bluuebunny/crossref_metadata_2025 huggingface dataset:
Allylic and Benzylic Carbanions Substituted by Heteroatoms
Authors: Biellmann Jean‐François , Ducep Jean‐Bernard
Published: March 2007

This review covers allylic and benzylic carbanions in which a heteroatom and the double bond may be part of a conjugated system. Propargylic and allenic systems are also included. The cation is an alkaline or alkaline‐earth element; transition metals are excluded. The chapter by Gilman and Morton in 1954 was restricted to lithium derivatives. Reviews covering part of the subject include those on organometallic compounds, on reagents for nucleophilic acylation, on olefin synthesis with P(O)‐activated reagents, on the formation and reactions of carbanions derived from allylic sulfoxides, dithianes, nitrosoamines, thioethers and ethers, selenium compounds, on base‐catalyzed isomerization, and on rearrangements of carbanions.

Allylic and benzylic carbanions adjacent to the following
heteroatoms
have been described: boron, nitrogen, oxygen, silicon, phosphorus, sulfur, chlorine, selenium, bromine, tellurium.

The basicity and structures of these anions are considered first. This discussion is followed by sections on methods of generation of carbanions, reactions occurring during preparation, decomposition, and rearrangements of carbanions, reactions with electrophiles, regioselectivity and stereochemical aspects of the reactions, transformations of the reaction products, and some applications of these carbanions in synthesis.
TheFriedländer Synthesis of Quinolines
Authors: Cheng Chia‐Chung , Yan Shou‐Jen
Published: March 2007

Friedländer prepared quinoline in 1882 by the condensation ofo‐aminobenzaldehyde with acetaldehyde in the presence of sodium hydroxide. This type of reaction has since been extensively explored and, in its most general form, can be defined as an acid‐ or base‐catalyzed condensation followed by a cyclodehydration between ano‐amino‐substituted aromatic aldehyde, ketone, or derivative thereof with an appropriately substituted aldehyde, ketone, or other carbonyl compound containing a reactive α‐methylene group. Some quinolines can also be prepared simply by heating a mixture of the reactants with or without a solvent.

Because both reactants contain a carbonyl group, certain quinolines can be prepared from a single starting compound. Of historic interest is the formation of the dye flavaniline from acetanilide. When acetanilide is heated with zinc chloride, the acetyl group of some molecules migrates to theorthoposition, and that of others migrates to theparaposition. The resulting mixture ofo‐acetylaniline andp‐acetylaniline then undergoes Friedländer condensation to form flavaniline.

Two related quinoline syntheses, the Pfitzinger reaction and the Niementowski reaction, can be considered as extensions of the Friedländer synthesis. The Pfitzinger reaction uses an isatic acid or isatin and the Niementowski reaction uses an anthranilic acid for condensation to form a 4‐quinolinecarboxylic acid and a 4‐hydroxyquinoline, respectively.

Several other related reactions, such as the Combes quinoline synthesis, the Doebner–Miller quinoline synthesis, and the Skraup quinoline synthesis, use different types of starting compounds. It is of interest that all of the six aforementioned syntheses of quinolines were discovered within a period of 14 years in the latter part of the nineteenth century, undoubtedly reflecting many scientific interests and commercial activities at that time, including the isolation of quinolines from coal tar, the manufacture of dyes, and studies of natural products such as alkaloids.
Replacement of Alcoholic Hydroxyl Groups by Halogens and Other Nucleophiles via Oxyphosphonium Intermediates
Authors: Castro Bertrand R.
Published: March 2007

The Michaelis–Arbuzov reaction involves the formation of dialkyl alkylphosphonates by heating alkyl halides with trialkyl phosphites, via an intermediate phosphonium salt. In recent years it has been found that phosphonium salts can be formed by reaction of a variety of trivalent phosphorus compounds with oxidizing electrophiles, and that the resulting phosphonium intermediates can be trapped with an alcohol to form alkoxyphosphonium cations. These cations can then undergo nucleophilic displacements, either with their own counterions or with added nucleophiles.

This chapter is limited to species formed
in situ
from trivalent phosphorus compounds and various oxidants. The most commonly used trivalent phosphorus compounds are triphenyl phosphite, triphenylphosphine, and tris(dimethylamino)phosphine. The most commonly used oxidants are molecular halogens, alkyl halides, carbon tetrahalides,
N
‐haloamides,
N
‐haloamines, and diethyl azodicarboxylate (DEAD). Other oxidants that have been used include mercuric salts, peroxides, dithioesters, and sulfenamides. The more common combinations of phosphorus(III) compounds and oxidants are summarized.

The replacement of hydroxyl groups by halogen, the most common use of oxyphosphonium intermediates, is the principal subject of this chapter. However, the replacement of hydroxyl groups by oxygen, nitrogen, sulfur, and carbon nucleophiles is also discussed. This review is restricted to alcoholic hydroxyl groups, and does not include a discussion of carboxylic hydroxyl groups.

The principal combinations covered are triphenylphosphine–diethyl azodicarboxylate, triphenyl phosphite–methiodide, triphenylphosphine–halogen, triphenylphosphine–tetrahalomethane, triphenylphosphine–N‐haloimide, and tris(dimethylamino)phosphine–tetrahalomethane. Some of these combinations have been discussed in recent reviews.
Reductive Dehalogenation of Polyhalo Ketones with Low‐Valent Metals and Related Reducing Agents
Authors: Noyori Ryoji , Hayakawa Yoshihiro
Published: March 2007

α‐Halo ketones play a significant role in organic synthesis because of their ready availability and the diversity of their chemical reactions, which reflect the various functionalities in the molecule,viz., a reactive halogencarbon bond, acidic hydrogen atoms, and a carbonyl moiety. An important reaction of halo ketones is removal of the halogen atom(s) by low‐valent transition metals and related reducing agents to generate reactive species that are capable of undergoing carboncarbon bond‐forming reactions. The cyclocoupling reactions of α,α′‐dihalo or more highly halogenated ketones across 1,3‐dienic or olefinic substrates to give seven‐ or five‐membered ketones, respectively, are especially noteworthy from the synthetic viewpoint.

The direct preparation of odd‐membered carbocycles has remained a persistent problem, and until recently only a few methods of synthesis were available. The existing methods for obtaining seven‐membered carbocycles have been limited to expansion of six‐membered rings and certain cyclization reactions. The construction of five‐membered carbocyclic systems has generally been accomplished only by intramolecular condensation of open‐chain dicarbonyl compounds or dicarboxylic acid derivatives, ring contraction of six‐membered cyclic ketones, or ring expansion of four‐membered cyclic ketones. These methods, however, are not always useful because of the limited availability of the starting materials in certain reactions. In principle the most direct method for construction of seven‐membered carbocycles is the cyclo‐condensation between three‐carbon and four‐carbon units,viz., 1,3‐dienes, for preparation of five‐membered carbocycles, the combination of three‐carbon and two‐carbon units,viz., olefinic substances, or one‐carbon and four‐carbon units, respectively, can be considered. However, these reactions are not achieved easily because of the difficulty of generating reactive three‐carbon and one‐carbon units that are capable of undergoing cycloaddition across the unsaturated substrates. Reactions of low‐valent metals and α,α′‐dihalo or more highly halogenated ketones generate such bifunctional three‐carbon species that can enter into both types of cycloaddition reactions. Moreover, these reactive species also undergo [3 + 2] cycloadditions across certain unsaturated bonds containing heteroatoms, thereby giving rise to five‐membered heterocycles. Thus these [3 + 4] and [3 + 2] annulations have allowed easy access to a wide range of organic frameworks that are of theoretical or practical importance. The scope and limitations of these cyclocoupling reactions and their synthetic applications are the main concern of this chapter, which briefly describes other examples of dehalogenation of α‐mono‐ and α,α′‐polyhalo ketones using low‐valent transition metals and related reducing agents. Also described are the mechanistic aspects of the reductions and several representative experimental procedures.
ThePasserini Reaction
Authors: Banfi Luca , Riva Renata
Published: March 2007

Isocyanides are a very special class of organic compounds, which may behave as acyl anion equivalents. However, with very few exceptions, isocyanides do not react with carbonyl compounds in the absence of an acid. In this chapter, all reactions of a carbonyl compound or an acetal with an isocyanide are considered. These are processes that frequently, but not invariably, result in the incorporation of an acid residue in the final product. In the classic Passerini reaction, discovered in 1921 by Mario Passerini, the acid is always a carboxylic acid and the products alpha‐acyloxy amides. A more recent variation, which is often referred to as the Passerini reaction as well, employs a variety of mineral (H+) or Lewis acids (LA) to afford alpha‐hydroxy amides. These compounds may also be formed in the presence of carboxylic acids such as formic acid or trifluoracetic acid. Interactions of isocyanides with carbonyl compounds and some protic or Lewis acids can also lead to a large variety of products other than alpha‐hydroxy amides, including several heterocyclic systems. These Passerini‐type reactions are discussed. Acetals can also react with isocyanides in the presence of Lewis acids. The usual products are alpha‐alkoxy amides.

The classic Passerini reaction is one of the oldest multicomponent reactions and is the first based on isocyanides to be discovered. This method is experiencing a growing interest. Its scope has been expanded by employing bifunctional substrates able to undergo secondary reactions. In this way, a larger variety of products can be synthesized and complex biologically active substances can be accessed quickly. Modifications that form products different from alpha‐acyloxy amides or alpha‐hydroxy amides, especially those leading to heterocycles, may find useful applications in synthesis.
The Allylic Trihaloacetimidate Rearrangement
Authors: Overman Larry E. , Carpenter Nancy E.
Published: March 2007

Sigmatropic rearrangements of allylic systems have found wide application in organic synthesis, with carbon‐carbon bond forming rearrangements such as the Cope and Claisen rearrangements being particularly well known. The sigmatropic rearrangement of allylic imidates offers a valuable entry into the preparation of protected allylic amines. Conversion of an imidate to the amide is essentially irreversible, with the transformation of the imidate to the amide being exothermic by about 15 kcal/mol. Since the discovery of the thermal allylic imidate rearrangement in 1937, a number of systems have been investigated for the practical preparation of allylic amines by this route. However, it was the discovery and development of the rearrangement of allylic trichloroacetamidates that demonstrated the utility of this synthetic method.

This chapter is limited to the discussion of allylic trichloro‐ and trifluoracetamidate rearrangements. The [3,3]‐sigmatropic rearrangement of trichloracetamidates (now called the Overman rearrangement) or trifluoroacetimidates can be carried out either thermally or with Hg(II) or Pd(II) catalysis, The scope of this rearrangement is such that primary, secondary, and tertiary allylic amides are readily accessible, thus providing a wide entry into nitrogen‐containing products such as amino sugars, nucleotides, peptides, etc. The Overman rearrangement has found extensive application in the total synthesis of natural products. The recent development of the use of chiral Pd(II) catalysts bodes well for amine synthesis.
Asymmetric Dihydroxylation of Alkenes
Authors: Noe Mark C. , Letavic Michael A. , Snow Sheri L.
Published: March 2007

The oxidation of alkenes to vicinal diols using osmium tetroxide is one of the most selective and reliable transformations in organic synthesis. The reaction stereospecifically produces a cis‐1,2‐glycol and is tolerant of a wide array of functional groups. Methods have been developed to oxidize alkenes stoichiometrically, as well as in the presence of catalytic amounts of osmium tetroxide, when a suitable secondary oxidant is present. The latter process is particularly useful considering the expense and toxicity of osmium tetroxide. The utility of dihydroxylation in organic synthesis is enhanced by the facile transformations of the cis‐1,2‐diol products into other useful derivatives. Among the most versatile intermediates are the corresponding cyclic sulfates, which serve as reactive epoxide equivalents that can be used singly or doubly displaced with amine‐, oxygen‐, sulfur‐, or carbon‐based nucleophiles.

The reaction of osmium tetroxide with alkenes is accelerated by several orders of magnitude in the presence of coordinating amine ligands such as triethylamine, quinuclidine, or diazobicyclooctane. The logical extension to asymmetric osmylation of alkenes in the presence of chiral amine bases spurred the study of asymmetric dihydroxylation. The breakthrough of catalytic turnover in the cinchona alkaloid‐osmium tetroxide system revolutionized the field of asymmetric dihydroxylation. Specialized ligands have been developed to provide position selectivity in the dihydroxylation of polyenes, efficient kinetic resolution of racemic substrates, and high levels of enantioselectivity for each of six alkene classes.
Benzylic Activation and Stereochemical Control in Reactions of Tricarbonyl(arene)chromium Complexes
Authors: Uemura Motokazu
Published: March 2007

This chapter covers reactions of (η6‐arene) chromium complexes that occur in the side chain of the arene, and reactions that exhibit stereocontrol as a result of complexation. Reactions that focus on nucleophilic additions to the chromium‐coordinated aromatic ring and on directed lithiation of the arene ring are not covered.

The tricarbonyl(η6‐arene) complexes are readily prepared by several convenient methods, and these complexes are relatively stable to air and moisture. Most arenes will coordinate to the tricarbonyl fragment. Certain functional groups are incompatible and electron withdrawing groups, such as CHO and CO2H, retard complexation. Protection of these functional groups as acetals or esters followed by chromium complexation and hydrolysis procedures give the corresponding tricarbonylchromium complexes of benzaldehyde or benzoic acid in good yields. Electron‐donating substituents accelerate the rate of complexation. The chemical consequences of chromium complexation include (1) the activation of the aromatic ring to nucleophilic addition; (2) enhancement of acidity in the side chain; (3) enhancement of the rate of solvolysis in the side chain; (4) enhancement of acidity of aromatic hydrogens: (5) control of reactions by steric effects of the tricarbonylchromium fragment. After the reaction, the tricarbonylchromium fragment can be easily removed by mild oxidation. When the arene ring is disubstituted with different substituents at the ortho and meta positon, the complexes are planar chiral and the substrates are useful for asymmetric synthesis.
Phylogeography and population structure of the golden monkeys (Rhinopithecus roxellana): inferred from mitochondrial DNA sequences
Authors: Li Ming , Liu Zhijin , Gou Jinxun , Ren Baoping , Pan Ruliang , Su Yanjie , Funk Stephan M. , Wei Fuwen
Published: March 2007

The golden monkey (Rhinopithecus roxellana) is one of the most endangered primate species due to its dramatically shrinking distribution during the past 400 years. Its populations are restricted to three isolated regions, Qinglin (QL), Sichuan/Gansu (SG), and Shennongjia (SNJ) in China. As with other snub‐nosed monkeys in China and Vietnam, the biology and evolution of this species is still poorly known. To assess genetic differentiation and explore the relationships among populations of golden monkeys from different geographic locations, 379 bp of mitochondrial DNA control region (CR) hypervariable segment I (HVI) was studied from 60 individuals. Twelve haplotypes were identified from seven populations within the three regions. Haplotype diversity was high (0.845), whereas nucleotide diversity among all haplotypes was low (0.0331). The most recent common ancestor (TMRCA) among mtDNA haplotypes was estimated to have lived approximately 0.48–0.32 million years ago. None of the haplotypes is shared among any of the three regions. Phylogenetic analysis and AMOVA revealed clear and significant phylogeographic structure between the three regions. However, only SG contained haplotypes of the two main clades, indicating either incomplete random sorting of haplotypes or a complex history with phases of population subdivisions and merging of populations. The phylogeographic structure implies that R. roxellana should be regarded as separate management units (MUs) for each of the three regions. It is likely that recent phylogeographic history has shaped the pattern of genetic differentiation observed in the golden monkey and that its populations have suffered significant demographic fluctuation. Am. J. Primatol. 69:1195–1209, 2007. © 2007 Wiley‐Liss, Inc.
The link‐prediction problem for social networks
Authors: Liben‐Nowell David , Kleinberg Jon
Published: March 2007

Given a snapshot of a social network, can we infer which new interactions among its members are likely to occur in the near future? We formalize this question as the link‐prediction problem, and we develop approaches to link prediction based on measures for analyzing the “proximity” of nodes in a network. Experiments on large coauthorship networks suggest that information about future interactions can be extracted from network topology alone, and that fairly subtle measures for detecting node proximity can outperform more direct measures.
Nonspecific electrostatic binding characteristics of the heparin‐antithrombin interaction
Authors: Seyrek Emek , Dubin Paul L. , Henriksen Jens
Published: March 2007

We evaluated the role of nonspecific electrostatic binding in the interaction of antithrombin (AT) with heparin (Hp), a paradigmatic protein‐glycosaminoglycan (GAG) system. To do so, we obtained the ionic‐strength dependence of the binding constant, since a common feature in protein‐polyelectrolyte systems is a maximum in affinity in the ionic strength range 10 mM <I<30 mM (Seyrek et al, Biomacromolecules 2003, 4, 273‐282). Because this feature is seen for both synthetic and biological polyelectrolytes, and because the value of Imax correlates with protein size and charge asymmetry through the Debye length (Seyrek et al, Biomacromolecules 2003, 4, 273‐282), this behavior appears to be a signature of non‐specific electrostatic protein‐polyelectrolyte binding. Binding of AT to both standard (14 kDa) Hp and partially degraded (5 kDa) low molecular weight heparin (LMWH) exhibited this same behavior. Capillary electrophoresis (CZE) of Hp and LMWH yielded electropherograms whose remarkable breadth revealed the enormous heterogeneity of average charge density among the innumerable molecular species of Hp and LMWH. These distributions were somewhat reduced after affinity chromatography (AC) fractionation, indicating that the high‐affinity fraction was generally depleted of the lower‐charge species. Size‐exclusion chromatography coupled with Electrospray Mass Spectrometry confirmed lower levels of sulfation for the lower affinity fractions. Comparisons of LMWH with Dermatan sulfate (DS) by CZE and AC suggested a correlation between the relative absence of very highly charged components in DS and its weaker binding to AT. These findings point to a significant role of the charge density of GAG chains in their affinity for AT. © 2007 Wiley Periodicals, Inc. Biopolymers 86: 249–259, 2007.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
A scaleable manufacturing process for pro‐EP‐B2, a cysteine protease from barley indicated for celiac sprue
Authors: Vora Harmit , McIntire James , Kumar Pawan , Deshpande Milind , Khosla Chaitan
Published: March 2007

Celiac Sprue is an inflammatory disease of the small intestine triggered by ingestion of dietary gluten, a family of glutamine and proline rich proteins found in common foodgrains such as wheat, rye, and barley. One potential therapy for this lifelong disease anticipates using an oral protease to detoxify gluten in vivo. Recent studies have shown that EP‐B2 (endoprotease B, isoform 2) from barley is a promising example of such a glutenase, thus warranting its large‐scale production for animal safety and human clinical studies. Here we describe a scaleable fermentation, refolding and purification process for the production of gram to kilogram quantities of pro‐EP‐B2 (zymogen form of EP‐B2) in a lyophilized form. A fed‐batch E. coli fermentation system was developed that yields 0.3–0.5 g purified recombinant protein per liter culture volume. Intracellular degradation of pro‐EP‐B2 during the fermentation was overcome by manipulating the fermentation temperature and duration of protein expression. A simple refolding protocol was developed using a fast dilution method to refold the enzyme at concentrations greater than 0.5 mg/mL. Kinetic analysis showed that pro‐EP‐B2 refolding is a first‐order reaction with an estimated rate constant of 0.15 h−1. A lyophilization procedure was developed that yielded protein with 85% recoverable activity after 7 weeks of storage at room temperature. The process was successfully scaled up to 100 L with comparable purity and recovery. Biotechnol. Bioeng. 2007; 98: 177–185. © 2007 Wiley Periodicals, Inc.
Analysis of lipid hydrolytic activity by esterase on blotting membrane followed by separation using non‐denaturing two‐dimensional gel electrophoresis
Authors: Shimazaki Youji , Miyamoto Masayuki
Published: March 2007

After separation by microscale non‐denaturing two‐dimensional gel electrophoresis (2DE) and transferring to a blotting membrane, major proteins are detected by a staining of direct blue 71 in a neutral solution. The carboxylesterase on the membrane hydrolyzes phosphatidylcholine after the spot of carboxylesterase is excised from the membrane, and incubated with phosphatidylcholine. Lipids of human serum proteins and the purified human high density lipoprotein (HDL) are removed by enzymatic hydrolysis when human serum proteins and the purified HDL are respectively incubated with the spot of carboxylesterase on the membrane. These results indicate that carboxylesterase on the membrane hydrolyzes not only lipids such as phosphatidylcholine but also lipids of lipoproteins such as HDL after separation by the 2DE, transferring to the membrane and staining without impairing the activity. These results also indicate that a micro‐immobilized enzyme reactor on the membrane can be produced when biological enzymes are separated by microscale 2DE, transferred to the membrane and stained without impairing their activities. Biotechnol. Bioeng. 2007;98: 732–736. © 2007 Wiley Periodicals, Inc.
Determination of the Conformation of the Human VDAC1 N‐Terminal Peptide, a Protein Moiety Essential for the Functional Properties of the Pore
Authors: De Pinto Vito , Tomasello Flora , Messina Angela , Guarino Francesca , Benz Roland , La Mendola Diego , Magrì Antonio , Milardi Danilo , Pappalardo Giuseppe
Published: March 2007

Mitochondrial porin or VDAC (voltage‐dependent anion‐selective channel) is the most abundant protein in the mitochondrial outer membrane. The structure of VDAC has been predicted to be a transmembrane β‐barrel with an α‐helix at the N terminus. It is a matter of debate as to whether this putative α‐helix plays a structural role as a component of the pore walls or a function in the pore activity. We have synthesised the human VDAC1 (HVDAC1) N‐terminal peptide Ac‐AVPPTYADLGKSARDVFTK‐NH2 (Prn2–20) and determined its structure by CD and NMR spectroscopy. CD studies show that the Prn2–20 peptide exists in aqueous solvent as an unstructured peptide with no stable secondary structure. In membrane‐mimetic SDS micelles or water/trifluoroethanol, however, it assumes an amphipathic α‐helix conformation between Tyr5 and Val16, as deduced from NMR. No ordered structure was observed in dodecyl β‐maltoside. Differential scanning calorimetric measurements were carried out in order to examine the membrane affinity of the peptide. Upon interaction with the negatively charged 1,2 dipalmitoyl‐sn‐glycero‐3‐phosphoserine membrane, Prn2–20 exhibited distinctive behaviour, suggesting that electrostatics play an important role. Interaction between the peptide and artificial bilayers indicates that the peptide lies on the membrane surface. Recombinant HVDAC1 deletion mutants, devoid of seven or 19 N‐terminal amino acids, were used for transfection of eukaryotic cells. Over‐expression of HVDAC1 increases the number of Cos cells with depolarised mitochondria, and this effect is progressively reduced in cells transfected with HVDAC1 lacking those seven or 19 amino acids. The mitochondrial targeting of the deletion mutants is unaffected. The overall picture emerging from our experiments is that the VDAC N‐terminal peptide plays a role in the proper function of this protein during apoptotic events.
The impact of olive oil consumption pattern on the risk of acute coronary syndromes: the cardio2000 case–control study
Authors: Kontogianni Meropi D. , Panagiotakos Demosthenes B. , Chrysohoou Christina , Pitsavos Christos , Zampelas Antonis , Stefanadis Christodoulos
Published: March 2007

Background

According to epidemiological and metabolic studies monounsaturated fatty acids (MUFAs) seem to exert a protection against coronary heart disease (CHD) risk. The aim of the present study was to evaluate the association between the pattern of edible oils and fats consumption and the prevalence of a first, nonfatal event of an acute coronary syndrome (ACS) in a Greek sample.

Methods

Seven hundred males and 148 females patients with first event of an ACS and 1078 population‐based controls, age and sex matched, were randomly selected. Detailed information regarding their medical records, alcohol intake, physical activity and smoking habits was recorded. Nutritional habits were evaluated with a semi‐quantitative food‐frequency questionnaire and use of oils in daily cooking or preparation of food was also recorded. Multiple logistic regression analysis estimated the odds ratio (OR) of having ACS by types of oil used, after taking into account the effect of several confounders.

Results

Exclusive use of olive oil was associated with 47% (95% confidence interval (CI) 0.4–0.71) lower likelihood of having ACS, compared to nonuse, after adjusting for BMI, smoking, physical activity level, educational status, the presence of family history of CHD, as well as hypertension, hypercholesterolemia and diabetes. Consumption of olive oil in combination with other oils or fats was not significantly associated with lower odds of ACS compared to no olive oil consumption (p = 0.14).

Conclusions

Exclusive use of olive oil during food preparation seems to offer significant protection against CHD, irrespective of various clinical, lifestyle and other characteristics of the participants. Copyright © 2007 Wiley Periodicals, Inc.
Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer
Authors: Das Prajnan , Skibber John M. , Rodriguez‐Bigas Miguel A. , Feig Barry W. , Chang George J. , Wolff Robert A. , Eng Cathy , Krishnan Sunil , Janjan Nora A. , Crane Christopher H.
Published: March 2007

BACKGROUND

The objective of this study was to identify predictive factors for pathologic complete response and tumor downstaging after preoperative chemoradiation for rectal cancer.

METHODS

Between 1989 and 2004, 562 patients with nonmetastatic rectal adenocarcinoma received preoperative chemoradiation and underwent mesorectal excision. The median radiation dose was 45 Gray (Gy) (range, 19.8–58.6 Gy), 77% of patients received concurrent infusional 5‐fluorouracil, 20% of patients received concurrent capecitabine, and 3% of patients received other regimens.

RESULTS

Nineteen percent of patients achieved a pathologic complete response (CR), whereas 20% of patients had only microscopic residual disease at surgery, and 61% of patients had macroscopic residual disease at surgery. Downstaging of the tumor stage occurred in 57% of patients. The results from a univariate analysis indicated that tumor circumferential extent >60% (P = .033) and pretreatment carcinoembryonic antigen (CEA) level >2.5 ng/mL (P = .015) were associated significantly with lower pathologic CR rates. The univariate analysis also indicated that tumor circumferential extent >60% (P = .001), pretreatment CEA level >2.5 ng/mL (P = .006), and distance from the anal verge >5 cm (P = .035) were associated significantly with lower downstaging rates. The results from a multivariate logistic regression analysis indicated that greater circumferential extent of tumor (odds ratio [OR], 0.43; P = .033) independently predicted a lower pathologic CR rate. The multivariate logistic regression analysis also indicated that greater circumferential extent of tumor (OR, 0.49; P = .020) and greater distance from the anal verge (OR, 0.46; P = .010) independently predicted a lower downstaging rate.

CONCLUSIONS

Circumferential extent of tumor, CEA level, and distance from the anal verge predicted for the pathologic response to preoperative chemoradiation for patients with rectal cancer. Therefore, these factors may be used to predict outcomes for patients, to develop risk‐adapted treatment strategies, and to target patients who participate in trials of newer therapies. Cancer 2007. © 2007 American Cancer Society.
Clinicopathologic features and BRAFV600E mutation analysis in cutaneous metastases from well‐differentiated thyroid carcinomas
Authors: Erickson Lori A. , Jin Long , Nakamura Nobuki , Bridges Alina G. , Markovic Svetomir N. , Lloyd Ricardo V.
Published: March 2007

BACKGROUND

Cutaneous metastases from well‐differentiated thyroid carcinomas are rare and are usually identified in patients with widely disseminated disease. Occasionally, thyroid carcinomas can present as cutaneous metastases for which the primary site needs to be determined. Papillary thyroid carcinomas (PTCs) commonly have BRAFV600E mutation. A series of 16 cutaneous metastases were analyzed from well‐differentiated thyroid carcinomas to learn more about the clinicopathologic features and BRAFV600E mutation status.

METHODS

Eleven cases of PTC and 5 of follicular thyroid carcinoma (FTC) metastatic to the skin were evaluated. All cutaneous metastases were studied histologically and with thyroglobulin and thyroid transcription factor immunostains. All tumor samples were analyzed for mutations at nucleotide 1799 in exon 15 of the BRAF gene.

RESULTS

Two patients with FTC presented with cutaneous metastases. Fourteen of 16 patients died of disease and 2 were alive with disease at follow‐up. The histologic features of the cutaneous metastases were generally characteristic of the primary tumor; however, 2 of the 11 PTC metastases demonstrated cytoplasmic clearing not typical of classic PTC. BRAFV600E mutation (T1799A) was detected in 5 of 11 cases of PTC and in none of the 5 FTCs.

CONCLUSIONS

Cutaneous metastases from PTC may show prominent clear cell change requiring differentiation from clear cell hidradenoma, clear cell dermatofibroma, malignant melanoma with prominent clear cell change, and cutaneous metastasis from renal cell carcinoma. BRAFV600E mutation is identified in a subset of cutaneous metastases from PTC. Cutaneous metastases from PTC and FTC are associated with a very poor prognosis. Cancer 2007. © 2007 American Cancer Society.
Controlled Aggregation of Functionalized Gold Nanoparticles with a Novel Conjugated Oligomer
Authors: Liu Xiaofeng , He Xiaorong , Jiu Tonggang , Yuan Mingjian , Xu Jialiang , Lv Jing , Liu Huibiao , Li Yuliang
Published: March 2007

A new route is developed to control the self‐assembly of gold nanoparticles (AuNPs) functionalized with a novel pyridyl‐ended porphyrin–oligo(p‐phenylene vinylene) conjugated oligomer (P–OPV–Py) into branched‐rods, chain‐networks, uniform fractal‐like Au clusters, and larger nanoparticles. The techniques of optical spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering (DLS) are used to characterize the self‐assembly in various solvent systems (pure toluene, CHCl3/toluene, THF/toluene and n‐butanol/toluene). A combination of the ligand/AuNPs molar ratio and relative concentration serves as the driving force to control the size and shape of P–OPV–Py capped AuNPs.
International Society for Analytical Cytology Biosafety Standard for Sorting of Unfixed Cells
Authors: Schmid Ingrid , Lambert Claude , Ambrozak David , Marti Gerald E. , Moss Delynn M. , Perfetto Stephen P.
Published: March 2007

Background:

Cell sorting of viable biological specimens has become very prevalent in laboratories involved in basic and clinical research. As these samples can contain infectious agents, precautions to protect instrument operators and the environment from hazards arising from the use of sorters are paramount. To this end the International Society of Analytical Cytology (ISAC) took a lead in establishing biosafety guidelines for sorting of unfixed cells (Schmid et al., Cytometry 1997;28:99–117). During the time period these recommendations have been available, they have become recognized worldwide as the standard practices and safety precautions for laboratories performing viable cell sorting experiments. However, the field of cytometry has progressed since 1997, and the document requires an update.

Methods:

Initially, suggestions about the document format and content were discussed among members of the ISAC Biosafety Committee and were incorporated into a draft version that was sent to all committee members for review. Comments were collected, carefully considered, and incorporated as appropriate into a draft document that was posted on the ISAC web site to invite comments from the flow cytometry community at large. The revised document was then submitted to ISAC Council for review. Simultaneously, further comments were sought from newly‐appointed ISAC Biosafety committee members.

Results:

This safety standard for performing viable cell sorting experiments was recently generated. The document contains background information on the biohazard potential of sorting and the hazard classification of infectious agents as well as recommendations on (1) sample handling, (2) operator training and personal protection, (3) laboratory design, (4) cell sorter set‐up, maintenance, and decontamination, and (5) testing the instrument for the efficiency of aerosol containment.

Conclusions:

This standard constitutes an updated and expanded revision of the 1997 biosafety guideline document. It is intended to provide laboratories involved in cell sorting with safety practices that take into account the enhanced hazard potential of high‐speed sorting. Most importantly, it states that droplet‐based sorting of infectious or hazardous biological material requires a higher level of containment than the one recommended for the risk group classification of the pathogen. The document also provides information on safety features of novel instrumentation, new options for personal protective equipment, and recently developed methods for testing the efficiency of aerosol containment. Published 2007 Wiley‐Liss, Inc.
Dynamic centrifuge testing of a cantilever retaining wall
Authors: Ortiz L. A. , Scott R. F. , Lee J.
Published: March 2007

Two correctly‐scaled model cantilever retaining walls of different stiffnesses were tested under dynamic loading conditions in a centrifuge. A medium‐dense fine sand was retained with a range of backfill slopes. For the centrifuge model, an earthquake‐generating mechanism was designed to produce seismic shaking equivalent to that generated at ground surface in the epicentral area of an earthquake of approximate magnitude 5–5. The response of the model retaining walls to the input dynamic motion was measured by strain gauges, pressure transducers and accelerometers. From the measurements plots were constructed of moment, shear, pressure and displacement over the height of the walls as a function of time. The results are compared with calculations based on the quasi‐static Mononobe‐Okabe theory. Although the calculated resultant force is in reasonable agreement with the experiments, the moments can be substantially different. Residual values of all parameters at the end of shaking are considerably greater than the initial static values. It is recommended that dynamic behaviour be incorporated in the earthquake design of retaining walls.
Effect of radiation damping on earthquake response of pile‐supported offshore platforms
Authors: Nogami Toyoaki , Idriss I. M. , Power M. S. , Chang C.‐Y.
Published: March 2007

An economical approach was developed to examine the effect of radiation damping on earthquake response of pilesupported offshore platforms. Parameteric studies were conducted to evaluate the effects of radiation damping on response. Various features of this effect were found for pile head stiffnesses, and responses of platforms subjected to harmonic and earthquake excitations.
Building over faults: A procedure for evaluating risk
Authors: Berrill J. B.
Published: March 2007

This paper examines the risk from fault offset to a building constructed over the surface trace of a fault. An expression relating the magnitude of surface offset to its return period is derived using classical seismic hazard analysis. The risk from fault offset is compared with that due to ground shaking by comparing offsets and MM intensities with equal likelihoods of occurrence. The comparison of risks is useful since it enables risk from fault movement to be related to levels of community acceptance as expressed in building codes for design against ground shaking effects. Relative risk is independent of fault activity rate, but does depend on regional constants, principally those describing the attenuation of MM intensities. For a site over an isolated fault in the Wellington, New Zealand region the risk of damage from fault rupture appears to be about equal to that from ground shaking for buildings with poor earthquake resistance (e.g. unreinforced masonry structures). But for structures designed to have some resistance to ground shaking, the risk due to fault rupture is considerably greater than that due to ground shaking.
Effect of topography and subsurface inhomogeneities on seismic SV waves
Authors: Ohtsuki Akira , Harumi Kasaburo
Published: March 2007

The effect of topography and subsurface inhomogeneity on surface motion is investigated in the case of incident SV waves. Several types of topography, such as a cliff, a cliff with a soft layer and filled land, are considered. Computations are made using a new method combining a particle model with a finite element method. The accuracy of this method is discussed through comparisons with Wong's solutions, which are in good agreement. It is found that the surface displacement is very much influenced by surface irregularities when the incident wavelengths are comparable to the size of the topographic features. Rayleigh waves are strongly produced in the neighbourhoods of the slopes of a cliff and a cliff with a soft layer, the latter being a cliff adjacent to and covered at its foot by a soft layer. Thus, a zone of large amplification takes place near a slope, combining incident SV waves and Rayleigh waves. A large displacement also occurs at the upper corner of the slope. In filled land, vertical and horizontal displacements are produced, which are 3 times larger than those at a distance. The present results are considered to be significant from the viewpoint of engineering seismology.
Response of a nuclear power plant on aseismic bearings to horizontally propagating waves
Authors: Wolf John P. , Obernhuber Pius , Weber Benedikt
Published: March 2007

The nuclear island of Koeberg with a large basemat, a non‐linear base isolation effective in the horizontal direction only, founded on rock, is analysed for inclined body waves and for a combination of surface and body waves associated with prescribed horizontal and vertical components of the control motion.

When compared to vertical incidence, an additional rocking component arises, generated by the horizontally propagating vertical component. As the aseismic bearings do not isolate against this rocking component, the corresponding horizontal response bears comparison with that of a conventional structure. The ratio of the response for horizontally propagating waves and that for vertically incident waves is thus considerably larger for the base‐isolated structure than for a conventional one. However, the actual design incorporating other loading cases is affected much less.
Frequency‐independent impedances of soil‐structure systems in horizontal and rocking modes
Authors: Ghaffar‐Zadeh Mansour , Chapel François
Published: March 2007

The frequency‐independent foundation impedances, commonly used in soil‐structure dynamic interaction problems, are developed for a circular footing resting on a homogeneous halfspace. As they ignore the structure attached to the foundation, the error introduced in the structural response may be 50 per cent or more in the neighbourhood of the fundamental frequency of the soil‐structure system.

The present study proposes a new method developed for most dynamic soil‐structure interaction problems. The key idea is to retain for the frequency‐independent impedances values computed for the fundamental frequency of the soil‐structure system; thus these values include the dynamic characteristics of the whole soil‐structure system and lead to a satisfactory approximation of the exact solution over a wide frequency range. The method is developed here for the horizontal and rocking modes of a structure with a circular base resting on a homogeneous halfspace.

Numerical applications are given for a simple linear oscillator in order to make possible a thorough parametric study. The response of some idealized building‐foundation systems to harmonic excitation or to a seismic input is next examined in order to illustrate the efficiency of the proposed model.
Use of a Lanczos algorithm in dynamic analysis of structures
Authors: Smith I. M. , Heshmati E. E.
Published: March 2007

In this paper the Choleski factorization of the mass or the stiffness matrix and its use in reduction of the general free vibration equation to a standard eigenproblem prior to the application of the Lanczos method is described, and their effects on the necessary computing time in determination of the frequencies are discussed.
Effect of soil‐structure interaction on damping of structures
Authors: Novak M. , Hifnawy L. El
Published: March 2007

Damping of structures resting on flexible foundations is affected by soil‐structure interaction in two ways: (1) the structure gains damping through energy dissipation in soil, and (2) the damping the structure would have on a rigid foundation is reduced. These effects are evaluated using two approaches: an energy consideration which is a simple but approximate approach, and the complex eigenvalue analysis which is mathematically accurate but uses damped, non‐classical vibration modes. These two methods are compared and the accuracy of the more convenient energy approach is assessed. Examples of modal damping are given for rigid structures, buildings and towers.
Phenytoin immunoassay measurements in serum samples from patients with renal insufficiency: comparison with high‐performance liquid chromatography
Authors: Tutor‐Crespo Maria J. , Hermida Jesús , Tutor J. Carlos
Published: March 2007

The debate continues regarding the possible interference of phenytoin metabolites in phenytoin immunoassays, and its clinical importance for patients with renal failure. The aim of this study was to compare the results obtained using the Abbott fluorescence polarization immunoassay (FPIA), Dade enzyme‐multiplied immunoassay technique (EMIT), and high‐performance liquid chromatography (HPLC) to establish the significance of the differences in conditions of renal failure. Thirty‐six adult patients who had been treated with phenytoin and whose renal function ranged from normal to severely impaired were chosen for this study. In accordance with previously established validation criteria for analytical methods for the determination of drugs, a 15% bias from the HPLC phenytoin values was considered an acceptable limit. The mean (±SEM) glomerular filtration rate (GFR) of the patients was 37.5±4.6 mL/min (range = 10–102 mL/min).The mean values found using FPIA (10.8±1.2 µg/mL) and EMIT (10.8±1.3 µg/mL) presented acceptable deviations with respect to HPLC (10.5±1.2 µg/mL), and a high correlation was found among the results (N = 36) of the different methods (r≥0.987, P<0.001). An FPIA deviation above the 15% bias limit with respect to HPLC was found only in two cases with very low serum phenytoin concentrations and low GFR values (<20 mL/min), although it does not appear to be important in terms of adjusting drug dosage. According to our data, FPIA and EMIT gave accurate results for total phenytoin in serum samples from patients with renal failure. J. Clin. Lab. Anal. 21:119–123, 2007. © 2007 Wiley‐Liss, Inc.
Improved quantitative method for G6PD deficiency detection
Authors: Fan Yun‐Hua , Lazenbery LuAnn , Foster Elizabeth , Duelm Felix , Grant Earl
Published: March 2007

Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is a common hereditary enzyme defect that affects over 400 million people worldwide. Deficiency in G6PD can cause hemolytic anemia, which can be fatal if it is not treated properly. Mass qualitative G6PD‐deficiency screening methods have been available for some time; however, in this study we developed the first high‐throughput quantitative method for measuring G6PD activity. A patient's blood can be analyzed directly from the original collection tubes on a Hitachi P modular serum work area (SWA), which dramatically reduces the analysis time and the cost of the assay. The results presented here may enable the development of other improved, automated assays of whole‐blood samples. J. Clin. Lab. Anal. 21:107–113, 2007. © 2007 Wiley‐Liss, Inc.