bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of the Acid‐Mediated Thermal Fragmentation of 5‐Spirocyclobutane‐isoxazolidines
Authors: Cordero Franca M. , Vurchio Carolina , Brandi Alberto , Gandolfi Remo 
Published: July 2011

AbstractProtonation at the nitrogen of 5‐spirocyclopropane‐isoxazolidines induces clean thermal rearrangement/fragmentation to β‐lactams and ethylene. Under the same conditions, homologous 5‐spirocyclobutane‐isoxazolidines undergo unselective fragmentation to give cyclobutyl derivatives through a completely different mechanism. Experimental data and DFT calculations show that the process is initiated with less‐favored protonation at the isoxazolidine oxygen rather than nitrogen. Highly energetic O‐protonated isoxazolidines undergo N–O cleavage with concomitant endo‐ or exocyclic deprotonation to give iminium ions that, in the presence of trifluoroacetate, evolve into 2‐(1‐hydroxycyclobutyl)ethanones and N‐[2‐(1‐hydroxycyclobutyl)ethyl]trifluoroacetamides, respectively. DFT data validate protonation at oxygen of 5‐spirocyclobutane‐isoxazolidines, which requires higher energy than protonation at nitrogen, but can trigger the proposed process without any energy barrier. The N‐protonated derivatives could rearrange to give oxazaspirooctane, with enlargement of the spirocyclobutane ring, but this process, owing to its high energy barrier, cannot compete with the reaction channel promoted by oxygen protonation and, in fact, is not experimentally observed. Being independent of the presence of a strained spirofused ring, acid‐catalyzed fragmentation was also demonstrated to occur in normal isoxazolidines, such as those derived from cycloaddition of C–Ph–N–Me‐nitrone to norbornene, suggesting that isoxazolidines, widely used in organic synthesis, should not be heated in the presence of protic acids.
Synthesis of Tetrahedral Shape‐Persistent Tetranuclear Metal–salphens
Authors: Mastalerz Michael , Oppel Iris M. 
Published: July 2011

AbstractThe synthesis of two novel tetrakis(salicylaldehydes) based on a rigid tetraphenylmethane core is presented. These salicylaldehydes were used as precursors for the construction of three‐dimensional multimetallic salphens, as exemplified by the synthesis of rigid and shape‐persistent tetranuclearzinc–, nickel– and palladium–salphens with defined geometries and distances between the metal sites. The UV/Vis measurements of the tetranuclear metal complexes are presented.
Disgust Sensitivity and Anorexia Nervosa
Authors: Aharoni Ruth , Hertz Marianne M. 
Published: July 2011

AbstractBackgroundPrevious studies found inconsistent differences in disgust sensitivity between patients with a variety of eating disorders and normal controls.AimThe objective of this study was to compare disgust sensitivity between a larger and more specific sample of anorexia nervosa (AN) patients and control subjects.MethodWe compared the scores on the ‘disgust sensitivity scale’ of AN patients (N = 62) and control subjects (N = 62) using a multivariate analysis of variance. All subjects were women.ResultsAN patients scored consistently higher on all domains of disgust sensitivity. This difference was significant for six of eight disgust domains. The largest significant difference between the groups was on the domains food and magical thinking.ConclusionOur findings elaborate on previous findings and are in line with recent neurological findings suggesting that disgust and insular impairments are associated with AN. Clinical implications of our findings are discussed. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.
Improving uncertainty analysis in kinetic evaluations using iteratively reweighted least squares
Authors: Gao Zhenglei , Green John W , Vanderborght Jan , Schmitt Walter 
Published: July 2011

Abstract
Kinetic parameters of environmental fate processes are usually inferred by fitting appropriate kinetic models to the data using standard nonlinear least squares (NLS) approaches. Although NLS is appropriate to estimate the optimum parameter values, it implies restrictive assumptions on data variances when the confidence limits of the parameters must also be determined. Particularly in the case of degradation and metabolite formation, the assumption of equal error variance is often not realistic because the parent data usually show higher variances than those of the metabolites. Conventionally, such problems would be tackled by weighted NLS regression, which requires prior knowledge about the data errors. Instead of implicitly assuming equal error variances or giving arbitrary weights decided by the researcher, we use an iteratively reweighted least squares (IRLS) algorithm to obtain the maximum likelihood estimates of the model parameters and the error variances specific for the different species in a model. A study with simulated data shows that IRLS gives reliable results in the case of both unequal and equal error variances. We also compared results obtained by NLS and IRLS, with probability distributions of the parameters inferred with a Markov-Chain Monte-Carlo (MCMC) approach for data from aerobic transformation of different chemicals in soil. Confidence intervals obtained by IRLS and MCMC are consistent, whereas NLS leads to very different results when the error variances are distinctly different between different species. Because the MCMC results can be assumed to reflect the real parameter distribution imposed by the observed data, we conclude that IRLS generally yields more realistic estimates of confidence intervals for model parameters than NLS. Environ. Toxicol. Chem. 2011;30:2363–2371. © 2011 SETAC
Effects of slip conditions on stretching flow with ohmic dissipation and thermal radiation
Authors: Qasim M. , Hayat T. , Hendi Awatif. A. 
Published: July 2011

AbstractThe present work addresses the magnetohydrodynamic (MHD) flow and heat transfer over a permeable stretching sheet. Analysis has been carried out in the presence of thermal radiation and ohmic dissipation. The velocity and thermal slip effects are given main attention. The Rosseland approximation is used to describe the radiative heat flux in the energy equation. The non‐linear partial differential equations are reduced to a set of non‐linear ordinary differential equations which are solved analytically by the homotopy analysis method (HAM). The effects of emerging physical parameters on the velocity and temperature profiles are interpreted. Numerical data for skin friction coefficient and Nusselt number have been tabulated for various values of the parameters. The results have been compared with the known exact solution from the literature in a limiting sense. © 2011 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.20367
Secondary poisoning risk assessment of terrestrial birds and mammals exposed to Nickel
Authors: DeForest David K , Schlekat Christian E , Brix Kevin V , Fairbrother Anne 
Published: July 2011

Abstract
The European Union's Existing Substances regulation (EEC 793/93) was developed to assess the ecological risks posed by chemical substances such as Ni and includes the assessment of secondary poisoning risks. The basic structure of this secondary poisoning risk assessment followed the Technical Guidance Document on Risk Assessment and thus included development of predicted exposure concentrations (PECs) and predicted no-effect concentrations (PNECs). A PEC to PNEC ratio greater than 1.0 is indicative of potential risk. The Technical Guidance Document on Risk Assessment provides a generic framework for assessing secondary poisoning risks and prescribes the following terrestrial food chain: soil → earthworm → worm-eating bird or mammal. This secondary poisoning evaluation was conducted at the regional level, and it was found that the generic approach resulted in widespread estimates of potential risk, even at ambient Ni soil concentrations. Accordingly, a tiered approach was used with increasing levels of refinement, including consideration of bioavailability, consideration of a variable diet, and development of dose-based PNEC values. Based on the refined approach, all PEC to PNEC ratios were less than 1.0, except for a ratio of 1.4 in a scenario focused on a regional clay soil, which was of natural origin. This regional-level secondary poisoning evaluation highlighted key risk assessment components that should be considered in future localized secondary poisoning assessments of Ni and other metals, including ingestion rate to body weight ratios for the test organisms used to derive PNECs versus the representative wildlife species evaluated, the appropriateness of high assessment factors for deriving PNECs for naturally occurring essential elements, representative dietary compositions, relative metal bioavailability between the dietary toxicity study and natural diets, and ground-truthing of the risk predictions versus background concentrations. Integr Environ Assess Manag 2012;8:107–119. © 2011 SETAC
Assessment of risks to ground-feeding songbirds from lead in the Coeur d'Alene Basin, Idaho, USA
Authors: Sample Bradley E , Hansen James A , Dailey Anne , Duncan Bruce 
Published: July 2011

Abstract
Previous assessment of ecological risks within the Coeur d'Alene River Basin identified Pb as a key risk driver for ground-feeding songbirds. Because this conclusion was based almost exclusively on literature data, its strength was determined to range from low to moderate. With the support of the US Environmental Protection Agency (USEPA), the US Fish and Wildlife Service collected site-specific data to address the uncertainty associated with Pb risks to songbirds. These data, plus those from the previous Coeur d'Alene Basin ecological risk assessment, were integrated, and risks to ground-feeding songbirds were reevaluated. These site-specific data were also used to develop updated preliminary remedial goals (PRGs) for Pb in soils that would be protective of songbirds. Available data included site-specific Pb concentrations in blood, liver, and ingesta from 3 songbird species (American robin, song sparrow, and Swainson's thrush), colocated soil data, and soil data from other locations in the basin. Semi-log regression models based on the association between soil Pb and tissue Pb concentrations were applied to measured soil concentrations from the previous risk assessment to estimate Pb exposures in riparian and adjacent upland habitats throughout the Coeur d'Alene Basin. Measured and estimated tissue or dietary exposure was tabulated for 3 areas plus the reference, and then compared to multiple effects measures. As many as 6 exposure-effect metrics were available for assessing risk in any one area. Analyses of site-specific tissue- and diet-based exposure data indicate that exposure of ground-feeding songbirds to Pb in the Coeur d'Alene Basin is sufficient to result in adverse effects. Because this conclusion is based on multiple exposure-effect metrics that include site-specific data, the strength of this conclusion is high. Ecological PRGs were developed by integrating the site-specific regression models with tissue and dietary effect levels to create exposure models, which were solved for the soil concentration that produced an exposure estimate equal to the effect level (i.e., the ecological PRG). The lowest PRG obtained for any species' exposure-effect measure combination was 490 mg/kg for subclinical effects due to Pb in the blood of American robins; the highest was 7200 mg/kg for severe clinical effects due to Pb in the blood of song sparrows. Because the lowest ground-feeding songbird PRG was comparable to multiple cleanup goals developed for the basin (i.e., soil invertebrates, wildlife populations, and human health), in addition to the site-specific cleanup level of 530 mg Pb/kg sediment for the protection of waterfowl (USEPA 2002) the USEPA has made a risk-management determination that a site-specific Pb cleanup level of 530 mg/kg in soil would be protective of songbirds in the Coeur d'Alene Basin. Integr Environ Assess Manag 2011;7:596–611. © 2011 SETAC
Simultaneous targeting of Src kinase and receptor tyrosine kinase results in synergistic inhibition of renal cell carcinoma proliferation and migration
Authors: Bai Lanfang , Yang Joy C. , Ok Joon‐ha , Mack Philip C. , Kung Hsing‐Jien , Evans Christopher P. 
Published: July 2011

AbstractThere have been recent improvements in the treatment for metastatic renal cell carcinoma (RCC) with receptor tyrosine kinase (RTK) inhibitors being one of newer treatment options. We hypothesized that simultaneous targeting of Src kinase and the RTK may have synergistic effects to further improve therapies on metastatic RCC. The effects of Src kinase inhibitor saracatinib and multiple RTK inhibitor sunitinib on RCC cell line (ACHN) and Caki‐1 were studied. Saracatinib alone or in combination with sunitinib inhibited the migration of ACHN and Caki‐1 cells in vitro. Activation of migration related components FAK, P130Cas and Paxillin were blocked by saracatinib at 0.05‐ to 3‐μM concentrations. Combined treatment resulted in improved growth inhibition, greater loss of the S phase cell population and decreased clonogenic colony formation compared to sunitinib alone in the metastatic Caki‐1 line. Molecular studies in Caki‐1 showed that saracatinib alone and in combination with sunitinib inhibited phosphorylation of the cell progression regulator c‐Myc in a dose‐dependent manner. Sunitinib alone or in combination suppressed cyclin‐D1 expression with the combination showing greater dose‐dependent effect. Sunitinib inhibited vascular endothelial growth factor (VEGF) secretion through the inhibition of STAT3 signaling and VEGF biosynthesis. HIF1‐α expression in normoxic and hypoxic conditions in Caki‐1 cells was inhibited by either saracatinib or sunitinib when administered alone, however, a greater reduction occurred when these compounds were given in combination. Targeting Src kinase and RTK simultaneously with saracatinib and sunitinib resulted in 70–80% blockade of RCC cell migration, synergistic inhibition of cell growth and reduction of acquired drug resistance in Caki‐1 cells. The results show promise for combination targeted therapy of RCC.
Expression of C4.4A in precursor lesions of pulmonary adenocarcinoma and squamous cell carcinoma
Authors: Jacobsen Benedikte , Santoni‐Rugiu Eric , Illemann Martin , Kriegbaum Mette Camilla , Lærum Ole Didrik , Ploug Michael 
Published: July 2011

AbstractThe protein C4.4A, a structural homologue of the urokinase‐type plasminogen activator receptor, is a potential new biomarker in non‐small cell lung cancer, with high levels of expression recently shown to correlate to poor survival of adenocarcinoma patients. In this study, C4.4A immunoreactivity in precursor lesions of lung squamous cell carcinoma and adenocarcinoma was investigated by stainings with a specific anti‐C4.4A antibody. In the transformation from normal bronchial epithelium to squamous cell carcinoma, C4.4A was weakly expressed in basal cell hyperplasia but dramatically increased in squamous metaplasia. This was confined to the cell membrane and sustained in dysplasia, carcinoma in situ, and the invasive carcinoma. The induction of C4.4A already at the stage of hyperplasia could indicate that it is a marker of very early squamous differentiation, which aligns well with our earlier finding that C4.4A expression levels do not provide prognostic information on the survival of squamous cell carcinoma patients. In the progression from normal alveolar epithelium to peripheral adenocarcinoma, we observed an unexpected, distinct cytoplasmic staining for C4.4A in a fraction of atypical adenomatous hyperplasias, while most bronchioloalveolar carcinomas were negative. Likewise, only a fraction of the invasive adenocarcinomas was positive for C4.4A. With a view to the prognostic impact of C4.4A in adenocarcinoma patients, this finding might suggest that C4.4A could be an early biomarker for a possibly more malignant subtype of this disease.
Genetic determinants of oxidative stress‐mediated sensitization of drug‐resistant cancer cells
Authors: Maiti Amit K. 
Published: July 2011

AbstractDrug resistance in cancer is an overwhelming problem, because drug‐resistant cancer cells are harder to kill with the same drug. The mechanism of drug resistance differs for various cancers based on the type of drug being used for its treatment. Most current drugs are shown to increase reactive oxygen species (ROS) in respective cancer cells that induces apoptosis, but continuous treatment with the same drug may reduce cellular ROS levels and may convert drug sensitive cancer cells into drug resistant cells. In addition, exogenous elevation of ROS in conjunction with drug resensitizes drug‐resistant cancer cells. Thus, constant maintenance of higher ROS level in cancer cells may be a prerequisite for drug efficacy in certain type of cancer cells. Thus, modulation of ROS‐mediated genetic pathway genes could be an efficient alternative to maintain higher ROS level in cancer cells for “combinational chemotherapy” with the drug. In this review, I discuss whether ROS reduction in drug‐resistant cancer cells could be a general mechanism of drug resistance for most cancers with its specific drug, and whether elevation of ROS levels with the drug could be a valuable strategy for increasing drug efficacy in most cancers.
Toll‐like receptor genes and their association with colon and rectal cancer development and prognosis
Authors: Slattery Martha L. , Herrick Jennifer S. , Bondurant Kristina L. , Wolff Roger K. 
Published: July 2011

AbstractToll‐like receptors (TLRs) are mediators of inflammation in the gut and potentially important modulators of colon and rectal cancer risk. We use data from a population‐based study of incident colon cancer cases (n = 1,555) and controls (n = 1,956) and rectal cancer cases (n = 754) and controls (n = 959). We evaluate genetic variation in TLR2 (six SNPs), TLR3 (four SNPs) and TLR4 (eight SNPs) with risk of developing colon or rectal cancer and survival after diagnosis. TLR3 rs11721827 was associated with rectal cancer (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.02, 1.58 for AC/CC vs. AA genotype, Wald p = 0.035; adjusted p = 0.126); TLR3 rs3775292 and TLR4 rs11536898 were associated with colon cancer (OR 0.68, 95% CI 0.49, 0.95 for GG vs. CC/CG and OR 0.50. 95% CI 0.29, 0.87 for AA vs. CA/CC, respectively; Wald p = 0.023 and 0.015; adjusted p = 0.085 and 0.101, respectively). TLR2 rs7656411 and rs3804099, respectively, interacted with nonsteroidal anti‐inflammatory drug (NSAID) use and cigarette smoking to alter risk of colon cancer (adjusted p = 0.034 and 0.077); TLR3 rs11721827 interacted with NSAID use to alter risk of colon cancer (adjusted p = 0.071). TLR3 rs3775292 interacted with dietary carbohydrates to alter colon cancer risk and with dietary carbohydrates and saturated fat to alter rectal cancer risk (adjusted p = 0.064, 0.0035 and 0.025, respectively). Multiple SNPs in TLR2 and TLR4 were associated with colon cancer survival. Although few independent associations with TLR genes were observed, we observed significant interaction of TLR2 and TLR3 with hypothesized lifestyle factors. Interaction with dietary factors remained significant for rectal cancer after adjustment for multiple comparisons.
Implementing changes in institutions to improve young children's development
Authors: Groark Christina J. , Mccall Robert B. 
Published: July 2011

AbstractAn estimated 8‐million children, mostly birth to approximately 6 to 8 years of age, live in institutions worldwide. While institutional environments vary, certain characteristics are common, including relatively large groups; high children:caregiver ratios; many and frequently changing caregivers; homogeneous grouping by age and disability status; periodic graduations to new groups of peers and caregivers; and an “institutional style of caregiving'' that minimizes talking, provides rather dispassionate perfunctory care, and offers little warm, sensitive, contingently responsive caregiver–child interactions. The development of children in residence is usually delayed, sometimes extremely so, in every physical and behavioral domain. Although efforts are being made in many countries to care for children without permanent parents in family environments (e.g., domestic adoption, foster and kinship care, reunification with biological parents), it is not likely that transitions to family alternatives will be completed in all countries in the near future; thus, institutions are likely to exist for many years, if not decades. But institutions need not operate in the current manner; they can be modified to be substantially more family‐like in structure and in the behavior of caregivers. Research has indicated that when such changes are made, the development of children, both typically developing and those with special needs, is improved substantially. Based on the available literature and the authors' experience, this article describes steps that can be taken to implement such changes in residential institutions for infants and young children.
Acceleration of self‐consistent‐field convergence by combining conventional diagonalization and a diagonalization‐free procedure
Authors: Baldes Alexander , Klopper Wim , Šimunek Ján , Noga Jozef , Weigend Florian 
Published: July 2011

AbstractA new scheme that combines conventional matrix diagonalization with the recently proposed diagonalization‐free algorithm has been developed to obtain the density matrix for the next self‐consistent‐field iteration from the Fock matrix of the current iteration. In this manner, the advantages of the two methods are combined. The more rapid convergence of the diagonalization‐free algorithm for density matrices rather close to self consistence and the more robust convergence of the conventional matrix diagonalization further away from self‐consistence. The scheme has been implemented in the one‐ and two‐component self‐consistent‐field procedures in the program system TURBOMOLE. The number of iterations is typically reduced by about 10%, but savings are usually much larger for slowly converging cases. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Intramolecular hydrogen bond energy and cooperative interactions in α‐, β‐, and γ‐cyclodextrin conformers
Authors: Deshmukh Milind M. , Bartolotti Libero J. , Gadre Shridhar R. 
Published: July 2011

AbstractAccurate estimation of individual intramolecular hydrogen bond (H‐bond) energies is an intricate task for multiply H‐bonded systems. In such cases, the hydrogen bond strengths could be highly influenced by the cooperative interactions, for example, those between hydroxyl groups in sugars. In this work, we use the recently proposed molecular tailoring approach‐based quantification (Deshmukh, Gadre, and Bartolotti, J Phys Chem A 2006, 110, 12519) to the extended systems of cyclodextrins (CDs). Further, the structure and stability of different conformers of α‐, β‐, and γ‐CDs are explained based on the energetics and cooperative contribution to the strength of these H‐bonds. The estimated OH···O H‐bond energies in the various CD conformers are found to vary widely from 1.1 to 8.3 kcal mol−1. The calculated energy contributions to cooperativity toward the H‐bond strengths fall in the range of 0.25–2.75 kcal mol−1. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011