bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemical genomic screening reveals synergism between parthenolide and inhibitors of the PI-3 kinase and mTOR pathways
Authors: Hassane Duane C. , Sen Siddhartha , Minhajuddin Mohammad , Rossi Randall M. , Corbett Cheryl A. , Balys Marlene , Wei Liping , Crooks Peter A. , Guzman Monica L. , Jordan Craig T. 
Published: October 2010

Abstract
We have previously shown that the plant-derived compound parthenolide (PTL) can impair the survival and leukemogenic activity of primary human acute myeloid leukemia (AML) stem cells. However, despite the activity of this agent, PTL also induces cellular protective responses that likely function to reduce its overall cytotoxicity. Thus, we sought to identify pharmacologic agents that enhance the antileukemic potential of PTL. Toward this goal, we used the gene expression signature of PTL to identify compounds that inhibit cytoprotective responses by performing chemical genomic screening of the Connectivity Map database. This screen identified compounds acting along the phosphatidylinositol 3-kinase and mammalian target of rapamycin pathways. Compared with single agent treatment, exposure of AML cells to the combination of PTL and phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors significantly decreased viability of AML cells and reduced tumor burden in vitro and in murine xenotransplantation models. Taken together, our data show that rational drug combinations can be identified using chemical genomic screening strategies and that inhibition of cytoprotective functions can enhance the eradication of primary human AML cells.
C/EBPα regulated microRNA-34a targets E2F3 during granulopoiesis and is down-regulated in AML with CEBPA mutations
Authors: Pulikkan John A. , Peramangalam Philomina S. , Dengler Viola , Ho Phoenix A. , Preudhomme Claude , Meshinchi Soheil , Christopeit Maximilian , Nibourel Oliver , Müller-Tidow Carsten , Bohlander Stefan K. , Tenen Daniel G. , Behre Gerhard 
Published: October 2010

AbstractThe transcription factor, CCAAT enhancer binding protein alpha (C/EBPα), is crucial for granulopoiesis and is deregulated by various mechanisms in acute myeloid leukemia (AML). Mutations in the CEBPA gene are reported in 10% of human patients with AML. Even though the C/EBPα mutants are known to display distinct biologic function during leukemogenesis, the molecular basis for this subtype of AML remains elusive. We have recently showed the significance of deregulation of C/EBPα-regulated microRNA (miR) in AML. In this study, we report that miR-34a is a novel target of C/EBPα in granulopoiesis. During granulopoiesis, miR-34a targets E2F3 and blocks myeloid cell proliferation. Analysis of AML samples with CEBPA mutations revealed a lower expression of miR-34a and elevated levels of E2F3 as well as E2F1, a transcriptional target of E2F3. Manipulation of miR-34a reprograms granulocytic differentiation of AML blast cells with CEBPA mutations. These results define miR-34a as a novel therapeutic target in AML with CEBPA mutations.
Killer Ig–like receptor-mediated control of natural killer cell alloreactivity in haploidentical hematopoietic stem cell transplantation
Authors: Moretta Lorenzo , Locatelli Franco , Pende Daniela , Marcenaro Emanuela , Mingari Maria Cristina , Moretta Alessandro 
Published: October 2010

AbstractNatural killer (NK) cells are key members of the innate immune system. In a self-environment, they sense and kill target cells lacking major histocompatibility complex class I molecules and release various cytokines on activation. The discovery of human leukocyte antigen (HLA) class I specific inhibitory receptors (including the allotype-specific killer immunoglobulin-like receptors), and of various activating receptors and their ligands, provided the basis for understanding the molecular mechanism of NK-cell activation and function, mainly resulting from the balance between activating and inhibitory signals. In an allogeneic setting, such as T cell–depleted haploidentical hematopoietic stem cell transplantation, NK cells may express inhibitory killer immunoglobulin-like receptors that are not engaged by any of the HLA class I alleles present on allogeneic cells. Such “alloreactive” NK cells greatly contribute both to eradication of leukemia blasts escaping the preparative regimen and to clearance of residual host dendritic cells and T lymphocytes (thus preventing graft-versus-host disease and graft rejection, respectively). Improved prevention of graft-versus-host disease might be achieved by redirecting to lymph nodes adoptively transferred, alloreactive NK cells by inducing CCR7-uptake in vitro. Recent studies suggested that, after immune-suppressive therapy, alloreactive NK cells from an HLA-haploidentical donor may prevent leukemia recurrence also in patients who have not received allogeneic hematopoietic stem cell transplantation.
Interferon γ limits the effectiveness of melanoma peptide vaccines
Authors: Cho Hyun-Il , Lee Young-Ran , Celis Esteban 
Published: October 2010

AbstractThe development of effective therapeutic vaccines to generate tumor-reactive cytotoxic T lymphocytes (CTLs) continues to be a top research priority. However, in spite of some promising results, there are no clear examples of vaccines that eradicate established tumors. Most vaccines are ineffective because they generate low numbers of CTLs and because numerous immunosuppressive factors abound in tumor-bearing hosts. We designed a peptide vaccine that produces large numbers of tumor-reactive CTLs in a mouse model of melanoma. Surprisingly, CTL tumor recognition and antitumor effects decreased in the presence of interferon γ (IFNγ), a cytokine that can provide therapeutic benefit. Tumors exposed to IFNγ evade CTLs by inducing large amounts of noncognate major histocompatibility complex class I molecules, which limit T-cell activation and effector function. Our results demonstrate that peptide vaccines can eradicate large, established tumors in circumstances under which the inhibitory activities of IFNγ are curtailed.
Primary glomangiosarcoma of the lung: A case report
Authors: Kleontas Athanassios , Barbetakis Nikolaos , Asteriou Christos , Nikolaidou Anastasia , Baliaka Aggeliki , Kokkori Ioanna , Konstantinou Eleftheria , Grigoriou Anna , Antzel Jacob 
Published: October 2010

Abstract

Background
Glomus tumor is an uncommon neoplasm derived from cells of the neuromyoarterial glomus or glomus body. Most glomus tumours occur in the dermis and subcutaneous tissues. A case of a primary pulmonary glomus tumour originating in the right upper lobe is presented.

Case presentation
A 74-yr-old male was admitted with siccus cough, dyspnea and right-sided chest pain. Computed tomography of the thorax revealed a 4 cm growth of the right upper lobe. Fiberoptic bronchoscopy demonstrated an endobronchial hypervascular mass causing obstruction of the apical segmental bronchus. Pathology report was consistent with pulmonary glomus tumor. The patient underwent a typical right upper lobectomy with mediastinal lymph node dissection. Twelve months later he is free of disease.

Conclusion
Occasionally glomus tumors can occur in extracutaneous sites such as the gastrointestinal tract, bone, genitourinary system and respiratory tract. Primary pulmonary glomus tumors are very rare (our case is the 19th one presented in the international literature) and are often confused with other solid neoplasms such as carcinoids, hemangiopericytomas and tumors belonging to the family of Ewing's sarcoma/primitive neuroectodermal tumours.
Antitumor Activity of Hu14.18-IL2 in Patients With Relapsed/Refractory Neuroblastoma: A Children's Oncology Group (COG) Phase II Study
Authors: Shusterman Suzanne , London Wendy B. , Gillies Stephen D. , Hank Jacquelyn A. , Voss Stephan D. , Seeger Robert C. , Reynolds C. Patrick , Kimball Jennifer , Albertini Mark R. , Wagner Barrett , Gan Jacek , Eickhoff Jens , DeSantes Kenneth B. , Cohn Susan L. , Hecht Toby , Gadbaw Brian , Reisfeld Ralph A. , Maris John M. , Sondel Paul M. 
Published: October 2010

Purpose The hu14.18-IL2 fusion protein consists of interleukin-2 molecularly linked to a humanized monoclonal antibody that recognizes the GD2 disialoganglioside expressed on neuroblastoma cells. This phase II study assessed the antitumor activity of hu14.18-IL2 in two strata of patients with recurrent or refractory neuroblastoma. Patients and Methods Hu14.18-IL2 was given intravenously (12 mg/m2/daily) for 3 days every 4 weeks for patients with disease measurable by standard radiographic criteria (stratum 1) and for patients with disease evaluable only by [123I]metaiodobenzylguanidine (MIBG) scintigraphy and/or bone marrow (BM) histology (stratum 2). Response was established by independent radiology review as well as BM histology and immunocytology, and durability was assessed by repeat evaluation after more than 3 weeks. Results Thirty-nine patients were enrolled (36 evaluable). No responses were seen in stratum 1 (n = 13). Of 23 evaluable patients in stratum 2, five patients (21.7%) responded; all had a complete response (CR) of 9, 13, 20, 30, and 35+ months duration. Grade 3 and 4 nonhematologic toxicities included capillary leak, hypoxia, pain, rash, allergic reaction, elevated transaminases, and hyperbilirubinemia. Two patients required dopamine for hypotension, and one patient required ventilatory support for hypoxia. Most toxicities were reversible within a few days of completing a treatment course and were expected based on phase I results. Conclusion Patients with disease evaluable only by MIBG and/or BM histology had a 21.7% CR rate to hu14.8-IL2, whereas patients with bulky disease did not respond. Hu14.18-IL2 warrants further testing in children with nonbulky high-risk neuroblastoma.
A Drosophila model for primary coenzyme Q deficiency and dietary rescue in the developing nervous system
Authors: Grant Jennifer , Saldanha José W. , Gould Alex P. 
Published: October 2010

SUMMARY
Coenzyme Q (CoQ) or ubiquinone is a lipid component of the electron transport chain required for ATP generation in mitochondria. Mutations in CoQ biosynthetic genes are associated with rare but severe infantile multisystemic diseases. CoQ itself is a popular over-the-counter dietary supplement that some clinical and rodent studies suggest might be beneficial for neurodegenerative diseases. Here, we identify mutations in the Drosophila qless gene, which encodes an orthologue of the human PDSS1 prenyl transferase that synthesizes the isoprenoid side chain of CoQ. We show that neurons lacking qless activity upregulate markers of mitochondrial stress and undergo caspase-dependent apoptosis. Surprisingly, even though experimental inhibition of caspase activity did not prevent mitochondrial disruption, it was sufficient to rescue the size of neural progenitor clones. This demonstrates that, within the developing larval CNS, qless activity is required primarily for cell survival rather than for cell growth and proliferation. Full rescue of the qless neural phenotype was achieved by dietary supplementation with CoQ4, CoQ9 or CoQ10, indicating that a side chain as short as four isoprenoid units can provide in vivo activity. Together, these findings show that Drosophila qless provides a useful model for studying the neural effects of CoQ deficiency and dietary supplementation.
MnCl2·4H2O-catalyzed Potential Protocol for the Synthesis of Aryl/Vinyl Sulfides
Authors: Bandaru Madhav , Sabbavarpu Narayana Murthy , Katla Ramesh , Yadavalli Venkata Durga Nageswar 
Published: October 2010

Abstract
MnCl2·4H2O is described as an efficient catalytic system for the cross coupling of aryl/vinyl halides with thiols using KOH as base and DMSO as solvent. By using this new catalytic system various aryl/vinyl sulfides were synthesized in moderate to good yields. Retention of stereochemistry is observed in the case of vinyl sulfides.
Human Mesenchymal Stem Cell Behavior on Concentrated Polymer Brushes Presenting Different Surface Stiffness
Authors: Nam Kwangwoo , Fukaya Rie , Hashimoto Yoshihide , Ito Yukiko , Kimura Tsuyoshi , Kishida Akio 
Published: October 2010

Abstract
The graft density of poly[poly(ethylene glycol) methacrylate] (PPEGMA) was controlled using atom transfer radical polymerization to observe the change in the differentiation behavior of stem cells because the alteration in the graft density leads to the altered surface elasticity. However, since the cells do not adhere on the high graft density polymer brush, it is impossible to observe such behavior directly. We therefore immobilized collagen onto polymer brushs with controlled graft density to obtain a surface which is effective for cell adhesion and maintains its different surface matrix elasticity. For the cell adhesion, the human mesenchymal stem cell (hMSC) adhesion and differentiation was investigated on the surface of collagen-immobilized polymer brush. It was shown that the hMSC spreading tendency was altered by the surface elasticity implying that the behavior of hMSC would be altered by the stiffness of the polymer brush.
Importance of Biomarkers for Long-Term Mortality Prediction in Acutely Dyspneic Patients
Authors: Januzzi James L , Rehman Shafiq , Mueller Thomas , van Kimmenade Roland RJ , Lloyd-Jones Donald M 
Published: October 2010

BACKGROUND
Although numerous biomarkers may be prognostically meaningful in patients with acute dyspnea, few comparative analyses have addressed possible associations between a wide range of candidate biomarkers and clinical variables.

METHODS
Vital status was obtained for 517 acutely dyspneic patients at 4 years after emergency department presentation. A wide array of biomarkers was measured in this cohort, including natriuretic peptides, necrosis markers, inflammatory markers, hematologic markers, and renal markers. We performed statistical evaluation by using minimization of the Bayesian information criterion to evaluate predictors of 4-year mortality. Cox proportional hazards analysis was used to confirm results from the Bayesian information criterion. A final risk model was derived, and this model was then validated by applying it to patients from a separate cohort of acutely dyspneic patients.

RESULTS
By 4 years, there were 186 deaths (36%). In addition to several clinical variables, several biomarkers were significant predictors of death, including log-transformed concentrations of hemoglobin (hazard ratio=0.77; P &lt; 0.001), soluble ST2 (hazard ratio=1.38; P &lt; 0.001), and amino-terminal pro-B–type natriuretic peptide (hazard ratio=1.19; P &lt; 0.001). Risk models that used these significant variables were accurate in predicting 4-year mortality in both the training and validation sets.

CONCLUSIONS
When added to traditional clinical variables, selected biomarkers added significant value for long-term prognostication in acute dyspnea.
Liberatus von Karthago und die „Drei Kapitel“. Anmerkungen zum Breviarium causae Nestorianorum et Eutychianorum 8-10
Authors: Heil Uta 
Published: October 2010

ABSTRACT
The analysis of Breviarium 8-10 shows that Liberatus shares his positive view of Cyril with some of his sources. In his eyes, Cyril's theology is that of 433, so the later Miaphysites lack their leading figure. Liberatus concentrates upon Alexandria while he ignores the perspective of the other capitals like Antioch, Constantinople or even Rome. His perspective is typically Western, so Cyril's theology is in full accordance with the Tomus Leonis. For the Three-Chapters-Controversy only Theodore of Mopsuestia seems to be important.
Das Konzil von Chalkedon in der Darstellung des Liberatus von Karthago (Breviarium 11-14)
Authors: Wallraff Martin 
Published: October 2010

ABSTRACT
The analysis of Breviarium 11-14 raises various questions, e.g. why the theology of Chalcedon is nearly missing. Neither the Chalcedonense nor the Tomus Leonis are quoted. Only the position of Eutyches and that of Flavian become clear. Thus the tendency of the Breviarium seems to be sceptical towards interpretations according to which the Christological debate can be seen as victory of a clear position of the bishops of Rome. Even the canons of Chalcedon (with canon 28) are located on a wrong place in the narrative order, but here Liberatus follows only his sources.
Modellierung von Unsicherheiten und Zustandsschätzung mit Mengen von Wahrscheinlichkeitsdichten
Authors: Noack Benjamin , Klumpp Vesa , Lyons Daniel , Hanebeck Uwe D. 
Published: October 2010

Zusammenfassung
Die systematische Behandlung von Unsicherheiten stellt eine wesentliche Herausforderung in der Informationsfusion dar. Einerseits müssen geeignete Darstellungsformen für die Unsicherheiten bestimmt werden und andererseits darauf aufbauend effiziente Schätzverfahren hergeleitet werden. Im Allgemeinen wird zwischen stochastischen und mengenbasierten Unsicherheitsbeschreibungen unterschieden. Dieser Beitrag stellt ein Verfahren zur Zustandsschätzung vor, welches simultan stochastische und mengenbasierte Fehlergrößen berücksichtigen kann, indem unsichere Größen nicht mehr durch eine einzelne Wahrscheinlichkeitsdichte, sondern durch eine Menge von Dichten repräsentiert werden. Besonderes Augenmerk liegt hier auf den Vorteilen und Anwendungsmöglichkeiten dieser Unsicherheitsbeschreibung.
Modellbasierte Quellenverfolgung in räumlich ausgedehnten Phänomenen mittels Sensoreinsatzplanung
Authors: Kuwertz Achim , Huber Marco F. , Sawo Felix , Hanebeck Uwe D. 
Published: October 2010

Zusammenfassung
Bewegte Quellen können durch Emission räumlich ausgedehnte Phänomene wie beispielsweise Schadstoff- oder Temperaturverteilungen erzeugen. Zur Lokalisierung von Quellen mit unbekannter Position stehen in vielen Aufgabenstellungen Informationen nur indirekt durch die verteilte Vermessung des induzierten Phänomens zur Verfügung — etwa unter Verwendung stationärer oder mobiler Sensoren. Dieser Beitrag stellt modellbasierte Verfahren für eine echtzeitfähige Lokalisierung und Verfolgung von bewegten Quellen vor. Zur gezielten Maximierung des Informationsgehalts der Messungen wird dabei eine vorausschauende Sensoreinsatzplanung genutzt, welche eine hohe Lokalisierungsgüte bei geringem Aufwand ermöglicht.
Anomalieerkennung in Tracking-Datenbanken
Authors: Schüller Gereon , Koch Wolfgang , Biermann Joachim , Behrend Andreas , Manthey Rainer 
Published: October 2010

Zusammenfassung
Trackingsysteme stellen Bewegungsinformationen über Objekte zur Verfügung. Diese Bewegungsinformationen können mit zusätzlichen Daten kombiniert werden, um Higher-Level-Fusionssysteme zu konstruieren, die zur Erkennung von Verhaltens- und Bedrohungsmustern dienen und somit zur Situation Awareness beitragen. Muster, die interessante Situationen charakterisieren, können sich von Zeit zu Zeit ändern und hängen von der spezifischen Fragestellung ab. In diesem Artikel stellen wir eine Methode vor, Datenbanksysteme als zentrale Komponente in einem Higher-Level-Fusionssystem zur Entdeckung spezieller Situationen zu verwenden. Es wird eine Systemarchitektur präsentiert, die kommerzielle relationale Datenbankmanagementsysteme nutzt. Schließlich wird die Möglichkeit diskutiert, Muster zur Anomalieerkennung in Trackingszenarien mittels Relationaler Algebra auszudrücken.
Influence of preterm birth and small birth size on serum anti-Müllerian hormone levels in young adult women
Authors: Kerkhof G F , Leunissen R W J , Willemsen R H , de Jong F H , Visser J A , Laven J S E , Hokken-Koelega A C S 
Published: October 2010

Background/objectivesPreterm birth has been associated with reduced reproduction rates, and controversies remain regarding the effect of being born small for gestational age (SGA) on ovarian function. Recent findings in young men showed no effect of preterm and SGA birth on testis function. We hypothesised that follicle pool size in young adult women is also not affected by preterm and SGA birth.Design/methodsIn 279 young women of the PROGRAM/PREMS study, aged 18–24 years, the influence of gestational age, birth length and birth weight on serum levels of anti-Müllerian hormone (AMH) was analysed with multiple regression modelling. Additionally, AMH levels were analysed in preterm- versus term-born females and in three subgroups: females born SGA with either short stature or catch-up growth (SGA-CU), and females born term and appropriate for gestational age with normal stature (AGA controls).ResultsPreterm and SGA birth did not affect AMH and other hormone levels. Older age at menarche and oral contraceptive pill use (OC-use) were related to lower AMH levels, and maternal smoking during gestation was related to higher AMH levels. After correction for maternal smoking, lower socioeconomic status (SES) was associated with lower AMH levels. In subgroup comparisons, SGA-CU women showed higher AMH levels than AGA controls, also after adjustment for several factors.ConclusionPreterm and SGA birth did not affect AMH levels. Factors associated with serum AMH levels were OC-use, age at menarche, maternal smoking during gestation and SES. We conclude that preterm- and/or SGA-born females are not likely to have a reduced follicle pool size.
Persistent Increase of Prevalence of Metabolic Syndrome Among U.S. Adults: NHANES III to NHANES 1999–2006
Authors: Mozumdar Arupendra , Liguori Gary 
Published: October 2010

OBJECTIVE
To compare the prevalence in metabolic syndrome (MetSyn) between 1988–1994 and 1999–2006 among U.S. adults of different races or ethnicities.

RESEARCH DESIGN AND METHODS
Analysis of data on 6,423 adult men and nonpregnant women aged ≥20 years from Third National Health and Nutrition Examination Survey (NHANES III) and 6,962 participants from the combined NHANES 1999–2006 were done. The revised National Cholesterol Education Program Adult Treatment Panel III definition was used to calculate MetSyn.

RESULTS
Both the unadjusted prevalence (27.9 ± 1.1% to 34.1 ± 0.8%, P &lt; 0.001) and age-adjusted prevalence (29.2 ± 1.0% to 34.2 ± 0.7%, P &lt; 0.001) increased from NHANES III to NHANES 1999–2006, respectively. Although MetSyn prevalence was highest in Mexican Americans, significant increases in prevalence occurred among non-Hispanic whites and non-Hispanic blacks, especially among younger women.

CONCLUSIONS
The persistent increase of MetSyn among U.S. adults is a serious public health concern because it raises the likelihood of increased prevalence of type 2 diabetes.
Genetic Risk Reclassification for Type 2 Diabetes by Age Below or Above 50 Years Using 40 Type 2 Diabetes Risk Single Nucleotide Polymorphisms
Authors: de Miguel-Yanes Jose M. , Shrader Peter , Pencina Michael J. , Fox Caroline S. , Manning Alisa K. , Grant Richard W. , Dupuis Josèe , Florez Jose C. , D'Agostino Ralph B. , Cupples L. Adrienne , Meigs James B. ,   the MAGIC Investigators,   the DIAGRAM+ Investigators
Published: October 2010

OBJECTIVE
To test if knowledge of type 2 diabetes genetic variants improves disease prediction.

RESEARCH DESIGN AND METHODS
We tested 40 single nucleotide polymorphisms (SNPs) associated with diabetes in 3,471 Framingham Offspring Study subjects followed over 34 years using pooled logistic regression models stratified by age (&lt;50 years, diabetes cases = 144; or ≥50 years, diabetes cases = 302). Models included clinical risk factors and a 40-SNP weighted genetic risk score.

RESULTS
In people &lt;50 years of age, the clinical risk factors model C-statistic was 0.908; the 40-SNP score increased it to 0.911 (P = 0.3; net reclassification improvement (NRI): 10.2%, P = 0.001). In people ≥50 years of age, the C-statistics without and with the score were 0.883 and 0.884 (P = 0.2; NRI: 0.4%). The risk per risk allele was higher in people &lt;50 than ≥50 years of age (24 vs. 11%; P value for age interaction = 0.02).

CONCLUSIONS
Knowledge of common genetic variation appropriately reclassifies younger people for type 2 diabetes risk beyond clinical risk factors but not older people.