bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Sensitivity and Selectivity of Chemosensor for Malonate by Anchoring on Gold Nanoparticles
Authors: Liu Yanyun , Liu Yun , Liang Zhongshi , Li Xiangyang , Liu Shunying , Yu Jiahui
Published: March 2011

A novel organic‐inorganic nanohybrided receptor 4 functionalized with bis‐thiourea arms and then assembled on gold nanoparticles was synthesized. The preorganized system possesses phenylthiourea units for the spectrophotometric sensing of dicarboxylates, especially malonate, based on changes in the surface plasmon absorption of the gold nanoparticles (GNPs). The intensity of the absorbance band increases gradually with the concentration of dicarboxylates increasing. But such an ion‐selective change in the plasmon band was not observed in control tests carried out by mono‐thiourea‐modified GNPs, receptor 3and the free receptor2. As it is shown from the association constants, derived from quantitative titrations, receptor 4 can selectively recognize dicarboxylate anions of shorter carbon chain, and has the highest affinity to malonate. The interaction properties for anions of receptor 4 were evaluated by 1H NMR and UV‐vis spectroscopic methods.
Is resection of colorectal liver metastases after a second‐line chemotherapy regimen justified?
Authors: Brouquet Antoine , Overman Michael J. , Kopetz Scott , Maru Dipen M. , Loyer Evelyne M. , Andreou Andreas , Cooper Amanda , Curley Steven A. , Garrett Christopher R. , Abdalla Eddie K. , Vauthey Jean‐Nicolas
Published: March 2011

BACKGROUND:

Patient outcomes following resection of colorectal liver metastases (CLM) after second‐line chemotherapy regimen is unknown.

METHODS:

From August 1998 to June 2009, data from 1099 patients with CLM were collected prospectively. We retrospectively analyzed outcomes of patients who underwent resection of CLM after second‐line (2 or more) chemotherapy regimens.

RESULTS:

Sixty patients underwent resection of CLM after 2 or more chemotherapy regimens. Patients had advanced CLM (mean number of CLM ± standard deviation, 4 ± 3.5; mean maximum size of CLM, 5 ± 3.2 cm) and had received 17 ± 8 cycles of preoperative chemotherapy. In 54 (90%) patients, the switch from the first regimen to another regimen was motivated by tumor progression or suboptimal radiographic response. All patients received irinotecan or oxaliplatin, and the majority (42/60 [70%]) received a monoclonal antibody (bevacizumab or cetuximab) as part of the last preoperative regimen. Postoperative morbidity and mortality rates were 33% and 3%, respectively. At a median follow‐up of 32 months, 1‐year, 3‐year, and 5‐year overall survival rates were 83%, 41%, and 22%, respectively. Median chemotherapy‐free survival after resection or completion of additional chemotherapy administered after resection was 9 months (95% confidence interval, 4‐14 months). Synchronous (vs metachronous) CLM and minor (vs major) pathologic response were independently associated with worse survival.

CONCLUSIONS:

Resection of CLM after a second‐line chemotherapy regimen was found to be safe and was associated with a modest hope for definitive cure. This approach represents a viable option in patients with advanced CLM. Cancer 2011;. © 2011 American Cancer Society.
Corporate Reputation: A Combination of Social Responsibility and Industry
Authors: Melo Tiago , Garrido‐Morgado Alvaro
Published: March 2011

We use the technique of panel data in a sample of 320 American listed companies from 2003 to 2007 to estimate a model of corporate reputation, measured by the Fortune index. We propose that corporate social responsibility (CSR) is a key driver of corporate reputation given its potential to foster hard‐to‐duplicate competitive advantage. Our model embodies the multidimensional concept of CSR, presenting a five dimensional construct – employee relations, diversity issues, product issues, community relations, and environmental issues – and interact those with industrial effects. Our results indicate that the five dimensions of CSR have a significant impact on corporate reputation and this impact is moderated by the industry of the firm. The most salient dimensions were diversity of the work force – was positively relevant to eight of the nine industries; and product issues with a positive impact in five industries and negative in three. Copyright © 2011 John Wiley & Sons, Ltd and ERP Environment.
A novel variable frequency modulation technique to improve light‐load efficiency for multiphase synchronous rectified VRM
Authors: Ou Sheng‐Yuan , Hsiao Ho‐Pu , Su Huei‐Fa
Published: March 2011

A novel variable frequency modulation technique for multiphase synchronous rectified voltage regulator module (VRM) is proposed in this paper. The proposed technique provides zero voltage switching (ZVS) for high‐side and low‐side power switches under both light‐ and heavy‐load conditions, thereby increasing the efficiency as compared to the conventional approach. The dependency of switching frequency on the load condition for the proposed modulation technique and the related conduction loss are analyzed. It will be shown that the frequency increases for light‐load condition in order to retain ZVS and decrease the conduction loss. Although the switching loss will slightly increase due to the increase of switching frequency, the analysis and experimental results will show that the contribution of frequency increasing can cover this additional loss. Experimental results derived from a single‐phase and an eight‐phase synchronous rectified VRM show that the proposed modulation technique is superior to the conventional one and compared to conventional constant switching frequency techniques with 250 and 550thinspacekHz, the efficiency can be increased up to 17 and 5% for single‐phase VRM and 8 and 4% for eight‐phase VRM under various load conditions. Even an off‐the‐shelf controller with an additional simple and cheap control circuit comprising one switch, two operational amplifiers and several resistors is used to realize the proposed technique, that is, a very low cost and small circuitry is attached to gain the significant benefit. Copyright © 2011 John Wiley & Sons, Ltd.
Determination of flavour loading in complex delivery systems by time‐domain NMR
Authors: Hafner Valeria , Dardelle Gregory , Normand Valéry , Fieber Wolfgang
Published: March 2011

The determination of the flavour content of a newly developed encapsulation system based on yeast was attempted using time‐domain NMR (TD‐NMR) and compared to thermo gravimetric analysis (TGA). Flavour content as measured by TD‐NMR is systematically higher than by TGA. The constant discrepancy between the two techniques is attributed to the presence of the phospholipidic membrane inside the yeast. These phospholipids also contribute to the NMR signal as was revealed by high field NMR studies under magic angle spinning conditions. The signal obtained for the empty yeast matched the extra‐contribution to the signal of the flavoured yeast encapsulation system. A classical glassy encapsulation system was used as a comparison to highlight further the presence of the phospholipids in the yeast system. A two step procedure is proposed to correct the reading of the flavoured yeast for the contribution of the yeast cells themselves.

Practical applications: TD‐NMR is routinely used for the determination of the liquid content encapsulated in a solid matrix, where the liquid can be any oil, including lipids, or flavour and fragrance oils. As shown in the present study, in order to obtain accurate values of the oil loading, the nature of the carrier material of the encapsulation system must be taken into account. For example, with the conventional TD‐NMR method, flavour loading in encapsulation systems in yeast cells is systematically overestimated since the phospholipid bilayer contributes to the NMR signal of the flavour oil. With the two‐step procedure presented in this article, by subtracting the baseline value obtained for empty yeast cells, accurate loading values for yeast cell carriers can be determined. The modified testing approach is highly accurate and widely applicable to a variety of liquids including flavours, perfumes or nutritive fish oils encapsulated in solid delivery systems.
Total Synthesis of the (+)‐Antimycin A Family
Authors: Inai Makoto , Nishii Takeshi , Tanaka Ayako , Kaku Hiroto , Horikawa Mitsuyo , Tsunoda Tetsuto
Published: March 2011

An asymmetric aldol reaction using Oppolzer's sultam has provided a practical and efficient synthetic route (15 steps, overall yield ca. 24 %) to 12 compounds of the Antimycin A family and deisovalerylblastmycin, which were obtained in pure form on a 60–300 mg scale. In the syntheses, the nine‐membered dilactone ring was constructed successfully by lactonization of a 2‐pyridinethiol ester bearing a TIPS group on the 8‐OH by using the (CuOTf)2·PhH complex.
Influence of soil properties on the performance of Folsomia candida: Implications for its use in soil ecotoxicology testing
Authors: Domene Xavier , Chelinho Sónia , Campana Paolo , Natal-da-Luz Tiago , Alcañiz Josep M , Andrés Pilar , Römbke Jörg , Sousa Paulo
Published: March 2011

Nineteen Mediterranean natural soils with a wide range of properties and the Organisation for Economic Co-operation and Development (OECD) artificial soil were used to assess the influence of soil properties on the results of avoidance and reproduction tests carried out with the soil collembolan species Folsomia candida. Compared to natural soils, the OECD soil was mostly rejected by individuals when a natural soil was offered in avoidance tests, and the number of offspring produced was generally lower than the one obtained in natural soils. None of the soil properties assessed showed a significant influence on the avoidance behavior. More precisely, only soil moisture was included in the model explaining the avoidance response (avoidance increased with increasing differences in moisture), but its contribution was marginally not significant. The model derived explained only 16% of the variance in avoidance response. On the contrary, several soil properties significantly influenced reproduction (number of offspring increased with increasing moisture content, increasing coarse texture, and decreasing nitrogen content). In this case, the model explained 45% of the variance in reproduction. These results, together with the fact that most of the selected soils fulfilled the validity criteria in both avoidance and reproduction tests, confirm the literature experience showing that this species is relatively insensitive to soil properties and hence highly suitable to be used in ecotoxicological tests with natural soils. In addition, our study highlights the need for accuracy in soil moisture adjustment in soil ecotoxicological tests with this species. Otherwise, results of both avoidance and reproduction tests might be biased. Environ. Toxicol. Chem. 2011; 30:1497–1505. © 2011 SETAC
Molecular subclassification of diffuse gliomas: Seeing order in the chaos
Authors: Huse Jason T. , Phillips Heidi S. , Brennan Cameron W.
Published: March 2011

Diffuse gliomas such as astrocytomas and oligodendrogliomas are the most common form of intrinsic brain tumor in adults. Even within a single pathologic class, these tumors are both histologically and molecularly diverse, although not randomly so. Recent large‐scale genomic analyses have revealed patterns of molecular changes within tumor subclasses that harbor distinct underlying biology, clinical prognosis, and pathogenetic routes. Stereotypical mutations in isocitrate dehydrogenase genes (IDH) have been identified in a significant proportion of high‐grade gliomas and the large majority of lower‐grade astrocytomas and oligodendrogliomas. While the role of IDH mutation in oncogenesis is unclear, it appears to carry a positive prognosis and is also highly associated with other prognostic markers such as MGMT methylation, loss of 1p and 19q chromosome arms, and a newly recognized CpG island methylator phenotype (G‐CIMP). This constellation of positive prognostic molecular features is enriched in the transcriptionally defined Proneural glioma subclass and appears to reflect a route of pathogenesis distinct from that taken by other high‐grade diffuse gliomas. Another newly discovered and frequent alteration in glioma, deletion or mutation of the NF1 gene, is strongly correlated with the Mesenchymal transcriptomal signature associated with highly aggressive gliomas. Thus, while the unprecedented level of newly available molecular profiling data may seem at first to needlessly balkanize and complicate glioma subclassification, these analyses are in fact providing a more unified picture of key pathogenetic routes and potential avenues for therapeutic intervention. © 2011 Wiley‐Liss, Inc.
Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice
Authors: Hongthanakorn Chanunta , Chotiyaputta Watcharasak , Oberhelman Kelly , Fontana Robert J. , Marrero Jorge A. , Licari Tracy , Lok Anna S. F.
Published: March 2011

Virological breakthrough (VBT) is the first manifestation of antiviral drug resistance during nucleos(t)ide analogue (NUC) treatment of chronic hepatitis B (CHB), but not all VBTs are due to drug resistance. This study sought to determine the incidence of VBT and genotypic resistance (GR) in patients with CHB who were receiving NUCs in clinical practice. Records of patients with CHB who were receiving NUCs were reviewed. All patients with VBT were tested for drug resistance mutations. Of 148 patients included, 73% were men and mean age was 44.9 years. During a mean follow-up of 37.5 ± 20.1 months, 39 (26%) patients had at least 1 VBT. Of these 39 patients, 15 (38%) were not confirmed to have VBT on retesting, and 10 of these 15 had no evidence of GR. The cumulative probability of VBT, confirmed VBT, and GR at 5 years was 46.1%, 29.7%, and 33.9%, respectively. In multivariate analysis, failure to achieve undetectable hepatitis B virus (HBV) DNA was the only factor significantly associated with VBT. Among the 10 patients who had VBT but no confirmed VBT or GR and who were maintained on the same medications, serum HBV DNA decreased in all 10, and nine had undetectable HBV DNA at a mean of 6.8 months after the VBT. Four patients had persistently undetectable HBV DNA, six had transient increase in HBV DNA during follow-up, and none had GR.

Conclusion:

VBT was common in patients with CHB receiving NUCs in clinical practice, but nearly 40% of the VBTs were not related to antiviral drug resistance. Counseling of patients with CHB on medication adherence and confirmation of VBT and/or GR can avoid unnecessary changes in antiviral medications. (HEPATOLOGY 2011;)
Comparison of environmental risks of pesticides between tropical and nontropical regions
Authors: Sanchez-Bayo Francisco , Hyne Ross V
Published: March 2011

A comparison of environmental risks of pesticides between tropical and nontropical regions has been performed, using data from the literature and modeling outputs based on the physicochemical properties of the compounds. With a few exceptions, the level of risk of exposure for most pesticides in tropical agriculture is similar to that in other climatic regions of the world. Generally, dissipation of pesticides increases under the warm and wet conditions of the tropics, with most of the dissipation occurring through hydrolysis in water and biological degradation in water and soil. High temperatures in the tropics also foster volatilization rates, whereas high precipitation and poor soils tend to increase losses into runoff and, for certain chemicals, affects their leaching behavior. The environmental risk is determined by a balance of soil types, soil organic carbon, pH, and the rates of degradation in the various environmental compartments. Integr Environ Assess Manag 2011;7:577–586. © 2011 SETAC
Endothelin‐1 stimulates colon cancer adjacent fibroblasts
Authors: Knowles Jonathan P. , Shi‐Wen Xu , Haque Samer‐ul , Bhalla Ashish , Dashwood Michael R. , Yang Shiyu , Taylor Irving , Winslet Marc C. , Abraham David J. , Loizidou Marilena
Published: March 2011

Endothelin‐1 (ET‐1) is produced by and stimulates colorectal cancer cells. Fibroblasts produce tumour stroma required for cancer development. We investigated whether ET‐1 stimulated processes involved in tumour stroma production by colonic fibroblasts. Primary human fibroblasts, isolated from normal tissues adjacent to colon cancers, were cultured with or without ET‐1 and its antagonists. Cellular proliferation, migration and contraction were measured. Expression of enzymes involved in tumour stroma development and alterations in gene transcription were determined by Western blotting and genome microarrays. ET‐1 stimulated proliferation, contraction and migration (p < 0.01 v control) and the expression of matrix degrading enzymes TIMP‐1 and MMP‐2, but not MMP‐3. ET‐1 upregulated genes for profibrotic growth factors and receptors, signalling molecules, actin modulators and extracellular matrix components. ET‐1 stimulated colonic fibroblast cellular processes in vitro that are involved in developing tumour stroma. Upregulated genes were consistent with these processes. By acting as a strong stimulus for tumour stroma creation, ET‐1 is proposed as a target for adjuvant cancer therapy.
Synthetic Studies of Biomimetic Diels–Alder Processes toward the Helicterin Family of Natural Products
Authors: Snyder Scott A. , Kontes Ferenc
Published: March 2011

Although the [2.2.2]‐bicyclooctene core of the helicterin, helisorin, and helisterculin class of neolignan natural products could conceivably arise in Nature via Diels–Alder reactions, synthetic explorations have revealed that only under very non‐biomimetic conditions can such cycloadditions be performed. In this article, we provide a personal account of explorations towards this natural product family, sharing some additional unpublished synthetic work to test the viability of an alternate, Diels–Alder‐based, biogenetic hypothesis for the generation of this unique collection of secondary metabolites.
Terpenoid‐Alkaloids: Their Biosynthetic Twist of Fate and Total Synthesis
Authors: Cherney Emily C. , Baran Phil S.
Published: March 2011

Terpenes and alkaloids are ever‐growing classes of natural products that provide new molecular structures that inspire chemists and possess a broad range of biological activity. Terpenoid‐alkaloids originate from the same prenyl units that construct terpene skeletons. However, during biosynthesis, a nitrogen atom (or atoms) is introduced in the form of β‐aminoethanol, ethylamine, or methylamine. Nitrogen incorporation can occur either before, during, or after the cyclase phase. The outcome of this unique biosynthesis is the formation of natural products containing unprecedented structures. These complex structural motifs expose current limitations in organic chemistry, thus providing opportunities for invention. This review focuses on total syntheses of terpenoid‐alkaloids and unique issues presented by this class of natural products. More specifically, it examines how these syntheses relate to the way terpenoid‐alkaloids are made in Nature. Developments in chemistry that have facilitated these syntheses are emphasized, as well as chemical technology needed to conquer those that evade synthesis.
From Total Synthesis to Diverted Total Synthesis: Case Studies in the Amphidinolide Series
Authors: Fürstner Alois
Published: March 2011

Amphidinolides are a class of structurally rather unique macrolides of marine origin which stimulated a lot of creative work in the total synthesis arena over the last decade. This review summarizes the strategies and tactics pursued by our group en route to various amphidinolides of the B, G, H, T, V, X, and Y series. These projects were invariably benefitting from the power of transition metal catalysis, with olefin and alkyne metathesis, palladium‐ and iron cross‐coupling, as well as asymmetric oxidation and reduction chemistry playing particularly prominent roles. Once the total syntheses were completed, the flexibility of the underlying blueprints enabled the extension of our program toward the preparation of non‐natural analogues for biological testing, all of which feature deep‐seated structural modifications in keeping with the logic of “diverted total synthesis”.
Strategy Evolution in the Total Synthesis of Spirastrellolide A Methyl Ester
Authors: Paterson Ian , Dalby Stephen M. , Maltas Philip
Published: March 2011

This review highlights the many challenges overcome during our recent synthetic campaign towards spirastrellolide A, a structurally unprecedented antimitotic marine macrolide that potently and selectively inhibits protein phosphatases, and represents a promising lead for anticancer drug discovery. Faced with the initial stereochemical ambiguities, a flexible and modular synthetic strategy was adopted for the construction of increasingly elaborate fragments of the architecturally complex macrolactone to enable further structural elucidation by detailed NMR analysis. A reliable and convergent synthetic route evolved to encompass the use of boron‐mediated aldol reactions to install much of the required oxygenation pattern and associated stereocenters, together with a tandem double Sharpless asymmetric dihydroxylation and cyclization to efficiently access the signature DEF‐[5,6,6]‐bis‐spiroacetal region from a linear diene precursor. A pivotal sp2‐sp3 Suzuki fragment coupling, followed by a double hydroboration of the resulting diene, then provided an advanced C17‐C40 aldehyde which was coupled with a suitable C1‐C16 alkyne. Following BC‐spiroacetalization, a high yielding Yamaguchi macrolactonization afforded the C1‐C40 macrocyclic core, where the full side chain was then introduced by sequential olefin cross‐metathesis and π‐allyl Stille cross‐coupling, culminating in the first total synthesis of spirastrellolide A methyl ester.
Translating Nature’s Library: The Bryostatins and Function‐Oriented Synthesis
Authors: Wender Paul A. , Loy Brian A. , Schrier Adam J.
Published: March 2011

We review in part our computational, design, synthesis, and biological studies on a remarkable class of compounds and their designed analogs that have led to preclinical candidates for the treatment of cancer, a first‐in‐class approach to Alzheimer’s disease, and a promising strategy to eradicate HIV/AIDS. Because these leads target, in part, protein kinase C (PKC) isozymes, they have therapeutic potential even beyond this striking set of therapeutic indications. This program has given rise to new synthetic methodology and represents an increasingly important direction of synthesis focused on achieving function through synthesis‐informed design (function‐oriented synthesis).
Osteo‐renal regulation of systemic phosphate metabolism
Authors: Razzaque Mohammed Shawkat
Published: March 2011

Impaired kidney function and subsequent skeletal responses play a critical role in disrupting phosphate balance in chronic kidney disease (CKD) patients with mineral and bone disorder (CKD‐MBD). In patients with CKD‐MBD, the inability of the kidney to maintain normal mineral ion balance affects bone remodeling to induce skeletal fracture and extraskeletal vascular calcification. In physiological conditions, bone‐derived fibroblast growth factor 23 (FGF23) acts on the kidney to reduce serum phosphate and 1,25‐dihydroxyvitamin D levels. In humans, increased bioactivity of FGF23 leads to increased urinary phosphate excretion, which induces hypophosphatemic diseases (e.g., rickets/osteomalacia). However, reduced FGF23 activity is associated with hyperphosphatemic diseases (e.g., tumoral calcinosis). In patients with CKD, high serum levels of FGF23 fail to reduce serum phosphate levels and lead to numerous complications, including vascular calcification, one of the important determinants of mortality of CKD‐MBD patients. Of particular significance, molecular, biochemical and morphological changes in patients with CKD‐MBD are mostly due to osteo‐renal dysregulation of mineral ion metabolism. Furthermore, hyperphosphatemia can partly contribute to the development of secondary hyperparathyroidism in patients with CKD‐MBD. Relatively new pharmacological agents including sevelamer hydrochloride, calcitriol analogs and cinacalcet hydrochloride are used either alone, or in combination, to minimize hyperphosphatemia and hyperparathyroidism associated complications to improve morbidity and mortality of CKD‐MBD patients. This article will briefly summarize how osteo‐renal miscommunication can induce phosphate toxicity, resulting in extensive tissue injuries. © 2011 IUBMB IUBMB Life, 63(4): 240–247, 2011
Globins in Caenorhabditis elegans
Authors: Tilleman Lesley , Germani Francesca , De Henau Sasha , Geuens Eva , Hoogewijs David , Braeckman Bart P. , Vanfleteren Jacques R. , Moens Luc , Dewilde Sylvia
Published: March 2011

Extensive in silico search of the genome of Caenorhabditis elegans revealed the presence of 33 genes coding for globins that are all transcribed. These globins are very diverse in gene and protein structure and are localized in a variety of cells, mostly neurons. The large number of C. elegans globin genes is assumed to be the result of multiple evolutionary duplication and radiation events. Processes of subfunctionalization and diversification probably led to their cell‐specific expression patterns and fixation into the genome. To date, four globins (GLB‐1, GLB‐5, GLB‐6, and GLB‐26) have been partially characterized physicochemically, and the crystallographic structure of two of them (GLB‐1 and GLB‐6) was solved. In this article, a three‐dimensional model was designed for the other two globins (GLB‐5 and GLB‐26), and overlays of the globins were constructed to highlight the structural diversity among them. It is clear that although they all share the globin fold, small variations in the three‐dimensional structure have major implications on their ligand‐binding properties and possibly their function. We also review here all the information available so far on the globin family of C. elegans and suggest potential functions. © 2011 IUBMB IUBMB Life, 63(3): 166–174, 2011
Defective resolution of pH2AX foci and enhanced DNA breakage in ionizing radiation‐treated cockayne syndrome B cells
Authors: Ropolo Monica , Cappelli Enrico , Foresta Mara , Poggi Alessandro , Proietti‐De‐Santis Luca , Frosina Guido
Published: March 2011

We have previously shown that DNA repair of oxidized bases (either purines or pyrimidines) is inefficient in cells from patients with Cockayne syndrome (cs), a rare developmental and neurological genetic disorder. Here, we show for the first time that resolution of ionizing radiation (IR)‐induced pH2AX foci, an indicator of DNA double‐strand breaks, is significantly delayed in IR‐treated cells belonging to the B complementation group of cs (csb). Using alkaline single‐cell gel electrophoresis, which predominantly detects single‐strand breaks, we further demonstrate elevated DNA breakage in csb cells early after irradiation. Both the delayed resolution of pH2AX foci and the early DNA breakage of csb cells were partially complemented by expression of wild‐type CSB protein. Hence, the csb mutation impairs resolution of pH2AX foci and causes DNA fragility, broadening the spectrum of lesions whose processing is altered in this syndrome. © 2011 IUBMB IUBMB Life, 63(4): 272–276, 2011
The occupancy of endothelial protein C receptor by its ligand modulates the par‐1 dependent signaling specificity of coagulation proteases
Authors: Rezaie Alireza R.
Published: March 2011

Several recent studies have demonstrated that the activation of protease‐activated receptor 1 (PAR‐1) by thrombin and activated protein C (APC) on cultured vascular endothelial cells elicits paradoxical proinflammatory and antiinflammatory responses, respectively. Noting that the protective intracellular signaling activity of APC requires the interaction of the protease with its receptor, endothelial protein C receptor (EPCR), we recently hypothesized that the occupancy of EPCR by protein C may also change the PAR‐1‐dependent signaling specificity of thrombin. In support of this hypothesis, we demonstrated that EPCR is associated with caveolin‐1 in lipid rafts of endothelial cells and that the occupancy of EPCR by the Gla‐domain of protein C/APC leads to its dissociation from caveolin‐1 and recruitment of PAR‐1 to a protective signaling pathway through the coupling of PAR‐1 to the pertussis toxin sensitive Gi‐protein. Thus, when EPCR is bound by protein C, a PAR‐1‐dependent protective signaling response in cultured endothelial cells can be mediated by either thrombin or APC. This article will briefly review the mechanism by which the occupancy of EPCR by its natural ligand modulates the PAR‐1‐dependent signaling specificity of coagulation proteases. © 2011 IUBMB IUBMB Life, 63(6): 390–396, 2011
Stochastic search variable selection in vector error correction models with an application to a model of the UK macroeconomy
Authors: Jochmann Markus , Koop Gary , Leon‐Gonzalez Roberto , Strachan Rodney W.
Published: March 2011

This paper develops methods for stochastic search variable selection (currently popular with regression and vector autoregressive models) for vector error correction models where there are many possible restrictions on the cointegration space. We show how this allows the researcher to begin with a single unrestricted model and either do model selection or model averaging in an automatic and computationally efficient manner. We apply our methods to a large UK macroeconomic model. Copyright © 2011 John Wiley & Sons, Ltd.
Calibration and validation of a physiologically based model for soman intoxication in the rat, marmoset, guinea pig and pig
Authors: Chen Kaizhen , Seng Kok‐Yong
Published: March 2011

A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model has been developed for low, medium and high levels of soman intoxication in the rat, marmoset, guinea pig and pig. The primary objective of this model was to describe the pharmacokinetics of soman after intravenous, intramuscular and subcutaneous administration in the rat, marmoset, guinea pig, and pig as well as its subsequent pharmacodynamic effects on blood acetylcholinesterase (AChE) levels, relating dosimetry to physiological response. The reactions modelled in each physiologically realistic compartment are: (1) partitioning of C(±)P(±) soman from the blood into the tissue; (2) inhibition of AChE and carboxylesterase (CaE) by soman; (3) elimination of soman by enzymatic hydrolysis; (4) de novo synthesis and degradation of AChE and CaE; and (5) aging of AChE–soman and CaE–soman complexes. The model was first calibrated for the rat, then extrapolated for validation in the marmoset, guinea pig and pig. Adequate fits to experimental data on the time course of soman pharmacokinetics and AChE inhibition were achieved in the mammalian models. In conclusion, the present model adequately predicts the dose–response relationship resulting from soman intoxication and can potentially be applied to predict soman pharmacokinetics and pharmacodynamics in other species, including human. Copyright © 2011 John Wiley & Sons, Ltd.
Relationships between calcified atherosclerotic plaque and bone mineral density in African Americans with type 2 diabetes
Authors: Divers Jasmin , Register Thomas C , Langefeld Carl D , Wagenknecht Lynne E , Bowden Donald W , Carr J Jeffrey , Hightower R Caresse , Xu Jianzhao , Hruska Keith A , Freedman Barry I
Published: March 2011

Inverse relationships have been reported between bone mineral density (BMD) and calcified atherosclerotic plaque (CP). This suggests these processes may be related. We examined relationships between BMD and CP in 753 African Americans with type 2 diabetes from 664 families, accounting for the effects of modifiable cardiovascular disease (CVD) risk factors. Association analyses were performed using generalized estimating equations (GEEs) to assess cross-sectional relationships between computed tomography–determined measures of thoracic and lumbar vertebral volumetric BMD (vBMD) and CP in the coronary and carotid arteries and infrarenal aorta. Significant inverse associations were seen between thoracic and lumbar vBMD and CP in all three vascular beds in unadjusted analyses. A fully adjusted model accounting for age, sex, body mass index, systolic blood pressure, low-density lipoprotein cholesterol, C-reactive protein, hemoglobin A1c, smoking, and hormone-replacement therapy revealed significant inverse associations between thoracic vBMD and CP in coronary and carotid arteries and aorta, whereas lumbar vBMD was associated with CP in coronary artery and aorta. Inverse associations exist between vertebral BMD and calcified atherosclerotic plaque in African-American men and women with type 2 diabetes. This relationship was independent of conventional CVD risk factors and supports the hypothesis that bone metabolism and atherosclerotic plaque mineralization are related processes. © 2011 American Society for Bone and Mineral Research.
The expression of the pro‐apoptotic gene Air is inducible in human pancreatic adenocarcinoma cells
Authors: d'Avenia Morena , Rosati Alessandra , Belisario Maria Antonietta , Torino Mario , Torino Gaetano , Turco Maria Caterina , Pascale Maria
Published: March 2011

We previously identified apoptosis‐induced regulator (air) as a pro‐apoptotic transcript whose expression was repressed by NF‐κB/Rel activity in the human leukemia cell line Jurkat (Turco, Lamberti, Bisogni, Romano, Petrella, Ammirante, Rosati, d'Avenia, Arra, Spugnini, Venuta, 2007, Leukemia 21:2557–2559). In this paper, we report that air sequence is detectable by Southern blot in human healthy donors (HHD) leukocytes and in two pancreatic adenocarcinoma cell lines (AsPC‐1 and PANC‐1), providing the first definitive evidence of air gene presence in human genome. In addition, we demonstrate that air expression is induced in the tumor cell lines by a naturally occurring ROS‐inducing compound, phenethyl isothiocyanate (PEITC), a potential dietary cancer chemopreventive agent. Since PEITC inhibits NF‐κB activation, air induction by this agent is consistent with the suppressive effect of NF‐κB on air expression. This finding contributes a new clue to the role of NF‐κB in regulating oxidative stress‐induced pro‐apoptotic genes and identifies a novel potential tool for enhancing pancreas cancer response to treatment. J. Cell. Physiol. 226: 2207–2212, 2011. © 2011 Wiley‐Liss, Inc.
MAP kinase mediates silica‐induced fibrotic nodule formation and collagen accumulation in fibroblasts
Authors: Li Yunyuan , Kilani Ruhangiz T. , Hartwell Ryan , Ghahary Aziz
Published: March 2011

It is well known that silica generates fibrosis around them in animals and human. However, the pathogenesis and mechanism of silica‐induced fibrosis are still poorly understood. Here, we established a new strategy through which the effects of silica on fibrotic nodule formation, key extracellular matrix accumulation, and the mechanism involved were explored. To achieve this, human dermal fibroblasts were directly exposed to silica gel for various durations. Fibrotic nodule formation was evaluated by their microscopic appearance, type‐1 procollagen, and fibronection expression in cell lysate and MMP‐1 and‐3 in conditioned media were analyzed by Western blotting. The results show an easily formation of nodule‐like structures around silica gel in an in vitro‐cultured system. The findings further revealed that silica gel stimulates collagen and fibronectin expression, while down‐regulates matrix metalloproteinase‐1 and ‐3 (MMP‐1 and MMP‐3) released in conditioned medium. To explore the mechanism involved, P38 and ERK1/2 Mitogen‐Activated Protein Kinase (MAPK) signaling pathways were evaluated. Result showed that silica inhibits P38 and extracellular signal‐regulated kinases (ERK1/2) MAP kinase phosphorylation. The addition of ERK1/2 inhibitor increases silica‐stimulated type‐1 collagen expression, reduces MMP‐1 release and further enhances silica‐induced nodule formation in dermal fibroblasts. These findings indicate that the inhibition of ERK1/2 MAPK signaling pathway may contribute to silica‐caused fibrosis. In summary, our findings suggest that silica can directly cause fibrotic phenotype when fibroblasts contact with silica particles independent of any inflammation and other factors may exist in an in vivo condition. J. Cell. Physiol. 227: 328–338, 2012. © 2011 Wiley Periodicals, Inc.
Activation of survival and apoptotic signaling pathways in lymphocytes exposed to palmitic acid
Authors: Takahashi Hilton Kenji , Cambiaghi Tavane David , Luchessi Augusto Ducati , Hirabara Sandro Massao , Vinolo Marco Aurelio Ramirez , Newsholme Philip , Curi Rui
Published: March 2011

The toxicity of palmitic acid (PA) towards a human T‐lymphocyte cell line (Jurkat) has been previously investigated but the mechanism(s) of PA action were unknown. In the current study, Jurkat cells were treated with sub‐lethal concentrations of PA (50–150µM) and the activity of various signaling proteins was investigated. PA‐induced apoptosis and mitochondrial dysfunction in a dose‐dependent manner as evaluated by DNA fragmentation assay and depolarization of the mitochondrial membrane, respectively. PA treatment provoked release of cytochrome c from the inner mitochondrial membrane to the cytosol, activated members of the MAPK protein family JNK, p38, ERK, activated caspases 3/9, and increased oxidative/nitrosative stress. Exposure of cells to PA for 12 h increased insulin receptor (IR) and GLUT‐4 levels in the plasma membrane. Insulin treatment (10 mU/ml/30 min) increased the phosphorylation of the IR β‐subunit and Akt. A correlation was found between DNA fragmentation and expression levels of both IR and GLUT‐4. Similar results were obtained for PA‐treated lymphocytes from healthy human donors and from mesenteric lymph nodes of 48‐h starved rats. PA stimulated glucose uptake by Jurkat cells (in the absence of insulin), stimulated accumulation of neutral lipids (triglyceride), and other lipid classes (phospholipids and cholesterol ester) but reduced glucose oxidation. Our results suggest that parameters of insulin signaling and non‐oxidative glucose metabolism are stimulated as part of a coordinated response to prompt survival in lymphocytes exposed to PA but at higher concentrations, apoptosis prevails. These findings may explain aspects of lymphocyte dysfunction associated with diabetes. J. Cell. Physiol. 227: 339–350, 2012. © 2011 Wiley Periodicals, Inc.
Endothelial cell microparticles act as centers of matrix metalloproteinsase‐2 (MMP‐2) activation and vascular matrix remodeling
Authors: Lozito Thomas P. , Tuan Rocky S.
Published: March 2011

Endothelial cell (EC)‐derived microparticles (MPs) are small membrane vesicles associated with various vascular pathologies. Here, we investigated the role of MPs in matrix remodeling by analyzing their interactions with the extracellular matrix. MPs were shown to bind preferentially to surfaces coated with matrix molecules, and MPs bound fibronectin via integrin αV. MPs isolated from EC‐conditioned medium (Sup) were significantly enriched for matrix‐altering proteases, including matrix metalloproteinases (MMPs). MPs lacked the MMP inhibitors TIMP‐1 and TIMP‐2 found in the Sup and, while Sup strongly inhibited MMP activities but MPs did not. In fact, MPs were shown to bind and activate both endogenous and exogenous proMMP‐2. Taken together, these results indicate that MPs interact with extracellular matrices, where they localize and activate MMP‐2 to modify the surrounding matrix molecules. These findings provide insights into the cellular mechanisms of vascular matrix remodeling and identify new targets of vascular pathologies. J. Cell. Physiol. 227: 534–549, 2012. © 2011 Wiley Periodicals, Inc.
Treatment of dairy industry wastewater by EC and EF processes using hybrid FeAl plate electrodes
Authors: Yavuz Yusuf , Öcal Eren , Koparal Ali Savaş , Öğütveren Ülker Bakır
Published: March 2011

BACKGROUND: In this study electrochemical treatment of dairy industry wastewater (DW) was investigated using a combined electrode system consisting of iron and aluminum as sacrificial electrodes. The dairy industry generates strong wastewaters characterized by high biological oxygen demand and chemical oxygen demand concentrations. Dairy industry waste effluents are concentrated in nature, and the main contributors of organic load to these effluents are carbohydrates, proteins and fats originating from the milk. Since dairy waste streams contain high concentrations of organic matter, these effluents may cause serious environmental problems.

RESULTS: A pole changer device was employed to change polarization in given time intervals to generate iron and aluminum based coagulants respectively. The effects of current density, initial pH, sodium sulfate (Na2SO4) and H2O2 concentrations on the removal efficiency were investigated. The best experimental conditions obtained in electrochemical studies were as follows: current density = 15 mA cm−2, natural pH, without supporting electrolyte addition, H2O2 concentration = 3 × 1000 mg L−1. Under these conditions, 79.2% COD removal from DW was achieved.

CONCLUSION: According to the results, 20 min electrolysis is enough, since insignificant variations in COD removal were observed after this time. These methods were found to be successful for the treatment of DW. Copyright © 2011 Society of Chemical Industry
Short‐time estimation of biogas and methane potentials from municipal solid wastes
Authors: Ponsá Sergio , Gea Teresa , Sánchez Antoni
Published: March 2011

Biogas (GB) and methane (BMP) potentials are important parameters for the energy potential of the anaerobic digestion of municipal solid wastes (MSW) and to design full‐scale facilities. However, no standard protocol has been defined for this measure. Several samples of mixed MSW and the source‐selected organic fraction of municipal solid waste (OFMSW) obtained at different stages of their mechanical‐biological treatment were analyzed. GB and BMP values obtained at different times were correlated. Biogas potentials calculated at 3, 4, 5, 6, 7, 14, 21, 50 and 100 days correlated well for the OFMSW samples. In the case of the MSW samples, only GB values obtained at times of 14 or more days correlated well with the ultimate biogas production (considered at 100 days). The biogas potential analyzed at 21 days (as proposed in some standard methods) accounted for 77% of the total biogas potential in OFMSW samples and for 71% in the MSW samples. These results are useful for the correct design and operation of anaerobic digestion plants in terms of retention time estimation and expected biogas and methane production. Copyright © 2011 Society of Chemical Industry
Enhanced biodegradation of 2‐chloronitro‐benzene using a coupled zero‐valent iron column and sequencing batch reactor system
Authors: Xu Xiangyang , Lin Haizhuan , Zhu Liang , Yang Yanni , Feng Jiqin
Published: March 2011

BACKGROUND: This study focused on the effectiveness of the zero‐valent iron (ZVI) pre‐treatment for enhancing the biodegradability of 2‐chloronitrobenzene (2‐ClNB), and further to evaluate the performance and mechanism of a coupled ZVI column–sequencing batch reactor (SBR) system treating 2‐ClNB contained wastewater.

RESULTS: 2‐ClNB was readily transformed into 2‐chloroaniline (2‐ClAn) with the efficiency over 99.9% by ZVI column, and its biodegradability was significantly enhanced via ZVI pretreatment. The transformed effluent was subsequently fed into the SBR followed by 2‐ClAn loading of 3.4–117.2 g m−3 d−1 and COD loading around 1000 g m−3 d−1. A 2‐ClAn removal efficiency over 99.9% and COD removal efficiency of 82.0–98.1% were obtained. Moreover, 91.9 ± 0.1% TOC removal efficiency and 107.1 ± 6.0% chloride recovery efficiency during one cycle confirmed the complete biodegradation of 2‐ClAn in the coupled system. 16S rDNA PCR‐DGGE analysis suggested that ZVI pretreatment enhanced the diversity of the microbial community and promoted enrichment of the functional microorganisms degrading 2‐ClAn in the following SBR.

CONCLUSION: ZVI pretreatment significantly enhanced the biodegradability of 2‐ClNB, and the coupled ZVI–SBR system demonstrated excellent performance when treating wastewater containing 2‐ClNB. Copyright © 2011 Society of Chemical Industry
Adhesive compatibility of cribellar and viscous prey capture threads and its implication for the evolution of orb‐weaving spiders
Authors: Opell Brent D. , Tran Andrew M. , Karinshak Shannon E.
Published: March 2011

Evolution of orb‐weaving spiders that comprise the Orbiculariae clade involved a transition in the composition of prey capture thread that has been challenging to explain. The primitive cribellar threads spun by members of the Deinopoidea subclade resemble the capture threads of their non‐orb‐web‐weaving ancestors and are formed of thousands of fine, dry, protein cribellar fibrils. In contrast, the derived viscous capture threads spun by members of the Araneoidea subclade have regularly spaced, aqueous adhesive droplets. When second instar deinopoid spiderlings emerge from egg sacs they are unable to spin cribellar threads, and, therefore, do not construct orb‐webs; whereas second instar araneoids spin capture threads and construct orb‐webs. If, as we hypothesize, viscous material evolved to enable second instar spiderlings to construct orb‐webs, early araneoids may have spun composite cribellar–viscous capture threads. To examine the functional feasibility of such intermediate capture threads, we compared the adhesion of cribellar threads, viscous threads, and combined cribellar–viscous threads. The stickiness of these combined threads was greater than that of native cribellar or viscous threads alone. The viscous material of Araneus marmoreus threads exhibited a substantial increase in stickiness when combined with cribellar fibrils and that of Argiope aurantia threads a small increase in stickiness when combined with cribellar fibrils. Thus, if early araneoids retained their ability to spin cribellar threads after having evolved glands that produced viscous material, their composite threads could have formed a functional adhesive system that achieved its stickiness at no loss of material economy. J. Exp. Zool. 315:376–384, 2011. © 2011 Wiley‐Liss, Inc.
Synthesis and fungicidal activity of 1,3‐thiazoline derivatives bearing nitrophenyl group on the 2‐position
Authors: Zhao Qiuying , Li Jing , Yan Xiaojing , Yuan Huizhu , Qin Zhaohai , Fu Bin
Published: March 2011

Ortho‐, meta‐, or para‐nitro benzoic acid were refluxed with excess SOCl2 to give acyl chloride, which condensed with β‐amino alcohol in the presence of Et3N in dichloromethane to afford β‐hydroxyamide; finally, sulphonation and cyclization were simultaneously conducted to afford 1,3‐thiazoline derivatives. Fungicidal activity of these new thiazolines against eight agrocultural fungi were evaluated, and two of this type of compounds displayed good fungicidal activity comparable or superior to commercial fungicide chlorothalonil against two fungi at a concentration of 50 mg/L. J. Heterocyclic Chem., (2011).