bluuebunny/crossref_metadata_2025 huggingface dataset:
Shengjie Tongyu Granule Inhibits Vascular Remodeling in ApoE-Gene-Knockout Mice
Authors: Chen Min , Cheng Wenli , Shi Zaixiang , Tatsukazu Nishihara , Zhou Tongliang , Li Hong , Guo Jian
Published: June 2012

The aim of the present paper was to investigate the effect of Shengjie Tongyu granule on vascular remodeling in atherosclerotic mice and the relevant underlying mechanism. Sixty male ApoE-gene-knockout mice, fed a high-fat diet from 6 weeks of age, were randomized into a Shengjie Tongyu granule group (4.00 g/kg/d), a simvastatin group (9.01 mg/kg/d), and a control group (normal saline: 0.2 mL/d). At the ages of 30 and 40 weeks, we sacrificed the mice for various measurements. The results show that treatment with Shengjie Tongyu granule and simvastatin significantly decreased lumen and plaque areas in the aortic root at 30 and 40 weeks of age, decreased grade II elastic fiber lesions in the ascending aorta at 30 weeks of age, and decreased both grade II and III lesions at 40 weeks of age, compared to controls. The content of superoxide anions, and expression of MOMA-2, plasma ICAM-1, and NFκB p50 in 30- and 40-week-old mice in the Shengjie Tongyu granule and simvastatin groups were also significantly reduced compared to the control group. In conclusion, Shengjie Tongyu granule has a clear inhibitory effect on vascular remodeling and on inflammatory pathways in ApoE-gene-knockout mice.
Peroxisome Proliferator-Activated ReceptorαPlays an Important Role in the Expression of Monocyte Chemoattractant Protein-1 and Neointimal Hyperplasia after Vascular Injury
Authors: Peng Yu , Li Qiang , Zhang Lu , Bai Ming , Zhang Zheng
Published: June 2012

Peroxisome proliferator-activated receptorαis a member of the nuclear receptor superfamily. It modulates smooth muscle cell proliferation and inflammatory cytokines in vitro. In this study, we tested the hypothesis that PPARαwould decrease the expression of monocyte chemoattractant protein-1 and tissue factor, and inhibit neointimal formation in a murine double carotid artery injury model. Carotid artery injury was performed in the PPARαknockout and wild type (WT) mice, treated and untreated with Wy14643, a PPARαactivator. Up-regulated MCP-1 and TF expression and more neointimal formation were observed in the PPARα−/−mice compared with WT mice. The activation of PPARαresulted in further decreased neointimal formation. Our data further suggest that the decrease in neointimal formation is due to down-regulation of MCP-1 by PPARαresulting in decreased leukocyte infiltration and TF expression.
Nanofiber‐Membrane‐Supported TiO2 as a Catalyst for Oxidation of Benzene to Phenol
Authors: Basheer Chanbasha
Published: June 2012

We applied a simple, low‐cost design of glass capillary microreactor for the catalytic oxidation of benzene to phenol at ambient conditions. Polyvinylchloride‐nanofiber‐membrane‐supported titania nanoparticle (TiO2‐PVC) as catalyst and in situ production of hydroxyl radicals as oxidant. The reaction was monitored by gas chromatography‐mass spectrometry (GC‐MS). The reaction conditions were optimized and the performance of the microreactor was then compared with the conventional laboratory scale reaction which used hydrogen peroxide as oxidant. The microreactor gave a better yield of 14% for phenol compared to 0.14% in the conventional laboratory scale reaction. Reaction conditions such as reaction time, reaction pH, and applied potential were optimized. With optimized reaction conditions selectivity of >37% and >88% conversion of benzene were obtained.
Tankyrase and the Canonical Wnt Pathway Protect Lung Cancer Cells from EGFR Inhibition
Authors: Casás-Selves Matias , Kim Jihye , Zhang Zhiyong , Helfrich Barbara A. , Gao Dexiang , Porter Christopher C. , Scarborough Hannah A. , Bunn Paul A. , Chan Daniel C. , Tan Aik Choon , DeGregori James
Published: June 2012

Lung cancer is the leading cause of death worldwide. Adenocarcinomas, the most common histologic subtype of non-small cell lung cancer (NSCLC), are frequently associated with activating mutations in the epidermal growth factor receptor (EGFR) gene. Although these patients often respond clinically to the EGFR tyrosine kinase inhibitors erlotinib and gefitinib, relapse inevitably occurs, suggesting the development of escape mechanisms that promote cell survival. Using a loss-of-function, whole genome short hairpin RNA (shRNA) screen, we identified that the canonical Wnt pathway contributes to the maintenance of NSCLC cells during EGFR inhibition, particularly the poly-ADP-ribosylating enzymes tankyrase 1 and 2 that positively regulate canonical Wnt signaling. Inhibition of tankyrase and various other components of the Wnt pathway with shRNAs or small molecules significantly increased the efficacy of EGFR inhibitors both in vitro and in vivo. Our findings therefore reveal a critical role for tankyrase and the canonical Wnt pathway in maintaining lung cancer cells during EGFR inhibition. Targeting the Wnt-tankyrase-β-catenin pathway together with EGFR inhibition may improve clinical outcome in patients with NSCLC. Cancer Res; 72(16); 4154–64. ©2012 AACR.
Neuropilin-1 Stimulates Tumor Growth by Increasing Fibronectin Fibril Assembly in the Tumor Microenvironment
Authors: Yaqoob Usman , Cao Sheng , Shergill Uday , Jagavelu Kumaravelu , Geng Zhimin , Yin Meng , de Assuncao Thiago M. , Cao Ying , Szabolcs Anna , Thorgeirsson Snorri , Schwartz Martin , Yang Ju Dong , Ehman Richard , Roberts Lewis , Mukhopadhyay Debabrata , Shah Vijay H.
Published: June 2012

The tumor microenvironment, including stromal myofibroblasts and associated matrix proteins, regulates cancer cell invasion and proliferation. Here, we report that neuropilin-1 (NRP-1) orchestrates communications between myofibroblasts and soluble fibronectin that promote α5β1 integrin–dependent fibronectin fibril assembly, matrix stiffness, and tumor growth. Tumor growth and fibronectin fibril assembly were reduced by genetic depletion or antibody neutralization of NRP-1 from stromal myofibroblasts in vivo. Mechanistically, the increase in fibronectin fibril assembly required glycosylation of serine 612 of the extracellular domain of NRP-1, an intact intracellular NRP-1 SEA domain, and intracellular associations between NRP-1, the scaffold protein GIPC, and the nonreceptor tyrosine kinase c-Abl that augmented α5β1 fibronectin fibril assembly activity. Analysis of human cancer specimens established an association between tumoral NRP-1 levels and clinical outcome. Our findings indicate that NRP-1 activates the tumor microenvironment, thereby promoting tumor growth. These results not only identify new molecular mechanisms of fibronectin fibril assembly but also have important implications for therapeutic targeting of the myofibroblast in the tumor microenvironment. Cancer Res; 72(16); 4047–59. ©2012 AACR.
Cell Death via DR5, but not DR4, Is Regulated by p53 in Myeloma Cells
Authors: Surget Sylvanie , Chiron David , Gomez-Bougie Patricia , Descamps Géraldine , Ménoret Emmanuelle , Bataille Régis , Moreau Philippe , Le Gouill Steven , Amiot Martine , Pellat-Deceunynck Catherine
Published: June 2012

Myeloma cells are sensitive to TRAIL through the two death receptors DR4 and DR5. Because p53 directly modulates expression of death receptors, we investigated here whether p53 can modulate myeloma sensitivity to TRAIL. We found that p53 affects the sensitivity of myeloma cells to the DR5 agonistic human antibody lexatumumab but not the DR4 antibody mapatumumab. TP53 wild-type myeloma cells overexpressed DR5 in correlation with sensitivity to lexatumumab. Both nongenotoxic (nutlin-3a) and genotoxic (melphalan) p53-inducing stresses increased DR5 expression only in TP53 wild-type cells and synergistically increased lexatumumab efficiency yet did not increase DR4 expression, nor sensitivity to mapatumumab. Silencing of p53 strongly decreased DR5 expression and induced resistance to nutlin-3a and lexatumumab but did not modulate DR4 expression or sensitivity to mapatumumab. Increase of lexatumumab efficiency induced by nutlin-3a was related to a p53-dependent increase of DR5 expression. In primary myeloma cells, nutlin-3a increased DR5 expression and lexatumumab efficiency but did not increase mapatumumab efficiency. Taken together, our findings indicate that p53 controls the sensitivity of myeloma through DR5 but not DR4 and suggest that a subset of patients with multiple myeloma may benefit from DR5 therapy. Cancer Res; 72(17); 4562–73. ©2012 AACR.
The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator
Authors: Feldman Dafna , Roniger Maayan , Bar-Sinai Allan , Braitbard Ori , Natan Carmit , Love Dona C. , Hanover John A. , Hochman Jacob
Published: June 2012

Mouse mammary tumor virus (MMTV) is associated primarily with mammary carcinomas and lymphomas. The signal peptide of the MMTV envelope precursor is uniquely targeted to nucleoli of cells that harbor the virus, where it can function as a nuclear export factor for intron-containing transcripts. Antibodies to this signal peptide, which we refer to as p14, were previously shown to label nucleoli in a subset of human breast cancers. To look for additional cellular functions of p14, different mutants were ectopically expressed in the MCF-7 human breast cancer cell line. This approach identified motifs responsible for its nucleolar targeting, nucleocytoplasmic shuttling, target protein (B23, nucleophosmin) binding, and phosphorylation at serine 18 and 65 both in situ and in vitro. To test the role of these phosphorylation sites, we carried out in vivo tumorigenesis studies in severe combined immunodeficient mice. The findings show that the p14-Ser65Ala mutation is associated with impaired tumorigenicity, whereas the p14-Ser18Ala mutation is associated with enhanced tumorigenicity. Microarray analysis suggests that phosphorylation at serine 18 or at serine 65 is associated with transcriptional regulation of the L5 nucleolar ribosomal protein (a p14 target) and the Erb-B signal transduction pathway. Taken together, these results show that the phosphorylation status of p14 determines whether it functions as a pro-oncogenic or antioncogenic modulator. Mol Cancer Res; 10(8); 1077–86. ©2012 AACR.
Which Treatment Modality Is More Injurious to the Brain in Patients with Subarachnoid Hemorrhage? Degree of Brain Damage Assessed by Serum S100 Protein after Aneurysm Clipping or Coiling
Authors: Shim Jae-Hyun , Yoon Seok-Mann , Bae Hack-Gun , Yun Il-Gyu , Shim Jai-Joon , Lee Kyeong-Seok , Doh Jae-won
Published: June 2012

Background: Serum S100 protein has been known to reflect the severity of brain damage. The purpose of this study was to compare the degree of brain damage based on the serum S100 protein level between aneurysm clipping and coiling groups and to evaluate the prognostic value of S100 protein in patients with subarachnoid hemorrhage (SAH). Methods: Serum S100 protein was measured by Elecsys S100 immunoassay at admission, and at 6 and 24 h, and days 3 and 5 postoperatively for 100 consecutive SAH patients (clipping group: 56, coiling group: 44) and for 74 healthy controls. Hunt-Hess grade (HHG), Fisher grade (FG), the presence of intraventricular (IVH) or intracerebral hemorrhage (ICH), and outcome at discharge were evaluated. The time course of serum S100 was compared between the groups. The prognostic value of S100 protein was evaluated by logistic regression analysis. Results: The median S100 level in SAH patients on admission was significantly higher than in healthy controls (0.081 vs. 0.05 µg/l, p < 0.0001) and it was also higher as HHG and FG increased (p < 0.0001). Logistic regression analysis revealed that only the S100 value at admission was an independent prognostic factor for poor outcomes after adjusting for age, sex, HHG, presence of IVH or ICH, and treatment modality (OR: 100.5, 95% CI: 1.65–6,053.61). The baseline S100 value of 0.168 predicted poor outcomes with a sensitivity of 75% and a specificity of 83%. The time course of the median S100 level peaked at 6 h and then decreased serially in both clipping and coiling groups. However, the degree of S100 elevation was marked in the clipping group, especially at 6 h postoperatively (0.177 vs. 0.116 µg/l, p = 0.022), suggesting more severe brain damage in the clipping group. In the coiling group, the S100 value was significantly higher in patients who showed high signal intensity lesions in diffusion-weighted images, suggesting ischemic brain damage. Furthermore, even in patients who were categorized as good clinical grade at admission and as good outcome at discharge, the median S100 values at 6 and 24 h postoperatively were significantly higher in the clipping group than in the coiling group (p < 0.05). Conclusion: The initial S100 protein value is an independent prognostic factor for poor outcomes in SAH patients. Based on the S100 protein level, aneurysm clipping seems to provoke more brain damage than aneurysm coiling. Endovascular coiling should be considered the first therapeutic option for aneurysmal SAH patients.
Oxygen: How Do We Stand It?
Authors: Fridovich Irwin
Published: June 2012

The electronic structure of ground state oxygen, which is essential for the life of all aerobic organisms, makes it potentially dangerous for those organisms. Atmospheric oxygen contains two unpaired electrons with parallel spin states, which predisposes it to reduction by a univalent pathway. As a consequence, normal aerobic metabolism generates dangerous reactive intermediates of the reduction of O2. These include superoxide radical (O2–), hydrogen peroxide (H2O2), and hydroxyl radical (HO). These reactive oxygen species and others that they can engender can damage all cellular macromolecules and unless opposed by cellular defenses, would make aerobic life impossible. Such defenses include superoxide dismutases, catalases, and peroxidases, enzymes that decrease the concentration of the reactive oxygen species that are their substrates, and others that repair or recycle oxidatively damaged macromolecules. Any factor that stimulates reactive oxygen species production or suppresses the antioxidant systems would inevitably cause cell damage. The role of such oxidative damage in various diseases is well documented. In vivo detection of O2– and other reactive oxygen species is however hampered by the lack of easy, specific, and sensitive analytical methods. Potential artifacts and limitations of the most common detection methods currently in use are briefly discussed.
Dexpanthenol Modulates Gene Expression in Skin Wound Healing in vivo
Authors: Heise R. , Skazik C. , Marquardt Y. , Czaja K. , Sebastian K. , Kurschat P. , Gan L. , Denecke B. , Ekanayake-Bohlig S. , Wilhelm K.-P. , Merk H.F. , Baron J.M.
Published: June 2012

Topical application of dexpanthenol is widely used in clinical practice for the improvement of wound healing. Previous in vitro experiments identified a stimulatory effect of pantothenate on migration, proliferation and gene regulation in cultured human dermal fibroblasts. To correlate these in vitro findings with the more complex in vivo situation of wound healing, a clinical trial was performed in which the dexpanthenol-induced gene expression profile in punch biopsies of previously injured and dexpanthenol-treated skin in comparison to placebo-treated skin was analyzed at the molecular level by Affymetrix® GeneChip analysis. Upregulation of IL-6, IL-1β, CYP1B1, CXCL1, CCL18 and KAP 4–2 gene expression and downregulation of psorasin mRNA and protein expression were identified in samples treated topically with dexpanthenol. This in vivo study might provide new insight into the molecular mechanisms responsible for the effect of dexpanthenol in wound healing and shows strong correlations to previous in vitro data using cultured dermal fibroblasts.
Automated volumetric analysis of four cardiac chambers in pulmonary embolism
Authors: Sirota-Cohen Chen , Steinvil Arie , Keren Gad , Banai Shmuel , Sosna Jacob , Berliner Shlomo , Rogowski Ori , Aviram Galit
Published: June 2012

Identification of patients with acute pulmonary embolism (PE) who might be at risk of circulatory collapse by using a fast, automated system is highly desired. It was our objective to investigate whether automated cardiac volumetric analysis following computerised tomographic pulmonary angiography (CTPA) is useful to identify increased clot load and adverse prognosis in patients with acute PE. We retrospectively analysed a consecutive series of non-gated CTPA studies of 124 patients with acute PE and 43 controls. Right and left ventricular diameters (RV/LV) were measured on four-chamber view, while each cardiac chamber underwent automatic volumetric measurements. Findings were correlated to the pulmonary arterial obstruction index (PAOI). Outcome was expressed by admission to an intensive care unit (ICU) or mortality within 30 days. There was a significant positive correlation between the PAOI and the volumes of the right side cavities (r=0.25 for the atrium and r=0.49 for the ventricle), and between the right-to-left atrial and ventricular volume ratios (r=0.49 and r=0.57, respectively). Results for the combined outcome of mortality or ICU admission that fell in the upper tertile of the right atrial and right ventricular volumes yielded hazard ratios of 3.9 and 3.3, respectively, compared to those in the lower tertile. RV/LV diameter ratio did not correlate with outcome. In conclusion, adverse outcome and significant pulmonary clot load in patients with acute PE are associated with a volume shift towards right heart cavities, which correlates to prognosis better than the CT-measured RV/LV diameter ratio, suggesting the advantage of using fast fully automatic volumetric analysis to identify patients at risk.
Habitual Coffee Consumption and Risk of Heart Failure
Authors: Mostofsky Elizabeth , Rice Megan S. , Levitan Emily B. , Mittleman Murray A.
Published: June 2012

Background—

There have been discrepant findings on the association between coffee consumption and risk of incident heart failure.

Methods and Results—

We conducted a systematic review and a dose-response meta-analysis of prospective studies that assessed the relationship between habitual coffee consumption and the risk of heart failure. We searched electronic databases (MEDLINE, Embase, and CINAHL) from January 1966 through December 2011, with the use of a standardized protocol. Eligible studies were prospective cohort studies that examined the association of coffee consumption with incident heart failure. Five independent prospective studies of coffee consumption and heart failure risk, including 6522 heart failure events and 140 220 participants, were included in the meta-analysis. We observed a statistically significant J-shaped relationship between coffee and heart failure. Compared with no consumption, the strongest inverse association was seen for 4 servings/day and a potentially higher risk at higher levels of consumption. There was no evidence that the relationship between coffee and heart failure risk varied by sex or by baseline history of myocardial infarction or diabetes.

Conclusions—

Moderate coffee consumption is inversely associated with risk of heart failure, with the largest inverse association observed for consumption of 4 servings per day.
Systematic Review and Cost–Benefit Analysis of Radial Artery Access for Coronary Angiography and Intervention
Authors: Mitchell Matthew D. , Hong Jaekyoung A. , Lee Bruce Y. , Umscheid Craig A. , Bartsch Sarah M. , Don Creighton W.
Published: June 2012

Background—

Radial artery access for coronary angiography and interventions has been promoted for reducing hemostasis time and vascular complications compared with femoral access, yet it can take longer to perform and is not always successful, leading to concerns about its cost. We report a cost–benefit analysis of radial catheterization based on results from a systematic review of published randomized controlled trials.

Methods and Results—

The systematic review added 5 additional randomized controlled trials to a prior review, for a total of 14 studies. Meta-analyses, following Cochrane procedures, suggested that radial catheterization significantly increased catheterization failure (OR, 4.92; 95% CI, 2.69–8.98), but reduced major complications (OR, 0.32; 95% CI, 0.24–0.42), major bleeding (OR, 0.39; 95% CI, 0.27–0.57), and hematoma (OR, 0.36; 95% CI, 0.27–0.48) compared with femoral catheterization. It added approximately 1.4 minutes to procedure time (95% CI, −0.22 to 2.97) and reduced hemostasis time by approximately 13 minutes (95% CI, −2.30 to −23.90). There were no differences in procedure success rates or major adverse cardiovascular events. A stochastic simulation model of per-case costs took into account procedure and hemostasis time, costs of repeating the catheterization at the alternate site if the first catheterization failed, and the inpatient hospital costs associated with complications from the procedure. Using base-case estimates based on our meta-analysis results, we found the radial approach cost $275 (95% CI, −$374 to −$183) less per patient from the hospital perspective. Radial catheterization was favored over femoral catheterization under all conditions tested.

Conclusions—

Radial catheterization was favored over femoral catheterization in our cost–benefit analysis.
Perinatal Nicotine Exposure Increases Vulnerability of Hypoxic–Ischemic Brain Injury in Neonatal Rats
Authors: Li Yong , Xiao Daliao , Dasgupta Chiranjib , Xiong Fuxia , Tong Wenni , Yang Shumei , Zhang Lubo
Published: June 2012

Background and Purpose—

Maternal cigarette smoking increases the risk of neonatal morbidity. We tested the hypothesis that perinatal nicotine exposure causes heightened brain vulnerability to hypoxic–ischemic (HI) injury in neonatal rats through aberrant expression patterns of angiotensin II type 1 (AT
1
R) and type 2 (AT
2
R) receptors in the developing brain.

Methods—

Nicotine was administered to pregnant rats through subcutaneous osmotic minipumps. HI brain injury was determined in 10-day-old pups. AT
1
R and AT
2
R expression patterns were assessed through Western blotting, quantitative polymerase chain reaction, immunofluorescence, and confocal imaging.

Results—

Perinatal nicotine exposure significantly increased HI brain infarct size in male, but not female, pups. In fetal brains, nicotine caused a decrease in mRNA and protein abundance of AT
2
R but not AT
1
R. The downregulation of AT
2
R persisted in brains of male pups, and nicotine treatment resulted in a significant increase in methylation of CpG locus 3 bases upstream of TATA-box at the AT
2
R gene promoter. In female brains, there was an increase in AT
2
R but a decrease in AT
1
R expression. Both AT
1
R and AT
2
R expressed in neurons but not in astrocytes in the cortex and hippocampus. Central application of AT
1
R antagonist losartan or AT
2
R antagonist PD123319 increased HI brain infarct size in both male and female pups. In male pups, AT
2
R agonist CGP42112 abrogated nicotine-induced increase in HI brain infarction. In females, PD123319 uncovered the nicotine's effect on HI brain infarction.

Conclusion—

Perinatal nicotine exposure causes epigenetic repression of the AT
2
R gene in the developing brain resulting in heightened brain vulnerability to HI injury in neonatal male rats in a sex-dependent manner.
Governance of stem cell research: Public participation and decision-making in China, Japan, South Korea and Taiwan
Authors: Sleeboom-Faulkner Margaret , Hwang Seyoung
Published: June 2012

This article compares and explores forms of ‘public’ participation in the development of bioethical governance of human embryonic stem cell research (hESR) in four Asian societies, and in doing so it contributes to the wider discussions on expertise and public inclusion. The article aims to add nuance to the concept of ‘public consultation’ by focusing on the contested meanings and relationships through which public roles and public debates are defined. The analysis seeks to go beyond a straightforward comparison by interpreting public discussions of hESR as being influenced by both local conditions and interconnected global science institutions. An adequate understanding of the public participation in debates on science requires the analysis of (a) particular reasons for scientific issues to require public discussion; (b) pressures of transnational forces; (c) variability of publics relevant to bioethical regulation; and, (d) the effects of institutionalization of bioethics. This study uses data from fieldwork conducted between 2006 and 2010 in four Asian countries. Most of the interviews were conducted in the local languages and concerned various kinds of public participation in bioethics activities, as well as the views of stem cell scientists on the need to involve the public in discussions on the acceptability of their research.
A review of national municipal solid waste generation assessments in the USA
Authors: Tonjes David J , Greene Krista L
Published: June 2012

Municipal solid waste (MSW) is generated in very large quantities (probably between 200 and 400 million tonnes per year) in the USA. MSW is generated at millions of places and there is no one precise, general definition for MSW that is generally applied—despite US Environmental Protection Agency efforts. As an element of both commerce and politics, reporting may be framed towards particular ends. Therefore, the two best known assessments of the quantity of US MSW production differ by approximately 50%. The assessors understand some of the reasons for the differences, but our analysis suggests that there are profound factors, not openly discussed, that affect estimates of waste stream size. Many regulators propose that strict, universal formats be adopted so that there is consistency in waste reporting; we note that this will not change the materials requiring management, only what is counted. Therefore, the most accurate assessments may be those where controllable errors are minimized but which suffer from differing definitions of ‘MSW’.
Benzene-contaminated toluene and acute myeloid leukemia: a case series and review of literature
Authors: Peckham Trevor , Kopstein Melvyn , Klein Jason , Dahlgren James
Published: June 2012

We report seven cases of acute myeloid leukemia (AML) with occupational exposure to a toluene-based hydrocarbon solvent. The cases were employed at a facility, which manufactured rubber belts and hoses, between 1950 and 2005 for periods ranging from 21 to 37 total years. Detailed histories were obtained for three workers who were diagnosed with AML within a 3-year period (2003–2005). Death certificates, medical records, and accounts by workers were reviewed. Benzene, a known cause of AML, is typically a contaminant of toluene. Benzene contamination in toluene and other widely used solvents and the potential for concurrent benzene exposure during usage of these solvents in occupational settings are discussed.
Histomorphometric and biochemical studies on the liver of rainbow trout (Oncorhynchus mykiss) after exposure to sublethal concentrations of phenol
Authors: Monfared Ali louei , Salati Amir Parviz
Published: June 2012

Phenolic compounds are common water pollutants and include a wide variety of organic chemicals. The effects of three sublethal concentrations of phenol on liver histology and some biochemical parameters of Oncorhynchus mykiss after 8 weeks exposure were investigated in this study. A total of 80 rainbow trout ( O. mykiss) were randomly divided into four groups ( n = 20). Control group was kept in water without any add-on material, while experimental groups were exposed to the concentration of 0.6, 1.2 and 2.4 mg/L of phenol solution. At the end of the study period, the weight of liver, condition factor (CF) and hepatosomatic index (HSI) were measured. Tissue and blood samples were taken separately for histologic evaluation and serum biochemical parameters assay, respectively. In fish treated with phenol, significant reduction in liver weight, CF, HSI ratio, diameter of hepatocytes and hepatocytes nuclear diameter ( p < 0.05) was recorded. Total protein and albumin decreased significantly in treated fish in comparison with control ( p < 0.05), but levels of cholesterol, glucose, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in fish exposed to different concentrations of phenol showed a significant increase ( p < 0.05). These findings showed that phenol could cause its harmful impacts even in very low concentrations.
A dimension reduction observer-based guidance law accounting for dynamics of missile autopilot
Authors: Qu Pingping , Zhou Di
Published: June 2012

Accounting for the missile autopilot as second-order dynamics, a dimension reduction observer-based guidance law is designed using the dynamic surface control method. Certain first-order low-pass filters are introduced into the designing process to avoid the occurrence of high-order derivatives of the line of sight angle in the expression of guidance law such that it can be implemented in practical applications. The proposed guidance law is effective in compensating for the adverse influence of the autopilot lag on guidance accuracy. In simulations of intercepting non maneuvering targets, targets with step acceleration, and targets with sinusoidal acceleration respectively, the guidance law is compared with the adaptive sliding mode guidance law in the presence of missile autopilot lag. Simulation results show that the proposed dimension reduction observer-based guidance law is able to guide a missile to accurately intercept a maneuvering target, even if it escapes in a great and fast maneuver and the autopilot has a relatively large lag.
Dynamic control for morphing of bi-stable composites
Authors: Arrieta Andres F , Bilgen Onur , Friswell Michael I , Hagedorn Peter
Published: June 2012

Adaptive structures have been the focus of much research due to performance gains not possible to achieve using conventional designs. Within this context, the idea of morphing promises augmented capabilities in terms of manoeuvrability, fuel efficiency and the ability to perform dissimilar tasks in an optimal manner. To achieve morphing, materials capable of changing shape requiring minimum actuation are necessary. Bi-stable composites are a type of composite structures which have two statically stable configurations. This bi-stability property, resulting from locked in-plane residual stresses, has attracted considerable attention from the adaptive structure community for morphing structures as actuation is no required to hold each stable configuration. The change between stable states is physically realised as a jump phenomenon or snap-through, which is strongly non-linear in nature. Morphing strategies exploiting snap-through have been studied showing encouraging preliminary results. This article exploits the dynamic response of bi-stable composites as a means of augmenting the actuation for morphing control. A morphing strategy targeting modal frequencies leading to snap-through of the structure is successfully developed. This results in a full-state configuration control by inducing and reversing snap-through as desired. The strategy is tested on a specimen using Macro Fiber Composites as smart actuators validating the proposed concept.
Generational Role Choices Among Children in Four Cultures
Authors: Munroe Robert L.
Published: June 2012

In a previous publication, we reported that on the whole, young children in four cultures predictably made same-sex role choices (e.g., girls preferring daughter to son). But contrary to prediction, we found that children in two patricentric societies (patrilineal descent, etc.) made fewer same-sex role choices than did those from two societies without gender-biased social principles (bilateral descent, etc.) This surprising finding, which constituted an acknowledged puzzle for interpretation, prompted the current reanalysis of the dataset. Our new analysis has led to two conclusions: (a) children from the two patricentric societies, besides scoring lower on same-sex role choices, also scored a good deal lower on cognitive-performance tests, so they were generally poor test-takers; and (b) children in one of the patricentric societies—though not in any of the other samples—expressed a strong preference for higher-generation roles (i.e., mother and father). Discussion centers on plausible interpretations of these new-found results.
Friction and wear properties of the composite brake material for mine hoister under different initial velocities
Authors: Bao Jiusheng , Chen Guangzhu , Zhu Zhencai , Tong Minming , Yin Yan , Peng Yuxing
Published: June 2012

The initial velocity determines the energy input of a braking which affects the tribological performance of brake materials seriously. Aiming at emergency braking conditions of mine hoisters, some tribological experiments and scanning electron microscopy analysis was carried out to reveal its influence on the composite brake materials. It is found that when the initial velocity is increasing, the mean coefficient of friction and its stability coefficient all decreases first then rises and decreases again while the wear rate rises continually. By contrast, it rises slowly at a low velocity, fast at a middle velocity and slowly again at a high velocity. It is concluded that some tribological related films generated by braking load and heat oxidization weaken the friction at the beginning of braking. Its friction weakening influence appears more obviously under a braking with a lower initial velocity. However, the films may also help to reduce braking wear. As the impacting frequency and velocity between surface asperities are all affected by the initial velocity, a bigger initial velocity will cause a worse wear. For short braking time, only a thin material on the surface is destroyed. The main wear modality of the pairs may be mechanical wear: cutting wear on the brake disc, fatigue and grooving wear on the brake shoe.
Policing the “Penn State Crisis”
Authors: Giardina Michael D. , Denzin Norman K.
Published: June 2012

Within this article, the authors critically introduce and interrogate the ongoing crisis/scandal at Penn State University within the intersecting vectors of institutional violence, the commodification of higher education, media coverage of the event and its aftermath, spaces of resistance, and the complicated legacy of Joe Paterno. Additionally, and on a broader scale, they argue that within the privileged spaces of academia, scholars have a responsibility to their communities to push for greater transparency and accountability within their institutions, join and support faculty unions, and resist the further neoliberalization of higher education.
Penn State’s “Success With Honor”
Authors: Proffitt Jennifer M. , Corrigan Thomas F.
Published: June 2012

In the wake of the Penn State child sex tragedy, media coverage tended to focus on the individuals involved rather than the corporatized university’s economic motivations and the institutional structure under which officials’ (in)actions occurred. This article interrogates and critiques that institutional structure, arguing that the “brand logic” of big-time intercollegiate athletics programs places image and profits ahead of people. In conjunction with on-field success, image and branding play prominently in an athletics program’s ability to maximize new revenue streams (e.g., licensing and merchandising). Further, administrators argue that athletics function as a university’s “front porch,” returning (symbolic) value to the institution (e.g., community, visibility, branding, alumni giving, and student applications). Thus, university and athletics administrators constantly take brand logic into their decision-making. The fallout from the Penn State tragedy offers insights into the ways in which brand logics disincentivize ethical decision-making when image, reputation, and millions of dollars are on the line.
Teaching Students to Serve Niche Audiences
Authors: Coffey Amy Jo
Published: June 2012

In an increasingly fragmented media landscape where “narrowcasting” is more often the norm, it is important to teach today's students how to best understand and serve niche audiences. This case study of a Spanish language radio newscast examines student-reported learning and content outcomes, to demonstrate the value of this type of experiential learning about niche audiences. Among the findings, students reported a heightened sense of awareness of topics that are relevant and suitable for their niche audience, and commented on the experiences or tools that best helped them to understand their audience and how to best serve these listeners.
Absorption, Metabolism, and Excretion of [14C]‐Tivozanib, a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Healthy Male Participants: A Phase I, Open‐Label, Mass‐Balance Study
Authors: Cotreau Monette M. , Hale Christine L. , Jacobson Lindsey , Oelke Claudine S. , Strahs Andrew L. , Kochan Robert G. , Sanga Madhu , Slichenmyer William , Vargo Dennis L.
Published: June 2012

Objective: To evaluate the absorption, metabolism, and excretion of tivozanib, a new investigational drug for renal cell carcinoma and solid malignancies. Methods: Eight healthy male participants received a single 1.5‐mg (˜160 μCi) dose of oral [14C]‐tivozanib. Whole blood, serum, urine, and feces were evaluated up to 28 days postdose for pharmacokinetics, radioanalysis, and metabolites. Adverse events were recorded throughout the study. Results: [14C]‐tivozanib concentration peaked at 10.9 ± 5.84 hours. The mean serum half‐life for [14C]‐tivozanib was 89.3 ± 23.5 hours. The maximum concentration and area under the curve for [14C]‐tivozanib were 12.1 ± 5.67 ng/mL and 1084 ± 417.0 ng·h/mL, respectively. Mean recovery of total radioactivity was 91.0% ± 11.0%; 79.3% ± 8.82% of the radioactivity was recovered in feces both as unchanged tivozanib and metabolites. In the urine, 11.8% ± 4.59% was recovered only as metabolites. No unchanged tivozanib was found in the urine. Conclusion: Tivozanib had a long half‐life with no major circulating metabolite, was well tolerated as a single dose, and was primarily eliminated via feces with no unchanged tivozanib found in urine. These pharmacokinetic data of [14C]‐tivozanib are consistent with previous studies of unlabeled tivozanib.
A Single‐Dose Bioequivalence and Food Effect Study With Aprepitant and Fosaprepitant Dimeglumine in Healthy Young Adult Subjects
Authors: Shadle Craig R. , Murphy M. Gail , Liu Yang , Ho Maureen , Tatosian Daniel , Li Susie (Xiujiang) , Blum Robert A.
Published: June 2012

Fosaprepitant dimeglumine, a lyophilized prodrug, is rapidly converted to aprepitant, a substance P/neurokinin 1 (NK1) receptor antagonist. Intravenous (IV) fosaprepitant and oral aprepitant are used in combination with other antiemetics to prevent chemotherapy‐induced nausea and vomiting. This randomized, phase 1 study was designed to assess the aprepitant area under the curve (AUC0‐∞) equivalence of a single, oral 165‐mg or 185‐mg dose of aprepitant to a single 150‐mg fosaprepitant IV dose infused over 20 minutes, and to evaluate the effect of food on the bioavailability of the oral 165‐mg and 185‐mg aprepitant doses. Plasma samples were analyzed for aprepitant, and linear mixed‐effects models were applied to natural log‐transformed aprepitant AUC data. A 2 one‐sided tests procedure was used to evaluate bioequivalence; the adjusted P values for the AUC0‐∞ of both oral doses versus the IV dose were < .05, supporting the hypothesis that each single, oral dose of aprepitant is equivalent to the AUC0‐∞ of a single IV infusion of fosaprepitant. Food effect results suggest that dose adjustment would not be necessary with a single oral dose of aprepitant. Single‐dose administration of oral 165 mg and 185 mg aprepitant and IV 150 mg fosaprepitant was generally well tolerated.
Too low to measure, infectious nonetheless
Authors: Dustin Lynn B.
Published: June 2012

In this issue of Blood, Busch and colleagues examine the risk of hepatitis C virus (HCV) transmission by plasma collected before HCV is detectable by licensed clinical assays.1
Dynamics based alignment of proteins: an alternative approach to quantify dynamic similarity
Authors: Münz Márton , Lyngsø Rune , Hein Jotun , Biggin Philip C
Published: June 2012

Background

The dynamic motions of many proteins are central to their function. It therefore follows that the dynamic requirements of a protein are evolutionary constrained. In order to assess and quantify this, one needs to compare the dynamic motions of different proteins. Comparing the dynamics of distinct proteins may also provide insight into how protein motions are modified by variations in sequence and, consequently, by structure. The optimal way of comparing complex molecular motions is, however, far from trivial. The majority of comparative molecular dynamics studies performed to date relied upon prior sequence or structural alignment to define which residues were equivalent in 3-dimensional space.

Results

Here we discuss an alternative methodology for comparative molecular dynamics that does not require any prior alignment information. We show it is possible to align proteins based solely on their dynamics and that we can use these dynamics-based alignments to quantify the dynamic similarity of proteins. Our method was tested on 10 representative members of the PDZ domain family.

Conclusions

As a result of creating pair-wise dynamics-based alignments of PDZ domains, we have found evolutionarily conserved patterns in their backbone dynamics. The dynamic similarity of PDZ domains is highly correlated with their structural similarity as calculated with Dali. However, significant differences in their dynamics can be detected indicating that sequence has a more refined role to play in protein dynamics than just dictating the overall fold. We suggest that the method should be generally applicable.
MLPAinter for MLPA interpretation: an integrated approach for the analysis, visualisation and data management of Multiplex Ligation-dependent Probe Amplification
Authors: van Eijk Ronald , Eilers Paul HC , Natté Remco , Cleton-Jansen Anne-Marie , Morreau Hans , van Wezel Tom , Oosting Jan
Published: June 2012

Background

Multiplex Ligation-Dependent Probe Amplification (MLPA) is an application that can be used for the detection of multiple chromosomal aberrations in a single experiment. In one reaction, up to 50 different genomic sequences can be analysed. For a reliable work-flow, tools are needed for administrative support, data management, normalisation, visualisation, reporting and interpretation.

Results

Here, we developed a data management system, MLPAInter for MLPA interpretation, that is windows executable and has a stand-alone database for monitoring and interpreting the MLPA data stream that is generated from the experimental setup to analysis, quality control and visualisation. A statistical approach is applied for the normalisation and analysis of large series of MLPA traces, making use of multiple control samples and internal controls.

Conclusions

MLPAinter visualises MLPA data in plots with information about sample replicates, normalisation settings, and sample characteristics. This integrated approach helps in the automated handling of large series of MLPA data and guarantees a quick and streamlined dataflow from the beginning of an experiment to an authorised report.
Detecting sequence dependent transcriptional pauses from RNA and protein number time series
Authors: Emmert-Streib Frank , Häkkinen Antti , Ribeiro Andre S
Published: June 2012

Background

Evidence suggests that in prokaryotes sequence-dependent transcriptional pauses affect the dynamics of transcription and translation, as well as of small genetic circuits. So far, a few pause-prone sequences have been identified from in vitro measurements of transcription elongation kinetics.

Results

Using a stochastic model of gene expression at the nucleotide and codon levels with realistic parameter values, we investigate three different but related questions and present statistical methods for their analysis. First, we show that information from in vivo RNA and protein temporal numbers is sufficient to discriminate between models with and without a pause site in their coding sequence. Second, we demonstrate that it is possible to separate a large variety of models from each other with pauses of various durations and locations in the template by means of a hierarchical clustering and arandom forestclassifier. Third, we introduce anapproximate likelihood functionthat allows to estimate the location of a pause site.

Conclusions

This method can aid in detecting unknown pause-prone sequences from temporal measurements of RNA and protein numbers at a genome-wide scale and thus elucidate possible roles that these sequences play in the dynamics of genetic networks and phenotype.
Muscle transcriptomic profiles in pigs with divergent phenotypes for fatness traits
Authors: Cánovas Angela , Quintanilla Raquel , Amills Marcel , Pena Ramona N
Published: June 2012

Background

Selection for increasing intramuscular fat content would definitively improve the palatability and juiciness of pig meat as well as the sensorial and organoleptic properties of cured products. However, evidences obtained in human and model organisms suggest that high levels of intramuscular fat might alter muscle lipid and carbohydrate metabolism. We have analysed this issue by determining the transcriptomic profiles of Duroc pigs with divergent phenotypes for 13 fatness traits. The strong aptitude of Duroc pigs to have high levels of intramuscular fat makes them a valuable model to analyse the mechanisms that regulate muscle lipid metabolism, an issue with evident implications in the elucidation of the genetic basis of human metabolic diseases such as obesity and insulin resistance.

Results

Muscle gene expression profiles of 68 Duroc pigs belonging to two groups (HIGH and LOW) with extreme phenotypes for lipid deposition and composition traits have been analysed. Microarray and quantitative PCR analysis showed that genes related to fatty acid uptake, lipogenesis and triacylglycerol synthesis were upregulated in the muscle tissue of HIGH pigs, which are fatter and have higher amounts of intramuscular fat than their LOW counterparts. Paradoxically, lipolytic genes also showed increased mRNA levels in the HIGH group suggesting the existence of a cycle where triacylglycerols are continuously synthesized and degraded. Several genes related to the insulin-signalling pathway, that is usually impaired in obese humans, were also upregulated. Finally, genes related to antigen-processing and presentation were downregulated in the HIGH group.

Conclusion

Our data suggest that selection for increasing intramuscular fat content in pigs would lead to a shift but not a disruption of the metabolic homeostasis of muscle cells. Future studies on the post-translational changes affecting protein activity or expression as well as information about protein location within the cell would be needed to to elucidate the effects of lipid deposition on muscle metabolism in pigs.