bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospectively measured thyroid hormones and thyroid peroxidase antibodies in relation to breast cancer risk
Authors: Tosovic Ada , Becker Charlotte , Bondeson Anne‐Greth , Bondeson Lennart , Ericsson Ulla‐Britt , Malm Johan , Manjer Jonas 
Published: February 2012

AbstractThyroid hormones influence both normal breast cell differentiation and breast cancer cell proliferation and stimulate the angiogenesis of certain cancer forms. Several cross‐sectional studies have measured thyroid hormones/autoantibodies in breast cancer ceases vs. controls, but it is difficult to determine the cause–effect direction in these studies. Only three prospective studies have reported on the subject so far. The aim of our study was to investigate prediagnostically measured levels of thyroid hormones, thyrotropin (TSH) and thyroid autoantibodies in relation to subsequent risk of breast cancer. The Malmoe Diet and Cancer study examined 17,035 women between 1991 and 1996. Blood samples were collected at baseline and free triiodothyronine (T3), free thyroxin (T4), TSH and thyroid peroxidase autoantibodies (TPO‐Ab) levels were measured in 676 cases and 680 controls. Relative risks with 95% confidence intervals were assessed using a logistic regression analysis adjusted for potential confounders. Free T4 levels were positively associated with a high risk of breast cancer, and the OR for women with free T4 levels above vs. below the median was 1.40 (1.10–1.77). This association was most pronounced in overweight women (1.51:1.07–2.12). Women with high levels of TPO‐Ab had a lower risk of breast cancer, but only the analysis of TPO‐Ab as a continuous variable reached statistical significance. Free T4 was in our study positively associated with a high risk of breast cancer. This association was most pronounced in overweight/obese women. Women with a high level of TPO‐Ab had a relatively low risk of breast cancer.
Nuclear accumulation of seven in absentia homologue‐2 supports motility and proliferation of liver cancer cells
Authors: Malz Mona , Aulmann Antje , Samarin Jana , Bissinger Michaela , Longerich Thomas , Schmitt Sabrina , Schirmacher Peter , Breuhahn Kai 
Published: February 2012

AbstractStability of many tumor‐relevant proteins is partly mediated by E3 ligases, which determine substrate specificity within the ubiquitin system. Recent data demonstrated that increased nuclear expression of the E3 ligase seven in absentia homologue (SIAH)‐1 in human hepatocarcinogenesis supports tumor cell proliferation and migration. To define whether closely related SIAH‐2 synergizes with protumorigenic SIAH‐1, we systematically analyzed expression, localization and functional relevance of SIAH‐2 in human hepatocellular carcinoma (HCC). Nuclear accumulation of SIAH‐2 is detectable in more than 60% of all HCCs and correlates with tumor progression, cell proliferation and distant metastasis. An inverse correlation between nuclear SIAH‐1 and SIAH‐2 was detected, suggesting independent mechanisms for nuclear enrichment. Inhibition of nuclear SIAH‐2 by RNAi in HCC cell lines reduced proliferation as well as lateral tumor cell motility and transmigration; however, combined knock down of both SIAH‐1 and SIAH‐2 did not further amplify biological effects compared to single gene inhibition. Reduction of SIAH‐2 expression sensitizes HCC cells to the treatment with different cytostatic drugs, demonstrating that SIAH‐2‐targeting approaches may increase the response of HCC cells to conventional chemotherapy. Together, these data show that SIAH‐2—as described for SIAH‐1—accumulates in nuclei of HCC cells where it supports tumor growth and tumor cell dissemination. Because the nuclear pattern of SIAH‐2 differs in HCC tissues from the SIAH‐1 pattern and because the inactivation of SIAH‐2 is not compensated by SIAH‐1, the specific inhibition of SIAH‐2 (especially in combination with other drugs) represents a promising therapeutic strategy for HCC.
Plumbagin, a plant derived natural agent inhibits the growth of pancreatic cancer cells in in vitro and in vivo via targeting EGFR, Stat3 and NF‐κB signaling pathways
Authors: Hafeez Bilal Bin , Jamal Mohammad Sarwar , Fischer Joseph W. , Mustafa Ala , Verma Ajit Kumar 
Published: February 2012

AbstractPancreatic cancer (PC) is the most aggressive malignant disease, ranks as the fourth most leading cause of cancer‐related death among men and women in the United States. We present here that plumbagin (PL), a quinoid constituent isolated from the roots of the medicinal plant Plumbago zeylanica L, inhibits the growth of PC cells both in vitro and in vivo model systems. PL treatment induces apoptosis and inhibits cell viability of PC cells (PANC1, BxPC3 and ASPC1). In addition, i.p. administration of PL (2 mg/kg body weight, 5 days a week) in severe combined immunodeficiency (SCID) mice beginning 3 days after ectopic implantation of PANC1 cells resulted in a significant (P < 0.01) inhibition of both tumor weight and volume. PL treatment inhibited (1) constitutive expression of epidermal growth factor receptor (EGFR), pStat3Tyr705 and pStat3Ser727, (2) DNA binding of Stat3 and (3) physical interaction of EGFR with Stat3, in both cultured PANC1 cells and their xenograft tumors. PL treatment also inhibited phosphorylation and DNA‐binding activity of NF‐κB in both cultured PC cells (PANC1 and ASPC1) and in PANC1 cells xenograft tumors. Downstream target genes (cyclin D1, MMP9 and Survivin) of Stat3 and NF‐κB were similarly inhibited. These results suggest that PL may be used as a novel therapeutic agent against human PC.
Acid ceramidase‐mediated production of sphingosine 1‐phosphate promotes prostate cancer invasion through upregulation of cathepsin B
Authors: Beckham Thomas H. , Lu Ping , Cheng Joseph C. , Zhao Dan , Turner Lorianne S. , Zhang Xiaoyi , Hoffman Stanley , Armeson Kent E. , Liu Angen , Marrison Tucker , Hannun Yusuf A. , Liu Xiang 
Published: February 2012

AbstractInvasiveness is one of the key features of aggressive prostate cancer; however, our understanding of the precise mechanisms effecting invasion remains limited. The ceramide hydrolyzing enzyme acid ceramidase (AC), overexpressed in most prostate tumors, causes an aggressive and invasive phenotype through downstream effectors that have not yet been well characterized. Here, we demonstrate that AC, through generation of sphingosine‐1‐phosphate (S1P), promotes Ets1 nuclear expression and binding to the promoter region of matrix‐degrading protease cathepsin B. Through confocal microscopy and flow cytometry, we found that AC overexpression promotes pericellular localization of cathepsin B and its translocation to the outer leaflet of the cell membrane. AC overexpressing cells have an increased abundance of cathepsin B‐enriched invasive structures and enhanced ability to invade through a collagen matrix, but not in the presence of an inhibitor of cathepsin B. In human prostate tissues, AC and cathepsin B overexpression were strongly associated and may relate to poor outcome. These results demonstrate a novel pathway by which AC, through S1P, promotes an invasive phenotype in prostate cancer by causing overexpression and secretion of cathepsin B through activation and nuclear expression of Ets1. As prostate cancer prognosis is dramatically worse when invasion has occurred, this study provides critical insight into the progression toward lethal prostate cancer.
“Atypical femoral fractures” during bisphosphonate exposure in adult hypophosphatasia
Authors: Sutton Roger AL , Mumm Steven , Coburn Stephen P , Ericson Karen L , Whyte Michael P 
Published: February 2012

Abstract
We report a 55-year-old woman who suffered atypical subtrochanteric femoral fractures (ASFFs) after 4 years of exposure to alendronate and then zolendronate given for “osteoporosis.” Before alendronate treatment, she had low bone mineral density. After several months of therapy, metatarsal stress fractures began. Bisphosphonate (BP) administration was stopped following the ASFFs, and the adult form of hypophosphatasia (HPP) was diagnosed from low serum alkaline phosphatase (ALP) activity, high endogenous levels of two natural substrates for the “tissue-nonspecific” isoenzyme of ALP (TNSALP), and a heterozygous mutation within the gene that encodes this enzyme. Experience with other HPP families showed that her mutation (Arg71His) with a second defective TNSALP allele can cause severe HPP in infancy, and when heterozygous can cause mild HPP featuring premature loss of deciduous teeth in children. Because the skeletal disease of HPP results from extracellular accumulation of the TNSALP substrate inorganic pyrophosphate (PPi) and its inhibitory effect on mineralization, perhaps HPP patients or carriers will have adverse effects from BPs. BPs are analogues of PPi and can suppress bone turnover but also deactivate TNSALP. Our report is the first of BP exposure preceding ASFFs in adult HPP. To explore a potential role for TNSALP deactivation in ASFFs, mutation analysis of TNSALP should be studied in a cohort of these patients. Meanwhile, clinicians must suspect HPP when clinical or laboratory clues include premature loss of primary dentition, pseudofractures or recurrent poorly healing metatarsal stress fractures, a family history suggestive of HPP, or low serum ALP activity. If HPP is documented, BP treatment might be avoided. To establish the diagnosis of HPP, assays for two natural substrates for TNSALP and TNSALP mutation analysis are available in commercial laboratories. With positive findings, radiological or bone biopsy evidence of acquired osteomalacia would indicate the adult form of this inborn-error-of-metabolism. © 2012 American Society for Bone and Mineral Research.
Major and trace element characterization of tephra layers offshore Pantelleria Island: insights into the last 200 ka of volcanic activity and contribution to the Mediterranean tephrochronology
Authors: Tamburrino Stella , Insinga Donatella D. , Sprovieri Mario , Petrosino Paola , Tiepolo Massimo 
Published: February 2012

AbstractA detailed tephrochronological study was carried out on the deep‐sea core collected from Site 963A in the Sicily Channel during ODP Leg 160. The chronology of the succession is provided by an age–depth model based on isotope stratigraphy and quantitative eco‐biostratigraphy. Major, trace and rare earth element content was obtained on single glass grains through electron probe micro‐analysis and laser ablation–inductively coupled plasma mass spectrometry techniques from six well‐preserved tephra layers, characterized by a discrete thickness found along the succession. These deposits were correlated with the volcanic activity of Pantelleria and dated at 42.5, 127.5, 128.1, 129.1, 188.7 and 197.7 ka. This detailed chemical characterization of the studied deposits aims to provide a valuable reference database for scientists working on both proximal and distal products erupted at Pantelleria island during the Late Pleistocene. This study, moreover, offers the opportunity to better identify Pantelleria‐related marker tephras within the tephrochronological framework of the central and eastern Mediterranean area. Copyright © 2012 John Wiley & Sons, Ltd.
The Hekla 1947 tephra in the north of Ireland: regional distribution, concentration and geochemistry
Authors: Rea Heidi A. , Swindles Graeme T. , Roe Helen M. 
Published: February 2012

AbstractA cryptotephra layer from the eruption of Hekla in 1947 has recently been discovered in Irish peatlands. This tephra layer represents the most recent deposition of volcanic ash in the UK prior to the eruption of Eyjafjallajökull in 2010. Here we examine the concentration and geochemistry of the Hekla 1947 tephra in 14 peat profiles from across Northern Ireland. Electron probe microanalysis of individual tephra shards (n = 91) reveals that the tephra is of dacitic–andesitic geochemistry and is highly similar to the Hekla 1510 tephra, although spheroidal carbonaceous particle profiles can be used for successful discrimination of the two layers. The highest concentrations of Hekla 1947 are found in western sites, probably reflecting the pathway of the ash fall event due to the prevailing wind direction. Comparable tephra concentrations from two cores (1 km apart) from a single bog and from nearby sites may suggest that tephra shard concentrations in peat profiles reflect ash fallout densities across a specific region, rather than site‐specific factors associated with peatlands. This paper firmly establishes Hekla 1947 as a useful chronostratigraphic marker for the twentieth century, although within a restricted zone. Copyright © 2012 John Wiley & Sons, Ltd.
Creep and Dynamic Mechanical Analysis Studies of Peroxide‐Crosslinked Ethylene‐Octene Copolymer
Authors: Theravalappil Rajesh , Svoboda Petr , Poongavalappil Sameepa , Svobodova Dagmar 
Published: February 2012

AbstractAn ethylene‐octene copolymer (EOC) (45 wt% octene) is crosslinked using dicumyl peroxide (DCP). Differential scanning calorimetry (DSC) reveals a very low melting temperature (50 °C). The network density is evaluated by gel content. While 0.2–0.3 wt% of peroxide leads only to a molecular weight increase (samples completely dissolved in xylene), 0.4–0.6 wt% of peroxide caused network formation. High‐temperature creep was measured at 70, 120, and 200 °C at three stress levels. At 200 °C and above 0.6 wt% of peroxide, degradation due to chain scission is observed by rubber process analyzer (RPA) and is again supported by creep measurements. Residual strain at 70 °C is found to improve with increasing peroxide level. Dynamic mechanical analysis (DMA) reveals a strong influence of peroxide content on storage modulus and tan δ, in particular in the range 30–200 °C.magnified image
Bactericidal and Anticorrosion Properties in PVK/MWNT Nanocomposite Coatings on Stainless Steel
Authors: Santos Catherine M. , Milagros Cui Karina , Ahmed Farid , Tria Maria Celeste R. , Vergara Regina Aileen May V. , de Leon Al Christopher , Advincula Rigoberto C. , Rodrigues Debora F. 
Published: February 2012

AbstractA PVK/MWNT nanocomposite coating on stainless steel is developed and tested for antimicrobial and anticorrosion properties. The coating is prepared via electrochemical deposition onto SS surfaces and is monitored using cyclic voltammetry. High‐resolution XPS measurements of the C 1s and N 1s regions are used to estimate the film composition. AFM shows a homogeneous thin film of several µm thickness with well‐defined globular domains. The bactericidal functionality of the electrodeposited film is demonstrated by its antibacterial activity against Escherichia coli, even with low MWNT loading (≈6%). The excellent anticorrosion property of the coating is demonstrated after 7 d of exposure to NaCl (0.5 M) solution.magnified image
Effect of Silica‐Coated Poly(butyl methacrylate)‐block‐poly(methyl methacrylate) Double‐Shell Particles on the Mechanical Properties of PMMA Composites
Authors: Chakkalakal Golda Louis , Alexandre Michaël , Boschetti‐de‐Fierro Adriana , Abetz Volker 
Published: February 2012

AbstractSilica nanoparticles with an average diameter of 12 nm are grafted with PBMA‐b‐PMMA double shells through typical sequential ATRP from bromoisobutyrate initiators anchored at the silica surface using an epoxysilane. A commercially available PMMA homopolymer is used for the preparation of composites with unmodified, silane‐modified and double‐shell‐modified silica particles. Good mechanical properties are obtained for silica double shell containing systems. The silica content in double shell particle systems is varied from 0 to 2.5 wt%. A significant improvement in impact properties is observed. The surface‐modified silica particles are characterized by ATR‐FTIR, NMR, GPC, and thermal analyses. TEM analysis is used to analyze the nature of dispersion of particles in the composites. magnified image
Spaces of vector‐valued functions and their duals
Authors: Roth Walter 
Published: February 2012

AbstractWe consider spaces of continuous vector‐valued functions on a locally compact Hausdorff space, endowed with classes of locally convex topologies, which include and generalize various known ones such as weighted space‐ or inductive limit‐type topologies. The main result states that every continuous linear functional on such a function space can be expressed as an integral with respect to some canonical (dual space‐valued) vector measure.
Solubilization of a π‐Conjugating Hydrophobic Dendrimer in Aqueous Media
Authors: Imaoka Takane , Katsurayama Makoto , Yamanoi Yoshinori , Nishihara Hiroshi , Yamamoto Kimihisa 
Published: February 2012

AbstractPhenylazomethine dendrimers, which can be used as the template for precise metal nanoparticles, are soluble only in aprotic media. The use of a specific surfactant enabled their solubilization in aqueous solutions. Under dilute condition, they formed discrete micelles with a size close to the that of the dendrimer. Condensation resulted in their aggregation; however, they remained in a homogeneous solution without precipitation. Furthermore, each micelle was well isolated. The triplet‐excited state of the zinc porphyrin core in the micelles was significantly stable, suggesting the formation of rigid core‐shell micelles preventing any external molecules from approaching to the core.
Differentiation of isomeric amino acid residues in proteins and peptides using mass spectrometry
Authors: Hurtado Pilar Perez , O'Connor Peter B. 
Published: February 2012

AbstractCharacterization and differentiation of isomers in biological macromolecules using mass spectrometry is one of the most significant challenges facing scientists in the field. The capability of high‐resolution MS instruments along with the development of new fragmentation methods now provides the ability to indirectly differentiate between some isomers. This ability has enabled mass spectrometry to evolve into a multidisciplinary technique incorporating areas such as pharmaceutical research, proteomics, polymer science, medicine, environmental chemistry, and recently archeology. This article aims to review recent developments in mass spectrometry methodologies in the identification of structural and spatial isomers in biological macromolecules, such as aspartic acid and isoaspartic acid (Asp/IsoAsp), leucine and isoleucine (Leu/Ile), glutamic acid and γ‐glutamic acid, and D/L enantiomers. © 2012 Wiley Periodicals, Inc. Mass Spec Rev 31:609–625, 2012
On the Generalised Stretch Function
Authors: Kharlamov Alexander A. , Filip Petr 
Published: February 2012

AbstractThe tube theory represents a powerful tool for the description of polymer behaviour. In this theory, the term in the form of an integral over a full solid angle of a magnitude of deformed unit vector represents the stretch function. This term relates the lengths of the random walk of a molecule in deformed and undeformed states. For the case of the Doi‐Edwards model, the integrand is raised to a power of one, however, for other models the power differs from one. The aim of this contribution is to derive an analytical algebraic approximation of a general form of this integral with the integrand raised to an arbitrary power within the physically justified interval between zero and two. magnified image
CDC4/FBXW7 and the ‘just enough’ model of tumourigenesis
Authors: Davis Hayley , Tomlinson Ian 
Published: February 2012

AbstractThere is good evidence to show that cancer‐causing mutations are not always simple gain‐ and loss‐of‐function changes. One example is the APC gene, where the combination of mutations produces a ‘just‐right’ level of Wnt signalling. A recent article by Berger and colleagues posited a ‘continuum model’ in which increasing or decreasing gene expression of function was linearly associated with tumourigenesis. Berger also proposed an ‘obligate haploinsufficiency’ or ‘fail‐safe’ model, whereby heterozygous mutations produce sufficient derangement for tumourigenesis, yet homozygous mutations are cell‐lethal or senescence‐causing. One gene highlighted by Berger and colleagues as an example of a gene following a ‘continuum’ or ‘fail‐safe’ model was FBXW7/CDC4, a gene mutated in several different types of malignancy. We have analysed the COSMIC FBXW7 data. FBXW7 does not obviously follow a ‘continuum’ or ‘fail‐safe’ model and the most common mutant genotypes are mono‐allelic missense changes that affect critical arginine residues involved in interactions with substrates. There is no strong selection for complete loss of FBXW7 protein function, but bi‐allelic inactivating mutations do occur. For FBXW7, we suggest a variant of ‘just right’ which we call ‘just enough’. For FBXW7 mutations that occur away from the propellor tips, the heterozygote may have some effect on tumourigenesis, but there is selective pressure for a ‘second hit’. For propellor tip mutations, by contrast, there is weak pressure for a ‘second hit’ because they usually provide sufficient functional derangement on their own. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Estimate of deaths due to valvular insufficiency attributable to the use of benfluorex in France
Authors: Fournier Agnès , Zureik Mahmoud 
Published: February 2012

ABSTRACTPurposeTo estimate the number of deaths from valvular insufficiency caused by the use of the fenfluramine‐derivative benfluorex during the period 1976–2009 in France.MethodsOur calculation was based on (i) the exposure level to benfluorex in the French population, derived from sales figures for the period 1976–2009 and from the main characteristics of benfluorex use provided by the French health products safety agency; (ii) the relative risk of hospitalization for valvular insufficiency among exposed compared with unexposed individuals with diabetes, originating from a cohort study based on a French medico‐administrative database, with benfluorex exposure assessed in 2006; (iii) the incidence of hospitalization for valvular insufficiency among exposed individuals, originating from the same database; and (iv) the mortality associated with valvular heart disease.ResultsIn France, use of benfluorex during the period 1976–2009 is likely to be responsible for around 3100 hospitalizations and 1300 deaths due to valvular insufficiency. These figures may be underestimations.ConclusionsThe grave consequences benfluorex use have had for many people lend support to the public investigation, which has been set to understand the reasons that have contributed to the delay in withdrawing benfluorex from the French market. Copyright © 2012 John Wiley & Sons, Ltd.