bluuebunny/crossref_metadata_2025 huggingface dataset:
θ13, μτ SYMMETRY BREAKING AND NEUTRINO YUKAWA TEXTURES
Authors: ADHIKARY BISWAJIT , GHOSAL AMBAR , ROY PROBIR
Published: September 2013

Within the type-I seesaw and in the basis where charged lepton and heavy neutrino mass matrices are real and diagonal, μτ symmetric four and three zero neutrino Yukawa textures are perturbed by lowest order μτ symmetry breaking terms. These perturbations are taken to be the most general ones for those textures. For quite small values of those symmetry breaking parameters, permitting a lowest order analysis, current best-fit ranges of neutrino mass squared differences and mixing angles are shown to be accommodable, including a value of θ13 in the observed range, provided all the light neutrinos have an inverted mass ordering.
ON EXPONENTIAL MODIFIED GRAVITY
Authors: KRUGLOV S. I.
Published: September 2013

A modified theory of gravity with the function F(R) = R exp (αR) instead of Ricci scalar R in the Einstein–Hilbert action is considered and analyzed. The action of the model is converted into Einstein–Hilbert action at small value of the parameter α. From local tests we obtain a bound on the parameter α ≤ 10-6 cm 2. The Jordan and Einstein frames are investigated and the potential of the scalar field in Einstein's frame is found. The mass of a scalar degree of freedom as a function of curvature is obtained. The static solutions of the model are found corresponding to the Schwarzschild–de Sitter space. We show that the de Sitter space is unstable but a solution with zero curvature is stable. The cosmological parameters of the model are calculated. It was demonstrated that the model passes the matter stability test.
ASYMPTOTIC SHAPES OF SHOCK CURVES FOR SOME CRITICAL CASES
Authors: LI TIANHONG , LI XING
Published: September 2013

We consider the scalar conservation law with convex flux. When the antiderivative Φ of the initial data satisfies Φ(∞) > inf y∈ℝΦ(y), Lax obtained that asymptotic shapes of shock curves at the far ends are [Formula: see text] with some constant C. In this paper, we consider the critical case when Φ(∞) = inf y∈ℝΦ(y), and show that asymptotic shapes of shock curves are [Formula: see text] instead of [Formula: see text]. We give the formula for asymptotic curves, and provide examples showing rich phenomena of the critical case.
R 2 and the Economy
Authors: Morck Randall , Yeung Bernard , Yu Wayne
Published: September 2013

The characterization of firm-specific return volatility as the intensity with which firm-specific events occur reconciles many seemingly discordant results. A functionally efficient stock market allocates capital to its highest value uses, which often amounts to financing Schumpeterian creative destruction, wherein creative winner firms outpace destroyed losers, who could be the previous year’s winners. This rise in firm-specific fundamentals volatility elevates firm-specific return volatility in a sufficiently informationally efficient stock market. These linkages are interconnected feedback loops rather than unidirectional chains of causality.
The Fluid Mechanics of Carbon Dioxide Sequestration
Authors: Huppert Herbert E. , Neufeld Jerome A.
Published: September 2013

Humans are faced with a potentially disastrous global problem owing to the current emission of 32 gigatonnes of carbon dioxide (CO2) annually into the atmosphere. A possible way to mitigate the effects is to store CO2in large porous reservoirs within the Earth. Fluid mechanics plays a key role in determining both the feasibility and risks involved in this geological sequestration. We review current research efforts looking at the propagation of CO2within the subsurface, the possible rates of leakage, the mechanisms that act to stably trap CO2, and the geomechanical response of the crust to large-scale CO2injection. We conclude with an outline for future research.
The Druggable Genome: Evaluation of Drug Targets in Clinical Trials Suggests Major Shifts in Molecular Class and Indication
Authors: Rask-Andersen Mathias , Masuram Surendar , Schiöth Helgi B.
Published: September 2013

The largest innovations within pharmaceutical development come through new compounds that have unique and novel modes of action. These innovations commonly involve expanding the protein space targeted by pharmaceutical agents. At present, information about drugs and drug targets is available online via public databases such as DrugBank and the Therapeutic Targets Database. However, this information is biased, understandably so, toward established drugs and drug-target interactions. To gain a better overview of the drug-targeted portion of the human proteome and the directions of current drug development, we developed a data set of clinical trial drug-target interactions based on CenterWatch's Drugs in Clinical Trials Database, one of the largest databases of its kind. Our curation identified 475 potentially novel clinical trial drug targets. This review aims to identify trends in drug development based on the potentially novel targets currently being explored in clinical trials.
The effect of CSE gene deletion in caerulein-induced acute pancreatitis in the mouse
Authors: Ang Abel D. , Rivers-Auty Jack , Hegde Akhil , Ishii Isao , Bhatia Madhav
Published: September 2013

Hydrogen sulfide (H2S) has been reported to be involved in the signaling of the inflammatory response; however, there are differing views as to whether it is pro- or anti-inflammatory. In this study, we sought to determine whether endogenously synthesized H2S via cystathionine-γ-lyase (CSE) plays a pro- or anti-inflammatory role in caerulein-induced pancreatitis. To investigate this, we used mice genetically deficient in CSE to elucidate the function of CSE in caerulein-induced acute pancreatitis. We compared the inflammatory response and tissue damage of wild-type (WT) and CSE knockout (KO) mice following 10 hourly administrations of 50 μg/kg caerulein or saline control. From this, we found that the CSE KO mice showed significantly less local pancreatic damage as well as acute pancreatitis-associated lung injury compared with the WT mice. There were also lower levels of pancreatic eicosanoid and cytokines, as well as reduced acinar cell NF-κB activation in the CSE KO mice compared with WT mice. Additionally, in WT mice, there was a greater level of pancreatic CSE expression and sulfide-synthesizing activity in caerulein-induced pancreatitis compared with the saline control. When comparing the two saline-treated control groups, we noted that the CSE KO mice showed significantly less pancreatic H2S-synthesizing activity relative to the WT mice. These results indicate that endogenous H2S generated by CSE plays a key proinflammatory role via NF-κB activation in caerulein-induced pancreatitis, and its genetic deletion affords significant protection against acute pancreatitis and associated lung injury.
Degradation of cIAPs contributes to hepatocyte lipoapoptosis
Authors: Akazawa Yuko , Guicciardi Maria Eugenia , Cazanave Sophie C. , Bronk Steven F. , Werneburg Nathan W. , Kakisaka Keisuke , Nakao Kazuhiko , Gores Gregory J.
Published: September 2013

Hepatocyte apoptosis is a hallmark of nonalcoholic steatohepatitis. We have previously observed that the saturated free fatty acids (FFAs) induce hepatocyte apoptosis in part via a death receptor 5 (DR5)-mediated signaling pathway. Cellular inhibitor of apoptosis protein 1 and 2 (cIAP-1 and cIAP-2) proteins are potent inhibitors of death receptor-mediated apoptosis. However, the role of the cIAPs in FFA-mediated hepatocyte apoptosis is unexplored. Our aim was to determine whether cIAPs are dysregulated during hepatocyte lipoapoptosis. cIAP proteins underwent rapid cellular elimination following treatment with the saturated FFAs palmitate (PA) and stearate. In contrast, PA did not decrease cIAP-1 and cIAP-2 mRNA expression in the cells. Degradation of cIAPs was dependent on their E3-ligase activity, suggesting that cIAPs undergo autoubiquitination that leads to proteasomal degradation. Huh-7 cells stably expressing shRNA targeting cIAP-1, but not cIAP-2, displayed enhanced sensitivity to PA-mediated apoptosis. Incubation with the SMAC mimetic JP1584, which induces rapid degradation of cIAPs, also enhanced PA-mediated apoptosis. Hepatocytes isolated from DR5 knockout mice exhibited reduced apoptosis following treatment with PA plus JP1584, implying that degradation of cIAPs sensitizes to DR5-mediated cell death pathways. A decrease of cIAP-1 was also observed in tissue from patients with nonalcoholic steatohepatitis compared with normal obese subjects. Collectively, these results implicate proteasomal degradation of cIAPs by FFA as a mechanism contributing to hepatocyte lipoapoptosis.
Lysyl oxidase in colorectal cancer
Authors: Cox Thomas R. , Erler Janine T.
Published: September 2013

Colorectal cancer is the third most prevalent form of cancer worldwide and fourth-leading cause of cancer-related mortality, leading to ∼600,000 deaths annually, predominantly affecting the developed world. Lysyl oxidase is a secreted, extracellular matrix-modifying enzyme previously suggested to act as a tumor suppressor in colorectal cancer. However, emerging evidence has rapidly implicated lysyl oxidase in promoting metastasis of solid tumors and in particular colorectal cancer at multiple stages, affecting tumor cell proliferation, invasion, and angiogenesis. This emerging research has stimulated significant interest in lysyl oxidase as a strong candidate for developing and deploying inhibitors as functional efficacious cancer therapeutics. In this review, we discuss the rapidly expanding body of knowledge concerning lysyl oxidase in solid tumor progression, highlighting recent advancements in the field of colorectal cancer.
The effects of osteoarthritis and age on skeletal muscle strength, Na+-K+-ATPase content, gene and isoform expression
Authors: Perry Ben D. , Levinger Pazit , Serpiello Fabio R. , Caldow Marissa K. , Cameron-Smith David , Bartlett John R. , Feller Julian A. , Bergman Neil R. , Levinger Itamar , McKenna Michael J.
Published: September 2013

Knee osteoarthritis (OA) is a debilitating disorder prevalent in older populations that is accompanied by declines in muscle mass, strength, and physical activity. In skeletal muscle, the Na+-K+ pump (NKA) is pivotal in ion homeostasis and excitability and is modulated by disuse and exercise training. This study examined the effects of OA and aging on muscle NKA in 36 older adults (range 55–81 yr), including 19 with OA (69.9 ± 6.5 yr, mean ± SD) and 17 asymptomatic controls (CON, 66.8 ± 6.4 yr). Participants completed knee extensor strength testing and a physical activity questionnaire. A vastus lateralis muscle biopsy was analyzed for NKA content ([3H]ouabain binding sites), α1–3- and β1–3-isoform protein abundance (immunoblotting), and mRNA (real-time RT-PCR). The association between age and NKA content was investigated within the OA and CON groups and in pooled data. The NKA content was also contrasted between subgroups below and above the median age of 68.5 yr. OA had lower strength (−40.8%, P = 0.005), but higher NKA α2- (∼34%, P = 0.006) and α3-protein (100%, P = 0.016) abundance than CON and performed more incidental physical activity ( P = 0.035). No differences were found between groups for NKA content, abundance of other NKA isoforms, or gene expression. There was a negative correlation between age and NKA content within OA ( r = −0.63, P = 0.03) and with both groups combined ( r = −0.47, P = 0.038). The NKA content was 25.5% lower in the older (69–81 yr) than in the younger (55–68 yr) subgroup. Hence older age, but not knee OA, was related to lowered muscle NKA content in older adults.
Effect of Hydrogen Content in Intrinsic a-Si:H on Performances of Heterojunction Solar Cells
Authors: Cho Yun-Shao , Hsu Chia-Hsun , Lien Shui-Yang , Wuu Dong-Sing , Hsieh In-Cha
Published: September 2013

Influences of hydrogen content in intrinsic hydrogenated amorphous silicon (i-a-Si:H) on performances of heterojunction (HJ) solar cells are investigated. The simulation result shows that in the range of 0–18% of the i-layer hydrogen content, solar cells with higher i-layer hydrogen content can have higher degree of dangling bond passivation on single crystalline silicon (c-Si) surface. In addition, the experimental result shows that HJ solar cells with a low hydrogen content have a poor a-Si:H/c-Si interface. The deteriorate interface is assumed to be attributed to (i) voids created by insufficiently passivated c-Si surface dangling bonds, (ii) voids formed by SiH2clusters, and (iii) Si particles caused by gas phase particle formation in silane plasma. The proposed assumption is well supported and explained from the plasma point of view using optical emission spectroscopy.
Electroacupuncture Stimulation at CV12 Inhibits Gastric Motility via TRPV1 Receptor
Authors: Yu Zhi , Cao Xin , Xia Youbing , Ren Binbin , Feng Hong , Wang Yali , Jiang Jingfeng , Xu Bin
Published: September 2013

Gastric dysmotility is one of the major pathophysiological factors in functional gastrointestinal disorders. Acupuncture, as one of the alternative approaches, is efficacious in the treatment of gastrointestinal motility disorders; however, the mechanism underlying its action is unclear. In the present study, we used both capsazepine, a TRPV1 antagonist, and TRPV1 knockout mice. Animals were divided into wild-type group (WT), capsazepine injection group (CZP, 0.5 mg/kg, i.p.), and TRPV1 knockout mice group (TRPV1−/−). Each of these three groups was divided into three subgroups, which were subjected to EA stimulation at acupoint Zhongwan (CV12) at a different intensity (1, 2, or 4 mA). We demonstrated that electroacupuncture at Zhongwan (CV12) markedly inhibited gastric motility at 2 and 4 mA in an intensity-dependent manner in wild-type mice. The inhibitory effect was also observed in capsazepine-injected and TRPV1−/−mice but was no longer intensity dependent, indicating that TRPV1 is partially involved in the electroacupuncture-mediated modulation of gastric motility.
Feasibility Assessment of Thermal Management System for Green Power Sources Using Nanofluid
Authors: Hung Yi-Hsuan , Chen Jyun-Hong , Teng Tun-Ping
Published: September 2013

A thermal management system using alumina (Al2O3)/water as the nanofluid for green power sources was experimentally assessed in this paper. Basic thermal principles and formulas were utilized to evaluate the performance of an air‐cooled heat exchanger. The Al2O3/water nanofluid was produced at the concentrations of 0.5, 1.0, and 1.5 wt.%. The testing conditions of this experiments were above three concentrations, five coolant flow rates (0.8, 1.2, 1.6, 2.0, and 2.4 L/min.), and three heating powers (50, 100, and 150 W). Firstly, basic properties of nanoparticles were analyzed. Fundamental relationships of the Al2O3/water nanofluid with respect to temperatures and concentrations were measured such as: viscosity, density, and specific heat. Next, an innovative concept named efficiency factor (EF) was proposed to quantitatively evaluate the thermal system performance. The enhancement of thermal system performance compared with distilled water was then defined as an efficiency factor ratio (REF). The experimental results demonstrated that the efficiency factor ratios were optimal at low flow rate (0.8 L/min.) and low concentration (0.5%). Values of REF were all below 1.0 at high flow rates (1.2–2.4 L/min.). This research points out the direction of optimizing a thermal management system for green energy sources in the near future.
Exercise Ameliorates Renal Cell Apoptosis in Chronic Kidney Disease by Intervening in the Intrinsic and the Extrinsic Apoptotic Pathways in a Rat Model
Authors: Chen Kuan-Chou , Peng Chiung-Chi , Hsieh Chiu-Lan , Peng Robert Y.
Published: September 2013

We hypothesized that doxorubicin (DR) induced chronic kidney disease (CKD) could trigger the intrinsic and the extrinsic renal cell apoptotic pathways, while treadmill exercise could help prevent adverse effects. Male Sprague-Dawley rats were subjected to treadmill running exercise at a speed of 30 m/min, 30 or 60 min/day, 3 times per week, for a total period of 11 weeks. The physiological and biochemical parameters were seen substantially improved (DR-CKD control, 30 min, 60 min exercise): the ratio of kidney weight/body weight (0.89, 0.74, and 0.72); the WBC (1.35, 1.08, and 1.42 × 104 cells/μL); RBC (5.30, 6.38, and 6.26 × 106 cells/μL); the platelet count (15.1, 12.8, and 11.3 × 105/μL); serum cholesterol (659, 360, and 75 mg/dL); serum triglyceride (542, 263, and 211 mg/dL); BUN (37, 25, and 22 mg/dL). Bcl-2 and intramitochondrial cytochromecwere upregulated, while the levels of Bax, SOD, MDA, cleaved caspases 9, 3, 8, 12, and calpain were all downregulated in DRCKD groups with exercise. CHOP (GADD153) and GRP78 were totally unaffected. FAS (CD95) was only slightly suppressed in the 60 min exercise DRCKD group. Conclusively, exercise can ameliorate CKD through the regulation of the intrinsic and extrinsic apoptosis pathways. The 60 min exercise yields more beneficial effect than the 30 min counterpart.
Systemic and Nonrenal Adverse Effects Occurring in Renal Transplant Patients Treated with mTOR Inhibitors
Authors: Zaza Gianluigi , Tomei Paola , Ria Paolo , Granata Simona , Boschiero Luigino , Lupo Antonio
Published: September 2013

The mammalian target of rapamycin inhibitors (mTOR-I), sirolimus and everolimus, are immunosuppressive drugs largely used in renal transplantation. The main mechanism of action of these drugs is the inhibition of the mammalian target of rapamycin (mTOR), a regulatory protein kinase involved in lymphocyte proliferation. Additionally, the inhibition of the crosstalk among mTORC1, mTORC2, and PI3K confers the antineoplastic activities of these drugs. Because of their specific pharmacological characteristics and their relative lack of nephrotoxicity, these inhibitors are valid option to calcineurine inhibitors (CNIs) for maintenance immunosuppression in renal transplant recipients with chronic allograft nephropathy. However, as other immunosuppressive drugs, mTOR-I may induce the development of several adverse effects that need to be early recognized and treated to avoid severe illness in renal transplant patients. In particular, mTOR-I may induce systemic nonnephrological side effects including pulmonary toxicity, hematological disorders, dysmetabolism, lymphedema, stomatitis, cutaneous adverse effects, and fertility/gonadic toxicity. Although most of the adverse effects are dose related, it is extremely important for clinicians to early recognize them in order to reduce dosage or discontinue mTOR-I treatment avoiding the onset and development of severe clinical complications.
Nonlinear Super Integrable Couplings of Super Broer-Kaup-Kupershmidt Hierarchy and Its Super Hamiltonian Structures
Authors: Tao Sixing , Xia Tiecheng
Published: September 2013

Nonlinear integrable couplings of super Broer-Kaup-Kupershmidt hierarchy based upon an enlarged matrix Lie super algebra were constructed. Then its super Hamiltonian structures were established by using super trace identity, and the conserved functionals were proved to be in involution in pairs under the defined Poisson bracket. As its reduction, nonlinear integrable couplings of the classical integrable hierarchy were obtained.
Using the Delphi Approach to Identify Priority Areas for Health Visiting Practice in an Area of Deprivation
Authors: Bryar Rosamund , Anto-Awuakye Sandra , Christie Janice , Davis Claire , Plumb Karen
Published: September 2013

Families with children living in areas of high deprivation face multiple health and social challenges, and this high level of need has impacts on the work of health practitioners working in such areas. All families in the UK with children under five years have access to health visiting services, and health visitors have a key role in mitigating the effects of deprivation by addressing health needs through evidence based practice. This paper reports the first stage of a project in Tower Hamlets, London, an area of significant deprivation, which aims to develop an evidence-based toolkit to support health visitors in their practice with families. The first stage used a modified Delphi process to identify the priority health needs of families in the area between June and July 2012. The three-stage Delphi process involved 25 people: four health visitors, four other members of the health visiting service, and 17 representatives of other services working with families. A focus group event was followed by a second event where individuals completed a questionnaire ranking the 27 priorities identified in the first event. The consultation process concluded with participants completing a second questionnaire, by email, confirming or changing their prioritisation of the topics.
Optimization of Dairy Sludge for Growth ofRhizobiumCells
Authors: Singh Ashok Kumar , Singh Gauri , Gautam Digvijay , Bedi Manjinder Kaur
Published: September 2013

In this study dairy sludge was evaluated as an alternative cultivation medium forRhizobium. Growth of bacterial strains at different concentrations of Dairy sludge was monitored. Maximum growth of all strains was observed at 60% Dairy sludge concentration. At 60% optical density (OD) values are 0.804 forRhizobium trifolii(MTCC905), 0.825 forRhizobium trifolii(MTCC906), and 0.793 forRhizobium meliloti(MTCC100). Growth pattern of strains was observed at 60% Dairy sludge along with different synthetic media (tryptone yeast,Rhizobiumminimal medium and yeast extract mannitol). Growth in 60% Dairy sludge was found to be superior to standard media used forRhizobium. Media were optimized using 60% dairy sludge along with different concentrations of yeast extract (1–7 g/L) and mannitol (7–13 g/L) in terms of optical density at different time intervals, that is, 24, 48 and 72 hours. Maximum growth was observed in 6 g/L of yeast extract and 12 g/L of mannitol at 48-hour incubation period in all strains. The important environmental parameters such as pH were optimized using 60% dairy sludge, 60% dairy sludge +6 g/L yeast extract, and 60% dairy sludge +12 g/L mannitol. The maximum growth of all strains was found at pH 7.0. The present study recommends the use of 60% dairy sludge as a suitable growth medum for inoculant production.
PLA2R1 Mediates Tumor Suppression by Activating JAK2
Authors: Vindrieux David , Augert Arnaud , Girard Christophe A. , Gitenay Delphine , Lallet-Daher Helene , Wiel Clotilde , Le Calvé Benjamin , Gras Baptiste , Ferrand Mylène , Verbeke Stéphanie , de Launoit Yvan , Leroy Xavier , Puisieux Alain , Aubert Sébastien , Perrais Michael , Gelb Michael , Simonnet Hélène , Lambeau Gérard , Bernard David
Published: September 2013

Little is known about the physiological role of the phospholipase A2 receptor (PLA2R1). PLA2R1 has been described as regulating the replicative senescence, a telomerase-dependent proliferation arrest. The downstream PLA2R1 signaling and its role in cancer are currently unknown. Senescence induction in response to activated oncogenes is a failsafe program of tumor suppression that must be bypassed for tumorigenesis. We now present evidence that PLA2R1 functions in vitro as a tumor suppressor, the depletion of which is sufficient to escape oncogene-induced senescence (OIS), thereby facilitating oncogenic cell transformation. Furthermore, mice that are genetically deficient in PLA2R1 display increased sensitivity to RAS-induced tumorigenesis by facilitating OIS escape, highlighting its physiological role as a tumor suppressor. Unexpectedly, PLA2R1 activated JAK2 and its effector signaling, with PLA2R1-mediated inhibition of cell transformation largely reverted in JAK2-depleted cells. This finding was unexpected as the JAK2 pathway has been associated mainly with protumoral functions and several inhibitors are currently in clinical trials. Taken together, our findings uncover an unanticipated tumor suppressive role for PLA2R1 that is mediated by targeting downstream JAK2 effector signaling. Cancer Res; 73(20); 6334–45. ©2013 AACR.
c-Kit Is Suppressed in Human Colon Cancer Tissue and Contributes to L1-Mediated Metastasis
Authors: Gavert Nancy , Shvab Anna , Sheffer Michal , Ben-Shmuel Amir , Haase Gal , Bakos Eszter , Domany Eytan , Ben-Ze'ev Avri
Published: September 2013

The transmembrane neural cell adhesion receptor L1 is a Wnt/β-catenin target gene expressed in many tumor types. In human colorectal cancer, L1 localizes preferentially to the invasive front of tumors and when overexpressed in colorectal cancer cells, it facilitates their metastasis to the liver. In this study, we investigated genes that are regulated in human colorectal cancer and by the L1-NF-κB pathway that has been implicated in liver metastasis. c-Kit was the most highly suppressed gene in both colorectal cancer tissue and the L1-NF-κB pathway. c-Kit suppression that resulted from L1-mediated signaling relied upon NF-κB, which directly inhibited the transcription of SP1, a major activator of the c-Kit gene promoter. Reconstituting c-Kit expression in L1-transfected cells blocked the biological effects conferred by L1 overexpression in driving motility and liver metastasis. We found that c-Kit expression in colorectal cancer cells is associated with a more pronounced epithelial morphology, along with increased expression of E-cadherin and decreased expression of Slug. Although c-Kit overexpression inhibited the motility and metastasis of L1-expressing colorectal cancer cells, it enhanced colorectal cancer cell proliferation and tumorigenesis, arguing that separate pathways mediate tumorigenicity and metastasis by c-Kit. Our findings provide insights into how colorectal cancer metastasizes to the liver, the most common site of dissemination in this cancer. Cancer Res; 73(18); 5754–63. ©2013 AACR.
Inhibition of mTOR Pathway Sensitizes Acute Myeloid Leukemia Cells to Aurora Inhibitors by Suppression of Glycolytic Metabolism
Authors: Liu Ling-Ling , Long Zi-Jie , Wang Le-Xun , Zheng Fei-Meng , Fang Zhi-Gang , Yan Min , Xu Dong-Fan , Chen Jia-Jie , Wang Shao-Wu , Lin Dong-Jun , Liu Quentin
Published: September 2013

Aurora kinases are overexpressed in large numbers of tumors and considered as potential therapeutic targets. In this study, we found that the Aurora kinases inhibitors MK-0457 (MK) and ZM447439 (ZM) induced polyploidization in acute myeloid leukemia (AML) cell lines. The level of glycolytic metabolism was significantly increased in the polyploidy cells, which were sensitive to glycolysis inhibitor 2-deoxy-D-glucose (2DG), suggesting that polyploidy cells might be eliminated by metabolism deprivation. Indeed, inhibition of mTOR pathway by mTOR inhibitors (rapamycin and PP242) or 2DG promoted not only apoptosis but also autophagy in the polyploidy cells induced by Aurora inhibitors. Mechanically, PP242 or2DGdecreased the level of glucose uptake and lactate production in polyploidy cells as well as the expression of p62/SQSTM1. Moreover, knockdown of p62/SQSTM1 sensitized cells to the Aurora inhibitor whereas overexpression of p62/SQSTM1 reduced drug efficacy. Thus, our results revealed that inhibition of mTOR pathway decreased the glycolytic metabolism of the polyploidy cells, and increased the efficacy of Aurora kinases inhibitors, providing a novel approach of combination treatment in AML. Mol Cancer Res; 11(11); 1326–36. ©2013 AACR.
Liver Complications in Inflammatory Bowel Diseases
Authors: Wieser V. , Gerner R. , Moschen A.R. , Tilg H.
Published: September 2013

Diseases of the liver and the biliary tract are commonly observed in patients with inflammatory bowel diseases (IBD). Besides primary sclerosing cholangitis (PSC), drug-induced hepatotoxicity and non-alcoholic fatty liver disease (NAFLD) are the most frequent liver complications in IBD. PSC is a chronic inflammatory and commonly progressive disorder of unknown etiology associated with fibrosis and stricture development in the intrahepatic and extrahepatic biliary tree. Interestingly, this form of liver disease is mainly associated with ulcerative colitis. Development of PSC is highly relevant for IBD patients as cholestasis-associated problems increase over time resulting in biliary strictures, cholangitis, cholangiocarcinoma and importantly these patients also have a higher risk to develop colon cancer. Another major aspect regarding IBD and liver disease refers to drug-induced hepatotoxicity. Clinically, most relevant is liver toxicity caused by immunosuppressants such as azathioprine. Azathioprine and its derivate 6-mercaptopurine can cause a spectrum of liver injuries ranging from asymptomatic elevated liver enzymes to cholestasis and nodular regenerative hyperplasia. The third common IBD-associated liver disease is NAFLD, and first studies suggest that NAFLD might appear in IBD patients independent of classical risk factors such as obesity or insulin resistance. Overall, liver complications are observed in 10-20% of IBD patients, and therefore physicians have to be familiar with these complications to improve and to optimize patient care.
Osteoarticular Manifestations: Specific Treatments and/or Treating Intestinal Disease?
Authors: De Vos M. , Van Praet L. , Elewaut D.
Published: September 2013

Osteoarticular manifestations in inflammatory bowel diseases (IBD) belong to the concept of spondyloarthritis (SpA) including an axial and peripheral SpA according to predominant symptoms (inflammatory back pain vs. peripheral arthritis and enthesopathy). Careful examination of sacroiliac joints on MRI plays a crucial role in the recognition of an early axial SpA in young patients with inflammatory back pain and spinal inflammation on MRI but without structural changes on radiography (non-rx SpA). In this early form of SpA, chronic gut inflammation was already found in about 30% of patients. Moreover, more pronounced bone marrow edema was found in patients with axial SpA and chronic gut inflammation. Identification of a therapeutic window in patients with early gut and spine inflammation is important since anti-TNF suppresses inflammation and seems to prevent evolution to structural changes. Shared genetic factors probably predispose to both diseases. Careful analysis of the effect of medication on gut and spine inflammation in SpA and IBD patients is recommended in order to find new therapeutic agents.
Internetbasierte Therapie nach Verlust eines Kindes in der Schwangerschaft - Einfluss sozialer Unterstützung auf die Verarbeitung des Verlusts
Authors: Klinitzke Grit , Dölemeyer Ruth , Steinig Jana , Wagner Birgit , Kersting Anette
Published: September 2013

Hintergrund: Der Verlust eines Kindes in der Schwangerschaft stellt für die betroffenen Eltern eine hohe psychische Belastung dar, die zu manifesten psychischen Erkrankungen führen kann. Verschiedene Studien haben gezeigt, dass die wahrgenommene soziale Unterstützung durch das Umfeld der Betroffenen nach einem pränatalen Kindsverlust mit geringerer prolongierter Trauersymptomatik einhergeht. Methode: Untersucht wurden 99 Eltern, die ihr Kind während der Schwangerschaft verloren hatten. Sie nahmen an einem 5-wöchigen internetbasierten Behandlungsprogramm zur Schreibtherapie teil, welches die 3 Phasen «Selbstkonfrontation», «kognitive Umstrukturierung» und «Social Sharing» beinhaltete. Neben allgemeiner psychischer Belastung (BSI), prolongierter Trauer (ICG) und traumatischem Stress (IES-R) wurde auch die soziale Unterstützung (BSSS) mit den Dimensionen «wahrgenommene Unterstützung» und «erhaltene Unterstützung» bzw. «Bedürfnis nach Unterstützung» und «Suche nach Unterstützung» sowohl zum Zeitpunkt vor der Behandlung als auch nach deren Abschluss erhoben. Ergebnisse: Während das Bedürfnis nach sozialer Unterstützung im Verlauf der Behandlung signifikant abnahm, erhöhten sich die Werte der anderen 3 Dimensionen sozialer Unterstützung signifikant. Die wahrgenommene und erhaltene soziale Unterstützung waren signifikant invers mit der allgemeinen psychischen Belastung und der prolongierten Trauer nach einem pränatalen Verlust assoziiert. Erhaltene Unterstützung und die Suche nach Unterstützung gingen mit der Verbesserung verschiedener Symptome nach der internetbasierten Behandlung einher. Schlussfolgerung: Die Ergebnisse weisen darauf hin, dass sowohl die erhaltene Unterstützung als auch die aktive Suche nach Unterstützung für die Wirksamkeit des internetbasierten Behandlungsprogramms für Betroffene nach einem Kindsverlust relevant sind. Zudem kann das hier vorgestellte internetbasierte Behandlungsangebot nach dem pränatalen Verlust eines Kindes eine gute Unterstützungsmöglichkeit darstellen und aktivierend bei der Suche nach Unterstützung wirken.
CTP Synthase 1, a Smooth Muscle–Sensitive Therapeutic Target for Effective Vascular Repair
Authors: Tang Rui , Cui Xiao-Bing , Wang Jia-Ning , Chen Shi-You
Published: September 2013

Objective—

Vascular remodeling as a result of smooth muscle cell (SMC) proliferation and neointima formation is a major medical challenge in cardiovascular intervention. However, antineointima drugs often indistinguishably block re-endothelialization, an essential step toward successful vascular repair, because of their nonspecific effect on endothelial cells (ECs). The objective of this study is to identify a therapeutic target that differentially regulates SMC and EC proliferation.

Approach and Results—

Using both rat balloon injury and mouse wire injury models, we identified CTP synthase 1 (CTPS1) as one of the potential targets that may be used for developing therapeutics for treating neointima-related disorders. CTPS1 was induced in proliferative SMCs in vitro and neointima SMCs in vivo. Blockade of CTPS1 expression by small hairpin RNA or activity by cyclopentenyl cytosine suppressed SMC proliferation and neointima formation. Surprisingly, cyclopentenyl cytosine had much less effect on EC proliferation. Of importance, blockade of CTPS1 in vivo sustained the re-endothelialization as a result of induction of CTP synthesis salvage pathway enzymes nucleoside-diphosphate kinase A and B in ECs. Diphosphate kinase B seemed to preserve EC proliferation via use of extracellular cytidine to synthesize CTP. Indeed, blockade of both CTPS1 and diphosphate kinase B suppressed EC proliferation in vitro and the re-endothelialization in vivo.

Conclusions—

Our study uncovered a fundamental difference in CTP biosynthesis between SMCs and ECs during vascular remodeling, which provided a novel strategy by using cyclopentenyl cytosine or other CTPS1 inhibitors to selectively block SMC proliferation without disturbing or even promoting re-endothelialization for effective vascular repair after injury.
Effects of Topography on Assessing Wind Farm Impacts Using MODIS Data
Authors: Zhou Liming , Tian Yuhong , Chen Haishan , Dai Yongjiu , Harris Ronald A.
Published: September 2013

This paper uses the empirical orthogonal function (EOF) analysis to decompose satellite-derived nighttime land surface temperature (LST) for the period of 2003–11 into spatial patterns of different scales and thus to identify whether (i) there is a pattern of LST change associated with the development of wind farms and (ii) the warming effect over wind farms reported previously is an artifact of varied surface topography. Spatial pattern and time series analysis methods are also used to supplement and compare with the EOF results. Two equal-sized regions with similar topography in west-central Texas are chosen to represent the wind farm region (WFR) and nonwind farm region (NWFR), respectively. Results indicate that the nighttime warming effect seen in the first mode (EOF1) in WFR very likely represents the wind farm impacts due to its spatial coupling with the wind turbines, which are generally built on topographic high ground. The time series associated with the EOF1 mode in WFR also shows a persistent upward trend over wind farms from 2003 to 2011, corresponding to the increase of operating wind turbines with time. Also, the wind farm pixels show a warming effect that differs statistically significantly from their upwind high-elevation pixels and their downwind nonwind farm pixels at similar elevations, and this warming effect decreases with elevation. In contrast, NWFR shows a decrease in LST with increasing surface elevation and no warming effects over high-elevation ridges, indicating that the presence of wind farms in WFR has changed the LST–elevation relationship shown in NWFR. The elevation impacts on Moderate Resolution Imaging Spectroradiometer (MODIS) LST, if any, are much smaller and statistically insignificant than the strong and persistent signal of wind farm impacts. These results provide further observational evidence of the warming effect of wind farms reported previously.
Response of the Wintertime Northern Hemisphere Atmospheric Circulation to Current and Projected Arctic Sea Ice Decline: A Numerical Study with CAM5
Authors: Peings Yannick , Magnusdottir Gudrun
Published: September 2013

The wintertime Northern Hemisphere (NH) atmospheric circulation response to current (2007–12) and projected (2080–99) Arctic sea ice decline is examined with the latest version of the Community Atmospheric Model (CAM5). The numerical experiments suggest that the current sea ice conditions force a remote atmospheric response in late winter that favors cold land surface temperatures over midlatitudes, as has been observed in recent years. Anomalous Rossby waves forced by the sea ice anomalies penetrate into the stratosphere in February and weaken the stratospheric polar vortex, resulting in negative anomalies of the northern annular mode (NAM) that propagate downward during the following weeks, especially over the North Pacific. The seasonality of the response is attributed to timing of the phasing between the forced and climatological waves. When sea ice concentration taken from projections of conditions at the end of the twenty-first century is prescribed to the model, negative anomalies of the NAM are visible in the troposphere, both in early and late winter. This response is mainly driven by the large warming of the lower troposphere over the Arctic, as little impact is found in the stratosphere in this experiment. As a result of the thermal expansion of the polar troposphere, the westerly flow is decelerated and a weak but statistically significant increase of the midlatitude meanders is identified. However, the thermodynamical response extends beyond the Arctic and offsets the dynamical effect, such that the stronger sea ice forcing has limited impact on the intensity of cold extremes over midlatitudes.
Large-Eddy Simulation of Deep-Cycle Turbulence in an Equatorial Undercurrent Model
Authors: Pham Hieu T. , Sarkar Sutanu , Winters Kraig B.
Published: September 2013

Dynamical processes leading to deep-cycle turbulence in the Equatorial Undercurrent (EUC) are investigated using a high-resolution large-eddy simulation (LES) model. Components of the model include a background flow similar to the observed EUC, a steady westward wind stress, and a diurnal surface buoyancy flux. An LES of a 3-night period shows the presence of narrowband isopycnal oscillations near the local buoyancy frequency N as well as nightly bursts of deep-cycle turbulence at depths well below the surface mixed layer, the two phenomena that have been widely noted in observations. The deep cycle of turbulence is initiated when the surface heating in the evening relaxes, allowing a region with enhanced shear and a gradient Richardson number Rig less than 0.2 to form below the surface mixed layer. The region with enhanced shear moves downward into the EUC and is accompanied by shear instabilities and bursts of turbulence. The dissipation rate during the turbulence bursts is elevated by up to three orders of magnitude. Each burst is preceded by westward-propagating oscillations having a frequency of 0.004–0.005 Hz and a wavelength of 314–960 m. The Rig that was marginally stable in this region decreases to less than 0.2 prior to the bursts. A downward turbulent flux of momentum increases the shear at depth and reduces Rig. Evolution of the deep-cycle turbulence includes Kelvin–Helmholtz-like billows as well as vortices that penetrate downward and are stretched by the EUC shear.
A Review and Practical Guide to In-Flight Calibration for Aircraft Turbulence Sensors
Authors: Drüe Clemens , Heinemann Günther
Published: September 2013

A large number of quantities have to be measured and processed to determine the atmospheric-state variables, which are the actual measurands, from aircraft-based measurements. A great part of the dependencies between these quantities depends on the aerodynamic state of the aircraft. Aircraft-based meteorological measurements, hence, require in-flight calibration. Most operators of research aircraft perform some kind of calibration, but the schemes used and the degree they are documented greatly vary. The flight maneuvers and calculation methods required, however, are published in a number of partly overlapping and partly contradictory publications. Some methods are only presented as a minor issue in publications mainly focused on atmospheric processes and are therefore hard to find. For an aircraft user, it is hence challenging to either perform or verify a calibration because of missing comprehensive guidance. This lack was stated on occasion of the in-flight calibration of the German research aircraft Polar5 carried out for the field experiment Investigation of Katabatic Winds and Polynyas during Summer (IKAPOS). In the present paper, a comprehensive review of the existing literature on this field and a practical guide to the wind calibration of a research aircraft to be used for turbulent flux measurements are given.
Skill of the MJO and Northern Hemisphere Blocking in GEFS Medium-Range Reforecasts
Authors: Hamill Thomas M. , Kiladis George N.
Published: September 2013

Forecast characteristics of Northern Hemisphere atmospheric blocking and the Madden–Julian oscillation (MJO) were diagnosed using an extensive time series (December–February 1985–2012) of daily medium-range ensemble reforecasts based on a version of the NCEP Global Ensemble Forecast System (GEFS).

For blocking, (i) interannual variability of analyzed blocking frequency was quite large, (ii) the GEFS slightly underforecasted blocking frequency at longer leads in the Euro-Atlantic sector, (iii) predictive skill of actual blocking was substantially smaller than its perfect-model skill, (iv) block onset and cessation were forecast less well than overall blocking frequency, (v) there was substantial variability of blocking skill between half-decadal periods, and (vi) the reliability of probabilistic blocking forecasts degraded with increasing lead time.

For the MJO, (i) forecasts of strong Indian Ocean MJOs propagated too slowly, especially the component associated with outgoing longwave radiation (OLR), that is, convection; (ii) tropical precipitation was greatly overforecast at early lead times; (iii) the ensemble predictions were biased and/or underdispersive, manifested in U-shaped rank histograms of MJO indices (magnitude forecasts were especially U shaped); (iv) MJO correlation skill was larger for its wind than for its OLR component, and was larger for the higher-amplitude MJO events; (v) there was some half-decadal variability in skill; and (vi) probabilistic skill of the MJO forecast was modest, and skill was larger when measured relative to climatology than when measured relative to a lagged persistence forecast.

For longer-lead forecasts, the GEFS demonstrated little ability to replicate the changes in blocking frequency due to a strong MJO that were noted in analyzed data.
A Longitudinal Study of the Implementation of the Corporate Governance Code in a Developing Country
Authors: Mahadeo Jyoti Devi , Soobaroyen Teerooven
Published: September 2013

This exploratory study investigates firms’ implementation of a new corporate governance code in Mauritius, a developing economy. The authors rely on annual report disclosures during a four-year period (2004-2007). The authors analyze the level of corporate engagement with the code’s requirements, including corporate social responsibility initiatives, relative to a 2004 (when the code was enacted) benchmark over the three subsequent years. The study contributes to the literature in two ways. First, it provides much needed evidence of longitudinal implementation within developing economies that exhibit, or have started to exhibit, a combination of ownership and control features found in more advanced economies and characterized in the literature as an “emerging governance” model. Second, the authors develop a more comprehensive assessment of implementation using a scoring system that combines trichotomous weighting of each governance component (as 1, 3, or 5) and trichotomous rating of implementation of each component (as 0, 0.5, or 1). The authors argue that this system is superior to the un-weighted, dichotomous approach typically used in the literature. The analysis of weighted assessment scores for reveals a significant implementation of the code initially after 2004; but implementation began to level off by 2007 well below maximum assignable scores. Detailed requirements regarding directors’ appraisal and training, remuneration policies and remuneration information appear to be ignored by companies through 2007. A correlation analysis of the corporate governance scores and firm-based measures (level and changes) shows that the association between these different variables fluctuates significantly over the implementation window.
Impacts of Residential Self-Selection and Built Environments on Children’s Walking-to-School Behaviors
Authors: Yu Chia-Yuan , Zhu Xuemei
Published: September 2013

Despite the growing effort to promote walking to school through environmental interventions, the corresponding impact of residential self-selection has not been examined. This study investigated how built environments, social factors, and personal factors, including self-selection of a close-to-child’s-school home and a walkable neighborhood, influenced walking-to-school behaviors. Parental survey data from 20 elementary schools in Austin, Texas, were analyzed using structural equation models. Significant factors included self-selection variables, parental education, car ownership, number of adults/children in the household, school bus availability, parental perceived home-to-school distance, and the presence of convenience stores, bus stops, and office buildings en route to school. The self-selection of a close-to-child’s-school home had a smaller effect on walking-to-school behaviors than parental perception of home-to-school distance. The self-selection of a walkable neighborhood was significant, while parental perception of their neighborhood’s walkability was insignificant. Future efforts to promote walking to school should include both environmental interventions and educational programs.
Undergraduates’ Ability to Recognize Correlational and Causal Language Before and After Explicit Instruction
Authors: Mueller Jon F. , Coon Heather M.
Published: September 2013

The ability to distinguish between correlational and causal claims is core knowledge for scientific literacy. News reports of scientific research prominently feature these claims. Thus, this knowledge has significant real-world application, and distinguishing among claims is critical to making sense of the reported research. We constructed an introductory psychology course with a series of brief exercises and assessments designed to improve students’ abilities to both understand the core concepts of correlation and causation and to apply their knowledge to real-world situations. Pre–post data on definitions and research in the news headlines revealed that students improved on both tasks by the end of the term.