Aborigines. Correlations of pooled IGV values with certain subject characteristics were evaluated in the US Whites. Pooled IGV data were compared in subjects across the 4 ethnic groups. In US Whites, mean IGV and its variance were greater with higher age, lower nephron number, lower birth weight, and with gross obesity, hypertension and cardiovascular death. In comparisons by ethnic group, mean IGV and IGV ranges were higher in African-Americans and Australian Aborigines than in US Whites and African Senegalese subjects. We conclude that glomerular enlargement with volume heterogeneity marks more advanced age, relative nephron deficiency, lower birth weight, obesity, hypertension, and advanced cardiovascular disease. The findings in African-Americans and Australian Aborigines suggest that larger IGVs and volume heterogeneity might mark populations with accentuated susceptibility to hypertension and kidney disease, but the data need to be further examined in the context of the determining characteristics defined in the US Whites.
Advantages and Controversies in the Era of Intrarenal Volumetry
Authors: Pedersen Michael , Karstoft Kristian , Lødrup Anders , Jespersen Bente , Nyengaard Jens R.
Published: June 2011

Background/Aims: Ultrasound is the preferred imaging modality in nephrology. In many kidney diseases, however, more accurate methods are needed to distinguish between relevant intrarenal structures. MRI could be a solution, although the use of MRI contrast has caused severe complications in some cases, and invasive kidney biopsies may follow, even though such small specimens traditionally provide inaccurate quantitative data. We evaluated the usefulness of MRI volumetry and quantitative kidney biopsies to assess glomerular number and volume as well as cortical volume. Methods: We specifically highlight an experimental study in which different MRI scans were performed in healthy pigs as well as pigs with unilateral ureteral obstruction to assess intrarenal volume. Single-kidney glomerular filtration rate (GFR) was measured using ureteral cannulation and 51Cr-EDTA. Kidney biopsies were taken and evaluated employing stereological techniques to measure number and volume of glomeruli. Pigs were sacrificed and kidneys were removed for stereological analysis. Non-contrast-based MRI intrarenal volumes were – without significant difference to intrarenal volumes – obtained using contrast-enhanced MRI and ex vivo techniques. Results: Kidney biopsies gave valid estimates regarding quantitative parameters, such as mean number and volume of glomeruli in the cortex. Different structural parameters correlated with kidney GFR with high, although varying, correlation coefficients. Conclusion: Non-contrast MRI is suitable for estimating intrarenal volumes in healthy and diseased kidneys. We advocate further research in diagnostic modalities combining MRI and biopsies. Major challenges are the cortical architecture and heterogeneous distribution of glomeruli within the kidney.
Activation of Intrarenal Renin-Angiotensin System during Metabolic Acidosis
Authors: Ng Hwee-Yeong , Chen Hung-Chun , Tsai Yu-Che , Yang Yu-Kun , Lee Chien-Te
Published: June 2011

Background: Chronic metabolic acidosis is a common metabolic disturbance and its clinical impact can be severe and extensive. The role and the change of the intrarenal renin-angiotensin system (RAS) during metabolic acidosis are uncertain, and whether acidosis can evoke inflammation remains unclear. Methods: Male Sprague-Dawley rats were fed with water containing 0.14 M NH4Cl to induce metabolic acidosis for 1 and 8 weeks, respectively. They were compared with animals fed with deionized water (control) and equimolar sodium chloride water (NaCl). Gene expression analysis of RAS components included renin, renin/prorenin receptor, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II type 1 and 2 receptors (AT1R and AT2R). Histological examination was also performed to detect morphological change. Results: Acidosis was found in 1-week NH4Cl-treated rats but not in the 8-week group. More than twofold proteinuria and a significant decline of glomerular filtration rate (GFR) were observed in acid-loaded rats. Compared to the control and NaCl groups, angiotensinogen, ACE, AT1R and AT2R were significantly increased in the 1-week acidosis group (all p < 0.05). Sustained increase of AT1R expression was found as NH4Cl was continued for 8 weeks. There was no significant change in transforming growth factor-β and nuclear factor-ĸB. The architecture of tubular epithelial cells was affected during our experiment. Conclusion: Metabolic acidosis induced proteinuria and decline of GFR in association with activation of intrarenal RAS.
A Phase II Multi-Center Study of Triple Therapy with Paclitaxel, S-1 and Cisplatin in Patients with Advanced Gastric Cancer
Authors: Iwase H. , Shimada M. , Tsuzuki T. , Ina K. , Sugihara M. , Haruta J. , Shinoda M. , Kumada T. , Goto H.
Published: June 2011

Objectives: To carry out a phase II multi-center study on the efficacy and safety of triple combination therapy with paclitaxel, S-1, and cisplatin in patients with unresectable/metastatic gastric cancer. Methods: A total of 63 patients from 8 institutions were included in this study. Paclitaxel (160 mg/m2) was administered by infusion for 3 h on the first day. S-1 (70 mg/m2/day) was administered orally for 14 consecutive days from the first day. Cisplatin (60 mg/m2) was administered intravenously over 24 h on day 14 of every 28-day cycle. Results: All 63 patients were assessed for clinical efficacy and safety. A total of 259 cycles of treatment were administered (median 4, range 1–10). Grade 3–4 toxicities included neutropenia in 30.2%, thrombocytopenia in 12.7%, and anemia in 11.1%. There was no grade 3–4 non-hematological toxicity or treatment-related death. Complete response was observed in 6 patients and partial response in 34 patients. The overall response rate was 63.5%. The median progression-free survival and response duration were 8.0 and 8.8 months, respectively, and median survival time was 15 months. Conclusions: Triple combination therapy with paclitaxel, S-1, and cisplatin showed promising safety and efficacy profiles with the potential to become a standard regimen for unresectable/metastatic gastric cancer.
Moderate Caveolin-1 Downregulation Prevents NADPH Oxidase–Dependent Endothelial Nitric Oxide Synthase Uncoupling by Angiotensin II in Endothelial Cells
Authors: Lobysheva Irina , Rath Géraldine , Sekkali Belaïd , Bouzin Caroline , Feron Olivier , Gallez Bernard , Dessy Chantal , Balligand Jean-Luc
Published: June 2011

Objective—

We analyzed the role of caveolin-1 (Cav-1) in the cross-talk between NADPH oxidase and endothelial nitric oxide synthase (eNOS) signaling in endothelial caveolae.

Methods and Results—

In intact endothelial cells, angiotensin II (AII) concurrently increased NO and O
2
−·
production (to 158±12% and 209±5% of control). NO production was sensitive to inhibition of NADPH oxidase and small interfering RNA downregulation of nonreceptor tyrosine kinase cAbl. Reciprocally, N-nitro-
l
-arginine methyl ester, a NOS inhibitor, partly inhibited O
2
−·
stimulated by AII (by 47±11%), indicating eNOS uncoupling, as confirmed by increased eNOS monomer/dimer ratio (by 35%). In endothelial cell fractions separated by isopycnic ultracentrifugation, AII promoted colocalization of cAbl and the NADPH oxidase subunit p47phox with eNOS to Cav-1-enriched fractions, as confirmed by proximity ligation assay. Downregulation of Cav-1 by small interfering RNA (to 50%), although it preserved eNOS confinement, inhibited AII-stimulated p47phox translocation and NADPH oxidase activity in Cav-1-enriched fractions and reversed eNOS uncoupling. AII infusion produced hypertension and decreased blood hemoglobin-NO in Cav-1
+/+
mice but not in heterozygote Cav-1
+/−
mice with similar Cav-1 reduction.

Conclusion—

Cav-1 critically regulates reactive oxygen species–dependent eNOS activation but also eNOS uncoupling in response to AII, underlining the possibility to treat endothelial dysfunction by modulating Cav-1 abundance.
Autophagy and p62 in Cardiac Proteinopathy
Authors: Zheng Qingwen , Su Huabo , Ranek Mark J. , Wang Xuejun
Published: June 2011

Rationale:

Recent studies suggest an important role of autophagy in protection against αB-crystallin-based (CryAB
R120G
) desmin-related cardiomyopathies (DRC), but this has not been demonstrated in a different model of cardiac proteinopathy. Mechanisms underlying the response of cardiomyocytes to proteotoxic stress remain incompletely understood.

Objective:

Our first objective was to determine whether and how the autophagic activity is changed in a mouse model of desminopathy. We also investigated the role of p62 in the protein quality control of cardiomyocytes.

Methods and Results:

Using an autophagosome reporter and determining changes in LC3-II protein levels in response to lysosomal inhibition, we found significantly increased autophagic flux in mouse hearts with transgenic overexpression of a DRC-linked mutant desmin. Similarly, autophagic flux was increased in cultured neonatal rat ventricular myocytes (NRVMs) expressing a mutant desmin. Suppression of autophagy by 3-methyladenine increased, whereas enhancement of autophagy by rapamycin reduced the ability of a comparable level of mutant desmin overexpression to accumulate ubiquitinated proteins in NRVMs. Furthermore, p62 mRNA and protein expression was significantly up-regulated in cardiomyocytes by transgenic overexpression of the mutant desmin or CryAB
R120G
both in intact mice and in vitro. The p62 depletion impaired aggresome and autophagosome formation, exacerbated cell injury, and decreased cell viability in cultured NRVMs expressing the misfolded proteins.

Conclusions:

Autophagic flux is increased in desminopathic hearts, and as previously suggested in CryAB
R120G
-based DRC, this increased autophagic flux serves as an adaptive response to overexpression of misfolded proteins. The p62 is up-regulated in mouse proteinopathic hearts. The p62 promotes aggresome formation and autophagy activation and protects cardiomyocytes against proteotoxic stress.
A Novel Ryanodine Receptor Mutation Linked to Sudden Death Increases Sensitivity to Cytosolic Calcium
Authors: Meli Albano C. , Refaat Marwan M. , Dura Miroslav , Reiken Steven , Wronska Anetta , Wojciak Julianne , Carroll Joan , Scheinman Melvin M. , Marks Andrew R.
Published: June 2011

Rationale:

Mutations in the cardiac type 2 ryanodine receptor (RyR2) have been linked to catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT-associated RyR2 mutations cause fatal ventricular arrhythmias in young individuals during β-adrenergic stimulation.

Objective:

This study sought to determine the effects of a novel RyR2-G230C mutation and whether this mutation and RyR2-P2328S alter the sensitivity of the channel to luminal calcium (Ca
2+
).

Methods and Results:

Functional characterizations of recombinant human RyR2-G230C channels were performed under conditions mimicking stress. Human RyR2 mutant channels were generated by site-directed mutagenesis and heterologously expressed in HEK293 cells together with calstabin2. RyR2 channels were measured to examine the regulation of the channels by cytosolic versus luminal sarcoplasmic reticulum Ca
2+
. A 50-year-old white man with repeated syncopal episodes after exercise had a cardiac arrest and harbored the mutation RyR2-G230C. cAMP-dependent protein kinase–phosphorylated RyR2-G230C channels exhibited a significantly higher open probability at diastolic Ca
2+
concentrations, associated with a depletion of calstabin2. The luminal Ca
2+
sensitivities of RyR2-G230C and RyR2-P2328S channels were WT-like.

Conclusions:

The RyR2-G230C mutant exhibits similar biophysical defects compared with previously characterized CPVT mutations: decreased binding of the stabilizing subunit calstabin2 and a leftward shift in the Ca
2+
dependence for activation under conditions that simulate exercise, consistent with a “leaky” channel. Both RyR2-G230C and RyR2-P2328S channels exhibit normal luminal Ca
2+
activation. Thus, diastolic sarcoplasmic reticulum Ca
2+
leak caused by reduced calstabin2 binding and a leftward shift in the Ca
2+
dependence for activation by diastolic levels of cytosolic Ca
2+
is a common mechanism underlying CPVT.
Prehospital Notification by Emergency Medical Services Reduces Delays in Stroke Evaluation
Authors: Patel Mehul D. , Rose Kathryn M. , O'Brien Emily C. , Rosamond Wayne D.
Published: June 2011

Background and Purpose—

Individuals with stroke-like symptoms are recommended to receive rapid diagnostic evaluation. Emergency medical services (EMS) transport, compared with private modes, and hospital notification before arrival may reduce delays in evaluation. This study estimated associations between hospital arrival modes (EMS or private and with or without EMS prenotification) and times for completion and interpretation of initial brain imaging in patients with presumed stroke.

Methods—

Among patients with suspected stroke identified and enrolled by the North Carolina Stroke Care Collaborative registry in 2008 to 2009, we analyzed data on arrival modes, meeting recommended targets for brain imaging completion and interpretation times (<25 minutes and <45 minutes since hospital arrival, respectively) and patient- and hospital-level characteristics. We used modified Poisson regression to estimate adjusted risk ratios and 95% CIs.

Results—

Of 13 894 eligible patients, 21% had their brain imaging completed and 23% had their brain imaging interpreted by a physician within target times. Arrival by EMS (versus private transport) was associated with both brain imaging completed within 25 minutes of arrival (EMS with prenotification: risk ratio, 3.0; 95% CI, 2.1 to 4.1; EMS without prenotification: risk ratio, 1.9; 95% CI, 1.6 to 2.3) and brain imaging interpreted within 45 minutes (EMS with prenotification: risk ratio, 2.7; 95% CI, 2.3 to 3.3; EMS without prenotification: risk ratio, 1.7; 95% CI, 1.4 to 2.1).

Conclusions—

Patients with presumed stroke arriving to the hospital by EMS were more likely to receive brain imaging and have it interpreted by a physician in a timely manner than those arriving by private transport. Moreover, EMS arrivals with hospital prenotification experienced the most rapid evaluation.
Right–Left Propensity and Lesion Patterns Between Cardiogenic and Aortogenic Cerebral Embolisms
Authors: Kim Hye-Jin , Song Jong-Min , Kwon Sun U. , Kim Bum-Joon , Kang Duk-Hyun , Song Jae-Kwan , Kim Jong S. , Kang Dong-Wha
Published: June 2011

Background and Purpose—

Based on thrombus location and nature and anatomic features of aorta and cerebral arteries, we hypothesized that cardiogenic embolisms (CE) and aortogenic embolisms (AE) might have different right–left propensity and lesion patterns.

Methods—

We retrospectively reviewed patients with acute ischemic stroke with high-risk CE sources or moderate-or-severe aortic atherosclerotic plaques on transesophageal echocardiography. Lesion side and patterns on diffusion-weighted imaging were compared between CE and AE.

Results—

CE was identified in 123 and AE in 63. In multivariate analysis, right-sided lesions and corticosubcortical infarcts were independently associated with CE, and left-sided lesions and pial infarcts were independently associated with AE.

Conclusions—

CE and AE have different radiological characteristics, as shown by the right–left propensity and lesions patterns of cerebral infarcts.
Advancing the Remote Sensing of Precipitation
Authors: Sorooshian Soroosh , AghaKouchak Amir , Arkin Phillip , Eylander John , Foufoula-Georgiou Efi , Harmon Russell , Hendrickx Jan M. H. , Imam Bisher , Kuligowski Robert , Skahill Brian , Skofronick-Jackson Gail
Published: June 2011

No abstract available.
Sea Level Expression of Intrinsic and Forced Ocean Variabilities at Interannual Time Scales
Authors: Penduff Thierry , Juza Mélanie , Barnier Bernard , Zika Jan , Dewar William K. , Treguier Anne-Marie , Molines Jean-Marc , Audiffren Nicole
Published: June 2011

This paper evaluates in a realistic context the local contributions of direct atmospheric forcing and intrinsic oceanic processes on interannual sea level anomalies (SLAs). A ¼° global ocean–sea ice general circulation model, driven over 47 yr by the full range of atmospheric time scales, is quantitatively assessed against altimetry and shown to reproduce most observed features of the interannual SLA variability from 1993 to 2004. Comparing this simulation with a second driven only by the climatological annual cycle reveals that the intrinsic part of the total interannual SLA variance exceeds 40% over half of the open-ocean area and exceeds 80% over one-fifth of it. This intrinsic contribution is particularly strong in eddy-active regions (more than 70%–80% in the Southern Ocean and western boundary current extensions) as predicted by idealized studies, as well as within the 20°–35° latitude bands. The atmosphere directly forces most of the interannual SLA variance at low latitudes and in most midlatitude eastern basins, in particular north of about 40°N in the Pacific. The interannual SLA variance is almost entirely due to intrinsic processes south of the Antarctic Circumpolar Current in the Indian Ocean sector, while half of this variance is forced by the atmosphere north of it. The same simulations were performed and analyzed at 2° resolution as well: switching to this laminar regime yields a comparable forced variability (large-scale distribution and magnitude) but almost suppresses the intrinsic variability. This likely explains why laminar ocean models largely underestimate the interannual SLA variance.
Mooring Design Using Wave-State Estimate from the Southern Ocean
Authors: Schulz E. W. , Grosenbaugh M. A. , Pender L. , Greenslade D. J. M. , Trull T. W.
Published: June 2011

The Southern Ocean Flux Station was deployed near 47°S, 140°E. The extreme wind and wave conditions at this location require appropriate mooring design, which includes dynamic fatigue analysis and static analysis. An accurate estimate of the wave conditions was essential. A motion reference unit was deployed in a nearby test mooring for 6 months. The motion data provided estimates of significant wave height that agreed well with the Australian Bureau of Meteorology wave model, increasing confidence in the model performance in the Southern Ocean. The results of the dynamic fatigue analysis using three input wave datasets and implications for the mooring design are described. The design analysis predicts the fatigue life for critical mooring components and guided the final selection of links and chain shackles. The three input wave climatologies do not differ greatly, and this is reflected in minimal changes to mooring components for each of the fatigue analyses.
Modeling the Flash Rate of Thunderstorms. Part II: Implementation
Authors: Dahl Johannes M. L. , Höller Hartmut , Schumann Ulrich
Published: June 2011

In Part I of this two-part paper a new method of predicting the total lightning flash rate in thunderstorms was introduced. In this paper, the implementation of this method into the convection-permitting Consortium for Small Scale Modeling (COSMO) model is presented.

The new approach is based on a simple theoretical model that consists of a dipole charge structure, which is maintained by a generator current and discharged by lightning and, to a small extent, by a leakage current. This approach yields a set of four predictor variables, which are not amenable to direct observations and consequently need to be parameterized (Part I).

Using an algorithm that identifies thunderstorm cells and their properties, this approach is applied to determine the flash frequency of every thunderstorm cell in the model domain. With this information, the number of flashes that are accumulated by each cell and during the interval between the activation of the lightning scheme can be calculated.

These flashes are then randomly distributed in time and beneath each cell. The output contains the longitude, the latitude, and the time of occurrence of each simulated discharge.

Simulations of real-world scenarios are presented, which are compared to measurements with the lightning detection network, LINET. These comparisons are done on the cloud scale as well as in a mesoscale region composing southern Germany (two cases each). The flash rates of individual cumulonimbus clouds at the extreme ends of the intensity spectrum are realistically simulated. The simulated overall lightning activity over southern Germany is dominated by spatiotemporal displacements of the modeled convective clouds, although the scheme generally reproduces realistic patterns such as coherent lightning swaths.
Verification of Operational Analyses Using an Extremely High-Density Surface Station Network
Authors: Kann Alexander , Haiden Thomas , von der Emde Klaus , Gruber Christine , Kabas Thomas , Leuprecht Armin , Kirchengast Gottfried
Published: June 2011

Operational analyses of 2-m temperature, 2-m humidity, and 10-m wind speed are verified independently against observations obtained from the WegenerNet, an extremely high-density, grid-type surface station network in southeastern Austria with an average distance between stations of 1.4 km. The Integrated Nowcasting through Comprehensive Analysis (INCA) system provides high-resolution analyses in space (1 km) and time (1 h) over the eastern Alpine region and has been specially designed for use in complex terrain. The quality of the system is investigated within a small domain with gentle topography ranging in elevation from 250 to 500 m. A comprehensive validation of INCA relative to WegenerNet for a 3-yr period from December 2007 to November 2010 indicates high analysis skill during all seasons. A sensitivity study reveals the importance of a sufficiently dense station network used by the system and, even more important, the relevance of adequate representativeness of the observation data.
Politically Allocated Land Rights and the Geography of Electoral Violence
Authors: Boone Catherine
Published: June 2011

Large literatures in political theory and political economy argue that private property regimes help support liberal electoral regimes by constraining majoritarian politics, lowering the stakes of elections, and protecting “fundamental” or minority rights. This article probes implications of this argument for elections in sub-Saharan Africa, a mostly rural continent where only about 2% to 10% of all rural property (by country) is held under private title. Do Africa’s rural property regimes shape electoral dynamics and, if so, which ones, and how? This article examines the case of Kenya, focusing on 1991-1992 electoral dynamics in rural zones in which the state itself has exercised direct prerogative over land allocation. We show that in these zones, politicians manipulated land rights to mobilize supporters and punish opponents. They did so in ways that contributed directly to widespread land-related violence at election time. References to other African cases help generalize and set scope conditions on the argument.
Support for Polyarchy in the Americas
Authors: Carlin Ryan E. , Singer Matthew M.
Published: June 2011

This study measures support for the basic rights, liberties, and practices associated with polyarchy in 12 Latin American democracies. Specifically, it identifies five profiles of support for polyarchy’s core values and norms—public contestation, inclusive participation, limits on executive authority, and institutional checks and balances. Although citizens who fit the polyarch profile accept all of polyarchy’s principles, those who fit one of the four mixed support profiles ( power constrainer, power checker, power delegator, power restrainer) accept only some of them while rejecting other core democratic principles. Long-run factors emphasized by modernization and cultural theories (e.g., education, wealth, political engagement) are closely associated with the polyarch support profile. However, short-range performance factors (e.g., economic perceptions; crime, discrimination, and corruption victimization; voting for losing presidential candidates; presidential approval) may better explain why citizens fit one particular mixed profile over another and particularly explain willingness to delegate authority to the executive at the expense of other institutions.
The Early Development of Sight-Reading Skills in Adulthood
Authors: Penttinen Marjaana , Huovinen Erkki
Published: June 2011

In this study the effects of skill development on the eye movements of beginning adult sight-readers were examined, focusing on changes in the allocation of visual attention within metrical units as well as in the processing of larger melodic intervals. The participants were future elementary school teachers, taking part in a 9-month-long music training period. During this period, 15 novice sight-readers’ development was observed in three measurements, with 15 amateur musicians functioning as a comparison group. The novices’ allocation of fixation time within metrical units gradually approached a pattern demonstrated by the amateurs in which increased sensitivity to metrical divisions was evinced by larger average fixation times on the latter halves of bars. Concerning larger melodic skips in otherwise stepwise melodic contexts, an analysis of fixation times suggested that the novices’ visual processing of skips did not proceed in terms of note comparison across the skip but rather through a direct identification of the notational symbols involved. Skill development was seen, then, as increasing fluency of this identification process. These and similar findings may lead to a better understanding of the problems encountered by novice sight-readers and thus to advancements in the pedagogy of music reading.
Music Preferences and Family Language Background
Authors: Sakai Winfried
Published: June 2011

Turkish migrants are the largest national group in Germany. Nevertheless, neither in music psychology research nor in intercultural research can empirical data on the music preferences of Turkish-German primary schoolchildren in the migrational context be found. This study thus examined the music preference responses of children with Turkish language backgrounds, who were at the end of primary school education, to music examples representing the differences between occidental and oriental music systems. A total of 267 children participated in an investigation in the city of Ludwigshafen am Rhein that involved primary schools that had relatively high and relatively low numbers of children with migrational backgrounds. The data analysis indicated interesting coherences between the children’s family language backgrounds and their music preferences. In the context of migration, however, the children’s responses represented varied possibilities of locating in a local, transnational, or global music culture.
The Effect of Ensemble Performance Quality on the Evaluation of Conducting Expressivity
Authors: Silvey Brian A.
Published: June 2011

This study was designed to examine whether the presence of excellent or poor ensemble performances would influence the ratings assigned by ensemble members to conductors who demonstrated highly expressive conducting. Two conductors were videotaped conducting one of two excerpts from an arrangement of Frank Ticheli’s Loch Lomond. These videos subsequently were duplicated and synchronized with either excellent or poor performances that previously had been recorded with a university wind ensemble. To determine whether identical conducting performances would be evaluated differently on the basis of excellent or poor ensemble performance, college band, choir, and orchestra members ( N = 120) viewed each of the four 1-minute excerpts and rated conductor expressivity and ensemble performance quality on 10-point Likert-type scales and provided one brief written comment about each video. Results indicated that ensemble performance quality significantly affected ratings of conductor expressivity ( p < .001). However, the effect size was modest (partial η2 = .29). Participants’ written comments were directed most frequently to the conductor in the excellent-performance condition and to the ensemble in the poor-performance condition.
Chinese Undergraduates’ Explicit and Implicit Attitudes Toward Persons With Disabilities
Authors: Chen Shuang , Ma Li , Zhang Jian-Xin
Published: June 2011

The present study is aimed at examining implicit and explicit attitudes toward persons with disabilities among Chinese college students. The Implicit Association Test was used to measure their implicit attitudes, whereas their explicit attitudes toward persons with disabilities were measured by using a scale of three items. Participants were 56 randomly recruited undergraduate students at a university in Beijing. The results showed that implicit and explicit attitudes were antagonistic to each other. Students tended to hold negative attitudes implicitly and positive attitudes explicitly toward persons with disabilities. In particular, students from rural areas exhibited more negative implicit attitudes than those from urban areas; males demonstrated more negative explicit attitudes than females. Implications for rehabilitation counselors are discussed.
Challenging Code: A Sociological Reading of the KDE Free Software Project
Authors: Alleyne Brian
Published: June 2011

Free, Libre and Open Source Software (FLOSS) challenges the norms and relations of the capitalist software industry that is at the core of network society. Many people involved in FLOSS see themselves as activists in a new social movement. The article discusses the KDE (Kool Desktop Environment) project as a FLOSS case study. KDE is one of several projects intended to bring ease of use of a graphical user interface (GUI) to various free operating systems. (The operating system is the underlying software on top of which sit applications we use directly such as web browsers or word processors.) The article considers the KDE project from three broad perspectives — ‘cosmological’, technical, and organizational — in order to examine the expressed world-view and technical organization of the project through an established sociological approach to activism and social movements.
Kinship, Affinity and Connectedness: Exploring the Role of Genealogy in Personal Lives
Authors: Kramer Anne-Marie
Published: June 2011

Drawing on the 2008 Mass Observation Directive ‘Doing Family Research’, this article explores the role of genealogy in personal lives from the perspective of genealogists and non-genealogists in the UK. Analysing the ends to which genealogy is put, it finds that genealogy is a key kinship practice, mapping connectedness, offering a resource for identity-work, and allowing belonging in time. Engaging with anthropological work on kinship, relatedness and remembrance and with recent sociological work on identity and affinity, this article explores how family history as a creative and imaginative memory and kinship practice is simultaneously used to map affinities and connectedness, enact relatedness, and produce self-identity. It argues that examining the role of genealogy and the genealogical imaginary reveals that conventional as well as non-conventional kinship produces partial and insecure identities. This compels everyday personal engagement with the meaning and legacy of inheritance for collective and individual identification and identity.
The Moral Economy of Domestic and Care Labour: Migrant Workers in Naples, Italy
Authors: Näre Lena
Published: June 2011

This article proposes the notion of moral economy as a useful lens for the analysis of migrant domestic and care work. Drawing on ethnographic data collected in Naples, Southern Italy, it argues that paid domestic and care work relationships are based on a moral economy, i.e. on notions of good/bad, just/unjust rather than merely economic profit maximization. There is a tendency to transform labour relationships into family-like relationships due to the locus of domestic work within the privacy of households and the nature of domestic labour relationships as highly personalized. However, in contrast to the existing research literature, many migrant workers feel that being treated like part of the family characterizes the best possible work relationship.
The Quest for Victory: Collective Memory and National Identification among the Arab-Palestinian Citizens of Israel
Authors: Sorek Tamir
Published: June 2011

The interdependence of collective memory and national identification has become a widespread scholarly axiom. While the related literature recognizes the role of memories of victimization and heroic victories, this article illustrates the importance of a ‘semiotic balance’ between these two for the maintenance of national identification. The study is based on an individual-centered quantitative method, which has never been used to investigate the national identity—memory nexus before. Using a survey with a representative sample ( N = 530) of the Palestinian citizens of Israel, the association between individuals’ memories and national identification is examined. It was found that remembering a combination of victory and victimization is a better predictor of national identification than either theme separately. These findings indicate the crucial importance of a balanced mythical structure that includes both themes of victimization and triumph.
Lack of Effect of Brivanib on the Pharmacokinetics of Midazolam, a CYP3A4 Substrate, Administered Intravenously and Orally in Healthy Participants
Authors: Syed Shariq , Clemens Pamela L. , Lathers Deanne , Kollia Georgia , Dhar Arindam , Walters Ian , Masson Eric
Published: June 2011

Brivanib alaninate is the orally available prodrug of brivanib, a dual inhibitor of fibroblast growth factor and vascular endothelial growth factor signaling pathways that is under therapeutic investigation for various malignancies. Brivanib alaninate inhibits CYP3A4 in vitro, and thus there is potential for drug‐drug interaction with CYP3A4 substrates, such as midazolam. The present study evaluated pharmacokinetic parameters and safety/tolerability upon coadministration of brivanib alaninate and midazolam. Healthy participants received intravenous (IV) or oral midazolam with and without oral brivanib alaninate. Blood samples for pharmacokinetic analysis were collected up to 12 hours after midazolam and up to 48 hours after brivanib alaninate. Twenty‐four participants were administered study drugs; 21 completed the trial. No clinically relevant effect of brivanib alaninate on the overall exposure to midazolam following IV or oral administration was observed. Orally administered brivanib alaninate was generally well tolerated in the presence of IV or oral midazolam. The lack of a pharmacokinetic interaction between brivanib and midazolam indicates that brivanib alaninate does not influence either intestinal or hepatic CYP3A4 and confirms that brivanib alaninate may be safely coadministered with midazolam and other CYP3A4 substrates.
Dual Identity as a Two-Edged Sword
Authors: Baysu Gülseli , Phalet Karen , Brown Rupert
Published: June 2011

Some members of ethnic minority groups respond to identity threat in ways that are detrimental to their school career, while others persist despite an unwelcoming school environment. It was hypothesized that ethnic and national identities, as combined in “separated,” “assimilated,” or “dual identity” strategies, moderate consequences of identity threat for minority school performance and that the adaptive value of different identity strategies depends on the intergroup context. Random samples of Turkish Belgian young adults ( N = 576) were interviewed about their school performance (i.e., high, middle, or low success) and past experiences of discrimination in school as an indicator of identity threat. Results revealed that Turkish Belgians with “separated” or “assimilated” identity strategies were less likely than “dual” identifiers to disengage from school when perceived threat was high. Conversely, dual identifiers were most successful when perceived threat was low. Implications of the up- and downsides of dual identity for minority school performance are discussed.
Intergroup Conflict in Russia
Authors: Minescu Anca , Poppe Edwin
Published: June 2011

The group position model ( Blumer 1958 ; Bobo and Tuan 2006 ) assumes that attempting to secure a privileged position for the ingroup is a main determinant of perceived intergroup conflict. This assumption is tested with survey data collected in 1999 and 2000 among eight titular groups in autonomous republics of the Russian Federation. The survey included an experiment that was aimed at disentangling the effects of perceived threat and the fear of outgroup encroachment (growing outgroup influence). The findings indicate that more conflict was perceived when the ingroup was larger (corresponding to stronger entitlement claims to privilege), especially among those who felt more threatened. This association was further strengthened among those whose fear of outgroup encroachment was made salient. This study shows the relevance of the group position model in understanding perceived intergroup conflict among national minority groups with a local privileged status.
Association between Cerebrospinal Fluid Leak and Meningitis after Skull Base Surgery
Authors: Horowitz Gilad , Fliss Dan M. , Margalit Nevo , Wasserzug Oshri , Gil Ziv
Published: June 2011

Background

Meningitis and cerebrospinal fluid (CSF) leak are serious complications of skull base surgery, but whether postoperative CSF leak increases the risk of meningitis is unknown.

Objective

To evaluate any association between meningitis and CSF leak after open or endoscopic skull base resection.

Study Design and Setting

A retrospective case series with chart review in a tertiary care university‐affiliated medical center.

Methods

A total of 156 patients underwent intradural tumor resection in our institution between 1994 and 2009, 135 (86%) via the subcranial approach and 21 (14%) through the expanded endonasal approach. All occurrences of meningitis, brain abscess, and CSF leak had been recorded and were available for analysis.

Results

Nine patients (5.7%) had postoperative meningitis, and 3 patients had postoperative CSF leak (1.9%). The risk of meningitis in patients without CSF leak was 4.5% (7/153) compared to 66% (2/3) in those with CSF leak. A statistical analysis revealed a significant association between CSF leak and meningitis, with a relative risk of 14.6 (95% confidence interval, 4.95‐42; P =. 008).

Conclusion

Postoperative CSF leak significantly increases the risk of meningitis. Most cases of meningitis after skull base operation are probably associated with lumbar drainage infection or from an obscure leak.
Septal Perforation Repairing with Combination of Mucosal Flaps and Auricular Interpositional Grafts in Revision Patients
Authors: Taskin Umit , Yigit Ozgur , Sisman Sezim A.
Published: June 2011

Objectives

To examine the closure of nasal septal perforations with bilateral nasal floor flaps combined with auricular cartilage grafts and a normally functioning nose in revision patients.

Study Design

Case series with chart review.

Setting

A tertiary referral hospital in Turkey.

Subjects and Methods

Seventeen patients (11 men, 6 women) with nasal septal reperforation were treated surgically using combined bilateral nasal floor mucosal flaps with bilateral auricular cartilage interpositional grafts.

Results

The mean follow‐up was 15.2 (range, 9‐28) months. The average anteroposterior diameter of perforation was 28 ± 3 (range, 20‐38) mm, and the average vertical diameter was 23 ± 8 (range, 20‐27) mm at the widest site. The nasal septal perforations were closed completely in 16 cases; in 1 case, the perforation was not repaired completely.

Conclusions

A successful multilayer closure technique with good exposure was applied in patients with reperforation.