bluuebunny/crossref_metadata_2025 huggingface dataset:
Strength, power, fiber types, and mRNA expression in trained men and women with differentACTN3R577X genotypes
Authors: Norman Barbara , Esbjörnsson Mona , Rundqvist Håkan , Österlund Ted , von Walden Ferdinand , Tesch Per A.
Published: January 2009

α-Actinins are structural proteins of the Z-line. Human skeletal muscle expresses two α-actinin isoforms, α-actinin-2 and α-actinin-3, encoded by their respective genes ACTN2 and ACTN3. ACTN2 is expressed in all muscle fiber types, while only type II fibers, and particularly the type IIb fibers, express ACTN3. ACTN3 (R577X) polymorphism results in loss of α-actinin-3 and has been suggested to influence skeletal muscle function. The X allele is less common in elite sprint and power athletes than in the general population and has been suggested to be detrimental for performance requiring high power. The present study investigated the association of ACTN3 genotype with muscle power during 30-s Wingate cycling in 120 moderately to well-trained men and women and with knee extensor strength and fatigability in a subset of 21 men performing isokinetic exercise. Muscle biopsies were obtained from the vastus lateralis muscle to determine fiber-type composition and ACTN2 and ACTN3 mRNA levels. Peak and mean power and the torque-velocity relationship and fatigability output showed no difference across ACTN3 genotypes. Thus this study suggests that R577X polymorphism in ACTN3 is not associated with differences in power output, fatigability, or force-velocity characteristics in moderately trained individuals. However, repeated exercise bouts prompted an increase in peak torque in RR but not in XX genotypes, suggesting that ACTN3 genotype may modulate responsiveness to training. Our data further suggest that α-actinins do not play a significant role in determining muscle fiber-type composition. Finally, we show that ACTN2 expression is affected by the content of α-actinin-3, which implies that α-actinin-2 may compensate for the lack of α-actinin-3 and hence counteract the phenotypic consequences of the deficiency.
Noncationic Peptides Obtained From Azurin Preferentially Enter Cancer Cells
Authors: Taylor Brad N. , Mehta Rajeshwari R. , Yamada Tohru , Lekmine Fatima , Christov Konstantin , Chakrabarty Ananda M. , Green Albert , Bratescu Laura , Shilkaitis Anne , Beattie Craig W. , Das Gupta Tapas K.
Published: January 2009

Azurin, a member of the cupredoxin family of copper containing redox proteins, preferentially penetrates human cancer cells and exerts cytostatic and cytotoxic (apoptotic) effects with no apparent activity on normal cells. Amino acids 50 to 77 (p28) of azurin seem responsible for cellular penetration and at least part of the antiproliferative, proapoptotic activity of azurin against a number of solid tumor cell lines. We show by confocal microscopy and fluorescence-activated cell sorting that amino acids 50 to 67 (p18) are a minimal motif (protein transduction domain) responsible for the preferential entry of azurin into human cancer cells. A combination of inhibitors that interfere with discrete steps of the endocytotic process and antibodies for caveolae and Golgi-mediated transport revealed that these amphipathic, α-helical peptides are unique. Unlike the cationic cell-penetrating peptides, α-helical antennapedia-like, or VP22 type peptides, p18 and p28 are not bound by cell membrane glycosaminoglycans and preferentially penetrate cancer cells via endocytotic, caveosome-directed, and caveosome-independent pathways. Once internalized, p28, but not p18, inhibits cancer cell proliferation initially through a cytostatic mechanism. These observations suggest the azurin fragments, p18 and p28, account for the preferential entry of azurin into human cancer cells and a significant amount of the antiproliferative activity of azurin on human cancer cells, respectively. [Cancer Res 2009;69(2):537–46]
Arginine Deiminase as a Novel Therapy for Prostate Cancer Induces Autophagy and Caspase-Independent Apoptosis
Authors: Kim Randie H. , Coates Jodi M. , Bowles Tawnya L. , McNerney Gregory P. , Sutcliffe Julie , Jung Jae U. , Gandour-Edwards Regina , Chuang Frank Y.S. , Bold Richard J. , Kung Hsing-Jien
Published: January 2009

Arginine deprivation as an anticancer therapy has historically been met with limited success. The development of pegylated arginine deiminase (ADI-PEG20) has renewed interest in arginine deprivation for the treatment of some cancers. The efficacy of ADI-PEG20 is directly correlated with argininosuccinate synthetase (ASS) deficiency. CWR22Rv1 prostate cancer cells do not express ASS, the rate-limiting enzyme in arginine synthesis, and are susceptible to ADI-PEG20 in vitro. Interestingly, apoptosis by 0.3 μg/mL ADI-PEG20 occurs 96 hours posttreatment and is caspase independent. The effect of ADI-PEG20 in vivo reveals reduced tumor activity by micropositron emission tomography as well as reduced tumor growth as a monotherapy and in combination with docetaxel against CWR22Rv1 mouse xenografts. In addition, we show autophagy is induced by single amino acid depletion by ADI-PEG20. Here, autophagy is an early event that is detected within 1 to 4 hours of 0.3 μg/mL ADI-PEG20 treatment and is an initial protective response to ADI-PEG20 in CWR22Rv1 cells. Significantly, the inhibition of autophagy by chloroquine and Beclin1 siRNA knockdown enhances and accelerates ADI-PEG20–induced cell death. PC3 cells, which express reduced ASS, also undergo autophagy and are responsive to autophagy inhibition and ADI-PEG20 treatment. In contrast, LNCaP cells highly express ASS and are therefore resistant to both ADI-PEG20 and autophagic inhibition. These data point to an interrelationship among ASS deficiency, autophagy, and cell death by ADI-PEG20. Finally, a tissue microarray of 88 prostate tumor samples lacked expression of ASS, indicating ADI-PEG20 is a potential novel therapy for the treatment of prostate cancer. [Cancer Res 2009;69(2):700–8]
High Rate of BRAF and RET/PTC Dual Mutations Associated with Recurrent Papillary Thyroid Carcinoma
Authors: Henderson Ying C. , Shellenberger Thomas D. , Williams Michelle D. , El-Naggar Adel K. , Fredrick Mitchell J. , Cieply Kathleen M. , Clayman Gary L.
Published: January 2009

Purpose: Papillary thyroid carcinoma (PTC), the most common thyroid malignancy, usually possesses BRAF mutation or rearranged in translation (RET)/PTC rearrangements. PTC usually possesses BRAF mutation or RET/PTC rearrangements. The mutation status of patients with recurrent PTC has never been characterized in a large population.

Experimental Design: Mutation status was determined in a cohort of 54 patients with recurrent PTC and analyzed for clinicopathologic relationships. BRAF and ras mutations were determined by PCR and sequencing of genomic DNA. RET/PTC rearrangements were analyzed by reverse transcription-PCR.

Results: BRAF mutation in exon 15 (V600E) was found in 42/54 (77.8%) recurrent PTC patients. The RET/PTC rearrangements were detected in 9 of 54 (16.7%) patients. In addition, 5 of 54 (9.3%) recurrent PTC patients had both a BRAF mutation and a RET/PTC rearrangement. The prevalence of tumors with dual mutations found in the recurrent population far exceeds the frequency historically reported for patients with primary PTC. Patients with dual mutations were significantly older (80% older than 45 years) than patients with a BRAF mutation alone (38% older than 45 years).

Conclusions: Recurrent PTC is significantly associated with a predominant BRAF mutation. RET/PTC rearrangements, although commonly associated with primary PTCs in younger patients, are uncommonly found in recurrent PTC patients. In addition, the incidence of dual mutations was higher in patients with recurrent PTC than in those primary PTC, as reported by others.
Stromal Matrix Protein Expression Following Preoperative Systemic Therapy in Breast Cancer
Authors: Tokes Anna-Maria , Szasz Attila Marcell , Farkas Andrea , Toth Adrienn Ildiko , Dank Magdolna , Harsanyi Laszlo , Molnar Bela Akos , Molnar Istvan Arthur , Laszlo Zsolt , Rusz Zoltan , Kulka Janina
Published: January 2009

Purpose: Stromal alterations are observed following preoperative systemic therapy in breast cancer. The aim of the present study was to analyze the qualitative and quantitative changes of representative tumor stroma proteins in the context of neoadjuvant therapy and the response of patients undergoing preoperative systemic therapy.

Experimental Design: Fifty women receiving preoperative systemic therapy were evaluated for clinical and pathologic parameters. Clinical response was defined according to International Union against Cancer (UICC) criteria, whereas pathologic responses to preoperative systemic therapy were defined according to the Chevallier and Sataloff classifications. The expression of tenascin-C, syndecan-1, collagen IV, and smooth muscle actin proteins was investigated using morphometric analysis of immunohistochemical reactions. Quantitative reverse transcription-PCR was done to evaluate the mRNA expression level of syndecan-1 and tenascin-C. The data were compared with 20 breast cancer samples of patients not treated with preoperative systemic therapy.

Results: According to UICC criteria, the expression levels of collagen IV were up-regulated in all preoperative systemic therapy–treated patients (P = 0.002). Collagen IV was up-regulated in the preoperative systemic therapy group in both Chevallier and Sataloff classifications compared with the control cases (P = 0.025 and P = 001, respectively). There were no significant differences in the expression of smooth muscle actin between the treated and nontreated groups. The syndecan-1 proteoglycan level was significantly down-regulated in the preoperative systemic therapy group (Chevallier classes P = 0.015, Sataloff classes P = 0.015). Tenascin-C was up-regulated in women with progressive disease (P = 0.005).

Conclusion: We have observed that the stromal component of breast carcinomas following preoperative systemic therapy differs from the nontreated tumors, which can be evaluated with the analysis of the above mentioned proteins.
Molecular Characterization of Breast Cancer with High-Resolution Oligonucleotide Comparative Genomic Hybridization Array
Authors: Andre Fabrice , Job Bastien , Dessen Philippe , Tordai Attila , Michiels Stefan , Liedtke Cornelia , Richon Catherine , Yan Kai , Wang Bailang , Vassal Gilles , Delaloge Suzette , Hortobagyi Gabriel N. , Symmans W. Fraser , Lazar Vladimir , Pusztai Lajos
Published: January 2009

Purpose: We used high-resolution oligonucleotide comparative genomic hybridization (CGH) arrays and matching gene expression array data to identify dysregulated genes and to classify breast cancers according to gene copy number anomalies.

Experimental Design: DNA was extracted from 106 pretreatment fine needle aspirations of stage II-III breast cancers that received preoperative chemotherapy. CGH was done using Agilent Human 4 × 44K arrays. Gene expression data generated with Affymetrix U133A gene chips was also available on 103 patients. All P values were adjusted for multiple comparisons.

Results: The average number of copy number abnormalities in individual tumors was 76 (range 1-318). Eleven and 37 distinct minimal common regions were gained or lost in >20% of samples, respectively. Several potential therapeutic targets were identified, including FGFR1 that showed high-level amplification in 10% of cases. Close correlation between DNA copy number and mRNA expression levels was detected. Nonnegative matrix factorization (NMF) clustering of DNA copy number aberrations revealed three distinct molecular classes in this data set. NMF class I was characterized by a high rate of triple-negative cancers (64%) and gains of 6p21. VEGFA, E2F3, and NOTCH4 were also gained in 29% to 34% of triple-negative tumors. A gain of ERBB2 gene was observed in 52% of NMF class II and class III was characterized by a high rate of estrogen receptor–positive tumors (73%) and a low rate of pathologic complete response to preoperative chemotherapy (3%).

Conclusion: The present study identified dysregulated genes that could classify breast cancer and may represent novel therapeutic targets for molecular subsets of cancers.
Genomic and Molecular Profiling Predicts Response to Temozolomide in Melanoma
Authors: Augustine Christina K. , Yoo Jin Soo , Potti Anil , Yoshimoto Yasunori , Zipfel Patricia A. , Friedman Henry S. , Nevins Joseph R. , Ali-Osman Francis , Tyler Douglas S.
Published: January 2009

Purpose: Despite objective response rates of only ∼13%, temozolomide remains one of the most effective single chemotherapy agents against metastatic melanoma, second only to dacarbazine, the current standard of care for systemic treatment of melanoma. The goal of this study was to identify molecular and/or genetic markers that correlate with, and could be used to predict, response to temozolomide-based treatment regimens and that reflect the intrinsic properties of a patient's tumor.

Experimental Design: Using a panel of 26 human melanoma-derived cell lines, we determined in vitro temozolomide sensitivity, O6-methylguanine-DNA methyltransferase (MGMT) activity, MGMT protein expression and promoter methylation status, and mismatch repair proficiency, as well as the expression profile of 38,000 genes using an oligonucleotide-based microarray platform.

Results: The results showed a broad spectrum of temozolomide sensitivity across the panel of cell lines, with IC50 values ranging from 100 μmol/L to 1 mmol/L. There was a significant correlation between measured temozolomide sensitivity and a gene expression signature–derived prediction of temozolomide sensitivity (P < 0.005). Notably, MGMT alone showed a significant correlation with temozolomide sensitivity (MGMT activity, P < 0.0001; MGMT expression, P ≤ 0.0001). The promoter methylation status of the MGMT gene, however, was not consistent with MGMT gene expression or temozolomide sensitivity.

Conclusions: These results show that melanoma resistance to temozolomide is conferred predominantly by MGMT activity and suggest that MGMT expression could potentially be a useful tool for predicting the response of melanoma patients to temozolomide therapy.
10-Formyltetrahydrofolate Dehydrogenase–Induced c-Jun-NH2-Kinase Pathways Diverge at the c-Jun-NH2-Kinase Substrate Level in Cells with Different p53 Status
Authors: Ghose Sampa , Oleinik Natalia V. , Krupenko Natalia I. , Krupenko Sergey A.
Published: January 2009

10-Formyltetrahydrofolate dehydrogenase (FDH) suppresses cancer cell proliferation through p53-dependent apoptosis but also induces strong cytotoxicity in p53-deficient prostate cells. In the present study, we have shown that FDH induces apoptosis in PC-3 prostate cells through simultaneous activation of the c-Jun-NH2-kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways with JNK phosphorylating c-Jun and ERK1/2 phosphorylating Elk-1. The JNK1/2 inhibitor SP600125 or ERK1/2 inhibitor PD98059 prevented phosphorylation of c-Jun and Elk-1, correspondingly and partially protected PC-3 cells from FDH-induced cytotoxicity. Combination of the two inhibitors produced an additive effect. The contribution from the JNK cascade to FDH-induced apoptosis was significantly stronger than from the ERK pathway. siRNA knockdown of JNK1/2 or “turning off” the downstream target c-Jun by either siRNA or expression of the dominant-negative c-Jun mutant, TAM67, rescued PC-3 cells from FDH-induced apoptosis. The pull-down assays on immobilized c-Jun showed that c-Jun is directly phosphorylated by JNK2 in FDH-expressing cells. Interestingly, the FDH-induced apoptosis in p53-proficient A549 cells also proceeds through activation of JNK1/2, but the down-stream target for JNK2 is p53 instead of c-Jun. Furthermore, in A549 cells, FDH activates caspase 9, whereas in PC-3 cells, it activates caspase 8. Our studies indicate that the JNK pathways are common downstream mechanisms of FDH-induced cytotoxicity in different cell types, whereas the end point target in the cascade is cell type specific. JNK activation in response to FDH was inhibited by high supplementation of reduced folate leucovorin, further indicating a functional connection between folate metabolism and mitogen-activated protein kinase pathways. (Mol Cancer Res 2009;7(1):99–107)
A Necessary Role of miR-221 and miR-222 in Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia
Authors: Liu Xiaojun , Cheng Yunhui , Zhang Shuo , Lin Ying , Yang Jian , Zhang Chunxiang
Published: January 2009

MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate gene expression. Functionally, an individual miRNA is as important as a transcription factor because it is able to regulate the expression of its multiple target genes. Recently, miR-221 and miR-222 have been found to play a critical role in cancer cell proliferation. However, their roles in vascular smooth muscle cell (VSMC) biology are currently unknown. In the present study, the time course changes and cellular distribution of miR-221 and miR-222 expression were identified in rat carotid arteries after angioplasty, in which their expression was upregulated and localized in VSMCs in the injured vascular walls. In cultured VSMCs, miR-221 and miR-222 expression was increased by growth stimulators. Knockdown of miR-221 and miR-222 resulted in decreased VSMC proliferation in vitro. Using both gain-of-function and loss-of-function approaches, we found that p27(Kip1) and p57(Kip2) were 2 target genes that were involved in miR-221– and miR-222–mediated effect on VSMC growth. Finally, knockdown of miR-221 and miR-222 in rat carotid arteries suppressed VSMC proliferation in vivo and neointimal lesion formation after angioplasty. The results indicate that miR-221 and miR-222 are novel regulators for VSMC proliferation and neointimal hyperplasia. These findings may also represent promising therapeutic targets in proliferative vascular diseases.
Protection or Nonprotection in Carotid Stent Angioplasty
Authors: Jansen Olav , Fiehler Jens , Hartmann Marius , Brückmann Hartmut
Published: January 2009

Background and Purpose—

The use of protection devices (PDs) and stents with different cell designs in carotid artery stenting (CAS) is a subject of controversy, and no data on their benefit are available from independently controlled multi-center studies.

Methods—

We analyzed data from the prospective randomized SPACE trial, which included 563 patients randomized to CAS and treated per protocol. A total of 145 patients were treated with a PD and 418 without. Of the patients, 436 were treated with an open cell stent and 127 with a closed cell stent. Use of PDs and choice of device was chosen at the individual discretion of the interventionalist.

Results—

The outcome event (OE) of the analysis (ipsilateral stroke or ipsilateral stroke death within 30 days) was reached in 26/418 patients (6.2%, 95% CI: 4.1 to 9.0%) in the nonprotection group and in 12/145 (8.3%, 95% CI: 4.3 to 14.0%) patients in the protection group (
P
=0.40). The OE rate was significantly lower in patients treated with a closed cell stent (5.6% [95% CI: 3.7 to 8.2%]) than in those treated with an open cell stent.(11.0%, 95% CI: 6.2 to 17.8%;
P
=0.029). Predilatation showed a tendency to but no significant reduction of OE rate. Overall, 49% of all OEs occurred directly periinterventionally, 10% during the navigation procedure and 41% postinterventionally, including 10% of hyperperfusion syndromes. Time point of the event was not influenced by the use of a PD.

Conclusions—

This secondary analysis of data from the SPACE trial does not support the need for a PD in CAS. Stent design seems to have an impact on the OE rate. Our analysis demonstrates that the choice of the interventional material may have an impact on the periprocedural complication rate in CAS and that the development of more specific stent systems for the treatment of carotid stenosis may reduce the complication rate significantly.
BFL: a node and edge betweenness based fast layout algorithm for large scale networks
Authors: Hashimoto Tatsunori B , Nagasaki Masao , Kojima Kaname , Miyano Satoru
Published: January 2009

Background

Network visualization would serve as a useful first step for analysis. However, current graph layout algorithms for biological pathways are insensitive to biologically important information, e.g. subcellular localization, biological node and graph attributes, or/and not available for large scale networks, e.g. more than 10000 elements.

Results

To overcome these problems, we propose the use of a biologically important graph metric, betweenness, a measure of network flow. This metric is highly correlated with many biological phenomena such as lethality and clusters. We devise a new fast parallel algorithm calculating betweenness to minimize the preprocessing cost. Using this metric, we also invent a node and edge betweenness based fast layout algorithm (BFL). BFL places the high-betweenness nodes to optimal positions and allows the low-betweenness nodes to reach suboptimal positions. Furthermore, BFL reduces the runtime by combining a sequential insertion algorim with betweenness. For a graph with n nodes, this approach reduces the expected runtime of the algorithm to O(n
2) when considering edge crossings, and to O(n log n) when considering only density and edge lengths.

Conclusion

Our BFL algorithm is compared against fast graph layout algorithms and approaches requiring intensive optimizations. For gene networks, we show that our algorithm is faster than all layout algorithms tested while providing readability on par with intensive optimization algorithms. We achieve a 1.4 second runtime for a graph with 4000 nodes and 12000 edges on a standard desktop computer.
Post abortion family planning counseling as a tool to increase contraception use
Authors: Ceylan Ali , Ertem Meliksah , Saka Gunay , Akdeniz Nurten
Published: January 2009

Background

To describe the impact of the post-abortion family planning counseling in bringing about the contraceptive usage in women who had induced abortion in a family planning clinic.

Method

The Diyarbakir Office of Turkish Family Planning Association (DTFPA) is a nonprofit and nongovernmental organization which runs a family planning clinic to serve the lower socio-economic populations, in Diyarbakir-Turkey. Post abortion counseling is introduced by using proper communication skills and with using appropriate methods to women. In this study we introduced contraceptive usage of women who had induced abortion one year ago and followed by DTFPA's clinic.

Results

55.3% of our clients were not using contraceptive methods before abortion. At the end of the one year, 75.9% of our followed-up clients revealed that they were using one of the modern contraceptive methods. There was no woman with IUD before induced abortion. At the end of one year 124 (52.3%) women had IUD. "A modern method was introduced immediately after abortion" was the most important factor increasing modern method usage.

Conclusion

Our results advocate that post-abortion counseling may be an effective tool to increase the usage of contraceptives. Improved and more qualified post-abortion family planning counseling should be an integral part of abortion services.
Identification of two distinct structural regions in a human porcine endogenous retrovirus receptor, HuPAR2, contributing to function for viral entry
Authors: Marcucci Katherine T , Argaw Takele , Wilson Carolyn A , Salomon Daniel R
Published: January 2009

Background

Of the three subclasses of Porcine Endogenous Retrovirus (PERV), PERV-A is able to infect human cells via one of two receptors, HuPAR1 or HuPAR2. Characterizing the structure-function relationships of the two HuPAR receptors in PERV-A binding and entry is important in understanding receptor-mediated gammaretroviral entry and contributes to evaluating the risk of zoonosis in xenotransplantation.

Results

Chimeras of the non-permissive murine PAR and the permissive HuPAR2, which scanned the entire molecule, revealed that the first 135 amino acids of HuPAR2 are critical for PERV-A entry. Within this critical region, eighteen single residue differences exist. Site-directed mutagenesis used to map single residues confirmed the previously identified L109 as a binding and infectivity determinant. In addition, we identified seven residues contributing to the efficiency of PERV-A entry without affecting envelope binding, located in multiple predicted structural motifs (intracellular, extracellular and transmembrane). We also show that expression of HuPAR2 in a non-permissive cell line results in an average 11-fold higher infectivity titer for PERV-A compared to equal expression of HuPAR1, although PERV-A envelope binding is similar. Chimeras between HuPAR-1 and -2 revealed that the region spanning amino acids 152–285 is responsible for the increase of HuPAR2. Fine mapping of this region revealed that the increased receptor function required the full sequence rather than one or more specific residues.

Conclusion

HuPAR2 has two distinct structural regions. In one region, a single residue determines binding; however, in both regions, multiple residues influence receptor function for PERV-A entry.
Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol
Authors: Machijima Yoshiaki , Ishikawa Chie , Sawada Shigeki , Okudaira Taeko , Uchihara Jun-nosuke , Tanaka Yuetsu , Taira Naoya , Mori Naoki
Published: January 2009

Background

Adult T-cell leukemia/lymphoma (ATLL) is a malignancy derived from T cells infected with human T-cell leukemia virus type 1 (HTLV-1), and it is known to be resistant to standard anticancer therapies. Indole-3-carbinol (I3C), a naturally occurring component ofBrassicavegetables such as cabbage, broccoli and Brussels sprout, is a promising chemopreventive agent as it is reported to possess antimutagenic, antitumorigenic and antiestrogenic properties in experimental studies. The aim of this study was to determine the potential anti-ATLL effects of I3C bothin vitroandin vivo.

Results

In thein vitrostudy, I3C inhibited cell viability of HTLV-1-infected T-cell lines and ATLL cells in a dose-dependent manner. Importantly, I3C did not exert any inhibitory effect on uninfected T-cell lines and normal peripheral blood mononuclear cells. I3C prevented the G1/S transition by reducing the expression of cyclin D1, cyclin D2, Cdk4 and Cdk6, and induced apoptosis by reducing the expression of XIAP, survivin and Bcl-2, and by upregulating the expression of Bak. The induced apoptosis was associated with activation of caspase-3, -8 and -9, and poly(ADP-ribose) polymerase cleavage. I3C also suppressed IκBα phosphorylation and JunD expression, resulting in inactivation of NF-κB and AP-1. Inoculation of HTLV-1-infected T cells in mice with severe combined immunodeficiency resulted in tumor growth. The latter was inhibited by treatment with I3C (50 mg/kg/day orally), but not the vehicle control.

Conclusion

Our preclinical data suggest that I3C could be potentially a useful chemotherapeutic agent for patients with ATLL.
Development and application of versatile high density microarrays for genome-wide analysis of Streptomyces coelicolor: characterization of the HspR regulon
Authors: Bucca Giselda , Laing Emma , Mersinias Vassilis , Allenby Nicholas , Hurd Douglas , Holdstock Jolyon , Brenner Volker , Harrison Marcus , Smith Colin P
Published: January 2009

Background

DNA microarrays are a key resource for global analysis of genome content, gene expression and the distribution of transcription factor binding sites. We describe the development and application of versatile high density ink-jet in situ-synthesized DNA arrays for the G+C rich bacterium Streptomyces coelicolor. High G+C content DNA probes often perform poorly on arrays, yielding either weak hybridization or non-specific signals. Thus, more than one million 60-mer oligonucleotide probes were experimentally tested for sensitivity and specificity to enable selection of optimal probe sets for the genome microarrays. The heat-shock HspR regulatory system of S. coelicolor, a well-characterized repressor with a small number of known targets, was exploited to test and validate the arrays for use in global chromatin immunoprecipitation-on-chip (ChIP-chip) and gene expression analysis.

Results

In addition to confirming dnaK, clpB and lon as in vivo targets of HspR, it was revealed, using a novel ChIP-chip data clustering method, that HspR also apparently interacts with ribosomal RNA (rrnD operon) and specific transfer RNA genes (the tRNAGln/tRNAGlu cluster). It is suggested that enhanced synthesis of Glu-tRNAGlu may reflect increased demand for tetrapyrrole biosynthesis following heat-shock. Moreover, it was found that heat-shock-induced genes are significantly enriched for Gln/Glu codons relative to the whole genome, a finding that would be consistent with HspR-mediated control of the tRNA species.

Conclusions

This study suggests that HspR fulfils a broader, unprecedented role in adaptation to stresses than previously recognized - influencing expression of key components of the translational apparatus in addition to molecular chaperone and protease-encoding genes. It is envisaged that these experimentally optimized arrays will provide a key resource for systems level studies of Streptomyces biology.
Multipotent stem cells in the Malpighian tubules of adultDrosophila melanogaster
Authors: Singh Shree Ram , Hou Steven X.
Published: January 2009

Excretion is an essential process of an organism's removal of the waste products of metabolism to maintain a constant chemical composition of the body fluids despite changes in the external environment. Excretion is performed by the kidneys in vertebrates and by Malpighian tubules (MTs) in Drosophila. The kidney serves as an excellent model organ to investigate the cellular and molecular mechanisms underlying organogenesis. Mammals and Drosophila share common principles of renal development. Tissue homeostasis, which is accomplished through self-renewal or differentiation of stem cells, is critical for the maintenance of adult tissues throughout the lifetime of an animal. Growing evidence suggests that stem cell self-renewal and differentiation is controlled by both intrinsic and extrinsic factors. Deregulation of stem cell behavior results in cancer formation, tissue degeneration, and premature aging. The mammalian kidney has a low rate of cellular turnover but has a great capacity for tissue regeneration following an ischemic injury. However, there is an ongoing controversy about the source of regenerating cells in the adult kidney that repopulate injured renal tissues. Recently, we identified multipotent stem cells in the MTs of adult Drosophila and found that these stem cells are able to proliferate and differentiate in several types of cells in MTs. Furthermore, we demonstrated that an autocrine JAK-STAT (Janus kinase–signal transducers and activators of transcription) signaling regulates stem cell self-renewal or differentiation of renal stem cells. The Drosophila MTs provide an excellent in vivo system for studying the renal stem cells at cellular and molecular levels. Understanding the molecular mechanisms governing stem cell self-renewal or differentiation in vivo is not only crucial to using stem cells for future regenerative medicine and gene therapy, but it also will increase our understanding of the mechanisms underlying cancer formation, aging and degenerative diseases. Identifying and understanding the cellular processes underlying the development and repair of the mammalian kidney may enable more effective, targeted therapies for acute and chronic kidney diseases in humans.
Der Nachname als Vorname – Neues zum Vornamensrecht
Authors: Grünberger Michael
Published: January 2009

Der BGH hat entschieden, dass die Eltern den Namen »Lütke« zum Vornamen für ihren Sohn bestimmen können, obwohl es sich dabei um den Familiennamen des Vaters handelt. Damit schließt er sich der vom BVerfG angestoßenen Neukonzeption des Vornamensrechts an.
Sensuous Pagans and Righteous Jews: Changing Concepts of Jewish Identity in Ernest Bloch's Jézabel and Schelomo
Authors: Móricz Klára
Published: January 2009

Disappointed in the reception of his opera Macbeth and torn between what he considered opposing French and German musical aesthetics, Ernest Bloch, together with his librettist and friend Edmond Fleg, turned to Jewish topics under the influence of another friend, the anti-Semite Robert Godet. Relying on archival documents and musical analysis, this article traces the development of Bloch's assumed Jewish identity from his projected opera Jézabel through his violoncello rhapsody Schelomo. Although both works display similar stylistic characteristics, the change between what is conceived as “Jewish” in the one and the other is significant. In Jézabel Bloch depicted an imaginary pure world of the Jews with diatonic, simple melodies and painted the pagan Jezebel with the lush chromaticism associated with Oriental sensuality; in Schelomo he interpreted the chromatic, augmented-second-ridden style as expressive of Jewishness. Schelomo thus fulfilled the expectations of Bloch's audiences by playing into stereotypes of Jewish music. Ironically then, the anti-Semitism that was a major factor in driving Bloch to find a particularly Jewish voice also inspired the corroboration of a musical style that, like the society around him, marked Jews as others.
Hearing Debussy Reading Mallarmé: Music après Wagner in the Prélude à l'après-midi d'un faune
Authors: Code David J.
Published: January 2009

Debussy's Prélude à Vaprès-midi d'un faune has so far been thought to relate only obliquely to Mallarmé's poem L'Après-midi d'un faune. The actual sophistication of Debussy's reading of Mallarmé becomes apparent through a newly precise formal analysis of the poem, and a new analytical emphasis on the orchestration of the prelude. In adapting the conventions of classical pastoral, notably the quasi-dramatic textual presentation of both Virgil's Eclogues and Theocritus's Idylls, Mallarmé focuses his text on an irresolvable moment of conflict between sensuous speech and literary writing. The faun, the poem's main "character," comes to symbolize the reader's divided experience of a text composed on the cusp of a loss of Romantic lyricism to modernist impersonality. In Debussy's reading, a recurring contrast between strings and winds audibly tracks Mallarmé's poetic template and also, more subtly, signals an esoteric layer of puns on Wagnerian leitmotifs in its syntax. A division between hearing and analytical reading is created, which encapsulates a historical moment in which the Romantic orchestral poetics exemplified in Berlioz's influential treatise is losing its immediacy, and the Romantic harmony that attained an expressive limit in Wagner's music dramas is being broken up by systematic analysis.
Terror and Transcendence in the Operatic Prison, 1790–1815
Authors: Meyer Stephen
Published: January 2009

Act 2, scene 1 of Beethoven's 1814 version of Fidelio and the recitative and aria for Amenaïïde from Rossini's Tancredi are the only prison scenes from the period 1790–1815 that are still a part of the performing repertory, but prison scenes were a common feature in operas from these decades. The revolutionary and post-revolutionary period was also a time in which ideas about incarceration were undergoing profound changes—changes that are reflected on the operatic stage. This essay examines the political and aesthetic meanings of the operatic prison scene, providing a broader context for the revisions that Beethoven made to Florestan's recitative and aria. The famous oboe melody that introduces the final section of this scene marks both a turning point in the drama and a self-reflexive moment in the history of opera, in which the dramaturgy of the prison intersects with the philosophy of musical idealism. In this sense, the passage from terror to transcendence is not merely a common topos of prison scene plots; it is also a paradigm for composition, reception, and musico-dramatic meaning in early nineteenth-century opera.
Gregorian Chant and the Romans
Authors: Levy Kenneth
Published: January 2009

A central problem in plainchant studies has been the relationship between the two “Roman” repertories, “Old Roman” (ROM) and “Gregorian” (GREG). Many attempts have been made to penetrate the “mystérieuse alchimie” that links them. Almost without exception, these have embraced the notion that ROM music was the supplier of GREG. This paper advances an alternative hypothesis. It recognizes initial transfers of ROM musical material to the Franks under Pippin III (before 768)—ROM music that was generally improvisational in process and style. However, still under Pippin or later under Charlemagne, the Franks rejected the ROM music and, in their effort to establish GREG, turned to familiar Gallican chants, which tended to have fixed, memorable melodies. Later, perhaps during the tenth century renovatio imperii under Otto I, though perhaps even during Charlemagne's reign, the authorized GREG repertory reached Rome, where it was supposed to supplant the local ROM. But the Roman musicians resisted; rather than abandon ROM, they compromised by accepting certain portions of GREG music and remodeling them so they conformed with ROM style. This sequence of events would explain the musical relationships between ROM and GREG.
Investigation of renal function in liver transplant patients: MDRD or Cockroft–Gault?
Authors: Pájer Petra , Fehérvári Imre
Published: January 2009

Heveny és idült májbetegségek egyaránt hatással vannak a vese működésére. A májátültetést követően további funkcióromlással kell számolnunk az alkalmazott kalcineurininhibitorok nephrotoxicus hatása miatt, így a veseműködés nyomon követése alapvető feladattá válik a májtranszplantáltak körében. Vizsgálatunk során arra kerestük a választ, hogy a szérumkreatinin-szintet alapul vevő formulák eredményei között van-e szignifikáns különbség a kiválasztott betegcsoportban: vajon az albumint is felhasználó MDRD ténylegesen más értéket ad-e, mint a Cockroft–Gault? A 187 betegnél végzett retrospektív elemzés során kitüntetett időpontokban (műtét előtt, műtét után, egy hét és egy hónap múlva) vetettük össze a két képlettel kapott eredményeket. A Cockroft–Gault mindegyik időpontban magasabb GFR-értéket adott: a fenti időpontokban az átlagos eltérés 19,56%, 17,33%, 37,18% és 28,8%. Az idült veseelégtelenség harmadik és negyedik stádiumában, azaz 15-60 ml/perc GFR mellett az MDRD-vel közel kétszer annyi beteget találtunk, mint a Cockroft–Gault-formulával. A Cockroft–Gault-formulánál a medián 93,8 ml/perc, 78 ml/perc, 70,1 ml/perc, 69,4 ml/perc, az MDRD-nél 79 ml/perc, 65,1 ml/perc, 52 ml/perc, 49,5 ml/perc, minden értéknél szignifikáns (
p
< 0,001). Több tanulmány összehasonlította már végstádiumú vesebetegeknél a képleteket, eredményük szerint az MDRD alkalmas 30 ml/perc alatti GFR-tartományban is, míg a Cockroft–Gault csak e fölött mutat jó egyezést az izotópos módszerekkel mért valós GFR-rel. Vizsgálatunk során hasonló következtetésre jutottunk a tanulmányozott betegcsoportban. Összegezve elmondhatjuk, hogy az MDRD alkalmasabbnak bizonyult a májátültetett betegek körében a veseműködés megítélésére.
Dual‐plate OLED display (DOD) based on amorphous‐silicon (a‐Si) TFT backplane
Authors: Han Chang‐Wook , Tak Yoon‐Heung , Kang In Byeong , Ahn Byung‐Chul , Chung In Jae
Published: January 2009

Abstract— An improved AMOLED with an a‐Si TFT backplane based on a unique structure is reported. The new structure is refered to as a dual‐plate OLED display (DOD). While a top‐emission OLED array is directly fabricated on a TFT backplane, the DOD consists of an upper OLED substrate and a lower TFT substrate, which are independently fabricated. Because the OLED substrate, which is fabricated through the process flow of bottom emission, is attached to the TFT substrate, the light is emitted in the opposite direction to the TFT backplane. The DOD enables the design of large‐sized TFTs and a complicated pixel circuit. It can also not only achieve higher uniformity in luminance in large‐sized displays due to the low electrical resistance of the common electrode, but also wider viewing angles.
Measurement of exo‐electron emission from MgO thin film of ACPDPs
Authors: Yoon Sang‐Hoon , Hong Cho‐Rong , Ko Jae Jun , Yang Hee‐Sun , Kim Yong‐Seog
Published: January 2009

Abstract— Exo‐electron emission from MgO thin film was measured by attaching a high‐precision current sensor to the address electrode of the rear plate of an ACPDP test panel. The measured results revealed that the exo‐electron emission currents can vary very sensitively with the type of doping elements used in MgO film and the measuring temperature. The activation energy of the exo‐electron emission estimated from the emission curves indicated that the trap levels are between 0.05 and 0.32 eV below the bottom of its conduction band. This suggests that shallow electron‐trap levels within MgO film are mainly responsible for the exo‐electron emission.
An 82‐in. ultra‐definition 120‐Hz LCD TV using new driving scheme and advanced Super PVA technology
Authors: Kim Sang Soo , You Bong Hyun , Cho Jung Hwan , Kim Dong Gyu , Berkeley Brian H. , Kim Nam Deog
Published: January 2009

Abstract— An ultra‐definition (UD or 3840 × 2160) resolution 82‐in. product with 120‐Hz high‐frame‐rate driving has been developed for LCD‐TV applications. The resolution increase from full HD to UD greatly reduces the available charging time. This problem has been overcome by employing a half‐gate two‐data‐line design (hG‐2D) for Super PVA pixels. Additionally, cost‐effective single‐bank driving has been achieved by adopting a vertical‐quarter‐partitioned (VQP) driving scheme. A viewing angle of 180°, contrast ratio of 2200:1, and brightness of 550 nits have been achieved while maintaining all of the other advantages of the Super‐PVA structure.
Active‐matrix sensor in AMLCD detecting liquid‐crystal capacitance with LTPS‐TFT technology
Authors: Kanda Eiji , Eguchi Tsukasa , Hiyoshi Yasunori , Chino Taketo , Tsuchiya Yasushi , Iwashita Takahiro , Ozawa Tokuro , Miyazawa Takao , Matsumoto Tomotaka
Published: January 2009

Abstract— An active‐matrix capacitive sensor for use in AMLCDs as an in‐cell touch screen has been developed. Pixel sensor circuits are embedded in each pixel by using low‐temperature polycrystalline‐silicon (LTPS) TFT technology. It detects a change in the liquid‐crystal capacitance when it is touched. It is thin, light weight, highly sensitive, and detects three or more touch events simultaneously.
Mechanism and kinetics of glass-ceramics formation in the LiO2-SiO2-CaO-P2O5-CaF2 system
Authors: Palou Martin , Kuzielová Eva , Vitkovič Martin , Noaman Maha
Published: January 2009

Two glasses based on lithium disilicate (LS2), with and without fluorapatite (FA), were synthesised in the Li2O-SiO2-CaO-P2O5-CaF2 system with P2O5: CaO: CaF2 ratios corresponding to fluorapatite. Glass-ceramics have then been prepared by thermal treatment. The mechanism and kinetics of crystallization as functions of grain size and rate of heating were investigated using thermal analysis methods. The smaller particles crystallize preferentially by surface crystallization, which is replaced by volume crystallization at larger particle sizes. Inclusion of FA in the LS2 favours crystallization through the surface mechanism. The onset limit for volume crystallization replacing the surface mechanism is at about 0.3 mm for pure LS2 glass and 0.9 mm for glass containing FA. The calculated activation energies of the glasses (299 ± 1 kJ mol-1 for pure LS2 glass and 288 ± 7 kJ mol−1 for glass containing FA according to Kissinger, or 313 ± 1 kJ mol-1 for pure LS2 glass and 303 ± 8 kJ mol-1 for glass containing FA according to Ozawa) indicate that the tendency of the glasses to crystallize is supported by the FA presence. Bioactivity of all samples has been proved in vitro by the formation of new layers of apatite-like phases after soaking in SBF.
Social Context of Activity Scheduling
Authors: Habib Khandker M. N. , Carrasco Juan Antonio , Miller Eric J.
Published: January 2009

Activity-based approaches to travel demand modeling are increasingly moving from theoretical to operational models. Agent-based microsimulation models are a promising approach as they explicitly conceive travel as an emergent phenomenon from people's activity characteristics and, more explicitly, from their activity-scheduling processes. Activity-scheduling processes are influenced by individuals’ characteristics as well as by the people with whom they interact. Thus, the activity-scheduling process has an intrinsic social context. With social activities used as a case study, the objective of this paper is to investigate empirically the relationship between social context (measured by with whom respondents interacted) and two key aspects of activity scheduling: start time and duration. Econometric models of the combined decisions of with whom to participate and when to start or how much time to spend are estimated to investigate the correlations between “with whom” and start time and duration decisions. Data collected by a 7-day activity diary survey were used for model development. Findings suggest that social context has a relevant role in activity-scheduling processes. For example, with whom people socialize influences social activity-scheduling processes more than do travel time or distances to social travel. In addition to theoretical understanding of the questions investigated here, the models serve as an empirical support for agent-based microsimulation models that could incorporate the role of social networks in activity-scheduling attributes.
Freeway Access to Public Transport
Authors: Molin Eric , van Gelder Michel
Published: January 2009

This paper presents a hierarchical choice model of travelers’ choices for a multimodal transport system with highway access, which may be regarded as an origin-based park-and-ride system. The model is based on hierarchical information integration experiments, which involves devising three rating-based experiments to evaluate different aspects of the multimodal transport systems. In addition, an integrating choice experiment is devised, in which respondents choose between a door-to-door car alternative, a multimodal alternative, and the current public transport alternative, which varied in terms of construct evaluations and time and cost attributes. One of the main results is that time-related attributes affect multimodal transport choice more than comfort-related attributes do. Furthermore, the results indicate that only a few utility differences exist among the categories of background variables.