bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymer flocculation of calcite: Experimental results from turbulent pipe flow
Authors: Heath Alex R. , Bahri Parisa A. , Fawell Phillip D. , Farrow John B.
Published: December 2005

The kinetics of aggregation/breakage of calcite particles flocculated with a high‐molecular‐weight polymer flocculant has been studied in turbulent pipe flow. The mean flocculation residence time was varied by changing the length of pipe between the flocculant injection point and the in‐stream particle‐sizing probe (Lasentec FBRM). A variety of pipe sizes and flow rates were used to produce a range of mean fluid shear rates. The mean shear rate was calculated from the pressure drop along the pipe reactor, as measured by manometer, and was found to vary markedly as a function of both the solid fraction and aggregate size. Increased fluid shear increased the initial mixing and aggregation rates, but ultimately lead to a reduced final aggregate size due to increased aggregate breakage. Several other process variables were also studied, with the aggregate size increased with flocculant dosage and primary particle size, but reduced at higher solid fraction. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Monitoring a crystallization induced by compressed CO2 with Raman spectroscopy
Authors: Vega‐González Arlette , Marteau Philippe , Subra‐Paternault Pascale
Published: December 2005

The application of on‐line Raman spectroscopy for detecting and monitoring a CO2 antisolvent process (GAS) is explored for the first time. Griseofulvin precipitations were carried out in a batch vessel from an acetone liquor, in which the CO2 was introduced at specific rates. Changes of griseofulvin and acetone concentrations upon addition of CO2 were monitored through specific wavenumbers at different pressurization rates (0.10 and 0.45 MPa/min) and courses (continuous or stepwise introduction, final pressure of 10 or 4.8 MPa). The ratio between the solute and solvent signals allowed for accurately detecting the onset of crystallization, for monitoring the depletion of the solution in solute as a function of time, and for estimating the mass of precipitated solids during the crystallization course. Moreover, the Raman spectroscopy provided experimental evidence of the predicted scenario of a crystallization induced by supercritical fluid. © 2005 American Institute of Chemcial Engineers AIChE J, 2006
Expression and genetic variability of PCDH11Y, a gene specific to Homo sapiens and candidate for susceptibility to psychiatric disorders
Authors: Durand Christelle M. , Kappeler Caroline , Betancur Catalina , Delorme Richard , Quach Hélène , Goubran‐Botros Hany , Melke Jonas , Nygren Gudrun , Chabane Nadia , Bellivier Franck , Szoke Andrei , Schurhoff Franck , Rastam Maria , Anckarsäter Henrik , Gillberg Christopher , Leboyer Marion , Bourgeron Thomas
Published: December 2005

Synaptogenesis, the formation of functional synapses, is a crucial step for the development of the central nervous system. Among the genes involved in this process are cell adhesion molecules, such as protocadherins and neuroligins, which are essential factors for the identification of the appropriate partner cell and the formation of synapses. In this work, we studied the expression and the genetic variability of two closely related members of the protocadherin family PCDH11X/Y, located on the X and the Y chromosome, respectively. PCDH11Y is one of the rare genes specific to the hominoid lineage, being absent in other primates. Expression analysis indicated that transcripts of the PCDH11X/Y genes are mainly detected in the cortex of the human brain. Mutation screening of 30 individuals with autism identified two PCDH11Y polymorphic amino acid changes, F885V and K980N. These variations are in complete association, appeared during human evolution approximately 40,000 years ago and represent informative polymorphisms to study Y chromosome variability in populations. We studied the frequency of these variants in males with autism spectrum disorders (n = 110), attention deficit hyperactivity disorder (ADHD; n = 61), bipolar disorder (n = 61), obsessive‐compulsive disorder (n = 51), or schizophrenia (n = 61) and observed no significant differences when compared to ethnically‐matched control populations. These findings do not support the role of PCDH11Y, or more generally of a frequent specific Y chromosome, in the susceptibility to these neuropsychiatric disorders. © 2005 Wiley‐Liss, Inc.
Automated sequence screening of the entire dystrophin cdna in Duchenne dystrophy: Point mutation detection
Authors: Hamed Sherifa Ahmed , Hoffman Eric P.
Published: December 2005

This is the first report of direct sequencing of the complete 11 kb coding sequence of the dystrophin gene affording high sensitivity for all types of mutations of both coding sequence and splicing. Direct automated capillary gel sequence analysis of dystrophin reverse‐transcribed polymerase chain reaction (RT‐PCR) products was carried out in 15 Duchenne muscular dystrophy (DMD) patient muscle biopsies (170,000 bp sequenced). We identified mutations in 67% of patients tested (10/15); including premature stop codons (n = 5) and small deletions/duplications (n = 5). Mutation‐negative patients (n = 5) were also negative for promoter mutations. All were tested for the possibility of transcription abnormalities using quantitative multiplex fluorescence polymerase chain studies (QMF‐PCR), however, equal ratios of mRNA transcripts were identified at the 5′and 3′ regions, with mild reduction in overall quantity, suggesting that transcription abnormalities were less likely. We suggested that such patients might have a problem with the 3.5 kb 3′ UTR, polyA site or undetected stop codons. It is also possible that splicing defects could result in addition of intron sequence which could lead to preferential amplification of low level residual normal transcript skipping. © 2005 Wiley‐Liss, Inc.
Phylogenetic analysis of major African genotype (Af2) of JC virus: Implications for origin and dispersals of modern Africans
Authors: Takasaka Tomokazu , Kitamura Tadaichi , Sugimoto Chie , Guo Jing , Zheng Huai‐Ying , Yogo Yoshiaki
Published: December 2005

Both mtDNA and the Y chromosome have been used to investigate how modern humans dispersed within and out of Africa. This issue can also be studied using the JC virus (JCV) genotype, a novel marker with which to trace human migrations. Africa is mainly occupied by two genotypes of JCV, designated Af1 and Af2. Af1 is localized to central/western Africa, while Af2 is spread throughout Africa and in neighboring areas of Asia and Europe. It was recently suggested that Af1 represents the ancestral type of JCV, which agrees with the African origin of modern humans. To better understand the origin of modern Africans, we examined the phylogenetic relationships among Af2 isolates worldwide. A neighbor‐joining phylogenetic tree was constructed based on the complete JCV DNA sequences of 51 Af2 isolates from Africa and neighboring areas. According to the resultant tree, Af2 isolates diverged into two major clusters, designated Af2‐a and ‐b, with high bootstrap probabilities. Af2‐a contained isolates mainly from South Africa, while Af2‐b contained those from the other parts of Africa and neighboring regions of Asia and Europe. These findings suggest that Af2‐carrying Africans diverged into two groups, one carrying Af2‐a and the other carrying Af2‐b; and that the former moved to southern Africa, while the latter dispersed throughout Africa and to neighboring regions of Asia and Europe. The present findings are discussed with reference to relevant findings in genetic and linguistic studies. Am J Phys Anthropol, 2006. © 2005 Wiley‐Liss, Inc.
Who were the ancient Egyptians? Dental affinities among Neolithic through postdynastic peoples
Authors: Irish Joel D.
Published: December 2005

Qualitative and quantitative methods are employed to describe and compare up to 36 dental morphological variants in 15 Neolithic through Roman‐period Egyptian samples. Trait frequencies are determined, and phenetic affinities are calculated using the mean measure of divergence and Mahalanobis D2statistics for discrete traits; the most important traits in generating this intersample variation are identified with correspondence analysis. Assuming that the samples are representative of the populations from which they derive, and that phenetic similarity provides an estimate of genetic relatedness, these affinities are suggestive of overall population continuity. That is, other than a few outliers exhibiting extreme frequencies of nine influential traits, the dental samples appear to be largely homogenous and can be characterized as having morphologically simple, mass‐reduced teeth. These findings are contrasted with those resulting from previous skeletal and other studies, and are used to appraise the viability of five Egyptian peopling scenarios. Specifically, affinities among the 15 time‐successive samples suggest that: 1) there may be a connection between Neolithic and subsequent predynastic Egyptians, 2) predynastic Badarian and Naqada peoples may be closely related, 3) the dynastic period is likely an indigenous continuation of the Naqada culture, 4) there is support for overall biological uniformity through the dynastic period, and 5) this uniformity may continue into postdynastic times. Am J Phys Anthropol, 2006. © 2005 Wiley‐Liss, Inc.
Modeling and remodeling responses to normal loading in the human lower limb
Authors: Drapeau Michelle S.M. , Streeter Margaret A.
Published: December 2005

Limb bones are designed to be strong enough to support the body and yet be energetically conservative during locomotion. Bones of the distal segment, which are relatively costly to move, are often more slender than bones of the proximal segments, even though they must sustain proportionally greater loads. As a result, they are expected to experience a higher incidence of microdamage. With this constraint in mind, Lieberman and Crompton (1998 Principles of Animal Design, Cambridge: Cambridge University Press, p. 78–86) proposed that bones response to strain varies along the proximo‐distal axis of the limb. In order to avoid fatigue fractures due to the accumulation of microdamage, the distal segment, in comparison to the proximal segment, will have an increase in remodeling events to replace damaged bone. In this paper, we test the hypothesis of Lieberman and Crompton (1998) with respect to the human lower limb. With a sample of adult individuals, we compare tibiae and femora for mid‐diaphyseal cross‐sectional geometry and Haversian remodeling differences. Our results indicate that the human limb is not designed like that of quadrupedal cursorial animals. The tibia is not less resistant in bending and torsion, and does not remodel more than the femur. Our findings fail to support the hypothesis of Lieberman and Crompton (1998) and suggest, instead, that the human lower limb is not designed like a cursorial animal limb. In addition, our results support previous observations that remodeling is not uniform within the cross section of a bone, probably a reflection of different loading histories within the different regions of the cross section. Am J Phys Anthropol, 2006. © 2005 Wiley‐Liss, Inc.
Loud calling, spacing, and cohesiveness in a nocturnal primate, the Milne Edwards' sportive lemur (Lepilemur edwardsi)
Authors: Rasoloharijaona Solofonirina , Randrianambinina Blanchard , Braune Pia , Zimmermann Elke
Published: December 2005

Dispersed pair‐living primates provide a unique model for illuminating the evolution of mechanisms regulating spacing and cohesiveness in permanently cohesive groups. We present for the first time data on the spatiotemporal distribution and loud‐calling behavior of the Milne Edwards' sportive lemur, known to forage solitarily during the night, but to form stable male‐female sleeping groups during the day. Data include radio‐tracking observations of sleeping associations, and focal follows of pair partners during dispersal in the evenings and reunions in the mornings. Male‐female pairs forming stable sleeping associations during the day were pair‐bonded. They used sleeping sites and home ranges exclusively, and exchanged loud calls at potentially restricted resources during dispersal in the evenings and during reunion in the mornings. Direct agonistic conflicts between pairs and others were rare. The acoustic analysis of loud calls revealed nine major call types. They carry signatures for sex and pair identity, and provide the substrate for signaling and the potential for recognizing pair ownership. Thus, pairs use loud call exchanges as a vocal display for signaling territory ownership, thus limiting direct aggressive encounters between neighbors and strangers. Altogether, our findings provide the first empirical evidence for the hypothesis that loud calling has evolved as a key mechanism for regulating space use and cohesiveness in dispersed pair‐living primates. Am J Phys Anthropol, 2006. © 2005 Wiley‐Liss, Inc.
Early sexual maturity in male hamadryas baboons (Papio hamadryas hamadryas) and its reproductive implications
Authors: Zinner Dietmar , Krebs Ellen , Schrod Annette , Kaumanns Werner
Published: December 2005

We present data on sexual maturity in young hamadryas baboon males (Papio hamadryas hamadryas) and its reproductive consequences in a large captive baboon colony. Hamadryas baboons live in a multilevel social system, with one‐male units (OMUs) as the smallest social entity. Male leaders of OMUs are believed to monopolize matings within their OMUs; hence mating is believed to be polygynous and monandrous. In a captive colony of hamadryas baboons, we found evidence that young males less than 4 years old fathered at least 2.5% of 121 offspring born subsequent to vasectomy of all adult males, and males aged 4–5 years fathered at least 16.5% of the offspring. Additional evidence that these young males are able to sire offspring came from a morphological comparison of sperm from hamadryas males of different ages. The sperm of a 48‐month‐old hamadryas baboon were morphologically indistinguishable from viable sperm from adult males, whereas sperm from a 45‐month‐old male showed some aberrations. If successful copulations by adolescent males constitute a regular pattern even in free‐ranging hamadryas baboons, a hamadryas male's chances to reproduce would not be limited to his role as an OMU leader as previously assumed, and a male's reproductive career would consist of two phases: the adolescent phase, and the OMU leader male phase. Am J Phys Anthropol, 2006. © 2005 Wiley‐Liss, Inc.
Differential expression of protein phosphatase type 1 isotypes and nucleolin during cell cycle arrest
Authors: Morimoto Hiroyuki , Ozaki Akiko , Okamura Hirohiko , Yoshida Kaya , Amorim Bruna Rabelo , Tanaka Hiroaki , Kitamura Seiichiro , Haneji Tatsuji
Published: December 2005

In the present study, we examined the expression and cytolocalization of protein phosphatase type 1 (PP1) isoforms and nucleolin in human osteoblastic cell line MG63 cells at two boundaries in the cell cycle. We treated MG63 cells with hydroxyurea and nocodazole to arrest the cells at the G1/S and G2/M boundaries, respectively. As judged from the results of Western blot analysis, PP1 isoforms were expressed differently at each boundary of the cell cycle. Nucleolin was also shown to have a different expression pattern at each boundary. In the hydroxyurea‐treated cells, nucleolus‐like bodies were bigger in size and decreased in number compared with those in asynchronized cells. However, the subcellular localization of PP1s and nucleolin was not changed. Anti‐nucleolin antibody interacted with 110‐kDa and 95‐kDa proteins present in asynchronized cells and in the cells treated with hydroxyurea. Treatment of the cells with nocodazole decreased the level of the 95‐kDa form of nucleolin. In the nocodazole‐treated cells, it was impossible to distinguish the distribution of each protein. The phosphorylation status of nucleolin in the cell cycle arrested samples was examined by 2D–IEF–PAGE followed by Western blot analysis. In the case of asynchronized cells or hydroxyurea‐treated ones, nucleolin was located at a basic isoelectric point (dephosphorylated status); whereas in the G2/M arrest cells, the isoelectric point of nucleolin shifted to an acidic status, indicating that nucleolin was phosphorylated. The present results indicate that PP1 and nucleolin were differently expressed at G1/S and G2/M boundaries of the cell cycle and acted in a different fashion during cell‐cycle progression. Copyright © 2005 John Wiley & Sons, Ltd.
Large tube section is the key to successful coronary thrombus aspiration: Findings of a standardized bench test
Authors: Rioufol Gilles , Collin Bertrand , Vincent‐Martin Michel , Buffet Phillipe , Lorgis Luc , L'Huillier Isabelle , Zeller Marianne , Finet Gérard , Rochette Luc , Cottin Yves
Published: December 2005

Thrombus removal by aspiration is one of the adjunctive techniques used to avoid embolization during PCI for acute myocardial infarction. Numerous devices are now available, but little is known about the mechanical rationale used in comparing them. The aim of the present study was to determine parameters to obtain optimal thrombus aspiration (TA). Heparin‐ and antiplatelet‐free blood samples were aspirated into 3 mm diameter standardized glass tubes to create a 30 mm long thrombus. Thrombus formation took place at room temperature over a period of 6 or 12 hr. Various catheters were tested using a variable vacuum device: three with right‐angle distal tip (0.038″, 0.067″, and 0.070″) and one with a beveled distal (length of the beveled, 0.054″; inner diameter catheter, 0.040″). The single endpoint was complete thrombus aspiration. A total of 103 TAs were presented for the four catheters. For 6‐ or 12‐hr‐old thrombus for a given catheter, there was no significant difference in vacuum pressure required to succeed TA (P = 0.47). For 6‐ or 12‐hr‐old thrombus, the larger the contact area is, the lower the pressure needed to aspirate the thrombus. Moreover, a beveled distal tip length (0.054″) does not make it possible to succeed TA at a lower pressure. The main factor for successful TA for thrombi ≥ 6 hr is inner diameter and not immediate thrombus contact area. © 2005 Wiley‐Liss, Inc.
New technique to seal a long giant coronary aneurysm with PTFE‐covered stents: A case report
Authors: Orlic Dejan , Vitrella Giancarlo , Corvaja Nicola , Colombo Antonio
Published: December 2005

We report a case with a large aneurysm of right coronary artery (RCA) associated with coronary artery disease. The aneurysm was sealed with two PTFE‐covered stents using a sequential technique from proximal to distal to overcome the lack of long PTFE‐covered stents and existence of complex coronary anatomy. A bare metal stent was subsequently deployed to treat a lesion in the mid part of RCA. At 4‐month follow‐up, aneurysm was completely sealed and no restenosis occurred. Usage of sequential PTFE‐covered stents enables treatment of large coronary artery aneurysms. © 2005 Wiley‐Liss, Inc.
Technical considerations for closing secundum atrial septal defect in the small child with the HELEX septal occluder via transhepatic access
Authors: Javois Alexander J. , Van Bergen Andrew H. , Husayni Tarek S.
Published: December 2005

We describe closure of an atrial septal defect in a symptomatic 4.6 kg child with the HELEX Septal Occluder (W.L. Gore and Associates, Flagstaff, AZ) via transhepatic approach. Technical considerations are discussed. © 2005 Wiley‐Liss, Inc.
Estimates of stage‐specific survival are altered by changes in the 2002 American Joint Committee on Cancer staging system for melanoma
Authors: Ben‐Porat Leah , Panageas Katherine S. , Hanlon Christine , Patel Ami , Halpern Allan , Houghton Alan N. , Coit Daniel
Published: December 2005

BACKGROUND

The objectives of the current study were to examine how the estimated stage‐specific survival is altered in the 2002 American Joint Committee on Cancer (AJCC) melanoma staging system compared with the 1997 AJCC staging system and to contrast the predictive accuracy of the 2 staging systems.

METHODS

There were 5847 consecutive melanoma patients who presented to Memorial Sloan‐Kettering Cancer Center from 1996 to 2004 and who were entered prospectively into a data base. These patients were staged according to both the 1997 and 2002 AJCC staging criteria. Overall survival estimates were determined using the Kaplan–Meier method. The overall predictive accuracy of the two staging systems was compared using concordance estimation.

RESULTS

In total, 1035 patients were shifted to a lower stage in the 2002 staging system, whereas only 15 patients were upstaged. The number of patients with Stage I melanoma increased by 697 under the 2002 system (n = 2166 patients) compared with the 1997 system (n = 1463 patients). Because of the changes in 2002, the estimated 5‐year overall survival for patients with Stage II melanoma decreased considerably, from 79% (1997) to 64% (2002). With the initiation of subgroups in 2002, it became apparent that patients with Stage III melanoma were very heterogeneous in terms of their survival probabilities (5‐yr overall survival ranged from 70% in patients with Stage IIIA disease to 24% in patients with Stage IIIC disease). Furthermore, in the 2002 system, there was substantial prognostic overlap between Stage II and Stage III. Despite the increased complexity of the 2002 system, the 2 staging systems had similar concordance estimates: 58% for the 1997 staging system compared with 58% (ignoring the subgroups) and 59% (with subgroups) for the 2002 system.

CONCLUSIONS

Estimates of stage‐specific survival were altered substantially by the changes made in the 2002 AJCC staging system for melanoma, particularly for Stage II. Stage subgroups that were added in the 2002 system resulted in a large diversity of risk within Stage III. This must be taken into account to stratify patients properly for clinical trials. The increased complexity of the 2002 system did not improve its predictive ability over the simpler 1997 system, highlighting the importance of developing individualized risk‐prediction models. Cancer 2006. © 2005 American Cancer Society.
Phase II study of sphingosomal vincristine in patients with recurrent or refractory adult acute lymphocytic leukemia
Authors: Thomas Deborah A. , Sarris Andreas H. , Cortes Jorge , Faderl Stefan , O'Brien Susan , Giles Francis J. , Garcia‐Manero Guillermo , Rodriguez Maria A. , Cabanillas Fernando , Kantarjian Hagop
Published: December 2005

BACKGROUND

Outcomes with salvage therapy for patients with recurrent or refractory acute lymphocytic leukemia (ALL) are poor, with complete response (CR) rates reported to be 20–30% and a median survival ranging from 2–6 months. New agents are needed to reduce the recurrence rate after frontline chemotherapy. Vincristine is an important component of ALL therapy. In animal models, the encapsulation of vincristine into sphingomyelin liposomes or “sphingosomes” for injection (SV) has improved efficacy compared with conventional vincristine.

METHODS

A Phase II clinical trial of single‐agent SV given at a dose of 2.0 mg/m2every 2 weeks was conducted in patients with recurrent or refractory ALL. Approximately half of the 16 patients who received SV had a first CR duration of less than 1 year, 19% had failed standard induction chemotherapy, and 50% had Philadelphia chromosome‐positive disease. SV was the first salvage attempt in 69% of the patients.

RESULTS

The overall response rate in the 14 evaluable patients was 14% (1 CR and 1 partial response). Five patients (36%) had transient reductions in bone marrow leukemia infiltrate with subsequent regrowth of the leukemia between SV infusions. Toxicity with limited treatment (median number of doses was two; range, one to five doses) was minimal with expected peripheral neuropathy.

CONCLUSIONS

Further study of SV in patients with ALL is warranted. A Phase I‐II clinical trial of weekly SV with pulse dexamethasone currently is ongoing. Cancer 2006. © 2005 American Cancer Society.
The developing mouse thyroid: Embryonic vessel contacts and parenchymal growth pattern during specification, budding, migration, and lobulation
Authors: Fagman Henrik , Andersson Louise , Nilsson Mikael
Published: December 2005

Normal mouse thyroid development has been revised to identify critical morphogenetic events. The early thyroid primordium associates with the aortic sac endothelium at the time of specification and budding. The vascular contact is lost after the thyroid buds from the pharyngeal endoderm, but is resumed before the gland divides to form two lobes. Lateral expansion of parenchyma takes place along the course of the third pharyngeal arch arteries. Thyroid precursor cells expressing Titf1/Nkx2.1 do not proliferate until the migration stage, implicating that progenitors likely are recruited from outside the thyroid placode. Early lobulation involves engulfment of the entire ultimobranchial bodies by the growing midline thyroid. At the same time, proliferation of the ultimobranchial body epithelium is silenced preceding the differentiation of C cells. Before folliculogenesis, thyroid lobe enlargement is reminiscent of a budding‐branching‐like growth pattern. It is suggested that thyroid inductive signals arise from embryonic vessels, and that this provides ideas to conceptually new pathogenetic mechanisms of thyroid dysgenesis. Developmental Dynamics 235:444–455, 2006. © 2005 Wiley‐Liss, Inc.
Glycerol as Ligand: The Synthesis, Crystal Structure, and Properties of Compounds [Ln2(H2L)2(H3L)4][Re6Q8(CN)6], Ln = La, Nd, Gd, Q = S, Se
Authors: Naumov Nikolai G. , Tarasenko Maria S. , Virovets Alexander V. , Kim Youngmee , Kim Sung‐Jin , Fedorov Vladimir E.
Published: December 2005

The interaction of aqueous solutions of octahedral cluster anions [Re6Q8(CN)6]4– with rare earth cations in the presence of glycerol resulted in the formation of a new family of compounds [Ln2(H2L)2(H3L)4][Re6Q8(CN)6] (where Ln = La, Nd, and Gd; Q = S, Se; H3L = glycerol; H2L– = glycerolate anion). All compounds are isostructural and crystallize in the P$\bar {1}$ space group. Crystal structures are built from octahedral cluster anions [Re6Q8(CN)6]4– and centrosymmetrical dimers [Ln2(H2L)2(H3L)4]4+ that have three different binding modes of glycerol. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
N‐Methylation Effects on the Coordination Chemistry of Cyclic Triamines with Divalent Transition Metals and Their CoII Dioxygen Carriers
Authors: Del Piero Silvia , Melchior Andrea , Polese Pierluigi , Portanova Roberto , Tolazzi Marilena
Published: December 2005

The thermodynamics of complex formation of CoII and CdII ions with the triaza macrocyclic ligand 1,4,7‐triazacyclononane (tacn) and its N‐methylated derivative 1,4,7‐trimethyl‐1,4,7‐triazacyclononane (Me3tacn) has been studied in dimethyl sulfoxide (DMSO) at 298.1 K and in an ionic medium (0.1 M Et4NClO4) by means of potentiometric, UV/Vis, calorimetric and FT‐IR techniques. The results are discussed by taking into account electronic and steric effects as well as solvation of the species concerned. Computational methods based on density functional theory (DFT) have been used to obtain structural information about the ligands and their complexes in order to provide further, independent insights into the effect of N‐methylation on the coordination affinity of the ligands towards the metal ions. The computational suggestions are of great help to correlate steric effects and thermodynamic results. The kinetics of dioxygen uptake for the formation of the Co(tacn)2O2 superoxo adduct has also been studied by means of UV/Vis measurements. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Synthesis and Functionalisation of 2,3‐Diheterocycle‐Substituted Aziridines
Authors: Troisi Luigino , Granito Catia , Carlucci Claudia , Bona Fabio , Florio Saverio
Published: December 2005

Polyfunctionalyzed aziridines each containing two heterocyclic moieties were prepared by Darzens reactions and the corresponding aziridinyl anions, generated by treatment with strong bases, were investigated. Coupling reaction with electrophiles allowed study of the configurational stability, highlighting the different stabilising effects of the heterocyclic substituents. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
From Berbines to Protopines: Regiocontrolled Hofmann Elimination/Hydroboration/Oxidation of N‐Substituted Berbinium Salts
Authors: Valpuesta María , Díaz Amelia , Suau Rafael , Torres Gregorio
Published: December 2005

An improved synthetic approach to protopines based on the sequential Hofmann elimination, hydroboration and oxidation of N‐(arylmethyl)berbinium salts has been designed. By using berberine chloride as the starting material, this sequence of reactions has provided two new nonnatural protopines, N‐benzyl‐N‐nordihydroallocriptopine and N‐(p‐methoxybenzyl)‐N‐nordihydroallocriptopine and the natural allocriptopine. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
A Metathesis Approach for the Preparation of Polyhydroxylated Compounds as Head Groups in Surfactant Synthesis
Authors: Neimert‐Andersson Kristina , Somfai Peter
Published: December 2005

Starting from methyl‐α‐D‐glucopyranoside, an efficient protocol for the preparation of polyhydroxylated surfactant head‐groups is demonstrated and applied in the synthesis of a typical surfactant. The key transformation is a metathesis reaction between two monosaccharide residues to afford an octahydroxydecen. The importance of a strategic protecting‐group constellation for a successful metathesis reaction is also investigated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Dimension Changes in a Chemomechanical Polymer Containing Ethylenediamine and Alkyl Functions as Selective Recognition Units
Authors: Schneider Hans‐Jörg , Tianjun Liu , Lomadze Nino
Published: December 2005

Treatment of polymethyl methacrylate with dodecylamine and diethylenetriamine produces a chemomechanical polymer, which undergoes large macroscopic motions as a result of selective recognition of substrates (effectors) in the surrounding aqueous solution. The kinetics of these fully reversible expansions and contractions are compared to those of effector absorption and desorption. The expansion correlates with a polymer particle weight increase, which is in turn found to be largely a function of the uptake of water necessary for solvation of the effector molecules. The selectivity of the motions depends on the nature and placement of the effector ionic sites, and also on the size and nature of the organic residues. Ion pairing between the protonated amine functions and inorganic anions or anionic groups of organic effectors plays a decisive role. The large effects seen with aromatic effectors such as nucleotides, in contrast with saturated analogues, point to cation–π and C–H–π interactions as essential elements for the distinction between different effectors, including isomeric compounds. The material exhibits symmetric expansion/pH profiles, which depend distinctly on the ionic strength of the solution. The strong dependence of the motions not only on the applied pH, but also on the concentrations of two simultaneously active effectors, such as AMP and phosphate, present chemically induced logical gate functions; this is tentatively explained by a two‐site binding model. In contrast, the large expansions produced by simultaneous action of, for example, copper or zinc and amino acids or peptides are due to co‐complexation between the metal ions and known organic chelators. With such ternary complexes, volume expansions by factors of up to 15 are possible with effector concentrations as low as 0.25 mM. The sensitivity can be further increased by miniaturization of the polymer particles; the velocity of the response can be optimized by increasing the surface‐to‐volume ratio. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
cycloSal Phosphates as Chemical Trojan Horses for Intracellular Nucleotide and Glycosylmonophosphate Delivery — Chemistry Meets Biology
Authors: Meier Chris
Published: December 2005

Pronucleotides represent a promising alternative to improve the biological activity of nucleoside analogs in antiviral and cancer chemotherapy. In addition, pronucleotides are valuable tools for studies regarding the nucleoside/nucleotide metabolism. The aim is to achieve nucleotide delivery into cells and thereby bypass limitations during intracellular formation of nucleotides from their nucleoside precursors. ThecycloSal approach is one of several conceptually different pronucleotide systems known but is the only approach in which a pronucleotide is cleaved successfully by simple but selective chemical hydrolysis. The basic concept, chemistry, different structural modifications, and their effects on the antiviral potency of thecycloSal d4TMP triesters are briefly discussed first. Then, the application of the approach to various biologically active nucleoside analogs against different targets is summarized. In the second part, the results of a conceptual extension of thecycloSal approach are presented: oncecycloSal pronucleotides have passed the membrane, they should be trapped inside the cells after an enzyme‐catalyzed process and then release the nucleotide. Finally, results are summarized that demonstrate that thecycloSal approach is not restricted to the delivery of bioactive nucleotides but is also applicable to the intracellular delivery of hexose‐1‐phosphates. Chemical synthesis, biophysical studies, and biological evaluation will be discussed in combination throughout this paper to demonstrate the strength of thecycloSal approach. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Oxidation of Alcohols and vic‐Diols with H2O2 by Using Catalytic Amounts of N‐Methylpyrrolidin‐2‐one Hydrotribromide
Authors: Joseph Jomy K. , Jain Suman L. , Sain Bir
Published: December 2005

A variety of secondary alcohols, 1,2‐diols and primary alcohols were selectively oxidized in excellent yields to their corresponding ketones, 1,2‐diketones and aldehydes with aqueous 30 % hydrogen peroxide in refluxing acetonitrile in the presence of catalytic amounts of N‐methylpyrrolidin‐2‐one hydrotribromide (MPHT). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
2‐Methoxy‐2,4‐diphenyl‐3(2H)‐furanone‐labeled gelatin zymography and reverse zymography: A rapid real‐time method for quantification of matrix metalloproteinases‐2 and ‐9 and tissue inhibitors of metalloproteinases
Authors: Min Danqing , Lyons James Guy , Jia Junhong , Lo Lisa , McLennan Susan V.
Published: December 2005

Measurement of matrix metalloproteinases (MMPs) and their specific tissue inhibitors of metalloproteinases (TIMPs) by the techniques of zymography and reverse zymography provide useful information regarding the status of matrix accumulation or breakdown. This report describes the use of 2‐methoxy‐2,4‐diphenyl‐3(2H)‐furanone (MDPF), a fluorescent compound which can be used to label gelatin as a substrate for detection of the gelatin degrading MMP‐2 and ‐9 by zymography. In addition, a modification of the zymographic technique by addition of excess MMPs enables the use of the MDPF‐labeled gelatin substrate for the identification and quantification of TIMPs by reverse zymography. Both systems are real‐time sensitive reliable quantification techniques, easily used for measurement of these MMPs and TIMPs in clinical, biological, and tissue culture samples.
Separation performance of single‐stranded DNA electrophoresis in photopolymerized cross‐linked polyacrylamide gels
Authors: Lo Roger C. , Ugaz Victor M.
Published: December 2005

Considerable effort has been directed toward optimizing performance and maximizing throughput in ssDNA electrophoresis because it is a critical analytical step in a variety of genomic assays. Ultimately, it would be desirable to quantitatively determine the achievable level of separation resolution directly from measurements of fundamental physical properties associated with the gel matrix rather than by the trial and error process often employed. Unfortunately, this predictive capability is currently lacking, due in large part to the need for a more detailed understanding of the fundamental parameters governing separation performance (mobility, diffusion, and dispersion). We seek to address this issue by systematically characterizing electrophoretic mobility, diffusion, and dispersion behavior of ssDNA fragments in the 70–1000 base range in a photopolymerized cross‐linked polyacrylamide matrix using a slab gel DNA sequencer. Data are collected for gel concentrations of 6, 9, and 12%T at electric fields ranging from 15 to 40 V/cm, and resolution predictions are compared with corresponding experimentally measured values. The data exhibit a transition from behavior consistent with the Ogston model for small fragments to behavior in agreement with the biased reptation model at larger fragment sizes. Mobility data are also used to estimate the mean gel pore size and compare the predictions of several models.
Nitric oxide, adenosine deaminase, xanthine oxidase and superoxide dismutase in patients with panic disorder: alterations by antidepressant treatment
Authors: Herken Hasan , Akyol Omer , Yilmaz H. Ramazan , Tutkun Hamdi , Savas Haluk A. , Ozen M. Eren , Kalenderoglu Aysun , Gulec Mukaddes
Published: December 2005

Objective

In the present study, we aimed to investigate whether nitric oxide (NO) levels and activities of xanthine oxidase (XO), superoxide dismutase (SOD), and adenosine deaminase (ADA) are associated with Panic disorder (PD) as well as impact of psychopharmacological treatments on NO, SOD, ADA, and XO levels in PD.

Method

In this study, 32 patients and 20 healthy controls were included. The serum levels of NO, XO, SOD, and ADA were measured in the patients and controls. The patients were treated with antidepressant.

Results

ADA and XO levels of the patients were significantly higher than the controls. SOD levels of the patients were significantly lower than the controls but the difference was not statistically significant. Although NO levels of the patients were higher than the controls, the difference was not statistically significant. There was no correlation between PAS and the parameters studied (SOD, ADA, XO, and NO) of the patients. After 8 weeks of antidepressant treatment, ADA and SOD activities were increased whereas NO and XO levels decreased significantly.

Conclusion

ADA, XO activity may have a pathophysiological role in PD, and prognosis of PD. Activity of these enzymes may be used to monitor effects of the antidepressant treatment. Copyright © 2005 John Wiley & Sons, Ltd.
Superiority of a cognitive education with photographs over ABCD criteria in the education of the general population to the early detection of melanoma: A randomized study
Authors: Girardi Sophie , Gaudy Caroline , Gouvernet Joanny , Teston Jacques , Richard Marie Aleth , Grob Jean‐Jacques
Published: December 2005

Most education campaigns for melanoma (MM) detection in the general population have used the “ABCD” algorithm, although recognition of objects in the real life is based on a holistic image recognition rather than on analytic criteria. The objective was to compare analytic (ABCD) and cognitive (photographs) strategies for teaching self‐recognition of MM. A prospective 4‐arm stratified randomized trial in 255 individuals compared 3 realistic educative interventions by leaflets: 1) ABCD algorithm (“ABCD”), 2) a set of photographs chosen to stimulate recognition of MM among benign pigmented lesions (“Cog”), 3) photographs + explanations (“Cog‐Ex” arm) and 4) no intervention (“NI”). A 40‐slides test was performed before intervention (T0), 1 week after (T1) and after induction of anxiety (T2). In the “ABCD” arm, sensitivity slightly improved (80 to 83.8%, p = 0.04), but specificity dropped from 65.1 to 56.3% (p < 0.001), with no benefit in accuracy as compared to “NI”. In “Cog”arm, there was no change in sensitivity, but a strong increase in specificity (65.9 to 81.1%, p < 0.001) and accuracy (42.1 to 53.1%, p < 0.001). “Cog‐ex” resulted in similar although lower benefit. Under stress (T2), there was a dramatic loss of specificity and accuracy in “ABCD”arm (65.1 to 44.1%, p < 0.001 and 40.8% to 35.8%, p ≤ 0.001) without higher gain in sensitivity, while sensitivity and accuracy increased (p < 0.005) after “Cog” leaflet, without decreasing specificity. Finally, the “ABCD” message alone does not seem efficacious and is even worse in the context of anxiety, whereas a quick look at a few photographs is sufficient to improve the ability of the laymen to recognize a MM just by optimizing their spontaneous image recognition capacities. Education by photographs is a realistic strategy which should replace or complete “ABCD” message in the campaigns for self‐detection of MM. © 2005 Wiley‐Liss, Inc.
Chemokine receptors in head and neck cancer: Association with metastatic spread and regulation during chemotherapy
Authors: Muller Anja , Sonkoly Eniko , Eulert Christine , Gerber Peter Arne , Kubitza Robert , Schirlau Kerstin , Franken‐Kunkel Petra , Poremba Christopher , Snyderman Carl , Klotz Lars‐Oliver , Ruzicka Thomas , Bier Henning , Zlotnik Albert , Whiteside Theresa L. , Homey Bernhard , Hoffmann Thomas K.
Published: December 2005

Head and neck carcinomas are histologically and clinically heterogeneous. While squamous cell carcinomas (SCC) are characterized by lymphogenous spread, adenoid cystic carcinomas (ACC) disseminate preferentially hematogenously. To study cellular and molecular mechanisms of organ‐specific metastasis, we used SCC and ACC cell lines and tumor tissues, obtained from patients with primary or metastatic disease. Comprehensive analysis at the mRNA and protein level of human chemokine receptors showed that SCC and ACC cells exhibited distinct and nonrandom expression profiles for these receptors. SCC predominantly expressed receptors for chemokines homeostatically expressed in lymph nodes, including CC chemokine receptor (CCR) 7 and CXC chemokine receptor (CXCR)5. No difference in expression of chemokine receptors was seen in primary SCC and corresponding lymph node metastases. In contrast to SCC, ACC cells primarily expressed CXCR4. In chemotaxis assays, ACC cells were responsive to CXCL12, the ligand for CXCR4. Exposure of ACC cells to cisplatin resulted in upregulation of CXCR4 on the cell surface, which was repressed by the transcriptional inhibitor, α‐amanitin. Treatment of ACC cells with CXCL12 resulted in the activation of Akt and ERK1/2 pathways. Furthermore, CXCL12 suppressed the rate of apoptosis induced by cisplatin in ACC cells, suggesting that signaling via CXCR4 may be part of a tumor cell survival program. Discrimination of the chemokine receptor profile in SCC and ACC in vitro and in tissues provided insights into their distinct biologic and clinical characteristics as well as indications that chemokine receptors might serve as future therapeutic targets in these malignancies. © 2005 Wiley‐Liss, Inc.
In vivo antitumor effect of the mTOR inhibitor CCI‐779 and gemcitabine in xenograft models of human pancreatic cancer
Authors: Ito Daisuke , Fujimoto Koji , Mori Tomohiko , Kami Kazuhiro , Koizumi Masayuki , Toyoda Eiji , Kawaguchi Yoshiya , Doi Ryuichiro
Published: December 2005

Mammalian target of rapamycin (mTOR) is considered to be a major effector of cell growth and proliferation that controls protein synthesis through a large number of downstream targets. We investigated the expression of the phosphatidylinositol 3′‐kinase (PI3K)/mTOR signaling pathway in human pancreatic cancer cells and tissues, and the in vivo antitumor effects of the mTOR inhibitor CCI‐779 with/without gemcitabine in xenograft models of human pancreatic cancer. We found that the Akt, mTOR and p70 S6 kinase (S6K1) from the PI3K/mTOR signaling pathway were activated in all of the pancreatic cancer cell lines examined. When surgically resected tissue specimens of pancreatic ductal adenocarcinoma were examined, phosphorylation of Akt, mTOR and S6K1 was detected in 50, 55 and 65% of the specimens, respectively. Although CCI‐779 had no additive or synergistic antiproliferative effect when combined with gemcitabine in vitro, it showed significant antitumor activity in the AsPC‐1 subcutaneous xenograft model as both a single agent and in combination with gemictabine. Furthermore, in the Suit‐2 peritoneal dissemination xenograft model, the combination of these 2 drugs achieved significantly better survival when compared with CCI‐779 or gemcitabine alone. These results demonstrate promising activity of the mTOR inhibitor CCI‐779 against human pancreatic cancer, and suggest that the inhibition of mTOR signaling can be exploited as a potentially tumor‐selective therapeutic strategy. © 2005 Wiley‐Liss, Inc.
Silencing of APAF‐1 in B‐CLL results in poor prognosis in the case of concomitant p53 mutation
Authors: Sturm Isrid , Bosanquet Andrew G. , Radetzki Silke , Hummel Michael , Dörken Bernd , Daniel Peter T.
Published: December 2005

Apoptosis protease‐activating factor 1 (APAF‐1), a transcriptional target of p53, is a cytosolic adaptor protein that links the mitochondrial apoptosis pathway to the caspase cascade. Here, we aimed to study the impact of APAF‐1 expression levels on cell death induced by anticancer drugs or ionizing irradiation (IR) and disease prognosis in B‐type chronic lymphocytic leukemia (B‐CLL) patients. Samples from 138 patients with B‐CLL were investigated for APAF‐1 expression and p53 mutations. The results were related to survival data, in vitro cytotoxicity of various cytotoxic drugs and IR and clinico‐pathological data. Variable APAF‐1 expression was observed in all investigated B‐CLL samples. Reduction in APAF‐1 expression was observed at both mRNA and protein level indicating transcriptional silencing whereas mutation of p53 or the immunoglobulin heavy chain variable genes (IgHV) had no impact on APAF‐1 expression. Surprisingly, APAF‐1 loss did not result in resistance to cytotoxic therapies. Likewise, APAF‐1 downregulation on its own showed no impact on disease prognosis. Nevertheless, a poor prognosis was observed in patients with loss of APAF‐1 expression and additional p53 mutation. Thus, loss of APAF‐1 may become relevant when additional core apoptosis signaling components are disrupted. © 2005 Wiley‐Liss, Inc.
Tissue microarrays for comparing molecular features with proliferation activity in breast cancer
Authors: Ruiz Christian , Seibt Silvia , Kuraya Khawla Al , Siraj Abdul K , Mirlacher Martina , Schraml Peter , Maurer Robert , Spichtin Hanspeter , Torhorst Joachim , Popovska Savelina , Simon Ronald , Sauter Guido
Published: December 2005

Tissue microarrays (TMAs) are potentially suited to find associations between molecular features and clinical outcome. Enhanced cell proliferation, as measured by Ki67 immunohistochemistry, is related to poor patient prognosis in many different tumor types. Ki67 expression shows considerable intratumoral heterogeneity. It is unclear if the TMA format is suitable for the analysis of potentially heterogeneous markers because of the small size of TMA spots. We have analyzed a breast cancer TMA containing 2,517 breast tissues, including 2,222 neoplastic and 295 normal or premalignant samples, for Ki67 labeling index (Ki67 LI) and additional markers with a known relationship to Ki67 LI by immunohistochemistry (ER, PR, Bcl‐2, Egfr, p16, p53) and Fluorescence in situ hybridization (HER2, MDM2, CCND1, MYC). A high Ki67 LI was linked to tumor phenotype including grade (p < 0.0001), stage (p < 0.0001), nodal stage (p = 0.0018), and patient prognosis (p < 0.0001), elevated protein levels of p53, p16 and Egfr, reduced levels of Bcl2, ER, and PR (p < 0.0001 each), as well as amplifications of HER2, MYC, CCND1 and MDM2 (p < 0.0001 each). In summary, all expected associations between Ki67 and the analyzed molecular markers could be reproduced with high statistical significance using a TMA containing only one tissue sample per tumor, measuring 0.6 mm in diameter. We conclude that associations with cell proliferation can be reliably analyzed in a TMA format. © 2005 Wiley‐Liss, Inc.