bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the proneural gene regulatory network during mouse telencephalon development
Authors: Gohlke Julia M , Armant Olivier , Parham Frederick M , Smith Marjolein V , Zimmer Celine , Castro Diogo S , Nguyen Laurent , Parker Joel S , Gradwohl Gerard , Portier Christopher J , Guillemot François 
Published: April 2008

AbstractBackgroundThe proneural proteins Mash1 and Ngn2 are key cell autonomous regulators of neurogenesis in the mammalian central nervous system, yet little is known about the molecular pathways regulated by these transcription factors.ResultsHere we identify the downstream effectors of proneural genes in the telencephalon using a genomic approach to analyze the transcriptome of mice that are either lacking or overexpressing proneural genes. Novel targets of Ngn2 and/or Mash1 were identified, such as members of the Notch and Wnt pathways, and proteins involved in adhesion and signal transduction. Next, we searched the non-coding sequence surrounding the predicted proneural downstream effector genes for evolutionarily conserved transcription factor binding sites associated with newly defined consensus binding sites for Ngn2 and Mash1. This allowed us to identify potential novel co-factors and co-regulators for proneural proteins, including Creb, Tcf/Lef, Pou-domain containing transcription factors, Sox9, and Mef2a. Finally, a gene regulatory network was delineated using a novel Bayesian-based algorithm that can incorporate information from diverse datasets.ConclusionTogether, these data shed light on the molecular pathways regulated by proneural genes and demonstrate that the integration of experimentation with bioinformatics can guide both hypothesis testing and hypothesis generation.
Involvement of a specificity proteins-binding element in regulation of basal and estrogen-induced transcription activity of the BRCA1gene
Authors: Hockings Jennifer K , Degner Stephanie C , Morgan Sherif S , Kemp Michael Q , Romagnolo Donato F 
Published: April 2008

Abstract
Introduction
Increased estrogen level has been regarded to be a risk factor for breast cancer. However, estrogen has also been shown to induce the expression of the tumor suppressor gene, BRCA1. Upregulation of BRCA1 is thought to be a feedback mechanism for controlling DNA repair in proliferating cells. Estrogens enhance transcription of target genes by stimulating the association of the estrogen receptor (ER) and related coactivators to estrogen response elements or to transcription complexes formed at activator protein (AP)-1 or specificity protein (Sp)-binding sites. Interestingly, the BRCA1 gene lacks a consensus estrogen response element. We previously reported that estrogen stimulated BRCA1 transcription through the recruitment of a p300/ER-α complex to an AP-1 site harbored in the proximal BRCA1 promoter. The purpose of the study was to analyze the contribution of cis-acting sites flanking the AP-1 element to basal and estrogen-dependent regulation of BRCA1 transcription.

Methods
Using transfection studies with wild-type and mutated BRCA1 promoter constructs, electromobility binding and shift assays, and DNA-protein interaction and chromatin immunoprecipitation assays, we investigated the role of Sp-binding sites and cAMP response element (CRE)-binding sites harbored in the proximal BRCA1 promoter.

Results
We report that in the BRCA1 promoter the AP-1 site is flanked upstream by an element (5'-GGGGCGGAA-3') that recruits Sp1, Sp3, and Sp4 factors, and downstream by a half CRE-binding motif (5'-CGTAA-3') that binds CRE-binding protein. In ER-α-positive MCF-7 cells and ER-α-negative Hela cells expressing exogenous ER-α, mutation of the Sp-binding site interfered with basal and estrogen-induced BRCA1 transcription. Conversely, mutation of the CRE-binding element reduced basal BRCA1 promoter activity but did not prevent estrogen activation. In combination with the AP-1/CRE sites, the Sp-binding domain enhanced the recruitment of nuclear proteins to the BRCA1 promoter. Finally, we report that the MEK1 (mitogen-activated protein kinase kinase-1) inhibitor PD98059 attenuated the recruitment of Sp1 and phosphorylated ER-α, respectively, to the Sp and AP-1 binding element.

Conclusion
These cumulative findings suggest that the proximal BRCA1 promoter segment comprises cis-acting elements that are targeted by Sp-binding and CRE-binding proteins that contribute to regulation of BRCA1 transcription.
Vasopressin and epinephrine in the treatment of cardiac arrest: an experimental study
Authors: Stroumpoulis Konstantinos , Xanthos Theodoros , Rokas Georgios , Kitsou Vassiliki , Papadimitriou Dimitrios , Serpetinis Ioannis , Perrea Despina , Papadimitriou Lila , Kouskouni Evangelia 
Published: April 2008

Abstract
Background
Epinephrine remains the drug of choice for cardiopulmonary resuscitation. The aim of the present study is to assess whether the combination of vasopressin and epinephrine, given their different mechanisms of action, provides better results than epinephrine alone in cardiopulmonary resuscitation.

Methods
Ventricular fibrillation was induced in 22 Landrace/Large-White piglets, which were left untreated for 8 minutes before attempted resuscitation with precordial compression, mechanical ventilation and electrical defibrillation. Animals were randomized into 2 groups during cardiopulmonary resuscitation: 11 animals who received saline as placebo (20 ml dilution, bolus) + epinephrine (0.02 mg/kg) (Epi group); and 11 animals who received vasopressin (0.4 IU/kg/20 ml dilution, bolus) + epinephrine (0.02 mg/kg) (Vaso-Epi group). Electrical defibrillation was attempted after 10 minutes of ventricular fibrillation.

Results
Ten of 11 animals in the Vaso-Epi group restored spontaneous circulation in comparison to only 4 of 11 in the Epi group (p = 0.02). Aortic diastolic pressure, as well as, coronary perfusion pressure were significantly increased (p < 0.05) during cardiopulmonary resuscitation in the Vaso-Epi group.

Conclusion
The administration of vasopressin in combination with epinephrine during cardiopulmonary resuscitation results in a drastic improvement in the hemodynamic parameters necessary for the return of spontaneous circulation.
Phase III Trial of Maintenance Gefitinib or Placebo After Concurrent Chemoradiotherapy and Docetaxel Consolidation in Inoperable Stage III Non–Small-Cell Lung Cancer: SWOG S0023
Authors: Kelly Karen , Chansky Kari , Gaspar Laurie E. , Albain Kathy S. , Jett James , Ung Yee C. , Lau Derick H.M. , Crowley John J. , Gandara David R. 
Published: April 2008

Purpose Early clinical studies with gefitinib showed promising efficacy and mild toxicity in patients with advanced non–small-cell lung cancer (NSCLC). Thus, gefitinib was an ideal agent to evaluate in a maintenance setting in stage III disease. Patients and Methods Untreated patients with stage III NSCLC, a performance score of 0 to 1, and adequate organ function were eligible. All patients received cisplatin 50 mg/m2 on days 1 and 8 plus etoposide 50 mg/m2 on days 1 to 5, every 28 days for two cycles with concurrent thoracic radiation (1.8- to 2-Gy fractions per day; total dose, 61 Gy) followed by three cycles of docetaxel 75 mg/m2. Patients whose disease did not progress were randomly assigned to gefitinib 250 mg/d or placebo until disease progression, intolerable toxicity, or the end of 5 years. The planned sample size was 672 patients to confer power of 0.89 to detect a 33% increase over the expected median survival time of 21 months (one-sided P = .025, log-rank test). Random assignment was stratified by stage, histology, and measurable versus nonmeasurable disease. Results Enrollment began in July 2001. An unplanned interim analysis conducted in April 2005 rejected the alternative hypothesis of improved survival at the P = .0015 level for 243 randomly assigned patients. The study closed, and preliminary results were reported. Now, with a median follow-up time of 27 months, median survival time was 23 months for gefitinib (n = 118) and 35 months for placebo (n = 125; two-sided P = .013). The toxic death rate was 2% with gefitinib compared with 0% for placebo. Conclusion In this unselected population, gefitinib did not improve survival. Decreased survival was a result of tumor progression and not gefitinib toxicity.
The Hateful Self: Substitution and the Ethics of Representing War
Authors: Bartley Aryn 
Published: March 2008

This essay reads the works of war journalists Michael Herr and Joe Sacco alongside Emmanuel Levinas's concepts of substitution, responsibility, and the "hatefulness" of the self in order to draw out the political possibilities of Levinas's thought. Where Herr and Sacco posit responsibility and hatefulness as pre-existing, they grapple with the political practice of substitution. Most importantly, their writings draw out the limit case of the practice of substitution. The marking of their inevitable failure to substitute, however, poses a necessary critique of political, economic, and social structures that privilege some lives over others.
Writing and the Paradox of the Self: Machiavelli’s Literary Vocation*
Authors: Bernard John 
Published: March 2008

AbstractThe respective roles ofvirtùandfortuna, never resolved in his political writings, are critical to understanding Machiavelli’s literary evolution. As his letters suggest, in the years between the fall of the Soderini republic and his reentry into public life withMandragola, Machiavelli came to understand the power of language to impose order on the anarchy of events. The fragmentaryL’Asinorecords his discovery that writing can achieve an agency denied to princes.Mandragola’s dialectic between the author and his protagonist demonstrates that the inventive plasticity of the writer is grounded in the inherent stability of the creative self.
Homer in the French Renaissance*
Authors: Ford Philip 
Published: March 2008

AbstractAlthough the works of Homer remained unknown in Western Europe for much of the Middle Ages, their reappearance was welcomed enthusiastically in France toward the end of the fifteenth century by the small band of scholars capable of reading Greek. The founding of the Collège des lecteurs royaux in 1530 gave a fillip to Homeric studies, and partial editions of Homer were printed in Paris, aimed at a student audience. French translations also helped to bring the poems to a wider audience. However, the question of the interpretation of Homer was central to the reception of the two epics, and, after examining the publishing history, this paper sets out to assess how succeeding generations of scholars set about reading and teaching the prince of poets.
Hercules and Albrecht Dürer’s Das Meerwunder in a Chantbook from Renaissance
Spain *
Authors: Candelaria Lorenzo 
Published: March 2008

Abstract

This article centers on two images from the life of Hercules and a
border painting modeled after Albrecht Dürer’s engraving Das
Meerwunder (ca. 1498) in a Kyriale produced ca. 1500 for a Dominican
convent in Toledo, Spain. It discusses the cultural significance of Hercules in
Spain, and Toledo in particular, then presents a contextually sensitive reading
of the image derived from Dürer’s enigmatic engraving, whose subject has yet to
be identified. The image in the Kyriale appears to represent Hercules’
once-famous rescue of the Trojan princess Hesione from a sea
monster.
Principles and Practice in the Civic Government of Fifteenth-Century Genoa*
Authors: Shaw Christine 
Published: March 2008

AbstractThis paper is an examination of the civic government of Genoa from 1435 to 1464, and of the principles that underlay how it was conducted. Despite the political instability caused by contenders for the dogeship, and the division of offices between Guelfs and Ghibellines and between nobles andpopolari,the civic government generally operated on a consensual basis. The principles and practices of the civic government restricted the power of the doges and prevented them from turning their position into an effectivesignoria.
Thomas Wyatt in Italy
Authors: Brigden Susan , Woolfson Jonathan 
Published: March 2008

AbstractThis article follows a young Thomas Wyatt (ca. 1503–42) — the Henrician poet and courtier —on his journeys to France and especially to Italy in 1526–27. It finds him at the greatest courts of Europe at a climacteric in European affairs, during which, by default, he had a part to play. It discovers the dramatic circumstances of his kidnap, ransom, and release. The article conjectures upon the ways in which Wyatt's Italian journey was formative for his political and poetic career, and upon the brilliance with which he transmuted the events of a life lived so intensely, so restlessly, into art.
For “Honor and Profit”: Benvenuto Cellini’s Medal of Clement VII and His Competition with Giovanni Bernardi
Authors: Holman Beth L. 
Published: March 2008

AbstractThis article examines the frameworks of artistic competition embodied in a 1534 contract for a contest of medalmaking between Benvenuto Cellini and Giovanni Bernardi, and in descriptions of other competitions, especially in Cellini’s autobiography. Strategies, decorum, and rhetoric of such competitions were embedded in notions of honor. In addition to personal and professional honor, court status and patronage were also at stake. By means of his competition with Bernardi and his medal of Pope Clement VII, Cellini hoped to recoup lost standing and favor, along with concomitant commissions and emoluments at the papal court — specifically, it is argued, an appointment at the Roman mint, where Cellini had been replaced by Bernardi in 1534. Cellini, however, was never rehabilitated at Clement’s court, and within days of the death of his patron, he murdered Pompeo de’ Capitaneis, the rival goldsmith whom he blamed for his loss of honor and profit.
Visualizing Imperium:The Virgin of the Seafarersand Spain’s Self-Image in the Early Sixteenth Century*
Authors: Carla Rahn Phillips 
Published: March 2008

AbstractThe Virgin of the Seafarers(1531–36) by Alejo Fernández was designed as the central panel of an altarpiece for the chapel in the House of Trade’s Hall of Audiences in Seville. Little attention has been paid to the central panel and almost none to the four side panels, yet they are crucial to our understanding of how the Spanish monarchy defined its mission overseas. The iconography of the altarpiece as a whole made visible Spain’s self-image as the creator and guarantor of a militant, evangelical Christian empire, dedicated to spreading the Gospel as well as fomenting trade and colonization.
Maximilian I as Archeologist*
Authors: Wood Christopher S. 
Published: March 2008

AbstractEmperor Maximilian I was intensely engaged with material relics of the ancient Roman and medieval German past. Maximilian’s historical imagination, creative and participatory rather than objective and distancing, guided his own monumental projects. This essay analyzes, among other episodes, the quest for the bones of the historical Siegfried in Worms and an apparently archeological drawing by Albrecht Dürer.
Just, in Time: Ethical Implications of Serial Predictions of Death and Morbidity for Ventilated Premature Infants
Authors: Meadow William , Lagatta Joanne , Andrews Bree , Caldarelli Leslie , Keiser Amaris , Laporte Johanna , Plesha-Troyke Susan , Subramanian Madhu , Wong Sam , Hron Jon , Golchin Nima , Schreiber Michael 
Published: April 2008

OBJECTIVES. For a cohort of extremely premature, ventilated, newborn infants, we determined the power of either serial caretaker intuitions of “die before discharge” or serial illness severity scores to predict the outcomes of death in the NICU or neurologic performance at corrected age of 2 years.METHODS. We identified 268 premature infants who were admitted to our NICU in 1999–2004 and required mechanical ventilation. For each infant on each day of mechanical ventilation, we asked nurses, residents, fellows, and attending physicians the following question: “Do you think this child is going to live to go home or die before hospital discharge?” In addition, we calculated illness severity scores until either death or extubation.RESULTS. A total of 17066 intuition profiles were obtained on 5609 days of mechanical ventilation in the NICU. One hundred (37%) of 268 profiled infants had ≥1 intuition of die before discharge. Only 33 infants (33%) with an intuition of die actually died in the NICU. Of 48 infants with even 1 day of corroborated intuition of die in the NICU, only 7 (14%) were alive with both Mental Developmental Index and Psychomotor Developmental Index scores of &gt;69, and only 2 (4%) were alive with both Mental Developmental Index and Psychomotor Developmental Index Scores of &gt;79 at corrected age of 2 years. On day of life 1, the Score for Neonatal Acute Physiology II value for nonsurvivors (38.2 ± 18.1) was significantly higher than that for survivors (26.3 ± 12.7). However, this difference decreased steadily over time as scores improved for both groups.CONCLUSIONS. Illness severity scores become progressively less helpful over time in distinguishing infants who will either die in the NICU or survive with low Mental Developmental Index/Psychomotor Developmental Index scores. Serial caretaker intuitions of die before discharge also fail to identify prospective nonsurviving infants. However, corroborated intuitions of die before discharge identify a subset of infants whose likelihood of surviving to 2 years with both MDI and PDI &gt;80 is approximately 4%.
Impact of Admission-Day Crowding on the Length of Stay of Pediatric Hospitalizations
Authors: Lorch Scott A. , Millman Andrea M. , Zhang Xuemei , Even-Shoshan Orit , Silber Jeffrey H. 
Published: April 2008

OBJECTIVE. Increased crowding may affect the care that is delivered to hospitalized patients, particularly around the time of admission. There is little information about the impact of admission-day crowding on the outcome of children who are hospitalized with common pediatric conditions.
METHODS. A population cohort was constructed of children who were aged 1 to 17 years and were hospitalized in Pennsylvania and New York between April 1, 1996, and June 30, 1998, with 1 of 19 common pediatric conditions (N = 116235). Condition-specific Cox regression and logit models were developed to estimate the effect of admission-day occupancy on 4 outcome measures after controlling for illness severity and site of care: length of stay; 21-day readmission; prolonged stay or a stay longer than the typical, uncomplicated stay for that condition as a measure of care delivered to patients with uncomplicated courses; and conditional length of stay as a measure of care delivered to patients whose stays are prolonged.
RESULTS. For children who were admitted with respiratory disease, increasing admission-day occupancy from 60% to 100% was associated with a 0.25-day increase in the average length of stay. Increased admission-day occupancy above 60% was also associated with higher odds of a prolonged stay but not with a change in 21-day readmission rates or conditional length of stay. For children who were admitted with nonrespiratory conditions, increased admission-day occupancy was not associated with changes to any length-of-stay outcome.
CONCLUSIONS. Increased admission-day occupancy was associated with longer lengths of stay for less complicated respiratory admissions but not for children who were admitted with the most serious conditions. These results suggest that medical professionals, during times of increased workload, first focus their attention on more acutely ill children with a complicated course and thus delay treatment of children who have less complicated courses but require time-consuming management and treatment.
Volumetric MRI Study of Brain in Children With Intrauterine Exposure to Cocaine, Alcohol, Tobacco, and Marijuana
Authors: Rivkin Michael J. , Davis Peter E. , Lemaster Jennifer L. , Cabral Howard J. , Warfield Simon K. , Mulkern Robert V. , Robson Caroline D. , Rose-Jacobs Ruth , Frank Deborah A. 
Published: April 2008

OBJECTIVE. The objective of this study was to use volumetric MRI to study brain volumes in 10- to 14-year-old children with and without intrauterine exposure to cocaine, alcohol, cigarettes, or marijuana.METHODS. Volumetric MRI was performed on 35 children (mean age: 12.3 years; 14 with intrauterine exposure to cocaine, 21 with no intrauterine exposure to cocaine) to determine the effect of prenatal drug exposure on volumes of cortical gray matter; white matter; subcortical gray matter; cerebrospinal fluid; and total parenchymal volume. Head circumference was also obtained. Analyses of each individual substance were adjusted for demographic characteristics and the remaining 3 prenatal substance exposures.RESULTS. Regression analyses adjusted for demographic characteristics showed that children with intrauterine exposure to cocaine had lower mean cortical gray matter and total parenchymal volumes and smaller mean head circumference than comparison children. After adjustment for other prenatal exposures, these volumes remained smaller but lost statistical significance. Similar analyses conducted for prenatal ethanol exposure adjusted for demographics showed significant reduction in mean cortical gray matter; total parenchymal volumes; and head circumference, which remained smaller but lost statistical significance after adjustment for the remaining 3 exposures. Notably, prenatal cigarette exposure was associated with significant reductions in cortical gray matter and total parenchymal volumes and head circumference after adjustment for demographics that retained marginal significance after adjustment for the other 3 exposures. Finally, as the number of exposures to prenatal substances grew, cortical gray matter and total parenchymal volumes and head circumference declined significantly with smallest measures found among children exposed to all 4.CONCLUSIONS. These data suggest that intrauterine exposures to cocaine, alcohol, and cigarettes are individually related to reduced head circumference; cortical gray matter; and total parenchymal volumes as measured by MRI at school age. Adjustment for other substance exposures precludes determination of statistically significant individual substance effect on brain volume in this small sample; however, these substances may act cumulatively during gestation to exert lasting effects on brain size and volume.
Association Between Living With Children and Adherence to Highly Active Antiretroviral Therapy in the Women's Interagency HIV Study
Authors: Merenstein Daniel J. , Schneider Michael F. , Cox Christopher , Schwartz Rebecca , Weber Kathleen , Robison Esther , Gandhi Monica , Richardson Jean , Plankey Michael W. 
Published: April 2008

OBJECTIVE. The purpose of this work was to evaluate whether living with children adversely affects adherence to highly active antiretroviral therapy in HIV-infected women.PARTICIPANTS AND METHODS. We conducted a prospective cohort study between October 1998 and September 2005. The study outcome was ≥95% adherence to highly active antiretroviral therapy evaluated at 5832 semiannual visits among 1366 HIV-infected women in the Women's Interagency HIV Study. The primary exposure defined at the visit immediately before outcome ascertainment was the number of children ≤18 years of age reported living in the household.RESULTS. The percentage of women who reported ≥2 children in the household who also reported ≥95% adherence ranged from 68% to 75% compared with adherence when either 1 child or no children were reported. Each additional child reported living in the household was associated with a 6% decrease in the odds of ≥95% adherence.CONCLUSION. The impact of living with a child on the ability to take medications by HIV-infected women has not been examined thoroughly. Our data suggest that adherence to highly active antiretroviral therapy is inversely associated with the number of children living in the household.