bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of SiO2 porosity on activity profiles and comonomer incorporation in slurry ethylene/butene‐1 polymerization by (SiO2/MgCl2/TEOS/TiCl4) catalyst system
Authors: Vakili Mohammad , Arabi Hassan , Salehi Mobarakeh Hamid 
Published: December 2011

AbstractTo investigate the influence of support porosity parameters e.g., average pore volume (APV), pore diameter (PD), and pore surface area distribution (PSAD) on activity‐profile of catalyst and comonomer incorporation, a series of silica‐supports with different porosity were prepared through sol–gel method and used to synthesize corresponding (SiO2/MgCl2/TEOS/TiCl4) catalysts. Polymerization of ethylene/butene‐1 showed that increasing of APV from 0.75 to 2.2 cm3 g increase initial activity from 120 to 400 (gpoly/gcat.bar.hr) followed by appearance of secondary peaks in activity‐profile which could be attributed to the variation of PSAD. It is found that the effect of support in polymerization is a complicated issue which depends not only on the porosity parameters also on the comonomer concentration. The catalyst with PD of 300 Å gives higher comonomer incorporation and polymers with 15–20% lower crystallinity in contrast to catalyst with PD of 100 Å. Porosity effect was quantitatively studied by modifying of conventional Z‐N catalyst polymerization mechanism through introducing fragmentation term to achieve a new tool in designing and developing of polyolefin catalysts. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
The Origin of Living Polymerization with an o‐Fluorinated Catalyst: NMR Spectroscopic Characterization of Chain‐Carrying Species
Authors: Möller Heiko M. , Baier Moritz C. , Mecking Stefan , Talsi Evgenii P. , Bryliakov Konstantin P. 
Published: December 2011

AbstractTo characterize the origin of living polymerization with nonmetallocene titanium‐based catalysts containing o‐fluoroaryl substituents, ethene polymerization by an o‐fluorinated bis(enolatoimine) titanium catalyst and its nonfluorinated counterpart has been studied by multinuclear NMR spectroscopy by using methylaluminoxane (MAO) or AlMe3/CPh3B(C6F5)4 as activators. Formation of ion pairs of the type [TiL2Me][MeMAO] and [TiL2Me][B(C6F5)4] has been observed for both catalysts. These ion pairs react with ethene to afford the chain‐propagating species [TiL2P][MeMAO] and [TiL2P][B(C6F5)4], respectively (P=growing polymeryl chain). For the o‐F‐substituted catalyst species of the second type, NMR spectroscopy provides evidence that the o‐F substituents interact with the metal center. This interaction is proposed to keep the polymerization catalysis living by suppressing chain transfer to AlMe3 and β‐hydrogen transfer processes.
Study of the Anticancer Properties of Tin(IV) Carboxylate Complexes on a Panel of Human Tumor Cell Lines
Authors: Rocamora‐Reverte Lourdes , Carrasco‐García Estefanía , Ceballos‐Torres Jesús , Prashar Sanjiv , Kaluđerović Goran N. , Ferragut José A. , Gómez‐Ruiz Santiago 
Published: December 2011

AbstractA group of organotin(IV) complexes were prepared: [SnCy3(DMNI)] (1), [SnCy3(BZDO)] (2), [SnCy3(DMFU)] (3), and [SnPh2(BZDO)2] (4), for which DMNIH=2,6‐dimethoxynicotinic acid, BZDOH=1,4‐benzodioxane‐6‐carboxylic acid, and DMFUH=2,5‐dimethyl‐3‐furoic acid. The cytotoxic activities of compounds 1–4 were tested against pancreatic carcinoma (PANC‐1), erythroleukemia (K562), and two glioblastoma multiform (U87 and LN‐229) human cell lines; they show very high antiproliferative activity, with IC50 values in the 150–700 nM range after incubation for 72 h. Distribution of cellular DNA upon treatment with 1–4 revealed that whereas compounds 1–3 induce apoptosis in most of the cell lines, compound 4 does not affect cell viability in any cell line tested, indicating a possible difference in cytotoxic mechanism. Studies with the daunomycin‐resistant K562/R cell line expressing P‐glycoprotein (Pgp) showed that compounds 1–4 are not substrates of this protein efflux pump, indicating that these compounds do not induce acquisition of multidrug resistance, which is associated with the overexpression of Pgp.
A Decade of the Human Genome Sequence—How Does the Medicinal Chemist Benefit?
Authors: Brunschweiger Andreas , Hall Jonathan 
Published: December 2011

AbstractMany have claimed that the sequencing of the human genome has failed to deliver the promised new era of drug discovery and development. Here, we argue that in fact, the availability of the human genome sequence and the genomics technologies that resulted from those research efforts have had a major impact on drug discovery. Medicinal chemists are actively using the data gleaned from structural genomics projects over the past decade to design more selective and more effective drug candidates. For example, large superfamilies of related enzymes, such as the kinome, proteome, proteasome, transportome, identified because of the sequencing of the human genome represent a huge number of potential drug targets. Ten years on, we′re able to design multitarget drugs where the selectivity for a certain subgroup of receptors can lead to increased efficacy rather than the side effects traditionally associated with “off‐targets”. New trends and discoveries in biomedical research are notoriously slow to show their value, and this is also true for genomics technologies. However, the examples we′ve selected show that these are firmly set in the drug‐discovery process, and without the human genome sequence, a number of current clinical candidates and promising drug leads would not have been possible.
Dose‐escalation of whole‐brain radiotherapy for brain metastasis in patients with a favorable survival prognosis
Authors: Rades Dirk , Panzner Annika , Dziggel Liesa , Haatanen Tiina , Lohynska Radka , Schild Steven E. 
Published: December 2011

AbstractBACKGROUND:Patients with brain metastases who have a favorable survival prognosis may benefit from intensive treatments, including neurosurgery and radiosurgery. However, many patients cannot receive such treatments, and whole‐brain radiotherapy (WBRT) alone is their only option. The most common WBRT schedule is 30 grays (Gy) in 10 fractions. In this retrospective study, the authors investigated whether these patients benefit from a dose escalation beyond 30 Gy.METHODS:Data from 109 patients who received 30 Gy in 10 fractions were compared with 75 patients who received 40 Gy in 20 fractions. All patients had a favorable survival prognosis. Both groups were compared for local control (LC) and overall survival (OS). Subgroup analyses were performed for patients who had less radiosensitive tumors (N = 27) and for other patients (N = 157).RESULTS:The LC rate at 1 year was 28% after 30 Gy and 44% after 40 Gy (P = .064). On multivariate analysis, the 40 Gy dose was associated with improved LC (P = .047). The survival rate at 1 year was 50% after 30 Gy and 61% after 40 Gy (P = .007). On multivariate analysis, the 40 Gy dose was associated with improved OS (P = .008). On subgroup analysis of patients who had less radiosensitive tumors, the 1‐year LC rate was 7% after 30 Gy and 38% after 40 Gy (P = .031); and the 1‐year OS rate was 40% and 73%, respectively (P = .008). On subgroup analysis of patients who had other tumor types, the 1‐year LC rate was 31% after 30 Gy and 45% after 40 Gy (P = .26); and the 1‐year OS rate was 52% and 59%, respectively (P = .08).CONCLUSIONS:Escalation of the WBRT dose beyond 30 Gy resulted in better outcomes, particularly for patients who had less radiosensitive tumors. Cancer 2012. © 2011 American Cancer Society.
Krüppel‐like factor 4 functions as a tumor suppressor in cervical carcinoma
Authors: Yang Wen‐Ting , Zheng Peng‐Sheng 
Published: December 2011

AbstractBACKGROUND:The Krüppel‐like factor 4 (KLF4) protein, a zinc finger transcription factor that is highly expressed in epithelial tissues such as the gut and skin, has been implicated in both tumor suppression and progression. However, the role of KLF4 in human cervical carcinoma is still unclear.METHODS:The expression of KLF4 in cervical carcinoma tissues and cervical cancer cell lines was examined with immunohistochemistry and Western blot assay. The effects of KLF4 silencing and overexpression on the cell proliferation, cell viability, and tumor formation of cervical cancer cells were investigated.RESULT:KLF4 protein expression showed a pattern of gradual decrease from normal cervix to cervical carcinoma in situ and then to invasive cervical carcinomas (P < .05). Overexpression of KLF4 in SiHa and C33A cells resulted in significantly inhibited cell growth and significantly attenuated tumor formation. Consistently, KLF4 silencing in HeLa cells significantly promoted cell growth and tumor formation. Furthermore, KLF4 overexpression caused cell cycle arrest at the G1/S transition, along with the up‐regulated expression of p27Kip1 protein. Promoter analysis revealed that KLF4 transactivated the expression of p27Kip1 through the specific motif that is between the nucleotides of −435 and −60 in its promoter. The results from chromatin immunoprecipitation assays demonstrated the physical interaction between KLF4 protein and this specific motif in p27Kip1 promoter.CONCLUSIONS:KLF4 may function as a tumor suppressor in cervical carcinoma by inhibiting cell growth and tumor formation. Cancer 2012. © 2011 American Cancer Society.
Immunomodulatory medicines for multiple sclerosis: Progress and prospects
Authors: Palmer Alan M. 
Published: December 2011

AbstractMultiple sclerosis (MS) is a neurodegenerative disease with a major inflammatory component that constitutes the most common progressive and disabling neurological condition in young adults. Current therapies are mainly biological agents (β‐interferons, a 4‐amino acid peptide, and a monoclonal antibody to a cell adhesion molecule on the blood CNS barrier) that either attenuate the inflammatory response or block the movement of immune cells into the CNS. The market landscape for MS drugs is set to change substantially in the near future with the market leaders coming off patent, which gives permission for the emergence of biosimilars. In addition, new small‐molecule immunomodulatory drugs are beginning to enter the market (Gilenya is the first to gain widespread approval), along with a number of immunomodulatory monoclonal antibodies. Both existing and emerging immunomodulatory medicines for MS are reviewed and their impact on the expression and progression of MS (in all its forms) considered, along with the rapidly changing landscape of MS pharmacotherapy. Drug Dev Res 72:664–673, 2011. © 2011 Wiley Periodicals, Inc.
Rheumatoid arthritis and pregnancy: Disease activity, pregnancy outcomes, and treatment options during pregnancy and lactation
Authors: Gogia Maneesh , Furst Daniel E. 
Published: December 2011

AbstractThe present work reviews the available data on rheumatoid arthritis (RA) during pregnancy and the postpartum period. The data generally support some improvement in RA during pregnancy, but these data are not consistent, and a subgroup of patients may have significant disability and flares. The literature supports a tendency toward postpartum flares. Babies born to mothers with RA are found to have lower birth weight, intrauterine growth restriction, and an increased risk of delivery by cesarean section. Limited safety information is available for medications used for treatment during pregnancy and lactation. There are many options for treatment during the first trimester and throughout pregnancy, but each decision must be made on an individual basis. Whereas methotrexate and leflunomide are contraindicated in pregnancy, sulfasalazine is generally considered useful, as is hydroxychloroquine (despite the latter's FDA pregnancy category C rating). Of the biologics, the tumor necrosis factor (TNFi) are classified as category B; the other biologics vary between categories B and C, but more human data are available on TNFi. Drug Dev Res 72:689–702, 2011. © 2011 Wiley Periodicals, Inc.
Tocilizumab, a humanized anti‐interleukin‐6 receptor antibody, for the treatment of autoimmune disorders
Authors: Tanaka Toshio , Hagihara Keisuke , Shima Yoshihito , Narazaki Masashi , Ogata Atsushi , Kumanogoh Atsushi 
Published: December 2011

AbstractThe cytokine interleukin (IL)‐6 has a wide range of biological activities. It contributes to host defense against pathogens by inducing immune responses, hematopoiesis, and acute‐phase reactions. However, dysregulation of IL‐6 production plays a significant pathological role in various autoimmune and chronic inflammatory disorders. Because IL‐6 blockade was anticipated to provide a novel strategy for the treatment of such diseases, tocilizumab, a humanized anti‐IL‐6 receptor antibody, was developed. Clinical trials have demonstrated the efficacy of tocilizumab for patients with moderate to severe rheumatoid arthritis, resulting in approval in more than 90 countries worldwide of this innovative biologic for the treatment of rheumatoid arthritis. Tocilizumab was also approved in Japan for the treatment of Castleman's disease and juvenile idiopathic arthritis. Results of recent pilot or case studies have indicated that tocilizumab may become a novel drug for various other autoimmune disorders, including systemic lupus erythematosus, systemic sclerosis, polymyositis, and vasculitis syndrome, as well as inflammatory disorders such as adult‐onset Still's disease, Crohn's disease, amyloid A amyloidosis, polymyalgia rheumatica, and spondylarthritides. It has been demonstrated that an imbalance of CD4‐positive T‐helper subsets [Th17 and/or Th1 >> regulatory T cells (Treg)] plays a major role in the development of several autoimmune disorders. In murine models of autoimmune disorders, the anti‐IL‐6 receptor antibody induced Treg and inhibited Th17 and/or Th1 differentiation, indicating that tocilizumab treatment may be able to repair this imbalance in human diseases as well. Drug Dev Res 72:717–732, 2011. © 2011 Wiley Periodicals, Inc.
Predictors of medication adherence in patients with rheumatoid arthritis
Authors: Salt Elizabeth , Frazier Susan K. 
Published: December 2011

AbstractMedication adherence is a significant problem in patients with rheumatoid arthritis (RA), a prevalent autoimmune disease. Because of the equivocal results reported in the research, consistent predictors of medication adherence in patients with RA are undetermined. A cross‐sectional descriptive, predictive study of 108 patients with RA was used to: (1) describe self‐reported medication adherence to disease‐modifying anti‐rheumatic drugs (DMARDs); (2) compare demographic (age, residence, marital status, employment status, years of education, and ethnicity) and clinical (duration of disease and number of medications) factors of adherent and nonadherent individuals; and (3) determine the predictive power of demographic and clinical factors for DMARD adherence using various cut‐points (research‐based, mean, and median) on a validated, self‐report scale measuring medication adherence. Independent samples t‐tests, Chi‐square analyses, and logistic regression modeling were used to analyze these data. Approximately 90% of the individuals with RA reported adherence with their prescribed DMARD prescriptions. The only demographic and clinical difference between the adherent and nonadherent group was ethnicity (P = 0.04); non‐Caucasian individuals reported significantly less adherence with their prescribed DMARDs when compared with Caucasian individuals. Logistic regression models identified ethnicity (OR = 3.34–10.1; P<0.05) and the number of medications taken (OR = 1.7; P<0.05) as predictors of medication nonadherence. These data provide evidence that ethnicity and taking an increased number of prescribed medications are independent predictors of medication adherence in patients with RA. These findings confirm the presence of a health disparity and an area in which further research is needed to optimize patient outcomes. Drug Dev Res 72:756–763, 2011. © 2011 Wiley Periodicals, Inc.
Inverse vaccination with islet autoantigens to halt progression of autoimmune diabetes
Authors: Hinke Simon A. 
Published: December 2011

AbstractThe incidence of autoimmune diabetes mellitus is growing worldwide; currently the only treatment is injection of insulin formulations to maintain glycemic control. Islet transplantation has been examined as a potential cure for diabetes. However, it has several limitations, including side effects of immunosuppressive agents required to prevent graft rejection. Other approaches have been to examine immune modulation to halt or prevent the autoimmune attack, with the hope that by preventing tissue damage, it will eventually regenerate and permit patients to be free from insulin injections. The focus of the current review is the three major antigen‐based vaccines, insulin, glutamic acid decarboxylase 65 (GAD65; Diamyd), and heat shock protein 60 (Hsp60; DiaPep277), with respect to their mechanism of action, preclinical results, and published results from clinical trials. Despite promising results with these three antigens in mice and humans, efficacy has been limited in clinical trials. Drug Dev Res 72:788–804, 2011. © 2011 Wiley Periodicals, Inc.
Diarylheptanoid Glucosides from Pyrostria major and Their Antiprotozoal Activities
Authors: Beniddir Mehdi A. , Grellier Philippe , Rasoanaivo Philippe , Loiseau Philippe M. , Bories Christian , Dumontet Vincent , Guéritte Françoise , Litaudon Marc 
Published: December 2011

AbstractEight new diarylheptanoid glucosides 1–8 have been isolated from the leaves of Pyrostria major (A. Rich & DC.) Cavaco [syn. Canthium major (A. Rich & DC.)] Cavaco. Their structures were determined by 1D and 2D NMR spectroscopic and HRMS analyses. The absolute configurations of the diarylheptanoids 1–4 were determined to be 3S and 5S by the application of the CD exciton chirality method to the corresponding 3,5‐bis(p‐bromobenzoyl) (1–3) and 3,5‐bis(p‐dimethylaminobenzoyl) (4) derivatives. Their antiparasitic activities against Plasmodium falciparum, Leishmania donovani (amastigote forms), and Trypanosoma brucei (trypomastigote bloodstream forms) as well as their cytotoxic activities against the HL‐60, KB, and MRC5 cell lines of naturally occurring diarylheptanoid glucosides and their derivatives are reported.
A Lead Film Electrode for Adsorptive Stripping Voltammetric Analysis of Ultratrace Tungsten(VI) in Acidic Medium
Authors: Tyszczuk‐Rotko Katarzyna , Maj Joanna 
Published: December 2011

AbstractFor the first time an in situ plated lead film electrode was applied to adsorptive stripping voltammetry at relatively strong acidic conditions of, e.g., pH 2. As an example of the application of such electrode a procedure for ultratrace W(VI) determination by adsorptive stripping voltammetry was elaborated. The procedure is based on the preconcentration of the W(VI)‐Alizarin Red S complex at an in situ plated lead film electrode held at −0.575 V (vs. Ag/AgCl), followed by a negatively sweeping square wave voltammetric scan. The proposed voltammetric procedure was applied to W(VI) determination in natural water samples.
Carbon dioxide fluxes and DOC concentrations of eroding blanket peat gullies
Authors: Clay Gareth D. , Dixon Simon , Evans Martin G. , Rowson James G. , Worrall Fred 
Published: December 2011

ABSTRACTUK peatlands are affected by severe gully erosion with consequent impacts on ecosystem services from these areas. Incision into the peat can damage the vegetation and hydrology and lead to increases in carbon loss and sediment transfer downstream. Gullies represent then a conduit for and a hotspot of carbon loss but the relatively high water tables of gullies have meant that they have been identified as areas with a high restoration potential because of easily restored peat‐forming conditions. This study uses a series of gully sites, subject to different restoration interventions, to investigate differences in carbon pathways (DOC, CO2) and hydrology between restoration strategies and gully position. The results show that the position within the gully (interfluve, gully side, or gully floor) does not significantly affect water quality but that it plays a significant role in CO2 exchange. Gully floors are areas of high photosynthesis and ecosystem respiration, though net ecosystem exchange is not significantly different across the gully. While gully position plays a role in the cycling of some carbon species, this study highlights the importance of vegetation as a key control on carbon cycling. Copyright © 2012 John Wiley & Sons, Ltd.
The origins of mechanical conservation principles and variational calculus in the 17th century
Authors: Stein Erwin 
Published: December 2011

AbstractThe 17th century is considered as the cradle of modern natural sciences and technology as well as the begin of the age of enlightenment with the invention of analytical geometry by R. Descartes (1637), infinitesimal calculus by I. Newton (1668) and G. W. Leibniz (1674), and based on the rational mechanics by I. Newton (1687), initiated by G. Galilei (1638). In 1696, Johann Bernoulli posed the so‐called brachistochrone problem in Acta Eruditorum, asking for solutions within a year's time. Seven solutions were submitted and published in 1697, the most famous one by his brother Jacob Bernoulli, anticipating L. Euler's idea of discrete equidistant support points and triangular test functions between three neighboured points, followed by the infinitesimal limit. Johann Bernoulli himself presented two intelligent solutions by joining geometrical and mechanical observations. G.W. Leibniz submitted a geometrical integration method for the differential equation of the cycloid and, what is important for this article, a short draft of a discrete or “direct variational” numerical approximation method, also using triangular test functions between neighboured support points with finite distances. This can be considered as a precursor of the finite element method. In connection with the brachistochrone, more general tautochrony problems were investigated, e.g. by Ch. Huygens and I. Newton. In conclusion many important developments of energy methods in mechanics using variational methods were already invented in the 17th century (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Die Entwicklung der Analytischen Mechanik von Euler, Lagrange und Hamilton aus studentischer Sicht
Authors: Gerstner Maximilian , Schmitt Patrick R. , Steinmann Paul 
Published: December 2011

AbstractDie mit der Analytischen Mechanik entwickelten Techniken und Methoden spielen gerade heute immer noch eine entscheidende Rolle in vielen Bereichen der Physik, der Ingenieurwissenschaften und für zahlreiche technische Anwendungsfälle. Im vorliegenden Beitrag soll die historische Entwicklung dieser Theorie durch Leonhard Euler (1707–1783), Joseph‐Louis Lagrange (1736–1813) und Sir William Rowan Hamilton (1805–1865) kurz dargestellt und anhand des einfachen Beispiels des Fadenpendels oder auch mathematischen Pendels illustriert werden. In der Zusammenfassung wird kurz die weitere Entwicklung dieser Theorie in der modernen Mathematik und Physik geschildert und auf wenige ausgewählte Anwendungsfälle eingegangen (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)