bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of extra information on TV viewers' visual attention, message processing ability, and cognitive workload
Authors: Kallenbach Jan , Narhi Silja , Oittinen Pirkko
Published: January 2008

This article explores how viewers respond to and remember extra information shown on television. Its purpose is to investigate the effects of typical print content on TV viewers' visual attention, message processing ability, and cognitive workload when print content appears simultaneously with video. Test subjects looked at various video clips simultaneously with print, while variable text and graphics changed the structural complexity of the message. Data of psychophysiological measurements such as eye-tracking and skin-conductivity were obtained during the test; memory and cognitive workload measurements were self-reported afterwards. The results show that visual attention was equally balanced between video and print content for lengthy texts, whereas short texts with an increasing number of images caused subjects to look longer and more often at the video. Both video and text recognition were better on lengthy texts. Subjective cognitive workload data shows that lengthy texts resulted in higher ratings for psychological stress than short ones did. We conclude that variable text influences visual attention, memory, and cognitive workload more than pictorial information does; this conclusion supports the limited capacity model.
Quantitative and visual analysis of the impact of music on perceived emotion of film
Authors: Parke Rob , Chew Elaine , Kyriakakis Chris
Published: January 2008

This article presents quantitative and visual methods for the analysis of the effect of music on emotion perceived in film. We discover strong, visible, and quantifiable trends in the effect of music on perceived emotion of film. We perform studies using both selected classical and composed music segments annotated with diverse emotions, paired with ambiguous film clips. We collect and analyze viewers' ratings of stress, activity, and dominance in the silent film, and film with various music soundtracks. The results are mapped onto a three-dimensional emotion space for visual and quantitative analysis. Aggregate scatter plots and center of mass results are presented using this emotion space. We find that the center of mass of the perceived emotion of film and music combined is consistently situated on a path between the center of mass of the musicalone response and that of the film-alone response. Regression analysis based on this trajectory observation results in coefficients with high R
2
values (R
2
= 0.675 for stress, R
2
= 0.817 for activity, and R
2
= 0.813 for dominance) for the first study with classical music selections, and lower R
2
values (R
2
= 0.199 for stress, R
2
= 0.405 for activity, and R
2
= 0.660 for dominance) for the second study with composed music. We conclude that continuous treatment of the two-dimensional emotion space provides a metric for comparing and assessing emotion ratings, and that spatial interpolation in this space provides a viable method for predicting the effect of music on perceived emotion of film.
Computing in pervasive cyberspace
Authors: Agha Gul
Published: January 2008

Freed from the temporal constraints of hardware, software could be the ultimate cyberorganism---a mind taking a body as needed to fulfill a particular function or mission.
Near-optimal hashing algorithms for approximate nearest neighbor in high dimensions
Authors: Andoni Alexandr , Indyk Piotr
Published: January 2008

In this article, we give an overview of efficient algorithms for the approximate and exact nearest neighbor problem. The goal is to preprocess a dataset of objects (e.g., images) so that later, given a new query object, one can quickly return the dataset object that is most similar to the query. The problem is of significant interest in a wide variety of areas.
Accessmonkey
Authors: Bigham Jeffrey P.
Published: January 2008

This paper proposes the Accessmonkey Framework for collaborative web accessibility improvement. The goal of the system is to provide a common platform on which end users and developers can create, share and use scripts that specify accessibility improvements. We propose browser plugins that will automatically retrieve user scripts from a common repository and apply helpful transformations to pages visited by users. End user interfaces will allow anyone to create and share new improvements and developer interfaces will allow content creators to edit and save changes scripts make to web content. Accessmonkey seeks to enable those most impacted by web accessibility challenges to directly and independently improve them. This work is being pursued with close consultation and participation by blind web users.
Simulating HCI for special needs
Authors: Biswas Pradipta
Published: January 2008

Computers offer valuable assistance to people with physical disabilities. However designing human-computer interfaces for these users is complicated. The range of abilities is more diverse than for able-bodied users, which makes analytical modelling harder. Practical user trials are also difficult and time consuming. We are developing a simulator to help with the evaluation of assistive interfaces. It can predict the likely interaction patterns when undertaking a task using a variety of input devices, and estimate the time to complete the task in the presence of different disabilities and for different levels of skill.
How does energy consumption impact performance in Bluetooth?
Authors: Cano Juan-Carlos , Cano José-Manuel , González Eva , Calafate Carlos , Manzoni Pietro
Published: January 2008

In this paper we investigate the power characteristics of the Bluetooth technology when supporting low-power modes. We provide accurate power consumption measurements for different Bluetooth operating modes. Such information could be used to drive technical decisions on battery type and design of Bluetooth-based end systems. Finally, we examine the trade-off between power consumption and performance for a commercial off-the-shelf Bluetooth device. We find that the use of the
sniff
mode could be quite compatible with the use of multi-slot data packets. However, when the channel conditions require selecting single slot data packets, the
sniff
mode highly impact performance, and so the power/delay trade-off must be taken into consideration.
High-level approach to modeling of observed system behavior
Authors: Begin Thomas , Brandwajn Alexandre , Baynat Bruno , Wolfinger Bernd E. , Fdida Serge
Published: January 2008

Current computer systems and communication networks tend to be highly complex, and they typically hide their internal structure from their users. Thus, for selected aspects of capacity planning, overload control and related applications, it is useful to have a method allowing one to find good and relatively simple approximations for the observed system behavior. This paper investigates one such approach where we attempt to represent the latter by adequately selecting the parameters of a set of queueing models. We identify a limited number of queueing models that we use as "Building Blocks" (BBs) in our procedure. The selected BBs allow us to accurately approximate the measured behavior of a range of different systems. We propose an approach for selecting and combining suitable BB, as well as for their calibration. Finally, we validate our methodology and discuss the potential and the limitations of the proposed approach.
Towards fairness and efficiency in storage systems
Authors: Gulati Ajay , Varman Peter , Merchant Arif , Uysal Mustafa
Published: January 2008

Fairness and overall I/O efficiency are two opposing forces when it comes to sharing I/O among different applications. Although providing QoS guarantees for applications sharing a storage server are desirable under many scenarios, existing work has not been able to make a convincing case for using fairness mechanisms for disk scheduling, mainly due to their impact on overall throughout. In this work, we plan to investigate two major issues: (1) study the trade-off between fairness and efficiency, and develop mechanisms to improve the I/O efficiency of fair schedulers (2) provide performance guarantees to applications in terms of higher-level application metrics (such as transactions/sec), by changing the parameters in a fairness algorithm that affect the allocations at the block level.
Flows of Dense Granular Media
Authors: Forterre Yoël , Pouliquen Olivier
Published: January 2008

We review flows of dense cohesionless granular materials, with a special focus on the question of constitutive equations. We first discuss the existence of a dense flow regime characterized by enduring contacts. We then emphasize that dimensional analysis strongly constrains the relation between stresses and shear rates, and show that results from experiments and simulations in different configurations support a description in terms of a frictional visco-plastic constitutive law. We then discuss the successes and limitations of this empirical rheology in light of recent alternative theoretical approaches. Finally, we briefly present depth-averaged methods developed for free surface granular flows.
Oceanic Rogue Waves
Authors: Dysthe Kristian , Krogstad Harald E. , Müller Peter
Published: January 2008

Oceanic rogue waves are surface gravity waves whose wave heights are much larger than expected for the sea state. The common operational definition requires them to be at least twice as large as the significant wave height. In most circumstances, the properties of rogue waves and their probability of occurrence appear to be consistent with second-order random-wave theory. There are exceptions, although it is unclear whether these represent measurement errors or statistical flukes, or are caused by physical mechanisms not covered by the model. A clear deviation from second-order theory occurs in numerical simulations and wave-tank experiments, in which a higher frequency of occurrence of rogue waves is found in long-crested waves owing to a nonlinear instability.
Transport and Deposition of Particles in Turbulent and Laminar Flow
Authors: Guha Abhijit
Published: January 2008

This article reviews the physical processes responsible for the transport and deposition of particles and their theoretical modeling. Both laminar and turbulent processes are considered, emphasizing the physical understanding of the various transport mechanisms. State-of-the-art computational methods for determining particle motion and deposition are discussed, including stochastic Lagrangian particle tracking and a unified Eulerian advection-diffusion approach. The theory presented includes Brownian and turbulent diffusion, turbophoresis, thermophoresis, inertial impaction, gravitational settling, electrical forces, and the effects of surface roughness and particle interception. The article describes two example applications: the deposition of particles in the human respiratory tract and deposition in gas and steam turbines.
Elastic Modeling of Biomembranes and Lipid Bilayers
Authors: Brown Frank L.H.
Published: January 2008

The simulation of biological membranes over length and time scales relevant to cellular biology is not currently feasible using conventional (fully atomic or molecularly detailed) simulation strategies. Given the wide disparity between what is possible on today's computers and the problems one might like to study, it seems unlikely this situation will change for several decades. An appealing alternative to traditional computational approaches is to employ simpler, continuum-based models developed within the frameworks of elasticity theory, fluid dynamics, and statistical mechanics. Although such models have seen wide use in analytical descriptions of membrane behavior, the extension of these methods to more general situations and numerical analysis is just beginning to be explored. This article reviews continuum models for membrane behavior with an emphasis on the use of such models in computational studies. Two applications are explored to demonstrate the utility of this level of coarse-grained modeling.
Why Is the Developed World Obese?
Authors: Bleich Sara N. , Cutler David , Murray Christopher , Adams Alyce
Published: January 2008

Obesity has risen dramatically in the past few decades. However, the relative contribution of energy intake and energy expenditure to rising obesity is not known. Moreover, the extent to which social and economic factors tip the energy balance is not well understood. This exploratory study estimates the relative contribution of increased caloric intake and reduced physical activity to obesity in developed countries using two methods of energy accounting. Results show that rising obesity is primarily the result of consuming more calories. We estimate multivariate regression models and use simulation analysis to explore technological and sociodemographic determinants of this dietary excess. Results indicate that the increase in caloric intake is associated with technological innovations as well as changing sociodemographic factors. This review offers useful insights to future research concerned with the etiology of obesity and suggests that obesity-related policies should focus on encouraging lower caloric intake.
Nonredundant function of secretory carrier membrane protein isoforms in dense core vesicle exocytosis
Authors: Liao Haini , Zhang Jie , Shestopal Svetlana , Szabo Gabor , Castle Anna , Castle David
Published: January 2008

Five secretory carrier membrane proteins (SCAMP-1, -2, -3, -4, and -5) have been characterized in mammalian cells. Previously, SCAMP-1 and -2 have been implicated to function in exocytosis. RNA inhibitor-mediated deficiency of one or both of these SCAMPs interferes with dense core vesicle (DCV) exocytosis in neuroendocrine PC12 cells as detected by amperometry. Knockdowns of these SCAMPs each decreased the number and frequency of depolarization-induced exocytotic events. SCAMP-2 but not SCAMP-1 depletion also delayed the onset of exocytosis. Both knockdowns, however, altered fusion pore dynamics, increasing rapid pore closure and decreasing pore dilation. In contrast, knockdowns of SCAMP-3 and -5 only interfered with the frequency of fusion pore opening and did not affect the dynamics of newly opened pores. None of the knockdowns noticeably affected upstream events, including the distribution of DCVs near the plasma membrane and calcium signaling kinetics, although norepinephrine uptake/storage was moderately decreased by deficiency of SCAMP-1 and -5. Thus, SCAMP-1 and -2 are most closely linked to the final events of exocytosis. Other SCAMPs collaborate in regulating fusion sites, but the roles of individual isoforms appear at least partially distinct.
Aerobic capacity-dependent differences in cardiac gene expression
Authors: Bye Anja , Langaas Mette , Høydal Morten A. , Kemi Ole Johan , Heinrich Garrett , Koch Lauren G. , Britton Steven L. , Najjar Sonia M. , Ellingsen Øyvind , Wisløff Ulrik
Published: January 2008

Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between inborn aerobic capacity and cardiac gene expression we examined genome-wide gene expression in hearts of rats artificially selected for high and low running capacity (HCR and LCR, respectively) over 16 generations. The artificial selection of LCR caused accumulation of risk factors of cardiovascular disease similar to the metabolic syndrome seen in human, whereas HCR had markedly better cardiac function. We also studied alterations in gene expression in response to exercise training in these animals. Left ventricle gene expression of both sedentary and exercise-trained HCR and LCR was characterized by microarray and gene ontology analysis. Out of 28,000 screened genes, 1,540 were differentially expressed between sedentary HCR and LCR. Only one gene was found differentially expressed by exercise training, but this gene had unknown name and function. Sedentary HCR expressed higher amounts of genes involved in lipid metabolism, whereas sedentary LCR expressed higher amounts of the genes involved in glucose metabolism. This suggests a switch in cardiac energy substrate utilization from normal mitochondrial fatty acid β-oxidation in HCR to carbohydrate metabolism in LCR, an event that often occurs in diseased hearts. LCR were also associated with pathological growth signaling and cellular stress. Hypoxic conditions seemed to be a common source for several of these observations, triggering hypoxia-induced alterations of transcription. In conclusion, inborn high vs. low aerobic capacity was associated with differences in cardiac energy substrate, growth signaling, and cellular stress.
Thromboxane A2 Receptors in Prostate Carcinoma: Expression and Its Role in Regulating Cell Motility via Small GTPase Rho
Authors: Nie Daotai , Guo Yande , Yang Dianer , Tang Yong , Chen Yakun , Wang Man-Tzu , Zacharek Alex , Qiao Yan , Che Mingxin , Honn Kenneth V.
Published: January 2008

Thromboxane A2 (TxA2) is a prostanoid formed by thromboxane synthase using the cyclooxygenase product prostaglandin H2 as the substrate. Previously, increased expression of thromboxane synthase was found in prostate tumors, and tumor cell motility was attenuated by inhibitors of thromboxane synthase. This study was undertaken to elucidate how tumor motility is regulated by TxA2. Here, we report that human prostate cancer cells express functional receptors for TxA2 (TP). Ligand binding assay found that PC-3 cells binded to SQ29548, a high-affinity TP antagonist, in a saturable manner with Kd of 3.64 nmol/L and Bmax of 120.4 fmol per million cells. Treatment of PC-3 cells by U46619, a TP agonist, induced PC-3 cell contraction, which was blocked by pretreatment with the TP antagonist SQ29548 or pinane TxA2. The migration of prostate cancer cells was significantly inhibited either by sustained activation of TP or by blockade of TP activation, suggesting that TP activation must be tightly controlled during cell migration. Further studies found that small GTPase RhoA was activated by TP activation, and pretreatment of PC-3 cells with Y27632, a Rho kinase (ROCK) inhibitor, blocked U46619-induced cell contraction. A dominant-negative mutant of RhoA also blocked U46619-induced cell contraction. Taken together, the data suggest that TPs are expressed in prostate cancer and activation of TPs regulates prostate cancer cell motility and cytoskeleton reorganization through activation of Rho. [Cancer Res 2008;68(1):115–21]
Crucial Role of Phospholipase Cε in Skin Inflammation Induced by Tumor-Promoting Phorbol Ester
Authors: Ikuta Shuzo , Edamatsu Hironori , Li Mingzhen , Hu Lizhi , Kataoka Tohru
Published: January 2008

In two-stage skin chemical carcinogenesis, phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) acts as a promoter essential for clonal expansion of the initiated cells carrying the activated ras oncogenes. Although protein kinase C (PKC) isozymes are the main targets of TPA, their role in tumor promotion remains controversial. We previously reported that mice lacking a Ras/Rap effector phospholipase Cε (PLCε−/− mice) exhibited marked resistance to tumor formation in the two-stage skin carcinogenesis. PLCε−/− mice also failed to exhibit basal layer cell proliferation and epidermal hyperplasia induced by TPA, suggesting a role of PLCε in tumor promotion. Here, we show that PLCε−/− mice exhibit resistance to TPA-induced skin inflammation as assessed by reduction in edema, granulocyte infiltration, and expression of a proinflammatory cytokine, interleukin-1α (IL-1α). On the other hand, the proliferative potentials of keratinocytes or dermal fibroblasts in culture remain unaffected by the PLCε background, suggesting that the PLCε's role in tumor promotion may be ascribed to augmentation of inflammatory responses. In dermal fibroblast primary culture, TPA can induce activation of the PLCε lipase activity, which leads to the induction of IL-1α expression. Experiments using small interfering RNA–mediated knockdown indicate that this activation is mediated by Rap1, which is activated by a TPA-responsive guanine nucleotide exchange factor RasGRP3. Moreover, TPA-induced activation of Rap1 and PLCε is inhibited by a PKC inhibitor GF109203X, indicating a crucial role of PKC in signaling from TPA to PLCε. These results imply that two TPA targets, RasGRP3 and PKC, are involved in TPA-induced inflammation through PLCε activation, leading to tumor promotion. [Cancer Res 2008;68(1):64–72]
Allelic Imbalance at rs6983267 Suggests Selection of the Risk Allele in Somatic Colorectal Tumor Evolution
Authors: Tuupanen Sari , Niittymäki Iina , Nousiainen Kari , Vanharanta Sakari , Mecklin Jukka-Pekka , Nuorva Kyösti , Järvinen Heikki , Hautaniemi Sampsa , Karhu Auli , Aaltonen Lauri A.
Published: January 2008

A common single nucleotide polymorphism (SNP), rs6983267, at 8q24.21 has recently been shown to associate with colorectal cancer (CRC). Three independent SNP association studies showed that rs6983267 contributes to CRC with odds ratios (OR) of 1.17 to 1.22. Here, we genotyped a population-based series of 1,042 patients with CRC and 1,012 healthy controls for rs6983267 and determined the contribution of SNP to CRC in Finland, using germ line DNA, as well as the respective cancer DNA in heterozygous patients. The comprehensive clinical data available from the 1,042 patients and their first-degree relatives enabled us to thoroughly examine the possible association of this variant with different clinical features. As expected, a significant association between the G allele of rs6983267 and CRC [OR, 1.22; 95% confidence interval (CI), 1.08–1.38; P = 0.0018] was found, confirming the previous observations. A trend towards association of the G allele with microsatellite-stable cancer (OR, 1.37; 95% CI, 1.02–1.85; P = 0.04) and family history of cancers other than CRC was seen (OR, 1.20; 95% CI, 1–1.43; P = 0.05). Four hundred and sixty-six GT heterozygotes identified in this study were analyzed for allelic imbalance at rs6983267 in the respective cancer DNA. One hundred and one tumors showed allelic imbalance (22%). The risk allele G was favored in 67 versus 34 tumors (P = 0.0007). This finding implicates that the underlying germ line genetic defect in 8q24.21 is a target in the somatic evolution of CRC. [Cancer Res 2008;68(1):14–7]
Both Germ Line and Somatic Genetics of the p53 Pathway Affect Ovarian Cancer Incidence and Survival
Authors: Bartel Frank , Jung Juliane , Böhnke Anja , Gradhand Elise , Zeng Katharina , Thomssen Christoph , Hauptmann Steffen
Published: January 2008

Purpose: Although p53 is one of the most studied genes/proteins in ovarian carcinomas, the predictive value of p53 alterations is still ambiguous.

Experimental Design: We performed analyses of the TP53 mutational status and its protein expression using immunohistochemistry. Moreover, the single nucleotide polymorphism SNP309 in the P2 promoter of the MDM2 gene was investigated. We correlated the results with age of onset and outcome from 107 patients with ovarian carcinoma.

Results: In our study, we identified a large group of patients with p53 overexpression despite having a wild-type gene (49% of all patients with wild-type TP53). This was associated with a significantly shortened overall survival time (P = 0.019). Patients with p53 alterations (especially those with overexpression of wild-type TP53) were also more refractory to chemotherapy compared with patients with normal p53 (P = 0.027). The G-allele of SNP309 is associated with an earlier age of onset in patients with estrogen receptor–overexpressing FIGO stage III disease (P = 0.048). In contrast, in patients with FIGO stage III disease, a weakened p53 pathway (either the G-allele of SNP309 or a TP53 mutation) was correlated with increased overall survival compared with patients whose tumors were wild-type for both TP53 and SNP309 (P = 0.0035).

Conclusion: Our study provides evidence that both germ line and somatic alterations of the p53 pathway influence the incidence and survival of ovarian carcinoma, and it underscores the importance of assessing the functionality of p53 in order to predict the sensitivity of platinum-based chemotherapies and patient outcome.
The Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Kinase Inhibitor AZD6244 (ARRY-142886) Induces Growth Arrest in Melanoma Cells and Tumor Regression When Combined with Docetaxel
Authors: Haass Nikolas K. , Sproesser Katrin , Nguyen Thiennga K. , Contractor Rooha , Medina C. Angelica , Nathanson Katherine L. , Herlyn Meenhard , Smalley Keiran S.M.
Published: January 2008

Purpose: Disseminated melanoma is highly therapy resistant. The finding that 66% of melanomas harbor the activating BRAFV600E mutation has raised expectations for targeting the Ras/RAF/mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway in melanoma. This study addresses the anti-melanoma activity of the MEK inhibitor AZD6244 (ARRY-142886).

Experimental Design: We recently have shown that growing melanoma cells as three-dimensional collagen-implanted spheroids enhances resistance to the MEK inhibitor U0126. Here, we investigated the anti-melanoma activity of AZD6244 in two-dimensional cell culture, the three-dimensional spheroid model, and an in vivo model.

Results: In two-dimensional cell culture, AZD6244 was cytostatic and reduced the growth of melanoma cells in a concentration-dependent fashion through the induction of G1-phase cell cycle arrest. In our three-dimensional spheroid model, the effects of AZD6244 were largely cytostatic and reversible, with drug washout leading to spheroid regrowth. Finally, 1205Lu cells were grown as tumor xenografts in severe combined immunodeficient mice. After tumor establishment, mice were dosed twice daily with 0, 10, or 30 mg/kg AZD6244 p.o. AZD6244 treatment decreased phospho-ERK in the tumors and significantly suppressed tumor growth. The original tumors remained viable, suggesting that AZD6244 monotherapy was largely cytostatic, and not proapoptotic in this model. Further studies showed that co-administration of AZD6244 (30 mg/kg) with docetaxel (15 mg/kg) led to tumor regression, indicating the potential for MEK inhibitor/chemotherapy drug combinations.

Conclusions: Inhibition of MEK is cytostatic as a monotherapy in melanoma, but cytotoxic when combined with docetaxel.
Identification of Patients with (Atypical) MUTYH-Associated Polyposis by KRAS2 c.34G > T Prescreening Followed by MUTYH Hotspot Analysis in Formalin-Fixed Paraffin-Embedded Tissue
Authors: van Puijenbroek Marjo , Nielsen Maartje , Tops Carli M.J. , Halfwerk Hans , Vasen Hans F.A. , Weiss Marjan M. , van Wezel Tom , Hes Frederik J. , Morreau Hans
Published: January 2008

Purpose: To assess the feasibility of identifying patients with (atypical) MUTYH-associated polyposis (MAP) by KRAS2 c.34G > T prescreening followed by MUTYH hotspot mutation analysis in formalin-fixed paraffin-embedded tissue (FFPE).

Methods: We collected 210 colorectal FFPE tumors from 192 individuals who presented with <10 adenomas or familial mismatch repair proficient colorectal carcinomas with <10 concomitant adenomas. The tissues were tested for somatic KRAS2 mutations and for three Dutch hotspot MUTYH germ line mutations (p.Tyr165Cys, p.Gly382Asp, and p.Pro391Leu) by sequencing analysis.

Results: The c.34G > T, KRAS2 transversion was detected in 10 of 210 tumors. In one of these 10 cases, a monoallelic p.Gly382Asp MUTYH mutation was found and a full MUTYH analysis in leukocyte DNA revealed an unclassified variant p.Met269Val. This was in a 61-year-old patient with a cecum carcinoma and three adenomas. After further requests, her family case history revealed that her brother had had between 10 and 15 adenomas and turned out to carry both MUTYH germ line mutations. MUTYH hotspot mutation screening in 182 patients without the somatic c.34G > T KRAS2 mutation led to the detection of three monoallelic germ line MUTYH mutation carriers.

Conclusion: KRAS2 c.34G > T somatic prescreening, followed by MUTYH hotspot mutation analysis when positive, can identify patients with (atypical) MAP. If heterozygous hotspot MUTYH mutations are identified, a complete germ line MUTYH mutation screening should be carried out if possible. Immediate MUTYH hotspot mutation analysis is a practical alternative in patients with >10 adenomas or in cases of multiple colorectal carcinomas in one generation for which only FFPE tissue is available.
Induction of Tumor-Specific CD4+ and CD8+ T-Cell Immunity in Cervical Cancer Patients by a Human Papillomavirus Type 16 E6 and E7 Long Peptides Vaccine
Authors: Welters Marij J.P. , Kenter Gemma G. , Piersma Sytse J. , Vloon Annelies P.G. , Löwik Margriet J.G. , Berends-van der Meer Dorien M.A. , Drijfhout Jan W. , Valentijn A. Rob P.M. , Wafelman Amon R. , Oostendorp Jaap , Fleuren Gert Jan , Offringa Rienk , Melief Cornelis J.M. , van der Burg Sjoerd H.
Published: January 2008

Purpose: The study aims to evaluate the effect of a human papillomavirus type 16 (HPV16) E6 and E7 synthetic long peptides vaccine on the antigen-specific T-cell response in cervical cancer patients.

Experimental Design: Patients with resected HPV16-positive cervical cancer were vaccinated with an overlapping set of long peptides comprising the sequences of the HPV16 E6 and E7 oncoproteins emulsified in Montanide ISA-51. HPV16-specific T-cell immune responses were analyzed by evaluating the magnitude, breadth, type, and polarization by proliferation assays, IFNγ-ELISPOT, and cytokine production and phenotyped by the T-cell markers CD4, CD8, CD25, and Foxp3.

Results: Vaccine-induced T-cell responses against HPV16 E6 and E7 were detected in six of six and five of six patients, respectively. These responses were broad, involved both CD4+ and CD8+ T cells, and could be detected up to 12 months after the last vaccination. The vaccine-induced responses were dominated by effector type CD4+CD25+Foxp3− type 1 cytokine IFNγ-producing T cells but also included the expansion of T cells with a CD4+CD25+Foxp3+ phenotype.

Conclusions: The HPV16 E6 and E7 synthetic long peptides vaccine is highly immunogenic, in that it increases the number and activity of HPV16-specific CD4+ and CD8+ T cells to a broad array of epitopes in all patients. The expansion of CD4+ and CD8+ tumor-specific T cells, both considered to be important in the antitumor response, indicates the immunotherapeutic potential of this vaccine. Notably, part of the vaccine-induced T cells display a CD4+CD25+Foxp3+ phenotype that is frequently associated with regulatory T-cell function, suggesting that strategies to disarm this subset of T cells should be considered as components of immunotherapeutic modalities against HPV-induced cancers.
Prognostic Significance of Cyclooxygenase-2 Overexpression in Glottic Cancer
Authors: Sackett Melanie K. , Bairati Isabelle , Meyer François , Jobin Édith , Lussier Sébastien , Fortin André , Gélinas Michel , Nabid Abdenour , Brochet François , Têtu Bernard
Published: January 2008

Purpose: Cyclooxygenase-2 (COX-2) overexpression has been associated with a poor prognosis in many cancers. However, the role of COX-2 overexpression in head and neck cancers remains undetermined. The objective of this study was to evaluate whether COX-2 is a prognostic factor in glottic cancer.

Experimental Design: This study was part of a phase III placebo-controlled randomized trial evaluating the efficacy of α-tocopherol in reducing second primary cancers (SPC) in head and neck cancer patients. Immunohistochemical analyses were conducted on pretreatment biopsies of 301 patients with early-stage glottic cancer treated by radiotherapy. The median value of 50% of positive tumor cells was the cutoff point used to define COX-2 overexpression. Outcomes considered in the statistical analysis were recurrence, SPC, and death. The Cox proportional hazards model was used to estimate the hazard ratios (HR) and their 95% confidence intervals (95% CI).

Results: The HR associated with COX-2 overexpression was 0.94 (95% CI, 0.55-1.62) for recurrence. The HR associated with SPC was 2.63 (95% CI, 1.32-5.23) for the first 3.5 years of follow-up and 0.55 (95% CI, 0.22-1.32) for the following 3.5 years. The HR associated with COX-2 overexpression was 1.57 (95% CI, 1.01-2.45) for overall mortality.

Conclusions: COX-2 overexpression in glottic cancer was associated with increased overall mortality and an increased risk of SPC during the early follow-up period. Future studies are needed to explain observed effects on SPC. COX-2 expression may prove helpful in defining an individual patient's prognosis.
Perinatal Risk Factors for Ischemic Heart Disease
Authors: Kaijser Magnus , Bonamy Anna-Karin Edstedt , Akre Olof , Cnattingius Sven , Granath Fredrik , Norman Mikael , Ekbom Anders
Published: January 2008

Background—

Several studies have reported an association between low birth weight and ischemic heart disease, but it remains unclear whether the association is mediated through poor fetal growth or short gestational duration.

Methods and Results—

In a cohort study, we have identified all subjects born preterm or with a low birth weight at 4 major delivery units in Sweden from 1925 through 1949. For comparison, an equal number of subjects with none of these criteria were identified within the same source population. The study population consists of 6425 subjects, of whom 2931 were born before 37 weeks of gestation and 2176 had a birth weight <2500 g. Fetal growth was estimated through birth weight for gestational age. The cohort was followed up for occurrence of ischemic heart disease through the nationwide Hospital Discharge and Cause of Death Registries during the period of 1987 through 2002. In the cohort, 617 cases of ischemic heart disease occurred. Compared with subjects with a normal fetal growth, those born small for gestational age (birth weight ≤−2 SD below the mean) were at increased risk of ischemic heart disease (adjusted hazard ratio, 1.64; 95% confidence interval, 1.23 to 2.18). The negative association between fetal growth and risk of ischemic heart disease was independent of gestational duration.

Conclusions—

The association between low birth weight and adult risk of ischemic heart disease appears to be mediated entirely by poor fetal growth.
Differential D
1
and D
5
Receptor Regulation and Degradation of the Angiotensin Type 1 Receptor
Authors: Gildea John J. , Wang Xiaoli , Jose Pedro A. , Felder Robin A.
Published: January 2008

Renal sodium transport is increased by the angiotensin type 1 receptor (AT
1
R), which is counterregulated by dopamine via unknown mechanisms involving either the dopamine type 1 (D
1
R) or dopamine type 5 receptor (D
5
R) that belong to the D
1
-like receptor family of dopamine receptors. We hypothesize that the D
1
R and D
5
R differentially regulate AT
1
R protein expression and signaling, which may have important implications in the pathogenesis of essential hypertension. D
1
R and D
5
R share the same agonists and antagonists; therefore, the selective effects of either D
1
R or D
5
R stimulation on AT
1
R expression in human renal proximal tubule cells were determined using antisense oligonucleotides selective to either D
1
R or D
5
R. We also determined the role of receptor tyrosine kinase and the proteosome on the D
1
R/D
5
R-mediated effects on AT
1
R expression and internalization. In renal proximal tubule cells, D
5
R (not D
1
R) decreased AT
1
R expression (half-life: 0.47±0.18 hours) and AT
1
R-mediated extracellular signal–regulated kinase 1/2 phosphorylation (232±18.9 U with angiotensin II [10
−7
mol/L] versus 81±8.9 U with angiotensin II [10
−7
mol/L] and fenoldopam [D
1
R/D
5
R agonist; 10
−6
mol/L;
P
<0.05; n=6). The fenoldopam-induced decrease in AT
1
R expression was reversed by 4-amino-5-(4-chlorophenyl)-7-(
t
-butyl) pyrazolo (3,4-d) pyrimidine (c-Src tyrosine-kinase inhibitor) and clasto-lactacystin β-lactone (proteasome inhibitor), demonstrating that the fenoldopam-mediated decrease in total cell AT
1
R expression is a result of a c-Src- and proteasome-dependent process. D
5
R stimulation decreases AT
1
R expression and is c-Src and proteasome dependent. The discovery of differential regulation by D
1
R and D
5
R opens new avenues for the development of agonists selective to either receptor subtype as targeted antihypertensive agents that can decrease AT
1
R-mediated antinatriuresis.
Mitochondrial Dysfunction in the Hypertensive Rat Brain
Authors: Lopez-Campistrous Ana , Hao Li , Xiang Wang , Ton Dong , Semchuk Paul , Sander Joerg , Ellison Michael J. , Fernandez-Patron Carlos
Published: January 2008

The central nervous system plays a critical role in the normal control of arterial blood pressure and in its elevation in virtually all forms of hypertension. Mitochondrial dysfunction has been increasingly associated with the development of hypertension. Therefore, we examined whether mitochondrial dysfunction occurs in the brain in hypertension and characterized it at the molecular scale. Mitochondria from whole brain and brain stem from 12-week–old spontaneously hypertensive rats with elevated blood pressure (190±5 mm Hg) were compared against those from age-matched normotensive (134±7 mm Hg) Wistar Kyoto rats (n=4 in each group). Global differential analysis using 2D electrophoresis followed by tandem mass spectrometry–based protein identification suggested a downregulation of enzymes involved in cellular energetics in hypertension. Targeted differential analysis of mitochondrial respiratory complexes using the classical blue-native SDS-PAGE/Western method and a complementary combination of sucrose-gradient ultracentrifugation/tandem mass spectrometry revealed previously unknown assembly defects in complexes I, III, IV, and V in hypertension. Interestingly, targeted examination of the brain stem, a regulator of cardiovascular homeostasis and systemic blood pressure, further showed the occurrence of mitochondrial complex I dysfunction, elevated reactive oxygen species production, decreased ATP synthesis, and impaired respiration in hypertension. Our findings suggest that in already-hypertensive spontaneously hypertensive rats, the brain respiratory complexes exhibit previously unknown assembly defects. These defects impair the function of the mitochondrial respiratory chain. This mitochondrial dysfunction localizes to the brain stem and is, therefore, likely to contribute to the development, as well as to pathophysiological complications, of hypertension.
Decadal Trends in Sea Level Patterns: 1993–2004
Authors: Wunsch Carl , Ponte Rui M. , Heimbach Patrick
Published: January 2008

Estimates of regional patterns of global sea level change are obtained from a 1° horizontal resolution general circulation model constrained by least squares to about 100 million ocean observations and many more meteorological estimates during the period 1993–2004. The data include not only altimetric variability, but most of the modern hydrography, Argo float profiles, sea surface temperature, and other observations. Spatial-mean trends in altimetric data are explicitly suppressed to isolate global average long-term changes required by the in situ data alone. On large scales, some regions display strong signals although few individual points have statistically significant trends. In the regional patterns, thermal, salinity, and mass redistribution contributions are all important, showing that regional sea level change is tied directly to the general circulation. Contributions below about 900 m are significant, but not dominant, and are expected to grow with time as the abyssal ocean shifts. Estimates made here produce a global mean of about 1.6 mm yr−1, or about 60% of the pure altimetric estimate, of which about 70% is from the addition of freshwater. Interannual global variations may be dominated by the freshwater changes rather than by heating changes. The widely quoted altimetric global average values may well be correct, but the accuracies being inferred in the literature are not testable by existing in situ observations. Useful estimation of the global averages is extremely difficult given the realities of space–time sampling and model approximations. Systematic errors are likely to dominate most estimates of global average change: published values and error bars should be used very cautiously.
HIV/AIDS and Employment Research
Authors: Conyers Liza Marie
Published: January 2008

This article provides a reflection on the three articles that compose the Major Contribution on HIV/AIDS and employment research. It highlights the merits of the contribution in the broader context of HIV/AIDS employment research and recommends future directions for this area of inquiry, including theory integration, an investigation of HIV health outcomes, and an interdisciplinary approach to this complex line of research.
Foamability of Thermoplastic Vulcanizates Blown with Various Physical Blowing Agents
Authors: Kim Seong G. , Park Chul B. , Sain Mohini
Published: January 2008

Thermoplastic vulcanizate (TPV) is a special class of thermoplastic elastomers (TPEs) made of a rubber/plastic polymer mixture in which the rubber phase is highly vulcanized. It is prepared by melt mixing a thermoplastic with an elastomer and by in situ crosslinking of the rubber phase. Currently, TPV is replacing EPDM rubber dramatically because of the impressive advantages for automotive sealing applications. Some of the advantages of TPV compared to that of EPDM rubber are good gloss, recyclability, improved colorability, shorter cycle time, and design flexibility. The development of TPV foaming technology is to fulfill the requirement of achieving lower cost, lighter weight, and better fuel economy. Foaming of TPV has not been investigated extensively. The complete dissolution of the blowing agent in the molten polymer is the most critical step in TPV foaming processing, and this strongly depends on the solubility of the blowing agent, the saturation pressure, the degree of mixing, and residence time. In our study, we attempted to understand the foaming behavior of commercial TPVs in general, with various blowing agents. The effect of blowing agent type and concentration on the expansion behavior, the cell-number density, and the foam structure under the different processing conditions are examined. These experimental results will be used to determine optimized TPV formulations to ensure good foamability, while retaining the properties of TPV.
Chronic Myoclonia of Subcortical Origin With Antiglutamate Receptor Antibodies
Authors: Matsuo Muneaki , Takahashi Yukitoshi , Taniguchi Kazuto , Sasaki Kazuya , Hamasaki Yuhei
Published: January 2008

We report a 10-year-old girl with chronic nonprogressive continuous myoclonia with mild muscle weakness and dissociated sensory impairment of the ipsilateral side of myoclonic jerks. Irregular myoclonic jerks continuously appeared in the right upper limb. The jerk-locked back averaging of electroencephalographic activity failed to show any activity preceded by the muscle contraction. Magnetic resonance imaging of the brain and cervical spine revealed no abnormal findings. Single photon emission computed tomography showed an increased blood perfusion in the left thalamus. 18F-deoxyglucose-positron emission tomography (PET) also showed a slight high density in the posterior region of the left thalamus. Antiglutamate receptor ε2 and δ2 antibodies were detected in the serum and cerebrospinal fluid. The patient's symptoms have now been stable with clonazepam treatment for 2 years. The left thalamus was suspected to have been the region at least partly responsible for the patient's symptoms.
The Messy Relationship Between Feminisms and Globalizations
Authors: Desai Manisha
Published: January 2008

With some exceptions, feminist scholars have written either about gender and globalizations or about transnational feminisms but rarely examined the relationship between them. In this essay, the author wants to reflect on this relationship to highlight how they have shaped each other. She suggests that feminisms are important force-shaping globalizations. At the same time, the relationship between them is fraught and in some instances has furthered inequalities among feminists. But this does not preclude other possibilities as is evident in the work of feminists around the world.
Complementary and Alternative Medicine for Children's Asthma: Satisfaction, Care Provider Responsiveness, and Networks of Care
Authors: Freidin Betina , Timmermans Stefan
Published: January 2008

We explain why some caretakers opt for alternative medicine for the treatment of children's asthma whereas others do not. In the past 15 years, asthma care has been standardized, with clinical practice guidelines centered on advanced pharmacological regimes. Clinicians argue that with proper biomedical treatment and environmental control, asthma should be a manageable chronic disease. Yet many patients forego available pharmacological treatments for alternative medicine or complement prescribed drugs with unconventional treatments. On the basis of open-ended, in-depth qualitative interviews with 50 mothers of children with asthma, we argue that the experience with biomedical treatments, social influence in mother's network of care, concerns about adverse and long-term effects, health care providers' responsiveness to such concerns, and familiarity with alternative treatments explain why some families rely on alternative medicine and others do not.
Uncertainty of Social Network Members in the Case of Communication-Debilitating Illness or Injury
Authors: Donovan-Kicken Erin , Bute Jennifer J.
Published: January 2008

Uncertainty is a consequential aspect of chronic illness for patients as well as their family and friends, yet little research has focused on how non-ill individuals experience uncertainty about the condition of someone in their social network. Thirty-one individuals with loved ones who had a communication-debilitating illness or injury (CDI) participated in one-on-one interviews about their experiences. We analyzed transcripts for participants' sources of uncertainty and for ways that they managed the uncertainty. Participants' experiences with uncertainty included questions about the condition itself and involved the impaired communication resulting from the CDI. Participants described managing uncertainty through information seeking, changing the ways they communicated with the person with the CDI, and creating schemata to help reduce uncertainty. We discuss the findings in terms of predominant conceptualizations of uncertainty in illness and address the prevalence of communication as both a significant source of uncertainty and an important means of managing uncertainty.
Relations Among Spouse Acceptance, Remembered Parental Acceptance in Childhood, and Psychological Adjustment Among Married Adults in India
Authors: Parmar Parminder , Rohner Ronald P.
Published: January 2008

This study explored the way in which remembered childhood experiences of maternal and paternal acceptance mediated or influenced in other ways the relation between perceived intimate-partner acceptance and the psychological adjustment of married adults in India. Results of simple correlations based on data from four self-report questionnaires showed that the more accepting both men and women saw their spouses to be, the better was their psychological adjustment; similarly, the more accepting men and women remembered both their mothers and fathers to have been when the respondents were children, the better was their psychological adjustment. However, results of multiple regression analyses showed that remembered maternal acceptance no longer made a significant contribution to the psychological adjustment of either men or women when the influence of paternal and partner acceptance was partialed out. Remembered paternal acceptance was the best single predictor of psychological adjustment for both men and women, although perceived partner acceptance also made a robust contribution.