bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alexander of Aphrodisias and his Doctrine of the Soul 1400 Years of Lasting Significance
Authors: Kessler Eckhard 
Published: January 2011

AbstractThis piece of work intends to shed light on Alexander of Aphrodisias from the second-century Aristotle commentator through the history of Aristotelian psychology up to the sixteenth century's clandestine prompter of the new philosophy of nature. In the millennium after his death the head of the Peripatetic school in Athens served as the authority on Aristotle in the Neo-Platonic school, survived the Arabic centuries of philosophy as Averroes' exemplary exponent of the mortality of the soul and as such was not considered worthy of translation by the Latin Scholastics. This attitude changed only in the Late Middle Ages, when the resistance against Averroes grew fierce and Alexander emerged as the only Aristotelian alternative to him. In 1495 his account of Aristotle's psychology was translated and published and the underlying principles of a natural philosophy, based on sense perception and exempt from metaphysics, became accessible. The prompt reception and widespread endorsement of Alexander's teaching testify to his impact throughout the sixteenth century.
TIGGE: Comparison of the Prediction of Southern Hemisphere Extratropical Cyclones by Different Ensemble Prediction Systems
Authors: Froude Lizzie S. R. 
Published: January 2011

Abstract
The prediction of Northern Hemisphere (NH) extratropical cyclones by nine different ensemble prediction systems (EPSs), archived as part of The Observing System Research and Predictability Experiment (THORPEX) Interactive Grand Global Ensemble (TIGGE), has recently been explored using a cyclone-tracking approach. This paper provides a continuation of this work, extending the analysis to the Southern Hemisphere (SH). While the EPSs have larger error in all cyclone properties in the SH, the relative performance of the different EPSs remains broadly consistent between the two hemispheres. Some interesting differences are also shown. The Chinese Meteorological Administration (CMA) EPS has a significantly lower level of performance in the SH compared to the NH. Previous NH results showed that the Centro de Previsão de Tempo e Estudos Climáticos (CPTEC) EPS underpredicts cyclone intensity. The results of this current study show that this bias is significantly larger in the SH. The CPTEC EPS also has very little spread in both hemispheres. As with the NH results, cyclone propagation speed is underpredicted by all the EPSs in the SH. To investigate this further, the bias was also computed for the ECMWF high-resolution deterministic forecast. The bias was significantly smaller than the lower-resolution ECMWF EPS.
Seasonal Variations of Climate Feedbacks in the NCAR CCSM3
Authors: Taylor Patrick C. , Ellingson Robert G. , Cai Ming 
Published: January 2011

Abstract
This study investigates the annual cycle of radiative contributions to global climate feedbacks. A partial radiative perturbation (PRP) technique is used to diagnose monthly radiative perturbations at the top of atmosphere (TOA) due to CO2 forcing; surface temperature response; and water vapor, cloud, lapse rate, and surface albedo feedbacks using NCAR Community Climate System Model, version 3 (CCSM3) output from a Special Report on Emissions Scenarios (SRES) A1B emissions-scenario-forced climate simulation. The seasonal global mean longwave TOA radiative feedback was found to be minimal. However, the global mean shortwave (SW) TOA cloud and surface albedo radiative perturbations exhibit large seasonality. The largest contributions to the negative SW cloud feedback occur during summer in each hemisphere, marking the largest differences with previous results. Results suggest that intermodel spread in climate sensitivity may occur, partially from cloud and surface albedo feedback seasonality differences. Further, links between the climate feedback and surface temperature response seasonality are investigated, showing a strong relationship between the seasonal climate feedback distribution and the seasonal surface temperature response.
The 21st Century Crisis
Authors: Li Minqi 
Published: January 2011

Under the current trend, the world is on track towards an extreme greenhouse state that threatens to destroy human civilization and nearly all forms of life on Earth. Without an end to economic growth, it is virtually impossible for meaningful climate stabilization to be achieved. However, both capitalist enterprises and states are constantly driven to expand production and consumption. The climate change crisis is but one of several long-term historical trends that are now leading to the structural crisis of capitalism. The resolution of the crisis and the survival of humanity require the building of a fundamentally different social system. JEL classification: B51, P16, P20, Q54
An emerging model for publishing and using open educational resources in public health
Authors: Hemingway A. , Angell C. , Hartwell H. , Heller Richard F 
Published: January 2011

Introduction: The open source revolution has enabled the development of open educational resources (OER) and the potential for sharing lessons learned. We present a potential model for publishing OER in public health to inform workforce development. Methods: As part of the PHORUS (Public Health Open Resources for the University Sector) Project, a review of the literature relating to the development of OER was followed by an online search for OER resources relating specifically to public health. Furthermore, a Delphi study was conducted to identify and prioritize barriers and enablers to the production and use of public health OER. Results: A wide array of OER literature was identified, although there were a limited Number of public health-related papers. The key concepts influencing public health OER release found in the literature were identified as quality, ethics and values, rewards, risks and practical aspects, such as technological developments. These concepts were then further developed through the PHORUS project research findings to produce the basis of a potential model for OER development in public health. Discussion/Conclusion: The synthesis of a literature review and Delphi study has produced a potential model to guide the development of OER in public health. The model provides a matrix where the questions about whether and how an academic can produce and publish OER are answered, according to various risks and benefits to them and their institution. We hope that this will provide practical assistance and encouragement for the academic public health community to create and share OER.
FLT3 ligand impedes the efficacy of FLT3 inhibitors in vitro and in vivo
Authors: Sato Takashi , Yang Xiaochuan , Knapper Steven , White Paul , Smith B. Douglas , Galkin Steven , Small Donald , Burnett Alan , Levis Mark 
Published: January 2011

AbstractWe examined in vivo FLT3 inhibition in acute myeloid leukemia patients treated with chemotherapy followed by the FLT3 inhibitor lestaurtinib, comparing newly diagnosed acute myeloid leukemia patients with relapsed patients. Because we noted that in vivo FLT3 inhibition by lestaurtinib was less effective in the relapsed patients compared with the newly diagnosed patients, we investigated whether plasma FLT3 ligand (FL) levels could influence the efficacy of FLT3 inhibition in these patients. After intensive chemotherapy, FL levels rose to a mean of 488 pg/mL on day 15 of induction therapy for newly diagnosed patients, whereas they rose to a mean of 1148 pg/mL in the relapsed patients. FL levels rose even higher with successive courses of chemotherapy, to a mean of 3251 pg/mL after the fourth course. In vitro, exogenous FL at concentrations similar to those observed in patients mitigated FLT3 inhibition and cytotoxicity for each of 5 different FLT3 inhibitors (lestaurtinib, midostaurin, sorafenib, KW-2449, and AC220). The dramatic increase in FL level after chemotherapy represents a possible obstacle to inhibiting FLT3 in this clinical setting. These findings could have important implications regarding the design and outcome of trials of FLT3 inhibitors and furthermore suggest a rationale for targeting FL as a therapeutic strategy.
Chemotherapeutic agents circumvent emergence of dasatinib-resistant BCR-ABL kinase mutations in a precise mouse model of Philadelphia chromosome–positive acute lymphoblastic leukemia
Authors: Boulos Nidal , Mulder Heather L. , Calabrese Christopher R. , Morrison Jeffrey B. , Rehg Jerold E. , Relling Mary V. , Sherr Charles J. , Williams Richard T. 
Published: January 2011

Abstract
The introduction of cultured p185BCR-ABL-expressing (p185+) Arf−/− pre-B cells into healthy syngeneic mice induces aggressive acute lymphoblastic leukemia (ALL) that genetically and phenotypically mimics the human disease. We adapted this high-throughput Philadelphia chromosome–positive (Ph+) ALL animal model for in vivo luminescent imaging to investigate disease progression, targeted therapeutic response, and ALL relapse in living mice. Mice bearing high leukemic burdens (simulating human Ph+ ALL at diagnosis) entered remission on maximally intensive, twice-daily dasatinib therapy, but invariably relapsed with disseminated and/or central nervous system disease. Although relapse was frequently accompanied by the eventual appearance of leukemic clones harboring BCR-ABL kinase domain (KD) mutations that confer drug resistance, their clonal emergence required prolonged dasatinib exposure. KD P-loop mutations predominated in mice receiving less intensive therapy, whereas high-dose treatment selected for T315I “gatekeeper” mutations resistant to all 3 Food and Drug Administration–approved BCR-ABL kinase inhibitors. The addition of dexamethasone and/or L-asparaginase to reduced-intensity dasatinib therapy improved long-term survival of the majority of mice that received all 3 drugs. Although non–tumor-cell–autonomous mechanisms can prevent full eradication of dasatinib-refractory ALL in this clinically relevant model, the emergence of resistance to BCR-ABL kinase inhibitors can be effectively circumvented by the addition of “conventional” chemotherapeutic agents with alternate antileukemic mechanisms of action.
How I treat relapsed and refractory Hodgkin lymphoma
Authors: Kuruvilla John , Keating Armand , Crump Michael 
Published: January 2011

AbstractRelapsed or refractory Hodgkin lymphoma is a challenging problem for clinicians who treat hematologic malignancies. The standard management of these patients should include the use of salvage chemotherapy followed by autologous stem cell transplant (ASCT) in patients who are chemotherapy sensitive. Open issues in this area include the role of functional imaging, the specific chemotherapy regimen to be used before ASCT, and the role of consolidative radiotherapy. Some patients will not be eligible for ASCT, and alternative approaches with conventional chemotherapy alone or with salvage radiotherapy should be considered. Prognostic factors for relapsed/refractory disease have been identified but generally are not used as a part of risk-adapted therapy. Allogeneic transplantation may offer the potential of a graft-versus-lymphoma effect, but this therapy has significant toxicity and results in few long-term disease-free survivors; hence, it should only be offered in the context of disease-specific clinical trials. An expanding list of novel drugs has exhibited promising single-agent activity. Patients have effective options beyond primary therapy, and continued progress through controlled trials remains a tangible goal in the treatment of relapsed and refractory disease.
Noninvasive prenatal diagnosis of hemophilia by microfluidics digital PCR analysis of maternal plasma DNA
Authors: Tsui Nancy B. Y. , Kadir Rezan A. , Chan K. C. Allen , Chi Claudia , Mellars Gillian , Tuddenham Edward G. , Leung Tak Y. , Lau Tze K. , Chiu Rossa W. K. , Lo Y. M. Dennis 
Published: January 2011

AbstractHemophilia is a bleeding disorder with X-linked inheritance. Current prenatal diagnostic methods for hemophilia are invasive and pose a risk to the fetus. Cell-free fetal DNA analysis in maternal plasma provides a noninvasive mean of assessing fetal sex in such pregnancies. However, the disease status of male fetuses remains unknown if mutation-specific confirmatory analysis is not performed. Here we have developed a noninvasive test to diagnose whether the fetus has inherited a causative mutation for hemophilia from its mother. The strategy is based on a relative mutation dosage approach, which we have previously established for determining the mutational status of fetuses for autosomal disease mutations. In this study, the relative mutation dosage method is used to deduce whether a fetus has inherited a hemophilia mutation on chromosome X by detecting whether the concentration of the mutant or wild-type allele is overrepresented in the plasma of heterozygous women carrying male fetuses. We correctly detected fetal genotypes for hemophilia mutations in all of the 12 studied maternal plasma samples obtained from at-risk pregnancies from as early as the 11th week of gestation. This development would make the decision to undertake prenatal testing less traumatic and safer for at-risk families.
Single-lineage transcriptome analysis reveals key regulatory pathways in primitive erythroid progenitors in the mouse embryo
Authors: Isern Joan , He Zhiyong , Fraser Stuart T. , Nowotschin Sonja , Ferrer-Vaquer Anna , Moore Rebecca , Hadjantonakis Anna-Katerina , Schulz Vincent , Tuck David , Gallagher Patrick G. , Baron Margaret H. 
Published: January 2011

AbstractPrimitive erythroid (EryP) progenitors are the first cell type specified from the mesoderm late in gastrulation. We used a transgenic reporter to image and purify the earliest blood progenitors and their descendants from developing mouse embryos. EryP progenitors exhibited remarkable proliferative capacity in the yolk sac immediately before the onset of circulation, when these cells comprise nearly half of all cells of the embryo. Global expression profiles generated at 24-hour intervals from embryonic day 7.5 through 2.5 revealed 2 abrupt changes in transcript diversity that coincided with the entry of EryPs into the circulation and with their late maturation and enucleation, respectively. These changes were paralleled by the expression of critical regulatory factors. Experiments designed to test predictions from these data demonstrated that the Wnt-signaling pathway is active in EryP progenitors, which display an aerobic glycolytic profile and the numbers of which are regulated by transforming growth factor-β1 and hypoxia. This is the first transcriptome assembled for a single hematopoietic lineage of the embryo over the course of its differentiation.
Homozygosity mapping with SNP arrays confirms 3p21 as a recessive locus for gray platelet syndrome and narrows the interval significantly
Authors: Fabbro Shay , Kahr Walter H. A. , Hinckley Jesse , Wang Kai , Moseley Jack , Ryu Gi-Yung , Nixon Brie , White James G. , Bair Thomas , Schutte Brian , Di Paola Jorge 
Published: January 2011

Abstract
Gray platelet syndrome (GPS) is an inherited bleeding disorder characterized by thrombocytopenia and the absence of α-granules in platelets. Patients with GPS present with mild to moderate bleeding and many develop myelofibrosis. The genetic cause of GPS is unknown. We present 2 Native American families with a total of 5 affected persons and a single affected patient of Pakistani origin in which GPS appears to be inherited in an autosomal recessive manner. Homozygosity mapping using the Affymetrix 6.0 chips demonstrates that all 6 GPS-affected persons studied are homozygous for a 1.7-Mb region in 3p21. Linkage analysis confirmed the region with a logarithm of the odds score of 2.7. Data from our families enabled us to significantly decrease the size of the critical region for GPS from the previously reported 9.4-Mb region at 3p21.
Identification of novel DNA methylation inhibitors via a two-component reporter gene system
Authors: Lin Yi-Shiuan , Shaw Arthur Y , Wang Shi-Gang , Hsu Chia-Chen , Teng I-Wen , Tseng Min-Jen , Huang Tim HM , Chen Ching-Shih , Leu Yu-Wei , Hsiao Shu-Huei 
Published: January 2011

Abstract

Background
Targeting abnormal DNA methylation represents a therapeutically relevant strategy for cancer treatment as demonstrated by the US Food and Drug Administration approval of the DNA methyltransferase inhibitors azacytidine and 5-aza-2'-deoxycytidine for the treatment of myelodysplastic syndromes. But their use is associated with increased incidences of bone marrow suppression. Alternatively, procainamide has emerged as a potential DNA demethylating agent for clinical translation. While procainamide is much safer than 5-aza-2'-deoxycytidine, it requires high concentrations to be effective in DNA demethylation in suppressing cancer cell growth. Thus, our laboratories have embarked on the pharmacological exploitation of procainamide to develop potent DNA methylation inhibitors through lead optimization.

Methods
We report the use of a DNA methylation two-component enhanced green fluorescent protein reporter system as a screening platform to identify novel DNA methylation inhibitors from a compound library containing procainamide derivatives.

Results
A lead agent IM25, which exhibits substantially higher potency in GSTp1 DNA demethylation with lower cytotoxicity in MCF7 cells relative to procainamide and 5-aza-2'-deoxycytidine, was identified by the screening platform.

Conclusions
Our data provide a proof-of-concept that procainamide could be pharmacologically exploited to develop novel DNA methylation inhibitors, of which the translational potential in cancer therapy/prevention is currently under investigation.
Worm Phenotype Ontology: Integrating phenotype data within and beyond the C. elegans community
Authors: Schindelman Gary , Fernandes Jolene S , Bastiani Carol A , Yook Karen , Sternberg Paul W 
Published: January 2011

Abstract

Background

Caenorhabditis elegans gene-based phenotype information dates back to the 1970's, beginning with Sydney Brenner and the characterization of behavioral and morphological mutant alleles via classical genetics in order to understand nervous system function. Since then C. elegans has become an important genetic model system for the study of basic biological and biomedical principles, largely through the use of phenotype analysis. Because of the growth of C. elegans as a genetically tractable model organism and the development of large-scale analyses, there has been a significant increase of phenotype data that needs to be managed and made accessible to the research community. To do so, a standardized vocabulary is necessary to integrate phenotype data from diverse sources, permit integration with other data types and render the data in a computable form.

Results
We describe a hierarchically structured, controlled vocabulary of terms that can be used to standardize phenotype descriptions in C. elegans, namely the Worm Phenotype Ontology (WPO). The WPO is currently comprised of 1,880 phenotype terms, 74% of which have been used in the annotation of phenotypes associated with greater than 18,000 C. elegans genes. The scope of the WPO is not exclusively limited to C. elegans biology, rather it is devised to also incorporate phenotypes observed in related nematode species. We have enriched the value of the WPO by integrating it with other ontologies, thereby increasing the accessibility of worm phenotypes to non-nematode biologists. We are actively developing the WPO to continue to fulfill the evolving needs of the scientific community and hope to engage researchers in this crucial endeavor.

Conclusions
We provide a phenotype ontology (WPO) that will help to facilitate data retrieval, and cross-species comparisons within the nematode community. In the larger scientific community, the WPO will permit data integration, and interoperability across the different Model Organism Databases (MODs) and other biological databases. This standardized phenotype ontology will therefore allow for more complex data queries and enhance bioinformatic analyses.
ZINC-INDUCED FACILITATOR-LIKE family in plants: lineage-specific expansion in monocotyledons and conserved genomic and expression features among rice (Oryza sativa) paralogs
Authors: Ricachenevsky Felipe K , Sperotto Raul A , Menguer Paloma K , Sperb Edilena R , Lopes Karina L , Fett Janette P 
Published: January 2011

Abstract

Background
Duplications are very common in the evolution of plant genomes, explaining the high number of members in plant gene families. New genes born after duplication can undergo pseudogenization, neofunctionalization or subfunctionalization. Rice is a model for functional genomics research, an important crop for human nutrition and a target for biofortification. Increased zinc and iron content in the rice grain could be achieved by manipulation of metal transporters. Here, we describe the ZINC-INDUCED FACILITATOR-LIKE (ZIFL) gene family in plants, and characterize the genomic structure and expression of rice paralogs, which are highly affected by segmental duplication.

Results
Sequences of sixty-eight ZIFL genes, from nine plant species, were comparatively analyzed. Although related to MSF_1 proteins, ZIFL protein sequences consistently grouped separately. Specific ZIFL sequence signatures were identified. Monocots harbor a larger number of ZIFL genes in their genomes than dicots, probably a result of a lineage-specific expansion. The rice ZIFL paralogs were named OsZIFL1 to OsZIFL13 and characterized. The genomic organization of the rice ZIFL genes seems to be highly influenced by segmental and tandem duplications and concerted evolution, as rice genome contains five highly similar ZIFL gene pairs. Most rice ZIFL promoters are enriched for the core sequence of the Fe-deficiency-related box IDE1. Gene expression analyses of different plant organs, growth stages and treatments, both from our qPCR data and from microarray databases, revealed that the duplicated ZIFL gene pairs are mostly co-expressed. Transcripts of OsZIFL4, OsZIFL5, OsZIFL7, and OsZIFL12 accumulate in response to Zn-excess and Fe-deficiency in roots, two stresses with partially overlapping responses.

Conclusions
We suggest that ZIFL genes have different evolutionary histories in monocot and dicot lineages. In rice, concerted evolution affected ZIFL duplicated genes, possibly maintaining similar expression patterns between pairs. The enrichment for IDE1 boxes in rice ZIFL gene promoters suggests a role in Zn-excess and Fe-deficiency up-regulation of ZIFL transcripts. Moreover, this is the first description of the ZIFL gene family in plants and the basis for functional studies on this family, which may play important roles in Zn and Fe homeostasis in plants.