bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors affecting protein refolding yields in a fed‐batch and batch‐refolding system
Authors: Mannall Gareth J. , Titchener‐Hooker Nigel J. , Dalby Paul A.
Published: February 2007

The refolding of recombinant protein from inclusion bodies expressed in Escherichia coli can present a process bottleneck. Yields at industrially relevant concentrations are restricted by aggregation of protein upon dilution of the denatured form. This article studies the effect of five factors upon the dilution refolding of protein in a twin impeller fed‐batch system using refold buffer containing only the oxidized form of the redox reagent. Such a buffer is easier to prepare and more stable than a buffer containing both reduced and oxidized forms. The five factors chosen were: bulk impeller Reynolds number, mini‐impeller Reynolds number, injection rate of denatured protein, redox ratio, and guanidine hydrochloride (GdHCl) concentration. A 25 factorial experiment was conducted at an industrially relevant protein concentration using lysozyme as the test system. The study identified that in the system used, the guanidine hydrochloride concentration, redox ratio, and injection rate were the most important factors in determining refolding yields. Two interactions were found to be important: redox ratio/guanidine hydrochloride concentration and guanidine hydrochloride concentration/injection rate. Conditions were also found at which high refolding yields could be achieved even with rapid injection and poor mixing efficiency. Therefore, a comparative assessment was carried out with minimal mixing in a simple batch‐refolding mode of operation, which revealed different behavior to that of fed‐batch. A graphical (windows of operation) analysis of the batch data suggested that optimal yields and productivity are obtained at high guanidine hydrochloride concentrations (1.2 M) and redox ratios of unity or greater. Biotechnol. Bioeng. 2007; 97: 1523–1534. © 2007 Wiley Periodicals, Inc.
Oligoribonucleotide Analogues Containing a Mixed Backbone of Phosphodiester and Formacetal Internucleoside Linkages, Together with Vicinal 2′‐O‐Methyl Groups
Authors: Rozners Eriks , Katkevica Dace , Strömberg Roger
Published: February 2007

Oligoribonucleotides containing formacetal internucleoside linkages have been prepared and studied by UV melting experiments. In RNA duplexes, the formacetal substitution is stabilizing (Δtm=0 to +0.9 °C per modification) at physiological salt concentrations (0.1 M) but destabilizing (Δtm=−0.4 to −0.8 °C per modification) at high salt concentrations (1 M); this suggests that reduction of electrostatic repulsion contributes substantially to the stabilization. The presence of 2′‐O‐Me substituents increases the stabilities of the duplexes (Δtm=+0.5 to +1.1 °C per modification). The positive effects of formacetals and 2′‐O‐Me groups were independent and additive. 1H NMR studies on monomeric model compounds containing 3′‐(ethyl phosphate) or 3′‐O‐ethoxymethyl groups showed that the formacetal and 2′‐O‐Me substitutions shift the conformational equilibria of the ribose residues towards the North conformers by 5 to 12 %. Although the preference for the North conformers qualitatively correlates with increased duplex stabilities, changes in thermodynamic parameters (ΔH° and TΔS°) for formation of oligonucleotide duplexes and differences in dependence on concentrations of sodium acetate, sodium chloride and sodium perchlorate suggest that solvation effects are also important for the duplex stabilities. Overall the formacetal linkages fit well in A‐type RNA duplexes, making them potentially interesting modifications for RNA‐based gene‐control strategies (e.g., antisense and RNA interference).
Cover Picture: Exploiting the Substrate Tolerance of Farnesyltransferase for Site‐Selective Protein Derivatization (ChemBioChem 4/2007)
Authors: Nguyen Uyen T. T. , Cramer Janina , Gomis Joaquin , Reents Reinhard , Gutierrez‐Rodriguez Marta , Goody Roger S. , Alexandrov Kirill , Waldmann Herbert
Published: February 2007

The cover picture shows the crystal structure of farnesyltransferase (FTase), which recognizes a short cysteine‐containing C‐terminal sequence (CAAX box) on its substrates. The enzyme transfers a farnesyl moiety that is harbored in a hydrophobic pocket onto the cysteine of the CAAX box. FTase is an efficient protein‐derivatization tool as it modifies virtually any recombinant protein containing a C‐terminally grafted CAAX box. Moreover, it tolerates modifications in the scaffold of its lipid substrate; this was explored for the incorporation of functional groups. The enzyme prenylates CAAX box‐tagged proteins with azide and diene groups containing isoprenoids quantitatively. These modifications do not change the functionality or the folding of the test proteins. The functional groups on the isoprenoid analogues can then further serve as anchor points for chemical derivatization both by Staudinger ligation and by Diels–Alder cycloaddition. Further details can be found in the article by K. Alexandrov, H. Waldmann, et al. on p. 408 ff.
Shaping and Enforcing Coordination Spheres: The Implications of C3 and C1 Chirality in the Coordination Chemistry of 1,1,1‐Tris(oxazolinyl)ethane (“Trisox”)
Authors: Gade Lutz H. , Marconi Guido , Dro Clémence , Ward Benjamin D. , Poyatos Macarena , Bellemin‐Laponnaz Stéphane , Wadepohl Hubert , Sorace Lorenzo , Poneti Giordano
Published: February 2007

A key feature of tris(oxazolinyl)ethane (“trisox”) ligands, which have shown broad scope in asymmetric catalysis, is the orientation and steric demand of their oxazoline substituents. This, along with the modularity of their synthesis determines their coordination chemistry. The possibility to combine oxazolines, in which the stereogenic centers adjacent to the N‐donor atoms have different absolute configuration, whilst retaining their ability to coordinate as tripodal ligands, has been demonstrated by the synthesis of the enantiomerically pure C3‐symmetric iPr‐trisox(S,S,S) and C1‐symmetric iPr‐trisox(S,S,R) and their reaction with [Mo(CO)3(NCMe)3] yielding [Mo{iPr‐trisox(S,S,S)}(CO)3] (1 a) and [Mo{iPr‐trisox(S,S,R)}(CO)3] (1 b), respectively. The non‐autocomplementarity of two homochiral trisox ligands at one metal center has been demonstrated by reaction of rac‐C3 iPr‐trisox with one equivalent of [Co(ClO4)2]⋅6 H2O, giving the centrosymmetric heterochiral complex [Co(iPr‐trisox)2](ClO4)2 (3), whereas an analogous reaction with the enantiopure ligand yielded a mixture of CoII complexes, which is characterized by the total absence of a [(trisox)2Co]+/2+ ion. The scope of the trisox ligand in terms of facial coordination to both early and late transition metals was demonstrated by the synthesis and structural characterization of the mononuclear complexes [ScCl3(iPr‐trisox)] (4), [Fe(tBu‐trisox)(NCMe)3](BF4)2 (5), and [Ru(η6‐p‐cymene)(iPr‐trisox)](PF6)2 (6). The facial coordination of their three ligating atoms to a metal center may be impeded if the transition‐metal center stereoelectronically strongly favors a non‐deltahedral coordination sphere, which is generally the case for the heavier d8‐transition‐metal atoms/ions. Reaction of iPr‐trisox with [Rh(cod)2]BF4 led to the formation of the 16‐electron d8‐configured complex [Rh(iPr‐trisox)(cod)](BF4) (7), which is oxidized by CsBr3 to give the RhIII complex [RhBr3(iPr‐trisox)] (8) possessing a C3‐symmetric structure with a κ3‐N‐trisox ligand. The crystalline salts [M2(μ‐Cl3)(iPr‐trisox)2](PF6) (M=FeII: 9, CoII: 10, NiII: 11), were prepared by addition of one molar equivalent of iPr‐trisox and an excess of KPF6 to solutions of the anhydrous (FeCl2) or hydrated metal halides (CoCl2⋅6 H2O, NiCl2⋅6 H2O). All dinuclear complexes display weak magnetic coupling. For the mononuclear species [CuCl2(iPr‐trisox)] (12) the removal of a chloride anion and thus the generation of a dinuclear chloro‐bridged structure failed due to Jahn–Teller destabilization of a potential octahedral coordination sphere.
Allyl ansa‐Lanthanidocenes: Single‐Component, Single‐Site Catalysts for Controlled Syndiospecific Styrene and Styrene–Ethylene (Co)Polymerization
Authors: Rodrigues Anne‐Sophie , Kirillov Evgueni , Lehmann Christian W. , Roisnel Thierry , Vuillemin Bruno , Razavi Abbas , Carpentier Jean‐François
Published: February 2007

A series of new neutral allyl Group 3 metal complexes bearing ansa‐bridged fluorenyl/cyclopentadienyl ligands [{Flu‐EMe2‐(3‐R‐Cp)}Ln(η3‐C3H5)(THF)] (E=C, R=H, Ln=Y (2), La (3), Nd (4), Sm (5); R=tBu, Ln=Y (8), Nd (9); E=Si, R=H, Ln=Y (12), Nd (13)) were synthesized in good yields via salt metathesis protocols. The complexes were characterized by elemental analysis, NMR spectroscopy for diamagnetic complexes, and single‐crystal X‐ray diffraction studies for 2, 4, 9 and 12. Some of the allyl ansa‐lanthanidocenes, especially 4, are effective single‐component catalysts for the polymerization of styrene, giving pure syndiotactic polystyrenes (rrrr > 99 %) with low to high molecular weights (Mn=6000–135 000 g mol−1) and narrow polydispersities (Mw/Mn=1.2–2.6). The catalyst systems are remarkably stable, capable of polymerizing styrene up to 120 °C with high activities, while maintaining high syndiotacticity via chain‐end control as established by a Bernoullian analysis. Highly effective copolymerization of styrene with ethylene was achieved using neodymium complex 4 (activity up to 2530 kg PS‐PE mol−1 h−1) to give true copolymers void of homopolymers with Mn=9000–152 000 g mol−1 and narrow polydispersities (Mw/Mn=1.2–2.5). The nature of the resultant P(S‐co‐E) copolymers was ascertained by NMR, size‐exclusion chromatography/refractive index/UV, temperature rising elusion fractionation, and differential scanning calorimetry. It is shown that, regardless the amount of ethylene incorporated (1–50 mol %), P(S‐co‐E) copolymers have a microstructure predominantly made of long highly syndiotactic PS sequences separated by single or few ethylene units. Co‐monomers feed and polymerization temperature can be used straightforwardly to manipulate with the physical and mechanical characteristics of the P(S‐co‐E) copolymers (molecular weights and distributions, co‐monomer content, microstructure, Tm, Tg, Tc).
Cover Picture: Ionic Self‐Assembly of Ammonium‐Based Amphiphiles and Negatively Charged Bodipy and Porphyrin Luminophores (Chem. Eur. J. 8/2007)
Authors: Camerel Franck , Ulrich Gilles , Barberá Joaquín , Ziessel Raymond
Published: February 2007

Ionic self‐assembly has been used for the formation of well‐defined columnar mesophases. In their Full Paper on page 2189 ff., F. Camerel, R. Ziessel et al. discuss a new electrostatic “LEGO” system from wedge‐shaped ammonium amphiphiles and negatively charged functional molecules. The cover shows an assembly based upon a porphyrin derivative observed by means of optical microscopy between crossed polarizers.
How important is on‐site adequacy assessment for thyroid FNA? An evaluation of 883 cases
Authors: Zhu Weijian , Michael Claire W.
Published: February 2007

Immediate adequacy assessment (IADA) during fine‐needle aspiration (FNA) is not universal and the optimal numberof passes has not been well determined. The aim of this study was to evaluate the nondiagnostic rates (NDR) with and without the IADA forthyroid aspirates. Subsequent cytological and surgical follow‐upwere reviewed for nondiagnostic cases. In addition, we evaluated the numberof passes performed in each FNA to determine the optimal number.

Retrospective analysis of NDR was performed on 883 thyroid FNA specimens retrievedthrough a Computer SNOMED Search from our files between January 2001 toDecember 2003. For FNAs with IADA, one Diff‐Quick and one fixedsmear for each pass were prepared, and the needle was rinsed in CytoLytsolution for a ThinPrep and/or a cell‐block. FNAs without IADAwere received in CytoLyt solution, from which a ThinPrep and a cell‐block were prepared for each case.

Of the total 883 cases, 443 wereperformed with IADA, of which 417 cases were diagnostic. The remaining440 cases were performed without IADA, of which 300 cases were diagnostic.NDR for IADA was 5.9% (26 cases‐group‐I)compared to 31.8% (140 cases‐group‐II)without IADA. In group‐I, 5 cases were followed‐upby repeat FNA, 10 cases by surgical resection, and 11 cases received notissue follow‐up. In group‐II, 23 cases were followed‐up by repeat FNA, 36 by surgical resection, and 82 cases received notissue follow‐up. Interestingly, follow‐up in group‐Idid not reveal any missed malignancy, while that in group‐II resultedin a malignant diagnosis in 13.8% (8 cases). We alsofound that the optimal number of passes with least NDR was 4–6 passes.NDR was 25% for < 3 passes, 11% for 4 passes, 5.2% for 5 passes, 1.4% for 6 passes, and 2.5% for 7 passesor more. IADA significantly reduces the NDR and increases the sample adequacy for diagnosis. Optimal number of passes is 4–6 passes, and additionalpasses did not improve the diagnostic rate. Our study also emphasizesthe significance of repeat FNA or histological follow‐up for nondiagnostic cases, especially for those without IADA. Diagn. Cytopathol. 2007;35:183–186. © 2007 Wiley‐Liss, Inc.
Primary vascular neoplasms unique to the spleen: Littoral cell angioma and splenic hamartoma diagnosis by fine‐needle aspiration biopsy
Authors: Ramdall Risha B. , Alasio Teresa M. , Cai Guoping , Yang Grace C. H.
Published: February 2007

We report the fine‐needle aspiration (FNA) biopsy diagnosis of two rare cases of primary vascular neoplasms unique to the spleen: a littoral cell angioma from a 31‐yr‐old Caucasian woman and a splenic hamartoma from a 46‐yr‐old black man. The cytologic features of splenic hamartoma and of littoral cell angioma of the spleen were described three times in cytologic literature: two were bench‐top aspirates and one was FNA biopsy thought to be metastatic carcinoma. To the best of our knowledge, the current two cases were the first diagnosed by FNA biopsy. Our approach to the FNA biopsy diagnosis of these rare vascular neoplasms via compact cell block and immunohistochemistry is described. The differential diagnosis with other primary vascular splenic neoplasms is also discussed. Diagn. Cytopathol. 2007;35:137–142. © 2007 Wiley‐Liss, Inc.
Cervical cancer prevention for all the world's women: Genuine promise resides in skilled quality management rather than novel screening approaches
Authors: Suba Eric J. , Donnelly Amber D. , Furia Lisa M. , Huynh My Linh D. , Raab Stephen S.
Published: February 2007

The debate over the best route for cervical cancer prevention in developing countries may be considered part of a larger debate over whether the global health community has become enamored with the promise of new approaches at the expense of delivering available preventives today. Pap screening, which is feasible anywhere cervical screening is appropriate, is the only intervention currently available for the prevention of cervical cancer in developing countries, and the Pap test will be an essential component of future novel preventive approaches. Cervical cancer vaccination, the long‐term effectiveness of which is uncertain, will not eliminate screening requirements and is currently not affordable in developing countries. Root cause analyses, which may appropriately inform the best routes for improving health in developing countries, document that failures of cervical cancer prevention efforts are not attributable to factors specific to the Pap test but to lapses in programmatic quality management to which all screening tests are vulnerable. The genuine promise of cervical cancer prevention for all the world's women therefore resides in skilled quality management rather than novel screening approaches. We propose a global consensus policy by which Pap screening services will be provided in any setting where cervical screening is appropriate but unavailable, with consideration given to novel preventive approaches as they mature. Opportunity costs, borne by the underserved, are associated with prioritizing research on new approaches in any setting where established preventives are feasible but unavailable. Diagn. Cytopathol. 2007;35:187–191. © 2007 Wiley‐Liss, Inc.
Langerhans cell histiocytosis of the skull on cytologic squash preparations
Authors: Kobayashi Tadao K. , Ueda Masami , Nishino Toshihiro , Bamba Masamichi , Echigo Tadashi , Oka Hideki , Hino Akihiko , Fuse Ikuko , Fujimoto Masato , Katsumori Tetsuya , Kaneko Chiyuki
Published: February 2007

We present a case in which a primary cytodiagnosis of Langerhans cell histiocytosis (LCH) of the skull was made using squash preparations. The patient, a 25‐year‐old male, presented with raised intracranial pressure and decreased visual acuity. Magnetic resonance imaging revealed a large skull lesion with osteolytic features in the left frontal bone. The patient underwent surgical resection by the extended basal frontal epidural approach. The squash preparation smears were cellular and demonstrated a mixed population of small, mature lymphocytes, eosinophils, and a high histiocytes content. The histiocytes occurred as isolated or loosely cohesive and clustered. They possessed abundant cytoplasm with rounded cell shape and had characteristic nuclear features, composed of fine chromatin and delicate nuclear membranes. The cytologic features of these histiocytes were consistent with Langerhans cells (LCs). A final impression of LCH of the skull was rendered. Subsequent histopathology confirmed the diagnosis. LCs reacted with both S‐100 protein and CD1a immunohistochemically. The demonstration of Birbeck granules on electron microscopic study was also noted. Whenever squash preparation yields a mixed population of mature lymphocytes, eosinophils, and histiocytes, the cytologists should be aware of and consider LCH as a diagnostic possibility. Diagn. Cytopathol. 2007;35:154–157. © 2007 Wiley‐Liss, Inc.
The serotonergic phenotype is acquired by converging genetic mechanisms within the zebrafish central nervous system
Authors: Lillesaar Christina , Tannhäuser Birgit , Stigloher Christian , Kremmer Elisabeth , Bally‐Cuif Laure
Published: February 2007

To gain knowledge about the developmental origin of serotonergic precursors and the regulatory cascades of serotonergic differentiation in vertebrates, we determined the spatiotemporal expression profile of the Ets‐domain transcription factor‐encoding genepet1in developing and adult zebrafish. We show that it is an early, specific marker of raphe serotonergic neurons, but not of other serotonergic populations. We then usepet1expression together with tracing techniques to demonstrate that serotonergic neurons of rhombomeres (r) 1–2 largely originate from a progenitor pool at the midbrain–hindbrain boundary. Furthermore, by combining expression analyses ofpet1and the raphe tryptophan hydroxylase (Tph2) with rhombomere identity markers, we show that anterior and posterior hindbrain clusters of serotonergic precursors are separated by r3, rather than r4 as in other vertebrates. Our findings establish the origin of r1–2 serotonergic precursors, and strengthen the evidence for molecular, ontogenic and phylogenic heterogeneities among the vertebrate brain serotonergic cell populations. Developmental Dynamics 236:1072–1084, 2007. © 2007 Wiley‐Liss, Inc.
Molecular Recognition Utilizing Complexes with NH,NR‐Stabilized Carbene Ligands
Authors: Meier Nicole , Hahn F. Ekkehardt , Pape Tania , Siering Carsten , Waldvogel Siegfried R.
Published: February 2007

Tungsten complex [W(NHC)(CO)5] (1) (NHC=NH,N‐ethyl‐substituted benzimidazolin‐2‐ylidene ligand) was prepared by transmetallation of lithiated 1‐ethylbenzimidazole with the pentacarbonyltungsten complex fragment. The hydrogen‐bonding ability of the carbene‐NH group to substrates with carbonyl groups was investigated by NMR titration. Structural analogues to 1 with a catalytically active rhodium center show a distinct substrate‐selective hydrogenation behaviour.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
The Alpher, Bethe and Gamow of IEF, the alpha‐Centaury of electrokinetic methodologies. Part II: Immobilized pH gradients
Authors: Righetti Pier Giorgio
Published: February 2007

The present review (a follow up of Electrophoresis 2006, 27, 923–938 on conventional IEF) highlights the developmental steps of the IPG technology, from a nebulous start limiting the technique to just 1 pH unit intervals up to the description of extended pH gradients, encompassing as much as 8.5 pH units. Although computer algorithms had been developed for optimizing recipes so as to obtain the most precise and most linear pH gradients, it was also realized that nonlinear pH intervals, covering the pH 3–10 range, would be extremely beneficial in 2‐D map analysis, since they would follow the pI distribution of proteins in living systems. The synthesis of a number of Immobiline chemicals (the acrylamido weak acids and bases meant to be incorporated into the nascent polyacrylamide chains) is also reported. The review ends with preparative aspects of IPGs, with the introduction of multicompartment electrolyzers with Immobiline membranes.
Unequal crossover recombination – population screening for PHOX2B gene polyalanine polymorphism using CE
Authors: Hung Chia‐Cheng , Su Yi‐Ning , Tsao Po‐Nien , Chen Pau‐Chung , Lin Shio‐Jean , Lin Cheng‐Hui , Mu Shu‐Chi , Liu Chieh‐An , Chang Ying‐Chao , Lin Win‐Li , Hsieh Wu‐Shiun , Hsu Su‐Ming
Published: February 2007

Congenital central hypoventilation syndrome (CCHS) is a rare neurological disorder characterized by abnormal autonomic central nervous system control of breathing during sleep. Mutations in the paired‐like homeobox 2B (PHOX2B) gene, including point mutation, frameshift, and polyalanine expansion, are associated with the pathogenesis of CCHS. In this study, PHOX2B mutations were analyzed in seven CCHS patients, their family members, and 1520 healthy individuals from the general population using CE to provide high sensitivity and resolution screening for the PHOX2B polyalanine polymorphism. Seven mutations in the PHOX2B gene, including two frameshift mutations and five polyalanine expansions in the 20‐residue polyalanine tract, were identified. The various phenotypes observed in CCHS patients with PHOX2B mutations suggest that the size of the expansion allele is associated with the CCHS risk. In addition, significant differences were found in allele and genotype distributions between the healthy individuals. Alleles (GCN)20 and (GCN)15 had the highest population incidence rates of 94.84 and 4.51%, respectively, with the remaining alleles, (GCN)13 and (GCN)7, accounting for 0.59 and 0.06%, respectively. Therefore, it has been demonstrated that CE can be used to improve the detection of polyalanine expansions in the PHOX2B gene. The attractive alternative method is a promising tool for the detection of disorders involving trinucleotide repeat tracts.
CE‐ESI‐MS of biological anions in plastic capillaries at high pH
Authors: Benavente Fernando , Sanz‐Nebot Victoria , Barbosa José , van der Heijden Rob , van der Greef Jan , Hankemeier Thomas
Published: February 2007

In this study, the potential of poly(methylmethacrylate) (PMMA, Plexiglas) and polyether ether ketone (PEEK) tubing for CE‐ESI‐MS separations of anions at high pH values was examined. A set of model compounds of biological interest was used to investigate the main operational parameters for CE‐ESI‐MS, such as the sheath‐flow interface design, the polarity of the ionization voltage, the use of ammonia‐based separation electrolytes, and the sheath liquid composition. Optimum separations and detection sensitivities in negative ESI mode were obtained using a running electrolyte of 75 mM of ammonia at pH 11 and a sheath liquid of 60:40 v/v or 75:25 v/v isopropanol/water with 0.5% v/v of ammonia. At these experimental conditions, PMMA and PEEK capillaries show good hydrolytic stabilities and lower EOF values than fused‐silica columns. Better separation resolutions were obtained with PMMA capillary, but this plastic rapidly swelled and bled because of its limited chemical resistance to the sheath liquid. PMMA columns equipped with a fused‐silica tip were used for a safer exposure to the sheath liquid, but the inner surface of the fused‐silica tips had limited stability at pH 11. On the other hand, good separations and reproducibility on migration times and peak areas were obtained using PEEK capillaries without capillary column deterioration.
Analysis of electrokinetic pumping efficiency in capillary tubes
Authors: Chein Reiyu , Liao Jenchen
Published: February 2007

A mathematical model for predicting the maximum pumping efficiency and pressure difference generation by an electrokinetic‐driven fluid pumping system through a capillary tube is presented in this study. Both the maximum pumping efficiency and optimum pressure difference generation are found to depend on a single variable. This single variable is termed as the figure of merit since it determines the performance of electrokinetic pumping. The figure of merit is found to depend on three dimensionless parameters, the normalized Debye length, zeta potential, and Levine number indicating the nominal ratio of convective current to conductive current. All three parameters can be related to the pH value and concentration of aqueous salt solution by the introduction of concentration‐dependent electrical conductivity and pH‐dependent zeta potential. By presenting the maximum pumping efficiency and optimum pressure difference generation as functions of pH value, salt concentration, and capillary tube radius, it is found that both maximum pumping efficiency and optimum pressure difference generation increase with the decrease in capillary radius and salt concentration. The optimum pH values at which the maximum pumping efficiency and optimum pressure difference generation occur are found to be in the range between 6 and 9. For the salt concentration of <$>\displaystyle 10^{ ‐ 6} <$> M, pH 6.9, and a capillary tube radius value of 0.5 μm, the predicted maximum pumping efficiency is 5.4% which is close to the experimental measurement reported in the literature.
Electrokinetic transport and separations in fluidic nanochannels
Authors: Yuan Zhen , Garcia Anthony L. , Lopez Gabriel P. , Petsev Dimiter N.
Published: February 2007

This article presents a summary of theory, experimental studies, and results for the electrokinetic transport in small fluidic nanochannels. The main focus is on the effect of the electric double layer on the EOF, electric current, and electrophoresis of charged analytes. The double layer thickness can be of the same order as the width of the nanochannels, which has an impact on the transport by shaping the fluid velocity profile, local distributions of the electrolytes, and charged analytes. Our theoretical consideration is limited to continuum analysis where the equations of classical hydrodynamics and electrodynamics still apply. We show that small channels may lead to qualitatively new effects like selective ionic transport based on charge number as well as different modes for molecular separation. These new possibilities together with the rapid development of nanofabrication capabilities lead to an extensive experimental effort to utilize nanochannels for a variety of applications, which are also discussed and analyzed in this review.
FluoMEP: A new genotyping method combining the advantages of randomly amplified polymorphic DNA and amplified fragment length polymorphism
Authors: Chang Alex , Liew Woei Chang , Chuah Aaron , Lim Zijie , Lin Qifeng , Orban Laszlo
Published: February 2007

PCR‐based identification of differences between two unknown genomes often requires complex manipulation of the templates prior to amplification and/or gel electrophoretic separation of a large number of samples with manual methods. Here, we describe a new genotyping method, called fluorescent motif enhanced polymorphism (fluoMEP). The fluoMEP method is based on random amplified polymorphic DNA (RAPD) assay, but combines the advantages of the large collection of unlabelled 10mer primers (ca. 5000) from commercial sources and the power of the automated CE devices used for the detection of amplified fragment length polymorphism (AFLP) patterns. The link between these two components is provided by a fluorescently labeled “common primer” that is used in a two‐primer PCR together with an unlabeled RAPD primer. By using the same “common primer” and a series of RAPD primers, DNA templates can be screened quickly and effectively for polymorphisms. Our manuscript describes the optimization of the method and its characterization on different templates. We demonstrate by using several different approaches that the addition of the “common primer” to the PCR changes the profile of amplified fragments, allowing for screening various parts of the genome with the same set of unlabeled primers. We also present an in silico analysis of the genomic localization of fragments amplified by a RAPD primer with two different “common primers” and alone.
Expected loss‐based alarm threshold set for earthquake early warning systems
Authors: Iervolino Iunio , Giorgio Massimiliano , Manfredi Gaetano
Published: February 2007

Earthquake early warning systems (EEWS) seem to have potential as tools for real‐time seismic risk management and mitigation. In fact, although the evacuation of buildings requires warning time not available in many urbanized areas threatened by seismic hazard, they may still be used for the real‐time protection of critical facilities using automatic systems in order to reduce the losses subsequent to a catastrophic event. This is possible due to the real‐time seismology, which consists of methods and procedures for the rapid estimation of earthquake features, as magnitude and location, based on measurements made on the first seconds of the P‐waves. An earthquake engineering application of earthquake early warning (EEW) may be intended as a system able to issue the alarm, if some recorded parameter exceeds a given threshold, to activate risk mitigation actions before the quake strikes at a site of interest. Feasibility analysis and design of such EEWS require the assessment of the expected loss reduction due to the security action and set of the alarm threshold. In this paper a procedure to carry out these tasks in the performance‐based earthquake engineering probabilistic framework is proposed. A merely illustrative example refers to a simple structure assumed to be a classroom. Structural damage and non‐structural collapses are considered; the security action is to shelter occupants below the desks. The cost due to a false alarm is assumed to be related to the interruption of didactic activities. Results show how the comparison of the expected losses, for the alarm‐issuance and non‐issuance cases, allows setting the alarm threshold on a quantitative and consistent basis, and how it may be a tool for the design of engineering applications of EEW. Copyright © 2007 John Wiley & Sons, Ltd.
Predistortion and nonlinear detection for OFDM signals in the presence of nonlinear high power amplification
Authors: Han Huy Dung , Hoeher Peter Adam
Published: February 2007

Orthogonal frequency division multiplexing (OFDM) is characterised by a large peak‐to‐average‐power ratio and an orthogonal signal design. As a consequence, OFDM is particularly vulnerable with respect to nonlinear distortions caused, for example by a nonlinear high power amplifier (HPA). In the presence of nonlinear high power amplification, OFDM suffers from crosstalk between all subcarriers. Furthermore, the power density spectrum is significantly widened.

In this article, wesimultaneouslyuse a memoryless predistorter (PD) at the transmitter side and a nonlinear detector at the receiver side. The PD reduces the out‐of‐band power, whereas the nonlinear detector improves the bit error rate (BER). Since maximum‐likelihood detection is prohibitive, a novel reduced‐state symbol detector (RSSD) derived from the maximum‐likelihood detector is proposed. For a QPSK/OFDM system in the presence of a memoryless solid‐state power amplifier, it is shown that the PD is not only useful for spectral shaping, but also in order to reduce the computational complexity of the nonlinear detector and to provide more robustness, concerning an incomplete knowledge of the characteristics of the nonlinearity at the receiver. The overall raw bit error performance is shown to be close to that of a linear QPSK/OFDM system. Copyright © 2007 John Wiley & Sons, Ltd.
Soil resources of the Motul de San José Maya: Correlating soil taxonomy and modern Itzá Maya soil classification within a classic Maya archaeological zone
Authors: Jensen Christopher T. , Moriarty Matthew D. , Johnson Kristofer D. , Terry Richard E. , Emery Kitty F. , Nelson Sheldon D.
Published: February 2007

Investigations of soil resources in the department of Petén, Guatemala can provide important insight into the agricultural and land use strategies of the ancient Maya. The site of Motul de San José, located 3 km north of Guatemala's Lago Petén Itzá, is situated in the core zone of Classic Maya civilization and in an area currently inhabited by the modern Itzá Maya. This area was occupied and farmed from the Middle Preclassic period (˜600 B.C.) to the Early Postclassic (˜A.D. 1000). During the Late Classic period (˜A.D. 600–830), Motul de San José was one of many centers of intense population growth. The authors focused on examining soil resources in the Motul de San José area. Soil studies included chemical and physical evaluations of soils and an investigation of the traditional soil classification system used by modern Itzá Maya farmers in the community of San José. The results of these investigations, along with a subsequent carbon isotopic study of ancient vegetative signatures by Webb et al. (this issue, 291–312) provide a framework for assessment of ancient Maya land‐use strategies in the Motul de San José area. © 2007 Wiley Periodicals, Inc.
Therapeutic non‐adherence: a rational behavior revealing patient preferences?
Authors: Lamiraud Karine , Geoffard Pierre‐Yves
Published: February 2007

This paper offers an indirect measure of patient welfare based on whether patients comply with the prescription they receive. Adherence behavior is supposed to reveal patients' subjective valuations of particular therapies. We write a simple theoretical model of patient adherence behavior, that reflects the trade‐off between perceived costs and observed regimen efficacy. A discrete choice framework is then used for the estimation, i.e. the comparison of the incremental benefit of drug intake between two regimens. Consequently, the empirical analysis is based on the identification of patient and drug characteristics associated with adherence. The econometric approach is implemented through a bivariate panel two‐equation simultaneous system studying jointly the factors associated with adherence and response to treatment. The data come from a randomized clinical trial conducted in France between 1999 and 2001 and comparing the efficacy of two tritherapy strategies in HIV disease.

Both the theoretical and empirical results suggest that, for comparable clinical efficacy and toxicity levels, a higher adherence level is associated with higher patient welfare, thus adding valuable information to conclusions drawn by a mere biostatistical analysis. Therefore, from the perspective of the patient, the adherence‐enhancing drug must be favored. Our results based on panel data also stress that unobserved patient characteristics account substantially for drug valuation and that the assessment evolves during the course of the treatment. Furthermore, we provide a new framework for the analysis of adherence data. The microeconometric framework highlights that non‐adherence is an endogenous behavior, thus suggesting new ways for improving adherence. Copyright © 2007 John Wiley & Sons, Ltd.
Lectin binding properties of human follicular center lymphocytes and follicular (nodular) lymphomas
Authors: Strauchen James A.
Published: February 2007

The distribution of lectin binding receptors in normal human lymphoid tissue and follicular (nodular) lymphoma was studied in tissue sections using a panel of lectin‐peroxidase and lectin‐fluorescein conjugates: Concanavalin A (Con A), Peanut agglutinin (PNA), Lotus tetragonolobus agglutinin (LTA), Soybean agglutinin, Ulex europeus and Bandeiraea simplicifolia. Two lectins studied, PNA and LTA were found to bind selectively to the cell membranes of follicular centre lymphocytes in normal lymphoid tissue, and to the neoplastic cells of follicular (nodular) lymphomas. Con A, in contrast, bound selectively to follicular centre macrophages (tingible body cells) and identified in follicular (nodular) lymphomas a population of dendritic‐like cells not otherwise recognized and possibly corresponding to dendritic cells identified ultra‐structurally. Follicular (nodular) lymphomas share the lectin binding properties of non‐neoplastic follicular centres. The expression of receptors for lectins with blood group activity (PNA T‐like, LTA H‐like) on follicular lymphocytes may play a role in follicle formation.
Cytokinetic study on the effects of N4‐behenoyl‐1‐β‐d‐arabinofuranosylcytosine on murine leukemic cells L 1210: A comparison with the effects of 1‐β‐d‐arabinofuranosylcytosine
Authors: Maruo N. , Horiuchi H. , Nakabo T. , Kondo M. , Nakamura T.
Published: February 2007

The effects of N4‐behenoyl‐1‐β‐d‐arabinofuranosylcytosine (BH‐AC) on the cell cycle of murine leukemic cells (L 1210 cells) were compared with those of 1‐β‐d‐arabinofuranosylcytosine (ara‐C), known to be effective for acute leukemia. In a cytokinetic study, a combination of Feulgen microcytofluorometry and tritiated thymidine autoradiography (3H‐TdR ARG) was used to measure DNA content and to determine DNA synthesis simultaneously in a single cell. Administration of 200 mg/kg of BH‐AC significantly prolonged the survival time of mice bearing L 1210. In addition, the cells in the G1 + S1 phases increased with time, accounting for 94.4 per cent of all cells measured at 48 h after the administration, compared to 73.7 per cent before administration. On the other hand, following the administration of 86 mg/kg of ara‐C (equivalent to 200 mg/kg of BH‐AC), the percentage of cells in the S1 + S1 phases increased maximally to 75.9 per cent at 18 h. Cytokinetic studies further showed that BH‐AC administration blocks DNA synthesis of the cells in the S‐phase for a longer period than does ara‐C. These results suggest that the prolonged inhibition by BH‐AC on DNA synthesis allows cells to accumulate in the S‐phase to a greater degree.
Modifications in the classification of primary myelodysplastic syndromes: The addition of a scoring system
Authors: Varela B. L. , Chuang C. , Woll J. E. , Bennett J. M.
Published: February 2007

A retrospective series of patients with the primary myelodysplastic syndrome has been reviewed and the survival updated. A scoring system is proposed that has advantages in predicting survival outcome. The importance of either dysmegakaryocytopoiesis or dysgranulocytopoiesis is emphasized because of its prognostic impact on leukaemic progression. Over 50 per cent of the patients die from either acute leukaemia or consequences of defective marrow production of granulocytes and platelets. Although only a few cases were included, the RAEB‐T group has a very poor outcome and appears much closer to FAB M2in biologic behaviour than RAEB. Both the criteria for the FAB subtypes and the scoring system can be applied easily in each case of myelodysplasia.

Of the 56 patients only 9 were still alive as of April, 1984. Eight of these were in the RA‐S and RA categories (or using the scoring system grouping 7 were group 1). All of the 16 patients who progressed to overt AML died within 4 weeks, and none was treated with chemotherapy. Of the remaining 31 patients, half died as a result of infection and/or haemorrhage and the remainder from apparently unrelated causes (cardiovascular, carcinoma, renal failure). These latter deaths are not surprising in light of the median age of 72 years.
Heterogeneity of response and survival in diffuse histiocytic lymphoma after bacop therapy (bleomycin, doxorubicin, cyclophosphamide, vincristine, prednisone)
Authors: Levine Alexandra M. , Goldstein Mark , Meyer Paul R. , Forman Stephen J. , Parker John W. , Paganini‐Hill Annlia , Lukes Robert J. , Feinstein Donald I.
Published: February 2007

Diffuse ‘histiocytic’ lymphoma (DHL) is heterogeneous pathologically, consisting of four subtypes within Lukes–Collins; large‐cleaved (LC), large non‐cleaved (LNC), immunoblastic sarcoma of B cells (B‐IBS), and immunoblastic sarcoma of T‐cells (T‐IBS). This heterogeneity is also recognized in the Cooperative Working Formulation on non‐Hodgkin's lymphoma. Prior studies have suggested clinical heterogeneity of DHL as well, although conclusions were hampered by small numbers, and lack of therapeutic uniformity. We treated 57 patients with advanced DHL, using BACOP: 22 LNC, 16 T‐IBS, 13 B‐IBS, six LC. Complete remission rate for LNC was 64 per cent (14/22); B‐IBS was 54 per cent (7/13); LC was 33 per cent (2/6); T‐IBS was 25 per cent (4/16). (p=0.10). Median survival for LNC was 27.8 months, B‐IBS was 25.9, LC was 14, T‐IBS was 12.0. The survival was significantly shorter for T‐IBS patients when compared to the others (p=0.01). By multi‐variate analysis, histologic subtype (p=0.02), age (p=0.03), and stage (p=0.06) were significant and independent prognostic variables in predicting survival. We conclude that LNC may respond the most favourably to BACOP, whereas alternative regimens appear necessary for patients with T‐IBS.
Acute leukemias of childhood: Pathologic features
Authors: Swerdlow Steven H. , Glick Alan D. , Cousar John B. , Collins Robert D.
Published: February 2007

Major advances have been made in the diagnosis and therapy of childhood leukemia over the last two decades (Zuelzer and Flatz, 1960; Miller, 1980; Steinhorn and Myers, 1981; Kobrinsky et al., 1980).

Sophisticated phenotypic analysis of these leukemias has partially revealed their complexity; there are at least three to five distinct clinical pathological entities in the childhood leukemia groups. Improved therapy has resulted in marked increases in survival and cures. Less attention has been given to the pathology of childhood leukemia, although the frequency and complexity of tissue examinations have greatly increased. In particular, the pathologic manifestation of relapses, detection of focal leukemia after treatment and the pathology of complications have not been systematically reviewed.

Our goal was to look at all of the pathologic manifestations of leukemia and to relate these manifestations to homogeneous patient populations grouped by their type of leukemia. Therefore all of the cytologic, hematologic, histopathologic, ultrastructural and immunologic materials on a consecutive group of leukemic children seen at Vanderbilt from 1970 to 1981 were reviewed; pathologic manifestations of leukemia were then analysed in relationship to diagnostic categories.
Chronic myelomonocytic leukemia: Clinical features, cytogenetics, and prognosis in 30 consecutive cases
Authors: Alessandrino E. P. , Orlandi E. , Brusamolino E. , Lazzarino M. , Morra E. , Castagnola C. , Bernasconi C.
Published: February 2007

A retrospective analysis of 30 patients with chronic myelomonocytic leukemia (CrMML) was performed to define the natural history of the disease and the risk of acute transformation. Our patients fulfilled the following criteria of diagnosis: blood monocytosis over 1 × 109/1, blast cell percentage in bone marrow up to 30, and in peripheral blood less than 5. The most common presenting feature was anemia; seven patients had fever; three patients complained of purpura and bleeding. Anysopoikilocytosis and macrocytosis were frequent. Abnormal granulocyte morphology, defective granulation and abnormal leukocyte alkaline phos‐phatase were often observed. Blast cells in peripheral blood smears were found in 14 patients. Serum and urine lysozyme levels were increased in 82 per cent and 93 per cent, respectively. Dysplastic changes involving erythroid, granulocytic and megakaryocytic lineages were constant features in all cases. Agranulated blasts above 5 per cent of marrow nucleated cells were seen in 13 patients (43 per cent). Seven of the 20 patients showed non‐specific chromosomal abnormalities at diagnosis. Median survival from diagnosis was 18 months (range, 3‐112). Evolution into acute myeloid leukemia occurred in 11 patients. No difference in survival was found between patients who developed acute leukemia and patients who did not. A shorter survival has correlated to the following parameters: leukocytes > 10 × 109/1, the presence of blasts in peripheral blood and agranulated blasts in the marrow above 5 per cent.
An immunopathologic evaluation of lymph nodes from monkey and man with acquired immune deficiency syndrome and related conditions
Authors: Meyer Paul R. , Ormerod L. David , Osborn Kent G. , Lowenstine Linda J. , Hendrickson Roy V. , Modlin Robert L. , Smith Ron E. , Gardner Murray B. , Taylor Clive R.
Published: February 2007

Morphology and immunostaining of lymph nodes taken from rhesus monkeys and man are compared. The monkeys were inoculated with biologic materials known to transmit simian acquired immune deficiency syndrome (SAIDS) and the human biopsies were obtained from homosexual men with persistent generalized lymphadenopathy syndrome or acquired immune deficiency syndrome (AIDS). The lymph nodes from monkey and man share common immunohistochemical features, ranging from exhuberant follicular hyperplasia to lymphocyte depletion stage. The follicular hyperplasia differed from reactive controls by the larger follicular size and disorganization within the follicular centers as well as an increase in the number of cells with the T suppressor/cytotoxic phenotype. The lymphocyte depletion stage showed a loss of reactive follicles and small T lymphocytes with a predominance of mature monocytes/macrophages. Most monkeys and humans with the lymphocyte depletion morphology fulfilled the case definitions for AIDS and SAIDS while those with follicular hyperplasia usually had ‘prodromal’ findings.

The simian agent is associated with alterations in lymph node morphology and immunostaining which parallel the changes seen in spontaneous human cases supporting a similar pathogenesis for AIDS and SAIDS.
Staging and treatment with cyclophosphamide, vincristine and prednisone (CVP) in advanced cutaneous t‐cell lymphomas
Authors: Tirelli Umberto , Carbone Antonino , Zagonel Vittorina , Volpe Rachele , Veronesi Andrea , Galligioni Enzo , Tumolo Salvatore , Brema Fulvio , Trovo Mauro G. , Grigoletto Eligio
Published: February 2007

Twenty‐three consecutive patients with cutaneous T‐cell lymphomas were submitted to staging procedures including lymphangiography, bone marrow biopsy and aspiration, peripheral blood morphological examination, peritoneoscopy with liver and spleen biopsy, and in selected patients lymph node biopsies. Extracutaneous disease (lymph nodes, bone marrow, liver and spleen) was detected in 12 patients. Bone marrow was involved in 25 per cent of the patients at presentation (all patients had lymph node involvement) and in two of nine patients with advanced disease during the follow‐up. Peripheral blood was involved in 65 per cent of the patients at presentation (ten patients with advanced disease) and in six of nine patients with advanced disease during the follow‐up. In 16 patients with advanced disease (T3‐T4 and/or extracutaneous disease), CVP was given with a 50 per cent objective response rate and four complete remissions of 47+, 12+, 19 and 19 months duration. Median survival of patients with advanced disease was 4 years.
Aggressive angiofollicular lymph node hyperplasia (castleman's disease) treated with high dose melphalan and autologous bone marrow transplantation
Authors: Repetto L. , Jaiprakash M. P. , Selby P. J. , Gusterson B. A. , Williams H. J. H. , McElwain T. J.
Published: February 2007

A case of aggressive widespread angiofollicular lymph node hyperplasia in a 42‐year‐old male, treated with high dose melphalan is presented. The disease had failed to enter a durable remission after chemotherapy. High dose melphalan with autologous bone marrow transplantation achieved a complete remission which has lasted for 15 months to date. This approach can be considered when other measures fail.