bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-invasive molecular imaging and reporter genes
Authors: Serganova Inna , Moroz Ekaterina , Moroz Maxim , Pillarsetty Nagavarakishore , Blasberg Ronald
Published: March 2006

Molecular-genetic imaging in living organisms has become a new field with the exceptional growth over the past 5 years. Modern imaging is based on three technologies: nuclear, magnetic resonance and optical imaging. Most current molecular-genetic imaging strategies are “indirect,” coupling a “reporter gene” with a complimentary “reporter probe.” The reporter transgene usually encodes for an enzyme, receptor or transporter that selectively interacts with a radiolabeled probe and results in accumulation of radioactivity in the transduced cell. In addition, reporter systems based on the expression of fluorescence or bioluminescence proteins are becoming more widely applied in small animal imaging. This review begins with a description of Positron Emission Tomography (PET)-based imaging genes and their complimentary radiolabeled probes that we think will be the first to enter clinical trials. Then we describe other imaging genes, mostly for optical imaging, which have been developed by investigators working with a variety of disease models in mice. Such optical reporters are unlikely to enter the clinic, at least not in the near-term. Reporter gene constructs can be driven by constitutive promoter elements and used to monitor gene therapy vectors and the efficacy of gene targeting and transduction, as well as to monitor adoptive cell-based therapies. Inducible promoters can be used as “sensors” to monitor endogenous cell processes, including specific intracellular molecular-genetic events and the activity of signaling pathways, by regulating the magnitude of reporter gene expression.
Titelbild: Biomimetische Fluorapatit‐Gelatine‐Nanokomposite: Vorstrukturierung von Gelatine‐Matrices durch Ionenimprägnierung und Auswirkungen auf die Formentwicklung / Intrinsic Electric Dipole Fields and the Induction of Hierarchical Form Developments in Fluorapatite–Gelatine Nanocomposites: A General Principle for Morphogenesis of Biominerals? (Angew. Chem. 12/2006)
Authors: Tlatlik Harald , Simon Paul , Kawska Agnieszka , Zahn Dirk , Kniep Rüdiger , Lichte Hannes
Published: March 2006

Die Formentwicklung beim Wachstum von Fluorapatit‐Gelatine‐Nanokompositen wird durch Vorstrukturierung von Gelatine‐Matrices gesteuert. Das Titelbild zeigt das hierarchische fraktale Aggregat (Hintergrund), Strukturdetails eines fächerförmigen Aggregats und die Simulation des Einflusses auf die Versteifung eines Proteinmoleküls durch Ca2+‐Einbau. Diesen Effekt diskutieren R. Kniep et al. in der Zuschrift auf S. 1939 ff.; eine zweite Zuschrift auf S. 1945 ff. befasst sich mit dem Einfluss von elektrischen Dipolfeldern auf die Formentwicklung.
Curcumin Analogs as Potent Aldose Reductase Inhibitors
Authors: Du Zhi‐Yun , Bao Ya‐Dan , Liu Zhong , Qiao Wei , Ma Lin , Huang Zhi‐Shu , Gu Lian‐Quan , Chan Albert S. C.
Published: March 2006

In the present study, curcuminoids isolated fromcurcuma longawere demonstrated to possess inhibitory activities on bovine lens aldose reductase. In order to find more potent aldose reductase inhibitor, curcumin analogs were synthesized and evaluated for their ability to inhibit bovine lens aldose reductase enzyme. The results indicated that the compounds with tetrahydroxyl groups, 2,6‐bis(3,4‐dihydroxybenzylidene)cyclohexanone (A2), 2,5‐bis(3,4‐dihydroxybenzylidene)cyclopentanone (B2), 1,5‐bis(3,4‐dihydroxyphenyl)‐1,4‐pentadiene‐3‐one (C2), and 3,5‐bis(3,4‐dihydroxybenzylidene)‐4‐piperidone (D2) showed remarkably potent inhibitory effects on aldose reductase with IC50of 2.9 μM, 2.6 μM, 3.4 μM, and 4.9 μM, respectively. The structure‐activity relationship revealed that the curcumin analogs withortho‐dihydroxyl groups could form a more tight affinity with aldose reductase to exert more potential inhibitory activities.
A Study of Anti‐inflammatory Activity of Some Novel α‐Amino Naphthalene and β‐Amino Naphthalene Derivatives
Authors: Sharma Shalabh , Singh Tripti , Mittal Rajan , Saxena K. K. , Srivastava Virendra Kishore , Kumar Ashok
Published: March 2006

In the present study, some naphthalene derivatives have been synthesized by incorporating azetidinyl and thiazolidinyl moieties at its α‐ or β‐positions such as α‐(3‐chloro‐2‐oxo‐4‐substituted)aryl‐1‐azetidinyl)naphthalenes 6–10, α‐((substituted)aryl‐4‐oxo‐1,3‐thiazolidin‐3‐yl)naphthalenes 11–15, β‐(3‐chloro‐2‐oxo‐4‐substituted aryl‐1‐azetidinyl)naphthalenes 21–25, and β‐(substituted aryl‐4‐oxo‐1,3‐thiazolidin‐3‐yl)naphthalenes 26–30. These compounds have also been screened for acute toxicity and anti‐inflammatory and analgesic activities. Compounds which showed better anti‐inflammatory and analgesic activities were also examined for their ulcerogenic liability and underwent a cyclooxygenase assay. Two compounds, 12 and 28, were found to exhibit potent anti‐inflammatory activity as compared to the standard drugs phenylbutazone and naproxen.
Electrochemical High‐Content Screening of Nitric Oxide Release from Endothelial Cells
Authors: Borgmann Sabine , Radtke Ina , Erichsen Thomas , Blöchl Andrea , Heumann Rolf , Schuhmann Wolfgang
Published: March 2006

Release of nitric oxide (NO) is of high importance for regulating endothelial cell functions during vasodilatation, vascular remodeling, and angiogenesis. Thus, a direct and reliable real‐time method for NO detection that takes into account time‐dependent variations of the NO concentration in the complex reaction within the diffusion zone above the cells is vital for obtaining information about the role of NO in intracellular endothelial signal transduction and its impact on the surrounding cells. In this study, the time course of vascular endothelial growth factor E (VEGF‐E) stimulated NO release from transformed human umbilical vein endothelial cells (T‐HUVEC) was investigated by means of metalloporphyrin‐based NO sensors employed in an electrochemical robotic system. The NO sensor was obtained by electrochemically induced deposition of NiIItetrakis(p‐nitrophenylporphyrin) on a 50‐μm diameter platinum disk electrode which was integrated, together with a 25‐μm diameter platinum disk, in a double‐barrel electrode arrangement. The second electrode was used as a guidance sensor for the automatic and highly reproducible positioning of the NO sensor at a known distance from a layer of adherently growing cells by usingz‐approach curves in the negative feedback mode of scanning electrochemical microscopy (SECM). The electrochemical robotic system allows the fully automated detection of NO with high sensitivity and selectivity to be performed in real time within 96‐well microtiter plates. A functional cell assay was established to allow the standardized detection of NO released upon stimulation from T‐HUVEC with a sensor positioned at a known distance above the endothelial cells. The overall system was evaluated by automatic detection of NO release from T‐HUVEC upon stimulation with VEGF‐E after incubation with a variety of drugs that are known to act on different sites in the complex signal‐transduction pathway that finally invokes NO release.
Impact of the Guanidinium Group on Hybridization and Cellular Uptake of Cationic Oligonucleotides
Authors: Deglane Gaëlle , Abes Saïd , Michel Thibaut , Prévot Paul , Vives Eric , Debart Françoise , Barvik Ivan , Lebleu Bernard , Vasseur Jean‐Jacques
Published: March 2006

The grafting of cationic groups to synthetic oligonucleotides (ONs) in order to reduce the charge repulsion between the negatively charged strands of a duplex or triplex, and consequently to increase a complex's stability, has been extensively studied. Guanidinium groups, which are highly basic and positively charged over a wide pH range, could be an efficient ON modification to enhance their affinity for nucleic acid targets and to improve cellular uptake. A straightforward post‐synthesis method to convert amino functions attached to ONs (on sugar, nucleobase or backbone) into guanidinium tethers has been perfected. In comparison to amino groups, such cationic groups anchored to α‐oligonucleotide phosphoramidate backbones play important roles in duplex stability, particularly with RNA targets. This high affinity could be explained by dual recognition resulting from Watson–Crick or Hoogsteen base pairing combined with cationic/anionic backbone recognition between strands involving H‐bond formation and salt bridging. Molecular‐dynamics simulations corroborate interactions between the cationic backbones of the α‐ONs and the anionic backbones of the nucleic acid targets. Moreover, ONs with guanidinium modification increased cellular uptake relative to negatively charged ONs. The cellular localization of these new cationic phosphoramidate ONs is mainly cytoplasmic. The uptake of these ON analogues might occur through endocytosis.
The attribution of blame scale with an incarcerated sample: factor structure, reliability and validity
Authors: Fazio Roberto Di , Kroner Daryl G. , Forth Adelle E.
Published: March 2006

The factor structure, reliability and validity of the Attribution of Blame Scale (ABS) were examined in a sample of 323 incarcerated violent offenders. Principal component analysis of the items resulted in a two‐factor solution of external and internal attribution in contrast with the original scales of victim, offender, alcohol, and societal blame. Measures of alcohol abuse, perception of external control and psychopathy corresponded with external attribution. The two‐factor structure of the ABS meets some basic psychometric properties for measuring criminal attributions within an offender population. Copyright © 1997 Whurr Publishers Ltd.
Mental health review tribunal decisions in restricted hospital order cases at one medium secure unit, 1992–1996
Authors: Mohan Damian , Murray Kevin , Steed Penny , Mullee Mark A.
Published: March 2006

We examined the outcome of 80 consecutive English mental health review tribunals (MHRTs) considering applications from restricted hospital order (section 37/41 Mental Health Act 1983) patients from January 1992. There was a high level of agreement between the RMO's recommendation and the tribunal decision, irrespective of whether the recommendation was for continued detention or conditional discharge. There was some indication that patients transferred from special hospitals were more likely to be discharged by a tribunal than those admitted from other sources. Although for black Caribbean patients conditional discharge was more likely than continued detention, overall there was no statistically significant association between ethnic group and tribunal outcome. There were no discharges against the RMO's advice on the patient's first application to the tribunal. These associations were weak in comparison with the overall 86% concordance of MHRT decision with RMO recommendation. Whilst the measures used should be reproducible at other medium secure units, it may well be that local factors such as availability of a hostel place or quality of the patient's legal representation at the tribunal, which it was not possible to assess in a retrospective case note study, also had a major bearing on tribunal outcome. Given current concern regarding the function of MHRTs in relation to the most serious offender‐patients, this may be an area for further study. Copyright © 1998 Whurr Publishers Ltd.
The Effra Trust: a study of community care for forensic psychiatric patients
Authors: Robertson Graham , Gunn John
Published: March 2006

A description is given of a specialist hostel for mentally disordered offenders in south London. The hostel began to provide services for eight epileptic men in 1974 and has grown to embrace seven homes and two flats which provide 39 beds. Data are given for all referrals to the Trust between 1990 and 1995. All were men aged between 18 and 74, who had a criminal history and were suffering from a wide variety of mental disorders. A comparison was made between the resident and referral populations. The residents were less likely to be using illegal drugs and more likely to be sex offenders. Current residents identified three types of problems at the hostel: lack of money, difficulties with other residents, lack of freedom. A description is given of the Trust staff and their working conditions. Copyright © 1998 Whurr Publishers Ltd.
Aggression in delinquent adolescents vs controls in Northern Russia: relations with hereditary and environmental factors
Authors: Ruchkin Vladislav V. , Eisemann Martin , Hägglöf Bruno , Cloninger C. Robert
Published: March 2006

The relationships between aggression and both hereditary and social factors are still very unclear. To examine the interrelations between aggression, temperament and character dimensions and parental rearing factors, 188 delinquent adolescents and 118 same‐aged schoolchildren from north‐western Russia were studied by means of the Buss‐Durkee Hostility Inventory, Temperament and Character Inventory (TCI) and EMBU questionnaire on parental rearing. Delinquent adolescents differed significantly from non‐delinquents on the majority of variables under investigation. Overt aggression was most strongly related with novelty seeking, whereas covert aggression was related with harm avoidance. Furthermore, the aggression scores were related to lack of paternal emotional warmth. Our results point to the significant role of both temperament characteristics and parental rearing as background factors in the development of aggression among adolescents. Copyright © 1998 Whurr Publishers Ltd.
A review of the role of the legal adviser in police stations
Authors: Pearse John , Gudjonsson Gisli H.
Published: March 2006

This article undertakes a brief review of research concerning the frequency and the quality of legal advice provided in police stations in England and Wales. In particular it examines the various definitions and actual nature of the role of the legal adviser. Studies indicate that the presence of legal advisers has increased since the introduction of the Police and Criminal Evidence Act 1984 (PACE), although a number of studies have experienced difficulty in determining the actual status of advisers. Many legal advisers are not qualified solicitors and their ability to advise their clients has been called into question. The finding that many advisers adopt a passive or compliant role is discussed in relation to the inflexible definition of their role under PACE which, it is argued, fails to reflect the welfare and emotional needs of the client. The question of ‘fitness for interview’, which psychiatrists and forensic medical examiners are increasingly being asked to decide, is used as an example of the additional demands made on legal advisers that are not reflected under PACE. It is recommended that the definition of the role of the legal adviser under PACE is amended to reflect these demands. Copyright © 1996 Whurr Publishers Ltd.
Psychiatric disorder and policing the elderly offender
Authors: Needham‐Bennett Humprhey , Parrott Janet , Macdonald A.J.D.
Published: March 2006

Information relating to elderly offenders' mental state is necessary if the English Home Office statement that cautioning is suitable for all age‐groups is to be safely implemented by the police. This paper reports on the prevalence of mental disorder in a sample of 50 alleged offenders over the age of 60, and reports on the reasons given for the police action (i.e. taking no further action, cautioning or prosecution). Subjects were interviewed using the Geriatric Mental State (A) 3rd edition (GMSA3). Previous offending history and the stated reasons for the mode of disposal were obtained from the police. One hundred and fifty three individuals were identified and a sample of 50 were interviewed. Ninety‐seven of the 153 offences (63%) involved shoplifting. Fourteen (28%) of all those interviewed were identified as cases by Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT). Amongst shoplifters, 38% were identified as cases, with nine out of the 11 cases belonging to AGECAT organic and depressive syndrome groups. No association between first onset offending in late life (age 60 or over) and mental disorder was identified. ‘No further action’ was associated with denial of intent and unclear or unreliable admission of the offence. Cautions were associated with police perceptions of attitude to offence and having a ‘clean record’. The police referred only half of the people later identified as psychiatric cases to welfare agencies (the Social Services being used infrequently). They were unlikely to refer on non‐psychiatric cases (19%). Close cooperation between health care agencies and the police is required to ensure that offences that may be related to mental disorder in the elderly do not go unnoticed. Copyright © 1996 Whurr Publishers Ltd.
Split‐plot regression models with both design and spectroscopic variables
Authors: Måge Ingrid , Næs Tormod
Published: March 2006

The main object of this work is to compare two methods for combining spectroscopic measurements and design variables in a regression model, when the data has a split‐plot error structure. Focus of the comparison is on prediction ability and interpretation. The need for such regression models is present in many production processes, since the end‐product quality usually is affected by both raw material quality and processing. If the raw materials are complex, biological substances, it is often natural to characterise them by spectroscopic measurements. This paper presents a case from the fish feed industry, where a designed experiment was carried out to investigate if quality variations in a certain raw material affect the end product. It was not known which raw material properties that are important, and NIR spectroscopy was therefore used for characterisation. Recipe and process settings were also varied. Practical considerations imposed restrictions on the randomisation, and this led to a split‐plot design. The regression model was estimated by restricted maximum likelihood (REML), to account for the split‐plot structure. The two methods presented here combine design variables with either PCA or PLS on the spectra. We call the methods REML‐PCA and REML‐PLS. In this case, both methods perform equally well regarding model fit and prediction ability. However, REML‐PLS is easier to interpret as less components are needed and the components are directly connected to the response. Copyright © 2006 John Wiley & Sons, Ltd.
Solid‐State NMR and EXAFS Spectroscopic Characterization of Polycrystalline Copper(I) O,O′‐Dialkyldithiophosphate Cluster Compounds: Formation of Copper(I) O,O′‐Diisobutyldithiophosphate Compounds on the Surface of Synthetic Chalcocite
Authors: Rusanova Daniela , Pike Kevin J. , Persson Ingmar , Hanna John V. , Dupree Ray , Forsling Willis , Antzutkin Oleg N.
Published: March 2006

A number of polycrystalline copper(I) O,O′‐dialkyldithiophosphate cluster compounds with Cu4, Cu6, and Cu8 cores were synthesized and characterized by using extended X‐ray absorption fine‐structure (EXAFS) spectroscopy. The structural relationship of these compounds is discussed. The polycrystalline copper(I) O,O′‐diisobutyldithiophosphate cluster compounds, [Cu8{S2P(OiBu)2}6(S)] and [Cu6{S2P(OiBu)2}6], were also characterized by using 31P CP/MAS NMR (CP = cross polarization, MAS = magic‐angle spinning) and static 65Cu NMR spectroscopies (at different magnetic fields) and powder X‐ray diffraction (XRD) analysis. Comparative analyses of the 31P chemical‐shift tensor, and the 65Cu chemical shift and quadrupolar‐splitting parameters, estimated from the experimental NMR spectra of the polycrystalline copper(I) cluster compounds, are presented. The adsorption mechanism of the potassium O,O′‐diisobutyldithiophosphate collector, K[S2P(OiBu)2], at the surface of synthetic chalcocite (Cu2S) was studied by means of solid‐state 31P CP/MAS NMR spectroscopy and scanning electron microscopy (SEM). 31P NMR resonance lines from collector‐treated chalcocite surfaces were assigned to a mixture of [Cu8{S2P(OiBu)2}6(S)] and [Cu6{S2P(OiBu)2}6] compounds.
A new approach for the asymmetric total synthesis of umbelactone
Authors: Liu Huawei , Zhang Tao , Li Yulin
Published: March 2006

The asymmetric total syntheses of (R)‐(+)‐ and (S)‐(–)‐umbelactone were achieved by using the Sharpless asymmetric epoxidation reaction to generate the stereogenic center and a ring‐closing metathesis (RCM) for the formation of the lactone structure. Starting from 3‐methyl‐2‐buten‐1‐ol, the asymmetric total synthesis was achieved in an efficient 6‐step protocol with an overall yield of 16%. Chirality, 2006. © Wiley‐Liss, Inc.
Enantioselective chromatography and absolute configuration of N,N‐dimethyl‐3‐(naphthalen‐2‐yl)‐butan‐1‐amines: Potential sigma1 ligands
Authors: Collina Simona , Loddo Guya , Urbano Mariangela , Rossi Daniela , Mamolo Maria Grazia , Zampieri Daniele , Alcaro Stefano , Gallelli Andrea , Azzolina Ornella
Published: March 2006

We describe the preparation of racemic N,N‐dimethyl‐3‐(naphthalen‐2‐yl)‐butan‐1‐amines, potential sigma1 ligands, and their resolution via chiral HPLC. In order to obtain enantiopure compounds, direct chromatographic methods of separation using chiral stationary phases were investigated. Different methods suitable for both analytical and semipreparative purposes are proposed. The best resolutions were achieved using cellulose tris (3,5‐dimethylphenyl carbamate) (Chiralcel OD and OD‐H) and amylose tris (3,5‐dimethylphenyl carbamate) (Chiralpak AD). On the basis of the preliminary chromatographic results, the resolution of compound 1 was transferred onto a Chiralcel OD semipreparative column. The enantiomers were obtained in high enantiomeric excess. The configurational assignment was performed by circular dichroism. Computational analysis was used to explore the enantioselective recognition process of compound 1 with the Chiralcel OD stationary phase. Chirality, 2006. © 2006 Wiley‐Liss, Inc.
Biomolecular mirror‐image recognition: Reciprocal chiral‐specific DNA binding of synthetic enantiomers of zinc finger domain from GAGA factor
Authors: Negi Shigeru , Dhanasekaran Muthu , Hirata Tsuyoshi , Urata Hidehito , Sugiura Yukio
Published: March 2006

To experimentally demonstrate the mirror‐image recognition in protein and DNA interaction, we have designed a small DNA‐binding peptide based on the zinc‐finger domain of GAGA transcription factor. Circular dichroism data suggest that the conformations of peptide enantiomers as well as the DNA enantiomers have a mirror‐image relationship. The gel mobility shift assay showed that the synthetic enantiomers of the peptide showed reciprocal chiral‐specific interactions with the DNA; the natural L‐peptide binds specifically with the natural D‐DNA substrate, and the unnatural D‐peptide binds specifically with the unnatural L‐DNA substrate. The present data imply that the folding of the L‐ and D‐enantiomers of the peptide as well as the DNA substrates are exact mirror images of each other in 3‐D structure and biological activity, and generalize the chiral‐specific nature of biomolecular interaction. Chirality, 2006. © 2006 Wiley‐Liss, Inc.
Enantioselective LC/MS method for the determination of an antimalarial agent Fenozan B07 in dog plasma
Authors: Maraschiello Ciriaco , Vilageliu Jaume , Dorronsoro Isabel , Martinez Ana , Floriano Pablo , Gómez‐Acebo Eduardo
Published: March 2006

A chiral liquid chromatography/mass spectrometry (LC/MS) bioanalytical procedure has been developed for the analysis of the antimalaric agent Fenozan B07 in dog plasma. Normal‐phase chromatography involving a phenylcarbamate derivative of cellulose coated on silica gel as the chiral stationary phase was used to resolve (−)‐(S,S)‐B07 from (+)‐(R,R)‐B07. The enantiomers were detected by a mass spectrometer equipped with an atmospheric pressure chemical ionization (APCI) interface operated in the negative ion mode. A mass spectrum, characterized by a base peak of m/z 285, was obtained for each enantiomer. The m/z 285 ion was very specific for the analysis of both enantiomers in the plasma. The selected ion monitoring analysis of the plasma samples was therefore performed at m/z 285 for quantitative purposes. The enantiomers were extracted from the plasma in a basic medium and purified by solid‐phase extraction using a hydrophilic–lipophilic balanced sorbent. A lower limit of quantification of 2 ng/mL in plasma was achieved for both enantiomers. The quantitative procedure reported in this study was highly specific and sensitive, and was validated according to the FDA guidance on bioanalytical method validation. Chirality, 2006. © 2006 Wiley‐Liss, Inc.
Phase II investigation of docetaxel in pediatric patients with recurrent solid tumors
Authors: Zwerdling Ted , Krailo Mark , Monteleone Philip , Byrd Rebecca , Sato Judith , Dunaway Rose , Seibel Nita , Chen Zhengjia , Strain John , Reaman Gregory
Published: March 2006

BACKGROUND

Docetaxel, which is an antitubulin agent, has demonstrable activity against murine and human tumors. The current study was designed to determine response rates to docetaxel in various strata of recurrent solid tumors of childhood and to assess toxicity in a group of patients who were assigned to receive it.

METHODS

Docetaxel was given at a dose of 125 mg/m2 once every 21 days as a 1‐hour intravenous infusion for a maximum of 12 courses. From January 1997 to November 2001, 109 male patients and 68 female patients (total, 177 patients) were enrolled, and 173 patients were eligible. The median patient age at entry was 13 years (range, 1‐27 yrs). One hundred sixty patients were evaluable for response.

RESULTS

There were no deaths attributable to study drug. Hematologic toxicity was common during therapy. Dermatologic, neurologic, pulmonary, and infectious side effects as well as edema were significant. One patient each had acute myeloid leukemia, acute lymphoid leukemia, and high‐grade glioma reported as secondary malignancies. One patient with osteosarcoma and 1 patient with rhabdomyosarcoma achieved a complete response. Partial responses were observed in patients with Ewing sarcoma (3 patients), osteosarcoma (1 patient), squamous cell carcinoma (1 patient), and medulloblastoma (1 patient). Seventeen patients had stable disease. The 1‐year and 5‐year overall survival rates for the 160 evaluable patients were 24% (standard error = 4%) and 6% (standard error = 2%), respectively.

CONCLUSIONS

Docetaxel demonstrated activity in patients with recurrent Ewing sarcoma but was found to be ineffective for treating the other types of recurrent solid tumors that were studied. Cancer 2006. © 2006 American Cancer Society.
t(3;21)(q26;q22) in myeloid leukemia
Authors: Cameron Yin C. , Cortes Jorge , Barkoh Bedia , Hayes Kimberly , Kantarjian Hagop , Jones Dan
Published: March 2006

BACKGROUND

The t(3;21)(q26;q22) translocation is associated with myeloid leukemias and results in a chimeric oncoprotein containing AML1/RUNX1 variably fused to EAP, MDS1, and/or EVI1.

METHODS

The current study describes what to the authors' knowledge is the first large case series reported to date of 26 t(3;21)(q26;q22)‐associated leukemias, in which 24 cases arose after chemotherapy. Conventional G‐band karyotyping and flow cytometry immunophenotyping were performed. Reverse transcriptase–polymerase chain reaction (RT–PCR) was performed to detect fusion transcripts between AML1 and EAP, MDS1, or EVI1, followed by DNA sequencing.

RESULTS

In all 16 patients with chronic myeloproliferative disorders, including 14 with chronic myelogenous leukemia (CML), the occurrence of t(3;21) heralded myeloid blast transformation. Fifteen (93%) patients had been previously treated with hydroxyurea. Eight patients with chronic myeloproliferative disorders (CMPD) were found to have t(3;21) with t(9;22) as the sole cytogenetic abnormality; in 5 other patients this was accompanied by trisomy 8. Among 10 cases of t(3;21)‐associated acute myeloid leukemia, 8 were secondary tumors after chemotherapy for other neoplasms that had been treated with regimens including fludarabine and 5–fluorouracil in 3 patients each and etoposide in 2 patients. The immunophenotype of the blasts in all 22 tested cases was similar, with uniform expression of myeloid markers and CD34 and variable expression of CD7 and CD9, but minimal morphological myeloid maturation. Dysplastic micromegakaryocytes and bone marrow fibrosis were observed predominantly in CMPD cases. RT–PCR followed by DNA sequencing showed that the AML1‐/MDS1‐/EVI1 (AME) fusion transcript was detected in all 5 cases assessed. Among the patients with CMPD, 8 died of disease (at a median of 6.5 mos) and 5 achieved disease remission with bone marrow transplantation. Among patients with acute myeloid leukemia/myelodysplastic syndrome, 7 died of disease (at a median of 2 mos) and 2 had persistent leukemia with short follow‐up.

CONCLUSIONS

Activation of AME through t(3;21) defines a highly aggressive, therapy‐related leukemic blast syndrome. Prior treatment with hydroxyurea or other antimetabolites is implicated as a contributory cause. Cancer 2006. © 2006 American Cancer Society.
Electrochemical Characterization of Self‐Assembled Thiol‐Porphyrin Monolayers on Gold Electrodes by SECM
Authors: Lu Xiaoquan , Zhang Limin , Li Minrui , Wang Xiaoqiang , Zhang Yan , Liu Xiuhui , Zuo Guofang
Published: March 2006

Herein, the scanning electrochemical microscopy (SECM) approach is applied to study the formation of thiol‐porphyrin self‐assembled monolayer (SAMs). Using cyclic voltammetry (CV), the formation process is characterized adopting different probe molecules. The observed phenomena indicate that the formation process is affected by solution properties and the molecular structure of the probe molecules. In K3Fe(CN)6 , the SAMs show a strong electron‐transfer (ET) blocking effect on a pure porphyrin‐modified electrode. However, addition of metal ions to the porphyrin molecules leads to ET. A consistent tendency is observed throughout the modification process using CV and SECM methods. Furthermore, keff values, the apparent heterogeneous rate constants, obtained for different modification periods affirm the validity of these results. SECM images are used to collect surface information in the course of the modification process when the substrate potential is 0.5 V versus Ag/AgCl. The effect of the substrate potential indicates that the oxidation of the porphyrin molecules is supported by more positive potentials because of the similar bimolecular reaction of the porphyrin ring with positive charge and the probe molecules with negative charge.
Mechanism of Cysteine Oxidation by a Hydroxyl Radical: A Theoretical Study
Authors: Enescu Mironel , Cardey Bruno
Published: March 2006

Cysteine oxidation by HO. was studied at a high level of ab initio theory in both gas phase and aqueous solution. Potential energy surface scans in the gas phase performed for the model system methanethiol+HO. indicate that the reactants can form two intermediate states: a sulfur–oxygen adduct and a hydrogen bound reactant complex. However these states appear to play a minor role in the reaction mechanism as long as they are fast dissociating states. Thus the main reaction channel predicted at the QCISD(T)/6‐311+G(2df,2pd) level of theory is the direct hydrogen atom abstraction. The reaction mechanism is not perturbed by solvation which was found to induce only small variations in the Gibbs free energy of different reactant configurations. The larger size reactant system cysteine+HO. was treated by the integrated molecular orbital+molecular orbital (IMOMO) hybrid method mixing the QCISD(T)/6‐311+G(2df,2pd) and the UMP2/6‐311+G(d,p) levels of theory. The calculated potential energy, enthalpy, and Gibbs free energy barriers are slightly different from those of methanethiol. The method gave a rate constant for cysteine oxidation in aqueous solution, k=2.4×109 mol−1 dm3 s−1, which is in good agreement with the experimental rate constant. Further analysis showed that the reaction is not very sensitive to hydrogen bonding and electrical polarity of the molecular environment.
Highly Symmetrical Tetranuclear Cluster Complexes Supported by p‐tert‐Butylsulfonylcalix[4]arene as a Cluster‐Forming Ligand
Authors: Kajiwara Takashi , Kobashi Takanori , Shinagawa Reiko , Ito Tasuku , Takaishi Shinya , Yamashita Masahiro , Iki Nobuhiko
Published: March 2006

Square‐planar tetranuclear clusters [M4(L)(AcO)4(μ4‐OH)]– (M = MnII, CoII, and NiII) are synthesized using tetra‐anionic p‐tert‐butylsulfonylcalix[4]arene (L4–) as a cluster‐forming ligand. Three complexes are crystallographically isostructural, being crystallized in the triclinic crystal system with space group P$\bar {1}$. The calix[4]arene acts as a tetrakis fac‐tridentate ligand through four phenoxo and four sulfonyl oxygen atoms to form square arrangement of four metal ions, which are further bridged by four chelating acetate ions and one hydroxo ion in a μ4 manner to complete the hexacoordination of each metal center. Although the whole molecule of each complex is crystallographically independent, the molecule is highly symmetrical with a pseudo‐four‐fold axis lying on the μ4‐OH– group. The tetranuclear clusters are stable enough to maintain the core structures even in highly dilute solution (≈10 μM), which was confirmed by mass spectroscopic study, however, bridging acetates were easily exchanged by other carboxylate chelates to form derivatives such as [M4(L)(BzO)4(OH)]–. Metal–metal interactions were investigated by means of magnetic susceptibility, and it was revealed that both ferro‐ and antiferromagnetic interactions occur in the NiII complex depending on the bridging angles of Ni–O–Ni. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Utilization of high‐oleic rapeseed oil for deep‐fat frying of French fries compared to other commonly used edible oils
Authors: Matthäus Bertrand
Published: March 2006

Changes in chemical, physical and sensory parameters of high‐oleic rapeseed oil (HORO) (NATREON™) during 72 h of deep‐fat frying of potatoes were compared with those of commonly used frying oils, palm olein (PO), high‐oleic sunflower oil (HOSO) and partially hydrogenated rapeseed oil (PHRO). In addition to the sensory evaluation of the oils and the potatoes, the content of polar compounds, oligomer triacylglycerols and free fatty acids, the oxidative stability by Rancimat, the smoke point and the anisidine value were determined. French fries obtained with HORO, PO and HOSO were still suitable for human consumption after 66 h of deep‐fat frying, while French fries fried in PHRO were inedible after 30 h. During the frying period, none of the oils exceeded the limit for the amount of polar compounds, oligomer triacylglycerols and free fatty acids recommended by the German Society of Fat Science (DGF) as criteria for rejection of used frying oils. After 72 h, the smoke point of all oils was below 150 °C, and the amount of tocopherols was reduced to 5 mg/100 g for PHRO and 15 mg/100 g for HORO and HOSO. Remarkable was the decrease of the oxidative stability of HOSO measured by Rancimat. During frying, the oxidative stability of this oil was reduced from 32 h for the fresh oil to below 1 h after 72 h of frying. Only HORO showed still an oxidative stability of more than 2 h. From the results, it can be concluded that the use of HORO for deep‐fat frying is comparable to other commonly used oils.
Bis‐methylene‐interrupted octadecadienoic fatty acids in Bulgarian bovine butter fats
Authors: Nikolova Diana , Antonova Daniela , Marekov Ilko , Nikolova‐Damyanova Boryana
Published: March 2006

Preparative silver nitrate thin‐layer chromatography of fatty acid methyl esters and gas chromatography‐mass spectrometry of 4,4‐dimethyloxazoline derivatives were applied in combination to analyze the cis,cis octadecadienoic (18:2) fraction in commercial samples of bovine butter fat in Bulgaria. The main component, 9,12–18:2 was accompanied by a series of bis‐methylene‐interrupted isomers, cis,cis‐5,9‐; 6,10‐; 9,13‐ and 11,15–18:2, which were unambiguously identified by their specific mass spectra. The latter are characterized by the presence of very intensive diagnostic fragments which help to correctly locate the position of the double bond system in the carbon chain. The cis,cis‐5,9–18:2 isomer was found for the first time in butter fat, and the 6,10–18:2 isomer has not been described as yet.
Revisiting the formation of trans isomers during partial hydrogenation of triacylglycerol oils
Authors: Dijkstra Albert J.
Published: March 2006

The decisions to limit (Europe) or declare (USA) the trans isomer content of certain fatty foodstuffs have caused a demand for hardstocks with a reduced trans isomer content. One way to produce such hardstocks is by interesterifying high‐melting components such as palm stearin or fully hydrogenated vegetable oils with lauric or liquid oils. Another way is to modify the hydrogenation process. Possible modifications are reviewed. A moderate reduction in trans isomer content results from operating the hydrogenation process at much reduced temperature, but this also leads to an increase in saturates. Larger reductions in trans isomers may well be made possible by the recent development of new catalysts. One development involves the use of zeolites that allow the rather straight trans isomer to enter the pores while keeping the more curved cis isomers outside. The other development involves a precious metal catalyst that may have been modified in such a way that it has a reduced affinity for monounsaturated fatty acid moieties.
Photochemical, Electrochemical and Enzymatic Methods for Ether‐Bond Cleavage
Authors: Stolarzewicz Andrzej , Grobelny Zbigniew , Pisarski Wojciech , Łosiewicz Bożena , Piekarnik Beata , Swinarew Andrzej
Published: March 2006

The objective of this review is to outline the photochemical, electrochemical, and enzymatic methods that are currently used for ether‐bond cleavage. Key results have been extracted from publications covering the past 15 years of research activity in this field. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Perchloric Acid Impregnated on Silica Gel (HClO4/SiO2): A Versatile Catalyst for Michael Addition of Thiols to the Electron‐Deficient Alkenes
Authors: Khan Abu T. , Ghosh Subrata , Choudhury Lokman H.
Published: March 2006

Perchloric acid adsorbed on silica gel (HClO4/SiO2) has been found to be a highly efficient and versatile catalyst for the Michael addition of thiols to a wide variety of conjugated alkenes such as α,β‐unsaturated ketones, carboxylic esters, nitriles, amides and chalcones in dichloromethane or methanol at room temperature. The reactions are completed within 2–20 min in high yields. Some of the additional advantages are: no aqueous work‐up is necessary, and the catalyst is also reusable. Moreover, the solid product can be obtained without chromatographic separation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Laboratory simulation of the salt weathering of schist: 1. Weathering of schist blocks in a seasonally wet tropical environment
Authors: Wells Tony , Binning Philip , Willgoose Garry , Hancock Greg
Published: March 2006

Data describing sediment generation focusing on the temporal evolution of size gradation are required for the prediction of long‐term landform evolution. This paper presents such data for the salt weathering of a quartz‐chlorite schist obtained from the Ranger Uranium Mine in northern Australia. Rock fragment samples are subjected to three different climate regimes: (1) a dry season climate; (2) a wet season climate (both based on observations at the Ranger site); and (3) an oven‐drying sequence designed to test the sensitivity of the weathering process by exposing the rocks to more extreme temperatures. Two MgSO4 salt solutions are applied, one being typical of wet season runoff and the other a more concentrated solution. Salt solution is applied daily in the wet season experiments and once only at the beginning of the dry season experiments. Results of the experiments reveal four stages of weathering. The kinetics of each stage are described and related to the formation of sediment of different sizes. Wet season climate conditions are shown to produce greater moisture variability and lead to faster weathering rates. However, salt concentrations in the wet season are typically lower and so when climate is combined with observed salt concentrations, the dry and wet season experiments weather at approximately equal rates. Finally, small variations in rock properties were shown to have a large impact on weathering rates, leading to the conclusion that rock weathering experiments need to be carefully designed if results are to be used to help predict weathering behaviour at the landscape scale. Copyright © 2006 John Wiley & Sons, Ltd.
Rock temperatures as an indicator of weathering processes affecting rock art
Authors: Hœrlé Stéphane
Published: March 2006

To aid rock art conservation, rock temperatures have been monitored at different depths and at low (30 min) and high (1 min) acquisition rates in a painted rock shelter in the uKhahlamba‐Drakensberg Park (South Africa). Preliminary data for winter (cold and dry) show that in that season cryoclasty is unlikely to occur (rare subzero thermal events and probable reduced moisture availability) and thermal shocks are improbable (highest measured ΔT/Δt < 2 °C min−1). High amplitude (about 30 °C) rock temperature cycles accompanied by reversals of the thermal gradient have been observed to occur almost daily and hint at the possibility of thermal stress fatigue. Copyright © 2006 John Wiley & Sons, Ltd.
Job separation in a non‐stationary search model: a structural estimation to evaluate alternative unemployment insurance systems
Authors: García‐Pérez J. Ignacio
Published: March 2006

This paper considers a job search model in which the environment is not constant throughout the unemployment spell and where jobs do not last for ever. In this situation, reservation wages can be lower than they would be in a model without consideration of such separations, but they can initially be higher precisely because of the non‐constant environment. The model is estimated structurally by using Spanish data for the period 1985–1996. The main finding is that, after controlling for unobserved heterogeneity, the unemployment hazard rate is almost flat during the first six months. However, after this duration, the highly decreasing job offer arrival rate comes to be the only significant factor, given that acceptance probabilities become equal to one. The estimated parameters are used to evaluate different unemployment insurance designs. We conclude that a non‐monotonic pattern in unemployment benefits, joint with a tax paid by workers and based on unemployment duration, makes this duration 13.2% lower than it currently is in Spain. Copyright © 2006 John Wiley & Sons, Ltd.
Estimation of multivariate models for time series of possibly different lengths
Authors: Patton Andrew J.
Published: March 2006

We consider the problem of estimating parametric multivariate density models when unequal amounts of data are available on each variable. We focus in particular on the case that the unknown parameter vector may be partitioned into elements relating only to a marginal distribution and elements relating to the copula. In such a case we propose using a multi‐stage maximum likelihood estimator (MSMLE) based on all available data rather than the usual one‐stage maximum likelihood estimator (1SMLE) based only on the overlapping data. We provide conditions under which the MSMLE isnot lessasymptotically efficient than the 1SMLE, and we examine the small sample efficiency of the estimators via simulations. The analysis in this paper is motivated by a model of the joint distribution of daily Japanese yen–US dollar and euro–US dollar exchange rates. We find significant evidence of time variation in the conditional copula of these exchange rates, and evidence of greater dependence during extreme events than under the normal distribution. Copyright © 2006 John Wiley & Sons, Ltd.
SG‐0: A small standard grid for DFT quadrature on large systems
Authors: Chien Siu‐Hung , Gill Peter M. W.
Published: March 2006

We report the development of a new standard quadrature grid for DFT calculations. Standard Grid 0 (SG‐0) is designed to be approximately half as large as, and to provide approximately half the accuracy of, the established SG‐1 grid. It is based on MultiExp and Lebedev quadrature for radial and angular coordinates, respectively. We find that SG‐0 is typically 50% faster than SG‐1 for energy, gradient, and hessian calculations for the exchange–correlation energy. This leads to a 35–38% speedup in the total gradient and hessian computations, and we particularly recommend its use for preliminary calculations on moderately large biochemical systems. It has been implemented as the default grid for DFT calculations in the Q‐Chem 3.0 package. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 730–739, 2006
Balancing an accurate representation of the molecular surface in generalized born formalisms with integrator stability in molecular dynamics simulations
Authors: Chocholoušová Jana , Feig Michael
Published: March 2006

Different integrator time steps in NVT and NVE simulations of protein and nucleic acid systems are tested with the GBMV (Generalized Born using Molecular Volume) and GBSW (Generalized Born with simple SWitching) methods. The simulation stability and energy conservation is investigated in relation to the agreement with the Poisson theory. It is found that very close agreement between generalized Born methods and the Poisson theory based on the commonly used sharp molecular surface definition results in energy drift and simulation artifacts in molecular dynamics simulation protocols with standard 2‐fs time steps. New parameters are proposed for the GBMV method, which maintains very good agreement with the Poisson theory while providing energy conservation and stable simulations at time steps of 1 to 1.5 fs. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 719–729, 2006
Photochemical treatment with endosomally localized photosensitizers enhances the number of adenoviruses in the nucleus
Authors: Engesæter Birgit Ø. , Tveito Siri , Bonsted Anette , Engebraaten Olav , Berg Kristian , Mælandsmo Gunhild M.
Published: March 2006

Background

In the present study the physical targeting technique photochemical internalization (PCI) has been used in combination with adenovirus. We have previously shown that PCI enhances transgene expression from AdhCMV‐lacZ, and the aim of the present study was to further increase the understanding of photochemically mediated adenoviral transduction.

Methods

Two colorectal carcinoma cell lines, WiDr and HCT116, were pre‐incubated with the photosensitizer TPPS2a or methylene blue derivates (MBD) followed by infection with adenovirus and light exposure. Transgene expression was measured by flow cytometry. Real‐time polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) were used to quantify the level of viral DNA in the nuclei. Real‐time PCR was also used to measure the level of β‐galactosidase mRNA in samples infected with AdhCMV‐lacZ.

Results

Exposing TPPS2a‐treated cells to light enhanced the quantity of viral DNA in the nucleus, the mRNA level of the transgene and the transgene expression compared to non‐illuminated cells. The increased transgene expression was independent of the promoter used, but dependent on the time of light exposure and the cellular localization of the photosensitizer.

Conclusions

The enhanced transgene expression observed after photochemical treatment is most likely not a result of one event, but more an interplay between various mechanisms. An increased level of adenoviral DNA in the nucleus and a dependency of endosomal localization of the photosensitizer to obtain enhanced transgene expression suggested that endosomal rupture facilitated the transport of adenoviruses to the nucleus. Copyright © 2006 John Wiley & Sons, Ltd.