bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial analysis of metal concentrations in the brown shrimp Crangon crangon (Linnaeus, 1758) from the southern North Sea
Authors: Jung Kristine , Stelzenmüller Vanessa , Zauke Gerd-Peter
Published: January 2009

Spatial distributions of Cu, Pb, Cd, Ni and Zn concentrations in brown shrimps Crangon crangon (Linnaeus, 1758) collected on a cruise of FRV Walther Herwig III to the southern North Sea in January 2004, were investigated on a scale of 18 x 18 km to evaluate the range of spatial autocorrelations for the different variables under study. Semivariogram models obtained by geostatistical procedures indicated a distinct increase in variability for most variables with sampling distance. Only if samples are taken at distances above the estimated values for the practical range of the semivariogram can stochastic independence of the data be assumed. These are 6.6 km for Cd, 3.0 km for Ni and 5.2 km for Pb. Contour plots revealed a clear coincidence of high values for Cd, Ni and Pb with low shrimp mean body wet weight. Nevertheless, spatial autocorrelations were rather weak, since classical and geostatistical population estimates for the means and the 95% confidence intervals were in good agreement. The low detected concentrations of Pb in C. crangon were in good agreement with reported data for decapod crustaceans from other regions. For Zn reported values were distinctly below our 95% confidence intervals, while for Cu they were slightly above and for Cd distinctly above concentrations in C. crangon from this study. For Ni no comparative values exist. We conclude that with this integrated biomonitoring approach metal concentrations could be assessed more precisely and relations between biotic and abiotic variables could be evaluated.
Density, size structure, shell orientation and epibiontic colonization of the fan mussel Pinna nobilis L. 1758 (Mollusca: Bivalvia) in three contrasting habitats in an estuarine area of Sardinia (W Mediterranean)
Authors: Addis Piero , Secci Marco , Brundu Gianni , Manunza Andrea , Corrias Stefano , Cau Angelo
Published: January 2009

We investigated the spatial distribution, size structure, shell orientation and valve colonization by epibionts of the endangered Mediterranean bivalve Pinna nobilis in three continuous but different habitats in the Gulf of Oristano (Sardinia, western Mediterranean). The sampling stations chosen were: an estuarine area (E) of coastal salt-marshes characterized by unvegetated sea-bottoms; and two areas in a seagrass meadow characterized by an extensive Posidonia oceanica meadow (Mw) and patched mixed meadows of P. oceanica and Cymodocea nodosa (Me). We found significant differences in mean densities among stations and the highest value was found in the estuarine area. Shell orientation showed that there was uniform circular distribution of specimens in the Mw station and a unimodal distribution in the Me and E stations, where specimens were set at 0°N and 10°NNE, which is a pattern related to sea drift. Shell epibiosis displayed differences between habitats. The highest valve colonization was in the estuary, with filamentous dark algae and Ostrea edulis reaching almost 90 percent of shell coverage. This study provides new information on habitat preferences and data for assessing local populations of P. nobilis that is useful for its conservation and improving the knowledge of its ecology.
Otolith growth of European sea bass (Dicentrarchus labrax L.) larvae fed with constant or varying food levels
Authors: Aguilera Belén , Catalán Ignacio A. , Palomera Isabel , Olivar M. Pilar
Published: January 2009

Otolith growth and the value and properties of the Recent Otolith Growth Index (ROGI) were studied in sea bass (Dicentrarchus labrax L.) larvae that were reared for the first month of life with four different feeding regimes: fed, non-fed, late-feeding and late two-day fast. A marking experiment using alizarin complexone was previously carried out to validate increment deposition. Daily increment deposition was observed to take place from day two after hatching (DAH). The different feeding regimes did not significantly affect the periodicity of otolith increment deposition but did affect increment width. The ROGI was used as a tool for assessing feeding-induced differences in condition. Non-fed larvae had significantly smaller otoliths than fed larvae at the same age. In the late-feeding larvae (food available from 13 DAH), increment width increased progressively once food was supplied, and reached values similar to those for fed larvae after one week of feeding. Deprivation of food for two days in post-flexion larvae (in the fourth week of larval development) was reflected in the formation of progressively narrower increments which had still not returned to normal width two days after feeding was resumed. Our results show that the width of the outermost otolith increments reflect the past feeding history and that the ROGI can be used to distinguish well fed from suboptimally nourished larvae.
Short spatio-temporal variations in the population dynamics and biology of the deep-water rose shrimp Parapenaeus longirostris (Decapoda: Crustacea) in the western Mediterranean
Authors: Guijarro Beatriz , Massutí Enric , Moranta Joan , Cartes Joan E.
Published: January 2009

The deep-water rose shrimp Parapenaeus longirostris is a demersal decapod crustacean that is commercially exploited by trawl fleets. The present work compares its population dynamics, biology and condition in two locations (southern and north-western Mallorca in the Balearic Islands, western Mediterranean, separated by a distance of 120 km) with different environmental conditions and explores the relationships between the species and certain environmental factors. Six multidisciplinary bimonthly surveys were carried out during 2003 and 2004 in these two locations (between 150 and 750 m depth) in order to collect data on the demersal species with bottom trawl, the hydrography (temperature and salinity) with CTD casts, and trophic resources (zooplankton in the water column and suprabenthos with Bongo net and Macer-GIROQ sledge respectively) and sediments with a Shipeck dredge. The trawl fleets from both locations were monitored by monthly on board sampling and daily landings obtained from sales bills. Additional data was obtained from other trawl surveys. Temporal differences were detected both annually, with a decreasing trend over the last years in species abundance, and seasonally, in the biological indexes analysed. Bathymetric differences were also found in abundance, mean length, sex-ratio and condition of females. There were clear differences between the two locations studied, with higher abundance, condition and mean length and a lower length at first maturity for females in the north-western location. Trophic conditions could act as a link between geo-physical and biological changes. These short spatio-temporal differences could be due to the higher productivity found at this location, with higher density of preferred prey for the studied species together with adequate seafloor topography, sediment composition and hydrographical characteristics.
Highly Efficient Organocatalyzed Direct Asymmetric Aldol Reactions of Hydroxyacetone and Aldehydes
Authors: Wu Xiaoyu , Ma Zhixiong , Ye Zhengqing , Qian Shan , Zhao Gang
Published: January 2009

Novel organocatalysts derived from L‐threonine and L‐leucine have been synthesized for catalyzing direct aldol reactions of hydroxycetone and unactivated aliphatic aldehydes with as low as 2 mol% loading of the catalyst, good to excellent yields and excellent enantioselectivities have been achieved for aliphatic aldehydes, whereas aromatic aldehydes yield only moderate enantioselectivities.
The Ion Tag Strategy as a Route to Highly Efficient Organocatalysts for the Direct Asymmetric Aldol Reaction
Authors: Lombardo Marco , Easwar Srinivasan , Pasi Filippo , Trombini Claudio
Published: January 2009

The installation of an imidazolium tag via acetate connection to the C‐4 of cis‐4‐hydroxy‐L‐proline provides a highly efficient catalyst for the direct asymmetric aldol reaction, that works in a remarkably low catalyst loading (0.1 mol%) affording TONs up to 930 in the case of electron‐poor aromatic aldehydes with ee up to >99%.
Stereoselective Synthesis of Three Isomers of tert‐Butyl 5‐Hydroxy‐4‐methyl‐3‐oxohexanoate through Alcohol Dehydrogenase‐Catalyzed Dynamic Kinetic Resolution
Authors: Lüdeke Steffen , Richter Michael , Müller Michael
Published: January 2009

Regioselective reduction of the 5‐keto group of tert‐butyl 4‐methyl‐3,5‐dioxohexanoate (1) leads to a stereodiad of tert‐butyl 5‐hydroxy‐4‐methyl‐3‐oxohexanoate (2). Alcohol dehydrogenases from Lactobacillus brevis (LBADH), Rhodococcus sp. (RS 1‐ADH) and Saccharomyces cerevisiae (YGL157w) reduce 1 under dynamic kinetic resolution conditions, thereby establishing two chiral carbons with a single reduction step. While it had been shown previously that LBADH reduction of 1 stereoselectively leads to syn‐(4S,5R)‐2, alcohol dehydrogenase‐mediated dynamic kinetic resolution now allows easy access to syn‐(4R,5S)‐2 (RS 1‐ADH; 97.6% ee, syn:anti=92:8, 66% conversion, 37% isolated yield) and anti‐(4S,5S)‐2 (YGL157w; 90% ee, anti:syn=93:7, 64% conversion, 42% isolated yield), as well. Thus three out of four possible stereoisomers were formed selectively upon reduction of 1.
Preferential crystallization: Multi‐objective optimization framework
Authors: Bhat Shrikant A. , Huang Biao
Published: January 2009

A four objective optimization framework for preferential crystallization of D‐L threonine solution is presented. The objectives are maximization of average crystal size and productivity, and minimization of batch time and the coefficient of variation at the desired purity while respecting design and operating constraints. The cooling rate, enantiomeric excess of the preferred enantiomer, and the mass of seeds are used as the decision variables. The optimization problem is solved by using adaptation of the nondominated sorting genetic algorithm. The results obtained clearly distinguish different regimes of interest during preferential crystallization. The multi‐objective analysis presented in this study is generic and gives a simplified picture in terms of three zones of operations obtained because of relative importance of nucleation and growth. Such analysis is of great importance in providing better insight for design and decision making, and improving the performance of the preferential crystallization that is considered as a promising future alternative to chromatographic separation of enantiomers. © 2009 American Institute of Chemical Engineers AIChE J, 2009
Asthma management: Reinventing the wheel in sickle cell disease
Authors: Morris Claudia R.
Published: January 2009

Asthma is a common comorbidity in sickle cell disease (SCD) with a reported prevalence of 30–70%. The high frequency of asthma in this population cannot be attributed to genetic predisposition alone, and likely reflects in part, the contribution of overlapping mechanisms shared between these otherwise distinct disorders. There is accumulating evidence that dysregulated arginine metabolism and in particular, elevated arginase activity contributes to pulmonary complications in SCD. Derangements of arginine metabolism are also emerging as newly appreciated mechanism in both asthma and pulmonary hypertension independent of SCD. Patients with SCD may potentially be at risk for an asthma‐like condition triggered or worsened by hemolysis‐driven release of erythrocyte arginase and low nitric oxide bioavailability, in addition to classic familial asthma. Mechanisms that contributed to asthma are complex and multifactorial, influenced by genetic polymorphisms as well as environmental and infectious triggers. Given the association of asthma with inflammation, oxidative stress and hypoxemia, factors known to contribute to a vasculopathy in SCD, and the consequences of these factors on sickle erythrocytes, comorbid asthma would likely contribute to a vicious cycle of sickling and subsequent complications of SCD. Indeed a growing body of evidence documents what should come as no surprise: Asthma in SCD is associated with acute chest syndrome, stroke, pulmonary hypertension, and early mortality, and should therefore be aggressively managed based on established National Institutes of Health Guidelines for asthma management. Barriers to appropriate asthma management in SCD are discussed as well as strategies to overcome these obstacles in order to provide optimal care. Am. J. Hematol., 2009. © 2008 Wiley‐Liss, Inc.
Stabile Fünfring‐Allene mit ausschließlich Elementen der 2. Periode: keine Allene, sondern Zwitterionen
Authors: Christl Manfred , Engels Bernd
Published: January 2009

Ein Pyrazolderivat, das Dyker, Bertrand et al. für ein stabiles fünfgliedriges cyclisches Allen 1 a hielten, wird als Zwitterion 1 b reinterpretiert. Es wird dargelegt, dass die für Allene charakteristischen Bindungsverhältnisse für die Struktur 1 a nicht möglich sind. Ar = 2,6‐Dimethylphenyl.

magnified image
Synthesis and characterization of poly(aryl ether ketone) oligomers terminated with metallophthalocyanine to be used for oxidative decomposition of TCP
Authors: Zhang Yunhe , Guo Meimei , Guan Shaowei , Zhang Ying , Jiang Zhenhua
Published: January 2009

A series of metallophthalocyanine‐terminated poly(aryl ether ketone) oligomers were synthesized from dicyanobenzene‐terminated poly(aryl ether ketone) oligomers with different metal chloride and phthalonitrile. All polymers exhibited high glass transition temperature and good thermal stability. These polymers showed optical absorption in the visible region and had different colors in chloroform solution. Cobalt phthalocyanine‐terminated poly(aryl ether ketone) oligomers exhibited good catalytic activity in oxidative decomposition of 2,4,6‐trichlorophenol (TCP) under H2O2 and KHSO5. The catalytic activity of KHSO5 is much better than H2O2, and more than 70% of initial TCP was decomposed within 7 h. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Insights into prevention of human neural tube defects by folic acid arising from consideration of mouse mutants
Authors: Harris Muriel J.
Published: January 2009

Almost 30 years after the initial study by Richard W. Smithells and coworkers, it is still unknown how maternal periconceptional folic acid supplementation prevents human neural tube defects (NTDs). In this article, questions about human NTD prevention are considered in relation to three groups of mouse models: NTD mutants that respond to folate, NTD mutants and strains that do not respond to folate, and mutants involving folate‐pathway genes. Of the 200 mouse NTD mutants, only a few have been tested with folate; half respond and half do not. Among responsive mutants, folic acid supplementation reduces exencephaly and/or spina bifida aperta frequency in the Sp2H, Sp, Cd, Cited2, Cart1, and Gcn5 mutants. Prevention ranges from 35 to 85%. The responsive Sp2H (Pax3) mutant has abnormal folate metabolism, but the responsive Cited2 mutant does not. Neither folic nor folinic acid reduces NTD frequency in Axd, Grhl3, Fkbp8, Map3k4, or Nog mutants or in the curly tail or SELH/Bc strains. Spina bifida frequency is reduced in Axd by methionine and in curly tail by inositol. Exencephaly frequency is reduced in SELH/Bc by an alternative commercial ration. Mutations in folate‐pathway genes do not cause NTDs, except for 30% exencephaly in folate‐treated Folr1. Among folate‐pathway mutants, neural tube closure is normal in Cbs, Folr2, Mthfd1, Mthfd2, Mthfr, and Shmt1 mutants. Embryos die by midgestation in Folr1, Mtr, Mtrr, and RFC1 mutants. The mouse models point to genetic heterogeneity in the ability to respond to folic acid and also to heterogeneity in genetic cause of NTDs that can be prevented by folic acid. Birth Defects Research (Part A) 2009. © 2008 Wiley‐Liss, Inc.
Greening from the front to the back door? A typology of chemical and resource management services
Authors: Anttonen Markku
Published: January 2009

Though services and product–service systems have been promoted as a promising way towards more eco‐efficient and sustainable societies, they have not turned into reality as expected. Chemical and resource management services are among the few operational examples. They aim to align the service provider's and customer's actions to reduce chemical usage and waste, improve supply chain management and increase resource efficiency. Arguably, they also create new business and higher profit margins compared with merely selling chemicals or handling industrial waste. Thus far they have been viewed as a single business model. In contrast, this study shows through the construction of five ideal types that the actual services and their focus vary. They range from the management of the chemical supply to operations, waste reduction, combined logistics services, process management, IT and other technologies. Consequently this affects the value creation, organization and environmental efficiencies of these services. Copyright © 2008 John Wiley & Sons, Ltd and ERP Environment.
Assessing Carbohydrate–Carbohydrate Interactions by NMR Spectroscopy: The Trisaccharide Epitope from the Marine Sponge Microciona prolifera
Authors: Santos J. Ignacio , Carvalho de Souza Adriana , Cañada F. Javier , Martín‐Santamaría Sonsoles , Kamerling Johannis P. , Jiménez‐Barbero Jesús
Published: January 2009

Weak recognition processes: Weak calcium‐mediated carbohydrate–carbohydrate interactions have been detected by DOSY and TRNOESY NMR methods by employing a gold glyconanoparticle as a multivalent system. In addition, 3D models of trisaccharide‐CaII‐trisaccharide complexes based on results from molecular dynamics simulations are proposed.

magnified image

Diffusion‐ordered NMR spectroscopy (DOSY‐NMR) and TR‐NOESY‐NMR experiments are used to detect ligand binding to macromolecular receptors. These techniques have been applied to detect weak carbohydrate–carbohydrate self‐recognition in solution, making use of sugar‐decorated gold nanoparticles as the “macromolecule” and the same carbohydrate as the ligand. Changes in the diffusion coefficient of the free carbohydrate in the presence of the glyconanoparticle (only with CaII ions in the sample solution), as well as changes in the sign of the sugar NOE peaks—positive for the free sugar (in the presence or absence of CaII) and negative for the sugar only in the simultaneous presence of the glyconanoparticle and CaII ions—have been taken as proof of weak CaII‐mediated carbohydrate–carbohydrate interactions in solution. Although different methods such as SPR, TEM, and AFM have been used in the past to detect carbohydrate–carbohydrate interactions with the aid of gold nanoparticles and gold selfassembled monolayers, they are restricted to high‐affinity ranges. The methods used in this study allow expansion of the number of techniques to tackle this relevant biological problem, also for approaching ligand–receptor interactions below the high‐affinity range. Additionally, 3D models of trisaccharide‐CaII‐trisaccharide complexes based on results from molecular dynamics simulations are proposed.
Enzymatic Synthesis of Enantiopure α‐ and β‐Amino Acids by Phenylalanine Aminomutase‐Catalysed Amination of Cinnamic Acid Derivatives
Authors: Wu Bian , Szymanski Wiktor , Wietzes Piet , de Wildeman Stefaan , Poelarends Gerrit J. , Feringa Ben L. , Janssen Dick B.
Published: January 2009

The phenylalanine aminomutase (PAM) from Taxus chinensis catalyses the conversion of α‐phenylalanine to β‐phenylalanine, an important step in the biosynthesis of the N‐benzoyl phenylisoserinoyl side‐chain of the anticancer drug taxol. Mechanistic studies on PAM have suggested that (E)‐cinnamic acid is an intermediate in the mutase reaction and that it can be released from the enzyme's active site. Here we describe a novel synthetic strategy that is based on the finding that ring‐substituted (E)‐cinnamic acids can serve as a substrate in PAM‐catalysed ammonia addition reactions for the biocatalytic production of several important β‐amino acids. The enzyme has a broad substrate range and a high enantioselectivity with cinnamic acid derivatives; this allows the synthesis of several non‐natural aromatic α‐ and β‐amino acids in excellent enantiomeric excess (ee >99 %). The internal 5‐methylene‐3,5‐dihydroimidazol‐4‐one (MIO) cofactor is essential for the PAM‐catalysed amination reactions. The regioselectivity of amination reactions was influenced by the nature of the ring substituent.
Regio‐, Peri‐, and Torquoselectivity in Hydroxy Heptatrienyl Cation Electrocyclizations: The Iso/Homo‐Nazarov Reaction
Authors: Faza Olalla Nieto , López Carlos Silva , Álvarez Rosana , de Lera Ángel R.
Published: January 2009

Competition: The electrocyclizations of 1‐ and 3‐hydroxyheptatrienyl cations (see scheme) have been computationally studied at the B3LYP/6‐311G(d) level. The 1‐hydroxy system clearly favors a 4e−over a 6e−process, while for the 3‐hydroxy isomer these mechanisms compete.

magnified image

The electrocyclizations of 1‐ and 3‐hydroxyheptatrienyl cations have been computationally studied at the B3LYP/6‐311G(d) level. The 1‐hydroxy system clearly favors a 4πe−over a 6πe−process, while for the 3‐hydroxy isomer these mechanisms compete. Substituents can either enhance or invert this periselectivity through steric or electronic effects, respectively. Houk's model of torquoselectivity helps to explain the activation energy differences between the alternative 4πe−electrocyclizations available for each system. The cyclopentenyl cations thus obtained can evolve, either through intramolecular trapping by the vinyl group or by 1,3‐proton migration, along reaction coordinates which could correspond to either very asynchronous concerted mechanisms, or two‐step reactions with very shallow or non‐existent intermediates.
Total Syntheses of Casuarine and Its 6‐O‐α‐Glucoside: Complementary Inhibition towards Glycoside Hydrolases of the GH31 and GH37 Families
Authors: Cardona Francesca , Parmeggiani Camilla , Faggi Enrico , Bonaccini Claudia , Gratteri Paola , Sim Lyann , Gloster Tracey M. , Roberts Shirley , Davies Gideon J. , Rose David R. , Goti Andrea
Published: January 2009

Selective glucosylation: Total synthesis of naturally occurring casuarine (1) and the first total synthesis of casuarine 6‐O‐α‐glucoside (2) were achieved through complete stereoselective nitrone cycloaddition, Tamao–Fleming oxidation and selective α‐glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes.

magnified image

Total synthesis of naturally occurring casuarine (1) and the first total synthesis of casuarine 6‐O‐α‐glucoside (2) were achieved through complete stereoselective nitrone cycloaddition, Tamao–Fleming oxidation and selective α‐glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes. The structural determination of the complexes of NtMGAM with 1 and of Tre37A with 2 revealed interesting similarities in the catalytic sites of these two enzymes which belong to different families and clans.
Density Functional Study of Proline‐Catalyzed Intramolecular Baylis–Hillman Reactions
Authors: Duarte Filipe J. S. , Cabrita Eurico J. , Frenking Gernot , Santos A. Gil
Published: January 2009

A rationalization of stereoselectivity: The mechanisms of proline‐catalyzed and imidazole‐co‐catalyzed intramolecular Baylis–Hillman reactions have been studied by using density functional theory methods. The computational data has allowed us to rationalize the experimental outcome, validating some of the mechanistic steps proposed in the literature, as well as to propose new ones that considerably change and improve our understanding of the full reaction path (see scheme).

magnified image

The mechanisms of proline‐catalyzed and imidazole‐co‐catalyzed intramolecular Baylis–Hillman reactions have been studied by using density functional theory methods at the B3LYP/6‐31G(d,p) level of theory. A polarizable continuum model (PCM B3LYP/6‐31++G(d,p)//B3LYP/6‐31G(d,p)) was used to describe solvent effects. Different reaction pathways were investigated, which indicated that water is an important catalyst in the imine/enamine conversion step in the absence of imidazole. When imidazole is used as a co‐catalyst, water is still important in the imidazole addition step, but is not present in the Baylis–Hillman cyclization step. The computational data has allowed us to rationalize the experimental outcome of the intramolecular Baylis–Hillman reaction, validating some of the mechanistic steps proposed in the literature, as well as to propose new ones that considerably change and improve our understanding of the full reaction path.
Stereoselective Allylation of Ketones: Explanation for the Unusual Inversion of the Induced Stereochemistry in the Auxiliary‐Mediated Crotylation and Pentenylation of Butanone by DFT Calculations
Authors: Tietze Lutz F. , Kinzel Tom , Schmatz Stefan
Published: January 2009

The solvent makes the difference: While attack at the Re face of the intermediate oxocarbenium ion becomes less energy demanding with increasing size of R′, it is the solvent effect that makes this attack the main trajectory, leading to inversed stereochemistry (see picture).

magnified image

Auxiliary‐mediated domino crotylations and pentenylations of butanone yield homoallylic ethers with two newly formed stereogenic centers. With our norpseudoephedrine‐derived auxiliary, we observed the formation of anti isomers exclusively, and the nature of the major isomer was independent of the substrate double bond geometry. Interestingly, there is a switch in induced selectivity when going from crotylation to pentenylation. Here, we present the computational rationalization for this behavior by identification of the relevant transition states (TSs), the energies of which were determined by using the B3LYP/6‐31+G(d) level of theory in combination with the PCM/UAKS method to include the effects exerted by the solvent dichloromethane. To quickly narrow down the number of potentially relevant TSs from the whole set of 288 and 864 TSs for the crotylation and pentenylation, respectively, we employed a screening process based on B3LYP//AM1 energies. The predicted selectivities are in good agreement with experimentally determined ones. Furthermore, the obtained results also facilitate an explanation of the selectivities obtained in hexenylations and heptenylations. Finally, activation energies were determined that account for the significantly longer reaction times than those for the domino allylation with unsubstituted trimethylallylsilane.
High serum des‐gamma‐carboxy prothrombin level predicts poor prognosis after radiofrequency ablation of hepatocellular carcinoma
Authors: Kobayashi Masahiro , Ikeda Kenji , Kawamura Yusuke , Yatsuji Hiromi , Hosaka Tetsuya , Sezaki Hitomi , Akuta Norio , Suzuki Fumitaka , Suzuki Yoshiyuki , Saitoh Satoshi , Arase Yasuji , Kumada Hiromitsu
Published: January 2009

BACKGROUND:

Currently, surgical resection is considered the first‐line treatment for early stage hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) has been an alternative choice for unresectable HCC. However, RFA is expected to have similar therapeutic efficacy for early stage HCC with fewer invasions.

METHODS:

The authors retrospectively analyzed 199 patients who underwent surgery and 209 patients who underwent RFA for HCC with a maximum diameter of ≤3 cm and tumors numbering ≤3. All patients were complicated with Child‐Pugh A cirrhosis.

RESULTS:

The 3‐ and 5‐year survival rates of the resection (90.3%, 79.0%, respectively) and RFA groups were similar (87.4%, 74.8). The 1‐ and 3‐year tumor recurrence‐free survival rates of the resection group (83.1%, 51.0%, respectively) were higher than in the RFA group (82.7%, 41.8%;P= .011). Multivariate analysis identified prothrombin time ≥80% (hazard ratio [HR], 2.72; 95% confidence interval [CI], 1.56‐4.74;P< .001) as an independent prognostic factor for survival in the resection group. Des‐gamma‐carboxy prothrombin (DCP) <100 arbitrary units (AU)/L (HR, 5.49; CI, 2.23‐13.5;P< .001) and platelet count ≥1.0 × 105(HR, 2.70; CI, 1.24‐5.88;P= .012) were significant markers in the RFA group. Among patients with DCP ≥100 AU/L, treatment procedure (HR, 1.26; CI, 1.04‐1.53;P= .020) was a significant prognostic factor for survival.

CONCLUSIONS:

High DCP levels reflect the biologic aggressiveness and progression of HCC tumors. In the aforementioned cases, we recommend surgical resection rather than RFA for such patients. Cancer 2009. © 2008 American Cancer Society.
Induction of human tumor‐associated differentially expressed gene‐12 (TADG‐12/TMPRSS3)‐specific cytotoxic T lymphocytes in human lymphocyte antigen‐A2.1–positive healthy donors and patients with advanced ovarian cancer
Authors: Bellone Stefania , Anfossi Simone , O'Brien Timothy J. , Cannon Martin J. , Silasi Dan‐Arin , Azodi Masoud , Schwartz Peter E. , Rutherford Thomas J. , Pecorelli Sergio , Santin Alessandro D.
Published: January 2009

BACKGROUND:

Tumor‐associated differentially expressed gene‐12 (TADG‐12) is a serine protease recently found highly differentially expressed in epithelial ovarian cancer. The goal of this study was to identify potential immunogenic peptides derived from TADG‐12 for immunotherapy of ovarian carcinoma.

METHODS:

A bioinformatics approach (ie, the BIMAS algorithm, National Institutes of Health, http://bimas.dcrt.nih.gov/molbio/hla_bind) was used to identify multiple immunogenic peptides derived from TADG‐12 that bind to human leukocyte antigen‐A2.1 and elicit peptide‐specific human cytotoxic T lymphocyte (CTL) responses in healthy individuals and in patients with advanced stage ovarian cancer.

RESULTS:

CD8+ CTL populations generated against 5 TADG‐12–derived peptides were consistently able to induce lysis of autologous peptide‐loaded target cells above background. Importantly, TADG‐12 YLPKSWTIQV peptide‐specific CTLs from healthy donors and ovarian cancer patients were found to effectively kill ovarian cancer cells naturally expressing TADG‐12. Cytotoxicity was significantly inhibited by anti–human lymphocyte antigen (HLA)‐A2.1 (BB7‐2) and anti–HLA class I (W6 of 32) monoclonal antibodies, whereas natural killer–sensitive K562 cells were not lysed. TADG‐12 YLPKSWTIQV peptide‐specific CTL precursor frequency was low in peripheral blood leukocytes of normal donors and ovarian cancer patients, as determined by interferon‐γ production in enzyme‐linked immunosorbent spot‐forming cell assays. Intracellular cytokine expression measured by flow cytometry after OKT‐3 monoclonal antibody stimulation showed a type 1 cytokine profile in YLPKSWTIQV peptide‐specific CTLs.

CONCLUSIONS:

The TADG‐12 YLPKSWTIQV peptide is an immunogenic epitope in ovarian tumors and may represent an attractive target for immunotherapy of ovarian cancer. These data may pave the way for TADG‐12 peptide‐derived cell‐based therapy, including dendritic cell immunotherapy, for the vaccination of ovarian cancer patients harboring chemotherapy‐resistant or residual disease. Cancer 2009. © 2008 American Cancer Society.
Phase 1 study of an oxaliplatin and etoposide regimen in pediatric patients with recurrent solid tumors
Authors: McGregor Lisa M. , Spunt Sheri L. , Santana Victor M. , Stewart Clinton F. , Ward Deborah A. , Watkins Amy , Laningham Fred H. , Ivy Percy , Furman Wayne L. , Fouladi Maryam
Published: January 2009

BACKGROUND:

The combination of a platinating agent and etoposide has induced responses in various pediatric tumors. The study estimated the maximum tolerated dose (MTD) of an oxaliplatin and etoposide regimen in children with recurrent solid tumors.

METHODS:

Oxaliplatin was administered on Day 1 and etoposide on Days 1 to 3 of each 21‐day course. Cohorts of 3 to 6 patients were enrolled at 3 dose levels: 1) oxaliplatin at a dose of 130 mg/m2 and etoposide at a dose of 75 mg/m2, 2) oxaliplatin at a dose of 130 mg/m2 and etoposide at a dose of 100 mg/m2, and 3) oxaliplatin at a dose of 145 mg/m2 and etoposide at a dose of 100 mg/m2. Calcium and magnesium infusions were used at dose level 3 in an attempt to escalate the oxaliplatin dose past the single‐agent MTD.

RESULTS:

The 16 patients received a total of 63 courses. At dose level 1, dose‐limiting epistaxis, neuropathy, and neutropenia occurred in 1 of 6 patients. No dose‐limiting toxicity (DLT) occurred at dose level 2 (n = 6). At dose level 3, 2 of 4 patients experienced dose‐limiting neutropenia; none experienced grade 3 or 4 acute neuropathy. Six patients required prolongation of the oxaliplatin infusion because of acute sensory neuropathy. Responses were observed in patients with medulloblastoma (1 complete response) and pineoblastoma (1 partial response); 3 others with atypical teratoid rhabdoid tumor, ependymoma, and soft tissue sarcoma had prolonged disease stabilization.

CONCLUSIONS:

The MTD of this regimen was found to be oxaliplatin at a dose of 130 mg/m2 given on Day 1 and etoposide at a dose of 100 mg/m2/d given on Days 1 to 3. Neutropenia was found to be the DLT. Calcium and magnesium infusions did not allow escalation of the oxaliplatin dose. The combination was well‐tolerated and demonstrated antitumor activity. Cancer 2009. © 2008 American Cancer Society.
Bendamustine
Authors: Kalaycio Matt
Published: January 2009

Alkylating agents form the basis of most combination treatment regimens for low‐grade lymphoproliferative disorders. Bendamustine is a unique alkylating agent that has distinctive preclinical activity in cell lines resistant to other alkylators. Furthermore, clinical activity has been demonstrated in patients with alkylating agent resistant disease. Recently, larger studies have been organized to study the clinical effects of bendamustine further. In indolent B‐cell non‐Hodgkin lymphoma that is resistant to rituximab, bendamustine induced a remission in 77% of patients. Myelosuppression was identified as the most common toxicity. In 2 studies of similar populations of patients, the combination of bendamustine and rituximab induced remission 90% of patients with a median progression‐free survival of 23‐24 months. The overall remission rate was 59% in a prospective, randomized study of untreated patients with chronic lymphocytic leukemia, which was significantly greater than the rate of 26% in the chlorambucil control arm (P < 0.001). Combined with rituximab, bendamustine induces a remission in 67% of patients with relapsed or refractory chronic lymphocytic leukemia. Bendamustine is an active agent for the treatment of low‐grade lymphoproliferative disorders and more study is needed to determine which dose and schedule is optimal, and which patients will derive the greatest benefit from its use. Cancer 2009. © 2008 American Cancer Society.
Early changes in tumor size in patients treated for advanced stage nonsmall cell lung cancer do not correlate with survival
Authors: Birchard Katherine R. , Hoang Jenny K. , Herndon James E. , Patz Edward F.
Published: January 2009

BACKGROUND:

In clinical trials, change in tumor size is used to stratify patients into response categories. The objective of the current study was to: 1) determine whether early change in the tumor size were correlated with survival in patients with advanced nonsmall cell lung cancer (NSCLC) using modified response categories from the Response Evaluation Criteria in Solid Tumors (RECIST), and 2) to determine whether there was an optimal percentage change in tumor size that could be used to define a partial response that also correlated with survival.

METHODS:

A total of 99 consecutive patients presenting for the treatment of advanced NSCLC during the year 2003 who had computed tomography (CT) scans before and after treatment available for review were included in the study. The largest target thoracic lesion was measured on CT before treatment, and again 2 months to 3 months after the initiation of treatment. Percent change in tumor size was calculated. The relation between tumor response and patient survival was investigated.

RESULTS:

There was no definite relation noted between early tumor response and patient survival (P = .754). Patients who had any initial reduction in tumor size were not found to have a significantly different survival compared with patients with initial disease progression (P = .580). In addition, there was no particular percent reduction in tumor size that was found to optimally correlate with survival.

CONCLUSIONS:

There is no evidence of a relation between early changes in tumor size and survival among patients with advanced stage NSCLC. To predict survival in patients with advanced NSCLC, response criteria other than change in lesion size are needed. Cancer 2009. © 2008 American Cancer Society.
Characterisation of virgin olive oils from European olive cultivars introduced in Tunisia
Authors: Dabbou Samia , Issaoui Manel , Servili Maurizio , Taticchi Agnese , Sifi Samira , Montedoro Gian Francesco , Hammami Mohamed
Published: January 2009

The behaviour of three European olive varieties, Ascolana Tenera, Koroneiki and Picholine, cultivated in the north of Tunisia, was compared to an autochthonous variety, Chétoui. Most of the quality indices and the fatty acid composition showed significant variations between the olive oils. Among the introduced varieties, the Picholine cultivar had the highest value of oleic acid (61%) whereas the Ascolana Tenera cultivar was noteworthy for its lowest content of phenolic compounds (175 mg/kg) and presented the highest level of palmitic acid. The Chétoui variety presented a high content of oleic and linoleic acids. But all samples, both the autochthonous Chétoui and the introduced cultivars, have similar levels of antioxidant compounds, with the exception of phenols. The aroma composition showed significant differences between the oils from the foreign cultivars. The major volatile component was the C‐6 aldehyde fraction whose content varied greatly between the different varieties studied: The E‐2‐hexenal content ranged from 1.6 mg/kg of oil in the Ascolana Tenera variety to >5 mg/kg for the Picholine and Koroneiki cultivars, whereas the Chétoui variety had the lowest levels of volatile compounds, with the exception of the hexanal level which was tenfold higher than in the foreign cultivars. Therefore, our results showed that two of the introduced varieties, Koroneiki and Picholine, showed good adaptation to the Tunisian cultivation conditions. So far, we claim the possibility to develop the successful cultivation of these latter imported varieties in the country.
Characterization of grape seed oil from different grape varieties (Vitis vinifera)
Authors: Pardo Jose Emilio , Fernández Enrique , Rubio Manuela , Alvarruiz Andrés , Alonso Gonzalo Luis
Published: January 2009

In this work, oil obtained from seeds of different red grape varieties, grown in the Autonomous Regions of Castilla‐La Mancha and Murcia (Spain), was characterized by determining physicochemical and sensory quality parameters, stability, and the composition in fatty acids and sterols. The physicochemical quality parameters (free acidity, peroxide index, K270 and wax) scored high (meaning low quality) compared with virgin olive oils, while the negative sensory attributes stood out over the positive ones. Therefore, the oil was not considered suitable for table use without undergoing a refining process. The samples showed high linoleic and low linolenic acid contents, while β‐sitosterol was the main sterol found. Drying grape seeds with hot air before extraction gave higher physicochemical quality, total phenolic content and stability, and lower wax content in comparison to air‐drying of seeds. The drying process affected the sterol composition but not the fatty acid composition.
Highly accurate photopyroelectric measurement of thermal diffusivity of vegetable oils
Authors: Dadarlat Dorin , Neamtu Camelia , Streza Mihaela , Socaciu Carmen , Bele Constantin , Dulf Francisc
Published: January 2009

High‐accuracy photopyroelectric measurements, in the thermal‐wave‐resonator‐cavity configuration, were performed in order to measure the thermal diffusivity of some vegetable oils. The high resolution (relative error ±0.5%) of the above method allows for the detection of small changes in the values of this dynamic thermal parameter. The accuracy of the results is mainly due to the possibility to precisely control the variation (30‐nm step) of sample thickness, a proper selection of the range of the thickness scan (2 µm < Lm < 4 µm ˜ 5 µm), and an iterative procedure of data analysis. A correlation between thermal diffusivity and the fatty acid composition (obtained via gas chromatography) is suggested for some fresh (sunflower, hemp, flax, and soybean) oils and for hemp oil exposed to a microwave field: Thermal diffusivity appears to be determined by the overall content of polyunsaturated fatty acids.
Short‐path distillation of palm olein and characterization of products
Authors: Lin Siew Wai , Yoo Cheah Kien
Published: January 2009

Short‐path distillation (SPD) has been a technique used to purify products containing monoacylglycerols (MAG), diacylglycerols (DAG), etc. Palm oil and its fractions contain high contents of DAG, typically 5–8%, some of which have significant effects on the crystallization behavior of the fats. A possible way of reducing the DAG to lower levels using SPD is evaluated. Distillation of refined, bleached and deodorized palm olein was performed at different temperatures (220–250 °C) and flow rates (500 and 1000 g/h). Feed oil, residue oil and distillates were characterized in terms of composition and melting and cooling behavior. The DAG content of the feed oil was 6.5%. At high evaporating temperatures, the free fatty acid (FFA) concentration in the residue oil and the distillate oil decreased for the same flow rate. Increasing the feed flow rate while maintaining constant temperature led to a greater FFA concentration in both streams. The DAG content in the distillate increased at higher temperature, reaching 68% at 250 °C, while the residue oil achieved a level of 2.8% at lower flow feeding rates. Melting and cooling behavior were influenced by the composition of DAG and triacylglycerols. Thus, the distillate oils had higher melting profiles in contrast to the feed oil and the residue oil, which had similar profiles despite the removal of higher‐melting components.
Effect of unsaturated acyl chains on structural transformations in triacylglycerols
Authors: Mykhaylyk Oleksandr O. , Martin Christopher M.
Published: January 2009

Simultaneous time‐resolved small‐angle and wide‐angle X‐ray scattering has been used in the study of the isothermal crystallization behavior, after quenching, of triacylglycerols (TAG) with 18 carbons in the hydrocarbon chains. Saturated, unsaturated TAG, their blends and mixed saturated/unsaturated TAG were studied. The mixed saturated/unsaturated TAG and their blends form an α2‐phase with a longitudinal packing different from two‐chain and three‐chain packings, which distinguishes them from the other fats. The unstable α2‐phase, observed at the initial stage of crystallization of mixed saturated/unsaturated TAG, is classified as a transient mesophase. Two dimeric units proposed for a structural model of the α2‐phase have been used to describe the structural organization of TAG molecules in the liquid state.
Unique Regioselective Binding of Permethylated β‐Cyclodextrin with Azobenzene Derivatives
Authors: Shi Jun , Guo Dong‐Sheng , Ding Fei , Liu Yu
Published: January 2009

The binding behavior of permethylated β‐cyclodextrin (PM‐β‐CD) upon complexation with 4‐hydroxyazobenzene (4‐HAB) and 4‐aminoazobenzene (4‐AAB) was investigated by X‐ray crystallography, circular dichroism, 2D NMR spectra, and isothermal titration calorimetry. In comparison to the reported β‐cyclodextrin (β‐CD) complexes with 4‐HAB and 4‐AAB, PM‐β‐CD complexes 3 and 4 present not only unique binding regioselectivity with azobenzene guests but also have distinct spatial arrangements, that is, β‐CDs arrange in a head‐to‐head manner, whereas PM‐β‐CDs arrange in a head‐to‐tail manner. The results obtained from circular dichroism and 2D NMR spectra indicate that the binding modes of complexes 3 and 4 in solution are in accordance with those in the solid state. Furthermore, the binding abilities and thermodynamic parameters of β‐CD and PM‐β‐CD upon complexation with azobenzene derivatives were discussed from the viewpoints of the flexibilities of the frameworks of the hosts and driving forces. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Asymmetric Lewis Acid Catalysis in Water: α‐Amino Acids as Effective Ligands in Aqueous Biphasic Catalytic Michael Additions
Authors: Aplander Karolina , Ding Rui , Krasavin Mikhail , Lindström U. Marcus , Wennerberg Johan
Published: January 2009

This article explores the potential of native α‐amino acids as chiral ligands in aqueous asymmetric Lewis acid catalysis, employing the C–C bond forming Michael addition as a model reaction. Some insights are provided regarding the details of Yb(OTf)3/α‐amino acid‐catalyzed Michael additions in water through new kinetic data as well as studies on how both yield and selectivity are influenced by variations in metal/ligand ratio, pH, temperature, and structure of the α‐amino acid. Through this investigation it was found that reaction conditions that require only 5 mol‐% of the Lewis acid, provides enantiomeric excesses of up to 79 % and is applicable to a wider range of donors and acceptors than previously demonstrated. Importantly, it was also demonstrated that the α‐amino acid complexed ytterbium catalyst might have potential for large‐scale applications as it displays not only large ligand accelerations, but also good solubility and stability in water. It can be recycled multiple times without appreciable loss of activity. The result is a promising example of a water‐compatible chiral Lewis acid.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Enantiocomplementary Chemoenzymatic Asymmetric Synthesis of (R)‐ and (S)‐Chromanemethanol
Authors: Fuchs Michael , Simeo Yolanda , Ueberbacher Barbara T. , Mautner Barbara , Netscher Thomas , Faber Kurt
Published: January 2009

A non‐lipase‐based, enantiocomplementary chemoenzymatic route towards enantiopure (R)‐ and (S)‐chromanemethanol (12), which are the key building blocks for the synthesis of stereoisomerically pure α‐tocopherols, has been achieved by the biocatalytic resolution of a racemic 2,2‐disubstituted oxirane using an epoxide hydrolase and a halohydrin dehalogenase, which exhibit opposite enantiopreferences. The introduction of chirality at an early stage of the synthesis ensured a high efficiency, leading to total overall yields of 16 and 26 % for (R)‐ and (S)‐chromanemethanol (12), respectively.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
1,2‐Diarylethanols by Alternative Regioselective Reductive Ring‐Opening of 2,3‐Diaryloxiranes
Authors: Di Blasio Nadia , Lopardo Maria Teresa , Lupattelli Paolo
Published: January 2009

Non‐symmetrical trans‐2,3‐diaryloxiranes have been regioselectively opened by catalytic hydrogenation over Pd/C, NaBH4/Pd and [Cp2TiCl]/H2O. Although in the catalytic hydrogenation reactions the epoxides were mainly opened at the β‐carbon with respect to the substituted aryl ring in all cases, with the [Cp2TiCl]/H2O system the regioselectivity was affected by the electronic properties of the aryl residues, the epoxides being opened on the carbon bearing the most electron‐releasing or the least electron‐withdrawing group. With the NaBH4/Pd system different regioisomers were obtained depending on the substituents. Starting from enantioenriched epoxides, no loss of optical purity was observed in the alcohols formed.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)