bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cycle scheduling for in vitro fertilization with oral contraceptive pills versus oral estradiol valerate: a randomized, controlled trial
Authors: Hauzman Erik E , Zapata Azucena , Bermejo Alfonso , Iglesias Carlos , Pellicer Antonio , Garcia-Velasco Juan A 
Published: September 2013

Abstract

Background
Both oral contraceptive pills (OCPs) and estradiol (E2) valerate have been used to schedule gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles and, consequently, laboratory activities. However, there are no studies comparing treatment outcomes directly between these two pretreatment methods. This randomized controlled trial was aimed at finding differences in ongoing pregnancy rates between GnRH antagonist IVF cycles scheduled with OCPs or E2 valerate.

Methods
Between January and May 2012, one hundred consecutive patients (nonobese, regularly cycling women 18–38 years with normal day 3 hormone levels and <3 previous IVF/ICSI attempts) undergoing IVF with the GnRH antagonist protocol were randomized to either the OCP or E2 pretreatment arms, with no restrictions such as blocking or stratification. Authors involved in data collection and analysis were blinded to group assignment. Fifty patients received OCP (30 μg ethinyl E2/150 μg levonorgestrel) for 12–16 days from day 1 or 2, and stimulation was started 5 days after stopping OCP. Similarly, 50 patients received 4 mg/day oral E2 valerate from day 20 for 5–12 days, until the day before starting stimulation.

Results
Pretreatment with OCP (mean±SD, 14.5±1.7 days) was significantly longer than with E2 (7.8±1.9 days). Stimulation and embryological characteristics were similar. Ongoing pregnancy rates (46.0% vs. 44.0%; risk difference, –2.0% [95% CI –21.2% to 17.3%]), as well as implantation (43.5% vs. 47.4%), clinical pregnancy (50.0% vs. 48.0%), clinical miscarriage (7.1% vs. 7.7%), and live birth (42.0% vs. 40.0%) rates were comparable between groups.

Conclusions
This is the first study to directly compare these two methods of cycle scheduling in GnRH antagonist cycles. Our results fail to show statistically significant differences in ongoing pregnancy rates between pretreatment with OCP and E2 for IVF with the GnRH antagonist protocol. Although the study is limited by its sample size, our results may contribute to a future meta-analysis. An interesting future direction would be to extend our study to women with decreased ovarian reserve, as these are the patients in whom an increase in oocyte yield—due to the hypothetical beneficial effect of steroid pretreatment on follicular synchronization—could more easily be demonstrated.

Trial registration
ClinicalTrials.gov NCT01501448
Kennedy disease misdiagnosed as polymyositis: a case report
Authors: Harutunian Grigor M , Beydoun Said R , Rison Richard A 
Published: September 2013

Abstract

Background
Polymyositis is an immune-mediated myopathy with clinical features of proximal muscle weakness. Dysphagia and neck flexor weakness can develop along with respiratory muscle weakness as the disease progresses. Kennedy disease or X-linked spinobulbar muscular atrophy is a rare X-linked recessive disorder with clinical features of slowly progressive atrophy and weakness of limb and bulbar muscles. These two disorders may have overlapping clinical manifestations.

Case presentation
We present the case of a 52-year-old Filipino man with chronic weakness involving his proximal muscle groups who carried the diagnosis of polymyositis and was refractory to multiple immunomodulatory therapies. Further neurologic examination and history taking along with selective serologic and electrodiagnostic studies instead confirmed the diagnosis of Kennedy disease.

Conclusions
Distinction between polymyositis and Kennedy disease may be difficult given the potential overlapping clinical manifestations. However, with careful neurological history taking, examination, and selective serologic plus electrodiagnostic investigations the correct diagnosis may be made, thus sparing the patient ineffective therapy. One must always be sure of the diagnosis of polymyositis before it’s classified as refractory.
The favorable kinetics and balance of nebivolol-stimulated nitric oxide and peroxynitrite release in human endothelial cells
Authors: Mason R Preston , Jacob Robert F , Corbalan J Jose , Szczesny Damian , Matysiak Kinga , Malinski Tadeusz 
Published: September 2013

Abstract

Background
Nebivolol is a third-generation beta-blocker used to treat hypertension. The vasodilation properties of nebivolol have been attributed to nitric oxide (NO) release. However, the kinetics and mechanism of nebivolol-stimulated bioavailable NO are not fully understood.

Methods
Using amperometric NO and peroxynitrite (ONOO-) nanosensors, β3-receptor (agonist: L-755,507; antagonists: SR59230A and L-748,337), ATP efflux (the mechanosensitive ATP channel blocker, gadolinium) and P2Y-receptor (agonists: ATP and 2-MeSATP; antagonist: suramin) modulators, superoxide dismutase and a NADPH oxidase inhibitor (VAS2870), we evaluated the kinetics and balance of NO and ONOO- stimulated by nebivolol in human umbilical vein endothelial cells (HUVECs). NO and ONOO- were measured with nanosensors (diameter ~ 300 nm) placed 5 ± 2 μm from the cell membrane and ATP levels were determined with a bioluminescent method. The kinetics and balance of nebivolol-stimulated NO and ONOO- were compared with those of ATP, 2-MeSATP, and L-755,507.

Results
Nebivolol stimulates endothelial NO release through β3-receptor and ATP-dependent, P2Y-receptor activation with relatively slow kinetics (75 ± 5 nM/s) as compared to the kinetics of ATP (194 ± 10 nM/s), L-755,507 (108 ± 6 nM/s), and 2-MeSATP (105 ± 5 nM/s). The balance between cytoprotective NO and cytotoxic ONOO- was expressed as the ratio of [NO]/[ONOO-] concentrations. This ratio for nebivolol was 1.80 ± 0.10 and significantly higher than that for ATP (0.80 ± 0.08), L-755,507 (1.08 ± 0.08), and 2-MeSATP (1.09 ± 0.09). Nebivolol induced ATP release in a concentration-dependent manner.

Conclusion
The two major pathways (ATP efflux/P2Y receptors and β3 receptors) and several steps of nebivolol-induced NO and ONOO- stimulation are mainly responsible for the slow kinetics of NO release and low ONOO-. The net effect of this slow kinetics of NO is reflected by a favorable high ratio of [NO]/[ONOO-] which may explain the beneficial effects of nebivolol in the treatment of endothelial dysfunction, hypertension, heart failure, and angiogenesis.
Marshalin, a microtubule minus-end binding protein, regulates cytoskeletal structure in the organ of Corti
Authors: Zheng Jing , Furness David , Duan Chongwen , Miller Katharine K. , Edge Roxanne M. , Chen Jessie , Homma Kazuaki , Hackney Carole M. , Dallos Peter , Cheatham Mary Ann 
Published: September 2013

Summary
Dramatic structural changes in microtubules (MT) and the assembly of complicated intercellular connections are seen during the development of the cellular matrix of the sense organ for hearing, the organ of Corti. This report examines the expression of marshalin, a minus-end binding protein, during this process of cochlear development. We discovered that marshalin is abundantly expressed in both sensory hair cells and supporting cells. In the adult, prominent marshalin expression is observed in the cuticular plates of hair cells and in the noncentrosomal MT organization centers (MTOC) of Deiters' and pillar cells. Based upon differences in marshalin expression patterns seen in the organ of Corti, we identified eight isoforms ranging from 863 to 1280 amino acids. mRNAs/proteins associated with marshalin's isoforms are detected at different times during development. These isoforms carry various protein–protein interacting domains, including coiled-coil (CC), calponin homology (CH), proline-rich (PR), and MT-binding domains, referred to as CKK. We, therefore, examined membranous organelles and structural changes in the cytoskeleton induced by expressing two of these marshalin isoforms in vitro. Long forms containing CC and PR domains induce thick, spindle-shaped bundles, whereas short isoforms lacking CC and PR induce more slender variants that develop into densely woven networks. Together, these data suggest that marshalin is closely associated with noncentrosomal MTOCs, and may be involved in MT bundle formation in supporting cells. As a scaffolding protein with multiple isoforms, marshalin is capable of modifying cytoskeletal networks, and consequently organelle positioning, through interactions with various protein partners present in different cells.
Fascin 1 is dispensable for developmental and tumour angiogenesis
Authors: Ma Yafeng , Reynolds Louise E. , Li Ang , Stevenson Richard P. , Hodivala-Dilke Kairbaan M. , Yamashiro Shigeko , Machesky Laura M. 
Published: September 2013

Summary
The actin bundling protein fascin 1 is not expressed in adult epithelial tissues, but during development it is transiently expressed in many different cell types, and later in adults it is expressed in a subset of immune cells, nervous tissues, endothelial cells, smooth muscle cells and pericytes. In contrast to the wealth of knowledge about the role of fascin 1 in cancer cell migration and invasion, little is known about the involvement of fascin 1 in angiogenesis. We speculated that as angiogenesis involves migration and invasion of tissues by endothelial cells, fascin 1 might have a role in both normal and tumour angiogenesis. Here, we provide evidence that loss of fascin 1 causes relatively minor reductions to angiogenesis during embryonic, postnatal and cancerous development by examining E12.5 hindbrains, postnatal retinas and B16F0 tumour cell allografts in fascin 1-null mice. We also find that in fascin 1 null tissues, endothelial cells display reduced filopodia formation during sprouting. We thus propose that fascin 1 expression promotes angiogenesis via filopodia formation, but is largely dispensable for both normal and tumour angiogenesis.
Dimerization Reactions of 2-Bromo-3,5,6-trimethyl-1,4-benzoquinone
Authors: Azuma Shuhei , Ota Motohiro , Ishida Akito , Isozaki Katsuhiro , Takaya Hikaru , Nakamura Masaharu , Sasamori Takahiro , Tokitoh Norihiro , Kuramochi Kouji , Tsubaki Kazunori 
Published: September 2013

Abstract
The dimerization reactions of 2-bromo-3,5,6-trimethyl-1,4-benzoquinone have been examined. 2,2′-Dimeric benzoquinone was prepared via a Stille-type homocoupling, whereas an oxepin was formed by the treatment of the title quinone with hexamethylditin, CuI, and (±)-BINAP in DMF. Two dimerization reactions involving a hetero Diels–Alder reaction between quinones and quinone methides were also observed.
New NMR Tools for Characterizing the Dynamic Conformations and Interactions of Oligosaccharides
Authors: Zhang Ying , Yamaguchi Takumi , Kato Koichi 
Published: September 2013

Abstract
Oligosaccharides play pivotal roles in various molecular recognition events on cell surfaces and in intracellular environments. Although information about the three-dimensional structure of oligosaccharides is crucial for understanding the mechanisms underlying their biological functions and for designing drugs targeting carbohydrate recognition systems, their inherent flexibility hampers detailed conformational analysis. NMR spectroscopy has immense potential for providing atomic details of oligosaccharide structures in solution as well as in complexes with other biomolecules. However, the traditional NMR approach based on local conformational information provided by the nuclear Overhauser effect (NOE) is often precluded by insufficient information about long interatomic distances and hydrogen bonds involving hydroxy groups. To address these issues, new NMR techniques have recently been developed, exploiting the effects of introduced paramagnetic probes and stable isotopes to target oligosaccharides. Lanthanoid tagging and the spin labeling of oligosaccharides induce paramagnetic effects such as pseudocontact shift and paramagnetic relaxation enhancement, offering NOE-independent sources of long-distance information. Deuterium-induced isotope shifts of neighboring 13C resonances provide an experimental tool for the identification of hydrogen bonds involving oligosaccharide hydroxy groups. The uniform and position-selective 13C enrichment of oligosaccharides can be achieved by metabolic labeling using genetically engineered yeast cells. Furthermore, small ganglioside-embedding bicelles have been used for detailed NMR analyses of intermolecular interactions involving glycolipids in membrane environments. These NMR approaches, in conjunction with computational simulation, have opened up new vistas for the analysis of oligosaccharide conformations and interactions at atomic level.
Understanding the Effect of Advertising on Stock Returns and Firm Value: Theory and Evidence from a Structural Model
Authors: Vitorino Maria Ana 
Published: September 2013

This paper brings structural modeling to the literature on financial research in marketing. I propose a dynamic investment-based model to understand the impact of advertising expenditures on stock returns and firm value. In addition, by interpreting advertising expenditures as an investment in brand capital, the approach in this paper provides a novel way to measure brand equity grounded in economic theory. Using the Euler equations from the firm's maximization problem, I derive closed-form expressions for the firm's equilibrium stock returns and market value, which depend on observable firm characteristics. I test the model's predictions by the generalized method of moments and data from a large cross section of publicly traded firms. The model is able to match simultaneously the pattern of average stock returns and firm values of portfolios sorted on advertising expenditures that standard asset pricing models cannot. The estimation results also show that brand equity accounts for a substantial fraction of firm market value (about 23%), and that this value varies substantially across industries. Implications of the findings for research at the intersection of marketing and finance are discussed. This paper was accepted by Wei Xiong, finance.
Tolerance ofEscherichia colito Fluoroquinolone Antibiotics Depends on Specific Components of the SOS Response Pathway
Authors: Theodore Alyssa , Lewis Kim , Vulić Marin 
Published: September 2013

AbstractBacteria exposed to bactericidal fluoroquinolone (FQ) antibiotics can survive without becoming genetically resistant. Survival of these phenotypically resistant cells, commonly called “persisters,” depends on the SOS gene network. We have examined mutants in all known SOS-regulated genes to identify functions essential for tolerance in Escherichia coli. The absence of DinG and UvrD helicases and the Holliday junction processing enzymes RuvA and RuvB leads to a decrease in survival. Analysis of the respective mutants indicates that, in addition to repair of double-strand breaks, tolerance depends on the repair of collapsed replication forks and stalled transcription complexes. Mutation in recF results in increased survival, which identifies RecAF recombination as a poisoning mechanism not previously linked to FQ lethality. DinG acts upstream of SOS promoting its induction, whereas RuvAB participates in repair only. UvrD directly promotes all repair processes initiated by FQ-induced damage and prevents RecAF-dependent misrepair, making it one of the crucial SOS functions required for tolerance.
Adaptive Divergence in Experimental Populations ofPseudomonas fluorescens. V. Insight into the Niche Specialist Fuzzy Spreader Compels Revision of the ModelPseudomonasRadiation
Authors: Ferguson Gayle C , Bertels Frederic , Rainey Paul B 
Published: September 2013

AbstractPseudomonas fluorescens is a model for the study of adaptive radiation. When propagated in a spatially structured environment, the bacterium rapidly diversifies into a range of niche specialist genotypes. Here we present a genetic dissection and phenotypic characterization of the fuzzy spreader (FS) morphotype—a type that arises repeatedly during the course of the P. fluorescens radiation and appears to colonize the bottom of static broth microcosms. The causal mutation is located within gene fuzY (pflu0478)—the fourth gene of the five-gene fuzVWXYZ operon. fuzY encodes a β-glycosyltransferase that is predicted to modify lipopolysaccharide (LPS) O antigens. The effect of the mutation is to cause cell flocculation. Analysis of 92 independent FS genotypes showed each to have arisen as the result of a loss-of-function mutation in fuzY, although different mutations have subtly different phenotypic and fitness effects. Mutations within fuzY were previously shown to suppress the phenotype of mat-forming wrinkly spreader (WS) types. This prompted a reinvestigation of FS niche preference. Time-lapse photography showed that FS colonizes the meniscus of broth microcosms, forming cellular rafts that, being too flimsy to form a mat, collapse to the vial bottom and then repeatably reform only to collapse. This led to a reassessment of the ecology of the P. fluorescens radiation. Finally, we show that ecological interactions between the three dominant emergent types (smooth, WS, and FS), combined with the interdependence of FS and WS on fuzY, can, at least in part, underpin an evolutionary arms race with bacteriophage SBW25Φ2, to which mutation in fuzY confers resistance.
Noncoding RNAs of the Ultrabithorax Domain of the Drosophila Bithorax Complex
Authors: Pease Benjamin , Borges Ana C , Bender Welcome 
Published: September 2013

Abstract
RNA transcripts without obvious coding potential are widespread in many creatures, including the fruit fly, Drosophila melanogaster. Several noncoding RNAs have been identified within the Drosophila bithorax complex. These first appear in blastoderm stage embryos, and their expression patterns indicate that they are transcribed only from active domains of the bithorax complex. It has been suggested that these noncoding RNAs have a role in establishing active domains, perhaps by setting the state of Polycomb Response Elements A comprehensive survey across the proximal half of the bithorax complex has now revealed nine distinct noncoding RNA transcripts, including four within the Ultrabithorax transcription unit. At the blastoderm stage, the noncoding transcripts collectively span ∼75% of the 135 kb surveyed. Recombination-mediated cassette exchange was used to invert the promoter of one of the noncoding RNAs, a 23-kb transcript from the bxd domain of the bithorax complex. The resulting animals fail to make the normal bxd noncoding RNA and show no transcription across the bxd Polycomb Response Element in early embryos. The mutant flies look normal; the regulation of the bxd domain appears unaffected. Thus, the bxd noncoding RNA has no apparent function.
Regulation of Toll Signaling and Inflammation by β-Arrestin and the SUMO Protease Ulp1
Authors: Anjum Saima G , Xu Wenjian , Nikkholgh Niusha , Basu Sukanya , Nie Yingchao , Thomas Mary , Satyamurti Mridula , Budnik Bogdan A , Ip Y Tony , Veraksa Alexey 
Published: September 2013

Abstract
The Toll signaling pathway has a highly conserved function in innate immunity and is regulated by multiple factors that fine tune its activity. One such factor is β-arrestin Kurtz (Krz), which we previously implicated in the inhibition of developmental Toll signaling in the Drosophila melanogaster embryo. Another level of controlling Toll activity and immune system homeostasis is by protein sumoylation. In this study, we have uncovered a link between these two modes of regulation and show that Krz affects sumoylation via a conserved protein interaction with a SUMO protease, Ulp1. Loss of function of krz or Ulp1 in Drosophila larvae results in a similar inflammatory phenotype, which is manifested as increased lamellocyte production; melanotic mass formation; nuclear accumulation of Toll pathway transcriptional effectors, Dorsal and Dif; and expression of immunity genes, such as Drosomycin. Moreover, mutations in krz and Ulp1 show dosage-sensitive synergistic genetic interactions, suggesting that these two proteins are involved in the same pathway. Using Dorsal sumoylation as a readout, we found that altering Krz levels can affect the efficiency of SUMO deconjugation mediated by Ulp1. Our results demonstrate that β-arrestin controls Toll signaling and systemic inflammation at the level of sumoylation.
La démarche de projet dans l’enseignement/apprentissage d’une langue étrangère
Authors: Haramboure Françoise 
Published: September 2013

Bien que la compétence de communication soit depuis plusieurs années l’objectif majeur de l’enseignement/apprentissage d’une langue étrangère, la pratique montre qu’il existe un décalage important entre la compétence des étudiants et leur performance. La démarche de projet semble constituer une réponse adéquate à ce problème. Elle suppose que l’élève réalise des tâches d’apprentissage orientées vers la performance. Corollairement, elle implique que l’enseignant conçoive plusieurs catégories de tâches spécifiques et interdépendantes. Chacune de ces catégories vise l’acquisition de procédures transférables ; elle contribue à la performance globale des étudiants en langue cible et à leur autonomie.
Un investissement mouvementé : Solvay en Espagne, 1908-1942
Authors: Mioche Philippe 
Published: September 2013

Cet article relate l’implantation du groupe Solvay à Torrelavega (Cantabrie) à partir de 1908. L’usine s’installe près des salines qui constituent la matière première de la fabrication de la soude avec le procédé Solvay ; à proximité aussi d’un port à la Requejada permettant d’exporter les productions. Ce travail repose sur des archives inédites et examine l’adaptation de l’entreprise belge à l’environnement économique, social et politique découvert en Espagne. Conformément à ses pratiques, Solvay met en place en peu d’années un dispositif social et diverses réalisations architecturales. Entamée par une soudière à l’ammoniac en 1908, la production est considérablement étendue avec l’électrolyse en 1935. L’organisation syndicale ouvrière s’implante précocement et la première grève a lieu en 1911. La crise majeure intervient avec la grève insurrectionnelle d’octobre 1934, « La révolte des Asturies ». Lors du pronunciamiento de juillet 1936, l’usine se retrouve dans la poche républicaine du Nord, tout près du front. Pour autant, la production n’a quasiment jamais cessé.
IL-21 Is a Double-Edged Sword in the Systemic Lupus Erythematosus–like Disease of BXSB.Yaa Mice
Authors: McPhee Caroline G. , Bubier Jason A. , Sproule Thomas J. , Park Giljun , Steinbuck Martin P. , Schott William H. , Christianson Gregory J. , Morse Herbert C. , Roopenian Derry C. 
Published: September 2013

Abstract
The pleiotropic cytokine IL-21 is implicated in the pathogenesis of human systemic lupus erythematosus by polymorphisms in the molecule and its receptor (IL-21R). The systemic lupus erythematosus-like autoimmune disease of BXSB.Yaa mice is critically dependent on IL-21 signaling, providing a model for understanding IL-21/IL-21R signaling in lupus pathogenesis. In this study, we generated BXSB.Yaa mice selectively deficient in IL-21R on B cells, on all T cells, or on CD8+ T cells alone and examined the effects on disease. We found that IL-21 signaling to B cells is essential for the development of all classical disease manifestations, but that IL-21 signaling also supports the expansion of central memory, CD8+ suppressor cells and broadly represses the cytokine activity of CD4+ T cells. These results indicate that IL-21 has both disease-promoting and disease-suppressive effects in the autoimmune disease of BXSB.Yaa mice.