bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-genocide identity politics in Rwanda
Authors: Hintjens Helen
Published: February 2008

When the journal Ethnicities was launched in 2001, the first issue included an article by this author, which examined the politics of `race' and identity as central ingredients in the Rwanda genocide of 1994. This current article considers how political identities have been reconstructed since the genocide, especially from above. History, law and politics are examined, as central instruments in government efforts to construct a new Rwandan society and ensure that genocide will `never again' be possible. Evidence suggests that inequalities in income and land distribution have grown rapidly since 1994. At the same time, the poor and marginalized often find it difficult to openly express their views, including their political identities outside of officially circumscribed spaces and categories. Debates continue around numbers of victims and perpetrators, and new inter-elite conflicts have emerged along language lines. The article shows how race categories have been replaced with new terms, which arise from a particular reading of the genocide. A new foundation myth for Rwanda, a form of diasporic victim nationalism, is also briefly explored. Re-labelling Rwandans from above, the state continues to exercise tight control over the public expression of political identities. Open political debate is very difficult; the government frequently feels it is being attacked, and accuses critics of divisionism or harbouring a genocide mentality. If more inclusive forms of Rwandan-ness are to emerge in future, state controls will need to be relaxed, so that more complex forms of political identities can finally emerge.
Normalizing Cuban refugees
Authors: Current Cheris Brewer
Published: February 2008

This article examines the representation of Cuban refugees during the 1960s and 1970s in the USA. Positioning the Cuban refugees as `ideologically' valuable, the US government undertook a substantial public relations campaign that sought to secure public mandate for incoming refugees. In order to avoid a national anti-Cuban backlash, the US government and the popular media alike constructed `positive' portrayals of incoming Cuban refugees. These representations played up the refugees' purportedly universal anti-communist stance and the socially and racially desirable qualities of these `good immigrants', who were perceived as `white' and middle to upper class. In order to contextualize these representations, a history of US—Cuban relations and mid-20th-century refugee policies are discussed. Thus anti-communism, whiteness, and middle-class attributes were strategically linked and broadcasted by the US government and public media sources alike.
Advice to speak English in Australia
Authors: Martín Mario Daniel
Published: February 2008

This article addresses the issue of advice given to immigrant parents to speak English only with their children in Australia, as reflected in the Spanish-speaking community. The article shows that something that appears to be down to chance, i.e. whether this advice is given or not, has a social explanation. This social explanation is based on understanding several social variables such as the ethnic identity of the adviser and the year in which the advice was given, as well as social variables that define the individual who received the advice, notably, his/her physical appearance in the sense of how `Caucasian' the migrant looks. Such analysis sheds light on the changing perception of migrants in Australia. It was found that, throughout the 1980s and 1990s, when there was an Australian government-sponsored policy of multiculturalism, there was an increase in the number of people being advised to speak English only. It is hypothesized that such increase is linked to the conflict and contest that any recognition of linguistic and social rights for minorities precipitates.
The `Pragmatics` of Material Interaction
Authors: Dant Tim
Published: February 2008

Our everyday interactions with material objects are dependent on us making sense of what they mean and what actions will be effective in transforming them to suit our purposes. We perceive things by interpreting the information of our senses in the light of what we know of our material culture. We act on them through bodily gesture that changes them, both physically and their meaning as signs. Those who design and manufacture objects anticipate how they will be interacted with and how they will fit within the existing material culture. Their intentions are embedded within the form of the objects they produce and are responded to or `read' during interaction by consumers or users. Material interaction involves pragmatic relations that situate the meaning of objects in relation to other objects and the intentions of the designer and the user. This article attempts to set out the pragmatic features of everyday interaction with objects to enhance sociological understanding of design and consumption and illustrates the processes of material interaction with the examples of making flat-pack furniture and professional work on cars. The concept of `pragmatics' is derived from the writings of Pierce and Morris and their approach to the study of signs is developed with reference to Barthes. Meaningful material interaction involves the subject/object, person/thing relations of perception and gesture and these are developed from the theories of Merleau-Ponty and Leroi-Gourhan. The pragmatic dimensions of material interaction are proposed to be: intention, perception, orientation, manipulation and continuation.
Green Consumption
Authors: Connolly John , Prothero Andrea
Published: February 2008

In recent times, much has been written about consumers' co-responsibility for addressing environmental problems, with consumers expected to steer or regulate their consumption in an instrumental way. By drawing on data from in-depth interviews with green consumers in urban Ireland, this article examines how green consumers engage with environmental issues at an everyday level. The article considers green consumption through the theoretical lens of reflexive modernization, particularly its relevance to self-identity. We argue that although green consumption is important to the maintenance and constitution of a green subjectivity, it must be understood within the context of a process of increasing individualization, where individuals feel both responsible and empowered in dealing with environmental risks to both the wider global planet and themselves. However, such feelings are accompanied by doubts and insecurities about the choices to be made, creating a rather dichotomous situation. This challenges the idea that green consumption as some form of politics of choice can unambiguously form part of a strategy for environmental reform as it does not adequately address the fundamental dilemmas that people face.
The Culturization of Planning
Authors: Young Greg
Published: February 2008

Culture as an organizing concept and framework offers planning a new, deeper and more sustainable foundation. The fact that culture constitutes and is constituted by our geographies, histories and societies, is expanding, and is the world's leading intellectual resource, can be the basis for a new positionality for planning. A positionality of this kind is proposed as a new paradigm, and tagged with the neologism of `culturization'. As a specifically ethical, reflexive and critical approach, it stands in contrast to the broader, socio-economic trend to `culturalization' and its acknowledged commodification. For the purposes ofculturization, an integrated concept of culture and an integrated approach to planning research are described in order to engage all of the forms and dimensions of culture, and to link a plurality of cultural theory and communicative and postmodern planning theory to the enterprise. Further, innovations in theoretical writings and culturized planning practices that have emerged in recent times are cited for their relevance to a more systematic culturization of planning with greater sustainable and transformational potential.
Foucault's Dispositif and the City
Authors: Pløger John
Published: February 2008

Michel Foucault was concerned with the role of urban planning in `bio-politics'. Only a few authors, however, emphasize the crucial role of the dispositif in his thinking about space and discipline. This article emphasizes the dispositif ensemble as exemplary to understanding urban planning and to one of Foucault's main themes: the constitution of disciplinarian forces through relations of power, knowledge and space. The article explores the dispositif both categorically and in its common use, and indicates Foucault's understanding of dispositif by looking at his writings on `the healthy city' and the Panopticon.
The Efficacy of Long-Range Physical Planning
Authors: Macdonald Elizabeth
Published: February 2008

The long-range general plan has long been a foundation of city planning in North America, but its usefulness and purposes are much debated and comprehensive physical plans are not considered a dynamic, central part of city planning today. This article looks at the comprehensive physical plan prepared in the late 1920s by Harland Bartholomew and the local Town Planning Commission for Vancouver, British Columbia—a city known for its livability—and analyzes how the plan contributed to and is reflected in the city's public realm. It explores how key public realm proposals of the plan have continued to inform planning policy over the years. In the end, conclusions are reached regarding the power of simple yet visionary long-range ideas for a city's public realm, the value of building on good ideas, and the identity-building possibilities of building a public realm responsive to its unique natural context.
Recovery From Amnesic Confabulatory Syndrome After Right Fornix Lesion
Authors: Ruggeri Massimiliano , Sabatini Umberto
Published: February 2008

Background. Reports of amnesia due to bilateral fornix lesions are rare. A unilateral right fornix lesion is not known to cause an amnestic confabulatory syndrome. Objective. To investigate the role of right fornix lesion in amnesia, the association of confabulation with executive disorders, and to evaluate the long-term recovery of memory and executive functions after surgical removal of a pilocytic astrocytoma in the right orbitofrontal region extending to the right fornix. Methods. Neuropsychological testing was performed 3 and 17 months after surgery. Results. Severe anterograde global amnesia, mild retrograde amnesia, momentary and spontaneous confabulation, and mild executive deficits were found initially and mostly recovered by 17 months. Conclusions. The authors hypothesize that the lesion of the right fornix was sufficient to cause amnesia by disconnecting the hippocampal formations from the anterior thalamic nuclei and mammillary bodies and interrupting the cholinergic efferents to the hippocampus from the medial septum, according to the extended hippocampal system framework. Sparing of the left fornix may be sufficient to ensure a good recovery of memory. Confabulation is strongly associated with the improvement of executive functions, specifically the ability to suppress irrelevant memory traces.
Human invariant Vα24+ natural killer T cells acquire regulatory functions by interacting with IL-10–treated dendritic cells
Authors: Yamaura Ayako , Hotta Chie , Nakazawa Masatoshi , Van Kaer Luc , Minami Mutsuhiko
Published: February 2008

Glycolipid-reactive Vα24+ invariant natural killer T (iNKT) cells have been implicated in regulating a variety of immune responses and in the induction of immunologic tolerance. Activation of iNKT cells requires interaction with professional antigen-presenting cells, such as dendritic cells (DCs). We have investigated the capacity of distinct DC subsets to modulate iNKT cell functions. We demonstrate that tolerogenic DCs (tolDCs), generated by treatment of monocyte-derived DC with interleukin (IL)-10, induced regulatory functions in human iNKT cells. tolDCs, compared with immunogenic DCs, had reduced capacity to induce iNKT-cell proliferation, but these cells produced large amounts of IL-10 and acquired an anergic phenotype. These anergic Vα24+ iNKT cells were able to potently inhibit allogeneic CD4+ T-cell proliferation in vitro. Furthermore, the anergic Vα24+ iNKT cells could suppress DC maturation in vitro. We conclude that the interaction of iNKT cells with tolDCs plays an important role in the immune regulatory network, which might be exploited for therapeutic purposes.
Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia
Authors: Tomasson Michael H. , Xiang Zhifu , Walgren Richard , Zhao Yu , Kasai Yumi , Miner Tracie , Ries Rhonda E. , Lubman Olga , Fremont Daved H. , McLellan Michael D. , Payton Jacqueline E. , Westervelt Peter , DiPersio John F. , Link Daniel C. , Walter Matthew J. , Graubert Timothy A. , Watson Mark , Baty Jack , Heath Sharon , Shannon William D. , Nagarajan Rakesh , Bloomfield Clara D. , Mardis Elaine R. , Wilson Richard K. , Ley Timothy J.
Published: February 2008

Activating mutations in tyrosine kinase (TK) genes (eg, FLT3 and KIT) are found in more than 30% of patients with de novo acute myeloid leukemia (AML); many groups have speculated that mutations in other TK genes may be present in the remaining 70%. We performed high-throughput resequencing of the kinase domains of 26 TK genes (11 receptor TK; 15 cytoplasmic TK) expressed in most AML patients using genomic DNA from the bone marrow (tumor) and matched skin biopsy samples (“germline”) from 94 patients with de novo AML; sequence variants were validated in an additional 94 AML tumor samples (14.3 million base pairs of sequence were obtained and analyzed). We identified known somatic mutations in FLT3, KIT, and JAK2 TK genes at the expected frequencies and found 4 novel somatic mutations, JAK1V623A, JAK1T478S, DDR1A803V, and NTRK1S677N, once each in 4 respective patients of 188 tested. We also identified novel germline sequence changes encoding amino acid substitutions (ie, nonsynonymous changes) in 14 TK genes, including TYK2, which had the largest number of nonsynonymous sequence variants (11 total detected). Additional studies will be required to define the roles that these somatic and germline TK gene variants play in AML pathogenesis.
Red blood cells induce hypoxic lung inflammation
Authors: Kiefmann Rainer , Rifkind Joseph M. , Nagababu Enika , Bhattacharya Jahar
Published: February 2008

Hypoxia, which commonly associates with respiratory and cardiovascular diseases, provokes an acute inflammatory response. However, underlying mechanisms are not well understood. Here we report that red blood cells (RBCs) induce hypoxic inflammation by producing reactive oxygen species (ROS) that diffuse to endothelial cells of adjoining blood vessels. Real-time fluorescence imaging of rat and mouse lungs revealed that in the presence of RBC-containing vascular perfusion, hypoxia increased microvascular ROS, and cytosolic Ca2+, leading to P-selectin–dependent leukocyte recruitment. However, in the presence of RBC-free perfusion, all hypoxia-induced responses were completely inhibited. Because hemoglobin (Hb) autoxidation causes RBC superoxide formation that readily dismutates to H2O2, hypoxia-induced responses were lost when we inhibited Hb autoxidation with CO or nitrite, or when the H2O2 inhibitor, catalase was added to the infusion to neutralize the RBC-derived ROS. By contrast, perfusion with RBCs from BERK-trait mice that are more susceptible to Hb autoxidation and to hypoxia-induced superoxide production enhanced the hypoxia-induced responses. We conclude that in hypoxia, increased Hb autoxidation augments superoxide production in RBCs. Consequently, RBCs release H2O2 that diffuses to the lung microvascular endothelium, thereby initiating Ca2+-dependent leukocyte recruitment. These findings are the first evidence that RBCs contribute to hypoxia-induced inflammation.
Impact of clonal competition for peptide-MHC complexes on the CD8+ T-cell repertoire selection in a persistent viral infection
Authors: Wynn Katherine K. , Fulton Zara , Cooper Leanne , Silins Sharon L. , Gras Stephanie , Archbold Julia K. , Tynan Fleur E. , Miles John J. , McCluskey James , Burrows Scott R. , Rossjohn Jamie , Khanna Rajiv
Published: February 2008

CD8+ T-cell responses to persistent viral infections are characterized by the accumulation of an oligoclonal T-cell repertoire and a reduction in the naive T-cell pool. However, the precise mechanism for this phenomenon remains elusive. Here we show that human cytomegalovirus (HCMV)–specific CD8+ T cells recognizing distinct epitopes from the pp65 protein and restricted through an identical HLA class I allele (HLA B*3508) exhibited either a highly conserved public T-cell repertoire or a private, diverse T-cell response, which was uniquely altered in each donor following in vitro antigen exposure. Selection of a public T-cell receptor (TCR) was coincident with an atypical major histocompatibility complex (MHC)–peptide structure, in that the epitope adopted a helical conformation that bulged from the peptide-binding groove, while a diverse TCR profile was observed in response to the epitope that formed a flatter, more “featureless” landscape. Clonotypes with biased TCR usage demonstrated more efficient recognition of virus-infected cells, a greater CD8 dependency, and were more terminally differentiated in their phenotype when compared with the T cells expressing diverse TCR. These findings provide new insights into our understanding on how the biology of antigen presentation in addition to the structural features of the pMHC-I might shape the T-cell repertoire and its phenotype.
Analyzing the simplicial decomposition of spatial protein structures
Authors: Ördög Rafael , Szabadka Zoltán , Grolmusz Vince
Published: February 2008

Background

The fast growing Protein Data Bank contains the three-dimensional description of more than 45000 protein- and nucleic-acid structures today. The large majority of the data in the PDB are measured by X-ray crystallography by thousands of researchers in millions of work-hours. Unfortunately, lots of structural errors, bad labels, missing atoms, falsely identified chains and groups make dificult the automated processing of this treasury of structural biological data.

Results

After we performed a rigorous re-structuring of the whole PDB on graph-theoretical basis, we created the RS-PDB (Rich-Structure PDB) database. Using this cleaned and repaired database, we defined simplicial complexes on the heavy-atoms of the PDB, and analyzed the tetrahedra for geometric properties.

Conclusion

We have found surprisingly characteristic differences between simplices with atomic vertices of different types, and between the atomic neighborhoods – described also by simplices – of different ligand atoms in proteins.
Text-mining assisted regulatory annotation
Authors: Aerts Stein , Haeussler Maximilian , van Vooren Steven , Griffith Obi L , Hulpiau Paco , Jones Steven JM , Montgomery Stephen B , Bergman Casey M ,   The Open Regulatory Annotation Consortium
Published: February 2008

Background

Decoding transcriptional regulatory networks and the genomic cis-regulatory logic implemented in their control nodes is a fundamental challenge in genome biology. High-throughput computational and experimental analyses of regulatory networks and sequences rely heavily on positive control data from prior small-scale experiments, but the vast majority of previously discovered regulatory data remains locked in the biomedical literature.

Results

We develop text-mining strategies to identify relevant publications and extract sequence information to assist the regulatory annotation process. Using a vector space model to identify Medline abstracts from papers likely to have high cis-regulatory content, we demonstrate that document relevance ranking can assist the curation of transcriptional regulatory networks and estimate that, minimally, 30,000 papers harbor unannotated cis-regulatory data. In addition, we show that DNA sequences can be extracted from primary text with high cis-regulatory content and mapped to genome sequences as a means of identifying the location, organism and target gene information that is critical to the cis-regulatory annotation process.

Conclusion

Our results demonstrate that text-mining technologies can be successfully integrated with genome annotation systems, thereby increasing the availability of annotated cis-regulatory data needed to catalyze advances in the field of gene regulation.
De novo induction of antigen-specific CD4+CD25+Foxp3+ regulatory T cells in vivo following systemic antigen administration accompanied by blockade of mTOR
Authors: Kang Johnthomas , Huddleston Stephen J , Fraser Joanne M , Khoruts Alexander
Published: February 2008

Although regulatory CD4+CD25+ forkhead box p3+ (Foxp3+) T cells (Tregs) are generally thought to arise in the thymus as a separate lineage of CD4 T cells, they can also be induced de novo in the periphery. Peripheral development of Tregs from naïve T cells is favored by low-intensity activation and absence of inflammation. We show here that absence of CD28 costimulation results in a modest decrease in activation of naïve, antigen-specific CD4 T cells under noninflammatory conditions and benefits their initial Foxp3 induction. However, expression of Foxp3 following T cell activation without CD28 costimulation remains sensitive to the antigen dose. Furthermore, basal CD28 costimulation is critical for survival of the induced Foxp3+ CD4 T cells, and their accumulation is abrogated in the absence of CD28. In contrast, pharmacologic blockade of mammalian target of rapamycin enhances lasting induction of Tregs, irrespective of the initial antigen dose used to activate the antigen-specific T cells. This finding may have important practical, clinical implication in development of tolerance protocols.
Hypothalamic-Pituitary-Testicular Axis Disruptions in Older Men Are Differentially Linked to Age and Modifiable Risk Factors: The European Male Aging Study
Authors: Wu Frederick C. W. , Tajar Abdelouahid , Pye Stephen R. , Silman Alan J. , Finn Joseph D. , O'Neill Terence W. , Bartfai Gyorgy , Casanueva Felipe , Forti Gianni , Giwercman Aleksander , Huhtaniemi Ilpo T. , Kula Krzysztof , Punab Margus , Boonen Steven , Vanderschueren Dirk ,   The European Male Aging Study Group
Published: February 2008

Context: The cause of declining testosterone (T) in aging men and their relationships with risk factors are unclear.

Objective: The objective of the study was to investigate the relationships between lifestyle and health with reproductive hormones in aging men.

Design: This was a baseline cross-sectional survey on 3200 community-dwelling men aged 40–79 yr from a prospective cohort study in eight European countries.

Results: Four predictors were associated with distinct modes of altered function: 1) age: lower free T (FT; −3.12 pmol/liter·yr, P < 0.001) with raised LH, suggesting impaired testicular function; 2) obesity: lower total T (TT; −2.32 nmol/liter) and FT (−17.60 pmol/liter) for body mass index (BMI; ≥ 25 to < 30 kg/m2) and lower TT (−5.09 nmol/liter) and FT (−53.72 pmol/liter) for BMI 30 kg/m2 or greater (P < 0.001–0.01, referent: BMI < 25 kg/m2) with unchanged/decreased LH, indicating hypothalamus/pituitary dysfunction; 3) comorbidity: lower TT (−0.80 nmol/liter, P < 0.01) with unchanged LH in younger men but higher LH in older men; and 4) smoking: higher SHBG (5.96 nmol/liter, P < 0.001) and LH (0.77 U/liter, P < 0.01) with increased TT (1.31 nmol/liter, P < 0.001) but not FT, compatible with a resetting of T-LH-negative feedback due to elevated SHBG.

Conclusions: Complex multiple alterations in the hypothalamic-pituitary-testicular axis function exist in aging men against a background of progressive age-related testicular impairment. These changes are differentially linked to specific risk factors. Some risk factors operate independently of but others interact with age, in contributing to the T decline. These potentially modifiable risk factors suggest possible preventative measures to maintain T during aging in men.
Erectile Dysfunction in Patients with Hyper- and Hypothyroidism: How Common and Should We Treat?
Authors: Krassas Gerasimos E. , Tziomalos Kostas , Papadopoulou Fotini , Pontikides Nikolaos , Perros Petros
Published: February 2008

Context: Erectile dysfunction (ED) is associated with numerous diseases and aging.

Objective: The objective of the study was to investigate the impact of hyper- and hypothyroidism on male sexual health by using the Sexual Health Inventory for Males (SHIM).

Design: Seventy-one men, 27 hyper- and 44 hypothyroid and a similar number of controls were included in the study. A validated SHIM 5-item questionnaire was administered to all participants. Patients were asked to respond before and a year after initiation of treatment for thyroid dysfunction. A score between 25 and 22 is considered normal, between 21 and 11 diagnostic of mild to moderately severe ED, and 10 or less diagnostic of severe ED.

Results: Fifty-six men with thyroid dysfunction (78.9%; 19 hyperthyroid and 37 hypothyroid) had a SHIM score of 21 or less, compared with 24 controls (33.8%) (P < 0.0001). Twenty-one patients with ED (37.5%) had SHIM scores 10 or less, indicative of severe ED, compared with six controls (25%) (P < 0.01). ED was more prevalent in patients with hyperthyroidism and hypothyroidism, compared with controls (P < 0.001 and P < 0.0001, respectively). Positive correlation was found between SHIM scores and serum free T4 (r = 0.413, P = 0.005) and negative for TSH (r = −0.669, P < 0.001). After treatment a significant increase of SHIM scores was noted in both hyperthyroid (P < 0.0001) and hypothyroid (P < 0.0001) patients.

Conclusions: ED is extremely common in males with dysthyroidism. Treatment of the latter restores erectile function. Screening for thyroid dysfunction in men presenting with ED is recommended, whereas specific treatment for ED should be postponed in such patients for at least 6 months after achieving euthyroidism because the latter might be responsible for ED.
The hypopigmentary action of KI-063 (a new tyrosinase inhibitor) combined with terrein
Authors: Kim Dong-Seok , Lee Sangku , Lee Hyun-Kyung , Park Seo-Hyoung , Ryoo In-Ja , Yoo Ick-Dong , Kwon Sun-Bang , Baek Kwang Jin , Na Jung-Im , Park Kyoung-Chan
Published: February 2008

Resorcinol derivatives are known to inhibit melanin synthesis. In this study, resorcinol derivatives were synthesized and screened for their activity on melanogenesis. KI-063 (a tyrosinase inhibitor) was examined for its effects on melanogenesis using a spontaneously immortalized mouse melanocyte cell line (Mel-Ab). In a cell-free system, KI-063 directly inhibited tyrosinase, the rate-limiting melanogenic enzyme. Moreover, in a cell system, it inhibited melanin synthesis in a concentration-dependent manner. In addition, KI-063 inhibited the activity of cellular tyrosinase. Thus, this study examined the effects of a combination of KI-063 with terrein, an agent that down-regulates microphthalmia-associated transcription factor. The data suggest that KI-063 has an additive effect in combination with terrein. Thus, the suppression of tyrosinase activity by KI-063 and the inhibition of tyrosinase production by terrein appear to be an optimal combination for skin whitening.
Induction of apoptosis in human leukaemia HL-60 cells by furanone-coumarins from Murraya siamensis
Authors: Murata Tomiyasu , Itoigawa Masataka , Ito Chihiro , Nakao Keisuke , Tsuboi Masaru , Kaneda Norio , Furukawa Hiroshi
Published: February 2008

To identify potential anti-tumour agents, we screened five furanone-coumarins isolated from Murraya siamensis Craib (Rutaceae) for their ability to inhibit the growth of human leukaemia HL-60 cells. Among the furanone-coumarins tested, murrayacoumarin B (compound 2) showed significant cytotoxicity against HL-60 cells. Fluorescence microscopy with Hoechst 33342 staining revealed that the percentage of apoptotic cells with fragmented nuclei and condensed chromatin increased in a time-dependent manner after treatment with murrayacoumarin B. Interestingly, this furanone-coumarin induced the loss of the mitochondrial membrane potential. In addition, treatment with murrayacoumarin B stimulated the activities of caspase-9 and caspase-3, and caspase-9 and caspase-3 inhibitors suppressed the apoptosis induced by murrayacoumarin B. These results suggest that murrayacoumarin B induced apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway triggered by mitochondrial dysfunction.
Schisandrin B from Schisandra chinensis reduces hepatic lipid contents in hypercholesterolaemic mice
Authors: Pan Si-Yuan , Dong Hang , Zhao Xing-Ye , Xiang Chun-Jing , Fang Hai-Yan , Fong Wang-Fun , Yu Zhi-Ling , Ko Kam-Ming
Published: February 2008

The effects of schisandrin B (Sch B) on liver and serum lipid contents were investigated in mice with experimentally-induced hypercholesterolaemia. Hypercholesterolaemia was induced either by oral administration of a cholesterol/bile salts mixture (2/0.5 g kg−1) for four days or by feeding a high fat/cholesterol/bile salts (10/1/0.3%, w/w) diet for seven days. Daily co-administration of Sch B (50–200 mg kg−1, i.g.) for four or six days, respectively, decreased hepatic total cholesterol (TC) and triglyceride (TG) levels (by up to 50% and 52%, respectively) in hypercholesterolaemic mice. Sch B treatment also increased hepatic indices (14–84%) in hypercholesterolaemic mice. The results indicated that Sch B treatment could decrease hepatic TC and TG levels, and increase liver weight, in mouse models of hypercholesterolaemia. Fenofibrate treatment (100 mg kg−1) produced effects similar to those of Sch B on the hepatic index and lipid levels of hypercholesterolaemic mice.
Mechanisms underlying p53 regulation of PIK3CA transcription in ovarian surface epithelium and in ovarian cancer
Authors: Astanehe Arezoo , Arenillas David , Wasserman Wyeth W. , Leung Peter C. K. , Dunn Sandra E. , Davies Barry R. , Mills Gordon B. , Auersperg Nelly
Published: February 2008

Inactivation of the transcription factor and tumor suppressor p53, and overexpression or mutational activation of PIK3CA, which encodes the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K), are two of the most common deleterious genomic changes in cancer, including in ovarian carcinomas. We investigated molecular mechanisms underlying interactions between these two mediators and their possible roles in ovarian tumorigenesis. We identified two alternate PIK3CA promoters and showed direct binding of and transcriptional inhibition by p53 to one of these promoters. Conditional suppression of functional p53 increased p110α transcripts, protein levels and PI3K activity in immortalized, non-tumorigenic ovarian surface epithelial (OSE) cells, the precursors of ovarian carcinoma. Conversely, overexpression of p53 by adenoviral infection and activation of p53 by γ-irradiation both diminished p110α protein levels in normal OSE and ovarian cancer cells. The demonstration that p53 binds directly to the PIK3CA promoter and inhibits its activity identifies a novel mechanism whereby these two mediators regulate cellular functions, and whereby inactivation of p53 and subsequent upregulation of PIK3CA might contribute to the pathophysiology of ovarian cancer.
Design of a Command Shaper for Vibration Control of Flexible Systems: A Genetic Algorithm Optimisation Approach
Authors: Alam M. S. , Tokhi M. O.
Published: February 2008

This paper presents investigations into the design of a command-shaping technique for vibration control of flexible structure systems using genetic algorithms (GAs). Designing a command shaper requires a priori knowledge about the damping ratio and natural frequency of the system, which may not be available for complex flexible systems. Moreover, the amount of vibration reduction and response rise-time are usually in conflict with one another in most flexible systems due to their construction and modes of operation. Conventional methods can hardly provide a solution satisfying several objectives as demanded by a practical application due to the competing nature of these objectives. Assuming that the system parameters are unknown, GAs are used to determine the optimum amplitudes and corresponding time-locations of impulses that are convolved with the reference input to form the shaped command. A new objective function based on weighted sum approach is proposed that provides good solution within single-objective GA formulation and trades-off between these two objectives. In order to maintain and enhance diversity in the population and hence to improve search capability of the conventional GA, a new algorithm is also proposed in this work. Initially this algorithm works as a traditional GA then some individuals are replaced periodically based on shared fitness values in order to maintain diversity in the population set. A scaled and simplified version of practical helicopter is used as the experimental flexible set-up. The effectiveness of the control strategy is assessed in terms of controller performance on the test rig in vibration suppression, mainly, at dominant modes.
Compression Wave Generated by a High-Speed Train Entering a Tunnel Fitted with a Hood with a Long Slit Window
Authors: Iida M. , Howe M.S.
Published: February 2008

An investigation is made of the use of long, slit-like windows in the wall of a rectangular, tunnel-entrance hood to suppress the harmful environmental impact of the compression wave produced as a high-speed train enters a long tunnel. Model scale testing and numerical simulation indicate that when the cross-sectional area of the hood is larger than that of the tunnel, optima reduction in the maximum compression wave pressure gradient is achieved when the width of the slit window decreases inwards from the hood entrance, and when total length of the slit is no more than about 80% of the hood length. For a ‘low hood’ whose cross-sectional area is close to that of the tunnel, a more nearly optimal behaviour is furnished by a long uniform slit that extends over the whole length of the hood.
Parameter Identification and Damage Detection Using Structural Optimization and Static Response Data
Authors: Terlaje Augusto S. , Truman Kevin Z.
Published: February 2008

A new parameter identification method and algorithm will be presented that utilizes structural optimization concepts to correctly identify the stiffness in linear elastic models of civil structures. Displacement measurements resulting from applied static point loads are used as constraints in an optimization algorithm that employs optimality criterion methods to extract the cross sectional properties of elements within a mathematical model of a structure. Through simulated examples the algorithm will correctly identify stiffness parameters in a 10-bar truss structure and a two bay, two story moment frame. Once the parameter identification process has been illustrated in each example, the same algorithm and procedure is used to detect areas of simulated damage. Changes in the cross sectional properties of elements in the mathematical model of the structure are used to locate and quantify damage. Changes in cross section are used to simulate damage such as brittle fracture of steel members, spalling of concrete structures, and decay of wood structures. Lastly, the effects of measurement error on the damage detection results will be explored.
Advantages of Bi-Directional Evolutionary Structural Optimization (BESO) over Evolutionary Structural Optimization (ESO)
Authors: Huang X. , Xie Y. M. , Burry M. C.
Published: February 2008

The evolutionary structural optimization (ESO) method evolves a structure from the full design domain towards an optimum by gradually removing inefficient material. The bi-directional ESO (BESO) may start from any initial design and evolve a structure to an optimum by adding and removing material simultaneously. In this paper, a detailed comparison between ESO and BESO has been carried out for stiffness optimization problems. Both 2D and 3D examples shows that the BESO method possesses many advantages over the ESO method such as computational efficiency, robustness of the method and manufacturability of the final topology.
Optimum Geometry Design of Geodesic Domes Using Harmony Search Algorithm
Authors: Saka M. P.
Published: February 2008

The optimum geometry design of geodesic domes presents difficulty due to the fact that the height of the dome keeps on changing during the design process. This in turn makes it necessary to automate the computation of the coordinates of joints in the dome when the height of crown changes. The algorithm presented in this study carries out the optimum geometry design of single layer geodesic domes. It treats the height of the crown as design variable in addition to the cross-sectional designations of members. A procedure is developed that calculates the joint coordinates automatically for a given height of the crown. The serviceability and strength requirements are considered in the design problem as specified in BS5950–2000. This code makes use of limit state design concept in which structures are designed by considering the limit states beyond which they would become unfit for their intended use. This new addition contains revisions adopting European and international standards for materials, processes and loading. BS 5950 is adopted by many commonwealth countries as their steel design code. The optimum solution of the design problem is obtained using harmony search algorithm. This numerical technique imitates the musical performance process that takes place when a musician searches for a better state of harmony. Jazz improvisation seeks to find musically pleasing harmony similar to the optimum design process which seeks to find the optimum solution. The design examples considered have shown that harmony search algorithm obtains the optimum height and sectional designations for members in relatively less number of searches.
Topology Optimization of Multi-Loaded Structures with Mixed Finite Elements
Authors: Bruggi Matteo , Cinquini Carlo
Published: February 2008

The paper presents a topology optimization formulation that uses mixed-finite elements, here specialized for the design of multi-loaded structures. The discretization scheme adopts stresses as primary variables in addition to displacements which usually are the only variables considered. Two dual variational formulations based on the Hellinger-Reissner variational principle are presented in continuous and discrete form. The use of the mixed approach coupled with the choice of nodal densities as optimization variables of the topology problem lead to 0–1 checkerboard-free solutions even in the case of multi-loaded structures design. The method of moving asymptotes (MMA) by Svanberg (1984) is adopted as minimization algorithm. Numerical examples are provided to show the capabilities of the presented method to generate families of designs responding to different requirements depending on stiffness criteria for common structural multi-load problems. Finally the ongoing research concerning the presence of stress constraints and the optimization of incompressible media is outlined.
Optimal Design System Using Finite Element Package as the Analysis Engine
Authors: Leu L.J. , Lee C.H.
Published: February 2008

This paper is concerned with the development of an optimal design system using FE (Finite Element) package as the analysis engine. There are four main challenges when designing and implementing the system including execution of FE package, extraction of the FE analysis results, modification of the FE model, and linking of function evaluation of an optimal design problem with the FE analysis result. In order to develop a general-purpose and highly flexible optimal design system, modern software technologies including OO (Object-oriented) technology, design patterns and UML (Unified Modeling Language) diagrams are adopted. Various numerical examples demonstrate the proposed system is indeed powerful and can be used to solve complex optimal design problems such as plates, shells and nonlinear problems.
Analytical Shape and Thickness Sensitivities of Linear Shells
Authors: Petchsasithon A. , Gosling P. D.
Published: February 2008

This paper describes an efficient method to calculate sensitivity of shell structures. Sensitivity parameters of interest are shape and thickness of shell structures. An 18-node hexahedral shell is used in element formulation with inclusion of proposed methodologies to alleviate various locking phenomena. Automatic mesh generation scheme using the design element concept and isoparametric technique is employed to avoid re-meshing structures every iteration of optimization process. Numerical examples are performed and compared with exact solutions and forward finite differences to investigate the accuracy of proposed element formulation and sensitivity analysis.
Analysis and Design Optimization of Axially Moving Structures with Stability Constraint under Wind Excitations
Authors: Wang Yuefang , Lü Lefeng , Huang Lihua
Published: February 2008

This paper presents the stability problem of equilibrium configuration of axially moving strings with small sag-to-span ratios under wind excitations. The Galerkin approach is adopted for reduction of the string as a 4-degree-of-freedom system. The flutter instability is investigated based on the Routh-Hurwitz criterion after linearization at the equilibrium configuration of the string. Closed form conditions are presented for loss of stability and generation of limit cycles via the single and double Hopf bifurcations. To improve the operation stability the design optimization is performed to maximize the critical wind speed that may further lead to the flutter instability. Using the Relative Differential Method, the tensile rigidity and the transport speed are optimized considering the Hopf bifurcation constraints of the equilibrium. With the optimal design, the critical wind speed is maximized and the chance for the flutter instability toward the limit cycle response is reduced to the largest extent.
Obsessive compulsive symptoms and the simulation of future negative events
Authors: Keen Nadine , Brown Gary P. , Wheatley Jonathan
Published: February 2008

Objectives

To explore whether Kahneman and Tversky's (1982) simulation heuristic might help account for why the obsessions of people with obsessive compulsive disorder (OCD) are so compelling to them. It was predicted that participants would be better able to simulate a scenario relevant to a central OCD fear than they would scenarios related to other OCD and non‐OCD fears and that how well participants simulated feared scenarios would be associated with higher ratings of subjective probability for that outcome and consequently greater worry.

Design

Individuals with obsessive compulsive symptoms mentally simulated hypothetical scenarios so as to enable comparison of a personally relevant to less relevant scenarios.

Methods

Thirty participants recruited from OCD support groups simulated four scenarios each and completed symptom and relevant construct measures.

Results

Personally relevant scenarios were better simulated than less relevant scenarios. ‘Goodness of simulation’ (GOS) was related to worry about the feared outcome, but this was not mediated by raised subjective probabilities. GOS correlated with OCD symptomatology, anxiety, and depression but not with cognitive variables thought to be related to OCD phenomenology.

Conclusion

The overall findings converge with recent literature (O'Connor, 2002) emphasizing the importance of imagination and imaginary narratives in fuelling OCD symptoms.
Activity-Induced Synaptic Capture and Exocytosis of the Neuronal Serine Protease Neurotrypsin
Authors: Frischknecht Renato , Fejtova Anna , Viesti Miriam , Stephan Alexander , Sonderegger Peter
Published: February 2008

Extracellular proteolysis plays an essential role in synaptic remodeling that is indispensable for cognitive function. The extracellular serine protease neurotrypsin was implicated in cognitive function, because humans lacking a functional form of neurotrypsin suffer from severe mental retardation. By immunoelectron microscopy, neurotrypsin has been localized to presynaptic terminals, suggesting a local proteolytic function after its synaptic release. Here, we studied axonal trafficking and synaptic exocytosis of neurotrypsin by live imaging of hippocampal neurons expressing neurotrypsin fused with enhanced green fluorescent protein or its pH-sensitive variant, superecliptic pHluorin. In differentiated neurons, we identified neurotrypsin in mobile transport vesicles along axons and in both an intracellular and an extracellular pool at synapses. Short depolarization triggered rapid synaptic exocytosis of neurotrypsin. Once externalized, neurotrypsin lingered at its synaptic release site for several minutes before it disappeared. Cell depolarization also enhanced synaptic capture of intracellular neurotrypsin transport vesicles, and elevated synaptic activity increased both number and motility of mobile axonal neurotrypsin vesicles. We further observed trading of neurotrypsin vesicles between adjacent synapses. These activities may support the replenishment of neurotrypsin after activity-induced synaptic exocytosis. Together, the activity-dependent recruitment of neurotrypsin to synapses and its exocytosis and transient persistence at its synaptic release site argue for a spatially and temporally restricted proteolytic action at the synapse. Thereby, neurotrypsin may play a role in activity-dependent remodeling of the synaptic circuitry that is key to adaptive synaptic changes in the context of cognitive functions, such as learning and memory.
Chemokine Signaling Controls Intracortical Migration and Final Distribution of GABAergic Interneurons
Authors: López-Bendito Guillermina , Sánchez-Alcañiz Juan Antonio , Pla Ramón , Borrell Víctor , Picó Esther , Valdeolmillos Miguel , Marín Oscar
Published: February 2008

Functioning of the cerebral cortex requires the coordinated assembly of circuits involving glutamatergic projection neurons and GABAergic interneurons. Although much is known about the migration of interneurons from the subpallium to the cortex, our understanding of the mechanisms controlling their precise integration within the cortex is still limited. Here, we have investigated in detail the behavior of GABAergic interneurons as they first enter the developing cortex by using time-lapse videomicroscopy, slice culture, andin uteroexperimental manipulations and analysis of mouse mutants. We found that interneurons actively avoid the cortical plate for a period of ∼48 h after reaching the pallium; during this time, interneurons disperse tangentially through the marginal and subventricular zones. Perturbation of CXCL12/CXCR4 signaling causes premature cortical plate invasion by cortical interneurons and, in the long term, disrupts their laminar and regional distribution. These results suggest that regulation of cortical plate invasion by GABAergic interneurons is a key event in cortical development, because it directly influences the coordinated formation of appropriate glutamatergic and GABAergic neuronal assemblies.