bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiopulmonary function and oxygen delivery during total liquid ventilation
Authors: Tsagogiorgas Charalambos , Alb Markus , Herrmann Peter , Quintel Michael , Meinhardt Juergen P. 
Published: May 2011

AbstractIntroductionTotal liquid ventilation (TLV) with perfluorocarbons has shown to improve cardiopulmonary function in the injured and immature lung; however there remains controversy over the normal lung. Hemodynamic effects of TLV in the normal lung currently remain undetermined. This study compared changes in cardiopulmonary and circulatory function caused by either liquid or gas tidal volume ventilation.MethodsIn a prospective, controlled study, 12 non‐injured anesthetized, adult New Zealand rabbits were primarily conventionally gas‐ventilated (CGV). After instrumentation for continuous recording of arterial (AP), central venous (CVP), left artrial (LAP), pulmonary arterial pressures (PAP), and cardiac output (CO) animals were randomized into (1) CGV group and (2) TLV group. In the TLV group partial liquid ventilation was initiated with instillation of perfluoroctylbromide (12 ml/kg). After 15 min, TLV was established for 3 hr applying a volume‐controlled, pressure‐limited, time‐cycled ventilation mode using a double‐piston configured TLV. Controls (CGV) remained gas‐ventilated throughout the experiment.ResultsDuring TLV, heart rate, CO, PAP, MAP, CVP, and LAP as well as derived hemodynamic variables, arterial and mixed venous blood gases, oxygen delivery, PVR, and SVR did not differ significantly compared to CGV.ConclusionsLiquid tidal volumes suitable for long‐term TLV in non‐injured rabbits do not significantly impair CO, blood pressure, and oxygen dynamics when compared to CGV. Pediatr. Pulmonol. 2011; 46:964–975. © 2011 Wiley‐Liss, Inc.
Specificity of HCPTP variants toward EphA2 tyrosines by quantitative selected reaction monitoring
Authors: Balasubramaniam Deepa , Paul Lake N. , Homan Kristoff T. , Hall Mark C. , Stauffacher Cynthia V. 
Published: May 2011

AbstractEphA2 receptor tyrosine kinase and the human cytoplasmic protein tyrosine phosphatase (HCPTP) are overexpressed in a number of epithelial cancers. Overexpressed EphA2 in these cancers shows a significant decrease in phosphotyrosine content which results in suppression of receptor signaling and endocytosis and an increase in metastatic potential. The decreased phosphotyrosine content of EphA2 has been associated with decreased contact with its ligand, ephrin A1 and dephosphorylation by HCPTP. Potential specificity of the two HCPTP variants for tyrosines on EphA2 has not been investigated. We have used a mass spectrometry assay to measure relative rates of dephosphorylation for the two HCPTP variants at phosphotyrosine sites associated with control of the EphA2 kinase activity or interaction with downstream targets. Our results suggest that although both variants dephosphorylate the EphA2 receptor, the rate and specificity of dephosphorylation for specific tyrosines are different for HCPTP‐A and HCPTP‐B. The SAM domain tyrosine Y960 which has been implicated in downstream PI3K signaling is dephosphorylated exclusively by HCPTP‐B. The activation loop tyrosine (Y772) which directly controls kinase activity is dephosphorylated about six times faster by HCPTP‐A. In contrast, the juxtamembrane tyrosines (Y575, Y588 and Y594) which are implicated in both control of kinase activity and downstream signaling are dephosphorylated by both variants with similar rates. This difference in preference for dephosphorylation sites on EphA2 not only illuminates the different roles of the two variants of the phosphatase in EphA2 signaling, but also explains why both HCPTP variants are highly conserved in most mammals.
X‐ray structural studies of quinone reductase 2 nanomolar range inhibitors
Authors: Pegan Scott D. , Sturdy Megan , Ferry Gilles , Delagrange Philippe , Boutin Jean A. , Mesecar Andrew D. 
Published: May 2011

AbstractQuinone reductase 2 (QR2) is one of two members comprising the mammalian quinone reductase family of enzymes responsible for performing FAD mediated reductions of quinone substrates. In contrast to quinone reductase 1 (QR1) which uses NAD(P)H as its co‐substrate, QR2 utilizes a rare group of hydride donors, N‐methyl or N‐ribosyl nicotinamide. Several studies have linked QR2 to the generation of quinone free radicals, several neuronal degenerative diseases, and cancer. QR2 has been also identified as the third melatonin receptor (MT3) through in cellulo and in vitro inhibition of QR2 by traditional MT3 ligands, and through recent X‐ray structures of human QR2 (hQR2) in complex with melatonin and 2‐iodomelatonin. Several MT3 specific ligands have been developed that exhibit both potent in cellulo inhibition of hQR2 nanomolar, affinity for MT3. The potency of these ligands suggest their use as molecular probes for hQR2. However, no definitive correlation between traditionally obtained MT3 ligand affinity and hQR2 inhibition exists limiting our understanding of how these ligands are accommodated in the hQR2 active site. To obtain a clearer relationship between the structures of developed MT3 ligands and their inhibitory properties, in cellulo and in vitro IC50 values were determined for a representative set of MT3 ligands (MCA‐NAT, 2‐I‐MCANAT, prazosin, S26695, S32797, and S29434). Furthermore, X‐ray structures for each of these ligands in complex with hQR2 were determined allowing for a structural evaluation of the binding modes of these ligands in relation to the potency of MT3 ligands.
Dynamical cosmological term in modified gravity
Authors: Solà J. 
Published: May 2011

AbstractThe experimental evidence that the equation of state (EoS) of the dark energy (DE) could be evolving with time, suggests that the Λ‐term in the gravity action should rather be an effective quantity Λeff(t) involving new dynamical terms X(t). Remarkably, a class of these ΛXCDM models could be the clue for solving the old cosmological constant problem, including the cosmic coincidence problem. We propose a permanent (i.e. not just a late‐time) modification of gravity which is able to account for these problems, and without affecting the standard cosmological evolution of the universe.
Inhibition of Stat3 activation by sanguinarine suppresses prostate cancer cell growth and invasion
Authors: Sun Meng , Liu Chengfei , Nadiminty Nagalakshmi , Lou Wei , Zhu Yezi , Yang Joy , Evans Christopher P. , Zhou Qinghua , Gao Allen C. 
Published: May 2011

AbstractBACKGROUNDSignal transducer and activator of transcription 3 (Stat3) is an oncogenic transcriptional factor that plays a critical role in carcinogenesis and cancer progression and is a potential therapeutic target. Sanguinarine, a benzophenanthridine alkaloid derived primarily from the bloodroot plant, was identified previously as a novel inhibitor of survivin that selectively kills prostate cancer cells over “normal” prostate epithelial cells.METHODSDU145, C4‐2B, and LNCaP cells were treated with sanguinarine. The phosphorylation status of Stat3 and related proteins were measured with Western blots. Activation of transcription by Stat3 was measured with luciferase reporter assay. The effect of sanguinarine on anchorage‐independent growth was examined with soft agar assay, and on cell migration and invasion of DU145 cells were measured with scratch assay and invasion assay, respectively.RESULTSIn this study, we identified sanguinarine as a potent inhibitor of Stat3 activation which was able to suppress prostate cancer growth, migration, and invasion. Sanguinarine inhibits constitutive as well as IL6‐induced phosphorylation of Stat3 at both Tyr705 and Ser727 in prostate cancer cells. The inhibition of Stat3 phosphorylation by sanguinarine correlates with reduction of Janus‐activated Kinase 2 (Jak2) and Src phosphorylation. Sanguinarine downregulates the expression of Stat3‐mediated genes such as c‐myc and survivin and inhibits the Stat3 responsive element luciferase reporter activity. Sanguinarine inhibits the anchorage‐independent growth of DU145 and LN‐S17 cells expressing constitutively activated Stat3. Migration and invasion abilities of DU145 cells were also inhibited by sanguinarine in a manner similar to the dominant negative form of Stat3.CONCLUSIONSThese data demonstrate that sanguinarine is a potent Stat3 inhibitor and it could be developed as a therapeutic agent for prostate cancer with constitutive activation of Stat3. Prostate 72:82–89, 2012. © 2011 Wiley Periodicals, Inc.
HDAC inhibitor MS‐275 attenuates the inflammatory reaction in rat experimental autoimmune prostatitis
Authors: Zhang Zhi‐Yuan , Schluesener Hermann J. 
Published: May 2011

AbstractBACKGROUNDExperimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of male sex accessory glands and is characterized by a cellular and humoral prostate‐specific autoimmune response. EAP shares important clinical and immunological features with human chronic prostatitis and chronic pelvic pain syndrome. MS‐275, a potent histone deacetylase inhibitor, has promising anti‐inflammatory activities and might be a new agent in the therapy of prostate inflammation.METHODSEAP rats were treated with MS‐275 (5 mg/kg, i.p.) once daily. Using immunohistochemistry and PCR assay, we determined immune cellular responses and infiltration into the prostate glands, and changes of mRNA levels of representative inflammatory molecules in prostate tissue. Changes in Foxp3+CD4+ cell populations of lymph nodes and peripheral blood were analyzed by flow cytometry. Additionally, direct anti‐inflammatory effects of MS‐275 were investigated in vitro with a macrophage cell line.RESULTSMS‐275 treatment significantly reduced the local accumulation of immune cells and mRNA levels of representative pro‐inflammatory molecules in prostate tissue. Furthermore, MS‐275 treatment increased percentage of Foxp3+CD4+ Treg cells in lymph nodes and their proportion to CD4+ cells in peripheral blood, and induced a relative increase of ED2+ macrophage numbers in EAP prostate. Additional in vitro study showed that MS‐275 induced a switch of macrophages from classic M1 to anti‐inflammatory M2 phenotype.CONCLUSIONSIn summary, our data demonstrated that MS‐275 could effectively suppress inflammatory reaction in EAP, through suppressing immune cells and pro‐inflammatory molecules, and inducing anti‐inflammatory immune cells and molecules, which may suggest MS‐275 as a potential candidate for treatment of inflammatory prostatitis. Prostate 72:90–99, 2012. © 2011 Wiley Periodicals, Inc.
Imaging prostate cancer lymph node metastases with a multimodality contrast agent
Authors: Hall Mary A. , Kwon Sunkuk , Robinson Holly , Lachance Pier‐Anne , Azhdarinia Ali , Ranganathan Ranjani , Price Roger E. , Chan Wenyaw , Sevick‐Muraca Eva M. 
Published: May 2011

AbstractBACKGROUNDMethods to detect lymph node (LN) metastases in prostate cancer (PCa) are limited. Pelvic LN dissection is commonly performed during prostatectomy, but often followed by morbid complications. More refined methods for detecting LN invasion are needed.METHODSWe developed a dual‐labeled targeting agent having a near‐infrared (NIR) fluorophore for intraoperative guidance, and a conventional radiotracer for detection of LN metastasis. Nu/Nu mice were orthotopically implanted with DsRed‐expressing human PCa (PC3) cells. Antibody (Ab) specific for epithelial cell adhesion molecule was conjugated to DOTA, IRDye 800CW, and radiolabeled with 64Cu. Dual‐labeled Ab was administered intravenously at 10–12 weeks post‐implantation, and positron emission tomography/computed tomography (PET/CT) and fluorescence imaging were performed within 18–24 hr.RESULTSMetastasis to lumbar LNs was detected by DsRed fluorescence imaging, as well as pathology, in 75% of mice having pathology‐confirmed primary prostate tumors. These metastases were also detected by NIR fluorescence imaging. In some cases, metastases to sciatic, medial, renal, and axillary nodes were also detected. For all LNs examined, no significant differences were found between the percentages of metastases detected by NIR imaging (63%) and µPET/CT (64%) (P = 0.93), or between those detected by DsRed imaging (25%) and pathological examination (19%) (P = 0.12).CONCLUSIONThis study demonstrates that a multimodality contrast agent is useful for early detection of metastatic disease, and has applications for intraoperative PCa treatment. Further agent optimization is necessary to enhance specificity, and provide validation for prostate and other LN metastasizing epithelial cancers. Prostate 72:129–146, 2012. © 2011 Wiley Periodicals, Inc.
Early onset prostate cancer has a significant genetic component
Authors: Lange Ethan M. , Salinas Claudia A. , Zuhlke Kimberly A. , Ray Anna M. , Wang Yunfei , Lu Yurong , Ho Lindsey A. , Luo Jingchun , Cooney Kathleen A. 
Published: May 2011

AbstractBACKGROUNDProstate cancer (PCa) affects more than 190,000 men each year with ∼10% of men diagnosed at ≤55 years, that is, early onset (EO) PCa. Based on historical findings for other cancers, EO PCa likely reflects a stronger underlying genetic etiology.METHODSWe evaluated the association between EO PCa and previously identified single nucleotide polymorphisms (SNPs) in 754 Caucasian cases from the Michigan Prostate Cancer Genetics Project (mean 49.8 years at diagnosis), 2,713 Caucasian controls from Illumina's iControlDB database and 1,163 PCa cases diagnosed at >55 years from the Cancer Genetic Markers of Susceptibility Study (CGEMS).RESULTSSignificant associations existed for 13 of 14 SNPs (rs9364554 on 6q25, rs10486567 on 7p15, rs6465657 on 7q21, rs6983267 on 8q24, rs1447295 on 8q24, rs1571801 on 9q33, rs10993994 on 10q11, rs4962416 on 10q26, rs7931342 on 11q13, rs4430796 on 17q12, rs1859962 on 17q24.3, rs2735839 on 19q13, and rs5945619 on Xp11.22, but not rs2660753 on 3p12). EO PCa cases had a significantly greater cumulative number of risk alleles (mean 12.4) than iControlDB controls (mean 11.2; P = 2.1 × 10−33) or CGEMS cases (mean 11.9; P = 1.7 × 10−5). Notably, EO PCa cases had a higher frequency of the risk allele than CGEMS cases at 11 of 13 associated SNPs, with significant differences for five SNPs. EO PCa cases diagnosed at <50 (mean 12.8) also had significantly more risk alleles than those diagnosed at 50–55 years (mean 12.1; P = 0.0003).CONCLUSIONSThese results demonstrate the potential for identifying PCa‐associated genetic variants by focusing on the subgroup of men diagnosed with EO disease. Prostate 72:147–156, 2012. © 2011 Wiley Periodicals, Inc.
Alternol exerts prostate‐selective antitumor effects through modulations of the AMPK signaling pathway
Authors: Yeung Eddie D. , Morrison Alex , Plumeri Daniel , Wang Jingying , Tong Chao , Yan Xiaoyan , Li Ji 
Published: May 2011

AbstractBACKGROUNDAlternol is an original compound purified from the fermentation products of Alternaria alternata var. monosporus, a microorganism from the bark of the yew tree. It has been reported that Alternol can inhibit proliferation of mouse leukemia cells and human gastric carcinoma cells, the aim of this study was to investigate the effects of Alternol on prostate cancer cells in comparison to prostate cells.METHODSThe MTT assay was utilized to assess cell viability. Cell cycle was analyzed by flow cytometry with propidium iodide staining. Protein expression levels were examined by Western blotting.RESULTSAlternol treatment resulted in a significant decrease in the viability of prostate cancer cells but had lesser effects on prostate cells. Alternol inhibited AMP‐activated protein kinase (AMPK) phosphorylation in prostate cancer C4‐2 cells but stimulated AMPK phosphorylation in prostate RWPE‐1 cells. Inhibition of p27 phosphorylation was observed in C4‐2 cells whereas a promotion of p27 phosphorylation was seen in RWPE‐1 cells. Alternol treatment resulted in a profound increase in the LC3II/LC3I protein ratio in RWPE‐1 cells but not in C4‐2 cells. A dose‐dependent down‐regulation of Bcl‐2 protein was detected in C4‐2 cells but not in RWPE‐1 cells. Pretreatment of cells with Compound C (AMPK inhibitor) before Alternol treatment abolished the selective antitumor effect of Alternol.CONCLUSIONSThese results reveal for the first time that Alternol exerts a selective antitumor effect on prostate cancer cells when compared with RWPE‐1 prostate epithelial cells. In addition, the AMPK signaling pathway is responsible for the selective antitumor effects of Alternol. Prostate 72:165–172, 2012. © 2011 Wiley Periodicals, Inc.
Conserved conformational dynamics of membrane fusion protein transmembrane domains and flanking regions indicated by sequence statistics
Authors: Neumann Sindy , Langosch Dieter 
Published: May 2011

AbstractSNARE proteins and fusogenic viral membrane proteins represent the major classes of integral membrane proteins that mediate fusion of eukaryotic lipid bilayers. Although both classes have different primary structures, they share a number of basic architectural features. There is ample evidence that the fusogenic function of representative fusion proteins is influenced by the primary structure of the single transmembrane domain (TMD) and the region linking it to the soluble assembly domains. Here, we used comprehensive non‐redundant datasets to examine potential over‐ and underrepresentation of amino acid types in the TMDs and flanking regions relative to control proteins that share similar biosynthetic origins. Our results reveal conserved overall and/or site‐specific enrichment of β‐branched residues and Gly within the TMDs, underrepresentation of Gly and Pro in regions flanking the TMD N‐terminus, and overrepresentation of the same residue types in C‐terminal flanks of SNAREs and viral fusion proteins. Furthermore, the basic Lys and Arg are enriched within SNARE N‐terminal flanking regions. These results suggest evolutionary conservation of key structural features of fusion proteins and are discussed in light of experimental findings that link these features to the fusogenic function of these proteins. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Challenges in developing and implementing safety risk tolerance criteria
Authors: P.E. Walt Frank 
Published: May 2011

AbstractRisk quantification can help in understanding and managing risk. Establishing quantitative risk criteria can be a key component to risk decision‐making and many companies use such criteria, either formally or informally. The Center for Chemical Process Safety issued its guidance on developing quantitative safety risk criteria in 2009—Center for Chemical Process Safety Guidelines for Developing Quantitative Safety Risk Tolerance Criteria. This article addresses some of the more common challenges that users may face in developing and implementing safety risk tolerance criteria as they apply the Guidelines. © 2011 American Institute of Chemical Engineers Process Saf Prog, 2011
High integrity protective system design using a risk‐based approach
Authors: Stack Robert J. , Armstrong John , Eure Don , Johnson Ron , Tipler Scott , Wagner Tim , Werkmeister Sofka 
Published: May 2011

AbstractIn 2007, API 521/ISO 23251 [AANSI/API Standard 521, Petroleum and Natural Gas Industries Pressure‐Relieving and Depressuring Systems, 2007] published guidance on the use of high integrity protective systems (HIPS). The Dow Chemical Company (Dow) updated its internal work process to apply Dow's risk‐based work processes to HIPS design, application, and evaluation. Rather than just focusing on the vessel‐related consequences of substituting a HIPS for a pressure relief device (PRD), the work process calls for stepping back and looking at the overall scenario and all the potential consequence outcomes. Using a risk‐based methodology requires looking at a much wider consequence potential than what Dow has traditionally focused on for the design of relief systems.By using a very robust layer of protection analysis (LOPA) process to evaluate the consequences of the overpressure scenarios and to determine the consequence severity factor or LOPA target factor for each scenario (Dow has seven levels), the wider range of consequences is covered. The HIPS safety integrity level (SIL) is determined by the highest risk scenario, which is typically the scenario with the greatest LOPA consequence severity factor. The resulting SIL level for the HIPS is adjusted to close the HIPS scenario risk gap. Other applicable LOPA independent protection layers (IPLs) included in the LOPA HIPS scenario risk evaluation are validated. The HIPS design is verified by calculation to meet the required SIL level.There are PRD services for which PRDs cannot deliver the overpressure protection that Dow needs and expects. The updated work process also identifies key opportunities for using a HIPS when: a conventional PRD is not practical or possible, a conventional PRD will not be reliable or a conventional PRD will work but will result in high treatment cost. Each of these three opportunities is discussed.The overall result is an efficient process that links together the existing work processes for conventional relief design, LOPA, and safety instrumented systems. This produces a risk‐based method for applying and designing protection layers into a HIPS. This article gives an overview of this work process with some application examples and describes how this work process is used to improve safety while reducing risks and potentially reducing costs. © 2011 American Institute of Chemical Engineers Process Saf Prog, 2011
Soil microbial degradation of neonicotinoid insecticides imidacloprid, acetamiprid, thiacloprid and imidaclothiz and its effect on the persistence of bioefficacy against horsebean aphid Aphis craccivora Koch after soil application
Authors: Liu Zhonghua , Dai Yijun , Huang Guodong , Gu Yuyu , Ni Jueping , Wei Hua , Yuan Sheng 
Published: May 2011

AbstractBACKGROUND: The neonicotinoids imidacloprid, imidaclothiz, acetamiprid and thiacloprid consist of similar structural substituents but differ considerably with respect to soil use. Therefore, the effects of soil microbial activity on the degradation and bioefficacy persistence of the four neonicotinoids were evaluated.RESULTS: In unsterilised soils, 94.0% of acetamiprid and 98.8% of thiacloprid were degraded within 15 days, while only 22.5% of imidacloprid and 25.1% of imidaclothiz were degraded over a longer period of 25 days. In contrast, in sterilised soils, the degradation rates of acetamiprid and thiacloprid were respectively only 21.4% and 27.6%, whereas the degradation rates of imidaclothiz and imidacloprid were respectively 9.0% and almost 0% within 25 days. The degradation products of imidacloprid and imidaclothiz were identified as olefin, nitroso or guanidine metabolites, the degradation product of thiacloprid was identified as an amide metabolite and no degradation product of acetamiprid was detected. A bioefficacy assay revealed that the bioefficacy and persistence of imidacloprid, imidaclothiz, acetamiprid and thiacloprid against horsebean aphid A. craccivora were related to their degradation rate and the bioefficacy of their degradation products in soil.CONCLUSION: Soil microbial activity played a key role in the bioefficacy persistence of neonicotinoid insecticides and therefore significantly affected their technical profile after soil application. Copyright © 2011 Society of Chemical Industry