bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atomic Layer Deposition of Platinum for Solid Oxide Fuel Cells
Authors: Jiang Xirong , Bent Stacey F. 
Published: July 2007

We are exploring atomic layer deposition (ALD) for depositing components of a solid oxide fuel cell, including the current collector and catalyst. Using (methylcyclopentadienyl) trimethylplatinum (MeCpPtMe3) and oxygen precursors, Pt has been deposited by ALD on the surfaces of yttria-stabilized zirconia (YSZ), a solid oxide electrolyte, as well as on oxide- covered silicon. The film, as measured by ex situ analysis, is of high purity and low resistivity.	We have also investigated the use of area selective ALD to deposit patterned Pt. By coating these same substrates with octadecyltrichlorosilane (ODTS) self-assembled monolayers (SAMs), Pt ALD can be successfully blocked by the SAM resist. The ODTS SAMs are also transferred to the substrates by microcontact printing (uCP), and we show that platinum thin films are grown selectively on the SAM-free surface regions. Features with sizes as small as 2 um have been deposited by this combined ALD-uCP method.
Methyl-CpG Binding Domain Proteins and Their Involvement in the Regulation of the MAGE-A1, MAGE-A2, MAGE-A3, and MAGE-A12 Gene Promoters
Authors: Wischnewski Frank , Friese Olaf , Pantel Klaus , Schwarzenbach Heidi 
Published: July 2007

Abstract
Promoter hypermethylation is responsible for the restricted expression of the tumor-associated MAGE antigens. In order to elucidate the mechanism underlying methylation-dependent repression, we examined the involvement of methyl-CpG binding proteins, MBD1, MBD2a, and MeCP2, in silencing of MAGE-A1, MAGE-A2, MAGE-A3, and MAGE-A12 genes. Electrophoretic mobility shift assays displayed binding of MBD1 to the methylated and unmethylated MAGE-A promoters. Using chromatin immunoprecipitation assays, in vivo binding of MBD1 and MeCP2 to the promoters could be observed in MCF-7 and T47D cells. Transient transfection assays of MCF-7 cells were done with the transcriptional repression domains (TRD) of MBD1, MBD2a, and MeCP2, and MAGE-A1, MAGE-A2, MAGE-A3, and MAGE-A12 promoters. Whereas the TRD of MBD1 and MeCP2 repressed the MAGE-A promoters, the TRD of MBD2 had no inhibiting effect on the promoter activity. Furthermore, cotransfections of Mbd1-deficient mouse fibroblasts and MCF-7 cells with MBD2a, MeCP2, and the MBD1 splice variants, 1v1 and 1v3, showed that strong methylation-dependent repression of the MAGE-A promoters could not be further down-regulated by these proteins. However, the two MBD1 splice variants, 1v1 and 1v3, were able to repress the basal activity of unmethylated MAGE-A promoters. Additional cotransfection experiments with both isoforms of MBD1 and the transcription factor Ets-1 showed that Ets-1 could not abrogate the MBD1-mediated suppression. In contrast with the repressive effect mediated by MBD1, MBD2a was found to up-regulate the basal activity of the promoters. In conclusion, these data show, for the first time, the involvement of methyl-CpG binding domain proteins in the regulation of the MAGE-A genes. (Mol Cancer Res 2007;5(7):749–59)
Involvement of an Autocrine Stromal Cell–Derived Factor-1/CXCR4 System on the Distant Metastasis of Human Oral Squamous Cell Carcinoma
Authors: Uchida Daisuke , Onoue Tomitaro , Tomizuka Yoshifumi , Begum Nasima Mila , Miwa Yoshihiro , Yoshida Hideo , Sato Mitsunobu 
Published: July 2007

AbstractWe have previously shown that a stromal cell–derived factor-1 (SDF-1; CXCL12)/CXCR4 system is involved in the establishment of lymph node metastasis, but not in that of distant metastasis, in oral squamous cell carcinoma (SCC). In this study, we investigated the role of the autocrine SDF-1/CXCR4 system, with a focus on distant metastasis in oral SCC cells. The immunohistochemical staining of SDF-1 and CXCR4 using primary oral SCCs and metastatic lymph nodes showed a significantly higher number of SDF-1–positive cases among the metastatic lymph nodes than among the primary oral SCCs, which was associated with a poor survival rate among those of the former group. The forced expression of SDF-1 in B88 cells, which exhibit functional CXCR4 and lymph node metastatic potential (i.e., the autocrine SDF-1/CXCR4 system), conferred enhanced cell motility and anchorage-independent growth potential onto the cells. Orthotopic inoculation of the transfectant into nude mice was associated with an increase in the number of metastatic lymph nodes and more aggressive metastatic foci in the lymph nodes. Furthermore, the SDF-1 transfectant (i.e., the autocrine SDF-1/CXCR4 system) exhibited dramatic metastasis to the lung after i.v. inoculation, whereas the mock transfectant (i.e., the paracrine SDF-1/CXCR4 system) did not. Under the present conditions, AMD3100, a CXCR4 antagonist, significantly inhibited the lung metastasis of the SDF-1 transfectant, ameliorated body weight loss, and improved the survival rate of tumor-bearing nude mice. These results suggested that, in cases of oral SCC, the paracrine SDF-1/CXCR4 system potentiates lymph node metastasis, but distant metastasis might require the autocrine SDF-1/CXCR4 system. (Mol Cancer Res 2007;5(7):685–94)
AtmDeficiency Affects Both Apoptosis and Proliferation to Augment Myc-Induced Lymphomagenesis
Authors: Maclean Kirsteen H. , Kastan Michael B. , Cleveland John L. 
Published: July 2007

AbstractMyc oncoproteins are commonly activated in malignancies and are sufficient to provoke many types of cancer. However, the critical mechanisms by which Myc contributes to malignant transformation are not clear. DNA damage seems to be an important initiating event in tumorigenesis. Here, we show that although Myc does not directly induce double-stranded DNA breaks, it does augment activation of the Atm/p53 DNA damage response pathway, suggesting that Atm may function as a guardian against Myc-induced transformation. Indeed, we show that Atm loss augments Myc-induced lymphomagenesis and impairs Myc-induced apoptosis, which normally harnesses Myc-driven tumorigenesis. Surprisingly, Atm loss also augments the proliferative response induced by Myc, and this augmentation is associated with enhanced suppression of the expression of the cyclin-dependent kinase inhibitor p27Kip1. Therefore, regulation of cell proliferation and p27Kip1 seems to be a contributing mechanism by which Atm holds tumor formation in check. (Mol Cancer Res 2007;5(7):705–11)
Early specification of dopaminergic phenotype during ES cell differentiation
Authors: Parmar Malin , Li Meng 
Published: July 2007

Abstract
Background
Understanding how lineage choices are made during embryonic stem (ES) cell differentiation is critical for harnessing strategies for controlled production of therapeutic somatic cell types for cell transplantation and pharmaceutical drug screens. The in vitro generation of dopaminergic neurons, the type of cells lost in Parkinson's disease patients' brains, requires the inductive molecules sonic hedgehog and FGF8, or an unknown stromal cell derived inducing activity (SDIA). However, the exact identity of the responding cells and the timing of inductive activity that specify a dopaminergic fate in neural stem/progenitors still remain elusive.

Results
Using ES cells carrying a neuroepithelial cell specific vital reporter (Sox1-GFP) and FACS purification of Sox1-GFP neural progenitors, we have investigated the temporal aspect of SDIA mediated dopaminergic neuron specification during ES cell differentiation. Our results establish that SDIA induces a dopaminergic neuron fate in nascent neural stem or progenitor cells at, or prior to, Sox1 expression and does not appear to have further instructive role or neurotrophic activity during late neuronal differentiation of neural precursors. Furthermore, we show that dopaminergic neurons could be produced efficiently in a monolayer differentiation paradigm independent of SDIA activity or exogenous signalling molecules. In this case, the competence for dopaminergic neuron differentiation is also established at the level of Sox1 expression.

Conclusion
Dopaminergic neurons are specified early during mouse ES cell differentiation. The subtype specification seems to be tightly linked with the acquisition of a pan neuroectoderm fate.
A complete mitochondrial genome sequence of the wild two-humped camel (Camelus bactrianus ferus): an evolutionary history of camelidae
Authors: Cui Peng , Ji Rimutu , Ding Feng , Qi Dan , Gao Hongwei , Meng He , Yu Jun , Hu Songnian , Zhang Heping 
Published: July 2007

Abstract

Background
The family Camelidae that evolved in North America during the Eocene survived with two distinct tribes, Camelini and Lamini. To investigate the evolutionary relationship between them and to further understand the evolutionary history of this family, we determined the complete mitochondrial genome sequence of the wild two-humped camel (Camelus bactrianus ferus), the only wild survivor of the Old World camel.

Results
The mitochondrial genome sequence (16,680 bp) from C. bactrianus ferus contains 13 protein-coding, two rRNA, and 22 tRNA genes as well as a typical control region; this basic structure is shared by all metazoan mitochondrial genomes. Its protein-coding region exhibits codon usage common to all mammals and possesses the three cryptic stop codons shared by all vertebrates. C. bactrianus ferus together with the rest of mammalian species do not share a triplet nucleotide insertion (GCC) that encodes a proline residue found only in the nd1 gene of the New World camelid Lama pacos. This lineage-specific insertion in the L. pacos mtDNA occurred after the split between the Old and New World camelids suggests that it may have functional implication since a proline insertion in a protein backbone usually alters protein conformation significantly, and nd1 gene has not been seen as polymorphic as the rest of ND family genes among camelids. Our phylogenetic study based on complete mitochondrial genomes excluding the control region suggested that the divergence of the two tribes may occur in the early Miocene; it is much earlier than what was deduced from the fossil record (11 million years). An evolutionary history reconstructed for the family Camelidae based on cytb sequences suggested that the split of bactrian camel and dromedary may have occurred in North America before the tribe Camelini migrated from North America to Asia.

Conclusion
Molecular clock analysis of complete mitochondrial genomes from C. bactrianus ferus and L. pacos suggested that the two tribes diverged from their common ancestor about 25 million years ago, much earlier than what was predicted based on fossil records.
MADS-box gene family in rice: genome-wide identification, organization and expression profiling during reproductive development and stress
Authors: Arora Rita , Agarwal Pinky , Ray Swatismita , Singh Ashok Kumar , Singh Vijay Pal , Tyagi Akhilesh K , Kapoor Sanjay 
Published: July 2007

Abstract

Background
MADS-box transcription factors, besides being involved in floral organ specification, have also been implicated in several aspects of plant growth and development. In recent years, there have been reports on genomic localization, protein motif structure, phylogenetic relationships, gene structure and expression of the entire MADS-box family in the model plant system, Arabidopsis. Though there have been some studies in rice as well, an analysis of the complete MADS-box family along with a comprehensive expression profiling was still awaited after the completion of rice genome sequencing. Furthermore, owing to the role of MADS-box family in flower development, an analysis involving structure, expression and functional aspects of MADS-box genes in rice and Arabidopsis was required to understand the role of this gene family in reproductive development.

Results
A genome-wide molecular characterization and microarray-based expression profiling of the genes encoding MADS-box transcription factor family in rice is presented. Using a thorough annotation exercise, 75 MADS-box genes have been identified in rice and categorized into MIKCc, MIKC*, Mα, Mβ and Mγ groups based on phylogeny. Chromosomal localization of these genes reveals that 16 MADS-box genes, mostly MIKCc-type, are located within the duplicated segments of the rice genome, whereas most of the M-type genes, 20 in all, seem to have resulted from tandem duplications. Nine members belonging to the Mβ group, which was considered absent in monocots, have also been identified. The expression profiles of all the MADS-box genes have been analyzed under 11 temporal stages of panicle and seed development, three abiotic stress conditions, along with three stages of vegetative development. Transcripts for 31 genes accumulate preferentially in the reproductive phase, of which, 12 genes are specifically expressed in seeds, and six genes show expression specific to panicle development. Differential expression of seven genes under stress conditions is also evident. An attempt has been made to gain insight into plausible functions of rice MADS-box genes by collating the expression data of functionally validated genes in rice and Arabidopsis.

Conclusion
Only a limited number of MADS genes have been functionally validated in rice. A comprehensive annotation and transcriptome profiling undertaken in this investigation adds to our understanding of the involvement of MADS-box family genes during reproductive development and stress in rice and also provides the basis for selection of candidate genes for functional validation studies.
What is the empirical evidence that hospitals with higher-risk adjusted mortality rates provide poorer quality care? A systematic review of the literature
Authors: Pitches David W , Mohammed Mohammed A , Lilford Richard J 
Published: July 2007

Abstract

Background
Despite increasing interest and publication of risk-adjusted hospital mortality rates, the relationship with underlying quality of care remains unclear. We undertook a systematic review to ascertain the extent to which variations in risk-adjusted mortality rates were associated with differences in quality of care.

Methods
We identified studies in which risk-adjusted mortality and quality of care had been reported in more than one hospital. We adopted an iterative search strategy using three databases – Medline, HealthSTAR and CINAHL from 1966, 1975 and 1982 respectively. We identified potentially relevant studies on the basis of the title or abstract. We obtained these papers and included those which met our inclusion criteria.

Results
From an initial yield of 6,456 papers, 36 studies met the inclusion criteria. Several of these studies considered more than one process-versus-risk-adjusted mortality relationship. In total we found 51 such relationships in a widen range of clinical conditions using a variety of methods. A positive correlation between better quality of care and risk-adjusted mortality was found in under half the relationships (26/51 51%) but the remainder showed no correlation (16/51 31%) or a paradoxical correlation (9/51 18%).

Conclusion
The general notion that hospitals with higher risk-adjusted mortality have poorer quality of care is neither consistent nor reliable.
Effect of dsDNA binding to SmD-derived peptides on clinical accuracy in the diagnosis of systemic lupus erythematosus
Authors: Mahler Michael , Waka Aderajew , Hiepe F , Fritzler Marvin J 
Published: July 2007

AbstractSystemic lupus erythematosus is characterized by antibodies to a variety of intracellular self-antigens, such as dsDNA and Sm, and these serve as hallmarks in the diagnosis of systemic autoimmune diseases. Several studies have shown that SmD1 and SmD3 synthetic peptides represent highly functional antigens for autoantibody detection and thus for diagnostic applications. The present study analysed the technical and clinical accuracy of an anti-SmD1 (amino acids 83–119) and an anti-SmD3 (amino acids 108–122) ELISA for the detection of anti-Sm antibodies. Depending on the cut-off value of the SmD1 ELISA, we found a high degree of concordance between the two tests. At an optimized cut-off value of 100 units for SmD1 we found the same clinical sensitivity (12.5%) and specificity (100%) in a group of systemic lupus erythematosus patients (n = 48) and in controls (n = 99). The concordance at this cut-off value was 100% (P < 0.0001; χ2 = 127.61). Using a second panel of sera (n = 65) preselected based on positive anti-Sm results, we confirmed the high degree of concordance between the two assays. Using dsDNA-coated ELISA plates and biotinylated peptides we confirmed the high dsDNA binding properties for SmD1, which were significantly higher than the SmD3-derived peptide. However, no cross-linking of anti-dsDNA antibodies to SmD1 was observed after adding increasing amounts of dsDNA to anti-dsDNA positive, anti-SmD1 negative serum. We therefore conclude that the reported difference in the sensitivity is related to the different cut-off levels and not to the detection of anti-dsDNA antibodies bridged via dsDNA to the SmD1 peptide. Moreover, we found that a subpopulation of anti-Sm antibodies cross-reacted with SmD1 and SmD3. Taken together, the data indicate that both SmD peptide ELISAs represent accurate assays and may be used as important standards for the detection of anti-Sm antibodies.
Human meniscus cells express hypoxia inducible factor-1α and increased SOX9 in response to low oxygen tension in cell aggregate culture
Authors: Adesida Adetola B , Grady Lisa M , Khan Wasim S , Millward-Sadler S Jane , Salter Donald M , Hardingham Timothy E 
Published: July 2007

AbstractIn previous work we demonstrated that the matrix-forming phenotype of cultured human cells from whole meniscus was enhanced by hypoxia (5% oxygen). Because the meniscus contains an inner region that is devoid of vasculature and an outer vascular region, here we investigate, by gene expression analysis, the separate responses of cells isolated from the inner and outer meniscus to lowered oxygen, and compared it with the response of articular chondrocytes. In aggregate culture of outer meniscus cells, hypoxia (5% oxygen) increased the expression of type II collagen and SOX9 (Sry-related HMG box-9), and decreased the expression of type I collagen. In contrast, with inner meniscus cells, there was no increase in SOX9, but type II collagen and type I collagen increased. The articular chondrocytes exhibited little response to 5% oxygen in aggregate culture, with no significant differences in the expression of these matrix genes and SOX9. In both aggregate cultures of outer and inner meniscus cells, but not in chondrocytes, there was increased expression of collagen prolyl 4-hydroxylase (P4H)α(I) in response to 5% oxygen, and this hypoxia-induced expression of P4Hα(I) was blocked in monolayer cultures of meniscus cells by the hypoxia-inducible factor (HIF)-1α inhibitor (YC-1). In fresh tissue from the outer and inner meniscus, the levels of expression of the HIF-1α gene and downstream target genes (namely, those encoding P4Hα(I) and HIF prolyl 4-hydroxylase) were significantly higher in the inner meniscus than in the outer meniscus. Thus, this study revealed that inner meniscus cells were less responsive to 5% oxygen tension than were outer meniscus cells, and they were both more sensitive than articular chondrocytes from a similar joint. These results suggest that the vasculature and greater oxygen tension in the outer meniscus may help to suppress cartilage-like matrix formation.
Uptake and Intracellular Fate of Francisella tularensis in Human Macrophages
Authors: CLEMENS DANIEL L. , HORWITZ MARCUS A. 
Published: July 2007

Abstract:
Francisella tularensis is an intracellular pathogen that survives and multiplies within host mononuclear phagocytes. We have shown that uptake of the bacterium by human macrophages occurs by a novel process, “looping phagocytosis,” in which the bacterium is engulfed in a spacious, asymmetric, pseudopod loop. Whereas looping phagocytosis is resistant to treatment of the F. tularensis with formalin, proteases, or heat, the process is abolished by oxidation of the bacterial carbohydrates with periodate, suggesting a role for preformed surface carbohydrate molecules in triggering looping phagocytosis. Following uptake, F. tularensis initially resides in a spacious vacuole at the periphery of the cell, but this vacuole rapidly shrinks in size. The nascent F. tularensis vacuole transiently acquires early endosomal markers, but subsequently exhibits an arrested maturation, manifest by only limited amounts of lysosome‐associated membrane glycoproteins (consistent with limited interaction with late endosomes), nonfusion with lysosomes, and minimal acidification. In ultrastructural studies, we have observed that the F. tularensis phagosome displays a novel feature in that many of the phagosomes acquire an electron dense fibrillar coat. This fibrillar coat forms blebs and vesicles, and with time, is seen to be fragmented and disrupted. With increasing time after infection, increasing numbers of the F. tularensis are found free in the macrophage cytoplasm, such that by 14 h after infection, less than 15% of the bacteria are surrounded by any discernible phagosomal membrane. Further research is needed to determine the mechanisms underlying looping phagocytosis, and the maturational arrest, fibrillar coat formation, and disruption of the phagosome.
Tularemia: History, Epidemiology, Pathogen Physiology, and Clinical Manifestations
Authors: SJÖSTEDT ANDERS 
Published: July 2007

Abstract:
Francisella tularensis has been recognized as a human pathogen for almost 100 years and is the etiological agent of the zoonotic disease tularemia. Soon after its discovery, it became recognized as an important pathogen in several parts of the world, for example, in the United States and Soviet Union. The number of tularemia cases in the two countries peaked in the 1940s and has thereafter steadily declined. Despite this decline, there was still much interest in the pathogen in the 1950s and 1960s since it is highly infectious and transmissible by aerosol, rendering it a potent biothreat agent. In fact, it was one of the agents that was given the highest priority in the offensive programs of the United States and Soviet Union. After termination of the offensive programs in the 1960s, the interest in F. tularensis diminished significantly and little research was carried out for several decades. Outbreaks of tularemia during the last decade in Europe, for example, in Kosovo, Spain, and Scandinavia, led to a renewed public interest in the disease. This, together with a massive increase in the research funding, in particular in the United States since 2001, has resulted in a significant increase in the number of active Francisella researchers. This article summarizes, predominantly with a historical perspective, the epidemiology and clinical manifestations of tularemia and the physiology of F. tularensis.