bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Asymmetric Synthesis of Lometrexol ((6R)‐5,10‐Dideaza‐5,6,7,8‐ tetrahydrofolic Acid).
Authors: BARNETT C. J. , WILSON T. M. , WENDEL S. R. , WINNINGHAM M. J. , DEETER J. B.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Inhibitors of Glycinamide Ribonucleotide Formyltransferase as Potential Cytotoxic Agents. Synthesis of 5‐Deaza‐5,6,7,8‐ tetrahydrohomofolic Acid, 5‐Deaza‐5,6,7,8‐tetrahydroisohomofolic Acid, and 10‐Formyl‐5‐deaza‐5,6,7,8‐tetrahydroisohomofolic Acid.
Authors: TAYLOR E. C. , YOON C. , HAMBY J. M.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Stereoselective Reduction of β,δ‐Diketo Esters. A Novel Strategy for the Synthesis of Artificial HMG‐CoA Reductase Inhibitors.
Authors: HIYAMA T. , REDDY G. B. , MINAMI T. , HANAMOTO T.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis of Artificial HMG‐CoA Reductase Inhibitors Based on the Olefination Strategy.
Authors: HIYAMA T. , MINAMI T. , TAKAHASHI K.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis and Antibacterial Activities of 2‐Oxaisocephems.
Authors: TSUBOUCHI H. , TSUJI K. , YASUMURA K. , ISHIKAWA H.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: One‐Step Synthesis of Azetidinone Dithiocarboxylic Esters, Intermediates in the Preparation of 2‐Substituted Penems.
Authors: ENNIS D. S. , ARMITAGE M. A.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: FR901451, a Novel Inhibitor of Human Leukocyte Elastase from Flexibacter sp. Part 2. Pharmacological Effect of FR901451.
Authors: FUJITA T. , SHINGUH Y. , YAMAZAKI A. , NAKAHARA K. , OKAMOTO M. , OKUHARA M.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Panclicins, Novel Pancreatic Lipase Inhibitors. Part 1. Taxonomy, Fermentation, Isolation and Biological Activity.
Authors: MUTOH M. , NAKADA N. , MATSUKUMA S. , OHSHIMA S. , YOSHINARI K. , WATANABE J. , ARISAWA M.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Panclicins, Novel Pancreatic Lipase Inhibitors. Part 2. Structural Elucidation.
Authors: YOSHINARI K. , AOKI M. , OHTSUKA T. , NAKAYAMA N. , ITEZONO Y. , MUTOH M. , WATANABE J. , YOKOSE K.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Novel Antibiotics SF2738A, B and C, and Their Analogues Produced by Streptomyces sp.
Authors: GOMI S. , AMANO S. , SATO E. , MIYADOH S. , KODAMA Y.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Isolation and Characterization of a New 12‐Membered Macrolide FD‐895.
Authors: SEKI‐ASANO M. , OKAZAKI T. , YAMAGISHI M. , SAKAI N. , TAKAYAMA Y. , HANADA K. , MORIMOTO S. , TAKATSUKI A. , MIZOUE K.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Cepacidine A, a Novel Antifungal Antibiotic Produced by Pseudomonas cepacia. Part 1. Taxonomy, Production, Isolation and Biological Activity.
Authors: LEE C. , KIM S. , HYUN B. , SUH J. , YON C. , KIM CHANGONE , LIM Y. , KIM CHOONGSUP
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Cepacidine A, a Novel Antifungal Antibiotic Produced by Pseudomonas cepacia. Part 2. Physico‐Chemical Properties and Structure Elucidation.
Authors: LIM Y. , SUH J. , KIM S. , HYUN B. , KIM C. , LEE C.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Spectomycins, New Antibacterial Compounds Produced by Streptomyces spectabilis: Isolation, Structures, and Biosynthesis.
Authors: STALEY A. L. , RINEHART K. L.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Directed Biosynthesis of 5′′‐Fluoropactamycin in Streptomyces pactum.
Authors: ADAMS E. S. , RINEHART K. L.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Revised Structure of the Antibiotic GE 2270A.
Authors: TAVECCHIA P. , GENTILI P. , KURZ M. , SOTTANI C. , BONFICHI R. , LOCIURO S. , SELVA E.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Pheophorbide a, a Potent Endothelin Receptor Antagonist for Both ETA and ETB Subtypes.
Authors: OHSHIMA T. , HIRATA M. , ODA T. , SASAKI A. , SHIRATSUCHI M.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: A Total Synthesis of (‐)‐α‐Kainic Acid Involving a Pauson‐Khand Reaction as the Key Step.
Authors: YOO S. , LEE S. H.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis of 18‐Noranhydrocamptothecin Analogues Which Retain Topoisomerase I Inhibitory Function.
Authors: SNYDER L. , SHEN W. , BORNMANN W. G. , DANISHEFSKY S. J.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Metal Complexes of Antiinflammatory Drugs. Part 9. Piroxicam Complexes of Manganese(II), Iron(III), Cobalt(II), Nickel(II), Copper(II) and Zinc(II)
Authors: PIPE D. A. , MACBRAYNE J. C. , GOMM P. S. , GRAHAM A. W. , UNDERHILL A. E. , GOMM R. J. P.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Structure Activity Relationships of 4‐Substituted 1‐Acyl and 1,2‐ Diacyl‐1,2,4‐triazolidine‐3,5‐diones as Anti‐Inflammatory Agents in Rodents.
Authors: HALL I. H. , SIMLOT R. , IZYDORE R. A.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Recent Developments in the Chemistry of Binary Nitrogen‐Halogen Species
Authors: TORNIEPORTH‐OETTING I. C. , KLAPOETKE T. M.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Study of Divalent Rare Earth Iodides
Authors: WANG S.‐H.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Catalysis by Metals: From Extended Single Crystals to Small Clusters
Authors: GOODMAN D. W.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: The Role of Precursor States in Catalysis
Authors: BOWKER M.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Inorganic Supports and Catalysts ‐ An Overview
Authors: DIDDAMS P.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Conversion of SO2 to Sulfate in the Atmosphere
Authors: EATOUGH D. J. , CAKA F. M. , FARBER R. J.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Mono‐ and Dinuclear (Pentamethylcyclopentadienyl)iron‐Carbene Complexes
Authors: GUERCHAIS V.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Studies on the Molybdenum Cofactor. Synthesis of (.+‐.)‐Form B ( Dephospho)
Authors: TAYLOR E. C. , DARWISH I. S.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Phosphines and Phosphonium Salts
Authors: ALLEN D. W.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Tervalent Phosphorus Acid Derivatives
Authors: DAHL O.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Phosphazenes
Authors: ALLEN C. W.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Mass Spectrometric Techniques
Authors: FALICK A. M.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Mass‐Spectral Intermediate‐Ion Structures
Authors: SPLITTER J. S.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Hidden Stereochemistry in the Fragmentation Processes of Saturated Cyclic Molecular Ions with One or Two Atoms Between the Functional Group and the Ring
Authors: EADON G. A. , VALENTE H.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Asymmetric Syntheses with Catalytic Enantioselective Metal Carbene Transformations
Authors: DOYLE M. P.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Stereoselective Organic Synthesis via Dynamic Kinetic Resolution
Authors: NOYORI R. , TOKUNAGA M. , KITAMURA M.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Solar Processes for the Destruction of Hazardous Chemicals
Authors: BLAKE D. M.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Stereochemical Effects in Fragmentation Processes Involving the tert‐ Butyl Substituent
Authors: SPLITTER J. S.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Stereochemical Effects in the retro‐Diels‐Alder Fragmentation
Authors: MANDELBAUM A.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: The Use of Labeled Compounds (in Mass Spectrometry in Organic Stereochemistry)
Authors: TURECEK F.
Published: August 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Risk premiums and predictive ability of BAX futures
Authors: Gospodinov Nikolay , Jamali Ibrahim
Published: August 2010

This study provides an in‐depth analysis of risk premiums in the Canadian Bankers' Acceptances futures (BAX) market. The predictive regressions for excess and holding‐period returns on BAX futures lend empirical support to the presence of time‐varying risk premiums especially at longer horizons. Despite the evidence of time variation in the risk premium, however, the unbiasedness of the basis as a predictor of spot returns in forecast efficiency regressions cannot be rejected. The out‐of‐sample forecasts of spot returns demonstrate the excellent predictive ability of models that exploit the restrictions implied by the unbiasedness hypothesis. Overall, our findings support the presence of a slowly moving risk premium and entail important practical implications for measuring monetary policy expectations and portfolio allocation. © 2010 Wiley Periodicals, Inc. Jrl Fut Mark
Why do expiring futures and cash prices diverge for grain markets?
Authors: Aulerich Nicole M. , Fishe Raymond P. H. , Harris Jeffrey H.
Published: August 2010

In recent years, cash and futures prices have failed to converge at expiration for selected corn, soybean, and wheat commodity contracts. This lack of convergence raises questions about the effectiveness of arbitrage activities, and increases concerns about the usefulness of these contracts for hedging. We describe the delivery process for these contracts, and show that it embeds a valuable real option on the long side—the option to exchange the deliverable for another futures contract. As the relative volatility of cash and futures prices increases, this option increases in value, which disconnects the cash market from the deliverable instrument in a futures contract. Our estimates of this option's value show that it may create significant price divergence. We parameterize an option pricing model using data on these three commodities from 2000 to 2008 and show that the option model fits closely to recent episodes of non‐convergence, which lends support to the importance of real option effects. © 2010 Wiley Periodicals, Inc. Jrl Fut Mark

Hedging works primarily because changes in futures prices generally track with changes in cash prices. The delivery process forges the cash‐futures link. So strong is that link that the futures price equals the cash price at expiration at the futures delivery location.

—Chicago Board of Trade Handbook of Futures and Options (2006)
Broad copy neutral‐loss of heterozygosity regions and rare recurring copy number abnormalities in normal karyotype‐acute myeloid leukemia genomes
Authors: Barresi Vincenza , Romano Alessandra , Musso Nicolò , Capizzi Carmela , Consoli Carla , Martelli Maria Paola , Palumbo Giuseppe , Di Raimondo Francesco , Condorelli Daniele F.
Published: August 2010

We analyzed, by the latest high‐resolution SNP arrays, 19 Normal Karyotype (NK)‐AML patients at diagnosis (Dx) and remission (R) phases, to determine the number of tumor‐associated copy number abnormalities (CNAs) and copy neutral‐loss of heterozygosity (CN‐LOH) regions per patient and to identify possible recurring genomic abnormalities. The number of tumor‐associated CNAs was determined after comparison of matched Dx/R samples using stringent conditions able to reduce the number of false positive CNAs. With the exception of a single outlier case, a low number of CNAs per patient was detected (median value of 1 somatic loss or gain per patient). However, a high prevalence of CNAs (60–70% of the patients showed at least one tumor‐associated gain or loss) and few recurring CNAs were observed, thus providing new hints towards identification of cooperating mutations. An extensive search of all tumor‐associated CN‐LOH regions >1 Mb revealed only three broad regions (terminal 12Mb of 22q, terminal 27Mb of 1p and the whole chromosome 21) in three patients out of 19 (16%). CN‐LOH of the whole chromosome 21 was responsible for homozygosity of a missense mutation (R80C) of RUNX1/AML1. Our study suggests that a relative submicroscopic copy number stability NK‐AML genomes is associated with low recurrence of specific CNAs and CN‐LOH in NK‐AML patient population. Sequencing of candidate genes in the identified CNAs and CN‐LOH regions should be considered a priority in the search of novel driver mutations of AML. © 2010 Wiley‐Liss, Inc.
Array‐CGH analysis of microdissected chromosome 19 markers in ovarian carcinoma identifies candidate target genes
Authors: Micci Francesca , Skotheim Rolf I. , Haugom Lisbeth , Weimer Jörg , Eibak Anne Mette E. , Abeler Vera M. , Trope Claes G. , Arnold Norbert , Lothe Ragnhild A. , Heim Sverre
Published: August 2010

Alterations of chromosome 19 are among the most frequent cytogenetic changes in ovarian carcinomas. They usually occur as added extra material of unknown origin to 19p or, less frequently, 19q but sometimes as homogeneously staining regions. The precise nature of these markers, i.e., exactly which regions of chromosome 19 are involved and from which chromosome(s) the additional material comes, could only rarely be established. We have investigated by high resolution array‐CGH a series of 29 chromosome 19 markers after previous microdissection of ovarian carcinoma metaphases followed by FISH to determine where in chromosome 19 the rearrangements took place as well as from which partner chromosomes the additional material stems, obtaining informative results on 23 markers from 18 carcinomas. Along the entire chromosome 19, a total of nine regions were found gained in 10 or more carcinomas (from 10 to 16) whereas 15 regions were gained in 6 to 10 markers. The most commonly gained region (16 markers) was observed in 19p13 between 20.80 Mbp and 20.85 Mbp from 19pter. According to the human genome 18 (hg18) NCBI 36, a total of 43 genes reside in the most commonly gained regions. Most of them (n = 31) code for zinc finger proteins. None of these genes is known to be involved in human neoplasia (the only exception is the ZNF91, which is found highly expressed in seminomas) but their frequent gain in the examined tumors makes all of them candidates for a pathogenetic role in ovarian carcinogenesis. © 2010 Wiley‐Liss, Inc.
Use of cancer‐specific genomic rearrangements to quantify disease burden in plasma from patients with solid tumors
Authors: McBride David J. , Orpana Arto K. , Sotiriou Christos , Joensuu Heikki , Stephens Philip J. , Mudie Laura J. , Hämäläinen Eija , Stebbings Lucy A. , Andersson Leif C. , Flanagan Adrienne M. , Durbecq Virginie , Ignatiadis Michail , Kallioniemi Olli , Heckman Caroline A. , Alitalo Kari , Edgren Henrik , Futreal P. Andrew , Stratton Michael R. , Campbell Peter J.
Published: August 2010

Detection of recurrent somatic rearrangements routinely allows monitoring of residual disease burden in leukemias, but is not used for most solid tumors. However, next‐generation sequencing now allows rapid identification of patient‐specific rearrangements in solid tumors. We mapped genomic rearrangements in three cancers and showed that PCR assays for rearrangements could detect a single copy of the tumor genome in plasma without false positives. Disease status, drug responsiveness, and incipient relapse could be serially assessed. In future, this strategy could be readily established in diagnostic laboratories, with major impact on monitoring of disease status and personalizing treatment of solid tumors. © 2010 Wiley‐Liss, Inc.
Aging‐related alterations in the extracellular matrix modulate the microenvironment and influence tumor progression
Authors: Sprenger Cynthia C. , Plymate Stephen R. , Reed May J.
Published: August 2010

Age is the greatest risk factor for the development of epithelial cancers. In this minireview, we will examine key extracellular matrix and matricellular components, their changes with aging, and discuss how these alterations might influence the subsequent progression of cancer in the aged host. Because of the tight correlation between advanced age and the prevalence of prostate cancer, we will use prostate cancer as the model throughout this minireview.
Tumor associated mesenchymal stem cells protects ovarian cancer cells from hyperthermia through CXCL12
Authors: Lis Raphael , Touboul Cyril , Mirshahi Pejman , Ali Fadoua , Mathew Sharon , Nolan Daniel J. , Maleki Mahtab , Abdalla Salma A. , Raynaud Christophe M. , Querleu Denis , Al‐Azwani Eman , Malek Joel , Mirshahi Massoud , Rafii Arash
Published: August 2010

Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promise in treatment of ovarian carcinosis. Despite its efficiency for the treatment of peritoneal carcinosis from digestive tract neoplasia, it has failed to demonstrate significant benefit in ovarian cancers. It is therefore essential to understand the mechanism underlying resistance to HIPEC in ovarian cancers. Mesenchymal stem cells (MSC) play an important role in the development of ovarian cancer metastasis and resistance to treatments. A recent study suggests that MSCs may be cytotoxic for cancer cells upon heat shock. In contrast, we describe the protective role of MSC against hyperthermia. Using cytokine arrays we determined that the tumor associated MSC (TAMC) secrete pro‐tumoral cytokines. We studied the effect of hyperthermia in co‐culture setting of TAMC or BM‐MCS associated with ovarian cancer cell lines (SKOV3 and CaOV3) with polyvariate flow cytometry. We demonstrate that hyperthermia does not challenge survival of TAMC or bone marrow derived MSC (BM‐MSC). Both TAMC and BM‐MSC displayed strong protective effect inducing thermotolerance in ovarian cancer cells (OCC). Transwell experiments demonstrated the role of secreted factors. We showed that CXCL12 was inducing thermotolerance and that inhibition of CXCL12/CXCR4 interaction restored cytotoxicity of hyperthermia in co‐culture experiments. Contrary to the previous published study we demonstrated that TAMC and BM‐MSC co‐cultured with OCC induced thermotolerance in a CXCL12 dependant manner. Targeting the interaction between stromal and cancer cells through CXCL12 inhibition might restore hyperthermia sensitivity in ovarian cancers, and thus improve HIPEC efficiency.
The natural chemopreventive phytochemical R‐sulforaphane is a far more potent inducer of the carcinogen‐detoxifying enzyme systems in rat liver and lung than the S‐isomer
Authors: Abdull Razis Ahmad Faizal , Iori Renato , Ioannides Costas
Published: August 2010

The chemopreventive activity of the phytochemical sulforaphane, (‐)1‐isothiocyanato‐4R‐(methylsulfinyl)‐butane, present in cruciferous vegetables in substantial amounts in the form of glucosinolate, was demonstrated in animal models of cancer using the racemate, despite the fact that humans are exposed only to the R‐enantiomer through the diet. Since a principal mechanism of the chemopreventive activity of sulforaphane is modulation of the carcinogen‐metabolising enzyme systems, a study was conducted in precision‐cut rat liver and lung slices, and in FAO cells comparing the ability of R‐ and S‐sulforaphane to modulate these enzyme systems. R‐sulforaphane elevated hepatic glutathione S‐transferase and quinone reductase whereas the S‐enantiomer had no effect; moreover, the R‐enantiomer was more effective in up‐regulating GSTα, GSTμ and quinone reductase protein levels. In the lung, both enantiomers increased the same enzyme activities with the R‐enantiomer being more potent; in addition, the R‐enantiomer was more effective in up‐regulating GSTα and quinone reductase protein levels. Both isomers increased glutathione levels in both tissues, with R‐sulforaphane being more potent. Finally, R‐sulforaphane was the more effective of the two isomers in up‐regulating CYP1A1/1B1 apoprotein levels in both liver and lung, and CYP1A2 in the liver. Similarly, in FAO cells the R‐enantiomer was far more effective in up‐regulating quinone reductase and glutathione S‐transferase activities and protein levels compared with the S‐isomer. These studies demonstrate clearly the superiority of R‐sulforaphane, when compared with the S‐enantiomer, in stimulating detoxification enzymes, and raises the possibility that the animal studies that employed the racemate may have underestimated the chemopreventive activity of this isothiocyanate.
Alteration of strain background and a high omega‐6 fat diet induces earlier onset of pancreatic neoplasia in EL‐Kras transgenic mice
Authors: Cheon Eric C. , Strouch Matthew J. , Barron Morgan R. , Ding Yongzeng , Melstrom Laleh G. , Krantz Seth B. , Mullapudi Bhargava , Adrian Kevin , Rao Sambasiva , Adrian Thomas E. , Bentrem David J. , Grippo Paul J.
Published: August 2010

Diets containing omega‐6 (ω‐6) fat have been associated with increased tumor development in carcinogen‐induced pancreatic cancer models. However, the effects of ω‐6 fatty acids and background strain on the development of genetically‐induced pancreatic neoplasia is unknown. We assessed the effects of a diet rich in ω‐6 fat on the development of pancreatic neoplasia in elastase (EL)‐KrasG12D (EL‐Kras) mice in two different backgrounds. EL‐Kras FVB mice were crossed to C57BL/6 (B6) mice to produce EL‐Kras FVB6 F1 (or EL‐Kras F1) and EL‐Kras B6 congenic mice. Age‐matched EL‐Kras mice from each strain were compared to one another on a standard chow. Two cohorts of EL‐Kras FVB and EL‐Kras F1 mice were fed a 23% corn oil diet and compared to age‐matched mice fed a standard chow. Pancreata were scored for incidence, frequency, and size of neoplastic lesions, and stained for the presence of mast cells to evaluate changes in the inflammatory milieu secondary to a high fat diet. EL‐Kras F1 mice had increased incidence, frequency, and size of pancreatic neoplasia compared to EL‐Kras FVB mice. The frequency and size of neoplastic lesions and the weight and pancreatic mast cell densities in EL‐Kras F1 mice were increased in mice fed a high ω‐6 fatty acid diet compared to mice fed a standard chow. We herein introduce the EL‐Kras B6 mouse model which presents with increased frequency of pancreatic neoplasia compared to EL‐Kras F1 mice. The phenotype in EL‐Kras F1 and FVB mice is promoted by a diet rich in ω‐6 fatty acid.
CpG‐ODN increases the release of VEGF in a mouse model of lung carcinoma
Authors: Sorrentino Rosalinda , Morello Silvana , Giordano Maria Grazia , Arra Claudio , Maiolino Piera , Adcock Ian M. , Pinto Aldo
Published: August 2010

Vascular endothelial‐derived growth factor (VEGF) plays a fundamental role in the formation of new vessels within the tumour mass. Increasing evidence has highlighted the involvement of Toll‐like receptors (TLRs) in cancer. Of interest, TLR9 is over‐expressed in human lung carcinoma tissues. The aim of our study was to determine whether TLR9 activation could alter VEGF release in a mouse model of lung carcinoma. Lewis lung carcinoma cells were intravenously (i.v.) inoculated and 10 days later, tumour‐bearing mice were treated with CpG‐ODN (CpG, a TLR9 ligand) or PBS. CpG administration enhanced VEGF release, which was associated with increased tumour lesions in the lung. CpG induced high levels of IL‐6 expression and activation of STAT3 in tumour‐bearing mice. Moreover, CpG induced VEGF release from primary fibroblasts and endothelial cells, which correlated with IL‐6 and TGFβ production. This may explain the large influx of fibroblasts and the production of basic fibroblast growth factor (bFGF) in the tumour mass. The administration of a monoclonal antibody against VEGF A arrested tumour progression and induced a Th1‐like response in CpG‐treated tumour‐bearing mice. In conclusion, our study demonstrates that the combination of CpG with anti‐VEGF monoclonal antibody could be of potential therapeutic in lung carcinoma.
Reproducibility of diffusion tensor imaging in human forearm muscles at 3.0 T in a clinical setting
Authors: Froeling Martijn , Oudeman Jos , van den Berg Sandra , Nicolay Klaas , Maas Mario , Strijkers Gustav J. , Drost Maarten R. , Nederveen Aart J.
Published: August 2010

The aim of the present study was to evaluate a fast clinical protocol to enable diffusion tensor imaging of the human forearm and assess the reproducibility of six diffusion tensor imaging parameters, i.e., the tensor eigenvalues (λ1, λ2, and λ3), mean diffusivity, fractional anisotropy, and ellipsoid eccentricity. The right forearms of 10 healthy volunteers were scanned twice, with a 1‐week interval. Reproducibility of the diffusion tensor imaging parameters was interpreted using Bland‐Altman plots, coefficient of repeatability, repeatability index, and the intraclass correlation coefficient. Analysis was done for three regions of interest: the whole muscle volume, flexor digitorum profundus, and extensor digitorum. The Bland‐Altman analysis showed that there is good agreement between the two measurements. Based on the intraclass correlation coefficients, agreement was substantial (0.59 < intraclass correlation coefficient < 0.92) for all six parameters of the whole muscle volume and flexor digitorum profundus but only fair (0.18 < intraclass correlation coefficient < 0.64) for the extensor digitorum. Using a 7 min 40 sec scan protocol, which was well tolerated by the volunteers, the reproducibility of diffusion tensor imaging parameters was demonstrated. However, repeatability varies, depending on the region of interest and diffusion tensor imaging parameters. This should be taken into account when a longitudinal study is designed. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Simultaneous fMRI and local field potential measurements during epileptic seizures in medetomidine‐sedated rats using raser pulse sequence
Authors: Airaksinen Antti M. , Niskanen Juha‐Pekka , Chamberlain Ryan , Huttunen Joanna K. , Nissinen Jari , Garwood Michael , Pitkänen Asla , Gröhn Olli
Published: August 2010

Simultaneous electrophysiological and functional magnetic resonance imaging measurements of animal models of epilepsy are methodologically challenging, but essential to better understand abnormal brain activity and hemodynamics during seizures. In this study, functional magnetic resonance imaging of medetomidine‐sedated rats was performed using novel rapid acquisition by sequential excitation and refocusing (RASER) fast imaging pulse sequence and simultaneous local field potential measurements during kainic acid‐induced seizures. The image distortion caused by the hippocampal‐measuring electrode was clearly seen in echo planar imaging images, whereas no artifact was seen in RASER images. Robust blood oxygenation level–dependent responses were observed in the hippocampus during kainic acid‐induced seizures. The recurrent epileptic seizures were detected in the local field potential signal after kainic acid injection. The presented combination of deep electrode local field potential measurements and functional magnetic resonance imaging under medetomidine anesthesia, which does not significantly suppress kainic acid‐induced seizures, provides a unique tool for studying abnormal brain activity in rats. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Universality of protein reentrant condensation in solution induced by multivalent metal ions
Authors: Zhang Fajun , Weggler Sophie , Ziller Michael J. , Ianeselli Luca , Heck Benjamin S. , Hildebrandt Andreas , Kohlbacher Oliver , Skoda Maximilian W. A. , Jacobs Robert M. J. , Schreiber Frank
Published: August 2010

The effective interactions and phase behavior of protein solutions under strong electrostatic coupling conditions are difficult to understand due to the complex charge pattern and irregular geometry of protein surfaces. This distinguishes them from related systems such as DNA or conventional colloids. In this work, we discuss the question of universality of the reentrant condensation (RC) of proteins in solution induced by multivalent counterions, i.e., redissolution on adding further salts after phase separation, as recently discovered (Zhang et al., Phys Rev Lett 2008; 101:148101). The discussion is based on a systematic investigation of five different proteins with different charge patterns and five different multivalent counterions. Zeta potential measurements confirm the effective charge inversion of proteins in the reentrant regime via binding of multivalent counterions, which is supported by Monte Carlo simulations. Charge inversion by trivalent cations requires an overall negative net charge of the protein. Statistical analysis of a representative set of protein sequences reveals that, in theory, this effect could be possible for about half of all proteins. Our results can be exploited for the control of the phase behavior of proteins, in particular facilitating protein crystallization. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Models of membrane‐bound Alzheimer's Abeta peptide assemblies
Authors: Shafrir Yinon , Durell Stewart , Arispe Nelson , Guy H. Robert
Published: August 2010

Although it is clear that amyloid beta (Aβ) peptides play a pivotal role in the development of Alzheimer's disease, the precise molecular model of action remains unclear. Aβ peptide forms assemble both in aqueous solution and in lipid membranes. It has been proposed that deleterious effects occur when the peptides interact with membranes, possibly by forming Ca2+ permeant ion channels. In the accompanying manuscript, we propose models in which the C‐terminus third of six Aβ42 peptides forms a six‐stranded β‐barrel in highly toxic soluble oligomers. Here we extend this hypothesis to membrane‐bound assemblies. In these Aβ models, the hydrophobic β‐barrel of a hexamer may either reside on the surface of the bilayer, or span the bilayer. Transmembrane pores are proposed to form between several hexamers. Once the β‐barrels of six hexamers have spanned the bilayer, they may merge to form a more stable 36‐stranded β‐barrel. We favor models in which parallel β‐barrels formed by N‐terminus segments comprise the lining of the pores. These types of models explain why the channels are selective for cations and how metal ions, such as Zn2+, synthetic peptides that contain histidines, and some small organic cations may block channels or inhibit formation of channels. Our models were developed to be consistent with microscopy studies of Aβ assemblies in membranes, one of which is presented here for the first time. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Structural studies on the enzyme complex isopropylmalate isomerase (LeuCD) from Mycobacterium tuberculosis
Authors: Manikandan Karuppasamy , Geerlof Arie , Zozulya Alexey V. , Svergun Dmitri I. , Weiss Manfred S.
Published: August 2010

The absence of the leucine biosynthesis pathway in humans makes the enzymes of this pathway in pathogenic bacteria such as Mycobacterium tuberculosis potential candidates for developing novel antibacterial drugs. One of these enzymes is isopropylmalate isomerase (IPMI). IPMI exists as a complex of two subunits: the large (LeuC) and the small (LeuD) subunit. The functional LeuCD complex catalyzes the stereospecific conversion reaction of α‐isopropylmalate to β‐isopropylmalate. Three C‐terminally truncated variants of LeuD have been analyzed by X‐ray crystallography to resolutions of 2.0 Å (LeuD_1–156), 1.2 Å (LeuD_1–168), and 2.5 Å (LeuD_1–186), respectively. The two most flexible parts of the structure are the regions of residues 30–37, the substrate discriminating loop, and of residues 70–74, the substrate binding loop. The three determined structures were also compared with the structures of other bacterial LeuDs. This comparison suggests the presence of two LeuD subfamilies. A model for the structure of the inactive enzyme complex has been obtained from solution X‐ray scattering experiments. The crystal structure of LeuD was shown to be compatible with the solution X‐ray scattering data from the small subunit. In contrast, the solution scattering results suggest that the large subunit LeuC and the LeuCD complex have overall shapes, which are radically different from the ones observed in the crystals of the functional homolog mitochondrial aconitase. Proteins 2010. © 2010 Wiley‐Liss, Inc.
A CASSCF/MRCI study of the low‐lying electronic states of the BeS molecule
Authors: De Oliveira‐Filho Antonio G. S. , Alves Tiago V. , Ribas Vladir W. , Ferrão Luiz F. A. , Roberto‐Neto Orlando , Machado Francisco B. C. , Ornellas Fernando R.
Published: August 2010

Accurate potential energy curves, dipole moment functions, dissociation energies, and molecular constants for several low‐lying singlet and triplet electronic states of BeS were investigated using the CASSCF/MRCI methodology, and the cc‐pV5Z basis set for beryllium, and the aug‐cc‐pV(5+d)Z set for sulfur. Besides presenting improved results for the three lowest lying states, this study presents the first theoretical characterization of another set of nine excited states so far unknown experimentally. Our results are sufficiently accurate to reliably guide the experimental search and characterization of these states, and also to confirm the experimental assignment of the B
1Σ+ excited state. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
Heat transport through a biological membrane—An asymmetric property? Technical issues of nonequilibrium molecular dynamics methods
Authors: Müller Thomas J. , Müller‐Plathe Florian
Published: August 2010

To investigate heat transport across a biological membrane, we performed a series of reverse nonequilibrium molecular dynamics (RNEMD) simulations on a model dipalmitoylphosphatidylcholine (DPPC) bilayer system at the atomistic level. In a detailed analysis of the initially irritating results, we show how and to which extent the RNEMD method (in the special case of an ordered, heterogeneous system, like a bilayer in water) is influenced by simulation conditions. We prove that the interplay between the description of the long range forces and the nonequilibrium algorithm can lead to significant changes in the apparent local thermal conductivity profile across the membrane. As this is the first case reported where the otherwise robust RNEMD results are not directly interpretable, we discuss not only the reasons but also several concepts to handle this effect. Note that this is not a flaw of the RNEMD method but of the simulation framework it is performed in. Therefore, the considerations apply to other equilibrium and nonequilibrium molecular dynamics simulations of the thermal conductivities, too, and care must be taken when heterogeneous systems or interfaces appear in simulations. The complete understanding of the directly obtained results finally allows us to describe the heat flow across the membrane qualitatively. On this basis, we show that the tail–tail interface of the bilayer is the most hindering region for the heat flow, and thus, dominates the overall thermal conductivity of the membrane. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
Directional tendencies of halogen and hydrogen bonds
Authors: Shields Zenaida P. , Murray Jane S. , Politzer Peter
Published: August 2010

Halogen bonding, RX···B, and hydrogen bonding, RH···B, are electrostatically‐driven noncovalent interactions of covalently‐bonded halogens RX and hydrogens RH with negative sites B. A significant difference between halogen and hydrogen bonding is that the former is typically near‐linear (the R‐X‐B angles are close to 180°), whereas the latter is more likely to be nonlinear (R‐H‐B angles sometimes considerably less than 180°). In this work, we have looked at the properties of several RBr···B and RH···B complexes as functions of these angles. The differences in the directional tendencies in these interactions can be attributed to the presence of nonbonding valence electrons on the bromines, and their absence on hydrogen. We also found that for a given negative site, the halogen and hydrogen bonding interaction energies correlate very well with the positive electrostatic potentials created at it by RX and RH. This attests to the electrostatically‐driven nature of these interactions. Overall, this study provides support for regarding both halogen and hydrogen bonding as subsets of σ‐hole interactions. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010