bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for an hMSH3 defect in familial hamartomatous polyps
Authors: Huang Sherry C. , Lee Jeffrey K. , Smith E. Julieta , Doctolero Ryan T. , Tajima Akihiro , Beck Stayce E. , Weidner Noel , Carethers John M. 
Published: September 2010

AbstractBACKGROUND:Patients with hamartomatous polyposis syndromes have increased risk for colorectal cancer (CRC). Although progression of polyps to carcinoma is observed, pathogenic mechanisms remain unknown. The authors examined whether familial hamartomatous polyps harbor defects in DNA mismatch repair (MMR), and assayed for somatic mutation of PTEN, a gene inactivated in the germline of some hamartomatous polyposis syndrome patients.METHODS:Ten hamartomatous polyposis syndrome patients were genotyped for germline mutations. Epithelial and nonepithelial polyp DNA were assayed for microsatellite instability (MSI) and PTEN frameshift mutation. DNA MMR and PTEN protein expression were assessed in all polyps by immunohistochemistry. In addition, 99 MSI‐high sporadic CRCs and 50 each of hMLH1−/− and hMSH3−/− cell clones were examined for PTEN frameshifts.RESULTS:Twenty‐five (58%) of 43 hamartomatous polyposis syndrome polyps demonstrated dinucleotide or greater MSI in polyp epithelium, consistent with hMSH3 deficiency. MSI domains lost hMSH3 expression, and PTEN expression was lost in polyps from germline PTEN patients; sporadic hamartomatous polyps did not show any of these findings. PTEN analysis revealed wild type exon 7 and 8 sequences suggestive of nonexistent or rare events for PTEN frameshifts; however, MSI‐high sporadic CRC showed 11 (11%) of 99 frameshifts within PTEN, with 4 tumors having complete loss of PTEN expression. Subcloning hMLH1−/− and hMSH3−/− cells revealed somatic PTEN frameshifts in 4% and 12% of clones, respectively.CONCLUSIONS:Nondysplastic epithelium from hamartomatous polyposis syndrome polyps harbors hMSH3 defects, which may prime neoplastic transformation. Polyps from PTEN+/− patients lose PTEN expression, but loss is not a universal early feature of all hamartomatous polyposis syndrome. However, PTEN frameshifts can occur in hMSH3‐deficient cells, suggesting that hMSH3 deficiency could drive hamartomatous polyposis syndrome tumorigenesis. Cancer 2011. © 2010 American Cancer Society.
Current event‐free survival after sequential tyrosine kinase inhibitor therapy for chronic myeloid leukemia
Authors: Al‐Kali Aref , Kantarjian Hagop , Shan Jianqin , Bassett Roland , Quintás‐Cardama Alfonso , Borthakur Gautam , Jabbour Elias , Verstovsek Srdan , O'Brien Susan , Cortes Jorge 
Published: September 2010

AbstractBACKGROUND:Imatinib is an effective tyrosine kinase inhibitor (TKI) for patients with chronic myeloid leukemia (CML) in chronic phase (CP). Although some patients may fail on therapy with imatinib, effective salvage therapy is available with second‐generation TKIs. Current measurement of efficacy for each therapy is judged by its individual impact on overall survival and event‐free survival (EFS).METHODS:In total, 586 patients with CML in CP who received imatinib were included in this analysis in 2 cohorts: imatinib as front‐line therapy (n = 281) or after failure on interferon‐α (IFN‐α) (n = 305). By accounting for successful salvage treatment (ie, regain of complete cytogenetic response), the current EFS (CEFS) rate was calculated to obtain a more accurate impression of the outcome of patients with CML who received treatment with sequential TKIs.RESULTS:For patients who received imatinib after failing on IFN‐α, the 7‐year EFS rate was 61%, whereas the CEFS rate was 69%. The 7‐year EFS rate for patients who received imatinib as initial therapy was 81% compared with a 7‐year CEFS rate of 88%.CONCLUSIONS:CEFS provided a more accurate representation of the outcome of patients with CML in CP. These patients may frequently be treated successfully with subsequent TKIs after experiencing failure on the first TKI. Cancer 2011. © 2010 American Cancer Society
Partial regularity for weak heat flows into spheres
Authors: Chen Yunmei , Li Jiayu , Lin Fang‐Hua 
Published: September 2010

AbstractIn this paper we show that a weak heat flow of harmonic maps from a compact Riemannian manifold (possibly with boundary) into a sphere, satisfying the monotonicity inequality and the energy inequality, is regular off a closed set of m‐dimensional Hausdorff measure zero.
Toward a better understanding of depression and anxiety. The importance of tryptophan hydroxylase activation blockade: The origin of a unique anxiolytic antidepressant
Authors: Gittos Maurice W. 
Published: September 2010

AbstractThe serotonin (5‐HT) deficiency theory of depression has misled medical science. Inhibitors of 5‐HT reuptake were the basis of the hypothesis and display limited efficacy with a pronounced delay of onset in action coupled with a side‐effect profile that includes increased anxiety. In the present commentary, a recommendation for the reinstatement of the prolongation of the d‐amphetamine stereotypy test is made as a means to generate new molecules capable of blocking stress‐induced tryptophan hydroxylase (TPH) activation and its elevation of 5‐HT, now regarded as the cause of depression The selective TPH activation inhibitor, AGN 2979, is already known to exert powerful, rapid antidepressant and anxiolytic properties in the clinic with a notable lack of the side effects associated with monoamine reuptake inhibition. Drug Dev Res 71:331–334, 2010. © 2010 Wiley‐Liss, Inc.
Loss ofLhx1activity impacts on the localization of primordial germ cells in the mouse
Authors: Tanaka Satomi S. , Yamaguchi Yasuka L. , Steiner Kirsten A. , Nakano Toru , Nishinakamura Ryuichi , Kwan Kin Ming , Behringer Richard R. , Tam Patrick P.L. 
Published: September 2010

AbstractMouse embryos lackingLhx1(Lim1) activity display defective gastrulation and are deficient of primordial germ cells (PGCs) (Tsang et al. [2001]International Journal of Developmental Biology45:549–555). To dissect the specific role of Lhx1 in germ cell development, we studied embryos with conditional inactivation ofLhx1activity in epiblast derivatives, which, in contrast to completely null embryos, develop normally through gastrulation before manifesting a head truncation phenotype. Initially, PGCs are localized properly to the definitive endoderm of the posterior gut in the conditional mutant embryos, but they depart from the embryonic gut prematurely. The early exit of PGCs from the gut is accompanied by the failure to maintain a strong expression ofIfitm1in the mesoderm enveloping the gut, which may mediate the repulsive activity that facilitates the retention of PGCs in the hindgut during early organogenesis.Lhx1therefore may influence the localization of PGCs by modulatingIfitm1‐mediated repulsive activity. Developmental Dynamics 239:2851–2859, 2010. © 2010 Wiley‐Liss, Inc.
Water framework directive implementation in Greece: Introducing participation in water governance – the Case of the Evrotas River Basin management plan
Authors: Demetropoulou Leeda , Nikolaidis Nikolaos , Papadoulakis Vasilis , Tsakiris Kostas , Koussouris Theodore , Kalogerakis Nikolaos , Koukaras Kostas , Chatzinikolaou Anastasia , Theodoropoulos Kostas 
Published: September 2010

AbstractAccepting the positive results that public participation can bring in the implementation of the Water Framework Directive (WFD), this paper seeks to contribute to ongoing discussions on the rather problematic WFD implementation in southern Europe. Within this framework, we first focus on the national level and the analysis of ‘water governance’ and ‘public participation’ within the context of WFD implementation in Greece, and secondly on the examination of the participatory methods introduced locally for the preparation of the Evrotas River Basin management plan. The first section focuses on public participation as an indispensable ingredient of good water governance. The next focuses on the introduction of the WFD as an instance of governance that promotes participatory arrangements. We then present the centralized structure of the Greek state as an impediment to the introduction of public participation in water governance. The fourth section focuses on the Evrotas River Basin and describes the participatory arrangements for the preparation of the management plan. The paper concludes with the verification of the need for participatory processes to respect the context within which they are pursued and with specific alterations to the way public participation has been planned and implemented in Greece. Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment.
Effect of three‐dimensional expansion and cell seeding density on the cartilage‐forming capacity of human articular chondrocytes in type II collagen sponges
Authors: Francioli Silvia E. , Candrian Christian , Martin Katja , Heberer Michael , Martin Ivan , Barbero Andrea 
Published: September 2010

AbstractChondrocytes for tissue engineering strategies are typically expanded in monolayer (2D), leading to cell dedifferentiation but allowing to generate large cell numbers for seeding into scaffolds. Direct chondrocyte culture in scaffolds, instead, may support better maintenance of the differentiated phenotype but reduce the extent of proliferation and thus the resulting cell density. This study investigates whether the quality of cartilaginous tissues generated in vitro by human articular chondrocytes (HAC) on type II collagen sponges is enhanced (1) by direct expansion on the scaffolds (3D), as compared with standard 2D, or (2) by increasing cell seeding density, which in turn requires extensive 2D expansion. Three‐dimensional expansion of HAC on the scaffolds, as compared with 2D expansion for the same number of doublings, better maintained the chondrocytic phenotype of the expanded cells (13.7‐fold higher levels of type II collagen mRNA) but did not enhance their accumulation of glycosaminoglycan (GAG) following chondrogenic culture. Instead, increasing the HAC seeding density in the scaffolds (from 25 × 103 to 66 × 103 cells/mm3) significantly improved chondrogenesis (up to 3.3‐fold higher GAG accumulation and up to 9.3‐fold higher type II collagen mRNA), even if seeded cells had to be expanded and dedifferentiated more extensively in 2D to reach the required cell numbers. This study indicates that, under the specific conditions tested, a high‐seeding density of HAC in 3D scaffolds is more critical for the generation of cartilaginous constructs than the stage of cell differentiation reached following expansion. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Awake at 4 a.m.: treatment of insomnia with early morning awakenings among older adults
Authors: Fiorentino Lavinia , Martin Jennifer L. 
Published: September 2010

AbstractInsomnia is a common problem among older adults. In particular, older adults experience insomnia coupled with early morning awakenings due to an interaction between age‐related changes in circadian rhythm timing coupled with behavior changes that contribute to sustained poor sleep. Cognitive–behavioral therapy for insomnia (CBT‐I), at times coupled with circadian interventions (e.g., timed light exposure), are likely to be most successful in optimizing sleep quality. In delivering CBT‐I to older adults, modifications are sometimes necessary to accommodate for medical problems, lifestyle, social factors, and patient preferences. Addition of circadian interventions can ameliorate the negative effects of inappropriately timed sleep as well. These treatment methods can be highly effective and benefits can be long‐standing. A case example is used to illustrate these points. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 66:1–14, 2010.
AMP‐activated protein kinase: ‘a cup of tea’ against cholesterol‐induced neurotoxicity
Authors: Martínez de Morentin Pablo Blanco , González Carmen R , López Miguel 
Published: September 2010

AbstractDisturbances in brain cholesterol metabolism have been linked to Alzheimer's disease (AD) pathology. A high‐cholesterol diet increases fibrillar amyloid β peptide (Aβ) deposition, inflammation, and apoptosis that eventually results in neurodegeneration and learning and memory impairments. In the October 2010 issue of The Journal of Pathology, Lu and colleagues provided a novel and interesting mechanism that explains how quercetin, a flavonoid found at high concentrations in green and black teas, may help to protect against cholesterol‐induced neurotoxicity through activation of AMP‐activated protein kinase (AMPK), a metabolic energy gauge. Further work will be necessary to address whether AMPK may be a potential target to combat neurodegenerative diseases. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Invited Commentary for Lu et al. Quercetin activates AMP‐activated protein kinase by reducing PP2C expression protecting old mouse brain against high cholesterol‐induced neurotoxicity, Journal of Pathology, 2010; 222 199–212.
The knowledge, perceptions and practice of pharmacovigilance amongst community pharmacists in Lagos state, south west Nigeria
Authors: Oreagba I. A. , Ogunleye O. J. , Olayemi S. O. 
Published: September 2010

AbstractPurposeCommunity Pharmacists both have an important responsibility in monitoring the ongoing safety of medicines and are widely accessible to do it. This study aims to investigate the knowledge, perceptions and practice of Pharmacovigilance amongst community pharmacists in Lagos State, South West NigeriaMethodsA cross‐sectional observational survey was used in this study. A multistage random sampling technique was employed in the selection of 420 community pharmacies in Lagos.ResultsAbout 55% of respondents have ever heard of the word ‘Pharmacovigilance’ out of which less than half (representing only 18% of all respondents) could define the term ‘Pharmacovigilance’. Forty percent of the respondents stated that patients reported ADRs to them at least once a month, and 20% reported to the relevant authorities. However only 3% of respondents actually reported an ADR to the National Pharmacovigilance Centre. The most important reason for poor reporting was lack of knowledge about how to report ADRs (44.6%).Meanwhile, 90% of respondents believed that the role of the pharmacists in ADR reporting was important. Most community pharmacists were willing to practice pharmacovigilance if they were trained.ConclusionCommunity pharmacists in Lagos had poor knowledge about pharmacovigilance. Reporting rate was also poor. There is an urgent need for educational programs to train pharmacists about pharmacovigilance and ADR reporting. Copyright © 2010 John Wiley & Sons, Ltd.
Der Fehlersucher
Authors: Loos Andreas 
Published: September 2010

AbstractWenn zwei Astronomen denselben Sterndurchgang beobachten, dann weichen ihre Messungen stets ein wenig voneinander ab. Doch als erfahrener Astronom riecht der Gesuchte hinter solchen Unterschieden mehr als Zufall. Er hält sie für systematische Fehler, abhängig vom jeweiligen Beobachter und dessen Instrument. Das vermeintliche Phänomen tauft er die “persönliche Differenz.” Jahrelang versucht er, ihm auf die Spur zu kommen. Vergeblich.
Handfeste Emulsionen
Authors: Vilgis Thomas 
Published: September 2010

AbstractEmulsionen aus Öl und Wasser, wie Mayonnaisen, gehören zum Standardprogramm jeder kreativen Küche. Trotz der Formbeständigkeit der Mayonnaisehäubchen auf den Tellern bleibt die Emulsion eine Flüssigkeit. Kleine Scherkräfte reichen aus, und die Mayonnaise beginnt zu fließen. Für feste, schnittfeste Emulsionen hilft es, die kontinuierliche Phase zu gelieren.
Elastic properties of nanowires
Authors: Röhlig Claus‐Christian , Niebelschütz Merten , Brueckner Klemens , Tonisch Katja , Ambacher Oliver , Cimalla Volker 
Published: September 2010

AbstractThe elastic properties of metallic and semiconducting nanowires were analyzed by different techniques employing static and dynamic loads. The reliability of the methods is verified by analyzing well defined microstructures and a good agreement for the values of the Young's modulus determined by the different methods was achieved. For the investigated materials systems (Au, W, Si, InN), basically no differences in the Young's moduli were observed between microstructures, bulk material, and nanowires with radii of 20–300 nm. Microstructure, morphological undulation, defects, and contaminations, however, can drastically change the apparent Young's moduli of nanowires. Examples are given, where an apparent increasing or decreasing of the Young's modulus with decreasing diameter is caused by such effects. The same effects have also influence on the fracture strength in nanowires. While perfect Au nanowires exhibit fracture strengths exceeding the bulk values up to two orders of magnitude, any anomaly causes earlier failure. In addition, failure mechanisms are observed to be dependent on the microstructure. While single crystalline Au nanowires have shown a pure elastic deformation upon load, polycrystalline nanowires show a remarkable plastic deformation before breaking.
Simultaneous selective detection of organophosphate and phthalate esters using gas chromatography with positive ion chemical ionization tandem mass spectrometry and its application to indoor air and dust
Authors: Bergh Caroline , Torgrip Ralf , Östman Conny 
Published: September 2010

AbstractA selective and sensitive method for the simultaneous determination of 14 organophosphate and six phthalate esters using gas chromatography (GC) and mass spectrometry (MS) is presented. Both of these compound classes are frequently found in the indoor environment due to their use as bulk additives in numerous polymers, consumer products and building materials. GC/MS utilizing positive ion chemical ionisation (PICI) in selected reaction monitoring (SRM) mode with isobutane as the reagent gas was found to be the best of the tested methods; it proved superior to electron ionisation (EI) in selected ion monitoring (SIM) mode and to PICI using methane as the reagent gas. The method was applied to indoor air samples collected by active air sampling using solid‐phase extraction (SPE) cartridges. Organophosphates and phthalates were simultaneously determined with method detection limits (MDLs) in the range of 0.1–47 ng m−3. For most compounds the MDLs were ≤0.2 ng m−3, but due to the presence of some of these ubiquitous indoor air pollutants in the blanks, significantly higher MDLs were observed for a few compounds. Finally, the method was also applied in the screening of a much more complex sample matrix, indoor dust. Copyright © 2010 John Wiley & Sons, Ltd.
Liquid chromatography/tandem mass spectrometry assay for the absolute quantification of the expected circulating apelin peptides in human plasma
Authors: Mesmin Cédric , Dubois Mathieu , Becher François , Fenaille François , Ezan Eric 
Published: September 2010

AbstractApelin peptides are of great interest owing to their involvement in physiological and pathological processes and they have been proposed as novel biomarkers for heart failure. The plasma concentrations of bioactive peptides of 12 (apelin‐12), 13 (apelin‐13) and pyroglutamyl apelin‐13 (apelin‐p13), 17 (apelin‐17) and 36 (apelin‐36) amino acids are reported to range from 20 to 4000 pg/mL in healthy subjects. As standard immunoassays cannot specifically quantify each apelin peptide, we have developed a sensitive and targeted multiplexed liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for each plasma apelin fragment. The approach was based on a cation‐exchange extraction step of apelin forms present in human plasma. Apelin‐12, ‐13, ‐p13, ‐17 and ‐36 were quantified using a triple quadrupole mass spectrometer operating in the multiple reaction monitoring mode. Stable isotope‐labeled internal standards were used for quantification. Following assay validation, apelin peptide stability in plasma was investigated. Ten plasma samples from healthy donors were analyzed both with a standard immunoassay and with our LC/MS/MS method. The immunoassay results for the ten healthy donors showed immunoreactive plasma apelin concentrations ranging from 208 to 466 pg/mL. The lower limits of detection of our LC/MS/MS assay ranged from 10 to 50 pg/mL for apelin‐12, ‐13, ‐p13, ‐17, and ‐36. Surprisingly, none of the five expected circulating forms of apelin was detected. These results question the nature and/or the concentration of circulating apelin peptides as well as the specificity of the immunoassays that have hitherto been used for clinical applications. Copyright © 2010 John Wiley & Sons, Ltd.
Impact assessment in the automotive industry: mandatory market introduction of alternative powertrain technologies
Authors: Walther Grit , Wansart Jörg , Kieckhäfer Karsten , Schnieder Eckehard , Spengler Thomas S. 
Published: September 2010

AbstractIncreasing numbers of regulatory measures are being introduced worldwide to reduce emissions from the transportation sector. In California, whose low emission vehicle regulations have a leading position worldwide, automobile manufacturers must reduce greenhouse gas emissions of their vehicle fleet (GHG regulations) and sell increasing shares of zero emission vehicles (ZEV regulations). Manufacturers have to pay high penalties in case of non‐compliance. A dynamic simulation model examines fundamental automobile manufacturer strategies for compliance. Co‐evolutionary development of powertrain technologies, corresponding infrastructure coverage, vehicle types offered, and customer behavior during the adjustment to regulations, is considered. The model is applied to a case study considering the state of California. Results show that meeting requirements necessitates an early introduction of alternative powertrains in many vehicle segments. Feedback between GHG and ZEV regulations necessitates the development of joint compliance strategies. Recommendations are derived concerning appropriate manufacturer strategies for complying with California's regulations. Copyright © 2010 John Wiley & Sons, Ltd.
Adenomatous Polyposis Coli Is Essential for Both Neuronal Differentiation and Maintenance of Adult Neural Stem Cells in Subventricular Zone and Hippocampus
Authors: Imura Tetsuya , Wang Xiaohong , Noda Tetsuo , Sofroniew Michael V. , Fushiki Shinji 
Published: September 2010

Abstract
The tumor suppressor adenomatous polyposis coli (APC) is a multifunctional protein that not only inhibits the Wnt signaling pathway by promoting the degradation of β-catenin but also controls cell polarity, motility, and division. APC is abundantly expressed in the adult central nervous system, but its role in adult neurogenesis remains unknown. Using conditional deletion (or knockout) of APC (APC-CKO) from glial fibrillary acidic protein (GFAP)-expressing cells including adult neural stem cells (NSCs) in the subventricular zone and hippocampal dentate gyrus, we show that APC expression by these cells is a critical component of adult neurogenesis. Loss of APC function resulted in a marked reduction of GFAP-expressing NSC-derived new neurons, leading to the decreased volume of olfactory granule cell layer. Two distinct mechanisms account for impaired neurogenesis in APC-CKO mice. First, APC was highly expressed in migrating neuroblasts and APC deletion disturbed the differentiation from Mash1-expressing transient amplifying cells to neuroblasts with concomitant accumulation of β-catenin. As a result, migrating neuroblasts decreased, whereas Mash1-expressing dividing cells reciprocally increased in the olfactory bulb of APC-CKO mice. Second, APC deletion promoted an exhaustion of the adult germinal zone. Functional NSCs and their progeny progressively depleted with age. These findings demonstrate that APC expression plays a key role in regulating intracellular β-catenin level and neuronal differentiation of newly generated cells, as well as maintaining NSCs in the adult neurogenic niche.