bluuebunny/crossref_metadata_2025_split huggingface dataset:
NOS2 enhances KRAS‐induced lung carcinogenesis, inflammation and microRNA‐21 expression
Authors: Okayama Hirokazu , Saito Motonobu , Oue Naohide , Weiss Jonathan M. , Stauffer Jimmy , Takenoshita Seiichi , Wiltrout Robert H. , Hussain S. Perwez , Harris Curtis C. 
Published: May 2012

AbstractMutant KRAS in lung cancers induces molecular pathways that regulate cellular proliferation, survival and inflammation, which enhance tumorigenesis. Inducible nitric oxide synthase (NOS2) upregulation and sustained nitric oxide generation are induced during the inflammatory response and correlate positively with lung tumorigenesis. To explore the mechanistic contribution of NOS2 to KRAS‐induced lung tumorigenesis and inflammation, we used a genetic strategy of crossing NOS2 knockout (NOS2KO) C57BL6 inbred mice with a KRASG12D‐driven mouse lung cancer model. KRASG12D;NOS2KO mice exhibited delayed lung tumorigenesis and a longer overall survival time compared to that of KRASG12D;NOS2WT (wild‐type) controls. Correspondingly, tumors in KRASG12D;NOS2KO mice had reduced tumor cell proliferation in adenomas and carcinomas. NOS2 deficiency also led to markedly suppressed inflammatory response by attenuation of macrophage recruitment into alveoli and within tumor foci. In contrast, FOXP3+ regulatory T cells were increased in tumors from KRASG12D;NOS2KO mice. We further analyzed the expression of microRNA‐21 (miR‐21), an oncogenic noncoding RNA involved in oncogenic Ras signaling, by quantitative reverse‐transcription polymerase chain reaction and in situ hybridization. Lung carcinomas dissected from KRASG12D;NOS2KO mice showed a significantly reduced miR‐21 expression along with decreased tumor cell proliferation, suggesting that NOS2 deficiency could attenuate RAS signaling pathways that transactivate miR‐21 expression. Therefore, deletion of NOS2 decreases lung tumor growth as well as inflammatory responses initiated by oncogenic KRAS, suggesting that both KRAS and NOS2 cooperate in driving lung tumorigenesis and inflammation. Inhibition of NOS2 may have a therapeutic value in lung cancers with oncogenic KRAS mutations.
Abdominal obesity, weight gain during adulthood and risk of liver and biliary tract cancer in a European cohort
Authors: Schlesinger Sabrina , Aleksandrova Krasimira , Pischon Tobias , Fedirko Veronika , Jenab Mazda , Trepo Elisabeth , Boffetta Paolo , Dahm Christina C. , Overvad Kim , Tjønneland Anne , Halkjær Jytte , Fagherazzi Guy , Boutron‐Ruault Marie‐Christine , Carbonnel Franck , Kaaks Rudolf , Lukanova Annekatrin , Boeing Heiner , Trichopoulou Antonia , Bamia Christina , Lagiou Pagona , Palli Domenico , Grioni Sara , Panico Salvatore , Tumino Rosario , Vineis Paolo , HB Bueno‐de‐Mesquita , van den Berg Saskia , Peeters Petra H.M. , Braaten Tonje , Weiderpass Elisabete , Quirós J. Ramón , Travier Noémie , Sánchez María‐José , Navarro Carmen , Barricarte Aurelio , Dorronsoro Miren , Lindkvist Björn , Regner Sara , Werner Mårten , Sund Malin , Khaw Kay‐Tee , Wareham Nicholas , Travis Ruth C. , Norat Teresa , Wark Petra A. , Riboli Elio , Nöthlings Ute 
Published: May 2012

AbstractGeneral obesity has been positively associated with risk of liver and probably with biliary tract cancer, but little is known about abdominal obesity or weight gain during adulthood. We used multivariable Cox proportional hazard models to investigate associations between weight, body mass index, waist and hip circumference, waist‐to‐hip and waist‐to‐height ratio (WHtR), weight change during adulthood and risk of hepatocellular carcinoma (HCC), intrahepatic (IBDC) and extrahepatic bile duct system cancer [EBDSC including gallbladder cancer (GBC)] among 359,525 men and women in the European Prospective Investigation into Cancer and Nutrition study. Hepatitis B and C virus status was measured in a nested case–control subset. During a mean follow‐up of 8.6 years, 177 cases of HCC, 58 cases of IBDC and 210 cases of EBDSC, including 76 cases of GBC, occurred. All anthropometric measures were positively associated with risk of HCC and GBC. WHtR showed the strongest association with HCC [relative risk (RR) comparing extreme tertiles 3.51, 95% confidence interval (95% CI): 2.09–5.87; ptrend < 0.0001] and with GBC (RR: 1.56, 95% CI: 1.12–2.16 for an increment of one unit in WHtR). Weight gain during adulthood was also positively associated with HCC when comparing extreme tertiles (RR: 2.48, 95% CI: 1.49–4.13; <0.001). No statistically significant association was observed between obesity and risk of IBDC and EBDSC. Our results provide evidence of an association between obesity, particularly abdominal obesity, and risk of HCC and GBC. Our findings support public health recommendations to reduce the prevalence of obesity and weight gain in adulthood for HCC and GBC prevention in Western populations.
Vertebral fragility and structural redundancy
Authors: Fields Aaron J , Nawathe Shashank , Eswaran Senthil K , Jekir Michael G , Adams Mark F , Papadopoulos Panayiotis , Keaveny Tony M 
Published: May 2012

Abstract
The mechanisms of age-related vertebral fragility remain unclear, but may be related to the degree of “structural redundancy” of the vertebra; ie, its ability to safely redistribute stress internally after local trabecular failure from an isolated mechanical overload. To better understand this issue, we performed biomechanical testing and nonlinear micro-CT–based finite element analysis on 12 elderly human thoracic ninth vertebral bodies (age 76.9 ± 10.8 years). After experimentally overloading the vertebrae to measure strength, we used nonlinear finite element analysis to estimate the amount of failed tissue and understand the failure mechanisms. We found that the amount of failed tissue per unit bone mass decreased with decreasing bone volume fraction (r2 = 0.66, p &lt; 0.01). Thus, for the weak vertebrae with low bone volume fraction, overall failure of the vertebra occurred after failure of just a tiny proportion of the bone tissue (&lt;5%). This small proportion of failed tissue had two sources: the existence of fewer vertically oriented load paths to which load could be redistributed from failed trabeculae; and the vulnerability of the trabeculae in these few load paths to undergo bending-type failure mechanisms, which further weaken the bone. Taken together, these characteristics suggest that diminished structural redundancy may be an important aspect of age-related vertebral fragility: vertebrae with low bone volume fraction are highly susceptible to collapse because so few trabeculae are available for load redistribution if the external loads cause any trabeculae to fail. © 2012 American Society for Bone and Mineral Research.
Intermittent parathyroid hormone administration converts quiescent lining cells to active osteoblasts
Authors: Kim Sang Wan , Pajevic Paola Divieti , Selig Martin , Barry Kevin J , Yang Jae-Yeon , Shin Chan Soo , Baek Wook-Young , Kim Jung-Eun , Kronenberg Henry M 
Published: May 2012

Abstract
Intermittent administration of parathyroid hormone (PTH) increases bone mass, at least in part, by increasing the number of osteoblasts. One possible source of osteoblasts might be conversion of inactive lining cells to osteoblasts, and indirect evidence is consistent with this hypothesis. To better understand the possible effect of PTH on lining cell activation, a lineage tracing study was conducted using an inducible gene system. Dmp1-CreERt2 mice were crossed with ROSA26R reporter mice to render targeted mature osteoblasts and their descendents, lining cells and osteocytes, detectable by 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside (X-gal) staining. Dmp1-CreERt2(+):ROSA26R mice were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal days 3, 5, 7, 14, and 21. The animals were euthanized on postnatal day 23, 33, or 43 (2, 12, or 22 days after the last 4-OHTam injection). On day 43, mice were challenged with a subcutaneous injection of human PTH (1–34, 80 µg/kg) or vehicle once daily for 3 days. By 22 days after the last 4-OHTam injection, most X-gal (+) cells on the periosteal surfaces of the calvaria and the tibia were flat. Moreover, bone formation rate and collagen I(α1) mRNA expression were decreased at day 43 compared to day 23. After 3 days of PTH injections, the thickness of X-gal (+) cells increased, as did their expression of osteocalcin and collagen I(α1) mRNA. Electron microscopy revealed X-gal–associated chromogen particles in thin cells prior to PTH administration and in cuboidal cells following PTH administration. These data support the hypothesis that intermittent PTH treatment can increase osteoblast number by converting lining cells to mature osteoblasts in vivo. © 2012 American Society for Bone and Mineral Research.
Targeting the E3 ubiquitin casitas B-lineage lymphoma decreases osteosarcoma cell growth and survival and reduces tumorigenesis
Authors: Sévère Nicolas , Dieudonné François-Xavier , Marty Caroline , Modrowski Dominique , Patiño-García Ana , Lecanda Fernando , Fromigué Olivia , Marie Pierre J 
Published: May 2012

Abstract
Targeting receptor tyrosine kinase (RTK) degradation may be an interesting approach to reduce RTK cell signaling in cancer cells. Here we show that increasing E3 ubiquitin ligase casitas B-lineage lymphoma (c-Cbl) expression using lentiviral infection decreased osteosarcoma cell replication and survival and reduced cell migration and invasion in murine and human osteosarcoma cells. Conversely, c-Cbl inhibition using short hairpin RNA (shRNA) increased osteosarcoma cell growth and survival, as well as invasion and migration, indicating that c-Cbl plays a critical role as a bone tumor suppressor. Importantly, the anticancer effect of increasing c-Cbl expression in osteosarcoma cells was related mainly to the downregulation of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor alpha (PDGFRα). In a murine bone tumor model, increasing c-Cbl expression also reduced RTK expression, resulting in decreased tumor cell proliferation and survival and reduced tumor growth. Interestingly, increasing c-Cbl also markedly reduced lung metastasis in mice. Tissue microarray analysis revealed that low c-Cbl protein expression is associated with elevated EGFR and PDGFRα protein levels in human osteosarcoma with poor outcome. This study shows that increasing c-Cbl expression reduces osteosarcoma cell growth, survival, and metastasis in part through downregulation of RTKs, which supports the potential therapeutic interest of targeting c-Cbl in malignant bone diseases involving increased RTK. © 2012 American Society for Bone and Mineral Research.
Nuclear magnetic resonance J coupling constant polarizabilities of hydrogen peroxide: A basis set and correlation study
Authors: Kjær Hanna , Nielsen Monia R. , Pagola Gabriel I. , Ferraro Marta B. , Lazzeretti Paolo , P. A. Sauer Stephan 
Published: May 2012

AbstractIn this article, we present the so far most extended investigation of the calculation of the coupling constant polarizability of a molecule. The components of the coupling constant polarizability are derivatives of the nuclear magnetic resonance (NMR) indirect nuclear spin–spin coupling constant with respect to an external electric field and play an important role for both chiral discrimination and solvation effects on NMR coupling constants. In this study, we illustrate the effects of one‐electron basis sets and electron correlation both at the level of density functional theory as well as second‐order polarization propagator approximation for the small molecule hydrogen peroxide, which allowed us to perform calculations with the largest available basis sets optimized for the calculation of NMR coupling constants. We find a systematic but rather slow convergence with the one‐electron basis set and that augmentation functions are required. We observe also large and nonsystematic correlation effects with significant differences between the density functional and wave function theory methods. © 2012 Wiley Periodicals, Inc.
Quantum chemical insights into the aggregation induced emission phenomena: A QM/MM study for pyrazine derivatives
Authors: Wu Qunyan , Deng Chunmei , Peng Qian , Niu Yingli , Shuai Zhigang 
Published: May 2012

AbstractThere have been intensive studies on the newly discovered phenomena called aggregation induced emission (AIE), in contrast to the conventional aggregation quenching. Through combined quantum mechanics and molecular mechanics computations, we have investigated the aggregation effects on the excited state decays, both via radiative and nonradiative routes, for pyrazine derivatives 2,3‐dicyano‐5,6‐diphenylpyrazine (DCDPP) and 2,3‐dicyanopyrazino phenanthrene (DCPP) in condensed phase. We show that for DCDPP there appear AIE for all the temperature, because the phenyl ring torsional motions in gas phase can efficiently dissipate the electronic excited state energy, and get hindered in aggregate; while for its “locked”‐phenyl counterpart, DCPP, theoretical calculation can only give the normal aggregation quenching. These first‐principles based findings are consistent with recent experiment. The primary origin of the exotic AIE phenomena is due to the nonradiative decay effects. This is the first time that AIE is understood based on theoretical chemistry calculations for aggregates, which helps to resolve the present disputes over the mechanism. © 2012 Wiley Periodicals, Inc.
Regenerative cells and the architecture of beetle midgut epithelia
Authors: Nardi James B. , Bee Charles Mark 
Published: May 2012

AbstractThe architectural ground plan of beetle and other insect midguts is represented by a monolayer of epithelial cells arranged in a cylindrical configuration. Proliferation and differentiation of regenerative cells maintain the integrity of this monolayer in the face of continual losses of individual cells through cytoplasmic budding and/or expulsion of entire epithelial cells. Peritrophic membranes have conventionally been considered universal features of insect midguts that function to protect vulnerable microvillar surfaces of the midgut epithelium from abrasion by ingested food; however, peritrophic membranes were found in only a small fraction of the adult beetle species examined in this study. In adult beetles, midgut epithelial cells are continually replaced by cells recruited from populations of mitotic regenerative cells that are interspersed among the differentiated epithelial monolayer. To remain contiguous with the other cells in the midgut monolayer, some of these proliferating populations have adopted evaginated configurations of cells that extend for varying distances from the basal surface of the monolayer. These configurations are referred to as regenerative crypts or pouches and consist of progenitor cells and stem cells. The presence, the relative densities, and the relative lengths of these regenerative pouches vary considerably among families of beetles. Placement of longitudinal muscles of the midgut relative to the proximodistal axes of these regenerative pouches also varies among species of beetles. The presence, the size, and the density of regenerative cell populations are related to 1) feeding habits of adult beetles, 2) presence of peritrophic membranes, and 3) expulsion of entire midgut epithelial cells or fragments of these epithelial cells into midgut lumens. © 2012 Wiley Periodicals, Inc.
Age and innovation‐related behavior: The joint moderating effects of supervisor undermining and proactive personality
Authors: Ng Thomas W. H. , Feldman Daniel C. 
Published: May 2012

SummaryPrevious research has yielded mixed results regarding the effects of age on innovation‐related behavior (IRB; i.e., generating, disseminating, and implementing new ideas). This paper hypothesizes that the relationship of age with IRB is jointly moderated by undermining behavior on the part of the supervisor and the extent to which the employee possesses a proactive personality. We collected data from 196 employees at three points in time over a one‐year period. Results supported the hypothesized 3‐way interaction of age, supervisor undermining, and proactive personality on IRB. As predicted, highly proactive older workers responded to high supervisor undermining with more IRB, whereas older workers low on proactive personality responded to high supervisor undermining with less IRB. On the other hand, when supervisor undermining was low, proactive personality did not moderate the relationship of age with IRB. Copyright © 2012 John Wiley & Sons, Ltd.
Zoos, Sanctuaries and Turfs: Enactments and Uses of Gay Spaces during the Holidays
Authors: Blichfeldt Bodil Stilling , Chor Jane , Milan Nina Ballegaard 
Published: May 2012

ABSTRACTExtant theory suggests that the existence of gay space is an important (or even critical) element of gay people's holidays. However, more knowledge on the roles that gay spaces play during the holidays is needed. Drawing on interviews with 53 gay tourists, this paper suggests that the roles gay spaces play differ across gay tourists. Some interviewees enact gay spaces as ‘sanctuaries’, at which one can feel free and openly show one's sexuality. Others feel that gay spaces resemble ‘zoos’, i.e. tourist attractions at which straights gaze upon gays. Finally, some tourists find that gay spaces are too male oriented or even men's turfs. Copyright © 2012 John Wiley & Sons, Ltd.
Using recycled concrete aggregates in precast concrete hollow blocks
Authors: Matar P. , El Dalati R. 
Published: May 2012

AbstractAmong the construction waste that could be recycled, we can mention the aggregates resulting from crushed concrete. While the acquired knowledge about the use of recycled aggregates in new concrete mixes is fairly large, the use of such aggregates in the production of concrete blocks is very limited. This research aims to study the influence of the use of recycled aggregates in precast concrete hollow blocks on their compressive strength. Tests were carried out to determine the rate of recycled aggregates content to be used in the manufacture of concrete blocks in order to obtain blocks having suitable compressive strength. Tests were executed on several series of blocks whose composition includes recycled aggregates and on one series of reference blocks whose composition consisted exclusively of natural aggregates. Tests results have provided the maximum percentage of recycled aggregates that can be included in new concrete block mixes without affecting blocks compressive strength. Tests have shown that the use of recycled aggregates in concrete blocks could give a compressive strength similar to that of blocks manufactured without any recycled aggregates. It has been shown also that using recycled aggregates in the manufacture of concrete blocks without any natural aggregates is not economical at all because of the need to add a relatively high quantity of cement necessary to obtain the required compressive strength.
New way to take control of a structural grain size in the formation of nanomaterials by extrusion
Authors: Valíček J. , Čep R. , Rokosz K. , Łukianowicz C. , Kozak D. , Zeleňák M. , Koštial P , Hloch S. , Harničárová M. , Hlaváček P. , Haluzíková B. 
Published: May 2012

AbstractProduction of nanomaterials by formation of extreme plastic deformation ECAP (Equal‐Channel Angular Pressing) is a way of preparing nano‐structures of engineering materials. A development of a nanostructure in steel AISI 309 (EN X15CrNiSi20.20) with the technology of ECAP, and a new method for determination of the grain size are analysed here. In this study, we also make a comparison, analysis and prediction of the grain size with other technologies. Samples of steel of AISI 309 type were deformed by ECAP method using up to 35 passes.
Synthesis of SiC nanostructures through chemical vapor growth route
Authors: Chiew Y. L. , Cheong K. Y. 
Published: May 2012

AbstractIn this study, SiC nanorods and nanocolumns were synthesized using a catalyst‐free method with activated carbon powder and oxidized silicon wafer (oxidation time of the wafer varied from 1 to 12 min to produce different SiO2 thickness) as source materials. SiC nanorods were mostly found at the center of silicon wafer that was exposed to activated carbon powder while SiC nanocolumns were mostly found at the side of the wafer where it was in direct contact with graphite crucible. When thicker SiO2 was used, SiC nanorods at the center tended to agglomerate together into particles. SiC nanocolumns at the side of the wafer were also increased in amount as the oxidation time increased. Growth of SiC nanorods and nanocolumns could be attributed to chemical vapor growth via vapor‐solid mechanism.
The characteristics of unidirectional solidified Ni‐Al‐Mo alloys
Authors: Ishak M. , Takagi H. 
Published: May 2012

AbstractThe material composite was fabricated by the unidirectional solidification method in the eutectic composition alloy. Performing unidirectional solidification of Ni‐Al‐Mo alloy in eutectic composition produces γ phase ‐Ni and γ′ phase‐Ni3Al as a matrix, and the phase‐Mo growth into fibrous and lamellar‐like structure. The aim of this research was to study the characteristics of Ni‐Al‐Mo after various heat treatment conditions. The specimens were solution‐treated at temperatures of 1180°C and 1280°C, followed by water quenching. In addition, aging treatments were carried out at various temperatures (from 700°C to 1000°C) and at different time durations. The microstructure, mechanical properties and characteristics of non‐treated, solution‐treated and aging specimens were investigated. It was found that the mechanical properties of unidirectional solidified Ni‐Al‐Mo can be improved by solution treatment whilst the strength through performing an aging treatment. The optimized conditions were at 1280°C and 4 hours for water quenching (solution treatment), followed by an aging process at 800°C and 4 hours. These treatments led to an increase of mechanical properties due to uniformly precipitations of finely dispersed γ′ phase‐Ni3Al throughout the specimens.
Up‐regulation of p53 and mitochondrial signaling pathway in apoptosis by a combination of cox‐2 inhibitor, celecoxib and dolastatin 15, a marine mollusk linear peptide in experimental colon carcinogenesis
Authors: Piplani Honit , Vaish Vivek , Rana Chandan , Sanyal Sankar N. 
Published: May 2012

AbstractProgrammed cell death, also known as apoptosis, is an active process occurring in eukaryotic cells and it depends on various sets of pro and anti‐apoptotic proteins. Chemoprevention of colorectal cancer can be achieved by inducing apoptosis using synthetic compound, Celecoxib and natural peptide, Dolastatin 15 in an effective manner. But the apoptotic signaling by these two drugs remain unclear. The present study was thus focused on the role of Bcl2 family of proteins and their interplay with p53 in rats during the chemoprevention by these two drugs. After treatment for 6 wk with 1, 2‐dimethylhydrazine (DMH), animals showed a marked occurrence of multiple plaque lesions. However, a simultaneous treatment with Celecoxib and Dolastatin 15 decreases such number to a significant level. DMH treatment also decreases the number of apoptotic cells in the colonic enterocytes which were corrected to the normal level by Celecoxib and Dolastatin 15. An increased expression of Bcl2 while other proteins like Bax, Apaf‐1, cyt c, and caspases in the apoptotic pathway, and the tumor suppressor proteins, p53 and p21 get down‐regulated after DMH treatment which were reverted back to normal with Celecoxib and Dolastatin 15. Also, cells having high mitochondrial membrane potential had been seen to increase to significant levels which were reduced after the administration of these anti‐inflammatory drugs. In silico molecular docking studies also showed that Dolastatin 15 and Celecoxib may bind to the active site pocket of Bcl2, thus revealing the direct target of Dolastatin 15 and Celecoxib apart from binding to COX‐2. Copyright © 2012 Wiley Periodicals, Inc.