bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity of Phasic Cholinergic Signaling in Neocortical Neurons
Authors: Gulledge Allan T. , Park Susanna B. , Kawaguchi Yasuo , Stuart Greg J.
Published: November 2006

Acetylcholine (ACh) is a neurotransmitter critical for normal cognition. Here we demonstrate heterogeneity of cholinergic signaling in neocortical neurons in the rat prefrontal, somatosensory, and visual cortex. Focal ACh application (100 μM) inhibited layer 5 pyramidal neurons in all cortical areas via activation of an apamin-sensitive SK-type calcium-activated potassium conductance. Cholinergic inhibition was most robust in prefrontal layer 5 neurons, where it relies on the same signal transduction mechanism (M1-like receptors, IP3-dependent calcium release, and SK-channels) as exists in somatosensory pyramidal neurons. Pyramidal neurons in layer 2/3 were less responsive to ACh, but substantial apamin-sensitive inhibitory responses occurred in deep layer 3 neurons of the visual cortex. ACh was only inhibitory when presented near the somata of layer 5 pyramidal neurons, where repetitive ACh applications generated discrete inhibitory events at frequencies of up to ∼0.5 Hz. Fast-spiking (FS) nonpyramidal neurons in all cortical areas were unresponsive to ACh. When applied to non-FS interneurons in layers 2/3 and 5, ACh generated mecamylamine-sensitive nicotinic responses (38% of cells), apamin-insensitive hyperpolarizing responses, with or without initial nicotinic depolarization (7% of neurons), or no response at all (55% of cells). Responses in interneurons were similar across cortical layers and regions but were correlated with cellular physiology and the expression of biochemical markers associated with different classes of nonpyramidal neurons. Finally, ACh generated nicotinic responses in all layer 1 neurons tested. These data demonstrate that phasic cholinergic input can directly inhibit projection neurons throughout the cortex while sculpting intracortical processing, especially in superficial layers.
What Determines Blood Vessel Structure? Genetic Prespecification vs. Hemodynamics
Authors: Jones Elizabeth A. V. , le Noble Ferdinand , Eichmann Anne
Published: November 2006

Vascular network remodeling, angiogenesis, and arteriogenesis play an important role in the pathophysiology of ischemic cardiovascular diseases and cancer. Based on recent studies of vascular network development in the embryo, several novel aspects to angiogenesis have been identified as crucial to generate a functional vascular network. These aspects include specification of arterial and venous identity in vessels and network patterning. In early embryogenesis, vessel identity and positioning are genetically hardwired and involve neural guidance genes expressed in the vascular system. We demonstrated that, during later stages of embryogenesis, blood flow plays a crucial role in regulating vessel identity and network remodeling. The flow-evoked remodeling process is dynamic and involves a high degree of vessel plasticity. The open question in the field is how genetically predetermined processes in vessel identity and patterning balance with the contribution of blood flow in shaping a functional vascular architecture. Although blood flow is essential, it remains unclear to what extent flow is able to act on the developing cardiovascular system. There is significant evidence that mechanical forces created by flowing blood are biologically active within the embryo and that the level of mechanical forces and the type of flow patterns present in the embryo are able to affect gene expression. Here, we highlight the pivotal role for blood flow and physical forces in shaping the cardiovascular system.
Nomograms Provide Improved Accuracy for Predicting Survival after Radical Cystectomy
Authors: Shariat Shahrokh F. , Karakiewicz Pierre I. , Palapattu Ganesh S. , Amiel Gilad E. , Lotan Yair , Rogers Craig G. , Vazina Amnon , Bastian Patrick J. , Gupta Amit , Sagalowsky Arthur I. , Schoenberg Mark , Lerner Seth P.
Published: November 2006

Aims: To develop multivariate nomograms that determine the probabilities of all-cause and bladder cancer–specific survival after radical cystectomy and to compare their predictive accuracy to that of American Joint Committee on Cancer (AJCC) staging.

Methods: We used Cox proportional hazards regression analyses to model variables of 731 consecutive patients treated with radical cystectomy and bilateral pelvic lymphadenectomy for bladder transitional cell carcinoma. Variables included age of patient, gender, pathologic stage (pT), pathologic grade, carcinoma in situ, lymphovascular invasion (LVI), lymph node status (pN), neoadjuvant chemotherapy (NACH), adjuvant chemotherapy (ACH), and adjuvant external beam radiotherapy (AXRT). Two hundred bootstrap resamples were used to reduce overfit bias and for internal validation.

Results: During a mean follow-up of 36.4 months, 290 of 731 (39.7%) patients died; 196 of 290 patients (67.6%) died of bladder cancer. Actuarial all-cause survival estimates were 56.3% [95% confidence interval (95% CI), 51.8-60.6%] and 42.9% (95% CI, 37.3-48.4%) at 5 and 8 years after cystectomy, respectively. Actuarial cancer-specific survival estimates were 67.3% (62.9-71.3%) and 58.7% (52.7-64.2%) at 5 and 8 years, respectively. The accuracy of a nomogram for prediction of all-cause survival (0.732) that included patient age, pT, pN, LVI, NACH, ACH, and AXRT was significantly superior (P = 0.001) to that of AJCC staging–based risk grouping (0.615). Similarly, the accuracy of a nomogram for prediction of cancer-specific survival that included pT, pN, LVI, NACH, and AXRT (0.791) was significantly superior (P = 0.001) to that of AJCC staging–based risk grouping (0.663).

Conclusions: Multivariate nomograms provide a more accurate and relevant individualized prediction of survival after cystectomy compared with conventional prediction models, thereby allowing for improved patient counseling and treatment selection.
A Novel HSV-1 Virus, JS1/34.5−/47−, Purges Contaminating Breast Cancer Cells From Bone Marrow
Authors: Hu Jennifer C. , Booth Matthew J. , Tripuraneni Gopichand , Davies Derek , Zaidi Syed A.A. , Tamburo de Bella Manuela , Slade Martin J. , Marley Stephen B. , Gordon Myrtle Y.A. , Coffin Robert S. , Coombes R. Charles , Kamalati Tahereh
Published: November 2006

Purpose: Oncolytic herpes simplex virus type 1 (HSV-1) vectors show considerable promise as agents for cancer therapy. We have developed a novel recombinant HSV-1 virus (JS1/34.5−/47−) for purging of occult breast cancer cells from bone marrow of patients. Here, we evaluate the therapeutic efficacy of this oncolytic virus.

Experimental Design: Electron microscopy was used to determine whether human breast cancer and bone marrow cells are permissive for JS1/34.5−/47− infection. Subsequently, the biological effects of JS1/34.5−/47− infection on human breast cancer cells and bone marrow were established using cell proliferation and colony formation assays, and the efficiency of cell kill was evaluated. Finally, the efficiency of JS1/34.5−/47− purging of breast cancer cells was examined in cocultures of breast cancer cells with bone marrow as well as bone marrow samples from high-risk breast cancer patients.

Results: We show effective killing of human breast cancer cell lines with the JS1/34.5−/47− virus. Furthermore, we show that treatment with JS1/34.5−/47− can significantly inhibit the growth of breast cancer cell lines without affecting cocultured mononuclear hematopoietic cells. Finally, we have found that the virus is effective in destroying disseminated tumors cells in bone marrow taken from breast cancer patients, without affecting the hematopoietic contents in these samples.

Conclusion: Collectively, our data show that the JS1/34.5−/47− virus can selectively target breast cancer cells while sparing hematopoietic cells, suggesting that JS1/34.5−/47− can be used to purge contaminating breast cancer cells from human bone marrow in the setting of autologous hematopoietic cell transplantation.
Diallyl Trisulfide Suppresses Growth of PC-3 Human Prostate Cancer Xenograft In vivo in Association with Bax and Bak Induction
Authors: Xiao Dong , Lew Karen L. , Kim Young-Ae , Zeng Yan , Hahm Eun-Ryeong , Dhir Rajiv , Singh Shivendra V.
Published: November 2006

Purpose: The present study was undertaken to determine the effect of garlic constituent diallyl trisulfide (DATS) on growth of PC-3 human prostate cancer xenograft in vivo.

Experimental Design: DATS was given orally (6 μmoL, thrice weekly) to male athymic mice s.c. implanted with PC-3 cells. Tumor sections from control and DATS-treated mice were examined for apoptotic bodies by terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay. Protein levels of apoptosis and cell cycle regulating proteins in tumor tissues of control and DATS-treated mice were determined by immunoblotting. The effect of DATS treatment on in vivo angiogenesis was determined by immunohistochemical analysis of CD31 in tumors.

Results: Oral gavage of DATS significantly retarded growth of PC-3 xenografts in athymic mice without causing weight loss. For instance, 20 days after starting therapy, the average tumor volume in control mice was ∼3-fold higher compared with DATS-treated mice. Tumors from DATS-treated mice exhibited a markedly higher count of apoptotic bodies compared with control tumors. Consistent with the results in cultured PC-3 cells, the DATS-mediated suppression of PC-3 xenograft growth correlated with induction of proapoptotic proteins Bax and Bak. Although DATS treatment inhibited migration of cultured PC-3 cells in association with down-regulation of vascular endothelial growth factor receptor-2 protein, formation of new blood vessels was comparable in tumors of control and DATS-treated mice as judged by CD31 immunostaining.

Conclusions: The present study indicates that DATS administration inhibits growth of PC-3 xenografts in vivo in association with induction of Bax and Bak.
Of Spiders and Crabs: The Emergence of Lysophospholipids and Their Metabolic Pathways as Targets for Therapy in Cancer
Authors: Murph Mandi , Tanaka Tamotsu , Liu Shuying , Mills Gordon B.
Published: November 2006

Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), two small lysophospholipids, are potent inducers of many of the hallmarks of cancer including cell proliferation, survival, migration, invasion, and neovascularization in in vitro and in vivo tumor models. Furthermore, the enzymes metabolizing LPA and S1P and their receptors are aberrant in multiple cancer lineages and exhibit transforming activity altering patterns and targets for metastasis. Several recent studies show the remarkable activity of new chemical genomics and/or potential novel drugs in preclinical models. Combined with the physiologic and pathophysiologic activities of LPA and S1P, these studies suggest the implementation of preclinical and clinical evaluation of LPA and S1P as therapeutic targets.
Antimetastatic activity of insulin-like growth factor binding protein-3 in lung cancer is mediated by insulin-like growth factor–independent urokinase-type plasminogen activator inhibition
Authors: Oh Seung-Hyun , Lee Ok-Hee , Schroeder Claudia P. , Oh Yun W. , Ke Shi , Cha Hee-Jae , Park Rang-Woon , Onn Amir , Herbst Roy S. , Li Chun , Lee Ho-Young
Published: November 2006

Insulin-like growth factor binding protein-3 (IGFBP-3), a major IGF-binding protein in human serum, regulates the growth of non–small cell lung cancer (NSCLC) cells through IGF-dependent and IGF-independent mechanisms. However, the role of IGFBP-3 in lung cancer metastasis is not well known. In the present study, we showed that noncytotoxic doses of adenoviral or recombinant IGFBP-3 significantly decreased the migration and invasion of H1299 and A549 NSCLC cells. Furthermore, treatment of human lung fibroblasts with recombinant IGFBP-3 suppressed their ability to stimulate the invasion of H1299 cells. Overexpression of IGFBP-3 markedly reduced lung metastasis of A549 cells in an experimental animal model system and prolonged the survival time of the animals. Urokinase-type plasminogen activator (uPA) inhibitor treatment or uPA small interfering RNA transfection of A549 and H1299 cells resulted in a significant decrease in invasion. Corresponding ELISA, Western blot, gelatin zymogram, and semiquantitative reverse transcription-PCR analyses revealed that IGFBP-3 reduced the expression of uPA mRNA through IGF-independent mechanisms. The specific role of uPA in anti-invasive activity of IGFBP-3 was further confirmed in NSCLC cells, in which uPA expression/activity was suppressed by the transfection with synthetic small interfering RNA or by the treatment with uPA inhibitor or induced by the infection with an adenoviral vector. IGFBP-3 also decreased the expression/activity of matrix metalloproteinase-2 through IGF-dependent but uPA-independent pathways. Taken together, our data suggest that IGFPB-3 effectively block uPA- and matrix metalloproteinase-2–stimulated invasion pathways, ultimately reducing lung cancer cell metastasis. Our findings indicate that IGFBP-3 may be a promising anti-invasive and antimetastatic therapeutic agent in lung cancer. [Mol Cancer Ther 2006;5(11):2685–95]
Anti-CD146 monoclonal antibody AA98 inhibits angiogenesis via suppression of nuclear factor-κB activation
Authors: Bu Pengcheng , Gao Lizeng , Zhuang Jie , Feng Jing , Yang Dongling , Yan Xiyun
Published: November 2006

Our previous study showed that an anti-CD146 monoclonal antibody (mAb), AA98, which was raised against the vascular endothelial cells stimulated by a conditioned medium from hepatocarcinoma SMMC 7721 cells (SMMC 7721-CM), inhibited cell migration, angiogenesis, and tumor growth. However, the underlying mechanism was not elucidated. The objective of this study was to understand the mechanism by which mAb AA98 inhibits the endothelial cell migration and angiogenesis that is induced by SMMC 7721-CM. Using confocal imaging and biochemical studies, we found that SMMC 7721-CM induced nuclear factor κB (NF-κB) activation through the upstream p38 mitogen-activated protein kinase pathway, leading to the up-regulation of matrix metalloproteinase 9 and intercellular adhesion molecule 1 expression. Interestingly, all these activities stimulated by SMMC 7721-CM could be effectively inhibited by mAb AA98 in a dose- and time-dependent manner. Our data showed that the engagement of mAb AA98 with membrane protein CD146 inhibited p38 mitogen-activated protein kinase phosphorylation, suppressed NF-κB activation, and down-regulated matrix metalloproteinase 9 and intercellular adhesion molecule 1 expression, suggesting that the suppression of NF-κB is a critical point for the inhibitory function of mAb AA98 on endothelial cell migration, angiogenesis, and tumor metastasis. These results will provide clues for a better understanding of the mechanisms underlying tumor angiogenesis as well as antiangiogenesis therapy. [Mol Cancer Ther 2006;5(11):2872–8]
Pretherapy nuclear factor-κB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma
Authors: Izzo Julie G. , Correa Arlene M. , Wu Tsung-Teh , Malhotra Usha , Chao Clifford K.S. , Luthra Rajyalakshmi , Ensor Joe , Dekovich Alexander , Liao Zhongxing , Hittelman Walter N. , Aggarwal Bharat B. , Ajani Jaffer A.
Published: November 2006

Background: Transcriptional factor nuclear factor-κB (NF-κB) seems to be associated with aggressive clinical biology (chemoradiation resistance and metastatic progression) of esophageal cancer. We hypothesized that activated NF-κB would define clinical biology irrespective of the type of chemotherapy or sequence administered. Methods: Pretherapy and/or posttherapy cancer specimens were examined for activated NF-κB and correlated with pathologic response to chemoradiation, metastatic potential, overall survival, disease-free survival, and type of chemotherapy or sequence used. Findings: Eighty patients undergoing chemotherapy and concurrent radiation were studied. Activated NF-κB prior to any therapy was associated with the lack of complete pathologic response (pathCR, P = 0.006). Forty-five (78%) of 58 patients achieving <pathCR had activated NF-κB in pretherapy and/or posttherapy cancer specimens versus 2 (9%) of 22 patients with pathCR (P = 0.001). Twenty-four (51%) of 47 patients with activated NF-κB in cancer developed metastases versus 7 (21%) of 22 patients with negative NF-κB in cancer (P = 0.01). At a median follow-up of 32 months, 25 (53%) of 47 patients with activated NF-κB cancer had died versus 3 (9%) of 33 patients with negative NF-κB cancer. NF-κB activation was the only independent predictor of disease-free survival (P = 0.01) and overall survival (P = 0.007) in a multivariate model. The class of chemotherapy or its sequence had no effect on NF-κB expression or patient outcome. Conclusions: Our data are the first to show that pretreatment-activated NF-κB significantly correlates with clinical biology of esophageal cancer, and most importantly, with pathCR. To therapeutically exploit NF-κB-regulated genes and their pathways, further research is warranted. [Mol Cancer Ther 2006;5(11):2844–50]
Benzyl isothiocyanate–induced apoptosis in human breast cancer cells is initiated by reactive oxygen species and regulated by Bax and Bak
Authors: Xiao Dong , Vogel Victor , Singh Shivendra V.
Published: November 2006

Epidemiologic studies have revealed an inverse correlation between dietary intake of cruciferous vegetables and the risk of breast cancer. We now show that cruciferous vegetable constituent benzyl isothiocyanate (BITC) effectively suppresses growth of cultured human breast cancer cells (MDA-MB-231 and MCF-7) by causing G2-M phase cell cycle arrest and apoptosis induction. On the other hand, a normal mammary epithelial cell line (MCF-10A) is significantly more resistant to growth arrest and apoptosis by BITC compared with breast cancer cells. The BITC-mediated cell cycle arrest was associated with a decrease in levels of proteins involved in regulation of G2-M transition, including cyclin B1, cyclin-dependent kinase 1, and cell division cycle 25C. The BITC-induced apoptosis correlated with induction of proapoptotic proteins Bax (MCF-7) and Bak (MDA-MB-231 and MCF-7) and down-regulation of antiapoptotic proteins Bcl-2 and Bcl-xL (MDA-MB-231). The SV40-immortalized mouse embryonic fibroblasts derived from Bax and Bak double knockout mice were significantly more resistant to BITC-induced DNA fragmentation compared with wild-type mouse embryonic fibroblasts. The BITC treatment caused rapid disruption of the mitochondrial membrane potential, leading to cytosolic release of apoptogenic molecules, which was accompanied by formation of autophagosome-like structures as revealed by transmission electron microscopy. The BITC-mediated apoptosis was associated with generation of reactive oxygen species and cleavage of caspase-9, caspase-8, and caspase-3. Apoptosis induction by BITC was significantly attenuated in the presence of a combined superoxide dismutase and catalase mimetic EUK134 as well as caspase inhibitors. In conclusion, the present study reveals a complex signaling leading to growth arrest and apoptosis induction by BITC. [Mol Cancer Ther 2006;5(11):2931–45]
Telomere Biology and Cardiovascular Disease
Authors: Fuster José J. , Andrés Vicente
Published: November 2006

Accumulation of cellular damage with advancing age leads to atherothrombosis and associated cardiovascular disease. Ageing is also characterized by shortening of the DNA component of telomeres, the specialized genetic segments located at the end of eukaryotic chromosomes that protect them from end-to-end fusions. By inducing genomic instability, replicative senescence and apoptosis, shortening of the telomeric DNA is thought to contribute to organismal ageing. In this Review, we discuss experimental and human studies that have linked telomeres and associated proteins to several factors which influence cardiovascular risk (eg, estrogens, oxidative stress, hypertension, diabetes, and psychological stress), as well as to neovascularization and the pathogenesis of atherosclerosis and heart disease. Two chief questions that remain unanswered are whether telomere shortening is cause or consequence of cardiovascular disease, and whether therapies targeting the telomere may find application in treating these disorders (eg, cell “telomerization” to engineer blood vessels of clinical value for bypass surgery, and to facilitate cell-based myocardial regeneration strategies). Given that most research to date has focused on the role of telomerase, it is also of up most importance to investigate whether alterations in additional telomere-associated proteins may contribute to the pathogenesis of cardiovascular disease.
Huqūq Allāh and Huqūq al-'Ibād: A Legal Heuristic for a Natural Rights Regime
Authors: Emon Anver
Published: November 2006

This article shows that early Muslim jurists often created rules that had no foundation in the Qur'ān or Sunna. Their successors adopted these views as authoritative precedent, but not without further justifying them. Their justificatory reasons reflected background values concerning inherent qualities of the individual and the goods society must uphold in order to give substantive content to their legal determinations. Recourse to these values, whether implicit or explicit, illustrates how Muslim jurists incorporated naturalistic reasoning in their juridical analyses. To prove their implicit naturalism, this article focuses on how Sunnī Muslim jurists primarily from the 2nd/8th-10th/16th centuries used the conceptual heuristic of "rights of God" and "rights of individuals" (huqūq Allāh, huqūq al-i'ibād) as an interpretive mechanism to frame their naturalistic assumptions and apply them in legal analysis to create and distribute rights, duties, and public commitments.
Nature Seen through the Eyes of Faith: Understandings among Seminarians
Authors: Groenendyk Kathi , Curry Janel
Published: November 2006

Attitudes toward nature were surveyed among male and female seminary students at three seminaries, all of which were located in West Michigan. Mixed methodologies were used in the study, including questionnaires, visualization, and content analysis of discussion transcripts. The seminaries represented theological traditions that were either "communal" or "individualistic" in their perceptions of society. Previous research has confirmed that individualistic, fundamentalist belief systems hold together in such a way as to lead to a utilitarian view of nature. Beyond this fundamentalist social group, environmental attitudes were much more complex. Gender differences were present but not substantial. The results of this study began to clarify the elusive concept of stewardship. The participants from the seminary who most closely reflected this position rejected the general concept of rights, whether for humans or nature, and held neither a utilitarian nor a biocentric view of nature. However, they believed that God's sustaining power was present in nature, and that the human community was embedded in nature.
The Efforts to Limit the International Criminal Court's Jurisdiction Over Nationals of Non-Party States: A Comparative Study
Authors: Roscini Marco
Published: November 2006

The purpose of this article is to discuss and compare the multilateral and bilateral efforts to prevent the ICC from exercising its jurisdiction over nationals of states non-parties to the Rome Statute. In particular, the US secured the adoption of Security Council resolutions no. 1422 (2002), 1487 (2003), 1497 (2003), 1593 (2005) and launched a campaign for the conclusion of bilateral non-surrender agreements: the differences between the resolutions and between them and the agreements are analysed. None of the resolutions above can be qualified as an exercise of the Security Council's power to request the ICC not to commence or proceed with investigations or prosecutions under Article 16 of the Rome Statute, as this provision was not conceived to cover future and hypothetical cases. Furthermore, by adopting resolutions 1422 and 1487 and by including the paragraphs on the exclusive jurisdiction of the contributing state in resolutions 1497 and 1593, the Security Council acted ultra vires, since no threat to the peace can be found in order to justify the exercise of Chapter VII powers. The resolutions are also in contrast with the principles and purposes of the UN. As to the bilateral non-surrender agreements, they cannot be qualified as "international agreements pursuant to which the consent of the sending State is required to surrender a person of that State to the Court" as required by Article 98 (2) of the Statute, since they prohibit the surrender to the ICC of any individual who is "present" on the territory of the other party and they do not require the state to which the accused has been transferred to investigate and prosecute the case. Should Italy conclude a non-surrender agreement with the US, it would incur international responsibility. The law giving effect to such an agreement in the Italian legal order would also be in contrast with Articles 10 (1) and 11 of the Constitution.
Ex iure manum conserere: Symbolic violence in early Roman property disputes
Authors: Platschek Johannes
Published: November 2006

The technical term ex iure manum conserere known from the formulas of the old Roman procedure concerning ownership (legis actio sacramento in rem) means – exactly as in the words' common use – 'to come to blows according to the law'. It signifies an act of mutual violence regarding the thing in dispute for the purpose to prepare a trial. The judicial decision about who was entitled to use force is indirectly an acknowledgment of ownership. The terminology is in line with other institutes of Roman law, and there are parallels in Greek law. In contrast, Gellius interprets ex iure in opposition to in iure and therefore as 'out of court'. He explains manum conserere with reference to the procedure as it had already developed, viz. 'to seize the object jointly and claim it with the prescribed wording'. But his reconstruction is neither consistent nor supported by any other evidence.
Matching Achievement Contexts with Implicit Theories to Maximize Motivation After Failure: A Congruence Model
Authors: El-Alayli Amani
Published: November 2006

Previous research has shown that matching person variables with achievement contexts can produce the best motivational outcomes. The current study examines whether this is also true when matching entity and incremental beliefs with the appropriate motivational climate. Participants were led to believe that a personal attribute was fixed (entity belief) or malleable (incremental belief). After thinking that they failed a test that assessed the attribute, participants performed a second (related) task in a context that facilitated the pursuit of either performance or learning goals. Participants were expected to exhibit greater effort on the second task in the congruent conditions (entity belief plus performance goal climate and incremental belief plus learning goal climate) than in the incongruent conditions. These results were obtained, but only for participants who either valued competence on the attribute or had high achievement motivation. Results are discussed in terms of developing strategies for optimizing motivation in achievement settings.
Perceiving Intergroup Conflict: From Game Models to Mental Templates
Authors: Halevy Nir , Sagiv Lilach , Roccas Sonia , Bornstein Gary
Published: November 2006

This article puts forward a parsimonious framework for studying subjective perceptions of real-life intergroup conflicts. Four studies were conducted to explore how individuals perceive the strategic properties of the Israeli-Palestinian conflict. Studies 1 and 2 found theory-driven associations between people's subjective perception of the conflict's structure as a Chicken, Assurance, or Prisoner's Dilemma game and their ingroup/outgroup perceptions, national identification, religiosity, political partisanship, voting behavior, and right-wing authoritarianism. Studies 3 and 4 manipulated the saliency of the needs for cognitive closure and security, respectively, demonstrating that these needs affect people's endorsement of the game models as descriptions of the conflict.
Protecting Threatened Identity: Sticking with the Group by Emphasizing Ingroup Heterogeneity
Authors: Hutchison Paul , Jetten Jolanda , Christian Julie , Haycraft Emma
Published: November 2006

In two studies (Ns=163, 164), the authors tested the prediction that perceptions of group variability can steer and guide the way that loyalty is expressed in times of identity threat. In both studies, participants were classified as lower or higher identifiers on the basis of their scores on a group identification measure, and manipulations involved group variability perceptions (homogeneous ingroup vs. heterogeneous ingroup) and threat to the ingroup. Higher identifiers presented with a homogeneous ingroup perceived more ingroup homogeneity under threat than when there was no threat. In contrast, higher identifiers who perceived the ingroup initially as heterogeneous perceived more ingroup heterogeneity under threat than in no threat conditions. Lower identifiers perceived more ingroup heterogeneity under threat (vs. no threat) irrespective of manipulated group variability perceptions. Discussion focuses on different ways that group loyalty can be expressed in times of identity threat.
The Belief in a Just World and Immanent Justice Reasoning in Adults
Authors: Callan Mitchell J. , Ellard John H. , Nicol Jennifer E.
Published: November 2006

Deciding that negative experiences are punishment for prior misdeeds, even when plausible causal links are missing, is immanent justice (IJ) reasoning (Piaget, 1932/1965). Three studies examined a just world theory analysis of IJ reasoning in adults (Lerner, 1980). Studies 1 and 2 varied the valence of a target person's behavior prior to them experiencing an unrelated negative (car accident, Study 1) or positive (lottery win, Study 2) outcome. Participants viewed the outcomes as the result of prior behavior most when they fit deservingness expectations (good person won the lottery, bad person injured in automobile accident), suggesting that just world concerns influenced IJ reasoning. The lottery-winning finding (Study 2) also extends IJ reasoning to positive experiences. A third study found that a manipulation of just world threat in one context (prolonged or ended suffering of an HIV victim) influenced IJ responses in a subsequent unrelated context (automobile accident scenario).
Gender and Group versus Individual Target as Moderators of the Models of Crossed Categorisation Effects
Authors: Singh Ramadhar , Goh Hong Yi
Published: November 2006

It was hypothesised that men perceive women at the interpersonal level, but women perceive men at the intergroup level, and that the gender of the participants moderates the models of evaluating people categorised by race and gender. In Study 1 (N = 261) men and women differed along the hypothesised dimensions of comparison, competition, and social interaction in the perception of gender group. Men and women (Ns = 28) in Study 2 reported their attraction toward work groups formed by two persons, each categorised by race and gender, and preferences for one over another member of those groups as a colleague. As hypothesised, responses of women conformed to the model of category dominance by race, and those of men followed the additive model in group attraction and the hierarchical ordering model in member preference. Men were more attracted toward outgroup women than ingroup men. Implications of these findings are discussed.
Prosocial Reasoning and Behaviour among Indian Children
Authors: Chadha Neerja , Misra Girishwar
Published: November 2006

This study explored the nature and development of patterns of prosocial reasoning and behaviour of Indian children (N = 167), between 5 and 14 years of age, from low and high SES, in naturalistic contexts. Prosocial reasoning of children in real life contexts was characterised primarily by authority/punishment orientation, concern for needs of others, pragmatism, mutual gain orientation, and orientation to honouring request made. Orientation to physical needs of others and to honouring request made, increased with age. Some gender and SES differences in prosocial reasoning were noted. Prosocial behaviour, however, was not significantly influenced by age, SES, or gender. Apart from a low negative correlation with authority/punishment orientation, prosocial responding was found to be unrelated to the use of any reasoning category. In most cases of non-prosocial behaviour, children could nevertheless take the perspective of the potential recipient or perceive the need for prosocial behaviour. The observations and findings have been discussed from methodological and sociocultural perspectives.
Autonomy as a Psychological Need
Authors: Stewart Sunita Mahtani , Zaman Riffat Moazam , Dar Rabiya
Published: November 2006

In-depth interviews were conducted with 22 mothers of adolescents in Pakistan to explore the meaning of “autonomy” in this collective, highly gender-differentiated culture. Middle class mothers did not spontaneously mention autonomy as a basic human need; positive relationships were, however, readily emphasised. Nevertheless, on specific questioning, all mothers indicated that autonomy was a basic need for both sexes. Autonomy was seen as potentially threatening to important goals for both sexes. Female kin were frequently described as an important source of restriction on women's autonomy. In raising daughters, mothers discouraged autonomy, emphasising the central importance of marriage and the attendant requirement of adjustment to in-laws. Increasing autonomy was seen as part of the life cycle as women attained seniority within their married families. Autonomy was seen as an environmentally determined and life-staged related opportunity rather than a right. The study sheds light on a universally important psychological need and its manifestations in an understudied modernising collective group.
Such Stuff as Peoples are Made on
Authors: Hoppenbrouwers Peter
Published: November 2006

Peoples, or ethnic communities, ‘have been present in every period and continent’, says the cover of a recent volume on ethnicity.1If true, we should also be aware that ‘peoples’ in the recorded past are social entities which are always to a large extent constructed and constantly changing during continuous processes of state formation. This article aims at summarising the building blocks and leitmotifs, derived from Graeco-Roman and Judeo-Christian tradition, that medieval authors, in particular the clerical writers of histories, used in their construction of peoples in a time when political communities developed state-like features which required some measure of national identification. Understandably, the development of national identities in medieval Europe proved to be a complex interplay, in which the imagining of ‘Self’ was inextricably bound up with the judgement of ‘Other’ within the boundaries of that period's mental outlook.
What Happens When Special Issues Just Aren't “Special” Anymore?
Authors: Priem Richard L.
Published: November 2006

Are special issues becoming “too much of a good thing” in elite general management journals? Although a few special issues might serve to spur innovative research in important areas of management scholarship that otherwise are being overlooked, the author argues that profligate commissioning of special issues distorts the marketplace for ideas by commanding particular frequency distributions of preferred topics in journals. This results in a “command economy” for ideas that, ironically, can retard innovation. Scholars would be well served by being more selective when commissioning special issues in elite general management journals.
Stay in School, Don’t Become a Parent
Authors: Pacheco Julianna Sandell , Plutzer Eric
Published: November 2006

We investigate three important life transitions—becoming a parent, getting married, and dropping out or graduating from high school—on the development of civic engagement. We qualify the socioeconomic status and resources frameworks by arguing that effects should differ across racial and ethnic lines. We address these issues by analyzing data from a nationally representative, 12-year panel study comprising more than 12,000 eighth graders in 1988 (National Educational Longitudinal Survey, 1988-2000). We show that early parenthood can have important and lasting impacts on voter turnout many years later. For Whites, early parenthood leads to increased risk of dropping out of high school. High school interruption has major negative impacts on later turnout, even when the student eventually returned to earn a diploma. The findings advance our understanding of the crucial period of adolescence by showing how race and event timing condition the impact of formative life events on later political participation.
Optimising the angular resolution of EBSD
Authors: Brough I. , Bate P. S. , Humphreys F. J.
Published: November 2006

The factors which determine the angular resolution in electron backscatter diffraction (EBSD), and the operating conditions which optimise it are considered. On suitable samples the angular resolution may be substantially improved by data averaging using an edge preserving Kuwahara filter. It is shown that measurements of misorientation by direct comparison of diffraction patterns can reduce the angular resolution to below 0·02°, and the application of this method to linescans and EBSD maps is discussed. It is concluded that the applicability of pattern comparison methods for EBSD maps is limited by time and microstructural considerations, but linescans using this method are shown to produce high quality data in material containing small misorientations, which cannot readily be analysed by the conventional Hough transform EBSD method.
Processing and interpretation of EBSD data gathered from plastically deformed metals
Authors: Godfrey A. , Mishin O. V. , Liu Q.
Published: November 2006

The use of electron backscattered diffraction (EBSD) for the investigation of dislocation boundary microstructures formed during plastic deformation of metals is discussed. A quantitative description is given of the angular resolution limitation in EBSD mapping. The ability of filtering using orientation averaging to improve the angular resolution of the EBSD data is then considered. Orientation filtering is tested using both simulated EBSD maps where a certain orientation noise function and level are assumed and additionally by direct comparison of EBSD and orientation measurements taken in the transmission electron microscope from the same region of a thin foil. Orientation filtering results in an improvement of data quality, but filtering can also introduce artefacts that cannot be distinguished from real microstructural features. The main limitation at present in developing specific recommendations for the use of filtering methods is that more information is required about the nature of the orientation noise at or near dislocation boundaries.
Application of EBSD to analysis of microstructures in commercial steels
Authors: Ryde L.
Published: November 2006

Electron backscatter diffraction (EBSD) is a very powerful technique for microstructural characterisation and analysis of crystalline materials. Many of the structural parameters that control the properties and performance of the material can be derived from EBSD data, e.g. grain size, phase constituents, mechanical anisotropy and residual strain. This should make EBSD a valuable tool to control and develop microstructures of commercial metallic materials but technique has mainly been used in basic research at universities and not to the same extent for research and development in industry. The development in scanning electron microscopes and EBSD equipment in recent years makes it possible to measure ‘difficult’ structures, e.g. with higher dislocation content, but can it manage the complexity of the structures of commercial materials and achieve reliable data? During 2004 an EBSD round robin test on industrial metallic materials was coordinated by KIMAB to test the current status of the technique and most of the results presented here are from that project and participants in that test. The results and conclusions from the test will be published when it is accepted by the financing organisation but the present paper will focus on common problems or difficult tasks that appear during EBSD measurements of some complex or mixed structures in steel and how they can be solved. All participants experienced difficulties despite being familiar with the EBSD technique, which demonstrated the need for a comparative study of this sort and need for guidance in these topics.
Grain refinement mechanism of Fe–32Ni alloys during multiaxial forging
Authors: Han B. J. , Xu Z.
Published: November 2006

Warm deformation of Fe–32Ni alloy was studied in connection with microstructure developments in multiple axial forging at a temperature of 823 K (∼0·5 Tm) and a strain rate of 10−3 s−1. The microstructure evolution of the deformed alloys was investigated using EBSD and TEM. The structural changes are characterised by the evolution of many mutually crossing sub-boundaries at low to moderate strains, finally followed by the development of very fine grains with medium to large angle boundaries at large strains. These new grains are concluded to be evolved by a kind of continuous reaction, that is continuous dynamic recrystallisation; this process is that sub-boundaries crossing each other subdivide an austenite grain into several subgrains and these subgrains are gradually reoriented to new independent grains with their boundaries being transformed into large angle boundaries in subsequent deformation.
Pharmacogenetics, Pharmacogenomics and Personalized Medicine: Are We There Yet?
Authors: Davies Stella M.
Published: November 2006

The genetic basis of a differential response to drugs has been understood for a limited number of agents for over 30 years. This knowledge has generated hope that the individual basis for response to a wide range of drugs would be quickly known, and individualized drug selection and dosing would be possible for many or all disorders. Understanding the variable response to drugs seems particularly pressing in the field of oncology, in which the stakes are high (failure to cure cancer usually leads to death), drugs commonly have a narrow therapeutic index, and toxicities can be severe (a significant frequency of toxic death is a feature of most acute myeloid leukemia protocols, for example). However, in common with many new technologies, the generalizability and clinical application of pharmacogenetics has proved more challenging than expected. Difficulties include, in many examples, a modest clinical effect relative to genotype, therapy-specific, not broad, applicability and the very major challenge of unraveling the complexity of gene-gene interactions. In addition, ethical and economic challenges to the application of pharmacogenetics have moved to the fore in recent years, particularly in the context of racial differences in outcome of therapy. Genomic, rather than candidate gene approaches to identification of relevant loci are increasingly being explored, and significant progress is being made. However, greater understanding of the complexities of multiple gene modifiers of outcome, and the statistical challenge of understanding such data, will be needed before individualized therapy can be applied on a routine basis.
Deeper Insights into Hematological Oncology Disorders via Single-Cell Phospho-Signaling Analysis
Authors: Nolan Garry P.
Published: November 2006

An understanding of hematological cancer cell signaling processes poses one of the most complex and intractable problems in modern biomedical inquiry. While we understand some of the fundamental players that contribute to oncogenic processes, significant effort is focused upon determining how these individual players relay information to each other to create the composite functions of a cancer cell. Efforts designed to understand these processes at the single cell level will undoubtedly allow for understanding of the heterogeneity of hematological tumors as well as, simultaneously, the function of the ‘responding’ immune system. I will relate some of the insights our laboratory has developed over the last several years applying single-cell phospho-flow cytometry to the study of signaling in primary patient material and murine models. While it is clear that this analysis now allows us to accomplish phospho-signaling biochemistry at the single cell level with primary cell material, we are only beginning to develop some of the bioinformatics tools to appropriately display the vast amount of information collected by such approaches. These approaches, however, have already allowed us to develop approaches that prognosticate patient outcomes based on signaling status, prior to any treatment, as well as subgroup patient subtypes according to signaling states. The modest efforts to date presage a time where it should be possible to provide far more tailored therapies specific to the varied diseases represented by the hematological malignancies.
ABL Kinase Inhibitor Therapy for CML: Baseline Assessments and Response Monitoring
Authors: Hughes Timothy
Published: November 2006

For chronic phase chronic myeloid leukemia (CML) patients treated with imatinib, the essential pre-therapy assessments include bone marrow morphology and cytogenetics as well as a baseline real-time quantitative PCR (RQ-PCR) for BCR-ABL. Baseline assessments of clinical relevance include Sokal and Hasford prognostic scores. Several other baseline assays are likely to be predictive of response, including IC50imatinib, organic cation transporter-1 (OCT-1) mRNA level, and gene expression profiles, but further confirmation is required. RQ-PCR assays of blood at least every 3 months once patients have commenced imatinib is recommended. This will facilitate early identification of suboptimal responders who may benefit from higher doses of imatinib or alternative therapy, and identify at an early stage patients with acquired resistance. Management of the latter group can be further guided by the findings from cytogenetics and BCR-ABL kinase domain mutation screening. Bone marrow cytogenetics is indicated at least every 6 months until the patient achieves major molecular response. RQ-PCR is only clinically useful if it is conducted under a rigorous quality control regimen so that fluctuations in the BCR-ABL level can be confidently attributed to a biological cause rather than assay variation. To further improve the clinical value of RQ-PCR monitoring, expression of results on an international scale is needed. This will facilitate a more uniform and rational approach to management of suboptimal response and loss of response.