bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular Signal–Regulated Kinase 1/2 Activation, via Downregulation of Mitogen-Activated Protein Kinase Phosphatase 1, Mediates Sex Differences in Desoxycorticosterone Acetate-Salt Hypertension Vascular Reactivity
Authors: Giachini Fernanda R. , Sullivan Jennifer C. , Lima Victor V. , Carneiro Fernando S. , Fortes Zuleica B. , Pollock David M. , Carvalho Maria Helena C. , Webb R. Clinton , Tostes Rita C.
Published: November 2009

Extracellular signal–regulated kinase (ERK)1/2 has been reported to play a role in vascular dysfunction associated with mineralocorticoid hypertension. We hypothesized that, compared with female rats, an upregulation of ERK1/2 signaling in the vasculature of male rats contributes to augmented contractile responses in mineralocorticoid hypertension. Uninephrectomized male and female Sprague-Dawley rats received desoxycorticosterone acetate (DOCA) pellets (200 mg per animal) and saline to drink for 3 weeks. Control uninephrectomized rats received tap water to drink. Blood pressure, measured by telemetry, was significantly higher in male DOCA rats (191±3 mm Hg) compared with female DOCA rats (172±7 mm Hg; n=5). DOCA treatment resulted in augmented contractile responses to phenylephrine in aorta (22±3 mN; n=6) and small mesenteric arteries (13±2 mN; n=6) from male DOCA rats versus uninephrectomized male rats (16±3 and 10±2 mN, respectively;
P
<0.05) and female DOCA rats (15±1 and 11±1 mN, respectively). ERK1/2 inhibition with PD-98059 (10 μmol/L) abrogated increased contraction to phenylephrine in aorta (14±2 mN) and small mesenteric arteries (10±2 mN) from male DOCA rats, without any effects in arteries from male uninephrectomized or female animals. Compared with the other groups, phosphorylated ERK1/2 levels were increased in the aorta from male DOCA rats, whereas mitogen-activated protein kinase phosphatase 1 expression was decreased. Interleukin-10 plasma levels, which positively regulate mitogen-activated protein kinase phosphatase 1 activity, were reduced in male DOCA-salt rats. We speculate that augmented vascular reactivity in male hypertensive rats is mediated via activation of the ERK1/2 pathway. In addition, mitogen-activated protein kinase phosphatase 1 and interleukin 10 play regulatory roles in this process.
p21-Activated Kinase 1 Participates in Vascular Remodeling In Vitro and In Vivo
Authors: Hinoki Akinari , Kimura Keita , Higuchi Sadaharu , Eguchi Kunie , Takaguri Akira , Ishimaru Kazuhiro , Frank Gerald D. , Gerthoffer William T. , Sommerville Laura J. , Autieri Michael V. , Eguchi Satoru
Published: November 2009

Vascular smooth muscle cell hypertrophy, proliferation, or migration occurs in hypertension, atherosclerosis, and restenosis after angioplasty, leading to pathophysiological vascular remodeling. Angiotensin II and platelet-derived growth factor are well-known participants of vascular remodeling and activate a myriad of downstream protein kinases, including p21-activated protein kinase (PAK1). PAK1, an effector kinase of small GTPases, phosphorylates several substrates to regulate cytoskeletal reorganization. However, the exact role of PAK1 activation in vascular remodeling remains to be elucidated. Here, we have hypothesized that PAK1 is a critical target of intervention for the prevention of vascular remodeling. Adenoviral expression of dominant-negative PAK1 inhibited angiotensin II–stimulated vascular smooth muscle cell migration. It also inhibited vascular smooth muscle cell proliferation induced by platelet-derived growth factor. PAK1 was activated in neointima of the carotid artery after balloon injury in the rat. Moreover, marked inhibition of the neointima hyperplasia was observed in a dominant-negative PAK1 adenovirus-treated carotid artery after the balloon injury. Taken together, these results suggest that PAK1 is involved in both angiotensin II and platelet-derived growth factor–mediated vascular smooth muscle cell remodeling, and inactivation of PAK1 in vivo could be effective in preventing pathophysiological vascular remodeling.
Growth of Spread in Convection-Allowing and Convection-Parameterizing Ensembles
Authors: Clark Adam J. , Gallus William A. , Xue Ming , Kong Fanyou
Published: November 2009

During the 2007 NOAA Hazardous Weather Testbed Spring Experiment, a 10-member 4-km grid-spacing Storm-Scale Ensemble Forecast (SSEF) system was run in real time to provide experimental severe weather forecasting guidance. Five SSEF system members used perturbed initial and lateral boundary conditions (ICs and LBCs) and mixed physics (ENS4), and five members used only mixed physics (ENS4phys). This ensemble configuration facilitates a comparison of ensemble spread generated by a combination of perturbed ICs/LBCs and mixed physics to that generated by only mixed physics, which is examined herein. In addition, spread growth and spread-error metrics for the two SSEF system configurations are compared to similarly configured 20-km grid-spacing convection-parameterizing ensembles (ENS20 and ENS20phys). Twelve forecast fields are examined for 20 cases.

For most fields, ENS4 mean spread growth rates are higher than ENS20 for ensemble configurations with both sets of perturbations, which is expected as smaller scales of motion are resolved at higher resolution. However, when ensembles with only mixed physics are compared, mass-related fields (i.e., geopotential height and mean sea level pressure) in ENS20phys have slightly higher spread growth rates than ENS4phys, likely resulting from the additional physics uncertainty in ENS20phys from varied cumulus parameterizations that were not used at 4-km grid spacing. For 4- and 20-km configurations, the proportion of spread generated by mixed physics in ENS4 and ENS20 increased with increasing forecast lead time. In addition, low-level fields (e.g., 2-m temperature) had a higher proportion of spread generated by mixed physics than mass-related fields. Spread-error analyses revealed that ensemble variance from the current uncalibrated ensemble systems was not a reliable indicator of forecast uncertainty. Furthermore, ENS4 had better statistical consistency than ENS20 for some mass-related fields, wind-related fields, precipitation, and most unstable convective available potential energy (MUCAPE) with no noticeable differences for low-level temperature and dewpoint fields. The variety of results obtained for the different types of fields examined suggests that future ensemble design should give careful consideration to the specific types of forecasts desired by the user.
Assessing the Impact of Weather on Traffic Intensity
Authors: Cools Mario , Moons Elke , Wets Geert
Published: November 2009

This paper focuses on the effect of weather conditions on daily traffic intensities (the number of cars passing a specific segment of a road). The main objective is to examination whether or not weather conditions uniformly alter daily traffic intensities in Belgium, or in other words whether or not road usage on a particular location determines the size of the impacts of various weather conditions. This general examination is a contribution that allows policymakers to assess the appropriateness of countrywide versus local traffic management strategies. In addition, a secondary goal of this paper is to validate findings in international literature within a Belgian context. To achieve these goals, the paper analyzes the effects of weather conditions on both upstream (toward a specific location) and downstream (away from a specific location) traffic intensities at three traffic count locations typified by a different road usage. Perhaps the most interesting results of this study for policymakers are the heterogeneity of the weather effects between different traffic count locations, and the homogeneity of the weather effects on upstream and downstream traffic at specific locations. The results also indicate that snowfall, rainfall, and wind speed diminish traffic intensity, and high temperatures increase traffic intensity. Further generalizations of the findings might be possible by studying weather impacts on local roads and by shifting the focus of research toward travel behavior.
Deliberative Democracy and Inequality: Two Cheers for Enclave Deliberation among the Disempowered
Authors: Karpowitz Christopher F. , Raphael Chad , Hammond Allen S.
Published: November 2009

Deliberative democracy grounds its legitimacy largely in the ability of speakers to participate on equal terms. Yet theorists and practitioners have struggled with how to establish deliberative equality in the face of stark differences of power in liberal democracies. Designers of innovative civic forums for deliberation often aim to neutralize inequities among participants through proportional inclusion of disempowered speakers and discourses. In contrast, others argue that democratic equality is best achieved when disempowered groups deliberate in their own enclaves (interest groups, parties, and movements) before entering the broader public sphere. Borrowing from each perspective, the authors argue that there are strong reasons to incorporate enclave deliberation among the disempowered within civic forums. They support this claim by presenting case study evidence showing that participants in such forums can gain some of the same benefits of deliberation found in more heterogeneous groups (e.g., political knowledge, efficacy and trust), can consider a diversity of viewpoints rather than falling into groupthink and polarization, and can persuade external stakeholders of the legitimacy of the group’s deliberations.
Industrial Policy in the United States: A Neo-Polanyian Interpretation
Authors: Schrank Andrew , Whitford Josh
Published: November 2009

The conventional wisdom holds that U.S. political institutions are inhospitable to industrial policy. The authors call the conventional wisdom into question by making four claims: (1) the activities targeted by industrial policy are increasingly governed by decentralized production networks rather than markets or hierarchies, (2) “network failures” are therefore no less threatening to industrial dynamism than market or organizational failures, (3) the spatial and organizational decentralization of production have simultaneously increased the demand and broadened the support for American industrial policy, and (4) political decentralization is therefore likely to improve the functioning of industrial policies designed to combat network failures.
A Web-Based Tool to Support Data-Based Early Intervention Decision Making
Authors: Buzhardt Jay , Greenwood Charles , Walker Dale , Carta Judith , Terry Barbara , Garrett Matthew
Published: November 2009

Progress monitoring and data-based intervention decision making have become key components of providing evidence-based early childhood special education services. Unfortunately, there is a lack of tools to support early childhood service providers’ decision-making efforts. The authors describe a Web-based system that guides service providers through a decision-making process informed by child performance on Infant and Toddler IGDIs (Individual Growth and Development Indicators), the provider’s professional judgment, and information from the child’s primary caregiver. Using a case example, the authors describe how a service provider integrates the system into an existing service delivery model. Finally, they describe barriers and potential solutions to implementation within the context of a traditional early childhood service delivery model and implications for policy and practice.
Use of a Case-Based Hypermedia Resource in an Early Literacy Coaching Intervention With Pre-Kindergarten Teachers
Authors: Powell Douglas R. , Diamond Karen E. , Koehler Matthew J.
Published: November 2009

Use of a case-based hypermedia resource (HR) was examined in a Web-based early literacy coaching intervention with pre-kindergarten teachers of at-risk children. Web usage logs, written records of coach feedback to teachers on their instruction, and a teacher questionnaire were the primary data sources. Visits to the HR content pages were unevenly distributed across literacy topics, with 9 of 16 cases in the video-intensive HR receiving a majority of all page visits. Usage patterns of both teachers and coaches point to selective engagement of the Web’s resources rather than usage driven by the available number of items in each of the HR’s content areas. Teachers provided highly favorable assessments of the video exemplars, including their ecological validity. Implications for the design and uses of Web-based professional development are discussed.
Meaning and Porous Being
Authors: Smith Karl E.
Published: November 2009

In A Secular Age, Taylor introduces the idea of porous subjectivity by way of elucidating the mode of being typical of the enchanted pre-modern world, and juxtaposes it to the buffered self typical of the disenchanted modern world. The framing of the problem in this way, with the argument so clearly oriented as an attack on the latter position, risks a polarization that defaults to the former as the preferred option. These, though, are not our only choices. There is much to recommend Taylor’s notion of porous subjectivity as distinct from the buffered self of atomistic individualism. But Taylor associates the emergence of the disenchanted world with disengaged reason, and the existence of an enchanted world with a deeper mode of engagement in the world. If we instead focus upon modes of engagement with the world separate from the question of enchantment, we can perhaps further our understanding of human subjectivity and relations with others.
Taylor on Solidarity
Authors: Smith Nicholas H. , Laitinen Arto
Published: November 2009

After characterizing Taylor’s general approach to the problems of solidarity, we distinguish and reconstruct three contexts of solidarity in which this approach is developed: the civic, the socio-economic, and the moral. We argue that Taylor’s distinctive move in each of these contexts of solidarity is to claim that the relationship at stake poses normatively justified demands, which are motivationally demanding, but insufficiently motivating on their own. On Taylor’s conception, we need some understanding of extra motivational sources which explain why people do (or would) live up to the exacting demands. Taylor accepts that our self-understanding as members of either particular communities or humanity at large has some motivational power, but he suspects that in many cases the memberships are too thin to resonate deeply and enduringly within us. In Taylor’s view, a realistic picture of what moves people to solidarity has to account for the extra motivation, when it happens. We propose an alternative view in which morality, democracy and socio-economic cooperation can be seen as separate spheres or relations which are normatively justified, motivationally demanding, but also sufficiently motivating on their own.
Plus Ça Change: Charles Taylor On Accommodating Quebec’s mInority Cultures
Authors: Abbey Ruth
Published: November 2009

This article examines the 2008 report of the Quebec Government’s Consultation Commission on Accommodation Practices Related to Cultural Differences which was co-authored by Charles Taylor. Summarizing its main themes, it identifies points of intersection with Taylor’s political thought. Issues of citizen equality, including gender equality, secularism, integration and interculturalism, receive special attention.
Rethinking the Value of Residents’ Councils: Observations and Lessons From an Exploratory Study
Authors: O'Dwyer Ciara , Timonen Virpi
Published: November 2009

Little empirical research is available on residents’ councils (RCs) in care settings for older people. This article analyzes the operation of an RC in an Irish facility, drawing on direct observation of council meetings and interviews with resident participants and staff members. Though some participants benefited from having the opportunity to discuss their views during council meetings, few changes were introduced that affected nonparticipants. The article identified several barriers to the successful operation of the council, including the lack of independence of the council, inadequate skills in group facilitation, staffing shortages, lack of training, and management structures.
Family Perspectives
Authors: Lee Suk-Hyang , Turnbull Ann P. , Zan Fei
Published: November 2009

Educators can better serve students who come from diverse cultural backgrounds by understanding the differing cultural values of these students and their families. This article explores different cultural perspectives using a cultural prism approach, focused most specifically on the Korean and Chinese cultures.
A Theory of Collective Identity Making Sense of the Debate on a ‘European Identity’
Authors: Eder Klaus
Published: November 2009

This article argues for a robust notion of collective identity which is not reduced to a psychological conception of identity. In the first part, the debate on the concept of identity raised by several authors is taken up critically with the intention of defending a strong sociological conception of identity which by definition is a collective identity. The basic assumption is that collective identities are narrative constructions which permit the control of the boundaries of a network of actors. This theory is then applied to the case of Europe, showing how identity markers are used to control the boundaries of a common space of communication. These markers are bound to stories which those within such a space of communication share. Stories that hold in their narrative structures social relations provide projects of control. National identities are based on strong and exclusive stories. Europeanization (among other parallel processes at the global level) opens this space of boundary constructions and offers opportunities for national as well as sub-national as well as transnational stories competing with each other to shape European identity projects. The EU — this is the hypothesis — provides a case in which different sites offer competing opportunities to continue old stories, to start new stories or to import old stories from other sites, thus creating a narrative network on top of the network of social relations that bind the people in Europe together. European identity is therefore to be conceived as a narrative network embedded in an emerging network of social relations among the people living in Europe.
Tariq Ramadan vs. Daniel Cohn-Bendit or Why a European Model of Society Based on Weak Citizenship Is Not Such a Good Idea
Authors: Giorgi Liana
Published: November 2009

The boundaries, openness and character of the future European society will crucially depend on the degree and scope of identity politics. Religion, culture and nationality remain strong reference frameworks for individuals in their inter-personal but also political relations and tend, in practice, to favour weak rather than strong forms of citizenship. Whether this is a viable model for large and diverse democratic societies is an old debate known primarily from the discussions and theory on multiculturalism. How this debate is played out at European level and especially with respect to the role of religion is illustrated with reference to the ideas of Daniel Cohn-Bendit and Tariq Ramadan, two well-known public figures with a strong commitment to Europe and European identity, albeit from rather different perspectives and outlooks. At the substantive or philosophical level, it appears impossible to resolve the fundamental questions underlying the opposition between liberalism and communitarianism as represented by the two men. The usefulness of a middle-range pragmatic approach insofar as political solutions or societal compromises are concerned is scrutinized for its usefulness.
Power in Transition: An Interdisciplinary Framework to Study Power in Relation to Structural Change
Authors: Avelino Flor , Rotmans Jan
Published: November 2009

This article conceptualizes power in the context of long-term process of structural change. First, it discusses the field of transition studies, which deals with processes of structural change in societal systems on the basis of certain presumptions about power relations, but still lacks an explicit conceptualization of power. Then the article discusses some prevailing points of contestation in debates on power. It is argued that for the context of transition studies, it is necessary to develop an interdisciplinary framework in which power is explicitly conceptualized in relation to change. Subsequently, such a framework is presented, with reference to existing literature on power. Starting with a philosophical and operational definition of power, a typology is developed of the different ways in which power can be exercised, explicitly including innovative power and transformative power. Finally, the presented power framework is applied to transition studies, redefining pivotal transition concepts in terms of power and formulating hypotheses on the role of power in transitions. By doing so, the article not only offers an interdisciplinary framework to study power in the context of transition studies, but also contributes to power debates more generally by including innovation and transformation as acts of power, and thereby proposes a re-conceptualization of the relation between power and structural change.
Tailored Additive Release Rates in Extruded Plastic Films Produced With Smart Blending Machines
Authors: Jin X. , Zumbrunnen D.A. , Balasubramanian A. , Yam K.
Published: November 2009

Smart blenders controllably form multi-component polymer melts into a wide variety of fine-scale structural arrangements that can be retained in extruded plastics. The machines operate on the principle of chaotic advection, a recent subfield of fluid mechanics, and have been used to produce cast film and blown film but can also be used to extrude sheet, rod, tubing, and other products. Because and structure of a composite material influences greatly additive diffusion, and matrix dissolution, this processing method provides a means for producing packaging film, medications, and medical implants with tailored release rates of active compounds. In this article, an ability to alter release rates of tocopherol, a natural antioxidant of importance to food packaging, is specifically investigated via on-line specification of a process parameter governing blend morphology in extruded cast films. Blends of low-density polyethylene and polypropylene, and also low-density polyethylene and high-density polyethylene were used.
Inflammation induces lymphangiogenesis through up-regulation of VEGFR-3 mediated by NF-κB and Prox1
Authors: Flister Michael J. , Wilber Andrew , Hall Kelly L. , Iwata Caname , Miyazono Kohei , Nisato Riccardo E. , Pepper Michael S. , Zawieja David C. , Ran Sophia
Published: November 2009

The concept of inflammation-induced lymphangiogenesis (ie, formation of new lymphatic vessels) has long been recognized, but the molecular mechanisms remained largely unknown. The 2 primary mediators of lymphangiogenesis are vascular endothelial growth factor receptor-3 (VEGFR-3) and Prox1. The key factors that regulate inflammation-induced transcription are members of the nuclear factor-kappaB (NF-κB) family; however, the role of NF-κB in regulation of lymphatic-specific genes has not been defined. Here, we identified VEGFR-3 and Prox1 as downstream targets of the NF-κB pathway. In vivo time-course analysis of inflammation-induced lymphangiogenesis showed activation of NF-κB followed by sequential up-regulation of Prox1 and VEGFR-3 that preceded lymphangiogenesis by 4 and 2 days, respectively. Activation of NF-κB by inflammatory stimuli also elevated Prox1 and VEGFR-3 expression in cultured lymphatic endothelial cells, resulting in increased proliferation and migration. We also show that Prox1 synergizes with the p50 of NF-κB to control VEGFR-3 expression. Collectively, our findings suggest that induction of the NF-κB pathway by inflammatory stimuli activates Prox1, and both NF-κB and Prox1 activate the VEGFR-3 promoter leading to increased receptor expression in lymphatic endothelial cells. This, in turn, enhances the responsiveness of preexisting lymphatic endothelium to VEGFR-3 binding factors, VEGF-C and VEGF-D, ultimately resulting in robust lymphangiogenesis.
Malaria in patients with sickle cell anemia: burden, risk factors, and outcome at the outpatient clinic and during hospitalization
Authors: Makani Julie , Komba Albert N. , Cox Sharon E. , Oruo Julie , Mwamtemi Khadija , Kitundu Jesse , Magesa Pius , Rwezaula Stella , Meda Elineema , Mgaya Josephine , Pallangyo Kisali , Okiro Emelda , Muturi David , Newton Charles R. , Fegan Gregory , Marsh Kevin , Williams Thomas N.
Published: November 2009

Approximately 280 000 children are born with sickle cell anemia (SCA) in Africa annually, yet few survive beyond childhood. Falciparum malaria is considered a significant cause of this mortality. We conducted a 5-year prospective surveillance study for malaria parasitemia, clinical malaria, and severe malarial anemia (SMA) in Dar-es-Salaam, Tanzania, between 2004 and 2009. We recorded 10 491 visits to the outpatient clinic among 1808 patients with SCA and 773 visits among 679 patients without SCA. Similarly, we recorded 691 hospital admissions among 497 patients with SCA and 2017 in patients without SCA. Overall, the prevalence of parasitemia was lower in patients with SCA than in patients without SCA both at clinic (0.7% vs 1.6%; OR, 0.53; 95% CI, 0.32-0.86; P = .008) and during hospitalization (3.0% vs 5.6%; OR, 0.46; 95% CI, 0.25-0.94; P = .01). Furthermore, patients with SCA had higher rates of malaria during hospitalization than at clinic, the ORs being 4.29 (95% CI, 2.63-7.01; P < .001) for parasitemia, 17.66 (95% CI, 5.92-52.71; P < .001) for clinical malaria, and 21.11 (95% CI, 8.46-52.67; P < .001) for SMA. Although malaria was rare among patients with SCA, parasitemia during hospitalization was associated with both severe anemia and death. Effective treatment for malaria during severe illness episodes and further studies to determine the role chemoprophylaxis are required.
SnoRNAs from the filamentous fungus Neurospora crassa: structural, functional and evolutionary insights
Authors: Liu Na , Xiao Zhen-Dong , Yu Chun-Hong , Shao Peng , Liang Yin-Tong , Guan Dao-Gang , Yang Jian-Hua , Chen Chun-Long , Qu Liang-Hu , Zhou Hui
Published: November 2009

Background

SnoRNAs represent an excellent model for studying the structural and functional evolution of small non-coding RNAs involved in the post-transcriptional modification machinery for rRNAs and snRNAs in eukaryotic cells. Identification of snoRNAs from Neurospora crassa, an important model organism playing key roles in the development of modern genetics, biochemistry and molecular biology will provide insights into the evolution of snoRNA genes in the fungus kingdom.

Results

Fifty five box C/D snoRNAs were identified and predicted to guide 71 2'-O-methylated sites including four sites on snRNAs and three sites on tRNAs. Additionally, twenty box H/ACA snoRNAs, which potentially guide 17 pseudouridylations on rRNAs, were also identified. Although not exhaustive, the study provides the first comprehensive list of two major families of snoRNAs from the filamentous fungus N. crassa. The independently transcribed strategy dominates in the expression of box H/ACA snoRNA genes, whereas most of the box C/D snoRNA genes are intron-encoded. This shows that different genomic organizations and expression modes have been adopted by the two major classes of snoRNA genes in N. crassa . Remarkably, five gene clusters represent an outstanding organization of box C/D snoRNA genes, which are well conserved among yeasts and multicellular fungi, implying their functional importance for the fungus cells. Interestingly, alternative splicing events were found in the expression of two polycistronic snoRNA gene hosts that resemble the UHG-like genes in mammals. Phylogenetic analysis further revealed that the extensive separation and recombination of two functional elements of snoRNA genes has occurred during fungus evolution.

Conclusion

This is the first genome-wide analysis of the filamentous fungus N. crassa snoRNAs that aids in understanding the differences between unicellular fungi and multicellular fungi. As compared with two yeasts, a more complex pattern of methylation guided by box C/D snoRNAs in multicellular fungus than in unicellular yeasts was revealed, indicating the high diversity of post-transcriptional modification guided by snoRNAs in the fungus kingdom.
Impacts of feral horses on a desert environment
Authors: Ostermann-Kelm Stacey D , Atwill Edward A , Rubin Esther S , Hendrickson Larry E , Boyce Walter M
Published: November 2009

Background

Free-ranging horses (Equus caballus) in North America are considered to be feral animals since they are descendents of non-native domestic horses introduced to the continent. We conducted a study in a southern California desert to understand how feral horse movements and horse feces impacted this arid ecosystem. We evaluated five parameters susceptible to horse trampling: soil strength, vegetation cover, percent of nonnative vegetation, plant species diversity, and macroinvertebrate abundance. We also tested whether or not plant cover and species diversity were affected by the presence of horse feces.

Results

Horse trailing resulted in reduced vegetation cover, compacted soils, and in cases of intermediate intensity disturbance, increased plant species diversity. The presence of horse feces did not affect plant cover, but it did increase native plant diversity.

Conclusion

Adverse impacts, such as soil compaction and increased erosion potential, were limited to established horse trails. In contrast, increased native plant diversity near trails and feces could be viewed as positive outcomes. Extensive trailing can result in a surprisingly large impact area: we estimate that < 30 horses used > 25 km2 of trails in our study area.
A new synthetic protein, TAT-RH, inhibits tumor growth through the regulation of NFκB activity
Authors: Sorriento Daniela , Campanile Alfonso , Santulli Gaetano , Leggiero Eleonora , Pastore Lucio , Trimarco Bruno , Iaccarino Guido
Published: November 2009

Background

Based on its role in angiogenesis and apoptosis, the inhibition of NFκB activity is considered an effective treatment for cancer, hampered by the lack of selective and safe inhibitors. We recently demonstrated that the RH domain of GRK5 (GRK5-RH) inhibits NFκB, thus we evaluated its effects on cancer growth.

Methods

The role of GRK5-RH on tumor growth was assessed in a human cancer cell line (KAT-4). RH overexpression was induced by adenovirus mediated gene transfer; alternatively we administered a synthetic protein reproducing the RH domain of GRK5 (TAT-RH), actively transported into the cells.

Results

In vitro, adenovirus mediated GRK5-RH overexpression (AdGRK5-NT) in human tumor cells (KAT-4) induces IκB accumulation and inhibits NFκB transcriptional activity leading to apoptotic events. In BALB/c nude mice harboring KAT-4 induced neoplasias, intra-tumor delivery of AdGRK5-NT reduces in a dose-dependent fashion tumor growth, with the highest doses completely inhibiting it. This phenomenon is paralleled by a decrease of NFκB activity, an increase of IκB levels and apoptotic events. To move towards a pharmacological setup, we synthesized the TAT-RH protein. In cultured KAT-4 cells, different dosages of TAT-RH reduced cell survival and increased apoptosis. In BALB/c mice, the anti-proliferative effects of TAT-RH appear to be dose-dependent and highest dose completely inhibits tumor growth.

Conclusion

Our data suggest that GRK5-RH inhibition of NFκB is a novel and effective anti-tumoral strategy and TAT-RH could be an useful tool in the fighting of cancer.
Comparison of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assessment for Her-2 status in breast cancer
Authors: Sui Weiguo , Ou Minglin , Chen Jiejing , Wan Youhua , Peng Hongbo , Qi Minfang , Huang He , Dai Yong
Published: November 2009

Background

The concordance rate between IHC and FISH according to clinical performance is still controversial. We report a prospective study to reflect the concordance between IHC and FISH in Guilin city, People's Republic of China.

Methods

Fifty cases of invasive ductal carcinoma of breast tested by IHC and scored as 0, 1+, 2+ and 3+ by pathologists were further analyzed by FISH using a commercially available double-color probe, and the FISH findings were compared with IHC test results.

Results

A total concordance of 82.0% was observed with a Kappa coefficient of 0.640 (P < 0.001). A high discordance was observed in 30.0% of the patients with IHC 2+, 7.1% in IHC 3+, 19.2% overall in IHC 0 and 1+.

Conclusion

The IHC can be used firstly to screen the HER-2 status, and FISH can be used as a supplementary role to IHC and 2+ and some negative cases. And only those cases with Her-2 status of IHC 3+ or FISH positive should be treated with Herceptin.
yuDetecting the percent of peripheral blood mononuclear cells displaying p-STAT-3 in malignant glioma patients
Authors: Humphries William , Wang Yongtao , Qiao Wei , Reina-Ortiz Chantal , Abou-Ghazal Mohamed K , Crutcher Lamonne M , Wei Jun , Kong Ling-Yuan , Sawaya Raymond , Rao Ganesh , Weinberg Jeffrey , Prabhu Sujit S , Fuller Gregory N , Heimberger Amy B
Published: November 2009

Background

The signal transducer and activator of transcription 3 (STAT-3) is frequently overexpressed in cancer cells, propagates tumorigenesis, and is a key regulator of immune suppression in cancer patients. The presence of phosphorylated STAT-3 (p-STAT-3) in the tumor can induce p-STAT-3 in tumor-associated immune cells that can return to the circulatory system. We hypothesized that the number of peripheral blood mononuclear cells (PBMCs) displaying p-STAT-3 would be increased in glioma patients, which would correlate with the extent of tumor-expressed p-STAT-3, and that higher p-STAT-3 levels in peripheral blood would correlate with a higher fraction of immune-suppressive regulatory T cells (Tregs).

Methods

We measured the percentage of PBMCs displaying p-STAT-3 in 19 healthy donors and 45 patients with primary brain tumors. The level of p-STAT-3 in tumor tissue was determined by immunohistochemistry. The degree of immune suppression was determined based on the fraction of Tregs in the CD4 compartment.

Results

Healthy donors had 4.8 ± 3.6% of PBMCs that expressed p-STAT-3, while the mean proportion of PBMCs displaying p-STAT-3 in patients with GBM was 11.8 ± 13.5% (P = 0.03). We did not observe a correlation by Spearman correlation between the degree of p-STAT-3 levels in the tumor and the percent of PBMCs displaying p-STAT-3. Furthermore, the percent of PBMCs displaying p-STAT-3 in glioma patients was not directly correlated with the fraction of Tregs in the CD4 compartment.

Conclusion

We conclude that the percent of PBMCs displaying p-STAT-3 may be increased in malignant glioma patients.
Gain-loss frequency and final outcome in the Soochow Gambling Task: A Reassessment
Authors: Lin Ching-Hung , Chiu Yao-Chu , Huang Jong-Tsun
Published: November 2009

Background

Behavioral decision making literature suggests that decision makers are guided less by final outcome than by immediate gain-loss. However, studies of the Iowa Gambling Task (IGT) under dynamic and uncertain conditions reveal very different conclusions about the role of final outcome. Another research group designed a similar yet simpler game, the Soochow Gambling Task (SGT), which demonstrated that, in dynamic decision making, the effect of gain-loss frequency is more powerful than that of final outcome. Further study is needed to determine the precise effect of final outcome on decision makers. This experiment developed two modified SGTs to explore the effect of final outcome under the same gain-loss frequency context.

Methods

Each version of the SGT was performed by twenty-four undergraduate Soochow University students. A large-value (± $200, ± $550 and ± $1050) and a small-value (± $100, ± $150 and ± $650) contrast of SGT were conducted to investigate the final outcome effect. The computerized SGT was launched to record and analyze the choices of the participants.

Results

The results of both SGT versions consistently showed that the preferred decks A and B to decks C and D. Analysis of learning curves also indicated that, throughout the game, final outcome had a minimal effect on the choices of decision makers.

Conclusion

Experimental results indicated that, in both the frequent-gain context and the frequent-loss context, final outcome has little effect on decision makers. Most decision makers are guided by gain-loss frequency but not by final outcome.
Virtual colonoscopy in stenosing colorectal cancer
Authors: Coccetta Marco , Migliaccio Carla , La Mura Francesco , Farinella Eriberto , Galanou Ioanna , Delmonaco Pamela , Spizzirri Alessandro , Napolitano Vincenzo , Cattorini Lorenzo , Milani Diego , Cirocchi Roberto , Sciannameo Francesco
Published: November 2009

Background

Between 5 and 10% of the patients undergoing a colonoscopy cannot have a complete procedure mainly due to stenosing neoplastic lesion of rectum or distal colon. Nevertheless the elective surgical treatment concerning the stenosis is to be performed after the pre-operative assessment of the colonic segments upstream the cancer.

The aim of this study is to illustrate our experience with the Computed Tomographic Colonography (CTC) for the pre-operative assessment of the entire colon in the patients with stenosing colorectal cancers.

Methods

From January 2005 till March 2009, we observed and treated surgically 43 patients with stenosing colorectal neoplastic lesions. All patients did not tolerate the pre-operative colonoscopy. For this reason they underwent a pre-operative CTC in order to have a complete assessment of the entire colon. All patients underwent a follow-up colonoscopy 3 months after the surgical treatment. The CTC results were compared with both macroscopic examination of the specimen and the follow-up coloscopy.

Results

The pre-operative CTC showed four synchronous lesions in four patients (9.3% of the cases). The macroscopic examination of the specimen revealed three small sessile polyps (3 - 4 mm in diameter) missed in the pre-operative assessment near the stenosing colorectal cancer. The follow-up colonoscopy showed four additional sessile polyps with a diameter between 3 - 11 mm in three patients.

Our experience shows that CTC has a sensitivity of 83,7%.

Conclusion

In patients with stenosing colonic lesions, CTC allows to assess the entire colon pre-operatively avoiding the need of an intraoperative colonoscopy. More synchronous lesions are detected and treated at the time of the elective surgery for the stenosing cancer avoiding further surgery later on.
Virological pattern of hepatitis B infection in an HIV-positive man with fatal fulminant hepatitis B: a case report
Authors: Bagaglio Sabrina , Albarello Luca , Biswas Priscilla , Uberti-Foppa Caterina , Fortis Claudio , Morsica Giulia
Published: November 2009

Introduction

There seem to be no published data concerning the clinical impact of populations of hepatitis B virus (HBV) in the hepatic and extrahepatic compartments of HIV-infected people with severe acute hepatitis.

Case presentation

A 26-year-old Caucasian man presenting to our hospital with clinical symptoms suggesting acute hepatitis was found to have an acute hepatitis B profile upon admission. He developed fatal fulminant hepatitis and was found to be heavily immunocompromised due to HIV-1 infection. He had a high plasma HBV and HIV load, and analysis of the partial pre-S1/pre-S2 domain showed the presence of mixed infection with D and F genotypes. Analysis of the point mutations within this region revealed the presence of HBV strains with amino acid substitutions at the immunodominant epitopes involved in B or T cell recognition. A homogeneous population of a pre-core mutant strain harbouring the A1896G and A1899G affecting HBeAg expression was invariably found in the liver tissue, plasma and peripheral blood mononuclear cells despite active HBeAg secretion; it was the dominant strain in the liver only, and was characterised by the presence of two point mutations in the direct repeat 1 domain involved in HBV replication activity. Taken together, these mutations are indicative of a highly replicative virus capable of evading immune responses.

Conclusion

This case report provides clinical evidence of a possible association between the rapid spread of highly replicative escape mutants and the development of fulminant hepatitis in a heavily immunocompromised patient. Virological surveillance of severe acute hepatitis B may be important in establishing an early treatment strategy involving antiviral drugs capable of preventing liver failure, especially in individuals for whom liver transplantation is not accepted as a standard indication.
Y-Box–Binding Protein YB-1 Identifies High-Risk Patients With Primary Breast Cancer Benefiting From Rapidly Cycled Tandem High-Dose Adjuvant Chemotherapy
Authors: Gluz Oleg , Mengele Karin , Schmitt Manfred , Kates Ronald , Diallo-Danebrock Raihana , Neff Frauke , Royer Hans-Dieter , Eckstein Niels , Mohrmann Svjetlana , Ting Evelyn , Kiechle Marion , Poremba Christopher , Nitz Ulrike , Harbeck Nadia
Published: November 2009

Purpose

To investigate the potential of Y-box–binding protein YB-1, a multifunctional protein linked to tumor aggressiveness and multidrug resistance, to identify patients with breast cancer likely to benefit from dose-intensified chemotherapy regimens.

Patients and Methods

YB-1 was immunohistochemically determined in 211 primary tumors from the prospective, randomized West German Study Group WSG-AM-01 trial in high-risk (≥ 10 involved lymph-nodes) breast cancer (HRBC). Predictive impact of YB-1 was assessed by multivariate survival analysis, including time-varying factor-therapy interactions.

Results

At median follow-up of 61.7 months, patients receiving rapidly cycled tandem high-dose therapy (HD; two cycles [2×] epirubicin 90 mg/m2and cyclophosphamide 600 mg/m2every 14 days, followed by 2× epirubicin 90 mg/m2, cyclophosphamide 3,000 mg/m2, and thiotepa 400 mg/m2every 21 days) had better disease-free survival (DFS; hazard ratio [HR] = 0.62; 95% CI, 0.44 to 0.89) and overall survival (OS; HR = 0.59; 95% CI, 0.4 to 0.89) than those receiving conventional dose-dense chemotherapy (DD; 4× epirubicin 90 mg/m2and cyclophosphamide 600 mg/m2, followed by 3× cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2every 14 days). High YB-1 was associated with aggressive tumor phenotype (negative steroid hormone receptor status, positive human epidermal growth factor receptor 2 and p53 status, high MIB-1, unfavorable tumor grade) and poor OS (median 78 v 97 months; P = .01). In patients with high YB-1, HD yielded a 63-month median DFS (P = .001) and a 46-month median OS advantage (P = .002) versus DD. In multivariate models, patients with high B-1 receiving HD (v DD) had one third the hazard rate after 20 months for DFS and one sixth after 40 months for OS.

Conclusion

In a randomized prospective cancer therapy trial, for the first time, a strong predictive impact of YB-1 on survival has been demonstrated: enhanced benefit from HD (v DD) therapy occurs in HRBC with high YB-1. Future trials could therefore address optimal chemotherapeutic strategies,taking YB-1 into account.
Hodgkin's Lymphoma in Adolescents Treated With Adult Protocols: A Report From the German Hodgkin Study Group
Authors: Eichenauer Dennis A. , Bredenfeld Henning , Haverkamp Heinz , Müller Horst , Franklin Jeremy , Fuchs Michael , Borchmann Peter , Müller-Hermelink Hans-Konrad , Eich Hans T. , Müller Rolf-Peter , Diehl Volker , Engert Andreas
Published: November 2009

Purpose

The standard of care for adolescent patients with Hodgkin's lymphoma (HL) is undefined, particularly the choice between pediatric and adult protocols. Thus, we compared risk factors and outcome of adolescents and young adults treated within study protocols of the German Hodgkin Study Group (GHSG).

Patients and Methods

Three thousand seven hundred eighty-five patients treated within the GHSG studies HD4 to HD9 were analyzed; 557 patients were adolescents age 15 to 20 years, and 3,228 patients were young adults age 21 to 45 years.

Results

Large mediastinal mass and involvement of three or more lymph node areas were more frequent in adolescents (P < .001). The incidence of other risk factors did not differ significantly between age groups. With a median observation time of 81 months for freedom from treatment failure (FFTF) and 85 months for overall survival (OS), log-rank test showed no significant differences between age groups regarding FFTF (P = .305) and a superior OS (P = .008) for adolescents. Six-year estimates for FFTF and OS were 80% and 94%, respectively, for adolescents and 80% and 91%, respectively, for young adults. After adjustment for other predictive factors, Cox regression analysis revealed age as a significant predictor for OS (P = .004), with a higher mortality risk for young adults. Secondary malignancies were more common in young adults (P = .037).

Conclusion

Outcome of adolescent and young adult patients treated within GHSG study protocols is comparable. These data suggest that adult treatment protocols exhibit a safe and effective treatment option for adolescent patients with HL. However, longer follow-up, including assessment of late toxicity, is necessary for final conclusions.
Dose-Dense Adjuvant Doxorubicin and Cyclophosphamide Is Not Associated With Frequent Short-Term Changes in Left Ventricular Ejection Fraction
Authors: Morris Patrick G. , Dickler Maura , McArthur Heather L. , Traina Tiffany , Sugarman Steven , Lin Nancy , Moy Beverly , Come Steven , Godfrey Laura , Nulsen Benjamin , Chen Carol , Steingart Richard , Rugo Hope , Norton Larry , Winer Eric , Hudis Clifford A. , Dang Chau T.
Published: November 2009

Purpose

Doxorubicin and cyclophosphamide (AC) every 3 weeks has been associated with frequent asymptomatic declines in left ventricular ejection fraction (LVEF). Dose-dense (dd) AC followed by paclitaxel (P) is superior to the same regimen given every third week. Herein, we report the early cardiac safety of three sequential studies of ddAC alone or with bevacizumab (B).

Patients and Methods

Patients with HER2-positive breast cancer were treated on two trials: ddAC followed by P and trastuzumab (T) and ddAC followed by PT and lapatinib. Patients with HER2-normal breast cancer were treated with B and ddAC followed by B and nanoparticle albumin–bound P. Prospective LVEF measurement by multigated radionuclide angiography scan before and after every 2 week AC for 4 cycles and at month 6 from all three trials were aggregated to determine the early risks of cardiac dysfunction.

Results

From January 2005 to May 2008, 245 patients were enrolled. The median age was 47 years (range, 27 to 75 years). Median LVEF pre-ddAC was 68% (range, 52% to 82%). LVEF post-ddAC was available in 241 patients (98%) and the median was unchanged at 68% (range, 47% to 81%). Per protocol no patients were ineligible for subsequent targeted biologic therapy based on LVEF decline post-ddAC. In addition, LVEF was available in 222 patients (92%) at 6 months, at which time the median LVEF was similar at 65% (range, 24% to 80%). Within 6 months of initiating chemotherapy, three patients (1.2%; 95% CI, 0.25% to 3.54%) developed CHF, all of whom received T.

Conclusion

Dose-dense AC with or without concurrent bevacizumab is not associated with frequent acute or short-term declines in LVEF.