bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of Src function potentiates Chk1-inhibitor–induced apoptosis in human multiple myeloma cells in vitro and in vivo
Authors: Dai Yun , Chen Shuang , Shah Rena , Pei Xin-Yan , Wang Li , Almenara Jorge A. , Kramer Lora B. , Dent Paul , Grant Steven 
Published: December 2010

AbstractRas/MEK/ERK pathway activation represents an important compensatory response of human multiple myeloma (MM) cells to checkpoint kinase 1 (Chk1) inhibitors. To investigate the functional roles of Src in this event and potential therapeutic significance, interactions between Src and Chk1 inhibitors (eg, UCN-01 or Chk1i) were examined in vitro and in vivo. The dual Src/Abl inhibitors BMS354825 and SKI-606 blocked Chk1-inhibitor–induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, markedly increasing apoptosis in association with BimEL up-regulation, p34cdc2 activation, and DNA damage in MM cell lines and primary CD138+ MM samples. Loss-of-function Src mutants (K297R, K296R/Y528F) or shRNA knock-down of Src prevented the ERK1/2 activation induced by Chk1 inhibitors and increased apoptosis. Conversely, constitutively active Ras or mitogen-activated protein kinase/ERK kinase 1 (MEK1) significantly diminished the ability of Src inhibitors to potentiate Chk1-inhibitor lethality. Moreover, Src/Chk1-inhibitor cotreatment attenuated MM-cell production of vascular endothelial growth factor and other angiogenic factors (eg, ANG [angiogenin], TIMP1/2 [tissue inhibitor of metalloproteinases 1/2], and RANTES [regulated on activation normal T-cell expressed and secreted]), and inhibited in vitro angiogenesis. Finally, coadministration of BMS354825 and UCN-01 suppressed human MM tumor growth in a murine xenograft model, increased apoptosis, and diminished angiogenesis. These findings suggest that Src kinase is required for Chk1-inhibitor–mediated Ras → ERK1/2 signaling activation, and that disruption of this event sharply potentiates the anti-MM activity of Chk1 inhi-bitors in vitro and in vivo.
Gain-of-function GPIb ELISA assay for VWF activity in the Zimmerman Program for the Molecular and Clinical Biology of VWD
Authors: Flood Veronica H. , Gill Joan Cox , Morateck Patricia A. , Christopherson Pamela A. , Friedman Kenneth D. , Haberichter Sandra L. , Hoffmann Raymond G. , Montgomery Robert R. 
Published: December 2010

Abstractvon Willebrand disease (VWD) is a common bleeding disorder, but diagnosis is sometimes challenging because of issues with the current von Willebrand factor (VWF) assays, VWF antigen (VWF:Ag) and VWF ristocetin cofactor activity (VWF:RCo), used for diagnosis. We evaluated 113 healthy controls and 164 VWD subjects enrolled in the T.S. Zimmerman Program for the Molecular and Clinical Biology of VWD for VWF:Ag, VWF:RCo, and a new enzyme-linked immunosorbent assay (ELISA)–based assay of VWF-glycoprotein Ib (GPIb) interactions using a gain-of-function GPIb construct (tGPIbα235Y;239V) as a receptor to bind its ligand VWF in an assay independent of ristocetin (VWF:IbCo ELISA). Healthy controls, type 1, 2A, 2M, and 2N subjects had VWF:RCo/VWF:Ag ratios similar to the ratio obtained with VWF:IbCo ELISA/VWF:Ag. Type 2B VWD subjects, however, had elevated VWF:IbCo ELISA/VWF:Ag ratios. Type 3 VWD subjects had undetectable (< 1.6 U/dL) VWF:IbCo ELISA values. As previously reported, VWF:RCo/VWF:Ag ratio was decreased with a common A1 domain polymorphism, D1472H, as was direct binding to ristocetin for a 1472H A1 loop construct. The VWF:IbCo ELISA, however, was not affected by D1472H. The VWF:IbCo ELISA may be useful in testing VWF binding to GPIb, discrimination of type 2 variants, and in the diagnosis of VWD as it avoids some of the pitfalls of VWF:RCo assays.
Differential requirements for the Ets transcription factor Elf-1 in the development of NKT cells and NK cells
Authors: Choi Hak-Jong , Geng Yanbiao , Cho Hoonsik , Li Sha , Giri Pramod Kumar , Felio Kyrie , Wang Chyung-Ru 
Published: December 2010

AbstractE26 Transformation specific (Ets) family transcription factors control the expression of a large number of genes regulating hematopoietic cell development and function. Two such transcription factors, Ets-1 and myeloid Elf-1–like factor (MEF), have been shown to play critical roles in both natural killer (NK)– and NKT-cell development, but not in the development of conventional T cells. In this study, we address the role of E74-like factor 1 (Elf-1), another Ets family transcription factor that is closely related to MEF but divergent from Ets-1, in NK- and NKT-cell development using Elf-1–deficient (Elf-1−/−) mice. Whereas the proportion of NK cells in Elf-1−/− mice was normal, the proportion of NKT cells was significantly reduced in the thymus and periphery of Elf-1−/− mice compared with wild-type (WT) mice. Although Ets-1–deficient mice lack NKT cells altogether, Elf-1−/− mice exhibited only a partial block in NKT-cell development caused by a cell-intrinsic defect in the selection, survival, and maturation of NKT cells. In addition, residual NKT cells found in Elf-1−/− mice produced less cytokine upon antigen stimulation compared with WT NKT cells. Our data demonstrate that Elf-1 plays an important and nonredundant role in the development and function of NKT cells, but is not involved in NK-cell development.
RhoA-mediated signaling up-regulates hepatocyte growth factor gene and protein expression in response to apoptotic cells
Authors: Park Hyun-Jung , Choi Youn-Hee , Cho Young Joo , Henson Peter M , Kang Jihee Lee 
Published: December 2010

ABSTRACT
Clearance of apoptotic cells by macrophages induces HGF secretion. We examined the regulatory mechanisms of HGF mRNA and protein expression in macrophages upon exposure to apoptotic cells. The interaction of RAW 264.7 macrophages with apoptotic Jurkat cells, but not with viable cells, resulted in expression of HGF mRNA and protein. Exposure of RAW 264.7 cells to apoptotic cells induced activation of RhoA, the PI3K/Akt pathway, and MAPKs, including p38 MAPK, ERK, and JNK. Down-regulation of the RhoA/Rho kinase pathway by pharmacological inhibitors or a RhoA-specific siRNA suppressed HGF mRNA and protein expression by macrophages in response to apoptotic cells through the phosphorylation of Akt and the MAPKs. Inhibition of PI3K decreased phosphorylation of Akt and the MAPKs. Inhibition of JNK, but not p38 MAPK and ERK, reduced Akt phosphorylation. The pharmacological inhibitor of PI3K and the MAPKs blocked HGF mRNA and protein expression. Other types of apoptotic cells, such as HeLa cells and murine thymocytes, could also induce HGF mRNA through the RhoA-dependent pathway. Likely, the RhoA-dependent signaling pathway was required for HGF mRNA induction in primary cells of peritoneal macrophages in response to apoptotic cells. An HGFR-blocking antibody did not alter apoptotic cell-induced activation of RhoA, Akt, and the MAPKs, as well as HGF production. Overall, the data provide evidence that activation of the RhoA/Rho kinase pathway up-regulates transcriptional HGF production in response to apoptotic cells.
Quality–Speed Conundrum: Trade-offs in Customer-Intensive Services
Authors: Anand Krishnan S. , Paç M. Fazıl , Veeraraghavan Senthil 
Published: December 2010

In many services, the quality or value provided by the service increases with the time the service provider spends with the customer. However, longer service times also result in longer waits for customers. We term such services, in which the interaction between quality and speed is critical, as customer-intensive services. In a queueing framework, we parameterize the degree of customer intensity of the service. The service speed chosen by the service provider affects the quality of the service through its customer intensity. Customers queue for the service based on service quality, delay costs, and price. We study how a service provider facing such customers makes the optimal “quality–speed trade-off.” Our results demonstrate that the customer intensity of the service is a critical driver of equilibrium price, service speed, demand, congestion in queues, and service provider revenues. Customer intensity leads to outcomes very different from those of traditional models of service rate competition. For instance, as the number of competing servers increases, the price increases, and the servers become slower. This paper was accepted by Sampath Rajagopalan, operations and supply chain management.
Portfolio Choice Under Cumulative Prospect Theory: An Analytical Treatment
Authors: He Xue Dong , Zhou Xun Yu 
Published: December 2010

We formulate and carry out an analytical treatment of a single-period portfolio choice model featuring a reference point in wealth, S-shaped utility (value) functions with loss aversion, and probability weighting under Kahneman and Tversky's cumulative prospect theory (CPT). We introduce a new measure of loss aversion for large payoffs, called the large-loss aversion degree (LLAD), and show that it is a critical determinant of the well-posedness of the model. The sensitivity of the CPT value function with respect to the stock allocation is then investigated, which, as a by-product, demonstrates that this function is neither concave nor convex. We finally derive optimal solutions explicitly for the cases in which the reference point is the risk-free return and those in which it is not (while the utility function is piecewise linear), and we employ these results to investigate comparative statics of optimal risky exposures with respect to the reference point, the LLAD, and the curvature of the probability weighting. This paper was accepted by Wei Xiong, finance.
Sodium oxybate increases prolactin secretion in narcolepsy patients and healthy controls
Authors: Donjacour Claire E H M , Aziz N Ahmad , Frölich Marijke , Roelfsema Ferdinand , Overeem Sebastiaan , Lammers Gert Jan , Pijl Hanno 
Published: December 2010

ObjectiveHypocretin deficiency causes narcolepsy and may affect neuroendocrine systems, including TSH, ACTH and LH secretion. Symptoms can be treated effectively with sodium oxybate (SXB) in many patients. This study was performed to compare prolactin (PRL) secretion in patients and matched controls and establish the effect of SXB administration on PRL and sleep in both the groups.DesignOpen label intervention. Blood was sampled before and after 5 days of SXB treatment. The study was performed at the Leiden University Medical Centre, Leiden, The Netherlands.MethodsSubjects were admitted to the clinical research centre on both occasions.Patients or participantsEight male hypocretin-deficient narcolepsy with cataplexy patients and eight controls matched for sex, age, body mass index, waist-to-hip ratio and fat percentage were enrolled.InterventionsSXB two times 3 g per night for five consecutive nights.ResultsPatients and controls underwent 24 h blood sampling at 10 min intervals for measurement of PRL concentrations. The PRL concentration time series was analysed with a new deconvolution programme, approximate entropy (ApEn) and Cosinor analysis. Sleep was polygraphically recorded. Basal and pulsatile PRL secretion, as well as pulse regularity and frequency, ApEn and diurnal parameters were similar in patients and controls. SXB treatment caused similar nocturnal increase in PRL secretion, advance of the acrophase and decrease in ApEn in patients and controls. Slow wave sleep was increased to a similar extent in patients and controls.ConclusionThis detailed study did not demonstrate altered PRL secretion in hypocretin-deficient narcolepsy patients during the basal state or during SXB administration. Therefore, hypocretin signalling is unlikely to be a regulator of the lactotrophic system.
Approval Summary: Pemetrexed Maintenance Therapy of Advanced/Metastatic Nonsquamous, Non-Small Cell Lung Cancer (NSCLC)
Authors: Cohen Martin H. , Cortazar Patricia , Justice Robert , Pazdur Richard 
Published: December 2010

Abstract

Learning Objectives
After completing this course, the reader will be able to: Consider tumor histology when making treatment decisions for patients with NSCLC.Identify patients with NSCLC who may be appropriate candidates for maintenance therapy with pemetrexed.
This article is available for continuing medical education credit at CME.TheOncologist.com.
On July 2, 2009, the U.S. Food and Drug Administration approved pemetrexed injection (Alimta® Injection; Eli Lilly and Company, Indianapolis, IN) for maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based doublet induction chemotherapy.
A double-blind study of pemetrexed plus best supportive care versus placebo plus best supportive care was conducted. Pemetrexed, 500 mg/m2 i.v., was administered every 21 days until disease progression. Folic acid, vitamin B12, and a corticosteroid were given to all study patients.
There were 663 randomized patients (pemetrexed, 441; placebo, 222). Treatments were well balanced with respect to baseline disease characteristics and stratification factors.
The median overall survival (OS) time for intent-to-treat (ITT) patients was 13.4 months for patients receiving pemetrexed and 10.6 months for those receiving placebo (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.65–0.95; p = .012). Median OS times were 15.5 months versus 10.3 months for patients with nonsquamous histologies receiving pemetrexed and placebo, respectively (HR, 0.70; 95% CI, 0.56–0.88). The median OS time in patients with squamous histology receiving pemetrexed was 9.9 months, versus 10.8 months for those receiving placebo (HR, 1.07; 95% CI, 0.77–1.50). A significantly longer progression-free survival interval for both the ITT and nonsquamous patient populations receiving pemetrexed maintenance therapy was also observed.
The most common (&gt;5%) adverse reactions in patients receiving pemetrexed were hematologic toxicity, an increase in hepatic enzymes, fatigue, gastrointestinal toxicity, sensory neuropathy, and skin rash.
Waring’s problem with digital restrictions in $$
\mathbb{F}
$$
q[X]
Authors: Madritsch Manfred 
Published: December 2010

Abstract
We present a generalization of a result due to Thuswaldner and Tichy to the ring of polynomials over a finite fields. In particular, we want to show that every polynomial of sufficiently large degree can be represented as sum of kth powers, where the bases evaluated on additive functions meet certain congruence restrictions.
Un desangramiento frenético
Authors: Nouhaud Dorita 
Published: December 2010

R. Arenas committed suicide on the 7th of December 1990 in New York when he was in the last phase of HIV infection. However, before ending his life, he tried to complete his work El Color del verano, la Pentagonía,the first four volumes of which were already on sale. He finished his book of memories Antes que anochezca by revising the third poem of the poetic trilogy, Leprosorio. It’s hard to believe that he could set himself such an enormous task whilst enduring the last stages of disease. A sense of failure infuses his last three works but feelings of hatred become much more apparent when he refers to the cause of this failure, Fidel Castro. The most interesting aspect of the aesthetic representation is related to the changeable nature of memory and how the inconstancy of this exiled writer’s memories help to develop the work he started months or – in the instance of Leprosorio - even years ago. At the same time, those changes affect also his interpretation of the irreparable twilight that lights up at the last moment and which creates the certainty of unlimited liberty achievable at the final limits of life and by himself alone.
La mémoire et l’imaginaire utopique
Authors: Lani Soraya 
Published: December 2010

En 1964 la dictature militaire s’installe au Brésil créant la censure à tous les niveaux. A ce moment-là, l’écrivain juif brésilien Moacyr Scliar intègre le groupe d’écrivains latino-américains liés au courant littéraire du réalisme magique dont ses membres cherchent des subterfuges littéraires, tels que les discours allégorique et métaphorique, pour s’opposer au régime. L’émergence de cette nouvelle représentation esthétique suscite ainsi une relecture du passé, où la mémoire arrange esthétiquement le souvenir. Dans ce contexte, nous proposons d’analyser dans le roman « Sa Majesté des Indiens » (1997), où le temps du récit s’insère dans le contexte dictatorial brésilien, la manière dont Moacyr Scliar s’approprie l’histoire officielle, et comment, par le biais des personnages historiques, l’écrivain parvient à construire un imaginaire utopique basé sur une fusion culturelle et idéologique pour échapper à la répression.
Mémoires d'en bas
Authors: Galland Nathalie 
Published: December 2010

Il s'agit ici d'envisager la production discursive de l'Ejército Zapatista de Liberación Nacional (Mexique, 1994-2001) comme objet esthétique fondamentalement mémoriel. Les textes se donnent en effet comme trace finiséculaire de la résistance, alternative pour une reconstruction de la mémoire collective, transgressant idéologies et fatalités historiques et consacrant la mémoire vivante de ceux d'en bas. Et cette mémoire qui infuse dans des textes se fait tour à tour mémoire vagabonde qui liste son expérience du monde, mémoire du silence aussi, patiente et épiphanique. Ces représentations de la mémoire de surcroît s'inscrivent dans un process fondamentalement esthétique, c'est-à-dire esthésique, susceptible d'ébranler la chair par les mots, par la sensation, par le partage de l'émotion. Un seul et simple postulat semble présider à la production textuelle : celui que les communiqués, par le sensible, peuvent ou doivent modifier la représentation du passé et celle du possible, celui que la poésie fait sentir le sens, que le politique se pulvérise dans l'esthétique.
Les représentations esthétiques de la violence dans l’œuvre de Fernando Botero
Authors: Lassus Jean-Marie 
Published: December 2010

En 2005, le peintre colombien Fernando Botero expose à Rome une cinquantaine d'œuvres (triptyques, tableaux et dessins) sur les tortures commises par des soldats américains dans la prison d'Abou Ghraib, conséquences de la guerre en Irak et des attentats du 11 septembre 2001. Après avoir traité de la violence en Colombie, Botero élargit la portée de son témoignage esthétique, humain et politique sur un thème qui a aussi à voir avec la question des prisonniers de Guantánamo. Dans des sociétés de plus en plus mondialisées, ces œuvres permettent de s’interroger sur la nécessité de la représentation d’une « méta-mémoire » et sur les conséquences de l’impunité et de la violence d’Etat. Elles révèlent aussi l’interaction des discours sur l’art et les sociétés dans l’opération de mémoire : les références explicites à Goya et Picasso des commentateurs de ces œuvres, les relations entre les textes, les photos et les œuvres picturales, mais aussi les conditions de la représentation esthétique dans le cadre de l’histoire immédiate.
Histoire d’histoires, histoire d’images
Authors: Heches Dominique 
Published: December 2010

La Historia Oficial, 1985, de Aida Bortnik et Luis Puenzo, raconte un pan sanglant de l’histoire argentine. Historias mínimas, 2002, de Carlos Sorín, conduit le spectateur sur les routes de Patagonie. De Buenos Aires à la Patagonie, de la dictature à la démocratie, de l’enfermement à l’ouverture.La problématique à laquelle s’attache Puenzo est celle du faible décalage entre la sortie du film et les évènements racontés. Cette proximité donne du poids aux mots car il s’agit bien ici de dire l’indicible. Alicia part à la recherche de la vérité, inouïe, inimaginable et se confronte à l’inédit face aux Mères de la place de Mai. Le film montre comment l’histoire officielle est un mensonge qui se fissure pour laisser place à la mémoire et à une histoire qui n’était jusque là qu’officieuse. Puenzo s’intéresse donc à ce moment particulier, charnière entre mémoire et Histoire. Historias mínimas est-il pour autant un film amnésique de l’histoire ? Non, c’est une « action chargée de peu de matière », qui a pour cadre les paysages ouverts du sud. A la verticalité barbare de Buenos Aires s’oppose l’horizontalité apaisante de San Julian, là où tout a commencé.La Historia Oficial, 1985, directed by Aida Bortnik and Luis Puenzo, relates a blood-stained part of Argentinian history. Historias Minimas, 2002, directed by Carlos Sorin, takes the spectator along the roads of Patagonia. From Buenos Aires to Patagonia, from dictatorship to democracy, from closure to aperture.
The Human Glucocorticoid Receptor as an RNA-Binding Protein: Global Analysis of Glucocorticoid Receptor-Associated Transcripts and Identification of a Target RNA Motif
Authors: Ishmael Faoud T. , Fang Xi , Houser Kenneth R. , Pearce Kenneth , Abdelmohsen Kotb , Zhan Ming , Gorospe Myriam , Stellato Cristiana 
Published: December 2010

Abstract
Posttranscriptional regulation is emerging as a key factor in glucocorticoid (GC)-mediated gene regulation. We investigated the role of the human GC receptor (GR) as an RNA-binding protein and its effect on mRNA turnover in human airway epithelial cells. Cell treatment with the potent GC budesonide accelerated the decay of CCL2 mRNA (t1/2 = 8 ± 1 min versus 62 ± 17 min in DMSO-treated cells) and CCL7 mRNA (t1/2 = 15 ± 4 min versus 114 ± 37 min), but not that of CCL5 mRNA (t1/2=231 ± 8 min versus 266 ± 5 min) in the BEAS-2B cell line. This effect was inhibited by preincubation with an anti-GR Ab, indicating that GR itself plays a role in the turnover of these transcripts. Coimmunoprecipitation and biotin pulldown experiments showed that GR associates with CCL2 and CCL7 mRNAs, but not CCL5 mRNA. These methods confirmed CCL2 mRNA targeting by GR in human primary airway epithelial cells. Association of the GR was localized to the 5′ untranslated region of CCL2 mRNA and further mapped to nt 44–60. The collection of transcripts associated with GR, identified by immunoprecipitation of GR-mRNA complexes followed by microarray analysis, revealed 479 transcripts that associated with GR. Computational analysis of the primary sequence and secondary structures of these transcripts yielded a GC-rich motif, which was shown to bind to GR in vitro. This motif was used to predict binding of GR to an additional 7889 transcripts. These results indicate that cytoplasmic GR interacts with a subset of mRNA through specific sequences and can regulate turnover rates, suggesting a novel posttranscriptional role for GR as an RNA-binding protein.
Ets-1 Maintains IL-7 Receptor Expression in Peripheral T Cells
Authors: Grenningloh Roland , Tai Tzong-Shyuan , Frahm Nicole , Hongo Tomoyuki C. , Chicoine Adam T. , Brander Christian , Kaufmann Daniel E. , Ho I-Cheng 
Published: December 2010

Abstract
The expression of CD127, the IL-7–binding subunit of the IL-7 R, is tightly regulated during the development and activation of T cells and is reduced during chronic viral infection. However, the molecular mechanism regulating the dynamic expression of CD127 is still poorly understood. In this study, we report that the transcription factor Ets-1 is required for maintaining the expression of CD127 in murine peripheral T cells. Ets-1 binds to and activates the CD127 promoter, and its absence leads to reduced CD127 expression, attenuated IL-7 signaling, and impaired IL-7–dependent homeostatic proliferation of T cells. The expression of CD127 and Ets-1 is strongly correlated in human T cells. Both CD127 and Ets-1 expression are decreased in CD8+ T cells during HIV infection. In addition, HIV-associated loss of CD127 is only observed in Ets-1low effector memory and central memory but not in Ets-1high naive CD8+ T cells. Taken together, our data identify Ets-1 as a critical regulator of CD127 expression in T cells.