bluuebunny/crossref_metadata_2025_split huggingface dataset:
During EPO or anemia challenge, erythroid progenitor cells transit through a selectively expandable proerythroblast pool
Authors: Dev Arvind , Fang Jing , Sathyanarayana Pradeep , Pradeep Anamika , Emerson Christine , Wojchowski Don M. 
Published: September 2010

AbstractInvestigations of bone marrow (BM) erythroblast development are important for clinical concerns but are hindered by progenitor cell and tissue availability. We therefore sought to more specifically define dynamics, and key regulators, of the formation of developing BM erythroid cell cohorts. A unique Kit−CD71highTer119− “stage E2” proerythroblast pool first is described, which (unlike its Kit+ “stage E1” progenitors, or maturing Ter119+ “stage E3” progeny) proved to selectively expand ∼ 7-fold on erythropoietin challenge. During short-term BM transplantation, stage E2 proerythroblasts additionally proved to be a predominantly expanded progenitor pool within spleen. This E1→E2→E3 erythroid series reproducibly formed ex vivo, enabling further characterizations. Expansion, in part, involved E1 cell hyperproliferation together with rapid E2 conversion plus E2 stage restricted BCL2 expression. Possible erythropoietin/erythropoietin receptor proerythroblast stage specific events were further investigated in mice expressing minimal erythropoietin receptor alleles. For a hypomorphic erythropoietin receptor-HM allele, major defects in erythroblast development occurred selectively at stage E2. In addition, stage E2 cells proved to interact productively with primary BM stromal cells in ways that enhanced both survival and late-stage development. Overall, findings reveal a novel transitional proerythroblast compartment that deploys unique expansion devices.
Prospective assessment of thrombin generation test for dose monitoring of bypassing therapy in hemophilia patients with inhibitors undergoing elective surgery
Authors: Dargaud Yesim , Lienhart Anne , Negrier Claude 
Published: September 2010

Abstract
Clinical response to bypassing agents (BPAs) may vary between patients. Surgery is a particular situation, requiring effective hemostasis during the procedure and for several days postoperatively to obtain satisfactory wound healing. However, the optimal dose of BPA in different surgical situations has not been clearly established. We report here a prospective assessment of thrombin generation test (TGT) in monitoring the effectiveness of BPA during 10 elective invasive procedures performed in 6 patients with severe hemophilia and high-titer inhibitors. A standardized 3-step protocol was used in all cases to individually tailor BPA. Thrombin-generating capacity of patients increased after in vitro and ex vivo addition of BPA in a dose-dependent manner. Our results also showed a correlation between in vivo clinical response to BPA and thrombin-generating capacity. These data suggest that TGT may represent a surrogate marker for monitoring bypassing therapies in surgical situations.
Leukemia-initiating cells in human T-lymphoblastic leukemia exhibit glucocorticoid resistance
Authors: Chiu Priscilla P. L. , Jiang Hong , Dick John E. 
Published: September 2010

Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is associated with a significant risk of disease relapse, but the biological basis for relapse is poorly understood. Here, we identify leukemiainitiating cells (L-ICs) on the basis of functional assays and prospective isolation and report a role for L-ICs in T-ALL disease and relapse. Long-term proliferation in response to NOTCH1 activating signals in OP9-DL1 coculture system or capacity to initiate leukemia in xenografts by the CD7+CD1a− subset of primary T-ALL samples was superior to other subsets, refining the identity of T-ALL L-ICs. T-ALL engraftment was improved in nonobese diabetic/severe combined immunodeficiency (NOD/scid)IL2Rγnull (NSG) mice compared with NOD/scid with anti-CD122 treatment (NS122), but both showed changes in leukemia immunophenotype. Clonal analysis of xenografts using the TCRG locus revealed the presence of subclones of T-ALL L-ICs, some of which possess a selective growth advantage and correlated with the capacity of CD7+CD1a+ xenograft cells to engraft secondary NSG mice. Treatment of high-risk T-ALL xenografts eliminated CD1a+ T-ALL cells, but CD1a− cells were resistant and their number was increased. Our results establish that primary CD1a− T-ALL cells are functionally distinct from CD1a+ cells and that the CD7+CD1a− subset is enriched for L-IC activity that may be involved in mediating disease relapse after therapy.
Genome3D: A viewer-model framework for integrating and visualizing multi-scale epigenomic information within a three-dimensional genome
Authors: Asbury Thomas M , Mitman Matt , Tang Jijun , Zheng W Jim 
Published: September 2010

Abstract

Background
New technologies are enabling the measurement of many types of genomic and epigenomic information at scales ranging from the atomic to nuclear. Much of this new data is increasingly structural in nature, and is often difficult to coordinate with other data sets. There is a legitimate need for integrating and visualizing these disparate data sets to reveal structural relationships not apparent when looking at these data in isolation.

Results
We have applied object-oriented technology to develop a downloadable visualization tool, Genome3D, for integrating and displaying epigenomic data within a prescribed three-dimensional physical model of the human genome. In order to integrate and visualize large volume of data, novel statistical and mathematical approaches have been developed to reduce the size of the data. To our knowledge, this is the first such tool developed that can visualize human genome in three-dimension. We describe here the major features of Genome3D and discuss our multi-scale data framework using a representative basic physical model. We then demonstrate many of the issues and benefits of multi-resolution data integration.

Conclusions

Genome3D is a software visualization tool that explores a wide range of structural genomic and epigenetic data. Data from various sources of differing scales can be integrated within a hierarchical framework that is easily adapted to new developments concerning the structure of the physical genome. In addition, our tool has a simple annotation mechanism to incorporate non-structural information. Genome3D is unique is its ability to manipulate large amounts of multi-resolution data from diverse sources to uncover complex and new structural relationships within the genome.
Codon usage bias and the evolution of influenza A viruses. Codon Usage Biases of Influenza Virus
Authors: Wong Emily HM , Smith David K , Rabadan Raul , Peiris Malik , Poon Leo LM 
Published: September 2010

Abstract

Background
The influenza A virus is an important infectious cause of morbidity and mortality in humans and was responsible for 3 pandemics in the 20th century. As the replication of the influenza virus is based on its host's machinery, codon usage of its viral genes might be subject to host selection pressures, especially after interspecies transmission. A better understanding of viral evolution and host adaptive responses might help control this disease.

Results
Relative Synonymous Codon Usage (RSCU) values of the genes from segment 1 to segment 6 of avian and human influenza viruses, including pandemic H1N1, were studied via Correspondence Analysis (CA). The codon usage patterns of seasonal human influenza viruses were distinct among their subtypes and different from those of avian viruses. Newly isolated viruses could be added to the CA results, creating a tool to investigate the host origin and evolution of viral genes. It was found that the 1918 pandemic H1N1 virus contained genes with mammalian-like viral codon usage patterns, indicating that the introduction of this virus to humans was not through in toto transfer of an avian influenza virus.
Many human viral genes had directional changes in codon usage over time of viral isolation, indicating the effect of host selection pressures. These changes reduced the overall GC content and the usage of G at the third codon position in the viral genome. Limited evidence of translational selection pressure was found in a few viral genes.

Conclusions
Codon usage patterns from CA allowed identification of host origin and evolutionary trends in influenza viruses, providing an alternative method and a tool to understand the evolution of influenza viruses. Human influenza viruses are subject to selection pressure on codon usage which might assist in understanding the characteristics of newly emerging viruses.
Multi-targeted priming for genome-wide gene expression assays
Authors: Adomas Aleksandra B , Lopez-Giraldez Francesc , Clark Travis A , Wang Zheng , Townsend Jeffrey P 
Published: September 2010

Abstract

Background
Complementary approaches to assaying global gene expression are needed to assess gene expression in regions that are poorly assayed by current methodologies. A key component of nearly all gene expression assays is the reverse transcription of transcribed sequences that has traditionally been performed by priming the poly-A tails on many of the transcribed genes in eukaryotes with oligo-dT, or by priming RNA indiscriminately with random hexamers. We designed an algorithm to find common sequence motifs that were present within most protein-coding genes of Saccharomyces cerevisiae and of Neurospora crassa, but that were not present within their ribosomal RNA or transfer RNA genes. We then experimentally tested whether degenerately priming these motifs with multi-targeted primers improved the accuracy and completeness of transcriptomic assays.

Results
We discovered two multi-targeted primers that would prime a preponderance of genes in the genomes of Saccharomyces cerevisiae and Neurospora crassa while avoiding priming ribosomal RNA or transfer RNA. Examining the response of Saccharomyces cerevisiae to nitrogen deficiency and profiling Neurospora crassa early sexual development, we demonstrated that using multi-targeted primers in reverse transcription led to superior performance of microarray profiling and next-generation RNA tag sequencing. Priming with multi-targeted primers in addition to oligo-dT resulted in higher sensitivity, a larger number of well-measured genes and greater power to detect differences in gene expression.

Conclusions
Our results provide the most complete and detailed expression profiles of the yeast nitrogen starvation response and N. crassa early sexual development to date. Furthermore, our multi-targeting priming methodology for genome-wide gene expression assays provides selective targeting of multiple sequences and counter-selection against undesirable sequences, facilitating a more complete and precise assay of the transcribed sequences within the genome.
Cyst formation in the PKD2 (1-703) transgenic rat precedes deregulation of proliferation-related pathways
Authors: Koupepidou Panayiota , Felekkis Kyriacos N , Kränzlin Bettina , Sticht Carsten , Gretz Norbert , Deltas Constantinos 
Published: September 2010

Abstract

Background
Polycystic Kidney Disease is characterized by the formation of large fluid-filled cysts that eventually destroy the renal parenchyma leading to end-stage renal failure. Although remarkable progress has been made in understanding the pathologic mechanism of the disease, the precise orchestration of the early events leading to cyst formation is still unclear. Abnormal cellular proliferation was traditionally considered to be one of the primary irregularities leading to cyst initiation and growth. Consequently, many therapeutic interventions have focused on targeting this abnormal proliferation, and some have even progressed to clinical trials. However, the role of proliferation in cyst development was primarily examined at stages where cysts are already visible in the kidneys and therefore at later stages of disease development.

Methods
In this study we focused on the cystic phenotype since birth in an attempt to clarify the temporal contribution of cellular proliferation in cyst development. Using a PKD2 transgenic rat model (PKD2 (1-703)) of different ages (0-60 days after birth) we performed gene expression profiling and phenotype analysis by measuring various kidney parameters.

Results
Phenotype analysis demonstrated that renal cysts appear immediately after birth in the PKD2 transgenic rat model (PKD2 (1-703)). On the other hand, abnormal proliferation occurs at later stages of the disease as identified by gene expression profiling. Interestingly, other pathways appear to be deregulated at early stages of the disease in this PKD model. Specifically, gene expression analysis demonstrated that at day 0 the RAS system is involved. This is altered at day 6, when Wnt signaling and focal adhesion pathways are affected. However, at and after 24 days, proliferation, apoptosis, altered ECM signaling and many other factors become involved.

Conclusions
Our data suggest that cystogenesis precedes deregulation of proliferation-related pathways, suggesting that proliferation abnormalities may contribute in cyst growth rather than cyst formation.
Side effects of chaperone gene co-expression in recombinant protein production
Authors: Martínez-Alonso Mónica , García-Fruitós Elena , Ferrer-Miralles Neus , Rinas Ursula , Villaverde Antonio 
Published: September 2010

Abstract
Insufficient availability of molecular chaperones is observed as a major bottleneck for proper protein folding in recombinant protein production. Therefore, co-production of selected sets of cell chaperones along with foreign polypeptides is a common approach to increase the yield of properly folded, recombinant proteins in bacterial cell factories. However, unbalanced amounts of folding modulators handling folding-reluctant protein species might instead trigger undesired proteolytic activities, detrimental regarding recombinant protein stability, quality and yield. This minireview summarizes the most recent observations of chaperone-linked negative side effects, mostly focusing on DnaK and GroEL sets, when using these proteins as folding assistant agents. These events are discussed in the context of the complexity of the cell quality network and the consequent intricacy of the physiological responses triggered by protein misfolding.
Penta-O-galloyl-β-D-glucose induces G1arrest and DNA replicative S-phase arrest independently of P21 cyclin-dependent kinase inhibitor 1A, P27 cyclin-dependent kinase inhibitor 1B and P53 in human breast cancer cells and is orally active against triple-negative xenograft growth
Authors: Chai Yubo , Lee Hyo-Jeong , Shaik Ahmad Ali , Nkhata Katai , Xing Chengguo , Zhang Jinhui , Jeong Soo-Jin , Kim Sung-Hoon , Lü Junxuan 
Published: September 2010

Abstract
Introduction
Natural herbal compounds with novel actions different from existing breast cancer (BCa) treatment modalities are attractive for improving therapeutic efficacy and safety. We have recently shown that penta-1,2,3,4,6-O-galloyl-β-D-glucose (PGG) induced S-phase arrest in prostate cancer (PCa) cells through inhibiting DNA replicative synthesis and G1 arrest, in addition to inducing cell death at higher levels of exposure. We and others have shown that PGG through intraperitoneal (i.p.) injection exerts a strong in vivo growth suppression of human PCa xenograft models in athymic nude mice. This study aims to test the hypothesis that the novel targeting actions of PGG are applicable to BCa cells, especially those lacking proven drugable targets.

Methods
Mono-layer cell culture models of p53-wild type estrogen receptor (ER)-dependent MCF-7 BCa cells and p53-mutant ER-/progesterone receptor (PR)- and Her2-regular (triple-negative) MDA-MB-231 BCa were exposed to PGG for a comprehensive investigation of cellular consequences and molecular targets/mediators. To test the in vivo efficacy, female athymic mice inoculated with MDA-MB-231 xenograft were treated with 20 mg PGG/kg body weight by daily gavage starting 4 days after cancer cell inoculation.

Results
Exposure to PGG induced S-phase arrest in both cell lines as indicated by the lack of 5-bromo2'-deoxy-uridine (BrdU) incorporation into S-phase cells as well as G1 arrest. Higher levels of PGG induced more caspase-mediated apoptosis in MCF-7, in strong association with induction of P53 Ser15 phosphorylation, than in MDA-MB-231 cells. The cell cycle arrests were achieved without an induction of cyclin dependent kinase (CDK) inhibitory proteins P21Cip1 and P27Kip1. PGG treatment led to decreased cyclin D1 in both cell lines and over-expressing cyclin D1 attenuated G1 arrest and hastened S arrest. In serum-starvation synchronized MCF-7 cells, down-regulation of cyclin D1 was associated with de-phosphorylation of retinoblastoma (Rb) protein by PGG shortly before G1-S transition. In vivo, oral administration of PGG led to a greater than 60% inhibition of MDA-MB231 xenograft growth without adverse effect on host body weight.

Conclusions
Our in vitro and in vivo data support PGG as a potential drug candidate for breast cancer with novel targeting actions, especially for a triple negative BCa xenograft model.
Reevaluation of Quantitative ESR Spin Trapping Analysis of Hydroxyl Radical by Applying Sonolysis of Water as a Model System
Authors: Nakamura Keisuke , Kanno Taro , Ikai Hiroyo , Sato Emiko , Mokudai Takayuki , Niwano Yoshimi , Ozawa Toshihiko , Kohno Masahiro 
Published: September 2010

Abstract
Electron spin resonance (ESR) spin trapping using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) is commonly applied for quantitative analysis of hydroxyl radical. For better understanding of the analysis, we investigated kinetics related to formation and decay of hydroxyl radical spin adduct of DMPO compared with that of 3,3,5,5-tetramethyl-1-pyrroline N-oxide (M4PO) and 5-(diphenylphosphinoyl)-5-methyl-1-pyrroline N-oxide (DPPMPO). In our study where hydroxyl radical was generated by sonolysis of water, we found that (1) DMPO-OH formation was saturated even though hydroxyl radical was generated continuously and (2) the concentration of DMPO-OH decreased in inverse proportion to time after cessation of ultrasound irradiation, suggesting that the decay is a second-order reaction. Similar results were obtained in an experiment of DMPO-OH generated by photolysis of H2O2. Other than DMPO, M4PO, and DPPMPO also trapped hydroxyl radical but the spin trap efficiency was less than that of DMPO. Furthermore, M4PO-OH and DPPMPO-OH decayed more quickly than DMPO-OH. From this, we conclude that DMPO is more suitable for quantification of hydroxyl radical than M4PO and DPPMPO but results from the quantitative analysis must be interpreted with consideration of the kinetics related to formation and decay of DMPO-OH, especially in quantification of large amount of hydroxyl radical generation.
Synthesis, Characterization, and Catalytic Properties of Hollow γ-Fe2O3 Spheres toward Liquid-Phase Oxidation Using Hydrogen Peroxide
Authors: Mori Kohsuke , Tanimura Isamu , Yamashita Hiromi 
Published: September 2010

Abstract
Hollow γ-Fe2O3 nanospheres were synthesized using carboxylated polystyrene spheres as a core template by thermal treatment followed by calcination. The obtained material was characterized by FT-IR, N2 adsorption–desorption, TEM, XRD, and Fe K-edge XAFS measurements. The size of the hollow γ-Fe2O3 nanospheres were about 400–500 nm, which was assembled from primary particles with a size of approximately 10–20 nm. The phase transition of the composed particles from magnetite (Fe3O4) to maghemite (γ-Fe2O3) was identified after calcination in the presence of O2 at relatively low temperature. The hollow γ-Fe2O3 acted as an efficient heterogeneous catalyst for the liquid-phase selective oxidation of 1-phenylethanol using hydrogen peroxide (H2O2) as an oxidant. It exhibited enhanced catalytic activity compared to its bulk counterpart and also showed higher selectivity than nanosized γ-Fe2O3. Recovery of the hollow γ-Fe2O3 nanospheres from the reaction mixture could be attained by applying an external permanent magnet, and the spent catalyst could be recycled without any appreciable loss of its inherent catalytic ability.
Studies towards the development of lipophilic bifunctional N3S3 chelators for 68Ga
Authors: Riss P. , Hanik Nils , Rösch Frank 
Published: September 2010

Abstract
The present study is concerned with a concept of charge-neutral, lipophilic, macrocyclic bifunctional chelators, suitable for the introduction of a gallium-68 label into small molecules. The synthesis of a novel bifunctional N3S3-type chelator, derived from 1,4,7-triazacyclononane, initial 68Ga-radiolabelling and the determination of stability and calculated lipophilicity of the compound are described. The 68Ga-labelled chelate was obtained in a maximum radiochemical yield of 93±5% after a reaction time of 2 min. It remained intact over 3 h in a DTPA-challenge and a transferrin challenge experiment, indicating sufficient stability for PET studies.
Abbildung mit Millimeterwellen-Sensoren für Industrie- und Sicherheitsanwendungen
Authors: Feil Peter , Mayer Winfried , Kraus Thomas , Migliaccio Claire , Menzel Wolfgang 
Published: September 2010

Zusammenfassung
Die jüngsten Entwicklungen im Bereich automobiler Radaranwendungen fördern die Entwicklung und Verfügbarkeit von Komponenten und integrierten Schaltungen (MMICs) für den mm-Wellen-Frequenzbereich. Neben den Automobil-Sensoren können aber auch industrielle und Sicherheitsanwendungen von diesen Komponenten profitieren. In diesem Artikel werden verschiedene Sensoren und Anwendungen in den angesprochenen Gebieten beschrieben.
Passive CMOS-RFID-Tags mit Sensorfunktionalität
Authors: Brenk Daniel , Heidrich Jürgen , Eßel Jochen , Fischer Georg , Weigel Robert 
Published: September 2010

Zusammenfassung
Die Funktion aktuell verfügbarer passiver RFID-Transponder im UHF-Bereich ist limitiert auf einfache Identifikation. Der hier vorgestellte passive RFID-Chip weist verschiedene Eigenschaften auf, die bislang nur mit semi-passiven oder aktiven Transpondern möglich waren. Es werden zwei verschiedene Frequenzbereiche unterstützt, der Transponder ist ortbar und enthält neben der Identifikation über das EPC-Protokoll die Möglichkeit, interne und externe Sensoren auszulesen. Der Chip wurde in einer preiswerten Mainstream-CMOS-Technologie realisiert, um die Machbarkeit der Funktionalität bei gleichzeitiger kommerziell verwertbarer Perspektive nachzuweisen.
Effect of ZnO Nanowire Doping on the Properties of Poly(3-hexylthiophene) Schottky Diodes
Authors: Aga Rachel S. , Aga R. , Mu R. 
Published: September 2010

AbstractDoping polymers with inorganic nanomaterials to form hybrid nanocomposites is an attractive approach to develop new lightweight optoelectronic materials with unique or improved properties. In this work, poly(3-hexylthiophene) (P3HT) Schottky diodes, doped with ZnO nanowires at different P3HT-to-ZnO concentrations, were studied. Device fabrication was carried out by drop casting the nanocomposite on a Pt electrode followed by thermal evaporation of an Al top electrode. ZnO nanowires were prepared via a physical vapor method with Zn as a source. The nanowires were dispersed in chlorobenzene, then the P3HT powder was added. Properties of the diodes were investigated using capacitance-voltage and current-voltage measurements. In addition, electrical resistance of the nanocomposite films was also investigated using a two-point probe measurement with Pt as Ohmic contacts. Results showed that ZnO nanowire doping decreases the built in potential of the diode and the electrical resistance of the nanocomposite film.