bluuebunny/crossref_metadata_2025 huggingface dataset:
An Elastic-Plastic Thermal Stress Analysis of Cross-ply and Angle-ply Aluminum Metal-matrix Composite Arches
Authors: Çevik Mehmet
Published: February 2007

A thermal elastic-plastic stress analysis is carried out on cross-ply and angle-ply steel fiber reinforced aluminum metal-matrix laminated composite arch under uniform temperature distribution. The composite material is assumed to be strain hardening linearly and consists of 4, 8, 12, and 16 layers bonded symmetrically and anti-symmetrically. First yielding temperature, thermal residual stresses, and the distribution of these stresses under thermal loading are investigated by using the finite element method (FEM). The effects of orientation angle, layer number, and stacking sequence on the residual stresses are analyzed. The magnitudes of residual stress components increase gradually depending on the temperature increment. It is found that the orientation angle affects the yield point and the intensity of residual stresses significantly, while the layer number and stacking sequence result in slight differences.
Agro-hybrid Composite: The Effects on Mechanical and Physical Properties of Oil Palm Fiber (EFB)/Glass Hybrid Reinforced Polyester Composites
Authors: Khalil H. P. S. Abdul , Hanida S. , Kang C. W. , Fuaad N. A. Nik
Published: February 2007

In this research, the combination of oil palm fiber and glass fiber as reinforcing fibers in polyester composites was evaluated. The mechanical and physical properties of oil palm empty fruit bunch/glass hybrid reinforced polyester composites were studied. Hybrid laminate composites with different weight ratios (w/w) of chopped strand mat (CSM) glass fibers: oil palm empty fruit bunch fiber (EFB) 3: 7, 5: 5, 7: 3, 9: 1 were prepared. The hybrid effect of glass and EFB fibers on the tensile, flexural, impact, and hardness of the composites were investigated. Water absorption and thickness swelling were also conducted. In general the hybrid composites exhibited good properties compared to the EFB/polyester composites.
Moisture Effect on Degradation of Jute/Glass Hybrid Composites
Authors: Aquino E. M. F. , Sarmento L. P. S. , Oliveira W. , Silva R. V.
Published: February 2007

The aim of this work is to evaluate the moisture absorption effect on the mechanical properties of a hybrid sandwich composite formed by orthophthalic polyester resin, reinforced by bi-directional woven fabrics of glass and jute fibers, with a central layer of polyester fabric (coremat). For the composite characterization, were performed tensile and three-point-bend tests, damage mechanism analysis, and moisture absorption tests. A larger absorption was observed for the hybrid composite compared to commonly observed fiberglass composites. This behavior is related to jute fiber as well as the coremat. In the mechanical tests a strong influence of the moisture content on the mechanical properties was verified. The main characteristic of the three-point-bend test was the premature shearing fracture of the coremat under both dry and wet conditions.
We Don’t Share! The Social Representation Approach, Enactivism and the Ground for an Intrinsically Social Psychology
Authors: Verheggen Theo , Baerveldt Cor
Published: February 2007

Wolfgang Wagner is a current and productive advocate of the social representation approach. He developed a version of the theory in which social representations are freed from individual minds and instead conceived of as concerted interactions. These epistemological starting points come very close to the enactive outlook on consensually coordinated actions. Yet Wagner is not radical enough in that he continues to see concerted interaction as an expression of representations that are already shared by the actors constituting a group. In our view, the ubiquitous notion of sharedness—which is also found in studies on social models, cultural patterns, schemas, scenarios, and so forth—is conceptually problematic and reveals a misapprehension of how orchestrated actions come about. Moreover, it obscures a proper understanding of what really constitutes intrinsically social behavior. Enactivism provides a much more consistent epistemology for a psychology that is intrinsically social.
Child Sexual Abuse Interpretation as a Sign-Construction Process
Authors: Molina María Elisa , del Río María Teresa
Published: February 2007

This is a reflection on Tine Jensen’s article ‘The Interpretation of Signs of Child Sexual Abuse’ (2005) and Robert Innis’s considerations ‘The Sign of Interpretation’ (2005). The article considers first the theoretical consequences of temporality as irreversible flow in meaning making and its relative stability as a narrative. Second, it focuses on ambiguity in sign processing when constructing meaning, arguing that ambiguity is always present in various ways as intrapersonal and interpersonal elaboration and as an essential quality of the elaboration of signs by individuals. Third, it considers signs given by abused children and the complexity of interpretation by others. Finally, the article offers a cultural and dialogical frame for interpretation from Marková’s triad model to the phenomena of sexual abuse.
Globalization, Diversity and Universal Darwinism
Authors: Kashima Yoshihisa
Published: February 2007

Moghaddam’s ‘Catastrophic Evolution, Culture and Diversity Management Policy’ is a timely commentary on the bio-cultural implications of the ongoing process of globalization. In my commentary, his thesis is reframed within a conceptual apparatus of Universal Darwinism, a view of bio-cultural evolution that takes for granted the importance of both genetic and cultural transmission of information in Homo sapiens. Although Moghaddam’s thesis can be couched in Universal Darwinian terms, it also exposes some limitations of the current models of Universal Darwinism.
Reflections on Political Parties and Political Development, Four Decades Later
Authors: LaPalombara Joseph
Published: February 2007

Several generalizations about political parties that appear in the symposium volume, Political Parties and Political Development (1966), seem to be equally valid 40 years later, while some others do not. The decline of the political party as perhaps the chief instrument for integrating previously excluded groups into political participatory modes was already apparent then. Similarly, it was predictable that universal suffrage and elections would not necessarily lead to democracy. Less apparent back then was that a proliferation of political parties would both reflect and also radically change the cleavage structure of society and, consequently, attenuate the tendency of parties and party systems to ‘freeze’ into predictable and enduring patterns. Above all, it was not imagined that revolutionary technological changes of the past several decades would so profoundly affect the nature of elections, and the role of political parties in them, as to raise disturbing questions regarding the future of representative democratic polities.
Revisiting Goffman’s Stigma: the social experience of families with children requiring mechanical ventilation at home
Authors: Carnevale Franco A.
Published: February 2007

This article argues for a sociologically grounded theoretical orientation for the study of selected health phenomena. Erving Goffman’s theory of stigma provides a framework for better understanding the social dimension of the lives of disabled children and their families. First, the principal tenets of this theory are reviewed. Then, the findings from a study of the moral experience of families with children requiring mechanical ventilation at home are re-examined in light of Goffman’s Stigma. This analysis highlights how a sociological framework can help advance our understanding of medical problems as social problems and shed light on socialization processes that can help resolve the discrediting, isolation and distress lived by disabled children and their families.
Development of children’s assent documents using a child-centred approach
Authors: Ford Karen , Sankey Judy , Crisp Jackie
Published: February 2007

The call for researchers to obtain children’s informed assent, prior to their participation in medical procedures and research, has increased over recent years and parallels moves to implement child-centred approaches to health care. This article describes the processes used to include children in developing a research information sheet and assent form for use in future research into children’s understandings of their surgery and hospital experiences. The process involved primary school children aged between six and 12 years. Children worked in small groups to consider information to include in these documents. Their words were collated to construct the research information sheet and assent form. Working with children resulted in documents that were more understandable for their intended audience. The article includes discussion of ‘language’, ‘understandability’ and ‘readability’; concepts that researchers seeking to work with children need to come to terms with if they are to obtain ‘informed assent’.
‘If I was in my daughter’s body I’d be feeling devastated’: women’s experiences of mothering an overweight or obese child
Authors: Jackson Debra , Wilkes Lesley , Mcdonald Glenda
Published: February 2007

Overweight and obesity in children is a major and ongoing public health concern and the negative physical, social, and psychological sequelae of childhood obesity are well documented. Parents, particularly mothers, are implicated in discourses around childhood obesity; however, little is known about women’s experiences of mothering an overweight or obese child. This article reports findings from a narrative-based study that sought to develop understandings into women’s experiences of mothering an overweight or obese child. The findings provide insights into the experiences of mothering an overweight or obese child, and reveals how the climate of blame associated with mothering an overweight or obese child complicated the mothering experience for the women in this study. These insights can assist health, welfare and child care workers to understand the importance of establishing supportive and no-blame relationships with mothers of obese and overweight children, in order to develop supportive therapeutic alliances better.
Consumers with an intellectual disability and carers
Authors: Hayes Susan C. , Martin Fiona B.
Published: February 2007

As more people with an intellectual disability reside independently in the community, there is both the need and the opportunity for them to use financial services, including banks and credit unions, and products such as cash machine cards, credit cards and loans. There is a dearth of information about interactions between consumers with intellectual disabilities and their carers, and financial service providers.This study investigated the perceptions of 94 consumers with an intellectual disability and 53 carers regarding interactions with financial service providers. Consumers and carers mentioned a number of problems with banks, and reported a low rate of successful resolution of these difficulties. Carers mentioned more problems than consumers, and more frequently reported intangible problems such as discrimination. The ‘digital divide’ was evident, with few consumers having access to Internet or telephone banking. People with intellectual disabilities need education programmes about electronic banking, their rights as consumers and their access to problem resolution strategies.
Assessing learning styles of adults with intellectual difficulties
Authors: Lisle Angela Mary
Published: February 2007

The development of an electronic inventory to assess learning styles of adults with intellectual difficulties was seen as an inclusion strategy to aid learning and achievement. Some argue for the ‘centrality of e-learning to educational diversity’, for example. The use of VAK inventories (whether electronic or paper based), however, has been derogated as leading to theory-practice pedagogy that is misinterpreted and ill-informed. The focus here is dual in that the vigour and ‘user friendliness’ of the tool developed is analysed in the midst of a critical appraisal of its use. Assessments conducted using the inventory developed showed 34 percent of the participants have visual preferences, 34 percent have auditory, 23 percent have kinaesthetic, and 9 percent have multimodal learning preferences. Thus, this participant group requires a varied and diverse learning programme. The inventory was found to be user friendly but in need of further development, and would best be used as part of a self-reflective learning package.
When Pigs Fly: Anime, Auteurism, and Miyazaki’s Porco Rosso
Authors: Moist Kevin M. , Bartholow Michael
Published: February 2007

This article addresses Western views of the Japanese animation form known as ‘anime’ through an analysis of a lesser-known film by one of the most important anime filmmakers, Hayao Miyazaki. In seeking to build what scholar Thomas Lamarre refers to as a ‘relational’ understanding of anime, we address Miyazaki’s film Porco Rosso through the lens of film studies concepts of auteur theory, and also in relation to the medium of animation. In a range of aspects, from visual approach to its deeper themes, Miyazaki’s work is found to draw on a distinctive set of strategies that might be described as ‘creative traditionalism’. Using Porco Rosso as a case study, our broader argument is that anime, as a form of postmodern popular culture, can be best understood in the West through a triangulation of different approaches that balance issues of form, medium, cultural context, and individual creators.
The Animated Resurrection of the Legend of the White Snake in Japan
Authors: Hu Tze-yue G.
Published: February 2007

This article analyses and elucidates the factors involved in the animated reappearance of the Legend of the White Snake in Japan in the 1950s. Driven by the multiple demands of a new post-Second World War era in East and Southeast Asia, where the business of making new images was more urgent, profitable and competitive than ever before, the tale served both micro and macro purposes. Since the legendary tale was well known in the Chinese-speaking world and was initially a joint film project between Japan and Hong Kong, one would have expected the producers (Toei Animation Studio) to envisage the animated tale as primarily for Chinese audiences. However, the Japanese producers had, or later discovered, a wider hidden agenda in making the film that promised more lucrative and geopolitical rewards. Using the concept of ‘performativity’, this article interprets the course of the animated performance within several dimensions, and traces the history of the foundational role of Toei Animation Studio and its dream-making enterprise.
Adoptive transfer of tumor-primed, in vitro–activated, CD4+ T effector cells (TEs) combined with CD8+ TEs provides intratumoral TE proliferation and synergistic antitumor response
Authors: Wang Li-Xin , Shu Suyu , Disis Mary L. , Plautz Gregory E.
Published: February 2007

The importance of CD4+ Th1 cells during the effector phase of the antitumor response has been overshadowed by emphasis on CD8+ cytotoxic T lymphocytes (CTLs). To determine their respective functions, we purified antigen-primed T cells from tumor-draining lymph nodes and separately activated CD4+ and CD8+ subsets in vitro. Adoptive transfer of CD4+ T effector cells (TEs) combined with CD8+ TEs provided synergistic therapy for mice bearing subcutaneous, intracranial, or advanced pulmonary metastases. CD4+ TEs augmented IFN-γ production by CD8+ TEs when cells were stimulated by tumor digest–containing antigen-presenting cells (APCs). CD4+ TEs infiltrated and proliferated extensively in pulmonary tumors, while also stimulating tumor antigen–specific CD8+ T cells. By contrast, CD8+ TEs showed minimal intratumoral proliferation in the absence of CD4+ cells or when systemically transferred CD4+ cells were prevented from infiltrating pulmonary tumors by pretreatment with pertussis toxin. Irradiation of CD4+ T cells immediately prior to adoptive transfer abrogated their intratumoral proliferation and direct antitumor efficacy but did not block their capacity to stimulate intratumoral CD8+ TE proliferation or tumor regression. These results highlight the importance of cross-presentation of tumor antigens during the effector phase of immunotherapy and suggest that approaches to stimulate CD4+ TE function and boost APC cross-presentation within tumors will augment cancer immunotherapy.
Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants
Authors: Markert M. Louise , Devlin Blythe H. , Alexieff Marilyn J. , Li Jie , McCarthy Elizabeth A. , Gupton Stephanie E. , Chinn Ivan K. , Hale Laura P. , Kepler Thomas B. , He Min , Sarzotti Marcella , Skinner Michael A. , Rice Henry E. , Hoehner Jeffrey C.
Published: February 2007

The purpose of this study was to characterize a large group of infants with complete DiGeorge anomaly and to evaluate the ability of thymus transplantation to reconstitute immune function in these infants. DiGeorge anomaly is characterized by varying defects of the heart, thymus, and parathyroid glands. Complete DiGeorge anomaly refers to the subgroup that is athymic (< 1%). The characteristics of 54 subjects at presentation and results from 44 consecutive thymus transplantations are reported. Remarkably, only 52% had 22q11 hemizygosity and only 57% had congenital heart disease requiring surgery. Thirty-one percent developed an atypical phenotype with rash and lymphadenopathy. To date, 33 of 44 subjects who received a transplant survive (75%) with post-transplantation follow-up as long as 13 years. All deaths occurred within 12 months of transplantation. All 25 subjects who were tested 1 year after transplantation had developed polyclonal T-cell repertoires and proliferative responses to mitogens. Adverse events developing after transplantation included hypothyroidism in 5 subjects and enteritis in 1 subject. In summary, diagnosis of complete DiGeorge anomaly is challenging because of the variability of presentation. Thymus transplantation was well tolerated and resulted in stable immunoreconstitution in these infants.
p53 status dictates responses of B lymphomas to monotherapy with proteasome inhibitors
Authors: Yu Duonan , Carroll Martin , Thomas-Tikhonenko Andrei
Published: February 2007

The proapoptotic function of p53 is thought to underlie most anticancer modalities and is also activated in response to oncogenic insults, such as overexpression of the Myc oncoprotein. Here we generated tractable B lymphomas using retroviral transduction of the MYC oncogene into hematopoietic cells with 2 knock-in alleles encoding a fusion between p53 and 4-hydroxytamoxifen (4OHT) receptor (p53ERTAM). In these polyclonal tumors, Myc is the only oncogenic lesion, and p53ERTAM status can be rapidly toggled between “off” and “on” with 4OHT, provided that the Trp53 promoter has been independently activated. Although 4OHT can trigger widespread apoptosis and overt tumor regression even in the absence of DNA-damaging agents, in tumors with high levels of Mdm2 these responses are blunted. However, cotreatment with proteasome inhibitors fully restores therapeutic effects in vivo. Similarly, human Burkitt lymphomas with wild-type p53 and overexpression of Hdm2 are highly sensitive to proteasome inhibitors, unless p53 levels are reduced using the HPV-E6 ubiquitin ligase. Therefore, proteasome inhibitors could be highly effective as a monotherapy against Myc-induced lymphomas, with no need for adjuvant chemotherapy or radiation therapy. On the other hand, their efficacy is crucially dependent on the wild-type p53 status of the tumor, placing important restrictions on patient selection.
Highly homologous T-cell receptor beta sequences support a common target for autoreactive T cells in most patients with paroxysmal nocturnal hemoglobinuria
Authors: Gargiulo Lucia , Lastraioli Sonia , Cerruti Giannamaria , Serra Martina , Loiacono Fabrizio , Zupo Simona , Luzzatto Lucio , Notaro Rosario
Published: February 2007

Deficiency of glycosylphosphatidylinositol (GPI)–anchored molecules on blood cells accounts for most features of paroxysmal nocturnal hemoglobinuria (PNH) but not for the expansion of PNH (GPI−) clone(s). A plausible model is that PNH clones expand by escaping negative selection exerted by autoreactive T cells against normal (GPI+) hematopoiesis. By a systematic analysis of T-cell receptor beta (TCR-β) clonotypes of the CD8+ CD57+ T-cell population, frequently deranged in PNH, we show recurrent clonotypes in PNH patients but not in healthy controls: 11 of 16 patients shared at least 1 of 5 clonotypes, and a set of closely related clonotypes was present in 9 patients. The presence of T-cell clones bearing a set of highly homologous TCR-β molecules in most patients with hemolytic PNH is consistent with an immune process driven by the same (or similar) antigen(s)—probably a nonpeptide antigen, because patients sharing clonotypes do not all share identical HLA alleles. These data confirm that CD8+ CD57+ T cells play a role in PNH pathogenesis and provide strong new support to the hypothesis that the expansion of the GPI− blood cell population in PNH is due to selective damage to normal hematopoiesis mediated by an autoimmune attack against a nonpeptide antigen(s) that could be the GPI anchor itself.
Protein kinase C inhibitor enzastaurin induces in vitro and in vivo antitumor activity in Waldenström macroglobulinemia
Authors: Moreau Anne-Sophie , Jia Xiaoying , Ngo Hai T. , Leleu Xavier , O'Sullivan Garrett , Alsayed Yazan , Leontovich Alexey , Podar Klaus , Kutok Jeffrey , Daley John , Lazo-Kallanian Suzan , Hatjiharissi Evdoxia , Raab Marc S. , Xu Lian , Treon Steven P. , Hideshima Teru , Anderson Kenneth C. , Ghobrial Irene M.
Published: February 2007

Waldenström macroglobulinemia (WM) is an incurable lymphoplasmacytic lymphoma with limited options of therapy. Protein kinase Cβ (PKCβ) regulates cell survival and growth in many B-cell malignancies. In this study, we demonstrate up-regulation of PKCβ protein in WM using protein array techniques and immunohistochemistry. Enzastaurin, a PKCβ inhibitor, blocked PKCβ activity and induced a significant decrease of proliferation at 48 hours in WM cell lines (IC50, 2.5-10 μM). Similar effects were demonstrated in primary CD19+ WM cells, without cytotoxicity on peripheral blood mononuclear cells. In addition, enzastaurin overcame tumor cell growth induced by coculture of WM cells with bone marrow stromal cells. Enzastaurin induced dose-dependent apoptosis at 48 hours mediated via induction of caspase-3, caspase-8, caspase-9, and PARP cleavage. Enzastaurin inhibited Akt phosphorylation and Akt kinase activity, as well as downstream p-MARCKS and ribosomal p-S6. Furthermore, enzastaurin demonstrated additive cytotoxicity in combination with bortezomib, and synergistic cytotoxicity in combination with fludarabine. Finally, in an in vivo xenograft model of human WM, significant inhibition of tumor growth was observed in the enzastaurin-treated mice (P = .028). Our studies therefore show that enzastaurin has significant antitumor activity in WM both in vitro and in vivo, providing the framework for clinical trials to improve patient outcome in WM.
The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells
Authors: de Leval Laurence , Rickman David S. , Thielen Caroline , Reynies Aurélien de , Huang Yen-Lin , Delsol Georges , Lamant Laurence , Leroy Karen , Brière Josette , Molina Thierry , Berger Françoise , Gisselbrecht Christian , Xerri Luc , Gaulard Philippe
Published: February 2007

The molecular alterations underlying the pathogenesis of angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, unspecified (PTCL-u) are largely unknown. In order to characterize the ontogeny and molecular differences between both entities, a series of AITLs (n = 18) and PTCLs-u (n = 16) was analyzed using gene expression profiling. Unsupervised clustering correlated with the pathological classification and with CD30 expression in PTCL-u. The molecular profile of AITLs was characterized by a strong microenvironment imprint (overexpression of B-cell– and follicular dendritic cell–related genes, chemokines, and genes related to extracellular matrix and vascular biology), and overexpression of several genes characteristic of normal follicular helper T (TFH) cells (CXCL13, BCL6, PDCD1, CD40L, NFATC1). By gene set enrichment analysis, the AITL molecular signature was significantly enriched in published TFH-specific genes. The enrichment was higher for sorted AITL cells than for tissue samples. Overexpression of several TFH genes was validated by immunohistochemistry in AITLs. A few cases with molecular TFH-like features were identified among CD30− PTCLs-u. Our findings strongly support that TFH cells represent the normal counterpart of AITL, and suggest that the AITL spectrum may be wider than suspected, as a subset of CD30− PTCLs-u may derive from or be related to AITL.
Racial variation in the relationship of anemia with mortality and mobility disability among older adults
Authors: Patel Kushang V. , Harris Tamara B. , Faulhaber Marion , Angleman Sara B. , Connelly Stephanie , Bauer Douglas C. , Kuller Lewis H. , Newman Anne B. , Guralnik Jack M.
Published: February 2007

Anemia is more common among older blacks than older whites. However, it is unclear whether anemia predicts adverse events similarly in both races. Data on 1018 black and 1583 white adults aged 71 to 82 years were analyzed. Anemia, as defined by World Health Organization (WHO) criteria, was used to predict mortality over 6 years and incidence of mobility disability over 4 years. In proportional hazards models of mortality in whites, the age-adjusted hazard ratio (HR) for anemia in men was 1.96 (95% confidence interval [CI]: 1.35, 2.83) and in women was 2.86 (95% CI: 1.69, 4.82). In contrast, anemia was not associated with mortality in black men (HR = 1.15 [95% CI: 0.77, 1.72]) or women (HR = 1.39 [95% CI: 0.91, 2.14]). Higher mortality rate was observed only in black men with hemoglobin values more than 20 g/L (2.0 g/dL) below the WHO cutoff, whereas mortality rates were elevated in white men with hemoglobin values 1 to 10, 11 to 20, and more than 20 g/L below the WHO cutoff. In conclusion, anemia was significantly associated with increased risk of death and mobility disability in community-dwelling older whites. Conversely, older blacks classified as anemic by WHO criteria were not at risk for adverse events, indicating that alternative criteria are warranted.
Predictive modeling of plant messenger RNA polyadenylation sites
Authors: Ji Guoli , Zheng Jianti , Shen Yingjia , Wu Xiaohui , Jiang Ronghan , Lin Yun , Loke Johnny C , Davis Kimberly M , Reese Greg J , Li Qingshun Quinn
Published: February 2007

Background

One of the essential processing events during pre-mRNA maturation is the post-transcriptional addition of a polyadenine [poly(A)] tail. The 3'-end poly(A) track protects mRNA from unregulated degradation, and indicates the integrity of mRNA through recognition by mRNA export and translation machinery. The position of a poly(A) site is predetermined by signals in the pre-mRNA sequence that are recognized by a complex of polyadenylation factors. These signals are generally tri-part sequence patterns around the cleavage site that serves as the future poly(A) site. In plants, there is little sequence conservation among these signal elements, which makes it difficult to develop an accurate algorithm to predict the poly(A) site of a given gene. We attempted to solve this problem.

Results

Based on our current working model and the profile of nucleotide sequence distribution of the poly(A) signals and around poly(A) sites in Arabidopsis, we have devised a Generalized Hidden Markov Model based algorithm to predict potential poly(A) sites. The high specificity and sensitivity of the algorithm were demonstrated by testing several datasets, and at the best combinations, both reach 97%. The accuracy of the program, called p oly(A) s ite s leuth or PASS, has been demonstrated by the prediction of many validated poly(A) sites. PASS also predicted the changes of poly(A) site efficiency in poly(A) signal mutants that were constructed and characterized by traditional genetic experiments. The efficacy of PASS was demonstrated by predicting poly(A) sites within long genomic sequences.

Conclusion

Based on the features of plant poly(A) signals, a computational model was built to effectively predict the poly(A) sites in Arabidopsis genes. The algorithm will be useful in gene annotation because a poly(A) site signifies the end of the transcript. This algorithm can also be used to predict alternative poly(A) sites in known genes, and will be useful in the design of transgenes for crop genetic engineering by predicting and eliminating undesirable poly(A) sites.
Respiratory Effect of Prolonged Electrical Weapon Application on Human Volunteers
Authors: Ho Jeffrey D. , Dawes Donald M. , Bultman Laura L. , Thacker Jenny L. , Skinner Lisa D. , Bahr Jennifer M. , Johnson Mark A. , Miner James R.
Published: February 2007

Background: Conducted electrical weapons (CEWs) are used by law enforcement to subdue combative subjects. Occasionally, subjects will die after a CEW has been used on them. It is theorized that CEWs may contribute to these deaths by impairing respiration.

Objectives: To examine the respiratory effects of CEWs.

Methods: Human volunteers received a 15‐second application of electrical current from a CEW while wearing a respiratory measurement device. Common respiratory parameters were collected before, during, and after exposure. Health histories and demographic information were also collected.

Results: Fifty‐two subjects were analyzed. Thirty‐four underwent a 15‐second continuous exposure, and 18 underwent three 5‐second burst exposures. In the continuous application group, the baseline mean tidal volume of 1.1 L increased to 1.8 L during application, the baseline end‐tidal CO2 level went from 40.5 mm Hg to 37.3 mm Hg after exposure, the baseline end‐tidal oxygen level went from 118.7 mm Hg to 121.3 mm Hg after exposure, and the baseline respiratory rate went from 15.9 breaths/min to 16.4 breaths/min after exposure. In the 5‐second burst group, the baseline mean tidal volume increased to 1.85 L during application, the baseline end‐tidal CO2 level went from 40.9 mm Hg to 39.1 mm Hg after exposure, the baseline end‐tidal oxygen level went from 123.1 mm Hg to 127.0 mm Hg after exposure, and the baseline respiratory rate went from 13.8 breaths/min to 14.6 breaths/min after exposure.

Conclusions: Prolonged CEW application did not impair respiratory parameters in this population of volunteers. Further study is recommended to validate these findings in other populations.
α-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains
Authors: Gromada Jesper , Franklin Isobel , Wollheim Claes B.
Published: February 2007

Glucagon, a hormone secreted from the α-cells of the endocrine pancreas, is critical for blood glucose homeostasis. It is the major counterpart to insulin and is released during hypoglycemia to induce hepatic glucose output. The control of glucagon secretion is multifactorial and involves direct effects of nutrients on α-cell stimulus-secretion coupling as well as paracrine regulation by insulin and zinc and other factors secreted from neighboring β- and δ-cells within the islet of Langerhans. Glucagon secretion is also regulated by circulating hormones and the autonomic nervous system. In this review, we describe the components of the α-cell stimulus secretion coupling and how nutrient metabolism in the α-cell leads to changes in glucagon secretion. The islet cell composition and organization are described in different species and serve as a basis for understanding how the numerous paracrine, hormonal, and nervous signals fine-tune glucagon secretion under different physiological conditions. We also highlight the pathophysiology of the α-cell and how hyperglucagonemia represents an important component of the metabolic abnormalities associated with diabetes mellitus. Therapeutic inhibition of glucagon action in patients with type 2 diabetes remains an exciting prospect.
Absence of Stabilizing Mutations of β-Catenin Encoded by CTNNB1 Exon 3 in a Large Series of Sporadic Parathyroid Adenomas
Authors: Costa-Guda Jessica , Arnold Andrew
Published: February 2007

Context: The molecular mechanisms underlying the pathogenesis of sporadic parathyroid adenomas are incompletely understood. Dysfunction of the Wnt signaling pathway is an established pathogenetic contributor to human tumorigenesis and, recently, the role of stabilizing mutations in β-catenin, a cause of abnormal Wnt signaling, has been examined in parathyroid tumors with conflicting results.

Objective: The objective of the present study was to determine the frequency of stabilizing mutations in exon 3 of CTNNB1, encoding β-catenin, in a large series of parathyroid adenomas.

Patients and Design: Ninety-seven sporadic parathyroid adenomas were examined for mutations in exon 3 of CTNNB1 by direct DNA sequencing.

Results: No mutations were identified in any of the adenomas.

Conclusions: The absence of stabilizing mutations of β-catenin, including the previously reported S37A, encoded in CTNNB1 exon 3 among 97 tumors suggests that such mutations contribute rarely if at all to the development of sporadic parathyroid adenomas. A primary role for abnormal Wnt signaling in parathyroid tumor formation remains to be established.
Tau impacts on growth-factor-stimulated actin remodeling
Authors: Sharma Vandana M. , Litersky Joel M. , Bhaskar Kiran , Lee Gloria
Published: February 2007

The microtubule-associated protein tau interacts with the SH3 domain of non-receptor Src family protein tyrosine kinases. A potential consequence of the SH3 interaction is the upregulation of tyrosine kinase activity. Here we investigated the activation of Src or Fyn by tau, both in vitro and in vivo. Tau increased the kinase activity in in vitro assays and in transfected COS7 cells. In platelet-derived growth factor (PDGF)-stimulated fibroblasts, tau appeared to prime Src for activation following PDGF stimulation, as reflected by changes in Src-mediated actin rearrangements. In addition, while fibroblasts normally recovered actin stress fibers by 5-7 hours after PDGF stimulation, tau-expressing cells showed sustained actin breakdown. Microtubule association by tau was not required for the observed changes in actin morphology. Inhibition of Src kinases or a mutant deficient in Src interaction reduced the effects, implicating Src family protein tyrosine kinases as a mediator of the effects of tau on actin rearrangements. Our results provide evidence that the interaction of tau with Src upregulates tyrosine kinase activity and that this interaction allows tau to impact on growth-factor-induced actin remodeling.
EHD1 regulates β1 integrin endosomal transport: effects on focal adhesions, cell spreading and migration
Authors: Jović Marko , Naslavsky Naava , Rapaport Debora , Horowitz Mia , Caplan Steve
Published: February 2007

β1 integrins bind to the extracellular matrix and stimulate signaling pathways leading to crucial cellular functions, including proliferation, apoptosis, cell spreading and migration. Consequently, control of β1 integrin function depends upon its subcellular localization, and recent studies have begun to unravel the complex regulatory mechanisms involved in integrin trafficking. We report that the C-terminal Eps15-homology (EH) domain-containing protein EHD1 plays an important role in regulating β1 integrin transport. Initially, we demonstrated that RNAi-knockdown of Ehd1 results in impaired recycling of β1 integrins and their accumulation in a transferrin-containing endocytic recycling compartment. Mouse embryonic fibroblast (MEF) cells derived from EHD1-knockout mice (Ehd1–/– MEF) exhibited lower overall levels of β1 integrins on the plasma membrane, but higher cell-surface-expressed activated β1 integrins, and larger, more prominent focal adhesions resulting from slower kinetics of focal adhesion disassembly. In addition, both migration and cell spreading on fibronectin were impaired in Ehd1–/– MEF cells, and these defects could be similarly induced by EHD1-RNAi treatment of normal Ehd1+/+ MEF cells. They could also be rescued by transfection of wild-type EHD1 into Ehd1–/– MEF cells. Our data support a role for EHD1 in β1 integrin recycling, and demonstrate a requirement for EHD1 in integrin-mediated downstream functions.
Decoding ubiquitin sorting signals for clathrin-dependent endocytosis by CLASPs
Authors: Traub Linton M. , Lukacs Gergely L.
Published: February 2007

Cargo selectivity is a hallmark of clathrin-mediated endocytosis. A wide range of structurally unrelated internalization signals specify the preferential clustering of transmembrane cargo into clathrin coats forming on the plasma membrane. Intriguingly, the classical endocytic adaptor AP-2 appears to recognize only a subset of these endocytic sorting signals. New data now reveal the molecular basis for recognition of other internalization signals, including post-translationally appended ubiquitin, by clathrin-coat-associated sorting proteins (CLASPs). Curiously, structurally related ubiquitin-recognition modules are shared by select CLASPs and the 26S proteasome, and recent work indicates that both display similar requirements for ubiquitin binding. During endocytosis, these modules engage oligoubiquitylated cargo in the form of polyubiquitin chains and/or multiple single ubiquitin molecules appended to different acceptor lysines. Functional separation between clathrin-mediated endocytosis and proteasome-dependent proteolysis is probably ensured by temporally regulated, local assembly of ubiquitin-tagged membrane cargo at sorting stations on the cell surface, shielding ubiquitin sorting signals from the proteasome. Thus, an expanded repertoire of CLASPs couples the process of clathrin-coat assembly with high-fidelity incorporation of assorted, cargo-specific sorting signals.
LAP2α-binding protein LINT-25 is a novel chromatin-associated protein involved in cell cycle exit
Authors: Naetar Nana , Hutter Sabine , Dorner Daniela , Dechat Thomas , Korbei Barbara , Gotzmann Josef , Beug Hartmut , Foisner Roland
Published: February 2007

Lamina-associated polypeptide 2α (LAP2α) is a nuclear protein dynamically associating with chromatin during the cell cycle. In addition, LAP2α interacts with A-type lamins and retinoblastoma protein and regulates cell cycle progression via the E2F-Rb pathway. Using yeast two-hybrid analysis and three independent in vitro binding assays we identified a new LAP2α interaction partner of hitherto unknown functions, which we termed LINT-25. LINT-25 protein levels were upregulated during G1 phase in proliferating cells and upon cell cycle exit in quiescence, senescence and differentiation. Upon cell cycle exit LINT-25 accumulated in heterochromatin foci, and LAP2α protein levels were downregulated by proteasomal degradation. Although LAP2α was not required for the upregulation and reorganization of LINT-25 during cell cycle exit, transient expression of LINT-25 in proliferating cells caused loss of LAP2α and subsequent cell death. Our data show a role of LINT-25 and LAP2α during cell cycle exit, in which LINT-25 acts upstream of LAP2α.
Suprabasal Dsg2 expression in transgenic mouse skin confers a hyperproliferative and apoptosis-resistant phenotype to keratinocytes
Authors: Brennan Donna , Hu Ying , Joubeh Sohaila , Choi Yoo Won , Whitaker-Menezes Diana , O'Brien Thomas , Uitto Jouni , Rodeck Ulrich , Mahoney Mỹ G.
Published: February 2007

Desmoglein 2 (Dsg2), a component of the desmosomal cell-cell adhesion structure, has been linked to invasion and metastasis in squamous cell carcinomas. However, it is unknown whether – and if so how – Dsg2 contributes to the malignant phenotype of keratinocytes. In this study, we addressed the consequences of Dsg2 overexpression under control of the involucrin promoter (Inv-Dsg2) in the epidermis of transgenic mice. These mice exhibited epidermal hyperkeratosis with slightly disrupted early and late differentiation markers, but intact epidermal barrier function. However, Inv-Dsg2 transgene expression was associated with extensive epidermal hyperplasia and increased keratinocyte proliferation in basal and suprabasal epidermal strata. Cultured Inv-Dsg2 keratinocytes showed enhanced cell survival in the anchorage-independent state that was critically dependent on EGF receptor activation and NF-κB activity. Consistent with the hyperproliferative and apoptosis-resistant phenotype of Inv-Dsg2 transgenic keratinocytes, we observed enhanced activation of multiple growth and survival pathways, including PI 3-kinase/AKT, MEK-MAPK, STAT3 and NF-κB, in the transgenic skin in situ. Finally, Inv-Dsg2 transgenic mice developed intraepidermal skin lesions resembling precancerous papillomas and were more susceptible to chemically induced carcinogenesis. In summary, overexpression of Dsg2 in epidermal keratinocytes deregulates multiple signaling pathways associated with increased growth rate, anchorage-independent cell survival, and the development of skin tumors in vivo.
Linezolid for the Treatment of Patients with Central Nervous System Infection
Authors: Ntziora Fotinie , Falagas Matthew E
Published: February 2007

Objective:

To review the available evidence regarding the use of linezolid for the treatment of patients with central nervous system (CNS) infections.

Data Sources:

Relevant studies were identified through searches of the PubMed, Current Contents, and Cochrane databases (publications archived until October 2006).

Study Selection and Data Extraction:

Case reports, case series, prospective and retrospective studies, and randomized controlled trials were eligible for inclusion in our review if they evaluated the effectiveness and safety of linezolid for the treatment of patients with CNS infections.

Data Synthesis:

In 18 (42.9%) of the 42 relevant cases identified, patients had undergone neurosurgical operations and/or had prosthetic devices. Meningitis was the most common CNS infection, accounting for 20 (47.6%) cases. Other CNS infections included brain abscesses (14; 33.3%), ventriculitis (5; 11.9%), and ventriculo-peritoneal shunt infection (3; 7.1%). In the 39 patients in whom the responsible pathogen was isolated, those predominantly responsible for the CNS infections were: penicillin–nonsusceptible Streptococcus pneumoniae (7; 17.9%), vancomycin-resistant enterococci (6; 15.4%), Nocardia spp. (5; 12.8%), methicillin-resistant Staphylococcus epidermidis (4; 10.3%), and methicillin-resistant Staphylococcus aureus (3; 7.7%). Of the 42 patients who received linezolid for the treatment of CNS infections, 38 (90.5%) were either cured or showed clinical improvement of the infection. The mean duration of follow-up was 7.2 months; no recurrent CNS infection was reported.

Conclusions:

The limited published data suggest that linezolid may be considered for the treatment of patients with CNS infections in cases of failure of previously administered treatment or limited available options.
Absence of Effect of Oral Rifaximin on the Pharmacokinetics of Ethinyl Estradiol/Norgestimate in Healthy Females
Authors: Trapnell Carol Braun , Connolly Margaret , Pentikis Helen , Forbes William P , Bettenhausen Doug K
Published: February 2007

Background:

Rifaximin is an oral rifampin analog, and its activity is targeted within the gastrointestinal tract. Some analogs induce the cytochrome P450 family of oxidative enzymes. Ethinyl estradiol (EE), commonly found in oral contraceptives (OCs), is a known CYP3A4 substrate.

Objective:

To determine the potential effect of rifaximin on EE and norgestimate pharmacokinetics.

Methods:

In an open-label, crossover study, healthy females received a single dose of OC (EE 0.07 mg/norgestimate 0.50 mg). Following a 1 week washout period, individuals received rifaximin 200 mg every 8 hours for 3 days, with a single dose of OC administered with the ninth rifaximin dose. During both treatment periods, blood samples were collected periodically for up to 96 hours after each OC dose. Plasma concentration–time profiles and pharmacokinetic parameters were characterized for EE and 2 major metabolites of norgestimate, norgestrel (NG) and 17-deacetyl norgestimate (17-DNGM). A drug–drug interaction was confirmed if the 90% CI for the 2 treatment period comparison was outside the 80–125% limit.

Results:

Twenty-six of 28 women completed the study. No differences in pharmacokinetic parameters were observed for EE, NG, or 17-DNGM when a single dose of the OC was administered alone or with rifaximin. In addition, the 90% CI for the bioavailability contrasts (OC alone vs OC with rifaximin) for the maximum plasma concentration, area under the plasma concentration–time curve from zero to the last measurable plasma concentration or to infinity for EE, NG. and 17-DNGM all ranged from 86–118%. These intervals were within the predefined range for equivalence; therefore, no interaction was observed between OC and rifaximin. Rifaximin was well tolerated.

Conclusions:

Administration of a 3 day dosing regimen of oral rifaximin was well tolerated and did not alter the pharmacokinetics of a commonly used combination OC containing EE and norgestimate.
Laboratory Evaluation of Potassium and Creatinine Among Ambulatory Patients Prescribed Spironolactone: Are We Monitoring for Hyperkalemia?
Authors: Raebel Marsha A , McClure David L , Chan K Arnold , Simon Steven R , Feldstein Adrianne C , Lafata Jennifer Elston , Andrade Susan E , Gunter Margaret J , Nelson Winnie W , Roblin Douglas , Platt Richard
Published: February 2007

Background:

Serum potassium and creatinine evaluation is recommended in patients prescribed spironolactone, yet the proportion of ambulatory patients chronically dispensed spironolactone receiving evaluation is not well understood.

Objective:

To estimate the rate of potassium and creatinine evaluation and identify factors associated with conducting these tests among ambulatory patients dispensed spironolactone.

Methods:

A retrospective cohort study was designed to evaluate patients at 10 health maintenance organizations with ongoing spironolactone dispensing for one year (N = 2257). Potassium and creatinine evaluation were determined from administrative data. Associations between patient characteristics and laboratory testing were assessed, using logistic regression modeling.

Results:

Serum creatinine and potassium were evaluated in 72.3% of patients during a 13 month period. The likelihood of potassium and creatinine monitoring was greater among patients who were older (OR 1.28; 95% CI 1.17 to 1.41 per decade of life); male (OR 1.25; 95% CI 1.01 to 1.54); had diabetes (OR 1.63; 95% CI 1.31 to 2.03); received concomitant therapy with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (OR 2.23; 95% CI 1.74 to 2.87), potassium supplements (OR 1.96; 95% CI 1.51 to 2.54), or digoxin (OR 2.10 95% CI 1.48 to 2.98); or had more outpatient visits (OR 1.31; 95% CI 1.19 to 1.44). Among patients with heart failure (n = 790), factors associated with the incidence of laboratory testing were diabetes (OR 1.64, 95% CI 1.14 to 2.34), outpatient visits (OR 1.20; 95% CI 1.02 to 1.41), and digoxin therapy (OR 2.26; 95% CI 1.38 to 3.69).

Conclusions:

Three-fourths of ambulatory patients dispensed spironolactone receive recommended laboratory evaluation, with monitoring more likely to be completed in patients prescribed concomitant therapy with drugs that increase hyperkalemia risk, older patients, and those with diabetes.