bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cycle lengths and phase portrait characteristics as probes for predator–prey interactions: comparing simulations and observed data
Authors: Holmengen Nina , Seip Knut Lehre 
Published: January 2009

In this paper we explore the cyclic interactions of prey–predator systems by examining the relationship between cycle lengths of both species and the strength of their interaction. As a probe of interaction strength, we use the degree of counter-clockwise rotation in phase plots with the prey on the x axis and the predator on the y axis. We compare the results from a 25-year time series from the Hudson’s Bay Company data on American mink ( Neovison vison (Schreber, 1777)) and muskrat ( Ondatra zibethicus (L., 1766)) with results from three simulation models. We found that the strength of interaction (rotation range: –0.4 to 1.1 rad/year) was strongest when the two cycle lengths were similar and that it increased with the amplitude of the cycles (cycle range: 4–10 years). The time difference between prey and predator cycles that corresponded to the highest interaction strength was 2–3 years. Similar results were obtained with simulation models; the most complex Hanski model showing the overall best fit with observations. However, none of the models were able to reproduce long ranges of stable cycles by only changing one of their parameters at a time (ranges 2–4 years), whereas the observed range of stable cycles was 4–10 years.
Evaluating capture stress and its effects on reproductive success in Svalbard reindeer
Authors: Omsjoe E. H. , Stien A. , Irvine J. , Albon S. D. , Dahl E. , Thoresen S. I. , Rustad E. , Ropstad E. 
Published: January 2009

Although many ecological studies of wild animal populations rely on capturing individuals at least once, few have investigated either the immediate stress responses of capture, restraint, and handling, or the longer term consequences on reproductive success. In this paper, we assume that the degree of stress increase with the time taken to capture and process an animal prior to release. The influence of time since onset of capture on body temperature and blood chemistry indicators of stress was investigated in 137 adult female Svalbard reindeer ( Rangifer tarandus platyrhynchus Vrolik, 1829) and 63 calves of both sexes captured by net in late-winter 2004 and 2005. In addition, we looked for evidence of negative effects of capture stress on reproductive success in marked animals over the period from 1995 to 2006. Body temperature increased with both chase time and the time the animals were restrained. In the latter case, body temperature increased twice as fast in nonpregnant animals (0.13 °C/min) compared with pregnant animals. Cortisol, glutamate dehydrogenase, and γ-glutamyltransferase all increased with time from onset of capture. However, the relationship for glucose with time since onset of capture increased initially before declining again. We found no evidence of a lower calving success in animals captured the previous winter when compared with animals that had not been captured the previous winter. Likewise, there was no relationship between the strength of the acute stress response (measured as cortisol concentrations) and the probability of pregnant females having a calf at foot the subsequent summer.
A THEORETICAL INVESTIGATION OF MECHANISM OF THE ADENOSINE DEAMINASE MODIFICATION: REACTION OF GLUTAMATE RESIDUE WITH WOODWARD REAGENT K
Authors: MAHNAM KARIM , BAHRAMI HOMAYOON , MOOSAVI-MOVAHEDI ALI AKBAR , SABOURY ALI AKBAR , IRANMANESH MEHDI , HAKIMELAHI GHOLAM HOSSEIN , RAD MOHAMMAD NAVID SOLTANI , KHALAFI-NEZHAD ALI 
Published: January 2009

The kinetics and mechanism of the modification of adenosine deaminase with N-ethyl-5-phenyl isoxazoliom-3′-sulfonate (WR-K) are investigated using molecular dynamics simulations, QM and QM/MM minimization methods. Two methodological algorithms are employed. In the first algorithm, a glutamate residue is dissected from ADA and its reaction with WR-K is studied by employing minimization and frequency calculations under the B3LYP method. Results obtained show that ketoketenimine is produced from the interaction of WR-K with OH-in an exergonic two-step reaction. In this process, an intermediate is consumed in the rate-determining step. Next, the dissected residue is modified using ketoketenimine in a three-step reaction. This reaction is accompanied by the production of two intermediates, with the first intermediate produced in the rate-determining step.For the second algorithm, modification of glutamate residue in the presence of water molecules and ions is investigated using conformational sampling, MM and QM/MM minimization. Stability of species in the reaction is evaluated using a combination of the B3LYP method and the WASA model. It is proved that the stability of an intermediate which is initially produced in the reaction of glutamate residue with ketoketenimine must be considered crucial when the reactivity of the different residues is compared. Results obtained indicate that these reactions have energetic features qualitatively similar to the glutamate-dissected case. It is also clear that protein structure plays a basic role in the formation of the product that arises from the reaction of ADA with ketoketenimine.
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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 &gt;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

Abstract
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 &lt; 0.005). Notably, MGMT alone showed a significant correlation with temozolomide sensitivity (MGMT activity, P &lt; 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

Abstract
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)
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

Abstract

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

Abstract

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.