bluuebunny/crossref_metadata_2025 huggingface dataset:
MiR-23a-mediated inhibition of topoisomerase 1 expression potentiates cell response to etoposide in human hepatocellular carcinoma
Authors: Wang Ning , Zhu Meifen , Tsao Sai-Wah , Man Kwan , Zhang Zhangjin , Feng Yibin
Published: October 2013

Background

microRNAs have been shown to regulate the chemosensitivity of cancer cells. The aim of this study is to investigate the role and mechanism of mir-23a in enhancing the anti-tumor effect of topoisomerase 2A (TOP2A) poison etoposide in human hepatocellular carcinoma (HCC).

Methods

The anti-tumor effect of chemotherapeutic agents in HCC cells were examined in vitro and in vivo xenograft model. Expression of mRNA and miRNAs were determined by quantitative real-time PCR. Protein expression was analyzed by immunoblotting.

Results

Overexpression of mir-23a could significantly potentiate the in vitro and in vivo anti-tumor effect of etoposide; however, ectopic expression of miR-23a fails to sensitize HCC cells to 5-fluorouracil treatment, indicating the miR-23a-induced cancer cell hypersensitivity in chemotherapy is TOP2A-specific though miR-23a overexpression could not directly up-regulate TOP2A expression. Topoisomerase 1(TOP1) is down-regulated in miR-23a-overexpressed HCC cells. MiR-23a could directly bind to 3′untranslated region of TOP1 mRNA, and suppress the corresponding protein expression and inhibition of miR-23a further arguments the expression of TOP1. MiR-23a was up-regulated during DNA damage in cancer cells in line with the p53 expression. Up-regulation of p53 induces mir-23a expression, while suppression of p53 inhibits miR-23a in HCC cells.

Conclusion

Our study sheds light on the role of miR-23a as a potential target in regulating chemosensitivity of HCC cells.
Chronic myeloid leukemia (CML): association of treatment satisfaction, negative medication experience and treatment restrictions with health outcomes, from the patient’s perspective
Authors: Hirji Ishan , Gupta Shaloo , Goren Amir , Chirovsky Diana R , Moadel Alyson B , Olavarria Eduardo , Victor Timothy W , Davis Catherine C
Published: October 2013

Background

The availability of the tyrosine-kinase inhibitor (TKI), imatinib, and later introduction of second generation TKIs, dasatinib and nilotinib, have not only improved clinical outcomes of patients with chronic myeloid leukemia (CML), but also provide multiple therapeutic options for CML patients. Despite the widespread use of these oral therapies, little is known about the impact of different treatment regimens on patient-reported outcomes (PROs) among CML patients. The objective of this study was to assess the impact of patient-reported treatment restrictions and negative medication experiences (NMEs) on satisfaction and other health outcomes among patients with CML treated with oral TKIs.

Methods

Participants recruited from survey panels and patient networks in the United States (US) and Europe completed an online questionnaire. Respondents included adults (≥18 years) with chronic-phase CML currently on TKI treatment. Study variables included treatment difficulty (i.e., difficulty in following treatment regimens), CML dietary/dosing requirements, NMEs, and validated PROs assessing treatment satisfaction, health-related quality of life (HRQoL), activity impairment, and non-adherence. Structural equation models assessed associations among variables, controlling for covariates.

Results

303 patients with CML (US n=152; Europe n=151; mean age 51.5 years; 46.2% male) completed the questionnaire. Approximately 30% of patients reported treatment difficulties; treatment difficulty was higher among nilotinib (63.3%) than among dasatinib (2.6%) or imatinib (19.2%) treated patients (p<0.0001). Non-adherence was generally low; however, patients on nilotinib vs. imatinib reported missing doses more often (p<0.05). Treatment satisfaction was associated with significantly increased HRQoL (p<0.05) and lower activity impairment (p<0.01). NMEs were associated with decreased treatment satisfaction (p<0.01) and HRQoL (p<0.05), and greater activity impairment (p<0.01). Higher overall treatment restrictions were associated with greater treatment difficulty (p<0.001), which correlated with non-adherence (p<0.01).

Conclusions

Treatment satisfaction and NMEs are important factors associated with HRQoL among patients with CML. Increased treatment restrictions and associated difficulty may affect adherence with TKIs. Choosing a CML treatment regimen that is simple and conveniently adaptable in patients’ normal routine can be an important determinant of HRQoL and adherence.
New clinical application of high-intensity focused ultrasound: local control of synovial sarcoma
Authors: Hu Xiaoye , Cai Hongke , Zhou Meiqi , He Haifei , Tian Wei , Hu Yue , Chen Lirong , Deng Yongchuan
Published: October 2013

High-intensity focused ultrasound (HIFU) is playing an increasingly important role in cancer therapy. Primary synovial sarcomas of the chest wall are extremely rare. We report the first case of noninvasive HIFU therapy for the control of synovial sarcoma. A 51-year-old man was diagnosed with spindle cell sarcoma on the left chest wall through lumpectomy. After four cycles of chemotherapy, local recurrence of the sarcoma was detected. Subsequent extended resection confirmed synovial sarcoma. After five cycles of a new chemotherapy option, the sarcoma relapsed again. Then the patient received five courses of HIFU; this completely ablated the sarcoma without complications. No chemotherapy, radiotherapy, or biological therapy has been applied since. Now the patient is stable and has a high quality of life.
Genetic variations of ND5 gene of mtDNA in populations of Anopheles sinensis (Diptera: Culicidae) malaria vector in China
Authors: Makhawi Abdelrafie M , Liu Xiao-Bo , Yang Shu-Ran , Liu Qi-Yong
Published: October 2013

Background

Anopheles sinensisis a principal vector forPlasmodium vivaxmalaria in most parts of China. Understanding of genetic structure and genetic differentiation of the mosquito should contribute to the vector control and malaria elimination in China.

Methods

The present study investigated the genetic structure ofAn. sinensispopulations using a 729 bp fragment of mtDNAND5among 10 populations collected from seven provinces in China.

Results

ND5was polymorphic by single mutations within three groups ofAn. sinensisthat were collected from 10 different geographic populations in China. Out of 140 specimens collected from 10 representative sites, 84 haplotypes and 71 variable positions were determined. The overall level of genetic differentiation ofAn. sinensisvaried from low to moderate across China and with aFSTrange of 0.00065 – 0.341. Genealogy analysis clustered the populations ofAn. sinensisinto three main clusters. Each cluster shared one main haplotype. Pairwise variations within populations were higher (68.68%) than among populations (31.32%) and with high fixation index (FST = 0.313). The results of the present study support population growth and expansion in theAn. sinensispopulations from China. Three clusters ofAn. sinensispopulations were detected in this study with each displaying different proportion patterns over seven Chinese provinces. No correlation between genetic and geographic distance was detected in overall populations ofAn. sinensis(R2 = 0.058;P = 0.301).

Conclusions

The results indicate that theND5gene of mtDNA is highly polymorphic inAn. sinensisand has moderate genetic variability in the populations of this mosquito in China. Demographic and spatial results support evidence of expansion inAn. sinensispopulations.
Assessing the influence of the multisensory environment on the whisky drinking experience
Authors: Velasco Carlos , Jones Russell , King Scott , Spence Charles
Published: October 2013

Background

Flavor perception depends not only on the multisensory integration of the sensory inputs associated with the food or drink itself, but also on the multisensory attributes (or atmosphere) of the environment in which the food/drink is tasted. We report two experiments designed to investigate whether multisensory atmospheric cues could be used to influence the perception of a glass of whisky (that is, a complex but familiar product). The pre-test (experiment 1) was conducted in the laboratory and involved a sample of 18 participants (12 females, 5 males, and 1 who did not specify gender), while the main study (experiment 2) was conducted at a large purpose-designed whisky-tasting event held in London, and enrolled a sample of 441 participants (165 female, 250 male, and 26 who failed to specify their gender). In the main experiment, participants were exposed to three different multisensory atmospheres/rooms, and rated various attributes of the whisky (specifically the nose, the taste/flavor, and the aftertaste) in each room.

Results

Analysis of the data showed that each multisensory atmosphere/room exerted a significant effect on participants’ ratings of the attributes that the atmosphere/room had been designed to emphasize (namely grassiness, sweetness, and woodiness). Specifically, the whisky was rated as being significantly grassier in the Nose (‘grassy’) room, as being significantly sweeter in the Taste (‘sweet’) room, and as having a significantly woodier aftertaste in the Finish (‘woody’) room. Overall, the participants preferred the whisky when they tasted it in the Finish room.

Conclusions

Taken together, these results further our understanding of the significant influence that a multisensory atmosphere can have on people’s experience and/or enjoyment of a drink (in this case, a glass of whisky). The implications of these results for the future design of multisensory experiences are discussed.
ATLAS: Randomized, Double-Blind, Placebo-Controlled, Phase IIIB Trial Comparing Bevacizumab Therapy With or Without Erlotinib, After Completion of Chemotherapy, With Bevacizumab for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer
Authors: Johnson Bruce E. , Kabbinavar Fairooz , Fehrenbacher Louis , Hainsworth John , Kasubhai Saifuddin , Kressel Bruce , Lin Chin-Yu , Marsland Thomas , Patel Taral , Polikoff Jonathan , Rubin Mark , White Leonard , Yang James Chih-Hsin , Bowden Chris , Miller Vincent
Published: October 2013

Purpose

This phase III trial was performed to assess the potential benefit of adding maintenance erlotinib to bevacizumab after a first-line chemotherapy regimen with bevacizumab for advanced non–small-cell lung cancer (NSCLC).

Patients and Methods

One thousand one hundred forty-five patients with histologically or cytologically confirmed NSCLC (stage IIIB with malignant pleural effusion, stage IV, or recurrent) received four cycles of chemotherapy plus bevacizumab. Seven hundred forty-three patients without disease progression or significant toxicity were then randomly assigned (1:1) to bevacizumab (15 mg/kg, day 1, 21-day cycle) plus either placebo or erlotinib (150 mg per day). The primary end point was progression-free survival (PFS).

Results

Median PFS from time of random assignment was 3.7 months with bevacizumab/placebo and 4.8 months with bevacizumab/erlotinib (hazard ratio [HR], 0.71; 95% CI, 0.58 to 0.86; P < .001). Median overall survival (OS) times from random assignment were 13.3 and 14.4 months with bevacizumab/placebo and bevacizumab/erlotinib, respectively (HR, 0.92; 95% CI, 0.70 to 1.21; P = .5341). During the postchemotherapy phase, there were more adverse events (AEs) overall, more grade 3 and 4 AEs (mainly rash and diarrhea), more serious AEs, and more AEs leading to erlotinib/placebo discontinuation in the bevacizumab/erlotinib arm versus the bevacizumab/placebo arm. The incidence of AEs leading to bevacizumab discontinuation was similar in both treatment arms.

Conclusion

The addition of erlotinib to bevacizumab significantly improved PFS but not OS. Although generally well tolerated, the modest impact on survival and increased toxicity associated with the addition of erlotinib to bevacizumab maintenance mean that this two-drug maintenance regimen will not lead to a new postchemotherapy standard of care.
Dose-Dense Temozolomide for Newly Diagnosed Glioblastoma: A Randomized Phase III Clinical Trial
Authors: Gilbert Mark R. , Wang Meihua , Aldape Kenneth D. , Stupp Roger , Hegi Monika E. , Jaeckle Kurt A. , Armstrong Terri S. , Wefel Jeffrey S. , Won Minhee , Blumenthal Deborah T. , Mahajan Anita , Schultz Christopher J. , Erridge Sara , Baumert Brigitta , Hopkins Kristen I. , Tzuk-Shina Tzahala , Brown Paul D. , Chakravarti Arnab , Curran Walter J. , Mehta Minesh P.
Published: October 2013

Purpose

Radiotherapy with concomitant and adjuvant temozolomide is the standard of care for newly diagnosed glioblastoma (GBM). O6-methylguanine-DNA methyltransferase (MGMT) methylation status may be an important determinant of treatment response. Dose-dense (DD) temozolomide results in prolonged depletion of MGMT in blood mononuclear cells and possibly in tumor. This trial tested whether DD temozolomide improves overall survival (OS) or progression-free survival (PFS) in patients with newly diagnosed GBM.

Patients and Methods

This phase III trial enrolled patients older than age 18 years with a Karnofsky performance score of ≥ 60 with adequate tissue. Stratification included clinical factors and tumor MGMT methylation status. Patients were randomly assigned to standard temozolomide (arm 1) or DD temozolomide (arm 2) for 6 to 12 cycles. The primary end point was OS. Secondary analyses evaluated the impact of MGMT status.

Results

A total of 833 patients were randomly assigned to either arm 1 or arm 2 (1,173 registered). No statistically significant difference was observed between arms for median OS (16.6 v 14.9 months, respectively; hazard ratio [HR], 1.03; P = .63) or median PFS (5.5 v 6.7 months; HR, 0.87; P = .06). Efficacy did not differ by methylation status. MGMT methylation was associated with improved OS (21.2 v 14 months; HR, 1.74; P < .001), PFS (8.7 v 5.7 months; HR, 1.63; P < .001), and response (P = .012). There was increased grade ≥ 3 toxicity in arm 2 (34% v 53%; P < .001), mostly lymphopenia and fatigue.

Conclusion

This study did not demonstrate improved efficacy for DD temozolomide for newly diagnosed GBM, regardless of methylation status. However, it did confirm the prognostic significance of MGMT methylation. Feasibility of large-scale accrual, prospective tumor collection, and molecular stratification was demonstrated.
Prostate-Specific Antigen Changes As Surrogate for Overall Survival in Men With Metastatic Castration-Resistant Prostate Cancer Treated With Second-Line Chemotherapy
Authors: Halabi Susan , Armstrong Andrew J. , Sartor Oliver , de Bono Johann , Kaplan Ellen , Lin Chen-Yen , Solomon Nicole C. , Small Eric J.
Published: October 2013

Purpose

Prostate-specific antigen (PSA) kinetics, and more specifically a ≥ 30% decline in PSA within 3 months after initiation of first-line chemotherapy with docetaxel, are associated with improvement in overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC). The objective of this analysis was to evaluate post-treatment PSA kinetics as surrogates for OS in patients receiving second-line chemotherapy.

Patients and Methods

Data from a phase III trial of patients with mCRPC randomly assigned to cabazitaxel plus prednisone (C + P) or mitoxantrone plus prednisone were used. PSA decline (≥ 30% and ≥ 50%), velocity, and rise within the first 3 months of treatment were evaluated as surrogates for OS. The Prentice criteria, proportion of treatment explained (PTE), and meta-analytic approaches were used as measures of surrogacy.

Results

The observed hazard ratio (HR) for death for patients treated with C + P was 0.66 (95% CI, 0.55 to 0.79; P < .001). Furthermore, a ≥ 30% decline in PSA was a statistically significant predictor of OS (HR for death, 0.52; 95% CI, 0.43 to 0.64; P < .001). Adjusting for treatment effect, the HR for a ≥ 30% PSA decline was 0.50 (95% CI, 0.40 to 0.62; P < .001), but treatment remained statistically significant, thus failing the third Prentice criterion. The PTE for a ≥ 30% decline in PSA was 0.34 (95% CI, 0.11 to 0.56), indicating a lack of surrogacy for OS. The values of R2 were < 1, suggesting that PSA decline was not surrogate for OS.

Conclusion

Surrogacy for any PSA-based end point could not be demonstrated in this analysis. Thus, the benefits of cabazitaxel in mediating a survival benefit are not fully captured by early PSA changes.
Negotiating Kingship in France at the Time of the Early Crusades: Suger and the Gesta Ludovici Grossi
Authors: Naus James
Published: October 2013

This article shows the crusading movement to be an optimal route into an understanding of Europe’s twelfth-century power structure by examining its impact on the valuation and practice of kingship in France. The article argues that Suger of Saint-Denis’s history of Louis VI, the Gesta Ludovici Grossi, can be read as one of several responses to the threat posed to kingship by the new crusade ideology and to the prestige attaching to former crusaders. Suger fuses Carolingian notions of sacred kingship with the newer crusade ideas to craft a highly selective narrative of Louis’s reign that foregrounds the motif of military actions prosecuted to vindicate justice and with ecclesiastical endorsement. Suger thereby exploits the unknown future of crusading to create a space into which the self-fashioning of Capetian kingship could insinuate itself and from which emerged the late medieval image of a “crusader king.”

Cet article présente les croisades comme le meilleur moyen de comprendre la structure du pouvoir en Europe au XIIe siècle, à travers l’examen de son impact sur l’évaluation et la pratique de la royauté en France. Plus précisément, cet article soutient que l’histoire de Louis VI par Suger de Saint-Denis, la Gesta Ludovici Grossi, peut être lue comme une réponse alternative à la menace que faisaient peser sur la royauté l’idéologie nouvelle des croisades et le prestige lié aux premiers croisés. Le texte mêle la notion carolingienne d’une royauté sacrée avec les idées nouvelles des croisades, pour rédiger un récit très sélectif du règne de Louis VI, où prédomine le thème des actions militaires engagées pour défendre la justice et obtenir l’approbation ecclésiastique. Suger exploite ainsi l’avenir inconnu des croisades pour créer un espace dans lequel se façonnerait le modèle de la royauté capétienne et d’où émergerait l’image médiévale tardive du « roi croisé ».
An Unlikely Pair: Satire and Jansenism in the Sarcelades, 1731-1764
Authors: Choudhury Mita
Published: October 2013

Between 1731 and 1764 unknown writer Nicolas Jouin eluded arrest and published fifteen satirical verses known as the sarcelades. The poems straddled the different areas of Jansenist political culture and the world of popular opinion and clandestine literature. Written in patois, the sarcelades featured the peasant Claude Fetu, who made ultramontane bishops, the Jesuits, and even the king the objects of derision and resentment. This character embodied certain Jansenist beliefs regarding the simple believer who bore witness on behalf of individuals persecuted for resisting the anti-Jansenist bull Unigenitus. The sarcelades suggest that theological debates had a place in the world of the impoverished and underrepresented, whose views were shaped both by spiritual conviction and material needs.

Entre 1731 et 1764 un auteur inconnu, Nicolas Jouin, échappa aux arrestations et publia quinze textes satiriques versifiés, les « sarcelades ». Ces poèmes évoquent à la fois diverses sphères de la culture politique janséniste et les mondes de l’opinion populaire et de la littérature clandestine. Ecrits en patois, les « sarcelades » mettent en scène le paysan Claude Fetu, qui fait des évêques ultramontains, des Jésuites et même du roi des objets de ridicule et de reproche. Ce personnage incarne une conception janséniste particulière du simple croyant qui témoigne au nom d’individus persécutés pour avoir résisté à la bulle anti-janséniste Unigenitus. Les « sarcelades » suggèrent que les débats théologiques avaient leur place parmi les pauvres et les sous-représentés, dont l’opinion était formée à la fois par leur conviction spirituelle et leurs besoins matériels.
Postnatal Ablation of Osteoblast Smad4 Enhances Proliferative Responses to Canonical Wnt Signaling via Interactions with β-catenin
Authors: Salazar Valerie S , Zarkadis Nicholas , Huang Lisa , Watkins Marcus , Kading Jacqueline , Bonar Sheri , Norris Jin , Mbalaviele Gabriel , Civitelli Roberto
Published: October 2013

Canonical Wnt/β-catenin (cWnt) signaling regulates osteoblast proliferation and differentiation to enhance bone formation. We previously reported that osteogenic action of β-catenin is dependent on BMP signaling. Here, we further examined interactions between cWnt and BMP in bone. In osteoprogenitors stimulated with BMP2, β-catenin localizes to the nucleus, physically interacts with Smad4, and is recruited to DNA-binding transcription complexes containing Smad4, R-Smads1/5, and TCF4. Furthermore, Tcf/Lef-dependent transcription, Ccnd1 expression, and proliferation all increase when Smad4, 1, or 5 levels are low, whereas TCF/Lef activities decrease when Smad4 expression is high. The ability of Smad4 to antagonize transcription of Ccnd1 is dependent on DNA-binding activity; Smad4-dependent transcription is not required. In mice, conditional deletion of Smad4 in Osterix+ cells increases mitosis of cells on trabecular bone surfaces as well as in primary osteoblast cultures from adult bone marrow and neonatal calvaria. By contrast, ablation of Smad4 delays differentiation and matrix mineralization by primary osteoblasts in response to Wnt3a, indicating that loss of Smad4 perturbs the balance between proliferation and differentiation in osteoprogenitors. We propose that Smad4 and Tcf/Lef transcription complexes compete for β-catenin, thus restraining Wnt/β-catenin-dependent proliferative signals while favoring the matrix synthesizing activity of osteoblasts.
Human skeletal muscle fibroblasts, but not myogenic cells, readily undergo adipogenic differentiation
Authors: Agley Chibeza C. , Rowlerson Anthea M. , Velloso Cristiana P. , Lazarus Norman R. , Harridge Stephen D. R.
Published: October 2013

We characterised the adherent cell types isolated from human skeletal muscle by enzymatic digestion, and demonstrate that even at 72 hours post-isolation these cultures consist predominantly of myogenic cells (CD56+, Desmin+) and fibroblasts (TE-7+, Collagen VI+, PDGFRα+, Vimentin+, Fibronectin+). To evaluate the behaviour of the cell types obtained, we optimised a double immuno-magnetic cell sorting method for the separation of myogenic cells from fibroblasts. This procedure gave purities of >96% for myogenic (CD56+/desmin+) cells. The CD56- fraction obtained from the first sort was highly enriched in TE-7+ fibroblasts. Using quantitative analysis of immunofluorescent staining for lipid content, lineage markers and transcription factors, we tested if the purified cell populations could differentiate into adipocytes in response to treatment with either fatty acids or Adipocyte Inducing Medium. Both treatments caused the fibroblasts to differentiate into adipocytes, as evidenced by loss of intracellular TE-7, upregulation of the adipogenic transcription factors PPARγ and C/EBPα, and adoption of a lipid-laden adipocyte morphology. In contrast, myogenic cells did not undergo adipogenesis and showed differential regulation of PPARγ and C/EBPα in response to these adipogenic treatments. The data show that human skeletal muscle fibroblasts are at least bipotent progenitors, capable of remaining as extracellular matrix-producing cells or differentiating into adipocytes.
Etv5a regulates the proliferation of ventral mesoderm cells and the formation of hemato-vascular derivatives
Authors: Chen Shin-Yi , Shih Hung-Yu , Lin Sheng-Jia , Hsiao Chung-Der , Li Zih-Cing , Cheng Yi-Chuan
Published: October 2013

Hematopoietic and vascular endothelial cells constitute the circulatory system and are both generated from the ventral mesoderm. However, the molecules and signaling pathways involved in ventral mesoderm formation and specification remain unclear. We found that zebrafish etv5a was expressed in the ventral mesoderm during gastrulation. Knockdown of Etv5a using morpholinos increased the proliferation of ventral mesoderm cells and caused defects in hematopoietic derivatives and in vascular formation. In contrast, the formation of other mesodermal derivatives, such as pronephros, somites and the gut wall, was not affected. Knockdown specificity was further confirmed by over-expression of an etv5a construct lacking its acidic domain. In conclusion, our data reveal that etv5a is essential for the inhibition of ventral mesoderm cell proliferation and for the formation of the hemato-vascular lineage.
Regulation of CYP3A genes by glucocorticoids in human lung cells
Authors: Roberts Jessica K , Moore Chad D , Romero Erin G , Ward Robert M , Yost Garold S , Reilly Christopher A
Published: October 2013

Inhaled glucocorticoids are the first-line treatment for patients with persistent asthma.  However, approximately thirty percent of patients exhibit glucocorticoid insensitivity, which may involve excess metabolic clearance of the glucocorticoids by CYP3A enzymes in the lung.  CYP3A4, 3A5, and 3A7 enzymes metabolize glucocorticoids, which in turn induce CYP3A genes.  However, the mechanism of CYP3A5 mRNA regulation by glucocorticoids in lung cells has not been determined.  In hepatocytes, glucocorticoids bind to the glucocorticoid receptor (GR), which induces the expression of the constitutive androstane receptor or pregnane X receptor; both of which bind to the retinoid X receptor alpha, leading to the induction of CYP3A4, 3A5, and 3A7.  There is also evidence to suggest a direct induction of CYP3A5 by GR activation in liver cells. In this study, these pathways were evaluated as the mechanism for CYP3A5 mRNA induction by glucocorticoids in freshly isolated primary tracheal epithelial, adenocarcinomic human alveolar basal epithelial (A549), immortalized bronchial epithelial (BEAS-2B), primary normal human bronchial/tracheal epithelial (NHBE), primary small airway epithelial (SAEC), and primary lobar epithelial lung cells. In A549 cells, beclomethasone 17-monopropionate ([M1]) induced CYP3A5 mRNA through the glucocorticoid receptor. CYP3A5 mRNA induction by five different glucocorticoids was attenuated by inhibiting the glucocorticoid receptor using ketoconazole, and for beclomethasone dipropionate, using siRNA-mediated knock-down of the glucocorticoid receptor. The constitutive androstane receptor was not expressed in lung cells. SAEC cells, a primary lung cell line, expressed CYP3A5, but CYP3A5 mRNA was not induced by glucocorticoid treatment despite evaluating a multitude of cell culture conditions. None of the other lung cells expressed CYP3A4, 3A5 or 3A7 mRNA. These studies demonstrate that CYP3A5 mRNA is induced by glucocorticoids in A549 cells via the glucocorticoid receptor, but that additional undefined regulatory processes exist in primary lung cells.
The Strategic Value of High-Cost Customers
Authors: Subramanian Upender , Raju Jagmohan S. , Zhang Z. John
Published: October 2013

Many firms today manage their existing customers differentially based on profit potential, providing fewer incentives to less profitable customers and firing unprofitable customers. Although researchers and industry experts advocate this practice, results have been mixed. We examine this practice explicitly accounting for competition and find that some conventional prescriptions may not always hold. We analyze a setting where customers differ in their cost to serve. We find that when a firm can discriminate among its customers but the rival cannot, customer base composition influences the rival's poaching behavior. Consequently, even though a low-cost customer is more profitable when viewed in isolation, a high-cost customer may be strategically more valuable by discouraging poaching. Therefore, contrary to conventional advice, it can be profitable for a firm to retain unprofitable customers. Moreover, some customers may become more valuable to retain and receive better incentives when they are less profitable. We further show that, in competitive settings, traditional customer lifetime value metrics may lead to poor retention decisions because they do not account for the competitive externality that actions toward some customers impose on the cash flows from other customers. Our results suggest that firms may need to evolve from a segmentation mindset, which views each customer in isolation, to a customer portfolio mindset, which recognizes that the value of different customers is interlinked.

This paper was accepted by J. Miguel Villas-Boas, marketing.
How Do Industry Peers Respond to Control Threats?
Authors: Servaes Henri , Tamayo Ane
Published: October 2013

This paper studies how industry peers respond when another firm in the industry is the subject of a hostile takeover attempt. The industry peers cut their capital spending, free cash flows, and cash holdings, and increase their leverage and payouts to shareholders. They also adopt more takeover defenses. The stock price reaction upon announcement of the takeover is positive and larger for peer firms with higher capital spending and higher free cash flows. Before the takeover attempt, the peer firms borrow less and invest more than predicted. Both stock returns and performance improve after the takeover attempt. These results are consistent with the argument that the control threat has important spillover effects for the other firms in the industry.

This paper was accepted by Wei Xiong, finance.
Moving Writing
Authors: Burrows Jonathan , Heathfield Adrian
Published: October 2013

This exchange, conducted over the period of a year, examines the relation between choreography and language, movement and writing, in relation to the aesthetics of contemporary dance. Moving from the authors’ different perspectives as a dancer and choreographer, and as a writer and curator, the dialogue questions the place of writing practice within dance creation, and the relative forces of corporeal and poetic expression. Turning over these questions in their different ways, the authors engage with the relations between the spontaneous and the pre-scripted, freedom and constraint, presence, authority and the free play of meanings.
Beneath the surface of the event: Immanent movement and the politics of affective registers
Authors: Gray Victoria
Published: October 2013

This article articulates the equation between subjectivity and time through performance. It discusses ways in which choreographic strategies of stillness and slowness have the capacity to interrupt the distribution of the senses and thus affect the production of subjectivity. In doing so I consider a series of solo performances titled Pressure Points (2010–2012). In this work, the act of crawling backwards in slowness, coupled with stillness and close proximity, aimed to shift the perceptibility of movement from kinetic to kinesthetic registers. The argument is positioned in relation to Erin Manning’s notion of ‘incipient action’ and Jacques Rancière’s ‘Distribution of the sensible’. These frameworks are expanded upon by being placed in the context of the turn to conceptual choreography of the early 1990s.
Minimum Payment Warnings and Information Disclosure Effects on Consumer Debt Repayment Decisions
Authors: Salisbury Linda Court
Published: October 2013

Public policy makers encourage lenders to disclose loan cost information as a way of enabling borrowers to make more-informed debt repayment decisions. For example, current regulation requires credit card lenders to include a “minimum payment warning” on borrowers' monthly statements, with the goal of encouraging borrowers to make larger monthly repayments each month and, consequently, decrease their debt levels. This research examines the effect of disclosing such information about future interest costs and time to pay off debt on consumers' repayment decisions. The results indicate that disclosing information about the effects of repaying the minimum has little impact on repayment decisions. However, disclosing information about the effect of choosing an alternative course of action (i.e., a larger repayment amount) yielded a robust effect on repayment decisions. The findings suggest that cost information increases repayment amount for some borrowers, whereas time information may decrease repayment for others, especially those with little knowledge of interest compounding. This research provides some initial evidence of the impact of the CARD Act as well as that of similar regulations in Australia and Canada.
Evidence of Improved Milk Intake After Frenotomy: A Case Report
Authors: Garbin Catherine Peta , Sakalidis Vanessa Susanna , Chadwick Lynda Maree , Whan Elizabeth , Hartmann Peter Edwin , Geddes Donna Tracy
Published: October 2013

Ankyloglossia (tongue tie) is a well-recognized cause of breastfeeding difficulties and, if untreated, can cause maternal nipple pain and trauma, ineffective feeding, and poor infant weight gain. In some cases, this condition will result in a downregulation of the maternal milk supply. Milk-production measurements (24-hour) for a breastfeeding infant with ankyloglossia revealed the ineffective feeding of the infant (78 mL/24 hours), and a low milk supply (350 mL/24 hours) was diagnosed. Appropriate management increased milk supply (1254 mL/24 hours) but not infant milk intake (190 mL/24 hours). Test weighing convincingly revealed the efficacy of frenotomy, increasing breastfeeding milk transfer from 190 to 810 mL/24 hours. Postfrenotomy, breastfeeding almost completely replaced bottle-feeding of expressed breast milk. This case study confirms that ankyloglossia may reduce maternal milk supply and that frenotomy can improve milk removal by the infant. Milk-production measurements (24-hour) provided the evidence to confirm these findings.
Filocrono e número de folhas da canola em diferentes condições ambientais
Authors: Dalmago Genei Antonio , Fochesatto Elizandro , Kovaleski Samuel , Tazzo Ivonete Fátima , Bolis Laise Maria , Cunha Gilberto Rocca da , Nied Astor Henrique , Bergamaschi Homero , Santi Anderson
Published: October 2013

O objetivo deste trabalho foi determinar o número de folhas e o filocrono de genótipos de canola, em resposta a variações térmicas associadas com datas de semeadura. Foram realizados dois experimentos, em delineamento de blocos ao acaso, com arranjo fatorial de genótipos por datas de semeadura (5x2, em 2009, e 2x3 em 2010) e quatro repetições. O número de folhas do caule principal e do primeiro ramo foi determinado três vezes por semana. O filocrono foi estimado pelo inverso do coeficiente angular entre a soma térmica e o número de folhas, para os subperíodos da roseta e do alongamento do caule. O número de folhas no caule variou de 11,5 a 16,4; nos ramos, este número foi, em média, 70% menor. O número de folhas no caule foi maior em semeaduras precoces, e o inverso ocorreu no ramo. O filocrono foi maior no subperíodo da roseta e variou entre 21,4 e 52,9 graus-dia por folha conforme o genótipo e a data de semeadura. Semeaduras tardias aumentaram o filocrono. Genótipos de ciclo precoce apresentam número de folhas e filocrono menores que genótipos de ciclo médio ou longo, e a variabilidade entre os genótipos acentua-se em semeaduras tardias.
Suscetibilidade magnética do solo e estimação da capacidade de suporte à aplicação de vinhaça
Authors: Peluco Rafael Gonçalves , Marques Júnior José , Siqueira Diego Silva , Pereira Gener Tadeu , Barbosa Ronny Sobreira , Teixeira Daniel de Bortoli , Adame Cássia Rita , Cortez Lucas Aguilar
Published: October 2013

O objetivo deste trabalho foi avaliar a eficiência da suscetibilidade magnética do solo para estimar a capacidade de suporte de áreas à aplicação de vinhaça. Foram coletadas 241 amostras de solo, de uma área de 380 ha, nas quais foram determinados os atributos químicos, os teores de argila e a suscetibilidade magnética do solo. Foram calculadas as doses de vinhaça recomendadas para cada amostra. Os dados foram submetidos à análise estatística descritiva, e foram desenvolvidos modelos de regressão entre a suscetibilidade magnética e os outros atributos avaliados. A análise da dependência espacial dos dados foi feita com uso da geoestatística. Foram construídos mapas de krigagem e variogramas cruzados, para averiguar a correlação espacial entre a suscetibilidade magnética e os atributos estudados. Com base no mapa de recomendação de vinhaça, nas classes de solo e nos mapas de krigagem, foram calculadas as doses médias de vinhaça e as capacidades de suporte médias, ponderadas pela área. A suscetibilidade magnética apresenta correlação espacial linear significativa com as doses de vinhaça recomendadas e com a capacidade de suporte do solo à aplicação desse efluente, e pode ser utilizada como componente da função de pedotransferência, na quantificação indireta da capacidade de suporte.
Identificação morfológica e molecular de Helicoverpa armigera (Lepidoptera: Noctuidae) e ampliação de seu registro de ocorrência no Brasil
Authors: Specht Alexandre , Sosa-Gómez Daniel Ricardo , Paula-Moraes Silvana Vieira de , Yano Silvia Akimi Cavaguchi
Published: October 2013

O objetivo deste trabalho foi descrever métodos para a caracterização morfológica e molecular de Helicoverpa armigera e ampliar o registro de ocorrência da praga no Brasil. As mariposas foram obtidas de lagartas coletadas nas culturas de algodão, milho e soja, com uso de armadilhas luminosas. As coletas foram realizadas na Bahia, no Distrito Federal, no Mato Grosso e no Paraná. A identificação foi baseada na genitália masculina e nas análises das sequências dos genes mitocondriais do citocromo B e da região cox1-tRNALeu-cox2. A genitália masculina foi comparada com as descrições morfológicas na literatura, e as sequências de genes, com as depositadas no GenBank. Ambas as análises confirmaram a presença de H. armigera nos locais de coleta. Ampliou-se o registro de ocorrência da praga para a região Sul do país.
Dispersal Mechanisms of the Invasive Alien Plant Species Buffalobur (Solanum rostratum) in Cold Desert Sites of Northwest China
Authors: Eminniyaz Amanulla , Qiu Juan , Tan Dunyan , Baskin Carol C. , Baskin Jerry M. , Nowak Robert S.
Published: October 2013

Dispersal mechanisms of the alien plant species buffalobur during its invasion of cold desert areas in Xinjiang, northwestern China, were investigated. Seeds and fruits were readily moved by water in irrigation canals in the transition zone between natural desert and a farmed oasis. Maximum flotation time in moving canal water was ∼ 4 h for seeds and > 48 h for fruits, and water moved fruits 279 m in 10 min. Also, 100% of the seeds remained viable during 8 wk of flooding in the laboratory. Mean dispersal distance was 3.4 m by wind-driven rolling of detached plants and 0.5 m by ants. Retention time for 50% of fruits on wool of live sheep was ∼ 4 h. Seeds and fruits that fall into the canals (which are without irrigation water from mid-October to April) are cold-stratified during winter, and then during canal cleaning in spring soil and germinable seeds are deposited along the sides of the canals. The disturbed soil is a highly favorable site for plants to grow. The local spread of buffalobur away from the sides of canals is facilitated by sheep, wind, and ants. We conclude that water in the irrigation canals is the primary dispersal agent for seeds of this invasive species and that the best way to control its spread is to prevent plants growing beside the canals from setting seed.
A programme for continuing professional development of managers in the construction industry
Authors: Strasheim Breda , Hugo Fred
Published: October 2013

The University of Stellenbosch construction management programme has been providing a four-week continuing professional development programme for construction managers since 1976. The programme is presented on an annual basis. It focuses on middle management in the construction industry which includes the building as well as civil engineering sectors of the industry. An overview of the present programme curriculum and curriculum development through the history of the programme is provided. Programme themes are selected to fit in with current management issues and topics. Key factors contributing to the success of the programme are also reviewed and analysed. The personal development and educational approach adopted as well as the philosophy of using a full immersion four-week residential course is discussed. The profile of types of delegates attending the programme is summarised. Programme faculty members are drawn from the major tertiary institutions in South Africa as well as selected institutions abroad. A formal delegate performance assessment system is used. The programme also has procedures in place through which extensive feedback from delegates is gathered and reviewed and used to drive incremental improvement of the content as well as the presentation style. The role of the active alumni network in sponsoring candidates for the programme as well as interacting with delegates is reviewed.
Physics and applications of superhydrophobic and superhydrophilic surfaces and coatings
Authors: Drelich Jaroslaw , Marmur Abraham
Published: October 2013

The terms superhydrophobicity and superhydrophilicity were introduced not very long ago, in 1996 and 2000, respectively. The former is used to describe exceptionally weak and the latter used to indicate strong interactions of materials and coatings with bulk water, controlled entirely by surface topography and material chemistry. An explosion of research on fabrication of superhydrophobic and superhydrophilic surfaces and coatings was noticed almost immediately after the concepts appeared in the technical literature, with hundreds of reports now published annually. The interest in this new class of surfaces/coatings is driven by an emerging market for water-repellant, snow- and ice-phobic products and formulations, water antifogging screens, windows and lenses, antifouling coatings, microfluidic devices, coatings for enhanced boiling heat transfer, foils for food packaging and many other products. The popularity of this emerging subdiscipline of surface chemistry can also be attributed to uncomplicated fabrication technologies that can produce superhydrophobic or superhydrophilic surfaces and coatings, in addition to the simplicity of the testing techniques used, such as contact angle measurements. In this article, the physics behind superhydrophobic and superhydrophilic effects are reviewed and several examples of applications of superhydrophobic and superhydrophilic surfaces and coatings are provided.
Surface modification of electrospun polycaprolactone fibers and effect on cell proliferation
Authors: Arabi Ahmad , Boggs Emily , Patel Manan R. , Zwiesler-Vollick Julie , Maerz Tristan , Baker Kevin , Tuck Samuel , Corey Joseph , Li Yawen
Published: October 2013

Surface modification is an essential tool in tissue engineering using synthetic biomaterial scaffolds. The authors report in this study a simple approach to modify the surface hydrophobicity, roughness and chemistry of electrospun polycaprolactone (PCL) fibers using a combination of oxygen plasma treatment, sodium hydroxide treatment and arginine–glycine–aspartic acid (RGD) immobilization. The modified surfaces were characterized using scanning electron microscopy, atomic force microscopy, water contact angle measurement and X-ray photoelectron spectroscopy (XPS). Plasma treatment decreased the water contact angle. Sodium hydroxide treatment further improved the hydrophilicity and increased the surface roughness. XPS analysis confirmed the presence of amide bonds on RGD-treated fibers. The enhancement of proliferation of ligament fibroblasts within 1 week of culturing on both the plasma- and sodium hydroxide–treated fibers was most likely due to improved wettability by the oxygen plasma treatment. The alignment and penetration of cells on PCL fibers suggested that these materials could be potential scaffold materials for the regeneration of fibrous tissues.
High Night Temperature and Abscisic Acid Affect Rice Productivity through Altered Photosynthesis, Respiration and Spikelet Fertility
Authors: Mohammed R. , Cothren J. T. , Tarpley L.
Published: October 2013

High night temperature (HNT) is among the important abiotic stresses limiting rice production. The impacts of abscisic acid (ABA) on higher plants have been the subject of many studies. However, little or no work has been performed on rice responses to ABA under HNT‐stress conditions. This study determined the effects of ABA on rice leaf photosynthetic rate (PN), photochemistry, respiration, and physiology under HNT. Plants were grown under ambient night temperature (ANT; 25°C) or HNT (30°C) with or without ABA (100 ppm) application from the boot stage of rice plants until harvest. The HNT decreased rice yield (11%), which was associated with decreasing PN (5%), pollen viability (11%), and spikelet fertility (5%) and increasing respiration rate (44%). In addition, HNT decreased grain width (4%) and increased grain chalkiness (65%), thereby decreasing grain quality. The ABA‐treated plants showed increased yield (15%) as a result of increased PN (6%) and spikelet fertility (6%) and decreased respiration (33%), under HNT. The increased PN under HNT as a result of ABA application is associated with increased stomatal conductance (22%) and decreased nonphotochemical quenching (NPQ; 29%). In addition, ABA‐treated plants grown under ANT also showed increased yield (9%) as a result of increased PN (7%) and spikelet fertility (7%) and decreased respiration (16%). The increased PN under ANT as a result of ABA application was due to increased quantum yield (8%) and electron transport rate (8%). This study shows that exogenous application of ABA has the potential to increase rice yields under HNT.
Genotype Plus Genotype × Block of Environments Biplots
Authors: Laffont Jean‐Louis , Wright Kevin , Hanafi Mohamed
Published: October 2013

Biplots have been widely used in recent years for the analysis of multi‐environment trials through the genotype plus genotype × environment (GGE) biplot analysis or through the additive main effects and multiplicative interaction analysis. Sometimes the environments are structured in blocks of environments, for example, regions or years. In this paper, we propose a new biplot technique for describing genotype × environment interactions that takes into account this additional information. We call it a GGB biplot for genotype plus genotype × block of environments biplot. This biplot has interesting geometrical properties that will be covered in this paper. Similarly to what was done for the GGE biplot (Laffont et al., 2007), we also establish a link between the partitioning of the total sum of squares provided by the GGB biplot and the partitioning provided by the analysis of variance. Simulated and real data are used to illustrate this new biplot.