bluuebunny/crossref_metadata_2025 huggingface dataset:
CXCR4 Inhibition Synergizes with Cytotoxic Chemotherapy in Gliomas
Authors: Redjal Navid , Chan Jennifer A. , Segal Rosalind A. , Kung Andrew L.
Published: November 2006

Purpose: The chemokine receptor CXCR4 is expressed in many different cancers. In malignant brain tumors, CXCR4 signaling has been implicated in tumor growth, survival, and migration, and pharmacologic inhibition of CXCR4 results in decreased tumor growth in preclinical models. To understand how CXCR4 inhibitors may be incorporated into clinical therapy, we examined determinants of responsiveness to CXCR4 inhibition. Because optimal use of CXCR4 inhibition will likely be a part of multimodality therapy, we also investigated the efficacy of CXCR4 inhibition combined with conventional cytotoxic chemotherapy.

Experimental Design: CXCR4 protein levels and responsiveness to the CXCR4 inhibitor AMD3100 were determined in a panel of glioblastoma multiforme cell lines. The effects of AMD3100, alone or in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), on cell growth were determined for several of these cell lines in vitro. We used an orthotopic model of glioblastoma multiforme to evaluate the antitumor efficacy of AMD3100 combined with BCNU in vivo.

Results: The level of CXCR4 protein expression in glioblastoma multiforme cells predicts the dose at which there is a response to AMD3100; cells that express higher levels of CXCR4 protein require higher doses for equivalent response. In all cell lines tested, treatment of glioblastoma multiforme cells with BCNU followed by AMD3100 results in synergistic antitumor efficacy in vitro. This synergy can also be seen in an orthotopic glioblastoma multiforme model. Treatment with subtherapeutic doses of BCNU in combination with AMD3100 results in tumor regression in vivo, and this reflects both increased apoptosis and decreased proliferation following combination therapy.

Conclusion: These studies support testing CXCR4 inhibitors in patients with glioblastoma multiforme and establish that inhibition of CXCR4 synergizes with conventional cytotoxic therapies in a clinically relevant combinatorial strategy.
Reprimo Methylation Is a Potential Biomarker of Barrett's-Associated Esophageal Neoplastic Progression
Authors: Hamilton James P. , Sato Fumiaki , Jin Zhe , Greenwald Bruce D. , Ito Tetsuo , Mori Yuriko , Paun Bogdan C. , Kan Takatsugu , Cheng Yulan , Wang Suna , Yang Jian , Abraham John M. , Meltzer Stephen J.
Published: November 2006

Purpose: Reprimo, a candidate tumor-suppressor gene, regulates p53-mediated cell cycle arrest at G2 phase, and tumor-suppressor gene methylation is involved in the pathogenesis and progression of esophageal cancer. Our aim was to determine whether and at what phase of neoplastic progression Reprimo methylation occurs in Barrett's adenocarcinogenesis, as well as its columnar or squamous cell-type specificity. We also sought to determine whether Reprimo expression could be restored in vitro by the demethylating agent 5-aza-deoxycytidine (5AzaC).

Experimental Design: Quantitative methylation-specific PCR for Reprimo was done using an ABI7700 (Taqman) apparatus on 175 endoscopic biopsy specimens. In addition, reverse transcription-PCR and quantitative methylation-specific PCR were done on esophageal carcinoma cells before and after treatment with 5AzaC.

Results: In Barrett's esophagus (BE; P = 0.001), high-grade dysplasia (HGD; P = 0.001), and esophageal adenocarcinoma (EAC; P = 0.00003), the level and frequency of Reprimo methylation were significantly higher than in normal esophagus (NE). There was no statistically significant difference between BE and EAC, HGD and EAC, or NE and esophageal squamous cell carcinoma (ESCC). Reprimo methylation occurred in 0 of 19 NE samples, 6 (13%) of 45 ESCC, 9 (36%) of 25 BE, 7 (64%) of 11 HGD, and 47 (63%) of 75 EAC. Analysis of Reprimo methylation in EAC versus NE revealed an area under the receiver-operator characteristic curve of 0.812 (P < 0.00001; 95% confidence interval, 0.73-0.90). In vitro 5AzaC treatment of OE33 EAC cells reduced Reprimo methylation and increased Reprimo expression.

Conclusions: Reprimo methylation occurs significantly more frequently in BE, HGD, and EAC than in NE or ESCC, suggesting that this epigenetic alteration is a specialized columnar, cell-specific early event with potential as a biomarker for the early detection of esophageal neoplasia.
Concomitant inhibition of epidermal growth factor and vascular endothelial growth factor receptor tyrosine kinases reduces growth and metastasis of human salivary adenoid cystic carcinoma in an orthotopic nude mouse model
Authors: Younes Maher N. , Park Young Wook , Yazici Yasemin Dakak , Gu Meirong , Santillan Alfredo A. , Nong Xiaolin , Kim Seungwon , Jasser Samar A. , El-Naggar Adel K. , Myers Jeffrey N.
Published: November 2006

We hypothesized that epidermal growth factor (EGF) receptor (EGFR) activation and vascular endothelial growth factor (VEGF)–induced angiogenic signals are important for the progression and metastasis of human salivary adenoid cystic carcinoma (ACC). To test this hypothesis, we evaluated the therapeutic effect of AEE788, a dual inhibitor of EGF and VEGF receptor (VEGFR) tyrosine kinases, on human salivary ACC. In clinical specimens of salivary ACC, EGF and VEGF signaling proteins were expressed at markedly higher levels than in adjacent normal glandular tissues. We examined the effects of AEE788 on salivary ACC cell growth and apoptosis and on the phosphorylation of EGFR and VEGFR-2 in salivary ACC cells. Treatment of salivary ACC cells with AEE788, alone or in combination with chemotherapy, led to growth inhibition, induction of apoptosis, and dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation. To determine the in vivo antitumor effects of AEE788, nude mice with orthotopic parotid tumors were randomized to receive oral AEE788 alone, paclitaxel alone, cisplatin alone, a combination of AEE788 plus paclitaxel, a combination of AEE788 plus cisplatin, or a placebo. AEE788 inhibited tumor growth and prevented lung metastasis in nude mice. To study the mechanism of interaction between AEE788 and chemotherapy, AEE788 was found to potentiate growth inhibition and apoptosis of ACC tumor cells mediated by chemotherapy. Tumors of mice treated with AEE788 and AEE788 plus chemotherapy exhibited down-regulation of activated EGFR and VEGFR-2, increased tumor and endothelial cell apoptosis, and decreased microvessel density, which correlated with a decrease in the level of matrix metalloproteinase-9 and matrix metalloproteinase-2 expression and a decrease in the incidence of vascular metastasis. These data show that EGFR and VEGFR can be molecular targets for therapy of salivary ACC. [Mol Cancer Ther 2006;5(11):2696–705]
Gene expression profiles do not consistently predict the clinical treatment response in locally advanced breast cancer
Authors: Sørlie Therese , Perou Charles M. , Fan Cheng , Geisler Stephanie , Aas Turid , Nobel Andrew , Anker Gun , Akslen Lars A. , Botstein David , Børresen-Dale Anne-Lise , Lønning Per Eystein
Published: November 2006

Neoadjuvant treatment offers an opportunity to correlate molecular variables to treatment response and to explore mechanisms of drug resistance in vivo. Here, we present a statistical analysis of large-scale gene expression patterns and their relationship to response following neoadjuvant chemotherapy in locally advanced breast cancers. We analyzed cDNA expression data from 81 tumors from two patient series, one treated with doxorubicin alone (51) and the other treated with 5-fluorouracil and mitomycin (30), and both were previously studied for correlations between TP53 status and response to therapy. We observed a low frequency of progressive disease within the luminal A subtype from both series (2 of 36 versus 13 of 45 patients; P = 0.0089) and a high frequency of progressive disease among patients with luminal B type tumors treated with doxorubicin (5 of 8 patients; P = 0.0078); however, aside from these two observations, no other consistent associations between response to chemotherapy and tumor subtype were observed. These specific associations could possibly be explained by covariance with TP53 mutation status, which also correlated with tumor subtype. Using supervised analysis, we could not uncover a gene profile that could reliably (>70% accuracy and specificity) predict response to either treatment regimen. [Mol Cancer Ther 2006;5(11):2914–8]
Histone deacetylase inhibitors and paclitaxel cause synergistic effects on apoptosis and microtubule stabilization in papillary serous endometrial cancer cells
Authors: Dowdy Sean C. , Jiang Shujuan , Zhou X. Clare , Hou Xiaonan , Jin Fan , Podratz Karl C. , Jiang Shi-Wen
Published: November 2006

The use of histone deacetylase (HDAC) inhibitors has shown promise for a variety of malignancies. In this investigation, we define the activity of this class of inhibitors in combination with traditional cytotoxic chemotherapy in endometrial cancer cells. Significant reductions in growth were observed in Ark2 and KLE endometrial cancer cells following treatment with paclitaxel, doxorubicin, carboplatin, or the HDAC inhibitor trichostatin A (TSA). However, only combined treatment with TSA/paclitaxel caused synergistic inhibition of cell growth. This combination also resulted in significant changes in cell morphology. Using cell cycle analysis, nuclear staining, and Western blot analysis for poly(ADP-ribose) polymerase and caspase-9 degradation products, TSA/paclitaxel showed the most dramatic activation of the apoptotic cascade. These effects were also observed when the HDAC inhibitors HDAC inhibitor-1 or oxamflatin were substituted for TSA. The anticancer properties of paclitaxel are known to result in part from inhibition of microtubule depolymerization, which results in apoptosis. We show that TSA administration also stabilizes microtubules via α-tubulin acetylation. Furthermore, using Western blot and immunohistochemical analysis, treatment with TSA/paclitaxel led to a significant increase in acetylated tubulin and microtubule stabilization. These effects were confirmed in a mouse xenograft model. Moreover, TSA/paclitaxel resulted in a 50% reduction in tumor weight compared with either agent alone. This study provides in vivo evidence of nonhistone protein acetylation as one possible mechanism by which HDAC inhibitors reduce cancer growth. The TSA/paclitaxel combination seems to hold promise for the treatment of serous endometrial carcinoma and other malignancies with limited sensitivity to paclitaxel. [Mol Cancer Ther 2006;5(11):2767–76]
Potentiation of radiation sensitivity in breast tumor cells by the vitamin D3 analogue, EB 1089, through promotion of autophagy and interference with proliferative recovery
Authors: DeMasters Gerald , Di Xu , Newsham Irene , Shiu Robert , Gewirtz David A.
Published: November 2006

1,25-Dihydroxyvitamin D3 and vitamin D3 analogues, such as EB 1089, potentiate the response to ionizing radiation in breast tumor cells. The current studies address the basis for this interaction by evaluating DNA damage and repair, the effect of interference with reactive oxygen generation, the involvement of p53 and caspase-3, signaling through c-myc, as well as the induction of senescence and multiple modes of cell death. EB 1089 failed to increase the extent of radiation-induced DNA damage or to attenuate the rate of DNA repair. The reactive oxygen scavengers N-acetyl-l-cysteine and reduced glutathione failed to protect the cells from the promotion of cell death by EB 1089 and radiation. Whereas MCF-7 cells expressing caspase-3 showed significant apoptosis with radiation alone as well as with EB 1089 followed by radiation, EB 1089 maintained its ability to confer susceptibility to radiation-induced cell killing, in large part by interference with proliferative recovery. In contrast, in breast tumor cells lacking p53, where radiation promoted extensive apoptosis and the cells failed to recover after radiation treatment, EB 1089 failed to influence the effect of radiation. EB 1089 treatment interfered with radiation-induced suppression of c-myc; however, induction of c-myc did not prevent senescence by radiation alone or radiation-induced cell death promoted by EB 1089. EB 1089 did not increase the extent of micronucleation, indicative of mitotic catastrophe, induced by radiation alone. However, EB 1089 did promote extensive autophagic cell death in the irradiated cells. Taken together, these studies suggest that the effect of EB 1089 treatment on the radiation response is related in part to enhanced promotion of autophagic cell death and in part to interference with the proliferative recovery that occurs with radiation alone in p53 wild-type breast tumor cells. [Mol Cancer Ther 2006;5(11):2786–97]
In vitro and in vivo activity of R547: a potent and selective cyclin-dependent kinase inhibitor currently in phase I clinical trials
Authors: DePinto Wanda , Chu Xin-Jie , Yin Xuefeng , Smith Melissa , Packman Kathryn , Goelzer Petra , Lovey Allen , Chen Yingsi , Qian Hong , Hamid Rachid , Xiang Qing , Tovar Christian , Blain Roger , Nevins Tom , Higgins Brian , Luistro Leopoldo , Kolinsky Kenneth , Felix Bernardo , Hussain Sazzad , Heimbrook David
Published: November 2006

The cyclin-dependent protein kinases are key regulators of cell cycle progression. Aberrant expression or altered activity of distinct cyclin-dependent kinase (CDK) complexes results in escape of cells from cell cycle control, leading to unrestricted cell proliferation. CDK inhibitors have the potential to induce cell cycle arrest and apoptosis in cancer cells, and identifying small-molecule CDK inhibitors has been a major focus in cancer research. Several CDK inhibitors are entering the clinic, the most recent being selective CDK2 and CDK4 inhibitors. We have identified a diaminopyrimidine compound, R547, which is a potent and selective ATP-competitive CDK inhibitor. In cell-free assays, R547 effectively inhibited CDK1/cyclin B, CDK2/cyclin E, and CDK4/cyclin D1 (Ki = 1–3 nmol/L) and was inactive (Ki > 5,000 nmol/L) against a panel of >120 unrelated kinases. In vitro, R547 effectively inhibited the proliferation of tumor cell lines independent of multidrug resistant status, histologic type, retinoblastoma protein, or p53 status, with IC50s ≤ 0.60 μmol/L. The growth-inhibitory activity is characterized by a cell cycle block at G1 and G2 phases and induction of apoptosis. R547 reduced phosphorylation of the cellular retinoblastoma protein at specific CDK phosphorylation sites at the same concentrations that induced cell cycle arrest, suggesting a potential pharmacodynamic marker for clinical use. In vivo, R547 showed antitumor activity in all of the models tested to date, including six human tumor xenografts and an orthotopic syngeneic rat model. R547 was efficacious with daily oral dosing as well as with once weekly i.v. dosing in established human tumor models and at the targeted efficacious exposures inhibited phosphorylation of the retinoblastoma protein in the tumors. The selective kinase inhibition profile and the preclinical antitumor activity of R547 suggest that it may be promising for development for use in the treatment of solid tumors. R547 is currently being evaluated in phase I clinical trials. [Mol Cancer Ther 2006;5(11):2644–58]
Mithramycin A sensitizes cancer cells to TRAIL-mediated apoptosis by down-regulation of XIAP gene promoter through Sp1 sites
Authors: Lee Tae-Jin , Jung Eun Mi , Lee Jung Tae , Kim Shin , Park Jong-Wook , Choi Kyeong Sook , Kwon Taeg Kyu
Published: November 2006

Mithramycin A is a DNA-binding antitumor agent, which has been clinically used in the therapies of several types of cancer and Paget's disease. In this study, we investigated the combined effect of mithramycin A and tumor necrosis factor-α–related apoptosis-inducing ligand (TRAIL) on apoptosis of cancer cells. In Caki renal cancer cells, which are resistant to TRAIL, cotreatment with subtoxic doses of mithramycin A and TRAIL resulted in a marked increase in apoptosis. This combined treatment was also cytotoxic to Caki cells overexpressing Bcl-2 but not to normal mesengial cells. Moreover, apoptosis by the combined treatment with mithramycin A and TRAIL was dramatically induced in various cancer cell types, thus offering an attractive strategy for safely treating malignant tumors. Mithramycin A–stimulated TRAIL-induced apoptosis was blocked by pretreatment with the broad caspase inhibitor zVAD-fmk or Crm-A overexpression, showing its dependence on caspases. We found that mithramycin A selectively down-regulated XIAP protein levels in various cancer cells. Luciferase reporter assay and the chromatin immunoprecipitation assay using the XIAP promoter constructs show that mithramycin A down-regulates the transcription of XIAP gene through inhibition of Sp1 binding to its promoter. Although XIAP overexpression significantly attenuated apoptosis induced by mithramycin A plus TRAIL, suppression of XIAP expression by transfection with its small interfering RNA prominently enhanced TRAIL-induced apoptosis. We present here for the first time that mithramycin A–induced suppression of XIAP transcription plays a critical role in the recovery of TRAIL sensitivity in various cancer cells. [Mol Cancer Ther 2006;5(11):2737–46]
Regulation of Vascular Inflammation and Remodeling by ETS Factors
Authors: Oettgen Peter
Published: November 2006

The ETS (
E
26
T
ransformation-specific
S
equence) factors are comprised of a family of transcription factors that share a highly conserved DNA binding domain. Although originally described for their role as protooncogenes in the development of several types of human cancer, they have subsequently been shown to regulate a wide variety of biological processes including cellular growth and differentiation under normal and pathological conditions. As transcription factors, they can either function as activators or repressors of gene expression. Several ETS family members are expressed in cells of vascular origin, including endothelial cells and vascular smooth muscle cells, where they regulate the expression of a number of vascular-specific genes. In the past few years, emerging evidence supports a novel role for selected ETS family members in the regulation of vascular inflammation and remodeling. ETS factor expression can be induced by proinflammatory cytokines, growth factors, and vasoactive peptides. Examples of some of the target genes regulated by ETS factors include adhesion molecules, chemokines, and matrix metalloproteinases. Targeted disruption of selected ETS family members such as Ets-1 in mice is associated with marked reductions in the recruitment of inflammatory cells and vascular remodeling in response to systemic administration of the vasoactive peptide angiotensin II. The purpose of this review is to provide an overview of recent advances that have been made in defining a role for selected members of the ETS transcription factor family in the regulation of vascular-specific gene expression, vascular inflammation, and remodeling.
Did Second Isaiah write Lamentations iii?
Authors: Middlemas Jill
Published: November 2006

In recent years, textual analyses of Lamentations have increasingly noted correspondences with Isaiah xl-lv. The alignment of the two has resulted in various proposals about influence with the recent work of Patricia Willey noticeable in its claim that the Lamentations iii geber provided the paradigm for the Suffering Servant figure of the third and fourth songs (Isa. lii, liii-liv). This article considers this discussion anew with the intent to ascertain the provenance of the Lamentations geber and his relationship to Second Isaiah. After a close analysis of some of the more persuasive correspondences between the two figures, it becomes clear that the geber fits uncomfortably in the book of Lamentations. Furthermore, his persona functions as a corrective to the responses to disaster found so prominently outside of chapter iii. The parenetic section which follows the geber's lament in vv. 22-39 defines the sufferer and uses his experience to teach sanctioned views of the deity and the human person. Bearing in mind the way the geber acts to admonish and teach in Lamentations leads to the view that the suffering figure has more commonality with images and thought stemming from the Golah community. The paper explores the implications for understanding a Golah view placed at the heart of Lamentations for interpreting the material.
Dancing for God or the Devil: Pentecostal Discourse on Popular Dance in Kinshasa
Authors: Pype Katrien
Published: November 2006

This article studies the dance poetics and politics of Christians in contemporary Kinshasa. For Kinois (inhabitants of Kinshasa), dance is one of the most important technologies to get in touch with an invisible Other, the divine or the occult. In sermons, and other modes of instruction, spiritual leaders inform their followers about the morality of songs and dances. These discourses reflect pentecostal thought, and trace back the purity of specific body movements to the choreography's source of inspiration. As the specific movements of so-called sacred dances borrow from a wide array of cultural worlds, ranging from traditional ritual dances and popular urban dance to biblical tales, the religious leaders state that not just the body movements, but also the space where people dance and the accompanying songs, define the Christian or pagan identity of the dancer. Therefore, both the reflections upon dance movements and the dance events within these churches will be discussed as moments in the construction of a Christian community.
Pursuit of Comfort and Pursuit of Harmony: Culture, Relationships, and Social Support Seeking
Authors: Kim Heejung S. , Sherman David K. , Ko Deborah , Taylor Shelley E.
Published: November 2006

This research examined whether people from collectivistic cultures are less likely to seek social support than are people from individualistic cultures because they are more cautious about potentially disturbing their social network. Study 1 found that Asian Americans from a more collectivistic culture sought social support less and found support seeking to be less effective than European Americans from a more individualistic culture. Study 2 found that European Americans' willingness to seek support was unaffected by relationship priming, whereas Asian Americans were willing to seek support less when the relationship primed was closer to the self. Study 3 replicated the results of Study 2 and found that the tendency to seek support and expect social support to be helpful as related to concerns about relationships. These findings underscore the importance of culturally divergent relationship patterns in understanding social support transactions.
Play It Safe or Go for the Gold? A Terror Management Perspective on Self-Enhancement and Self-Protective Motives in Risky Decision Making
Authors: Landau Mark J. , Greenberg Jeff
Published: November 2006

Terror management theory (TMT) posits that bolstering self-esteem buffers mortality concerns; accordingly, in past research, heightening mortality salience (MS) increases self-enhancement. However, risky self-esteem-relevant decisions often present a choice between enhancing self-esteem by striving for excellence and protecting self-esteem by avoiding potential failure. Which strategy is preferred under MS? Combining TMT with insights from Steele, Spencer, and Lynch's (1993) resource model, the authors hypothesized and found that MS leads high, but not low, self-esteem participants faced with a risky decision to pursue opportunities for excellence despite substantial risk of failure (Studies 1 and 2); in Study 3, using a more impactful decision, this effect was replicated and it was furthermore found that mortality-salient low-self-esteem participants become more risk-averse. Furthermore, in Study 2, a self-affirmation prime, previously shown to reduce MS-induced defenses, eliminated the self-enhancement effect among high-self-esteem participants. Implications for understanding self-esteem, TMT, and risky decision making are briefly discussed.
Emotional Ties That Bind: The Roles of Valence and Consistency of Group Emotion in Inferences of Cohesiveness and Common Fate
Authors: Magee Joe C. , Tiedens Larissa Z.
Published: November 2006

In three studies, observers based inferences about the cohesiveness and common fate of groups on the emotions expressed by group members. The valence of expressions affected cohesiveness inferences, whereas the consistency of expressions affected inferences of whether members have common fate. These emotion composition effects were stronger than those due to the race or sex composition of the group. Furthermore, the authors show that emotion valence and consistency are differentially involved in judgments about the degree to which the group as a whole was responsible for group performance. Finally, it is demonstrated that valence-cohesiveness effects are mediated by inferences of interpersonal liking and that consistency-common fate effects are mediated by inferences of psychological similarity. These findings have implications for the literature on entitativity and regarding the function of emotions in social contexts.
Positive Illusions in Marital Relationships: A 13-Year Longitudinal Study
Authors: Miller Paul J. E. , Niehuis Sylvia , Huston Ted L.
Published: November 2006

This study examined the long-term consequences of idealization in marriage, using both daily diary and questionnaire data collected from a sample of 168 newlywed couples who participated in a 4-wave, 13-year longitudinal study of marriage. Idealization was operationalized as the tendency for people to perceive their partner as more agreeable than would be expected based on their reports of their partner's agreeable and disagreeable behaviors. Spouses who idealized one another were more in love with each other as newlyweds. Longitudinal analyses suggested that spouses were less likely to suffer declines in love when they idealized one another as newlyweds. Newlywed levels of idealization did not predict divorce.
Television Viewing of Higher Secondary Students
Authors: Shejwal B.R. , Purayidathil Joy
Published: November 2006

The impact of TV viewing on academic achievement and mathematical reasoning was examined in a group of 654 higher secondary students (368 boys, 286 girls) from Maharashtra, India. Both among boys and girls, TV viewing had significant negative correlations with academic achievement. TV viewing and mathematical reasoning were negatively correlated among boys only. Heavy viewers of television were poor, compared to light viewers, in their academic achievement and mathematical reasoning. Significant gender differences were noted both in academic achievement and mathematical reasoning. TV viewing explained 13% of the variance in the academic achievement of the students.
Silkworms, Capital and Merchant Ships
Authors: Ertl Thomas
Published: November 2006

Silk represented a bridge connecting East Asia, the Middle East and the Occident in the exchange of art forms between A.D. 1000 and 1500. The study of medieval production, trade, and use of silk, therefore, provided the opportunity to examine the complex dependencies between the artistic mind, technical skills, entrepreneurial options and political conditions in different areas of Eurasia. The aim of this article is not only to explain the overwhelming rise of the late medieval Italian silk industry, but to show the pace of regional developments in Eurasia, at times diverging, at times in unison.
The Shaping of a Sacred Space
Authors: Ginio Eyal
Published: November 2006

The sicil, the archives of the kadi, of eighteenth-century Ottoman Salonica preserves about a dozen endowment deeds established by affluent Muslim Salonicans in favour of a new Sufi lodge (tekke), originally established by Zühuri Şeyh Ahmet Efendi in the city. These documents enable us to follow the shaping of a new sacred space in Salonica that became, for a limited period, a focal point for charitable activity during the middle of the eighteenth century. These endowment deeds likewise enable us to explore the interaction between the tekke and the community it served. By discussing the connections between the local saint, his tekke and the surrounding community, this article explores contemporary perceptions of charity, attitudes towards the deserving ‘poor’ and the negotiation of legitimacy through providing charity.
Gregorio Dati (1362–1435) and the Limits of Individual Agency
Authors: Epurescu-Pascovici Ionuţ
Published: November 2006

This article focuses on the diary of the Florentine Gregorio Dati (1362–1435) and its significance for the study of agency in pre-modern Europe. In particular, this article analyses Dati's ‘abeyance of individual agency’ in the context of his family affairs, business ventures, and participation in politics, as well as in relation to Dati's views on his personal development. The diary data, and in particular the private memoranda of 1404 and 1412, are corroborated with Dati's other writings and placed in the context of late-medieval and Renaissance culture. As such, this article draws attention to the role of cultural factors in the construction of agency, and aims to participate in a broader, interdisciplinary debate.
From Climbing Stairs to Riding Waves
Authors: Kayes D. Christopher
Published: November 2006

This article provides a model, measure, and theoretical background for understanding group critical thinking. A research study was designed to test group critical thinking and its relationship to the learning style composition of teams. Groups were composed using a randomized block design based on learning style, and responses to a group exercise were coded for type of critical thinking. Results showed support for a group-level measure of critical thinking based on interrater agreement on codes. Some support was found for differences in critical thinking based on learning style. However, critical thinking was not shown to relate to group cohesion, psychological safety, or efficacy. This study marks the first empirical evidence supporting critical thinking at the group level. It provides a measure that can be used in assessing the level of critical thinking for vocational education and assessing team performance on ill-structured problems.
Virtual Teams and Group Member Dissimilarity
Authors: Krebs Scott A. , Hobman Elizabeth V. , Bordia Prashant
Published: November 2006

The consequences of demographic dissimilarity for group trust in work teams was examined in a virtual (computer-mediated) and a face-to-face (FTF) environment. Demographic dissimilarity (based on age, gender, country of birth, enrolled degree) was predicted to be negatively associated with group trust in the FTF environment but not in the computer-mediated environment. Participants worked in small groups on a creative task for 3 consecutive days. In the computer-mediated environment, participants worked on the task for an hour per day. In the FTF environment, participants worked on the task for 20 minutes per day. Partial support was found for the effectiveness of computer-mediated groups in reducing the negative consequences of dissimilarity. Age dissimilarity was negatively related to trust in FTF groups but not in computer-mediated groups. Birthplace dissimilarity was positively related to trust in computer-mediated groups. Implications for the successful management of virtual teams are discussed.
The Craft of Translation
Authors: Gruber Daniel A.
Published: November 2006

Best-selling author Malcolm Gladwell talks about how he “simplifies and synthesizes” research in his books and articles with the goal of getting readers excited about the “academic study of ideas.” The self-described “conversation starter” gives a glimpse into how he puts together his articles and where his ideas emerge. The reader learns about Gladwell's relationship with academia, which he sees as an “important cog in the process” of disseminating research to a wider audience. Gladwell illuminates the power of narratives in presenting complex ideas. He also shares what he would like to teach and research at a business school, if given the opportunity. Finally, Gladwell's thoughts raise key questions to consider about the role and responsibility of scholars in translating research to audiences outside of the academy.
Developing the Process Model of Collective Corruption
Authors: Palmer Donald , Maher Michael W.
Published: November 2006

There are two explanations of organizational crime. The dominant one assumes that people make discrete decisions and develop positive dispositions to engage in crime before embarking on criminal behavior. An emerging alternative assumes that people often embark on criminal behavior through a process and without first developing positive dispositions. The authors review the dominant explanation of organizational crime, delve into its two main variants, and provide examples of each. They also review the emerging alternative explanation and outline a variant of this approach that analyzes collective corruption, a form of crime that involves the sustained coordination of multiple organizational participants. Then they propose five ways to extend this model of collective corruption and illustrate their extension by drawing on a detailed account of an illegal stock market transaction taken from Den of Thieves, by James Stewart. The authors conclude by considering the theoretical and policy implications of the alternative perspective.
Sticking Together
Authors: Campbell David E.
Published: November 2006

How does classroom racial diversity affect the civic dimension of American adolescents’ education? Does a high level of diversity correlate with more or less discussion of political issues, a key criterion for an effective civic education? Do different levels of political discussion, in turn, have consequences for the intention of adolescents to become informed voters? Using the International Association for the Evaluation of Educational Achievement Civic Education Study, this article puts these questions to the empirical test. Results show that racial diversity corresponds to a lower level of political discussion in the classroom. Less political discussion, in turn, correlates with a lower likelihood of adolescents’ stated intention of becoming an informed voter.
Measurement and prediction of deformation in plane strain compression tests of AA5182
Authors: Boldetti C. , Pinna C. , Howard I. C.
Published: November 2006

The present paper concerns the numerical prediction and experimental measurement of the distribution of strain in a plane strain compression test by means of a gridded insert. The insert was engraved with a 1 × 1 mm grid pitch and was embedded in an AA5182 sample. The tests were performed at 400°C with a reduction ratio of ∼20% and at a strain rate of 0·7 s−1. A thermocouple was used to record the temperature during the test. After the test, no detachment was observed between insert and sample, suggesting a close contact between them. The shape of the grid after deformation was analysed, and the in-plane component of the plastic strain calculated and compared with the numerical results obtained through finite element modelling of the test. In a comparison between experimental data and the results of a finite element (FE) model of the test that assumed perfect tool alignment, the fields of temperature agreed very well, while that for the in-plane component of strain was reasonable but inaccurate. However, significant misalignment of the tools was found in the experiments (a common occurrence in plane strain compression testing). When comparison was made with an FE model that included the geometry of the tool misalignment, the agreement was excellent. The paper discusses these effects and others such as the influence of 3D effects in the modelling.
Characterisation of nitride thin films by electron backscatter diffraction and electron channelling contrast imaging
Authors: Trager-Cowan C. , Sweeney F. , Winkelmann A. , Wilkinson A. J. , Trimby P. W. , Day A. P. , Gholinia A. , Schmidt N. H. , Parbrook P. J. , Watson I. M.
Published: November 2006

In the present paper the authors describe the use of electron backscatter diffraction (EBSD) mapping and electron channelling contrast imaging (in the scanning electron microscope) to study tilt, strain, atomic steps and dislocations in epitaxial GaN thin films. Results from epitaxial GaN thin films and from a just coalesced epitaxial laterally overgrown GaN thin film are shown. From the results it is deduced that EBSD may be used to measure orientation changes of the order of 0·02° and strain changes of order 2 × 10−4 in GaN thin films. It is also demonstrated that channelling contrast in electron channelling contrast images may be used to image tilt, atomic steps and threading dislocations in GaN thin films. In addition the authors will consider the results of the first many-beam dynamical simulations of EBSD patterns from GaN thin films, in which the intensity distributions in the experimental patterns are accurately reproduced.
Grain boundary populations in wet and dry NaCl
Authors: Pennock G. M. , Drury M. R. , Spiers C. J.
Published: November 2006

The presence of water causes significant weakening of polycrystalline NaCl because fluid assisted recrystallisation and diffusion creep occurs along grain boundaries. In metals and ceramics, special low energy boundaries are often not wetted by fluids and this affects properties. The aim of the present paper is to use EBSD to determine whether special boundaries exist in NaCl and whether these are wetted. Wet and dry polycrystalline NaCl were examined, deformed by dislocation creep and statically and dynamically recrystallised. Coincident site lattice (CSL) boundaries in recovered material occurred with frequencies expected from the texture, whereas boundary populations of recrystallised material were significantly different from those expected from the texture, and may have been influenced by special boundaries, approximately parallel to {100} planes. Coincident site lattice boundaries became discontinuous with increasing strain in dry NaCl because of subgrain rotation. Both CSL and special boundaries migrated like general boundaries at low temperatures and are therefore likely to have been wetted.
Disorders of Neutrophil Number and Function
Authors: Newburger Peter E.
Published: November 2006

This review of disorders of neutrophil number and function will discuss important research advances in the field and then provide a clinical diagnostic approach. The focus will be on two recent clinical developments in the field of phagocyte disorders. First, an important natural history study from the Severe Chronic Neutropenia International Registry has recently quantitated the incidence and risk factors for death from sepsis and for progression to myelodysplastic syndrome and acute myeloid leukemia in a large cohort of severe chronic neutropenia patients, many of whom were followed 10 or more years on treatment with granulocyte colony-stimulating factor. Second, in the past year, a multinational group has announced successful gene therapy of two adults with chronic granulomatous disease, the most common disorder of neutrophil function. However, monitoring of retroviral insertion sites revealed expansion of the multiclonal population of gene-modified cells, raising concerns about eventual leukemogenesis. The review also provides a pragmatic approach to the evaluation of a patient with a suspected disorder of neutrophil number or function.
Tumor-Specific Genetic Lesions and Their Influence on Therapy in Pediatric Acute Lymphoblastic Leukemia
Authors: Downing James R. , Mullighan Charles G.
Published: November 2006

Pharmacogenomics has traditionally focused on the identification of inherited genetic differences that influence a patient’s response to a specific therapeutic agent. These differences can range from inherited variability in the genes that affect drug absorption, distribution, intracellular transport, metabolism, and elimination, to variability in the genes that encode either the target of the drug or components of the pathway affected by the drug. The main goal of pharmacogenomics is to improve our understanding of how these variations, either individually or collectively, influence the therapeutic response. The genetic differences inherent within cancer cells constitute the other major variable in a patient’s ultimate response to therapy. In this review, we provide an overview of high-throughput genomic methods that can be used to identify genetic lesions within cancer cells. These efforts will ultimately allow the identification of the full complement of genetic lesions that underlie the establishment and maintenance of the leukemic clone. The identification of these lesions should provide the bases for defining the molecular “Achilles heels” against which new targeted therapies can be developed.
Evolving View of the In-Vivo Kinetics of Chronic Lymphocytic Leukemia B Cells
Authors: Chiorazzi Nicholas , Ferrarini Manlio
Published: November 2006

B-cell chronic lymphocytic leukemia (B-CLL) has long been considered a disease of “accumulation,” due to a presumed defect in programmed cell death. Recent data, however, suggest that B-CLL cells are born at a normal to an accelerated rate, with the rate of proliferation varying among patients. In addition, differences in birth rates, activation state, and inducibility appear to exist among subpopulations of cells within individual leukemic clones. The extent to which such dissimilarities influence clinical course and outcome is still unclear. This review examines the evidence supporting the existence of a proliferative compartment in B-CLL and the role that proliferating cells might play in the progression and evolution of this disease.
Controversies in Follicular Lymphoma: “Who, What, When, Where, and Why?” (Not Necessarily in That Order!)
Authors: Czuczman Myron S.
Published: November 2006

Follicular lymphoma (FL) is the most common subtype of indolent lymphoma. Specific “facts” about FL that were generated by past research and have been passed down as dogma to a majority of practicing oncologists over the past 20 to 30 years that need to be revisited, include: (1) do not initiate therapy soon after diagnosis in asymptomatic, advanced-stage patients since it does not change outcome; (2) initiate therapy with single-agent oral alkylators when intervention needed and “save” more aggressive combination chemotherapy for “later” since the standard chemotherapy regimen used did not seem to impact survival; (3) FL is an incurable disease and palliation of symptoms was an acceptable approach to the expected pattern of repeated relapses; (4) transformation of FL is independent of the type or timing of therapies received by a patient; (5) median overall survival (OS) for FL patients is 8–10 years. Although the heterogeneity of FL will never change, we are developing the scientific tools to identify and better understand the biologic and genetic features associated with its clinical variability. In the current exciting era of targeted therapies (e.g., rituximab, radioimmunoconjugates) and novel treatment approaches demonstrating an improvement in treatment outcomes (e.g., disease-free survival and OS), our old beliefs and historically accepted dogma need to be retested and revitalized. The optimal combination(s) of old and new agents and the optimal timing of when to initiate and how to sequence specific therapies will require data from well-designed clinical trials that should include important correlative laboratory studies.
Pathobiology of Peripheral T-cell Lymphomas
Authors: Jaffe Elaine S.
Published: November 2006

Peripheral T-cell lymphomas (PTLs) are uncommon, accounting for fewer than 10% of all non-Hodgkin lymphomas. Success in therapy of the PTLs has lagged behind that of aggressive B-cell lymphomas, and most PTLs have a poor prognosis. The molecular pathogenesis of most PTLs is also poorly understood. In the WHO classification, clinical features, in conjunction with morphological and immunophenotypic criteria, are relied on to define most disease entities.

Functionally, T-cell lymphomas are related to the two major arms of the immune system, the innate and adaptive immune systems. NK cells and T cells of the innate immune system recognize antigen in the absence of MHC antigens and are involved in mucosal immunity. The lymphomas derived from these cells often involve cutaneous and mucosal sites. The expression of cytotoxic molecules in these lymphomas may predispose to apoptosis by tumor cells and normal bystander cells. Hepatosplenic T-cell lymphoma is a systemic disease derived from functionally immature innate effector cells, most often of γδ T-cell origin. In contrast, most nodal T-cell lymphomas belong to the adaptive immune system.

Angioimmunoblastic T-cell lymphoma (AILT) is mostly likely derived from follicular helper T-cells (TFH), a finding that explains many of its pathological and clinical features. Studies of these neoplasms may assist in further unraveling the functional diversity of their normal counterparts.
ITP in the 21st Century
Authors: Beardsley Diana S.
Published: November 2006

Immune (or idiopathic) thrombocytopenic purpura (ITP) is commonly encountered by the practicing hematologist. Clinical management decisions have traditionally been guided by individual training and past experience. Input from the literature has been more from observational reports of case series than from scientific results of hypothesis-driven research. Practice guidelines and several surveys of clinical hematology practice have highlighted important questions in the field, and in the past 5 to 10 years both clinical and laboratory investigations have produced valuable new information. Thrombopoietin levels are normal or only slightly increased in ITP, and stimulation of thrombopoiesis appears to be a promising new therapeutic approach in clinical trials. Chronic, refractory ITP in children or adults remains a challenge for the hematologist. It is this group that has the greatest risk of serious bleeding, particularly among the elderly. The anti-B–cell monoclonal antibody, anti-CD20, has shown benefit in phase I/II clinical trials in patients who had failed a number of previous therapeutic modalities. The standard for clinical research into therapy for ITP has become evidence-based medicine, and more prospective, randomized clinical trials are being completed by multi-institutional study groups.
Red Cell Exchange in Sickle Cell Disease
Authors: Swerdlow Paul S.
Published: November 2006

Red cell exchange transfusions remain an effective but possibly underutilized therapy in the acute and chronic treatment of sickle cell disease. In sickle cell disease, increased blood viscosity can cause complications when the hemoglobin exceeds 10 g/dL even if this is due to simple transfusion. Red cell exchange can provide needed oxygen carrying capacity while reducing the overall viscosity of blood. Acute red cell exchange is useful in acute infarctive stroke, in acute chest and the multi-organ failure syndromes, the right upper quadrant syndrome, and possibly priapism. Neither simple or exchange transfusions are likely to hasten resolution of an acute pain episode.
Platelets: Testing, Dosing and the Storage Lesion—Recent Advances
Authors: Kaufman Richard M.
Published: November 2006

The demand for platelet transfusions continues to grow. Several complementary approaches that may help meet this demand in the future are reviewed. First, platelet bacterial testing is beginning to allow the extension of platelet storage beyond 5 days. Studies are also underway aimed at better preserving viability and function during ex vivo platelet storage: additive solutions and other approaches are being developed to try to negate the “platelet storage lesion.” Finally, new approaches to dosing platelets may help extend the limited supply.