bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Pyranometric and Pyrheliometric Methods for the Determination of Sunshine Duration
Authors: Hinssen Yvonne B. L. , Knap Wouter H.
Published: May 2007

Two pyranometric methods for the determination of sunshine duration (SD) from global irradiance measurements are evaluated by means of summated sunshine seconds derived from pyrheliometric measurements in combination with the WMO threshold of 120 W m−2 for the direct solar irradiance. The evaluation is performed using direct and global radiation measurements made at the Cabauw Baseline Surface Radiation Network (BSRN) site in the Netherlands for the period March 2005–February 2006. The “Slob algorithm” uses 10-min mean and extreme values of the measured global irradiance and parameterized estimates of the direct and diffuse irradiance. The “correlation algorithm” directly relates SD to 10-min mean measurements of global irradiance. The cumulative pyrheliometric SD for the mentioned period is 1429 h. Relative to this value, the Slob algorithm and correlation algorithm give −72 h (−5%) and +8 h (+0.6%). On a daily mean basis, the values are −0.22 ± 0.05 h day−1 and 0.03 ± 0.03 h day−1, respectively. By means of tuning the irradiance parameterizations of the Slob algorithm, the yearly cumulative and daily mean differences can be reduced to +7 h (+0.5%) and 0.02 ± 0.04 h day−1, respectively. It is concluded that, by use of either algorithm, it is possible to estimate daily sums of SD from 10-min mean measurements of global irradiance with a typical uncertainty of 0.5–0.7 h day−1. For yearly sums, the uncertainty typically amounts to 0.5%.
Fanon
Authors: Chan Stephen
Published: May 2007

Frantz Fanon has always been read as an apostle of violence — much of this owed to Sartre's Preface to Fanon's work, The Wretched of the Earth. There are, however, more nuanced possible readings of Fanon, readings that allow the possibility of new understandings of contemporary violence emanating from the Middle East. In this article, Fanon's intellectual trajectory is traced back to his first writings postulating an equality in which no slaves existed by virtue of there being no longer any masters. The psychological dimensions of Fanon's work are discussed and a hypothesis put forward about a moment of pure psychological lucidity and calm before the suicide bomber of today explodes his or her device. The work of Lacan and Kristeva is discussed in relation to a nuanced reading of Fanon, and an excursion into the Palestine of Hamas helps complete a complex meditation on Fanon's life and work.
Constructing a Swedish Conflict Prevention Policy Based on a Powerful Idea and Successful Practice
Authors: Björkdahl Annika
Published: May 2007

The story of how conflict prevention became an integral and legitimate part of Swedish foreign policy illustrates the relationship between successful practices and powerful ideas. This article suggests that the demonstration of an idea in practice empowers the idea and contributes not only to its selection, but also to its framing and institutionalization within foreign policy. Hence, the article sets out to explore the relationships between practice, ideas and foreign policy. Adopting a social constructivist perspective, the article provides a detailed process-tracing of the construction of a Swedish conflict prevention policy and concludes that conflict prevention was a powerful idea because it was morally appealing and persuasive as well as successfully demonstrated in practice. In fact, preventive practices spearheaded the advancement of the conflict prevention idea. In addition, the idea resonated with the Swedish foreign policy elite, with commonly held values and with the traditional Swedish foreign policy that stressed internationalism and solidarity.
Development of Design Analysis Methods for Carbon Silicon Carbide Composite Structures
Authors: Sullivan Roy M. , Murthy Pappu L.N. , Mital Subodh K. , Palko Joseph L. , Cuneo Jacques C. , Koenig John R.
Published: May 2007

The stress—strain behavior at room temperature and at 1100° C (2000°F) is measured for two carbon fiber-reinforced silicon carbide (C/SiC) composite materials: a two dimensional (2D) plain-weave quasi-isotropic laminate and a 3D angle interlock woven composite. Previously developed micromechanics-based material models are calibrated by correlating the predicted material property values with the measured values. Four-point beam-bending subelement specimens are fabricated with these two fiber architectures and four-point bending tests are performed at room temperature and at 1100°C. Displacements and strains are measured at the mid-span of the beam and recorded as a function of load magnitude. The calibrated material models are used in concert with a nonlinear finite-element solution using ABAQUS to simulate the structural response of the two materials in the four-point beam bending tests. The structural response predicted by the nonlinear analysis method compared favorably with the measured response for both materials and both test temperatures. Results show that the material models scale-up fairly well from coupons to subcomponent level.
Characterizing Nonlinear Rate-dependent Behaviors of Graphite/Epoxy Composites using a Micromechanical Approach
Authors: Tsai Jia-Lin , Chen Kuei-Han
Published: May 2007

This research aims to characterize the nonlinear rate-dependent behaviors of graphite/epoxy composites using micromechanical analysis. In this analysis, graphite fibers are considered as elastic solids, while the surrounding epoxy matrix exhibiting rate sensitivities are described using the three-parameter viscoplasticity model. By using Aboudi's generalized method of cells (GMC), the incremental form of the constitutive relations of the composites are expressed in terms of the constituent properties as well as the geometry parameters of the representative volume element. After a numerical iteration, the corresponding stress and strain relations of composites at different strain rates are generated. In order to verify the model predictions, off-axis graphite/epoxy composite specimens are tested at strain rates from 10 —4 to 550/s. For strain rates less than 1/s, the experiments are conducted using a hydraulic MTS machine, while high-strain-rate tests were carried out using a split Hopkinson pressure bar. Experimental results indicate that the stress and strain curves are quite sensitive to the strain rate; moreover, when the strain rates increase, the material stiffens. A comparison of model predictions with experimental results indicates that the rate-dependent behaviors of composites can be characterized effectively with the GMC model in conjunction with the viscoplastic properties of epoxy.
Steady States in the Evolution of New Englishes
Authors: Mukherjee Joybrato
Published: May 2007

The evolutionary model of New Englishes offered by Schneider posits a uniform pattern of five diachronic phases that are assumed to underlie the processes inherent in the emergence of all New Englishes worldwide. The present article applies this evolutionary model to Indian English and argues on the basis of linguistic and sociolinguistic evidence that present-day Indian English is best viewed as a phase 4 variety, marked by endonormative stabilization, in which, however, some features of phase 3 (i.e., nativization) coexist. It is suggested that the situation in which Indian English finds itself today could be seen as a stable, productive steady state in the evolutionary process in which there is an equilibrium between conflicting forces of progression and conservativism. This steady state in the diachronic development is linked to the synchronic view of present-day Indian English as a semiautonomous variety, which is characterized by three major determinants: common core, interference, and autonomy.
Student Speech and the Internet: A Legal Analysis
Authors: Graca Thomas J. , Stader David L.
Published: May 2007

This article lays the foundation of American First Amendment jurisprudence in public schools and examines recent cases relating to student Internet speech. Particular emphasis is placed on the ability of schools to regulate student off-campus Internet speech. School authorities who wish to regulate nonthreatening off-campus speech in the electronic media likely must demonstrate a nexus between the off-campus speech and substantial disruption at school.
Implementation of Learning Community Principles: A Study of Six High Schools
Authors: Wells Caryn , Feun Lindson
Published: May 2007

The transformation of a high school to a learning community is a slow and challenging process. This study tracked the efforts of teacher and administrative leaders from six high schools who worked to develop professional learning communities. Qualitative and quantitative analyses of interviews with school leaders revealed that the early days of transition to a learning community tend to focus on sharing materials and resources, whereas critical issues such as learning results or best practice are seldom discussed.
Surveillance and Regulation
Authors: Jones Jill B. , Chandler Susan
Published: May 2007

This article explores how one global work site—the casino—uses and abuses women workers' bodies. Women's “body stories” illuminate the endless ways in which corporate giants—in this case, the managers and owners of multinational casinos—control, regulate, and discipline women workers' bodies through the relentless application of biopower. These stories also demonstrate that in spite of oppressive working conditions, the women engage in creative and subversive expressions of resistance. In this, their struggle for workplace justice parallels that of women workers worldwide.
Ending Sex Trafficking of Children in Atlanta
Authors: Boxill Nancy A. , Richardson Deborah J.
Published: May 2007

In less than 16 months, a coalition of women in Atlanta, Georgia, identified the prostitution of young girls as a major and horrendous crisis in the community, developed and implemented a strategy to combat the problem, purchased property for a treatment facility, and began to serve victims of child prostitution. This article reports the story of the coalition's success. It is intended to move those who would protect children from shock to deliberate action. The authors guide the reader through identifying the problem, setting realistic goals, and organizing the community for real and sustainable public policy and social change. They are telling a story, believing that personal stories are the root of social change and that the connections that these stories hold offer possibilities for replication in communities throughout America.
The International Sexual Trafficking of Women and Children
Authors: Hodge David R. , Lietz Cynthia A.
Published: May 2007

The contemporary international slave trade has received little attention in the social work literature. In keeping with the profession's commitment to social justice and human rights, this article reviews perhaps the most prominent and fastest-growing component of the trade—the trafficking of young women and children for prostitution and other forms of sexual exploitation. The role of criminal networks in the globalization of sexual trafficking is discussed, along with the recruitment strategies used by the networks. Suggestions are offered for advocating on behalf of women and children, and information is provided to assist social workers in the provision of services to victims of trafficking.
The Impact of Feminism on Social Work Students in Hong Kong
Authors: Lai Ching Leung
Published: May 2007

This study found that social work students in Hong Kong are insensitive to gender issues in both their practice and life experiences. It has been suggested that feminism should be integrated into social work curricula to enable students to question the way in which their life experiences lead them to construct gender, which is a crucial step in the development of nonsexist social work practice. However, in Hong Kong, there are two barriers to the development of nonsexist practice. First, social work education is insensitive to gender inequalities and tends simply to add women's issues to the traditional curriculum, and second, students tend to opt for more practical options when they choose electives for professional training and are thus less likely to take elective courses on gender.
Bein' Womanish: Womanist Efforts in Child Saving During the Progressive Era
Authors: Perry Tonya Evette , Davis-Maye Denise
Published: May 2007

This article highlights the establishment by the Alabama Federation of Colored Women's Clubs in 1907 of Alabama's first and only reform school for African American youths, the Mt. Meigs Reformatory for Juvenile Negro Lawbreakers. Recognizing that the issues of African American women and the larger African American community were inextricably linked, courageous 19th-century African American women worked within a womanist ideological framework and harnessed their resources to develop purposeful agendas and creative responses to pressing problems in the African American community. Sorely neglected, this legacy begs for the attention of scholars who recognize the value of unearthing historical fragments to create enriched wholes.
Keeping the Unit Safe: The Anatomy of Escalation
Authors: Johnson Mary E. , Delaney Kathleen R.
Published: May 2007

BACKGROUND: Escalation has been depicted as a linear trajectory of behavioral eruption beginning with agitation and proceeding until the patient is out of control. This notion has influenced current descriptions of de-escalation strategies. OBJECTIVES: The study objective was to understand the context and conditions that influence how nursing staffs manage patients who are escalating out of control. DESIGN: Methods consistent with grounded theory were used to collect and analyze the data. Patient—staff interactions were observed for more than 400 hours on inpatient units. Sixteen staff members and 12 patients were interviewed. FINDINGS: Data analysis revealed a nonlinear process of escalation and de-escalation. Two conditions that influenced strategies used by staff members were the type and the trajectory of escalation. This report focuses on patterns of patient escalation. CONCLUSION: The data revealed a complex escalation and de-escalation process that necessitates ongoing assessments of patient status and the milieu and individualizing staff responses. J Am Psychiatr Nurses Assoc, 2007; 13(1), 42-52.
Tomorrow's Psychiatric Nurses: Where Are We Today in Providing Students' Clinical Experiences?
Authors: Patzel Brenda , Ellinger Patricia , Hamera Edna
Published: May 2007

BACKGROUND: The increased enrollment of students, scarcity of faculty, and reduction in psychiatric beds challenge traditional ways of providing clinical psychiatric nursing experience to undergraduates. OBJECTIVE: The purpose of the study was to describe the current clinical psychiatric nursing experiences of undergraduates throughout the country. STUDY DESIGN: An online survey was dispersed to undergraduate nurse educators to describe clinical experiences in psychiatric mental health nursing. The survey included demographic questions, questions about students' clinical experiences, and open-ended questions regarding choices of and obstacles to a successful clinical experience. RESULTS: The 160 respondents reported concerns such as availability and quality of clinical sites, poor nursing role models, number of clinical hours, and lack of valuing their expertise. The results raise questions about the minimum number of hours needed to achieve competencies in psychiatric nursing, what simulations or laboratory experiences are essential, and what types of clinical settings provide needed experience. J Am Psychiatr Nurses Assoc, 2007; 13(1), 53-60.
Satisfaction and Outcomes of Depressed Older Adults With Psychiatric Clinical Nurse Specialists in Primary Care
Authors: Saur Carol D. , Steffens David C. , Harpole Linda H. , Fan Ming-Yu , Oddone Eugene Z. , Unützer Jürgen
Published: May 2007

BACKGROUND: Recent models integrating depression care management into primary care have demonstrated improved clinical outcomes and patient satisfaction. To date, none have examined psychiatric—mental health clinical nurse specialists (PCNSs) as providers in primary care. OBJECTIVES: To describe patient perception of and satisfaction with care provided by PCNSs, to compare patients with high versus lower levels of satisfaction and clinical outcomes, and to explore patient preference for future depression treatment and willingness to copay for PCNS services. STUDY DESIGN: A postintervention survey after a 12-month late-life depression care program delivered by a PCNS in primary care. Participants were 105 adults age 60 or older with major depression and/or dysthymia. RESULTS: A majority of patients perceived PCNS care as excellent, were highly satisfied with the relationship with the PCNS, would seek future treatment with the PCNS, preferred the primary care physician's office for mental health care, and reported improved clinical and functional outcomes. CONCLUSIONS: PCNS services are well received by patients in the primary care setting. PCNSs are uniquely qualified to help patients achieve significant clinical improvement in collaboration with their primary care providers. J Am Psychiatr Nurses Assoc, 2007;13(1), 62-70.
Predicting Homicide Clearances in Chicago
Authors: Alderden Megan A. , Lavery Timothy A.
Published: May 2007

Few studies examine homicide clearances despite trends across many jurisdictions that show a decrease in homicides cleared each year. This study addresses that research gap using Chicago homicide data from 1991 to 2002 to identify predictive factors in homicide clearances. Across five logistic regression models we found that victim and incident characteristics were significant predictors of homicide clearances, although the number and types of significant predictors were varied across the analyses. Moreover, we found differences in the factors that significantly predicted clearances for three specific homicide circumstances: expressive, instrumental, and gang-related.
The TASER as a Less Lethal Force Alternative
Authors: White Michael D. , Ready Justin
Published: May 2007

Despite its adoption by more than 8,000 law enforcement agencies in the United States and abroad, there is little empirical research examining use of the TASER by police officers. This article investigates the use and effectiveness of the weapon by examining all TASER deployments by police officers in a large metropolitan department during a 3-year period (2002 to 2004; n = 243). Findings indicate that the TASER was used almost exclusively against violent suspects classified as “emotionally disturbed” by emergency service officers with supervisors present. Despite use on a population perceived as being higher risk for injury, findings indicate that the TASER was effective, as 85% of suspects were incapacitated and taken into custody without further incident. The article concludes with a discussion of implications for continued use of the TASER and the need for additional research before any definitive conclusions about use and effectiveness of the weapon can be drawn.
The Src family kinase Hck regulates mast cell activation by suppressing an inhibitory Src family kinase Lyn
Authors: Hong Hong , Kitaura Jiro , Xiao Wenbin , Horejsi Vaclav , Ra Chisei , Lowell Clifford A. , Kawakami Yuko , Kawakami Toshiaki
Published: May 2007

IgE/antigen-dependent mast cell activation plays a central role in immediate hypersensitivity and other allergic reactions. The Src family tyrosine kinase (SFK) Lyn is activated by the cross-linking of high-affinity IgE receptors (FcϵRI). Activated Lyn phosphorylates the FcϵRI subunits, β and γ, leading to subsequent activation of various signaling pathways. Lyn also plays a negative regulatory function by activating negative regulatory molecules. Another SFK, Fyn, also contributes to mast cell degranulation by inducing Gab2-dependent microtubule formation. Here we show that a third SFK, Hck, plays a critical role in mast cell activation. Degranulation and cytokine production are reduced in FcϵRI-stimulated hck−/− mast cells. The reduced degranulation can be accounted for by defects in Gab2 phosphorylation and microtubule formation. Importantly, Lyn activity is elevated in hck−/− cells, leading to increased phosphorylation of several negative regulators. However, positive regulatory events, such as activation of Syk, Btk, JNK, p38, Akt, and NF-κB, are substantially reduced in hck−/− mast cells. Analysis of lyn−/−hck−/−, lyn−/−FcϵRIβ−/−, and hck−/−FcϵRIβ−/− cells shows that Hck exerts these functions via both Lyn-dependent and Lyn-independent mechanisms. Thus, this study has revealed a hierarchical regulation among SFK members to fine-tune mast cell activation.
Hand is a direct target of the forkhead transcription factor Biniou during Drosophilavisceral mesoderm differentiation
Authors: Popichenko Dmitry , Sellin Julia , Bartkuhn Marek , Paululat Achim
Published: May 2007

Background

The visceral trunk mesoderm inDrosophila melanogasterdevelops under inductive signals from the ectoderm. This leads to the activation of the key regulators Tinman, Bagpipe and Biniou that are crucial for specification of the circular visceral muscles. How further differentiation is regulated is widely unknown, therefore it seems to be essential to identify downstream target genes of the early key regulators. In our report we focus on the analysis of the transcriptional control of the highly conserved transcription factor Hand in circular visceral muscle cells, providing evidence that thehandgene is a direct target of Biniou.

Results

Herein we describe the identification of a regulatory region in thehandgene essential and sufficient for the expression in the visceral mesoderm during embryogenesis. We found thathandexpression in the circular visceral mesoderm is abolished in embryos mutant for the FoxF domain containing transcription factor Biniou. Furthermore we demonstrate that Biniou regulateshandexpression by direct binding to a 300 bp sequence element, located within the 3rdintron of thehandgene. This regulatory element is highly conserved in differentDrosophilaspecies. In addition, we provide evidence that Hand is dispensable for the initial differentiation of the embryonic visceral mesoderm.

Conclusion

In the present report we show that cross species sequence comparison of non-coding sequences between orthologous genes is a powerful tool to identify conserved regulatory elements. Combining functional dissection experimentsin vivoand protein/DNA binding studies we identifiedhandas a direct target of Biniou in the circular visceral muscles.
The role of survivin in angiogenesis during zebrafish embryonic development
Authors: Ma Alvin CH , Lin Rachel , Chan Po-Kwok , Leung Joseph CK , Chan Loretta YY , Meng Anming , Verfaillie Catherine M , Liang Raymond , Leung Anskar YH
Published: May 2007

Background

Survivin is the smallest member of the inhibitor of apoptosis (IAP) gene family. Recently, the zebrafish survivin-1 gene has been cloned, showing remarkable sequence identity and similarity over the BIR domain compared with human and mouse survivin gene. Here we investigated the role of survivin in angiogenesis during zebrafish development. Morpholinos (MOs) targeting the 5' untranslated region (UTR) (SurUTR) and sequences flanking the initiation codon (SurATG) of zebrafish survivin-1 gene were injected into embryos at 1–4 cell stage. Vasculature was examined by microangiography and GFP expression in Tg(fli1:EGFP)

y1 embryos. Results: In embryos co-injected with SurUTR and SurATG-MOs, vasculogenesis was intact but angiogenesis was markedly perturbed, especially in the inter-segmental vessels (ISV) and dorsal longitudinal anastomotic vessels (DLAV) of the trunk, the inner optic circle and optic veins of developing eyes and the sub-intestinal vessels. Apoptosis was increased, as shown by TUNEL staining and increase in caspase-3 activity. Efficacy of SurUTR and SurATG-MOs was demonstrated by translation inhibition of co-injected 5'UTR survivin:GFP plasmids. The phenotypes could be recapitulated by splice-site MO targeting the exon2-intron junction of survivin gene and rescued by survivin mRNA. Injection of human vascular endothelial growth factor (VEGF) protein induced ectopic angiogenesis and increased survivin expression, whereas treatment with a VEGF receptor inhibitor markedly reduced angiogenesis and suppressed survivin expression. Conclusion: Survivin is involved in angiogenesis during zebrafish development and may be under VEGF regulation.
Three novel mutations in KIF21A highlight the importance of the third coiled-coil stalk domain in the etiology of CFEOM1
Authors: Chan Wai-Man , Andrews Caroline , Dragan Laryssa , Fredrick Douglas , Armstrong Linlea , Lyons Christopher , Geraghty Michael T , Hunter David G , Yazdani Ahmad , Traboulsi Elias I , Pott Jan WR , Gutowski Nicholas J , Ellard Sian , Young Elizabeth , Hanisch Frank , Koc Feray , Schnall Bruce , Engle Elizabeth C
Published: May 2007

Background

Congenital fibrosis of the extraocular muscles types 1 and 3 (CFEOM1/CFEOM3) are autosomal dominant strabismus disorders that appear to result from maldevelopment of ocular nuclei and nerves. We previously reported that most individuals with CFEOM1 and rare individuals with CFEOM3 harbor heterozygous mutations in KIF21A. KIF21A encodes a kinesin motor involved in anterograde axonal transport, and the familial and de novo mutations reported to date predictably alter one of only a few KIF21A amino acids – three within the third coiled-coil region of the stalk and one in the distal motor domain, suggesting they result in altered KIF21A function. To further define the spectrum of KIF21A mutations in CFEOM we have now identified all CFEOM probands newly enrolled in our study and determined if they harbor mutations in KIF21A.

Results

Sixteen CFEOM1 and 29 CFEOM3 probands were studied. Three previously unreported de novo KIF21A mutations were identified in three CFEOM1 probands, all located in the same coiled-coil region of the stalk that contains all but one of the previously reported mutations. Eight additional CFEOM1 probands harbored three of the mutations previously reported in KIF21A; seven had one of the two most common mutations, while one harbored the mutation in the distal motor domain. No mutation was detected in 5 CFEOM1 or any CFEOM3 probands.

Conclusion

Analysis of sixteen CFEOM1 probands revealed three novel KIF21A mutations and confirmed three reported mutations, bringing the total number of reported KIF21A mutations in CFEOM1 to 11 mutations among 70 mutation positive probands. All three new mutations alter amino acids in heptad repeats within the third coiled-coil region of the KIF21A stalk, further highlighting the importance of alterations in this domain in the etiology of CFEOM1.
Indole is an inter-species biofilm signal mediated by SdiA
Authors: Lee Jintae , Jayaraman Arul , Wood Thomas K
Published: May 2007

Background

As a stationary phase signal, indole is secreted in large quantities into rich medium by Escherichia coli and has been shown to control several genes (e.g., astD, tnaB, gabT), multi-drug exporters, and the pathogenicity island of E. coli; however, its impact on biofilm formation has not been well-studied.

Results

Through a series of global transcriptome analyses, confocal microscopy, isogenic mutants, and dual-species biofilms, we show here that indole is a non-toxic signal that controls E. coli biofilms by repressing motility, inducing the sensor of the quorum sensing signal autoinducer-1 (SdiA), and influencing acid resistance (e.g., hdeABD, gadABCEX). Isogenic mutants showed these associated proteins are directly related to biofilm formation (e.g., the sdiA mutation increased biofilm formation 50-fold), and SdiA-mediated transcription was shown to be influenced by indole. The reduction in motility due to indole addition results in the biofilm architecture changing from scattered towers to flat colonies. Additionally, there are 12-fold more E. coli cells in dual-species biofilms grown in the presence of Pseudomonas cells engineered to express toluene o- monooxygenase (TOM, which converts indole to an insoluble indigoid) than in biofilms with pseudomonads that do not express TOM due to a 22-fold reduction in extracellular indole. Also, indole stimulates biofilm formation in pseudomonads. Further evidence that the indole effects are mediated by SdiA and homoserine lactone quorum sensing is that the addition of N-butyryl-, N-hexanoyl-, and N-octanoyl-L-homoserine lactones repress E. coli biofilm formation in the wild-type strain but not with the sdiA mutant.

Conclusion

Indole is an interspecies signal that decreases E. coli biofilms through SdiA and increases those of pseudomonads. Indole may be manipulated to control biofilm formation by oxygenases of bacteria that do not synthesize it in a dual-species biofilm. Furthermore, E. coli changes its biofilm in response to signals it cannot synthesize (homoserine lactones), and pseudomonads respond to signals they do not synthesize (indole).
Characterizing structural features of cuticle-degrading proteases from fungi by molecular modeling
Authors: Liu Shu-Qun , Meng Zhao-Hui , Yang Jin-Kui , Fu Yun-Xin , Zhang Ke-Qin
Published: May 2007

Background

Serine proteases secreted by nematode and insect pathogenic fungi are bio-control agents which have commercial potential for developing into effective bio-pesticides. A thorough understanding of the structural and functional features of these proteases would significantly assist with targeting the design of efficient bio-control agents.

Results

Structural models of serine proteases PR1 from entomophagous fungus, Ver112 and VCP1 from nematophagous fungi, have been modeled using the homology modeling technique based on the crystal coordinate of the proteinase K. In combination with multiple sequence alignment, these models suggest one similar calcium-binding site and two common disulfide bridges in the three cuticle-degrading enzymes. In addition, the predicted models of the three cuticle-degrading enzymes present an essentially identical backbone topology and similar geometric properties with the exception of a limited number of sites exhibiting relatively large local conformational differences only in some surface loops and the N-, C termini. However, they differ from each other in the electrostatic surface potential, in hydrophobicity and size of the S4 substrate-binding pocket, and in the number and distribution of hydrogen bonds and salt bridges within regions that are part of or in close proximity to the S2-loop.

Conclusion

These differences likely lead to variations in substrate specificity and catalytic efficiency among the three enzymes. Amino acid polymorphisms in cuticle-degrading enzymes were discussed with respect to functional effects and host preference. It is hoped that these structural models would provide a further basis for exploitation of these serine proteases from pathogenic fungi as effective bio-control agents.
Rivoflavin may interfere with on-line monitoring of secreted green fluorescence protein fusion proteins in Pichia pastoris
Authors: Surribas Anna , Resina David , Ferrer Pau , Valero Francisco
Published: May 2007

Background

Together with the development of optical sensors, fluorometry is becoming an increasingly attractive tool for the monitoring of cultivation processes. In this context, the green fluorescence protein (GFP) has been proposed as a molecular reporter when fused to target proteins to study their subcellular localization or secretion behaviour. The present work evaluates the use of the GFP fusion partner for monitoring extracellular production of a Rhizopus oryzae lipase (ROL) in Pichia pastoris by means of 2D-fluorimetric techniques

Results

In this study, the GFP-ROL fusion protein was successfully produced as a secreted fusion form in P. pastoris batch cultivations. Furthermore, both the fusion enzyme and the fluorescent protein (GFP S65T mutant) retained their biological activity. However, when multiwavelength spectrofluorometry was used for extracellular fusion protein monitoring, riboflavin appeared as a major interfering component with GFP signal. Only when riboflavin was removed by ultrafiltration from cultivation supernatants, GFP fluorescence signal linearly correlated to lipase activity

Conclusion

P. pastoris appears to secrete/excrete significant amounts of riboflavin to the culture medium. When attempting to monitor extracellular protein production in P. pastoris using GFP fusions combined with multiwavelength spectrofluorimetric techniques, riboflavin may interfere with GFP fluorescence signal, thus limiting the application of some GFP variants for on-line extracellular recombinant protein quantification and monitoring purposes.
Receptor for advanced glycation end products (RAGE) in a dash to the rescue: inflammatory signals gone awry in the primal response to stress
Authors: Herold Kevan , Moser Bernhard , Chen Yali , Zeng Shan , Yan Shi Fang , Ramasamy Ravichandran , Emond Jean , Clynes Raphael , Schmidt Ann Marie
Published: May 2007

The multiligand receptor for advanced glycation end products (RAGE) of the Ig superfamily transduces the biological impact of discrete families of ligands, including advanced glycation end products, certain members of the S100/calgranulin family, high mobility group box-1, Mac-1 (αMβ2, CD11b/CD18), and amyloid-β peptide and β-sheet fibrils. Although structurally dissimilar, at least at the monomeric level, recent evidence suggests that oligomeric forms of these RAGE ligands may be especially apt to activate the receptor and up-regulate a program of inflammatory and tissue injury-provoking genes. The challenge in probing the biology of RAGE and its impact in acute responses to stress and the potential development of chronic disease is to draw the line between mechanisms that evoke repair versus those that sustain inflammation and tissue damage. In this review, we suggest the concept that the ligands of RAGE comprise a primal program in the acute response to stress. When up-regulated in environments laden with oxidative stress, inflammation, innate aging, or high glucose, as examples, the function of these ligand families may be transformed from ones linked to rapid repair to those that drive chronic disease. Identification of the threshold beyond which ligands of RAGE mediate repair versus injury is a central component in delineating optimal strategies to target RAGE in the clinic.
Provider Counseling About Health Behaviors Among Cancer Survivors in the United States
Authors: Sabatino Susan A. , Coates Ralph J. , Uhler Robert J. , Pollack Lori A. , Alley Linda G. , Zauderer Laura J.
Published: May 2007

Purpose

To examine provider discussion or counseling of US cancer survivors about diet, exercise, and tobacco use.

Methods

We used 2000 National Health Interview Survey data to examine whether US cancer survivors reported that, within 1 year, a provider (1) discussed diet, (2) recommended they begin or continue exercise, or (3) asked about smoking. We included survivors more than 1 year beyond diagnosis (n = 1,600) and adults without cancer (AWCs; n = 24,636) who saw/talked to a provider within 1 year. We used generalized linear contrasts in bivariable analyses and logistic regression to calculate predicted marginals adjusted for age, sex, comorbidity, usual source of care, and number of provider visits in the prior year.

Results

Few survivors reported discussions or recommendations for all three health behaviors (10% of survivors v 9% of AWCs; P = .57). Although report was more likely than among AWCs, few survivors reported diet discussions (30% of survivors v 23% of AWCs; P < .0001) or exercise recommendations (26% of survivors v 23% of AWCs; P < .005), and a minority were asked about smoking (42% of survivors v 41% of AWCs; P = .41). After adjustment, survivors were less likely to report exercise recommendations than were AWCs (22% v 24%, respectively; P = .02). Colorectal cancer survivors were less likely than were AWCs of similar age range to report exercise recommendations (16% v 27%, respectively; P < .003) or smoking discussions (31% v 41%, respectively; P < .05). Cervical cancer survivors were more likely than AWCs of similar age range to discuss smoking (58% v 43%, respectively; P < .001).

Conclusion

Findings from this nationally representative sample suggest that many providers may miss opportunities to counsel survivors about healthy behaviors, perhaps particularly colorectal cancer survivors.
Screening for a BRCA2 Rearrangement in High-Risk Breast/Ovarian Cancer Families: Evidence for a Founder Effect and Analysis of the Associated Phenotypes
Authors: Machado Patrícia M. , Brandão Rita D. , Cavaco Branca M. , Eugénio Joana , Bento Sandra , Nave Mónica , Rodrigues Paula , Fernandes Aires , Vaz Fátima
Published: May 2007

Purpose

BRCA2 rearrangements are rare genetic events. A large BRCA2 genomic insertion was recurrently observed in our participants, and we sought to characterize it at the molecular and phenotypic level.

Patients and Methods

We studied 210 high-risk breast/ovarian cancer families. Fifty-three probands were fully screened for BRCA1/2 mutations, and three of 53 had a large insertion in exon 3 of BRCA2. This finding was analyzed by polymerase chain reaction (PCR), reverse transcriptase PCR (RT-PCR), and sequencing. An additional 157 consecutive families were screened for this mutation by a three-step PCR method. Phenotype and haplotype analysis was also performed.

Results

Sixteen BRCA mutations were observed in 19 of 53 patients (36% detection rate). A recurrent Alu motif insertion in position c.156_157 was observed after sequencing of an abnormal fragment obtained after the amplification of BRCA2 exon 3. RT-PCR revealed exon 3 skipping. Screening of this rearrangement identified 14 additional families (out of 157). In total, 17 (8%) of 210 high-risk families ascertained in our clinic were positive for this mutation. Segregation of a common haplotype (from D13S260 to D13S1695) confirmed a common origin, estimated to have occurred 2,400 to 2,600 years ago. The following four cancer phenotypes were observed in the 17 positive families: female breast (n = 9), male breast (n = 4), breast/ovarian (n = 2), and heterogeneous (n = 2). Male breast cancer was more frequently observed in c.156_157insAlu–positive families compared with negative families (23% v 12%, respectively), and 33% of all male breast cancer families with an identified BRCA mutation were c.156_157insAlu positive.

Conclusion

c.156_157insAlu is a founder mutation of Portuguese origin and is the most frequent BRCA2 rearrangement described to date.
Impact of a Peer-Delivered Telephone Intervention for Women Experiencing a Breast Cancer Recurrence
Authors: Gotay Carolyn Cook , Moinpour Carol M. , Unger Joseph M. , Jiang Caroline S. , Coleman Dorothy , Martino Silvana , Parker Beverly J. , Bearden James D. , Dakhil Shaker , Gross Howard M. , Lippman Scott , Albain Kathy S.
Published: May 2007

Purpose

A first breast cancer recurrence creates considerable distress, yet few psychosocial interventions directed at this population have been reported. The Southwest Oncology Group conducted a phase III randomized trial to evaluate the effectiveness of a brief telephone intervention.

Patients and Methods

Three hundred five women experiencing a first recurrence of breast cancer were randomly assigned to standard care or intervention. The intervention consisted of four to eight telephone calls delivered over a 1-month period. The calls were conducted by trained peer counselors at a breast cancer advocacy organization, the Y-ME National Breast Cancer Organization, and followed a standard curriculum. Psychosocial distress (Cancer Rehabilitation Evaluation System–Short Form [CARES-SF]) and depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D]) outcomes were assessed at baseline and 3 and 6 months. The 3-month assessment was the primary end point and is the focus of this article.

Results

Analysis revealed no differences in distress or depressive symptoms at 3 months between the intervention and control groups; at 3 months, 70% of control patients and 66% of intervention patients reported psychosocial distress, and 40% of control patients and 47% of intervention patients exhibited depressive symptoms.

Conclusion

Telephone peer counseling did not lead to better psychosocial outcomes. The persistent distress in these women supports the urgent need for the development and testing of more intensive or different supportive interventions for this group of patients.
Multiple Drug Resistance in Osteogenic Sarcoma: INT0133 From the Children's Oncology Group
Authors: Schwartz Cindy L. , Gorlick Richard , Teot Lisa , Krailo Mark , Chen Zhengjia , Goorin Allen , Grier Holcombe E. , Bernstein Mark L. , Meyers Paul
Published: May 2007

Purpose

Multiple drug resistance due to P-glycoprotein (P-gp) expression has been reported to be a cause of disease recurrence in osteosarcoma. Tumor specimens derived from children and young adults with osteosarcoma enrolled onto a national Intergroup trial (INT0133) were analyzed prospectively to determine the role of multiple drug resistance in osteosarcoma.

Patients and Methods

From October 15, 1992, to November 25, 1997, 685 patients with localized, high-grade osteosarcoma were enrolled onto INT0133. Paraffin-embedded diagnostic tumor specimens were assayed for P-gp using monoclonal antibodies C-494 (139 patients) and JSB-1 (133 patients). Percent necrosis at the time of definitive surgery (NEC), event-free survival (EFS), and overall survival (OS) were evaluated as outcome measures for patients with P-gp–positive disease and were compared with patients with P-gp–negative disease.

Results

P-gp expression in the biopsy specimen did not significantly increase the risk for adverse outcomes as measured by EFS, OS, or NEC. EFS for those patients with C-494–positive tumors was 59% at 4 years versus 61% at 4 years for patients with C-494–negative tumors (P = .79), or 58% at 4 years versus 61% at 4 years for patients with JSB-1–positive versus JSB-1–negative tumors (P = .65). OS for patients with C-494–positive tumors was 82% at 4 years versus 82% at 4 years for patients with C-494–negative tumors (P = .61).

Conclusion

Prospective analysis of the role of multiple drug resistance in localized osteosarcoma did not find that immunohistochemical analysis of P-gp expression predicted outcome for patients treated on INT0133.
Phase III Study of Oral Compared With Intravenous Topotecan As Second-Line Therapy in Small-Cell Lung Cancer
Authors: Eckardt John R. , von Pawel Joachim , Pujol Jean-Louis , Papai Zsolt , Quoix Elisabeth , Ardizzoni Andrea , Poulin Ruth , Preston Alaknanda J. , Dane Graham , Ross Graham
Published: May 2007

Purpose

Single-agent intravenous (IV) topotecan is an effective treatment for small-cell lung cancer (SCLC) after failure of first-line chemotherapy. This open-label, randomized, phase III study compared oral and IV topotecan in patients with SCLC sensitive to initial chemotherapy.

Patients and Methods

Patients with limited- or extensive-disease SCLC, documented complete or partial response to first-line therapy, Eastern Cooperative Oncology Group performance status ≤ 2, and measurable recurrent disease (WHO criteria) with a treatment-free interval of ≥ 90 days were assigned to treatment with either oral topotecan 2.3 mg/m2/d on days 1 through 5 or IV topotecan 1.5 mg/m2/d on days 1 through 5 every 21 days. Primary end point was response rate as confirmed by an external reviewer blinded to treatment.

Results

A total of 309 patients were randomly assigned. In intent-to-treat analysis, response rates were 18.3% with oral topotecan (n = 153) and 21.9% with IV topotecan (n = 151), with a difference (oral –IV) of −3.6% (95% CI, −12.6% to 5.5%). Median survival time was 33.0 weeks for oral and 35.0 weeks for IV topotecan; 1- and 2-year survival rates were 32.6% and 12.4% for oral topotecan, respectively, and 29.2% and 7.1% for IV topotecan, respectively. Third-line chemotherapy was similar for both groups (33% for oral; 35% for IV). Incidence of grade 4 toxicity in patients who received oral and IV topotecan was as follows: neutropenia in 47% and 64%, thrombocytopenia in 29% and 18%, grade 3 or 4 anemia in 23% and 31%, and sepsis in 3% and 3%, respectively. The most frequent nonhematologic adverse events (all grades) included nausea (43% oral; 42% IV), alopecia (26% oral; 30% IV), fatigue (31% oral; 36% IV), and diarrhea (36% oral; 20% IV).

Conclusion

Oral topotecan demonstrates activity and tolerability similar to IV topotecan in chemotherapy-sensitive SCLC patients and offers patients a convenient alternative to IV therapy.
Predicting the Outcome of Salvage Radiation Therapy for Recurrent Prostate Cancer After Radical Prostatectomy
Authors: Stephenson Andrew J. , Scardino Peter T. , Kattan Michael W. , Pisansky Thomas M. , Slawin Kevin M. , Klein Eric A. , Anscher Mitchell S. , Michalski Jeff M. , Sandler Howard M. , Lin Daniel W. , Forman Jeffrey D. , Zelefsky Michael J. , Kestin Larry L. , Roehrborn Claus G. , Catton Charles N. , DeWeese Theodore L. , Liauw Stanley L. , Valicenti Richard K. , Kuban Deborah A. , Pollack Alan
Published: May 2007

Purpose

An increasing serum prostate-specific antigen (PSA) level is the initial sign of recurrent prostate cancer among patients treated with radical prostatectomy. Salvage radiation therapy (SRT) may eradicate locally recurrent cancer, but studies to distinguish local from systemic recurrence lack adequate sensitivity and specificity. We developed a nomogram to predict the probability of cancer control at 6 years after SRT for PSA-defined recurrence.

Patients and Methods

Using multivariable Cox regression analysis, we constructed a model to predict the probability of disease progression after SRT in a multi-institutional cohort of 1,540 patients.

Results

The 6-year progression-free probability was 32% (95% CI, 28% to 35%) overall. Forty-eight percent (95% CI, 40% to 56%) of patients treated with SRT alone at PSA levels of 0.50 ng/mL or lower were disease free at 6 years, including 41% (95% CI, 31% to 51%) who also had a PSA doubling time of 10 months or less or poorly differentiated (Gleason grade 8 to 10) cancer. Significant variables in the model were PSA level before SRT (P < .001), prostatectomy Gleason grade (P < .001), PSA doubling time (P < .001), surgical margins (P < .001), androgen-deprivation therapy before or during SRT (P < .001), and lymph node metastasis (P = .019). The resultant nomogram was internally validated and had a concordance index of 0.69.

Conclusion

Nearly half of patients with recurrent prostate cancer after radical prostatectomy have a long-term PSA response to SRT when treatment is administered at the earliest sign of recurrence. The nomogram we developed predicts the outcome of SRT and should prove valuable for medical decision making for patients with a rising PSA level.