bluuebunny/crossref_metadata_2025 huggingface dataset:
The Information Revolution, Security, and International Relations: (IR)relevant Theory?
Authors: Eriksson Johan , Giacomello Giampiero
Published: August 2006

The purpose of this article is twofold: to analyze the impact of the information revolution on security and to clarify what existing international relations theory can say about this challenge. These pertinent questions are initially addressed by a critical review of past research. This review shows that the concern for security issues is largely confined to a specialist literature on information warfare and cyber-security, while neither the general literature on information society nor security studies pay any serious attention to information-technology-related security issues. The specialist literature is mostly policy oriented, and only very rarely informed by theory, whether from the international relations discipline or any other field. In this article, three general international relations “schools” (realism, liberalism, and constructivism) are scrutinized with regard to what they can say about security in the digital age. It is argued that the liberal focus on pluralism, interdependence, and globalization, the constructivist emphasis on language, symbols, and images (including “virtuality”), and some elements of realist strategic studies (on information warfare) contribute to an understanding of digital-age security. Finally, it is suggested that pragmatism might help to bridge the gap between theory and practice, and overcome the dualistic, contending nature of international relations theories.
Access by Accident: Legitimacy Claims and Democracy Promotion in Authoritarian Central Asia
Authors: Schatz Edward
Published: August 2006

The adjective “authoritarian” to describe political regimes obscures much variety. What makes some regimes “soft” authoritarian and others “hard?” This article suggests that the involvement of democracy advocates helps to drive variation in Central Asia's authoritarian regimes. The role that these advocates play in the region, in turn, may be traced in part to unintended consequences. Specifically, elites made early choices about how to frame the legitimacy of the state, which, in turn, set the parameters for their maneuver in subsequent political transformations.
The punk cut
Authors: Sinapi Michèle
Published: August 2006

The punk movement, seen through its “riddle-like” texts, appears as a thoroughly singular and eminently political moment. Acting as an echo-chamber for a certain number of former cultural events such as Dadaism, or more contemporary ones such as Anglo-American psychoanalysis, this movement, closely attuned to post-war mutations, invented a number of minimalist formal means that managed to enact the collapse of ideals without succumbing to nihilism. Turning their backs on ideology of every stripe, the punks radicalized cultural criticism and held out a mirror to British (and European) society in considering the key political question of the post-war era: do states still possess some kind of legitimacy? How are we to cope with institutional nihilism? And with the contradictory injunctions of the post-Nazi era?
The philosophical implications of research on the social representations of human rights
Authors: Gély Raphaël , Sanchez-Mazas Margarita
Published: August 2006

The aim of this article is to show how human rights can be the object of another politics than the one Marcel Gauchet denounces as an “egalitarian ethnocentrism” and regards as grounding a “democratic counter-productivity”. Drawing upon the research developed by Willem Doise and his colleagues, we show that human rights, when they become social representations, rather than generating a society of undifferentiated individuals, allow the individual and collective differences to position themselves around a common stake. In this sense, the construction of shared social representations is an essential condition for the democratization process in our societies. We show how the use of human rights in the context of the French quarrel over the Muslim hijab has contributed to a gradual transformation of human rights into practical and representational matrices for the development of a truly democratic debate. Finally, the article addresses the need to reflect upon the conditions allowing the establishment of these social representations.
Utilization of social science knowledge in science policy: Systems of Innovation, Triple Helix and VINNOVA
Authors: Jacob Merle
Published: August 2006

The objective of this article is to analyse the utilization of two academic narratives about innovation policy in policy discourse by examining the policy statements issued by one Swedish agency that was specifically set up to promote innovation policy, the Swedish Agency for Innovation Systems, VINNOVA. The main findings of this analysis show that the deployment of the examined academic narratives in policy discourse is not accidental nor is it only limited to a role of legitimating policy decisions. The article shows that although the linear model of knowledge transfer has long been discredited, the notion of knowledge utilization is still useful to policy analysis and may be successfully deployed to understand what lies behind the assertions of mutual interplay between science and policy that characterize contemporary attempts to depict this relation.
Adorno and Mass Culture: Autonomous Art Against the Culture Industry
Authors: Markus György
Published: August 2006

Adorno’s extended conception of ‘culture industry’ renders the usual criticism of his views as ‘elitist’ meaningless. The same expansion creates, however, logical strains and contradictions in his analysis of the character and function of the culture industry: a strain in its ‘psychosocial’ and ‘status compulsion’ interpretation. In his late work Adorno attempts to solve this contradiction, but at a heavy price, by creating a conceptual barrier between pleasure and happiness.
Nonlinear Transient Analysis of Laminated Composite Shells
Authors: Kundu C. K. , Sinha P. K.
Published: August 2006

In this study the geometrically nonlinear transient response of the laminated composite doubly curved shells is investigated using the finite element method. The finite element model includes nonlinearity due to large deflection. A nine-noded isoparametric composite shell element including the first-order shear deformation is developed in curvilinear coordinates for the nonlinear transient analysis. The present formulation is based on the total Lagrangian approach and the material behavior is assumed to be linear and elastic. The governing equations have been solved by the Newton–Raphson iteration technique, wherein the Newmark method has been used for the time integration. The present results are found to compare well with those available in the literature. The nonlinear transient response of the cross-ply and three specially laminated spherical, cylindrical, and hyperbolic paraboloidal shell panels are also analyzed and the results are discussed.
Flow Visualization of Solder Ball Arrangement for Underfill Encapsulation of Flip Chip
Authors: Shen Y. K. , Lin P. T. , Yeh S. W.
Published: August 2006

The flip chip package has the advantages of low cost, low interface, and small volume in IC package. This study describes the analysis of underfill encapsulation between solder balls and microchip by experiment and 3D numerical simulation. The numerical simulation of underfill encapsulation is based on the concept of the control volume finite element method. The parameters of injection situation are used for central point, one line, L-line, and U-line injection types. The different processing parameters (solder ball arrangement, injection pressure, solder ball size, and injection situation) are used for underfill encapsulation. The results show that the free surface shape of the experiment is closer to that of the 3D numerical simulation on the plane flow situation for underfill encapsulation. The injection situation of L-line is the best underfill encapsulation of flip chip irrespective of the different arrangement of solder ball and size of the solder ball. The flow time has the biggest value for the different size of solder ball on an alternate arrangement of the solder ball. The flow time decreases as injection pressure increases. The free surface on the thickness direction is concave for the underfill process of the experiment. The contact angle of the free surface is the same for different injection pressures in underfill encapsulation. This situation indicates that the capillary effect dominates the flow situation in the underfill process.
Contextualizing the Criminal Justice Policy-Making Process
Authors: Ismaili Karim
Published: August 2006

This article is an attempt at improving the knowledge base on the criminal justice policy-making process. As the criminological subfield of crime policy leads more criminologists to engage in policy analysis, understanding the policy-making environment in all of its complexity becomes more central to criminology. This becomes an important step toward theorizing the policy process. To advance this enterprise, policy-oriented criminologists might look to theoretical and conceptual frameworks that have established histories in the political and policy sciences. This article presents a contextual approach to examine the criminal justice policy-making environment and its accompanying process. The principal benefit of this approach is its emphasis on addressing the complexity inherent to policy contexts. For research on the policy process to advance, contextually sensitive methods of policy inquiry must be formulated and should illuminate the social reality of criminal justice policy making through the accumulation of knowledge both of and in the policy process.
The Role of Policy Transfer in Assessing the Impact of American Ideas on British Social Policy
Authors: Hulme Rob
Published: August 2006

This article assesses the contribution of existing work on policy transfer to our understanding of policy change on the international stage. It explores the impact of American ideas and practices on aspects of social policy in the UK. It argues for a focus on the role of ‘epistemic communities’ and policy learning in the development of generic international agendas such as the ‘Americanized medical model’ of evidence-based practice adopted by the New Labour government in health and education. It argues that international social policy analysis should take account of the movement of ideas and practices at three levels: global/international, national and inter-organizational.
The Dubious Inheritance of Touch: Art History and Museum Access
Authors: Candlin Fiona
Published: August 2006

Numerous museums and galleries now offer tactile opportunities as part of their access provision. This article asks why touch is deemed to be more accessible than vision as a way of learning about art and what repercussions that has for blind and visually impaired audiences. While touch has been discussed in many different contexts, touch also has a specifically art historical lineage where it is characterized in predominantly pejorative terms. This then raises serious questions concerning the use of touch within contemporary access provision: is touch used in access provision because it is considered to be more basic, easier than seeing? Does touch remain an adjunct to vision, a lesser, substitutive form of seeing? Alternatively, are art historical stereotypes so outdated that they are irrelevant for current museum practice? In which case does access provision show touch to be a qualitatively different route to knowledge? And, if this is not the case, how can we start to construct a model of touch that interlinks with vision without being subsumed by it, where touch concerns thought as well as feeling?
At the Limits of Living: To Joseph Grigely
Authors: Kristeva Julia
Published: August 2006

This article draws attention to the singular exclusion suffered by people with disabilities. It argues not for the procedural integration of the disabled subject within Western society, but calls for a mutual interaction -a rebirth of our thinking -to take place between those with disabilities and the community to which they belong. Discussing her motivation to accept the role of Chair of the National Disability Council in France, as well as her conversation with American artist Joseph Grigely, Kristeva argues that the objectification of the disabled subject within consumerist contexts is best dismantled via a psychoanalytic ‘ear’. This attentiveness, attuned to the vulnerability shared by all speaking bodies, links shared experiences as well as recognizes - without trying to integrate - the irreparable in all subjects. The full political significance of psychoanalysis can thus be realized not by psychoanalysing all, but by working to create real, rather than well-meaning, interactions with others.
‘The body does not lie’: Identity, risk and trust in technoculture
Authors: Aas Katja Franko
Published: August 2006

The article suggests that surveillance of the body is gradually becoming a major source of identification, as well as a vital element of late-modern mechanisms of social exclusion. The increasing demand for technological verification of identity is a result of intricate connections between our notions of the self, order, efficiency and security. Behind the growing acceptance of these new technologies, such as biometric passports, biometric ID cards, drug testing, and DNA databases, are fears connected to those who may have a ‘stolen identity’, are unidentified, or ‘identity-less’, such as potentially fraudulent welfare recipients, ‘identity thieves’, terrorists, immigrants and asylum seekers. However, unlike Foucault's disciplinary power, the latest technologies no longer see the body as something that needs to be trained and disciplined, but rather as a source of unprecedented accuracy and precision. Bodies become ‘coded’ and function as ‘passwords’. This form of identification is particularly relevant since its mode of operation enables identification and denial of access at-a-distance, thus fitting perfectly into the contemporary modes of disembedded global governance.
Framing homicide narratives in newspapers: Mediated witness and the construction of virtual victimhood
Authors: Peelo Moira
Published: August 2006

This article identifies ways in which newspapers invite readers to identify with victims and victimhood as a route to engaging them in ‘human interest’ stories. Within this framing of homicide for readers as ‘mediated witness’, some of the authorial techniques are explored whereby newspapers engage readers in a stylized dialogue that contributes to the construction of public narratives about homicide. It is argued that researchers, as well as working at a macro level, need to research at the micro level of textual analysis when researching media (including visual media) in order to understand the framing that contributes to public narratives; hence there is analysis of techniques of (a) defamiliarization and (b) objectification of homicide victims. These are some of the means by which the reader is placed as witness, both apparently ‘experiencing’ crime for personal consumption yet, publicly, allowed to recover (unlike real victims of major crime). The recognition of a need for micro-level analysis raises questions about the functions of public narratives, particularly in expressing, exploring and containing public or social emotion, in an era in which public responses to crime have been placed at the top of a highly politicized crime agenda.
Mechanism for fetal hemoglobin induction by histone deacetylase inhibitors involves γ-globin activation by CREB1 and ATF-2
Authors: Sangerman Jose , Lee Moo Seung , Yao Xiao , Oteng Eugene , Hsiao Cheng-Hui , Li Wei , Zein Sima , Ofori-Acquah Solomon F. , Pace Betty S.
Published: August 2006

The histone deacetylase inhibitors (HDA-CIs) butyrate and trichostatin A activate γ-globin expression via a p38 mitogen-activating protein kinase (MAPK)-dependent mechanism. We hypothesized that down-stream effectors of p38 MAPK, namely activating transcription factor-2 (ATF-2) and cyclic AMP response element (CRE) binding protein (CREB), are intimately involved in fetal hemoglobin induction by these agents. In this study, we observed increased ATF-2 and CREB1 phosphorylation mediated by the HDACIs in K562 cells, in conjunction with histone H4 hyperacetylation. Moreover, enhanced DNA-protein interactions occurred in the CRE in the Gγ-globin promoter (G-CRE) in vitro after drug treatments; subsequent chromatin immunoprecipitation assay confirmed ATF-2 and CREB1 binding to the G-CRE in vivo. Enforced expression of ATF-2 and CREB produced Gγ-promoter trans-activation which was abolished by a 2-base pair mutation in the putative G-CRE. The data presented herein demonstrate that γ-gene induction by butyrate and trichostatin A involves ATF-2 and CREB1 activation via p38 MAPK signaling.
Immune competence of cancer-reactive T cells generated de novo in adult tumor-bearing mice
Authors: May Kenneth F. , Lute Kenneth , Kocak Ergun , Abdessalam Shahab , Yin Lijie , Li Ou , Guan Zhen , Philips Gary , Zheng Pan , Liu Yang
Published: August 2006

The impact of timing of antigen introduction into fetus and neonates leads to the suggestion that pre-existing antigens are tolerogenic to immunocompetent cells generated thereafter. This hypothesis predicts that in patients with cancer who are undergoing bone marrow transplantation, newly produced T cells with specificity for pre-existing tumor cells will be inactivated by the tumor antigens in the host. Because the effect of tumor cells on developing cancer-reactive T cells has not been investigated, we set out to systematically analyze the impact of tumor cells in the periphery on the development of tumor-reactive T cells in the thymus and their immunocompetence in the periphery. Our data demonstrate that in the host in which a tumor is established in the periphery, the cancer-reactive T cells develop normally, remain fully immunocompetent, become activated in the periphery, and cause regression of large established tumors. The immunocompetence of T cells generated in an antigen-bearing host is also confirmed in a skin graft transplantation model.
Involvement of suppressors of cytokine signaling in toll-like receptor–mediated block of dendritic cell differentiation
Authors: Bartz Holger , Avalos Nicole M. , Baetz Andrea , Heeg Klaus , Dalpke Alexander H.
Published: August 2006

Dendritic cells (DCs) are important sentinels within innate immunity, monitoring the presence of infectious microorganisms. They operate in 2 different maturation stages, with transition from immature to mature DCs being induced by activation of toll-like receptors (TLRs). However, TLRs are also expressed on precursor cells of DCs. Here we analyzed the effects of TLR stimulation during the process of granulocyte-macrophage–colony-stimulating factor (GM-CSF)–mediated in vitro generation of immature DCs from precursor cells. We show that TLR triggering deviated phenotypic and functional differentiation from CD14+ monocytes to CD1a+ DCs. Similar results were obtained when differentiation of murine myeloid DCs from bone marrow cells was analyzed. The inhibitory effects were independent of soluble factors. TLR stimulation in DC precursor cells induced proteins of the suppressor of cytokine signaling family (SOCS), which correlated with loss of sensitivity to GM-CSF. Overexpression of SOCS-1 abolished GM-CSF signal transduction. Moreover, forced SOCS-1 expression in DC precursors mimicked the inhibitory effects on DC generation observed for TLR stimulation. The results indicate that TLR stimulation during the period of DC generation interferes with and deviates DC differentiation and that these effects are mediated particularly by SOCS-1.
Comparative evolutionary genomics of the HADH2 gene encoding Aβ-binding alcohol dehydrogenase/17β-hydroxysteroid dehydrogenase type 10 (ABAD/HSD10)
Authors: Marques Alexandra T , Antunes Agostinho , Fernandes Pedro A , Ramos Maria J
Published: August 2006

Background

The Aβ-binding alcohol dehydrogenase/17β-hydroxysteroid dehydrogenase type 10 (ABAD/HSD10) is an enzyme involved in pivotal metabolic processes and in the mitochondrial dysfunction seen in the Alzheimer's disease. Here we use comparative genomic analyses to study the evolution of the HADH2 gene encoding ABAD/HSD10 across several eukaryotic species.

Results

Both vertebrate and nematode HADH2 genes showed a six-exon/five-intron organization while those of the insects had a reduced and varied number of exons (two to three). Eutherian mammal HADH2 genes revealed some highly conserved noncoding regions, which may indicate the presence of functional elements, namely in the upstream region about 1 kb of the transcription start site and in the first part of intron 1. These regions were also conserved between Tetraodon and Fugu fishes. We identified a conserved alternative splicing event between human and dog, which have a nine amino acid deletion, causing the removal of the strand βF. This strand is one of the seven strands that compose the core β-sheet of the Rossman fold dinucleotide-binding motif characteristic of the short chain dehydrogenase/reductase (SDR) family members. However, the fact that the substrate binding cleft residues are retained and the existence of a shared variant between human and dog suggest that it might be functional. Molecular adaptation analyses across eutherian mammal orthologues revealed the existence of sites under positive selection, some of which being localized in the substrate-binding cleft and in the insertion 1 region on loop D (an important region for the Aβ-binding to the enzyme). Interestingly, a higher than expected number of nonsynonymous substitutions were observed between human/chimpanzee and orangutan, with six out of the seven amino acid replacements being under molecular adaptation (including three in loop D and one in the substrate binding loop).

Conclusion

Our study revealed that HADH2 genes maintained a reasonable conserved organization across a large evolutionary distance. The conserved noncoding regions identified among mammals and between pufferfishes, the evidence of an alternative splicing variant conserved between human and dog, and the detection of positive selection across eutherian mammals, may be of importance for further research on ABAD/HSD10 function and its implication in the Alzheimer's disease.
Genomic structure and expression of uncoupling protein 2 genes in rainbow trout (Oncorhynchus mykiss)
Authors: Coulibaly Issa , Gahr Scott A , Palti Yniv , Yao Jianbo , Rexroad Caird E
Published: August 2006

Background

Uncoupling protein 2 (UCP2) belongs to the superfamily of mitochondrial anion carriers that dissociate the respiratory chain from ATP synthesis. It has been determined that UCP2 plays a role in several physiological processes such as energy expenditure, body weight control and fatty acid metabolism in several vertebrate species. We report the first characterization of UCP2 s in rainbow trout (Oncorhynchus mykiss).

Results

Two UCP2 genes were identified in the rainbow trout genome, UCP2A and UCP2B. These genes are 93% similar in their predicted amino acid sequences and display the same genomic structure as other vertebrates (8 exons and 7 introns) spanning 4.2 kb and 3.2 kb, respectively. UCP2A and UCP2B were widely expressed in all tissues of the study with a predominant level in macrophage-rich tissues and reproductive organs. In fry muscle we observed an increase in UCP2B expression in response to fasting and a decrease after refeeding in agreement with previous studies in human, mouse, rat, and marsupials. The converse expression pattern was observed for UCP2A mRNA which decreased during fasting, suggesting different metabolic roles for UCP2A and UCP2B in rainbow trout muscle. Phylogenetic analysis including other genes from the UCP core family located rainbow trout UCP2A and UCP2B with their orthologs and suggested an early divergence of vertebrate UCPs from a common ancestor gene.

Conclusion

We characterized two UCP2 genes in rainbow trout with similar genomic structures, amino acid sequences and distribution profiles. These genes appeared to be differentially regulated in response to fasting and refeeding in fry muscle. The genomic organization and phylogeny analysis support the hypothesis of a common ancestry between the vertebrate UCPs.
How are health professionals earning their living in Malawi?
Authors: Muula Adamson S , Maseko Fresier C
Published: August 2006

Background

The migration of health professionals from southern Africa to developed nations is negatively affecting the delivery of health care services in the source countries. Oftentimes however, it is the reasons for the out-migration that have been described in the literature. The work and domestic situations of those health professionals continuing to serve in their posts have not been adequately studied.

Methods

The present study utilized a qualitative data collection and analysis method. This was achieved through focus group discussions and in-depth interviews with health professionals and administrators to determine the challenges they face and the coping systems they resort to and the perceptions towards those coping methods.

Results

Health professionals identified the following as some of the challenges there faced: inequitable and poor remuneration, overwhelming responsibilities with limited resources, lack of a stimulating work environment, inadequate supervision, poor access to continued professionals training, limited career progression, lack of transparent recruitment and discriminatory remuneration. When asked what kept them still working in Malawi when the pressures to emigrate were there, the following were some of the ways the health professionals mentioned as useful for earning extra income to support their families: working in rural areas where life was perceived to be cheaper, working closer to home village so as to run farms, stealing drugs from health facilities, having more than one job, running small to medium scale businesses. Health professionals would also minimize expenditure by missing meals and walking to work.

Conclusion

Many health professionals in Malawi experience overly challenging environments. In order to survive some are involved in ethically and legally questionable activities such as receiving "gifts" from patients and pilfering drugs. The efforts by the Malawi government and the international community to retain health workers in Malawi are recognized. There is however need to evaluate of these human resources-retaining measures are having the desired effects.
Low grade Endometrial Stromal Sarcoma of uterine corpus, a clinico-pathological and survey study in 14 cases
Authors: Ashraf-Ganjoei Tahereh , Behtash Nadereh , Shariat Mamak , Mosavi Asamosadat
Published: August 2006

Background

Endometrial stromal sarcoma (ESS) is a rare disease with probably less than 700 new cases in the USA or Europe per year. The aim of this study was to evaluate the behavior of low-grade endometrial stromal sarcoma (LGESS) in relation to their clinical and pathological features and to identify possible prognostic factors.

Patients and methods

Fourteen patients with histologically proven ESS were included in the analysis. Endometrial stromal sarcoma is characterized by proliferations composed of cells with Endometrial stromal cell differentiation. Low-grade endometrial stromal sarcoma has an infiltrating margin and typically show extensive worm-like vessel invasion.

Results

The median age was 44.35 ± 6 years. The most common presenting symptom was vaginal bleeding, occurring in twelve patients (86%). Diagnosis was made through Fractional dilatation and curettage in four patients (28.5%). Eight patients had a total abdominal hysterectomy and salpingo-ophorectomy (57%). Radiotherapy as adjuvant therapy was administered to four patients (28.5%). The median follow-up time was 45.6 months (range 24–84). The median overall survival of the 14 patients was 45.35 ± 21 months (range 20–83). Three of 14 patients demonstrated a recurrence of disease at 9, 72, and 96 months respectively. The recurrent diseases were treated with surgery, chemotherapy, and radiotherapy. No patient died of the disease. Clinico-pathological parameters did not significantly differ between patients with and without recurrence, but patients with no myometrial invasion and low mitotic count <= 5/HPF showed longer disease-free survival.

Conclusion

Five-year survival rate was 93%. Survival probabilities were calculated by the product limit method of Kaplan and Meier that showed, patients with no myometrial invasion and low mitotic count <= 5/HPF have longer disease-free survival, but P value was not significant.
HTLV-1 Tax: centrosome amplification and cancer
Authors: Pumfery Anne , de la Fuente Cynthia , Kashanchi Fatah
Published: August 2006

During interphase, each cell contains a single centrosome that acts as a microtubule organizing center for cellular functions in interphase and in mitosis. Centrosome amplification during the S phase of the cell cycle is a tightly regulated process to ensure that each daughter cell receives the proper complement of the genome. The controls that ensure that centrosomes are duplicated exactly once in the cell cycle are not well understood. In solid tumors and hematological malignancies, centrosome abnormalities resulting in aneuploidy is observed in the majority of cancers. These phenotypes are also observed in cancers induced by viruses, including adult T cell lymphoma which is caused by the human T cell lymphotrophic virus Type 1 (HTLV-1). Several reports have indicated that the HTLV-1 transactivator, Tax, is directly responsible for the centrosomal abnormalities observed in ATL cells. A recent paper inNature Cell Biologyby Chinget al. has shed some new light into how Tax may be inducing centrosome abnormalities. The authors demonstrated that 30% of ATL cells contained more than two centrosomes and expression of Tax alone induced supernumerary centrosomes. A cellular coiled-coil protein, Tax1BP2, was shown to interact with Tax and disruption of this interaction led to failure of Tax to induce centrosome amplification. Additionally, down-regulation of Tax1BP2 led to centrosome amplification. These results suggest that Tax1BP2 may be an important block to centrosome re-duplication that is observed in normal cells. Presently, a specific cellular protein that prevents centrosome re-duplication has not been identified. This paper has provided further insight into how Tax induces centrosome abnormalities that lead to ATL. Lastly, additional work on Tax1BP2 will also provide insight into how the cell suppresses centrosome re-duplication during the cell cycle and the role that Tax1BP2 plays in this important cellular pathway.
Innate immune response to Francisella tularensis is mediated by TLR2 and caspase-1 activation
Authors: Li Hanfen , Nookala Suba , Bina Xiaowen R , Bina James E , Re Fabio
Published: August 2006

Francisella tularensis, a gram-negative, facultative, intracellular bacterium, is the etiologic agent of tularemia and a category A bioterrorism agent. Little is known about the mechanism of pathogenesis of tularemia. In this paper, we describe the interaction of the live vaccine strain of F. tularensis with the innate immune system. We have found that in human and mouse dendritic cells, F. tularensis elicited a powerful inflammatory response, characterized by production of a number of cytokines and chemokines. Using cells derived from TLR2-deficient mice and in vitro transfection assays, we demonstrated that this response was mediated by TLR2 and did not require the LPS-binding protein. F. tularensis appeared to activate TLR2/TLR1 and TLR2/TLR6 heterodimers. IL-1β secretion, a reflection of caspase-1 activation, was induced by live but not heat-killed F. tularensis, despite the fact that both forms of the bacterium equally induced the IL-1β transcript. Our results identified activation of TLR2 and caspase-1 as the two main cellular pathways responsible for the inflammatory response to F. tularensis.
ErbB-3 Predicts Survival in Ovarian Cancer
Authors: Tanner Berno , Hasenclever Dirk , Stern Katja , Schormann Wiebke , Bezler Martin , Hermes Matthias , Brulport Marc , Bauer Alexander , Schiffer Ilka B. , Gebhard Susanne , Schmidt Markus , Steiner Eric , Sehouli Jalid , Edelmann Jeanett , Läuter Jürgen , Lessig Rüdiger , Krishnamurthi K. , Ullrich Axel , Hengstler Jan Georg
Published: August 2006

Background

HER3 (erbB-3) is a member of the epidermal growth factor receptor (EGFR) family. After dimerization with other members of the EGFR family several signal transduction cascades can be activated, including phosphoinosite 3′-kinase (PI3-K)/Akt and extracellular signal-regulated kinase (ERK1/2). Here, we studied a possible association between HER3 expression and prognosis in patients with ovarian cancer.

Methods

Tumor tissue of 116 consecutive patients diagnosed with primary epithelial ovarian cancer between 1986 and 1995 was analyzed immunohistochemically for HER3 expression. A possible influence of HER3 expression on survival was studied by multivariate Cox regression adjusting for established clinical prognostic factors.

Results

A positive HER3 expression was observed in 53.4% of the patients. HER3 expression was associated with decreased survival in proportional hazard modeling, including the International Federation of Gynecology and Obstetrics (FIGO) stage, histologic grade and type, residual disease, and age. After likelihood ratio forward as well as backward selection, only HER3 expression (hazard ratio, 1.71; 95% CI, 1.10 to 2.67; P = .018), FIGO stage (hazard ratio, 4.78; 95% CI, 1.89 to 12.08; P = .001), residual tumor (hazard ratio, 2.69; 95% CI, 1.40 to 5.17; P = .003), and age (hazard ratio, 2.06; 95% CI, 1.17 to 3.65; P = .013) were found to be significant. Kaplan-Meier plots demonstrated a clear influence of HER3 expression on survival time. Median survival time was 3.31 years (95% CI, 1.93 to 4.68) for patients with low HER3 expression, compared with only 1.80 years (95% CI, 0.83 to 2.78) for patients with HER3 overexpression (log-rank test P = .0034).

Conclusion

HER3 may represent a new prognostic factor in primary epithelial ovarian cancer. Pending validation, exploration of therapeutic strategies to block HER3 could be warranted.
Phase II Trial of CHOP Chemotherapy Followed by Tositumomab/Iodine I-131 Tositumomab for Previously Untreated Follicular Non-Hodgkin's Lymphoma: Five-Year Follow-Up of Southwest Oncology Group Protocol S9911
Authors: Press Oliver W. , Unger Joseph M. , Braziel Rita M. , Maloney David G. , Miller Thomas P. , LeBlanc Michael , Fisher Richard I.
Published: August 2006

Purpose

Advanced follicular lymphoma (FL) is incurable with conventional chemotherapy and radiotherapy, and optimal front-line management is controversial. This study was performed to determine the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy followed by tositumomab/iodine I-131 tositumomab.

Patients and Methods

From 1999 to 2000, the Southwest Oncology Group (SWOG) conducted a phase II trial (S9911) to test a novel new regimen consisting of six cycles of CHOP chemotherapy followed 4 to 8 weeks later by tositumomab/iodine I-131 tositumomab in 90 eligible patients with previously untreated, advanced-stage FL.

Results

The overall response rate was 91%, including a 69% complete remission (CR) rate. After a median follow-up time of 5.1 years, the estimated 5-year overall survival (OS) rate was 87%, and the progression-free survival (PFS) rate was 67%. The 5-year estimates of OS and PFS were each 23% better (absolute difference) than the corresponding figures for patients treated on previous SWOG protocols with CHOP alone. An analysis according to the Follicular Lymphoma International Prognostic Index showed that 21% of patients had high-risk features, 44% had intermediate-risk features, and 34% had low-risk features. High-risk patients had worse OS than lower risk patients (P = .05), but differences in PFS were not statistically significant (P = .21). Serial monitoring of the t(14;18) translocation in bone marrow by polymerase chain reaction demonstrated that 32 of 38 informative patients obtained molecular CRs, including seven patients (18%) after CHOP and 24 additional patients (63%) after tositumomab/iodine I-131 tositumomab. (The timing of conversion of one patient was unclear.)

Conclusion

A prospective, phase III, randomized Intergroup Trial is currently underway comparing the efficacy of the promising CHOP + tositumomab/iodine I-131 tositumomab regimen with the efficacy of CHOP + rituximab.
DNA-Repair Gene Polymorphisms Predict Favorable Clinical Outcome Among Patients With Advanced Squamous Cell Carcinoma of the Head and Neck Treated With Cisplatin-Based Induction Chemotherapy
Authors: Quintela-Fandino Miguel , Hitt Ricardo , Medina Pedro P. , Gamarra Soledad , Manso Luis , Cortes-Funes Hernan , Sanchez-Cespedes Montserrat
Published: August 2006

Purpose

Cisplatin kills tumor cells through DNA cross linking. Alterations in the function of DNA repair genes may affect DNA repair proficiency and influence cancer patients' response to cisplatin. We studied whether single nucleotide polymorphisms (SNPs) of DNA repair genes predict the response to cisplatin or prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN).

Methods

A polymerase chain reaction–restriction fragment length polymorphism (RFLP) approach was used to determine the frequency of the SNPs: XPD-Asp312Asn, XPD-Lys751Gln, ERCC1-C8092A, and XRCC1-Arg399Gln in DNA from peripheral lymphocytes of 103 stage IV SCCHN patients.

Results

The frequencies of the distinct genotypes were, respectively, for the homozygous common allele, heterozygous and homozygous polymorphic variant: 53%, 40%, and 7% for ERCC1; 50%, 42%, and 8% for XPD-312; 35%, 57%, and 8% for XPD751; and 35%, 51%, and 13% for XRCC1. Patients with only common alleles at all the SNPs tested had a median overall survival of 5.1 months (range, 4.3 to 6.0 months) as compared with not reached for patients with at least one polymorphic variant (P < .001). Estimates from Cox's multivariate analysis suggest that the accumulation of each polymorphic variant decreases the probability of dying by a factor of 2.1 (P < .001; the presence of seven polymorphic variants confers a 175-fold protection). The accumulation of polymorphic variants increases by 2.94-fold the probability of achieving a complete response to treatment (P = .041).

Conclusion

Using a multivariate model, the presence of polymorphic variants in DNA-repair genes are powerful prognosis factors and response to cisplatin predictors among SCCHN patients.
99mTc-Depreotide Scintigraphy Versus18F-FDG-PET in the Diagnosis of Radioiodine-Negative Thyroid Cancer
Authors: Rodrigues Margarida , Li Shuren , Gabriel Michael , Heute Dirk , Greifeneder Michaela , Virgolini Irene
Published: August 2006

Background: Papillary and follicular thyroid cancer were found recently to express somatostatin receptors (SSTRs). 99mTc-depreotide binds with high affinity to SSTRs 2, 3, and 5.

Aim: The aim of this study was to evaluate the feasibility of applying 99mTc-depreotide scintigraphy to search for radioiodine-negative thyroid cancer; comparison is made to a standard approach using 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET).

Patients and Methods: Ten radioiodine-negative patients with suspicion of recurrent or metastatic thyroid cancer were investigated with 99mTc-depreotide scintigraphy and 18F-FDG-PET, performed with a time interval that ranged from 1–8 wk. Locoregional recurrence and metastases were confirmed by ultrasonography and/or computed tomography, together with cytology or histological examination in selected cases.

Results: True-positive results were obtained in nine patients (90%) with 99mTc-depreotide scintigraphy and in seven patients (70%) with 18F-FDG-PET. 99mTc-depreotide scintigraphy gave better results in terms of detection of recurrent or metastatic disease compared with 18F-FDG-PET in three patients, whereas 18F-FDG-PET identified metastatic disease that was not seen with 99mTc-depreotide in only one patient. 99mTc-depreotide scintigraphy portrayed lesions in three patients with negative morphological imaging.

Conclusions: Results indicate a potential value of 99mTc-depreotide scintigraphy for the diagnosis of thyroid cancer in the setting of detectable thyroglobulin and negative radioiodine scan. Furthermore, 99mTc-depreotide adds complementary information regarding the SSTR status of lesions, which may be helpful for individual therapy planning in this group of patients, which is hard to manage clinically.
Midkine, a Heparin-Binding Growth Factor, Selectively Stimulates Proliferation of Definitive Zone Cells of the Human Fetal Adrenal Gland
Authors: Ishimoto Hitoshi , Muench Marcus O. , Higuchi Takayuki , Minegishi Kazuhiro , Tanaka Mamoru , Yoshimura Yasunori , Jaffe Robert B.
Published: August 2006

Context: In the human fetal adrenal gland (HFA), the inner fetal zone (FZ) secretes dehydroepiandrosterone sulfate. The function of the outer definitive zone (DZ) is less clear; however, the DZ phenotype is that of a reservoir of progenitor cells, many of which are mitotically active. Midkine (MK) is a heparin-binding growth factor with various bioactivities.

Objective: The objective of this study was to investigate expression, proliferative effects, and ACTH regulation of MK in the HFA.

Design and Setting: RNA, cryosections, and primary cell cultures from HFAs (14–24 wk) and adult adrenal RNA were used.

Main Outcome Measures: The main outcome measures were MK mRNA levels (measured by quantitative real-time RT-PCR); MK localization (measured by immunostaining); MK proliferative effects and mechanism (measured by proliferation assays, flow cytometry, pharmacological interventions); and ACTH regulation (measured by quantitative real-time RT-PCR).

Results: HFA MK mRNA levels were 4-fold higher than in adult adrenals (P < 0.05) and were comparable to levels in fetal and adult brains (positive controls). MK immunoreactivity was abundant throughout the HFA. Exogenous MK caused proliferation of isolated DZ cells but not FZ cells (72 h, P < 0.05). In contrast, basic fibroblast growth factor induced proliferation of cells from both zones. Pharmacological interventions indicated that MK-induced DZ cell proliferation may be mediated by phosphatidylinositol 3-kinase, MAPK kinase, and Src family kinases. ACTH (1 nm) increased MK mRNA by 3.5-fold (48 h, P < 0.01) in isolated FZ cells.

Conclusions: MK likely plays a key role in HFA development. MK’s selective in vitro mitotic effects on DZ cells may provide insights into the mechanism underlying the distinct in vivo differences in mitotic activity between the DZ and FZ.
The Synthesis of Poly[N-(p-vinylbenzylidene)-t-butylamine N-oxide] and Characterizations of Reaction with Nitrogen Dioxide
Authors: Ren Jingzhu , Sakakibara Kazuhisa , Hirota Minoru
Published: August 2006

Polymer-supported spin trap, poly[N-(p-vinylbenzylidene)-t-butylamine N-oxide] (polyPBN), was prepared by using p-chlorostyrene as a starting material, followed by Grignard reaction, condensation with t-butylamine, reduction, polymerization, and oxidation. The adsorption ability of NO2 by polyPBN was investigated in a closed-circulation system. PolyPBN maintains its original NO2 adsorbing ability in the mixed gas of nitrogen and nitrogen dioxide saturated with water vapor even after repeated (5 times) use. However, when the gaseous phase is freed from water, polyPBN exhibits less efficiency to adsorb NO2 and its adsorbing ability decreases gradually with the repeated use.
ESR Studies of the Displacement Adsorption Behavior of Poly(methyl methacrylate) and Polystyrene System at the Solid–Liquid Interface
Authors: Kobayashi Kazutoshi , Dochi Atsuko , Yajima Hirofumi , Endo Ryuichi
Published: August 2006

The displacement adsorption behavior of a poly(methyl methacrylate) (PMMA) and polystyrene (PS) system onto a nonporous silica surface from a carbon tetrachloride solution was studied by utilizing the ESR method. The fractions of train segments for these polymers were determined from ESR spectra analyses; these values were compared with those of the individual adsorption. When PS was preadsorbed onto silica surface and PMMA solutions of various concentrations were added, the amount of PS desorbed from silica surface was proportional to an increase in the initial concentration of the PMMA solution; at the final concentration, PS was completely replaced by PMMA. This phenomenon was due to the stronger interaction of PMMA with the silica surface arising from its polar character, and the greater hydrogen bonding ability. The amount of adsorption for PMMA, which saturated the silica surface, was lower than that when adsorbed on silica surface individually. The adsorbed PMMA formed a more compressed polymer layer compared with that for the case in which PMMA was adsorbed alone. The amount and conformation of the adsorbed PMMA were affected by the presence of PS in the solution.
127I Mössbauer Spectra of Diphenyliodonium Halides
Authors: Ikezawa Hidenori , Takahashi Masashi , Takeda Masuo , Ito Yasuo
Published: August 2006

The 127I Mössbauer spectra have been obtained at 20 K for the diphenyliodonium halides, Ph2IX (X = Cl, Br) and their derivatives, (p-R–C6H4) IPhBr (R = CH3, CH3O, Cl, COOH and NO2). The valence electron populations of iodine are determined by the interactions with carbon atoms but not with bridging halogen atoms. The iodine–carbon bonds, having large p-character, are affected scarcely by the substituents at the para-position of the phenyl group. The large ηvalues for those compounds are explained in terms of a lone pair electrons on iodine(III) atoms.
Preparation, Crystal and Electronic Structures, and Electrical Resistivity of (BEDT-TTF)3Cl2.5(H5O2)
Authors: Mori Hatsumi , Hirabayashi Izumi , Tanaka Shoji , Maruyama Yusei
Published: August 2006

The crystal and electronic structures and electrical resistivity of new chlorine complex, (BEDT-TTF)3Cl2.5(H5O2), were investigated. The two-dimensional donor sheet and the anion layer stack alternately along the b-axis. The packing pattern of donors is similar to that of (BEDT-TTF)3(ClO4)2 and the sharp metal-insulator transition was observed at 170 K. It is interesting that not only donor and anion but also the third component cation, H+, determines the 3/4-filled band structure.
Formation of SrSO4·1/2H2O in an SrSO4–H2O System and Its Solid Solution in a CaSO4–SrSO4–H2O System
Authors: Takahashi Satoshi , Seki Masanobu , Setoyama Katsumi
Published: August 2006

In an SrSO4–H2O system the formation of a new compound of SrSO4·1/2H2O has been found by coprecipitation from solutions of Sr2+ and SO42−. This was found to have a similar crystal structure to CaSO4·1/2H2O of a hexagonal crystal system. The lattice constants thereof were calculated. It was also found that SrSO4·1/2H2O is not stable in water, but changes to a stable well-known orthorhombic anhydrous strontium sulfate. For a CaSO4–SrSO4–H2O system, a series of solid solutions of CaSO4·1/2H2O and SrSO4·1/2H2O was prepared, which had similar X-ray diffraction patterns to SrSO4·1/2H2O. These solid solutions were unstable in water, and converted with time to a mixture of stable anhydrous SrSO4 and CaSO4·2H2O.