bluuebunny/crossref_metadata_2025 huggingface dataset:
Bounded solutions of nonlinear Cauchy problems
Authors: Kreulich Josef
Published: December 2002

For a given closed and translation invariant subspace Y
of the bounded and uniformly continuous functions, we will give criteria for the existence of solutions u ∈ Y
to the equation u′(t) + A(u(t)) + ωu(t)∍f(t), t ∈ ℝ, or of solutions u asymptotically close to Y for the inhomogeneous differential equation u′(t) + A(u(t)) + ωu(t)∍f(t), t > 0, u(0) = u0, in general Banach spaces, where A
denotes a possibly nonlinear accretive generator of a semigroup. Particular examples for the space Y
are spaces of functions with various almost periodicity
properties and more general types of asymptotic behavior.
Association study between CAG trinucleotide repeats in the PCQAP gene (PC2 glutamine/Q‐rich‐associated protein) and schizophrenia
Authors: De Luca Alessandro , Conti Emanuela , Grifone Nicoletta , Amati Francesca , Spalletta Gianfranco , Caltagirone Carlo , Bonaviri Giuseppina , Pasini Augusto , Gennarelli Massimo , Stefano Bignotti , Berti Lucia , Mittler Gerhard , Meisterernst Michael , Dallapiccola Bruno , Novelli Giuseppe
Published: December 2002

Schizophrenia or schizoaffective disorders are quite common features in patients with DiGeorge/velocardiofacial syndrome (DGS/VCFS) as a result of hemizygosity of chromosome 22q11.2. We evaluated the PCQAP gene, which maps within the DGS/VCFS interval, as a potential candidate for schizophrenia susceptibility. PCQAP encodes for a subunit of the large multiprotein complex PC2, which exhibits a coactivator function in RNA polymerase II mediated transcription. Using a case–control study, we searched association between schizophrenia and the intragenic coding trinucleotide polymorphism. The distribution of the CAG repeat alleles was significantly different between patients and controls with the Mann‐Whitney test (z = −2.5694, P = 0.0051; schizophrenics: n = 378, W = 161,002.5, Mean rank = 425.9325; controls: n = 444, W = 177,250.5, Mean rank = 399.2128). This result may indicate a possible involvement of the multiprotein complex PC2 in schizophrenia susceptibility. © 2003 Wiley‐Liss, Inc.
Association between the dopamine receptor D4 (DRD4) gene and obsessive‐compulsive disorder
Authors: Millet Bruno , Chabane Nadia , Delorme Richard , Leboyer Marion , Leroy Sophie , Poirier Marie‐France , Bourdel Marie‐Chantal , Mouren‐Simeoni Marie‐Christine , Rouillon Fréderic , Loo Henri , Krebs Marie‐Odile
Published: December 2002

Obsessive‐compulsive disorder (OCD) is a frequent and disabling anxiety disorder. Dopamine (DA) might be involved in its pathophysiology, therefore DA receptors are candidate genes in OCD. A 48‐base pairs (bp) polymorphism located in the third exon of the dopamine receptor type 4 (DRD4) gene has been described. Previous case control studies, however, have reported inconclusive results in OCD. The aim of the study was to study this polymorphism in a family‐based association study of 55 trios. Extended transmission‐disequilibrium test (ETDT) for preferential allele transmission in this group showed an absence of transmission of the allele 2 for the 48 bp repeat polymorphism of the DRD4 gene (P = 0.005). Moreover, in a population‐based association study, we found a significantly lower frequency of the allele 2 in patients suffering from OCD compared to ethnically‐matched controls (P = 0.02). We found no association of DRD4 48 bp polymorphism with OCD in the subgroup of patients with comorbid tics. This study is the first to report on a significant association of variants of the DRD4 gene in OCD, found on both family‐ and population‐based studies. The results suggest that the 2 allele or a nearby genetic variation could have a protective effect against OCD symptoms. © 2003 Wiley‐Liss, Inc.
Early‐onset schizophrenia and dopamine‐related gene polymorphism
Authors: Iwata Yasuhide , Matsumoto Hideo , Minabe Yoshio , Osada Naoko , Nakamura Kazuhiko , Sekizawa Takahiro , Suzuki Katsuaki , Sekine Yoshimoto , Takei Nori , Mori Norio
Published: December 2002

Schizophrenic patients with an onset before age 16 years (early‐onset schizophrenia, EOS) would be a rare but attractive subpopulation for genetic studies. This study explored the relationship between the polymorphism of four dopamine‐regulating‐enzymes (tyrosine hydroxylase, dopamine‐β‐hydroxylase, catechol‐O‐methltransferase, monoamine oxidase‐A) genes, four dopamine‐receptors (dopamine D1, D2, D3, D4 receptors) genes and susceptibility to EOS in a Japanese sample. Subjects comprised 51 Japanese patients who met DSM‐IV criteria for schizophrenia with an onset before age 16 (by age 15) and 148 Japanese healthy controls. DNA was extracted from whole blood and genotyping was carried out by PCR‐RELP using each restriction endonuclease. No significant difference was found in the allele frequencies or genotype distributions of any of the eight genes examined between EOS and the control groups. We did not find the relationship between the polymorphism of eight dopamine‐related genes and susceptibility to EOS in a Japanese sample. © 2002 Wiley‐Liss, Inc.
Association study between the fibronectin gene and schizophrenia
Authors: Nakata Kenji , Ujike Hiroshi , Sakai Ayumu , Takaki Manabu , Imamura Takaki , Tanaka Yuji , Kuroda Shigetoshi
Published: December 2002

Fibronectin is one of the cell adhesion proteins. Adhesion molecules play an important role in neural and synaptic genesis, and their dysfunction may result in neurodevelopmental abnormalities, which have been assumed to be a factor in the pathogenesis of schizophrenia. To examine the possible involvement of fibronectin in the etiology of schizophrenia, we analyzed six polymorphisms, located in introns 2, 21, 24, and 26, and exons 20 and 28, in the human fibronectin gene (FN1) of schizophrenic patients in the Japanese population (n = 104) and age‐and gender‐matched controls (n = 104). No significant positive association was observed between either of the polymorphisms and schizophrenia, nor was an association found between either of the polymorphisms and any subtypes of schizophrenia. These data did not provide evidence for a contribution of the FN1 gene to susceptibility to schizophrenia. © 2002 Wiley‐Liss, Inc.
CAG repeat polymorphisms in KCNN3 (HSKCa3) and PPP2R2B show no association or linkage to schizophrenia
Authors: Laurent Claudine , Niehaus Dana , Bauché Stéphanie , Levinson Douglas F. , Soubigou Stéphane , Pimstone Simon , Hayden Michael , Mbanga Irena , Emsley Robin , Deleuze Jean‐François , Mallet Jacques
Published: December 2002

The purpose of this study was to determine whether genetic linkage or association could be observed between schizophrenia (SZ) and the CAG repeat polymorphisms within the genes KCNN3 (known previously as hSKCa3) and PPP2R2B (linked to Spino‐Cerebellar Atrophy 12) in the Xhosa population in South Africa. Neither locus has been studied previously in African populations. The polymorphisms were genotyped in 589 individuals to form samples for Transmission Disequilibrium Test (TDT) analysis (176 unrelated probands, 145 with both parents and 30 with one parent genotyped), linkage analysis (49 families with 54 independent affected sib pairs [ASPs]), and case‐control analyses (67 familial cases with a first‐degree SZ relative, 101 sporadic cases with no affected first‐ or second‐degree relative, and 90 control cases). No significant differences were found among familial cases, sporadic cases and controls in allele sizes (Kruskal‐Wallis tests) or the numbers of alleles with sizes above and below the mean size for each polymorphism. Allele size was not correlated with age of onset (Spearman correlation). No significant evidence for association was observed using TDT analyses for all triads and separately for the familial triads. No significant evidence for linkage was observed for either locus with affected sib pair analysis using the possible triangle method or with Non‐Parametric Linkage (NPL) analysis of the multiplex families. In conclusion, no significant evidence for linkage or association with SZ was observed for either polymorphism in this population. © 2002 Wiley‐Liss, Inc.
Hencky strain shifting of convergent flow measured effective elongational viscosity
Authors: Collier John R. , Petrovan Simioan , Patil Parag
Published: December 2002

The effective elongational viscosity data on a series of polyolefins as a function of the Hencky strain are shifted to a reference Hencky strain using an approach similar to that used for temperature shifting, shearing viscosity data. The basis of this shifting is the order that develops (i.e., the decrease in entropy that occurs) during forced flow through semihyperbolically convergent dies. The entropy decrease is proportional to the orientational contribution to the effective elongational viscosity. The Hencky strain shift factors are obtained from the convergent flow effective elongational rheology and the complex and capillary shear rheology. The commercial grades of polyolefins studied include polypropylene, high density polyethylene, and metallocene and conventionally catalyzed low density polyethylene. The combination of the temperature shift factors given in our companion article and the Hencky strain shift factors in this article enable the creation of master curves for the effective elongational rheology. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1397–1404, 2003
Effect of nano‐silica filler on the rheological and morphological properties of polypropylene/liquid‐crystalline polymer blends
Authors: Zhang L. , Tam K. C. , Gan L. H. , Yue C. Y. , Lam Y. C. , Hu X.
Published: December 2002

A fumed hydrophilic nano‐silica‐filled polypropylene (PP) composite was blended with a liquid‐crystalline polymer (LCP; Rodrun LC5000). The preblended polymer blend was extruded through a capillary die; this was followed by a series of rheological and morphological characterizations. The viscosity of the PP matrix increased with the addition of the hydrophilic nano‐silica. At shear rates between 50 and 200 s−1, the composite displays marked shear‐thinning characteristics. However, the incorporation of LC5000 in the PP composite eliminated the shear‐thinning characteristic, which suggests that LC5000 destroyed the agglomerated nano‐silica network in the PP matrix. Although the viscosity ratio of LCP/PP was reduced after the addition of nano‐silica fillers, the LCP phases existed as droplets and ellipsoids. The nano‐silicas were concentrated in the LC5000 phase, which hindered the formation of LCP fibers when processed at high shear deformation. We carried out surface modification of the hydrophilic nano‐silica to investigate the effect of modified nano‐silica (M‐silica) on the morphology of the PP/LC5000 blend system. Ethanol was successfully grafted onto the nano‐silica surface with a controlled grafting ratio. The viscosity was reduced for PP filled with ethanol‐M‐silica when compared to the system filled with untreated hydrophilic nano‐silica. The LC5000 in the (PP/M‐silica)/LC5000 blend existed mainly in the form of fibrils. At high shear rates (e.g., 3000 s−1), the LC5000 fibril network was formed at the skin region of the extrudates. The exclusion of nano‐silica in the LC5000 phase and the increased viscosity of the matrix were responsible for the morphological changes of the LCP phase. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1484–1492, 2003
Rice‐husk‐ash‐filled natural rubber. II. Partial replacement of commercial fillers and the effect on the vulcanization process
Authors: da Costa H. M. , Visconte L. L. Y. , Nunes R. C. R. , Furtado C. R. G.
Published: December 2002

In a previous investigation, we observed that in the presence of a conventional vulcanization system, the addition of white rice husk ash (WRHA) to natural rubber (NR) compounds increased the rate of crosslinking and lowered the apparent activation energy (Ea) of the vulcanization reaction more strongly than the other fillers used. In this work, commercial fillers, such as precipitated silica (Zeosil‐175) and carbon black (N762), were partially replaced by black rice husk ash and WRHA. Cure studies were carried out on a TI‐100 curometer at 150, 160, 170, and 180°C, and the overall rates and the Ea's for the vulcanization process were calculated for each compound, with the assumption that vulcanization followed first‐order kinetics. Again, WRHA showed some catalytic effect on the NR vulcanization. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1405–1413, 2003
Crosslinked acrylic pressure‐sensitive adhesives. I. Effect of the crosslinking reaction on the peel strength
Authors: Asahara Junko , Hori Naruhito , Takemura Akio , Ono Hirokuni
Published: December 2002

For pressure‐sensitive adhesives (PSAs) composed of poly(co‐ethyl acrylate‐2‐ethylhexyl acrylate‐2‐hydroxyethyl methacrylate) as a base resin and polyisocyanate as a crosslinker, the relationship between the crosslinking reaction and peel strength was investigated. A 90° peel test of cured PSA films under various storage conditions was carried out. At the same time, the isocyanate (NCO) consumption in these PSA films was monitored by attenuated total reflectance/Fourier transform infrared spectroscopy. The peel strength of the PSA compounded with the crosslinker decreased as the NCO groups were consumed. The elevation of the aging temperature promoted the crosslinking reaction and increased the decrement in the peel strength. The peel strength of noncrosslinked and crosslinked PSA films increased with the contact time. A high storage temperature made the increment in the peel strength increase. The addition of the crosslinker to the PSA films reduced the increment in the peel strength. Furthermore, PSA films with residual NCO groups possessed stronger peel strengths than fully cured films. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1493–1499, 2003
Rheological properties of calcium silicate‐filled isotactic polypropylene
Authors: Maiti S. N. , Singh Gurunam , Nordin Ibrahim Mohd.
Published: December 2002

The melt rheological behavior of calcium silicate‐filled isotactic polypropylene, with filler volume contents of 0–17.8%, was determined at 493 K. The composites followed the power law in shear stress versus shear rate variations and were shear thinning. Initially, apparent melt viscosity decreased until a critical filler volume content of 8.5% was reached. However, on further increase in calcium silicate concentration, apparent melt viscosity increased. Melt elasticity also showed an initial decrease until 8.5% filler content was reached and then an increase beyond this filler content. Surface treatment of calcium silicate with a titanate coupling agent, LICA 38, modified the rheological properties because of the plasticizing/lubricating effect of LICA 38. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1511–1518, 2003
Effect of iodine absorption on the characteristics of syndiotacticity‐rich high molecular weight poly(vinyl alcohol) microfibril
Authors: Ghim Han Do , Kim Jae Pil , Kwon Ick Chan , Lee Chul Joo , Lee Jinwon , Kim Sam Soo , Lee Sung Min , Yoon Won Sik , Lyoo Won Seok
Published: December 2002

Iodination of syndiotacticity‐rich high molecular weight poly(vinyl alcohol) (PVA) microfibril, which was obtained from the saponification of poly(vinyl pivalate) without a spinning procedure, was conducted before and after zone drawing at various conditions. The resulting PVA microfibrils were characterized by differential scanning calorimetry and scanning electron microscopy. Surface morphologies of these PVA microfibrils showed some differences between PVA microfibrils iodinated after and before drawing. Crude shapes of PVA microfibrils iodinated after drawing indicated that iodine decreased the structural regularity severely. On the other hand, PVA microfibrils iodinated before drawing showed relatively ordered surfaces. This was ascribed to the enhanced molecular ordering of PVA microfibrils due to zone drawing. Iodinated PVA microfibrils showed a decrease in the crystal melting temperature of about 100°C compared to the untreated sample. PVA microfibrils drawn after iodination showed a relatively higher crystal melting temperature than those of microfibrils iodinated after drawing. These results were considered as proof of the changes in the crystalline lattice of the PVA microfibrils by iodine absorption. Effects of the drawing temperature on the sublimation of iodine were also evaluated. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1519–1524, 2003
Polymerization of liquid propylene with a fourth‐generation Ziegler–Natta catalyst: Influence of temperature, hydrogen, monomer concentration, and prepolymerization method on powder morphology
Authors: Pater Jochem T. M. , Weickert Günter , Swaaij Wim P. M. Van
Published: December 2002

Liquid propylene was polymerized in a 5‐L autoclave batch reactor using a commercially available TiCl4/MgCl2/Al(ethyl)3/DCPDMS Ziegler–Natta catalyst, with a phthalate ester as internal electron donor. The powders from these polymerizations were characterized using laser diffraction particle size distribution (PSD) analysis, scanning electron microscopy (SEM), and bulk density measurements. These characteristics were analyzed as a function of the process conditions, including hydrogen and monomer concentration, polymerization temperature, and the prepolymerization method. It was shown that polymerization temperature influences the powder morphology to a large extent. At low temperatures, high‐density particles were obtained, showing regular shaped particle surfaces and low porosities. With increasing temperature, the morphology gradually was transferred into a more open structure, with irregular surfaces and poor replication of the shape of the catalyst particle. When using a prepolymerization step at a relatively low temperature, the morphology obtained was determined by this prepolymerization step and was independent from conditions in main polymerization. The morphology obtained was the same as that observed after a full polymerization at temperature. Even when using a short polymerization at an increasing temperature, the morphology was strongly influenced by the initial conditions. The effect of variation in hydrogen concentration supported the conclusion that the initial polymerization rate determines the powder morphology. In the absence of hydrogen, high bulk densities, and regularly shaped particles were obtained, even at high temperatures. With increasing hydrogen concentration, the reaction rates increased rapidly, and with that changed the morphology. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1421–1435, 2003
Relation of swelling and Tg depression to the apparent free volume of a particle‐filled, epoxy‐based adhesive
Authors: Chiang Martin Y. M. , Fernandez‐Garcia Marta
Published: December 2002

The effect of hygrothermal aging on a particle‐filled, epoxy‐based adhesive was studied using a gravimetric sorption technique. This study has explored moisture sorption characteristics as well as the associated behaviors of swelling and the depression of the glass transition temperature (Tg). We observed that the diffusion of water in this adhesive has a non‐Fickian behavior, and the depression of Tg proceeds to a definite value that is independent of the final equilibrium water content of the system. Our observations suggest that water diffuses into the polymer in a dual‐sorption mode, in which water resides in two populations. In one population, water is considered to occupy apparent free volume of the adhesive, and the second population water infiltrates polymer structure and forms hydrogen‐bonded clusters. Our results show that hygrothermal aging temperature and swelling do not alter the apparent free volume of this adhesive. We conclude that the constant value of Tg depression at saturation implies that only water in the apparent free volume is responsible for the Tg depression, whereas the swelling proceeds through the formation of hydrogen bonds in the adhesive. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1436–1444, 2003
Network crown ether resin with pendent sulfur ether group: Preparation, thermodegradation, and adsorption behavior
Authors: Meng Ling‐Zhi , Gong Shu‐Ling , Yin Yi‐Hua , Chen Yuan‐Yin , Wang You‐Wei
Published: December 2002

Network crown ether resin with the pendent sulfur ether group was prepared by ring‐opening copolymerization of 3‐thiopentyl glycidyl ether and diethylene glycol bisglycidyl ether with Na, NaOCH2CH2OCH2CH2OH, or BuLi as catalyst, respectively. The yield of network polymer and the conversion of functional monoepoxy monomer are varied from catalyst to catalyst, and the thermostability of the resin is related to the content of the sulfur ether group. The resins show high adsorption capacity toward Cu(II), Pb(II), especially, Hg(II) ions, but poor adsorption capacity toward Mg(II) ions. Corresponding thermodynamic parameter of Hg(II) ion was deduced, and could be expressed approximately with the Freundlich equation. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1445–1451, 2003
Shrinkage behavior after the heat setting of biaxially stretched poly(ethylene 2,6‐naphthalate) films and bottles
Authors: Schoukens Gustaaf , Samyn Pieter , Maddens Sara , Van Audenaerde Timothy
Published: December 2002

Amorphous preforms of poly(ethylene 2,6‐naphthalate) (PEN) were biaxially drawn into bottles up to the desired volume under industrial conditions. These bottles were used to characterize the shrinkage behavior of the drawn bottles with or without heat treatment and to study structural variations during heat setting. During drawing, a rigid phase structure was induced, and the amount of the induced rigid phase structure was linearly related to the square root of the extra first strain invariant under equilibrium conditions. During the production of these bottles, this equilibrium was not attained because of high stretching conditions and rapid cooling after stretching. The structure after orientation contained a rigid amorphous phase and an oriented amorphous phase. The shrinkage behavior was a function of the temperature and time of heat setting. Long heat‐setting times, around 30 min, were used to characterize the possible structural variations of the oriented PEN after heat setting at equilibrium. Under the equilibrium conditions of heat setting, the start temperature of the shrinkage was directly related to the heat‐setting temperature and moved from 60°C without heat treatment up to a temperature of 255°C by a heat‐setting temperature of 255°C; this contrasted with poly(ethylene terephthalate) (PET), for which the start temperature of shrinkage was always around 80°C. For heat‐setting temperatures higher than 220°C, the structural variations changed rapidly as a function of the heat‐setting time, and the corresponding shrinkage of the heat‐set samples sank below 1% in a timescale of 30–60 s for a film thickness of 500 μm. The heat treatment of the oriented films taken out of the bottle walls with fixed ends stabilized the induced structures, and the shrinkage of these heat‐set films was zero for temperatures up to the heat‐setting temperature, between 220 and 265°C, if the heat‐setting time was sufficient. According to the results obtained, a heat‐setting time of 30 s, for a film thickness of 500 μm, was sufficient at a heat‐setting temperature of 255°C to stabilize the produced biaxially oriented PEN bottles and to take them out the mold without further shrinkage. During the drawing of PEN, two different types of rigid amorphous phases seemed to be induced, one with a mean shrinkage temperature of 151°C and another rigid amorphous phase, more temperature‐stable than the first one, that shrank in the temperature range of 200–310°C. During heat setting at high temperatures, a continuous transformation of the less stable phase into the very stable phase took place. The heat‐set method after blow molding is industrially possible with PEN, without the complicated process of subsequent cooling before the molds are opened, in contrast to PET. This constitutes a big advantage for the blow molding of PEN bottles and the production of oriented PEN films. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1462–1473, 2003
Sorption and desorption of tetrachloroethylene in fluoropolymers: Effects of the chemical structure and crystallinity
Authors: Hedenqvist M. S. , Ritums J. E. , Condé‐Brana M. , Bergman G.
Published: December 2002

In 18 fluoropolymers with different repeating‐unit structures and crystallinities, the solubility, diffusivity, and permeability at 70°C of a polarizable nonpolar solute (tetrachloroethylene) were studied. The transport properties were mostly controlled by the polarity of the polymer and to a lesser degree by the polymer crystallinity. The highest permeability was observed in the dipole‐containing ethylene–chlorotrifluoroethylenes because of their high tetrachloroethylene solubility. The lowest permeability was observed in the hydrogen‐bonding poly(vinylidene fluoride) polymers because of the combination of low solute solubility and solute diffusivity. The tetrachloroethylene diffusivity was solute‐concentration‐dependent, and sorption curves were S‐shaped, indicating that the solute surface concentration was time‐dependent. The rate at which the surface concentration approached the saturation level was proportional to the product of Young's modulus, the square of the thickness of the dry polymer, and the logarithm of the solute diffusivity. Data for the water‐hyperbranched polymer and limonene–polyethylene conformed to the same relationship. Therefore, this provides a new tool for predicting the solute‐surface‐concentration time dependence from data obtained by independent measurements. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1474–1483, 2003
An evaluation of a trial of looking after children in the state of Victoria, Australia
Authors: Wise Sarah
Published: December 2002

The paper details the experience of implementing Looking After Children (LAC) in the out of home care system in the state of Victoria, Australia. Findings from an evaluation of the pilot project are also reported. These include observed changes in child outcomes and improvements in collaboration between different sectors of the child and family support system after implementation of LAC, as well as carer and child perceptions of the Assessment and Action Records. Findings suggest an improvement in the monitoring of children's developmental progress and developmental gains for some children after implementation. Perceptions of the Records were also generally positive. However, very few people in children's personal networks, including members of a child's family of origin took part in the assessment process. Carer reports also suggested difficulty in intersectoral working.
FIR Volterra kernel neural models and PAC learning
Authors: Najarian Kayvan
Published: December 2002

The probably approximately correct (PAC) learning theory creates a framework to assess the learning properties of static models for which the data are assumed to be independently and identically distributed (i.i.d.). The present article first extends the idea of PAC learning to cover the learning of modeling tasks with m‐dependent sequences of data. The data are assumed to be marginally distributed according to a fixed arbitrary probability. The resulting framework is then applied to evaluate learning of Volterra Kernel FIR models. © 2002 Wiley Periodicals, Inc.
Measurement of the distribution of red blood cell deformability using an automated rheoscope
Authors: Dobbe J. G. G. , Streekstra G. J. , Hardeman M. R. , Ince C. , Grimbergen C. A.
Published: December 2002

Background

Red blood cells (RBCs) have to deform markedly to pass through the smallest capillaries of the microcirculation. Techniques for measuring RBC deformability often result in an indication of the mean value. A deformability distribution would be more useful for studying diseases that are marked by subpopulations of less deformable cells because even small fractions of rigid cells can cause circulatory problems.

Methods

We present an automated rheoscope that uses advanced image analysis techniques to determine a RBC deformability distribution (RBC‐DD) by analyzing a large number of individual cells in shear flow. The sensitivity was measured from density‐separated fractions of one blood sample and from cells rendered less deformable by heat treatment. A preliminary experiment included the RBC‐DDs of a patient with sickle cell anemia, one on dialysis and being treated with erythropoietin, and one with elliptocytosis.

Results

Measurement of the RBC‐DD was highly reproducible. The sensitivity test showed markedly different deformability distributions of density‐separated cells and yielded distinct RBC‐DDs after each additional minute of heat treatment.

Conclusion

The automated rheoscope enabled the determination of RBC‐DDs from which less deformable subpopulations can be established. The shape of an RBC‐DD may be valuable in assessing cell fractions with normal and anomalous deformability within pathologic blood samples. Cytometry (Clin. Cytometry) 50:313–325, 2002. © 2002 Wiley‐Liss, Inc.
Assessment of tumor cell repopulation after chemotherapy for advanced ovarian cancer: Pilot study
Authors: Davis A. J. , Chapman W. , Hedley D. W. , Oza A. M. , Tannock I. F.
Published: December 2002

Background

Repopulation of clonogenic tumor cells appears to increase during fractionated radiation treatment and is recognized as an important factor affecting local control. Given the longer intervals between cycles and longer total duration of treatment, the impact of repopulation is likely to be greater after chemotherapy.

Methods

We assessed tumor cell repopulation with the proliferative marker Ki‐67 in 21 patients with ovarian carcinoma who received initial chemotherapy. Paraffin slides were evaluated from the diagnostic biopsy and from tumor obtained at debulking surgery after chemotherapy. Immunohistochemistry using the MIB‐1 antibody was performed on the paired samples and analyzed with a digital imaging device linked to a color camera mounted on a transmitted‐light microscope. The ratio of Ki‐67 positive to all nuclei was used as a proliferative index and compared for pre‐ and postchemotherapy specimens.

Results

All patients received platinum‐based chemotherapy and most showed a response to treatment. The median duration between last chemotherapy and debulking surgery was 33 days (range, 22–50 days). Four (19%) of 21 patients showed an increased proliferative index after chemotherapy, and the remainder showed a decrease (n = 12) or no significant change (n = 5).

Conclusions

Our results did not suggest an increase in proliferation of tumor cells after this type of chemotherapy in the majority of patients with ovarian cancer. Cytometry Part A 51A:1–6, 2003. © 2002 Wiley‐Liss, Inc.
Phagocytosis of apoptotic cells by human macrophages: Analysis by multiparameter flow cytometry
Authors: Jersmann Hubertus P. A. , Ross Katherine A. , Vivers Sharon , Brown Simon B. , Haslett Christopher , Dransfield Ian
Published: December 2002

Background

Phagocytic removal of apoptotic cells is an important regulatory event in development, tissue homoeostasis, and inflammation. There are several methodologic problems with most in vitro studies of the molecular mechanisms of apoptotic cell phagocytosis. First, cell loss occurs during rigorous washing of adherent macrophages required to ensure removal of noningested particles. Second, discrimination of adherent or internalised apoptotic cells is difficult. Third, microscopic quantification is time consuming and has the potential for significant interobserver error. Fourth, subsequent analysis of phagocyte populations is difficult.

Methods

We used a flow cytometric method that allows quantification of phagocytosis of fluorescently labelled apoptotic cells with the use of multiparameter flow cytometric analysis.

Results

Phagocytosis of apoptotic cells was validated by use of inhibitors (cytochalasins) or low temperature and counterstaining with cell surface markers for the phagocytic targets to exclude binding to the phagocytic surface. Populations of phagocytic macrophages were sorted, and the presence of internalized apoptotic material was validated by microscopy.

Conclusions

The technique we used in this study allows observer‐independent analysis of phagocytosis of apoptotic cells by macrophages. Importantly, phagocytic or nonphagocytic populations could be subjected to further characterization with the use of flow cytometry with additional fluorochrome reagents and can be re‐cultured to study underlying regulatory mechanisms. Cytometry Part A 51A:7–15, 2003. © 2002 Wiley‐Liss, Inc.
Evaluation of SDF‐1/CXCR4‐induced Ca2+ signaling by fluorometric imaging plate reader (FLIPR) and flow cytometry
Authors: Princen Katrien , Hatse Sigrid , Vermeire Kurt , De Clercq Erik , Schols Dominique
Published: December 2002

Background

The chemokine receptors CXCR4 and CCR5 are the main coreceptors for human immunodeficiency virus (HIV) 1 to enter its target cells. The antiviral activity of their natural ligands (stromal cell‐derived factor 1 [SDF‐1], regulated on activation normal T‐cell expressed and secreted, (RANTES) and macrophage inflammatory proteins 1α and 1β, MIP‐1α and MIP‐1β) and the finding that individuals deficient in CCR5 are relatively resistant to HIV infection led to the concept that chemokine receptor antagonists can play an important role in anti‐HIV therapy. AMD3100, the prototype compound of the bicyclams, is one of the most potent and selective CXCR4 antagonists described to date. The search for new chemokine receptor antagonists involves the evaluation of compounds for their ability to block the specific chemokine‐induced transient intracellular Ca2+ flux. We evaluated two cell‐based‐fluorescent methods with the use of the Fluorometric Imaging Plate Reader (FLIPR) system and a flow cytometric assay to measure the SDF‐1–induced intracellular Ca2+ mobilization via CXCR4. Both assay systems were compared for their sensitivity, advantages, and system‐dependent limitations.

Methods

CXCR4+ lymphocytic and monocytic cell lines commonly used in laboratories studying acquired immunodeficiency syndrome and freshly isolated peripheral blood mononuclear cells (PBMCs) were loaded with the Ca2+ indicator Fluo‐3. After washing, the cells were preincubated with the CXCR4 antagonist AMD3100. Then the increase in intracellular Ca2+ concentration after stimulation with SDF‐1 was examined by the FLIPR and the flow cytometer, which monitored the change in green fluorescence intensity of Ca2+‐bound Fluo‐3. Surface CXCR4 expression was also determined flow cytometrically.

Results

In all five CXCR4+ cell lines, SDF‐1 elicited a transient increase in intracellular Ca2+ concentration. For each cell line, the magnitude of response was related to the level of CXCR4 expression: the cells with the highest CXCR4 level showed the strongest Ca2+ response. AMD3100 effected a dose‐dependent inhibition of the SDF‐1–induced Ca2+ flux in all cell lines examined. The FLIPR was more sensitive than the flow cytometer in detecting minor Ca2+ responses. In freshly isolated PBMCs, the Ca2+ response was due solely to the stimulation of monocytes and granulocytes, whereas the lymphocyte population, although expressing CXCR4, did not respond at all. This phenomenon could be observed with the flow cytometer and not with the FLIPR.

Conclusions

The FLIPR system is a most adequate to monitor intracellular Ca2+ mobilization and to evaluate chemokine receptor antagonists. However, flow cytometry and its multiparameter analysis allow additional characterization of the cells involved in the chemokine receptor‐mediated signal transduction. Cytometry Part A 51A:35–45, 2003. © 2002 Wiley‐Liss, Inc.
Human B cells express a CD45 isoform that is similar to murine B220 and is downregulated with acquisition of the memory B‐cell marker CD27
Authors: Bleesing Jack J. H. , Fleisher Thomas A.
Published: December 2002

Background

Differences between human and murine B cells exist at all stages of B‐cell development, including the stage of memory B‐cell formation. B cells in mice are identified with the pan–B‐cell–specific CD45 isoform, B220. In initial studies in humans, it appeared that B220 expression did not include all B cells. This study was performed to expand on those preliminary findings.

Methods

Multiparameter flow cytometric detection of B220 expression on B cells was combined with a variety of B‐cell markers.

Results

In contrast to mice, B220 was not a pan–B‐cell marker in humans but was downregulated in the majority of B cells that acquired the human memory B‐cell marker, CD27, whereas a minor memory B‐cell subset remained B220+, suggesting differences in differentiation.

Conclusions

The B220 isoform in humans is developmentally regulated in humans, tied to the acquisition of a memory phenotype, and as such can be used as a differentiation‐specific CD45 isoform, akin to the use of CD45 isoforms to distinguish between naive and memory T‐cell subsets. Patients with immunodeficiency disorders, associated with defective memory B‐cell generation and absent or reduced CD27+ B cells, showed a corresponding lack of B220 downregulation consistent with altered differentiation of B‐cell subsets. Cytometry Part B (Clin. Cytometry) 51B:1–8, 2003. Published 2002 Wiley‐Liss, Inc.
Medical drugs from humus matter: Focus on mumie
Authors: Schepetkin Igor , Khlebnikov Andrei , Kwon Byoung Se
Published: December 2002

In this review, we focus on the medicinal drugs from humus matter such as peat, sapropel, and mumie. The most clinically available medicines, containing peat and sapropel extracts, are Torfot, Tolpa Peat Preparation (TPP), Peloidodistillate, Humisol, Peloidin, FiBS, and Eplir. Much attention in the review is concentrated on mumie composition, its pharmacological properties, and new pharmacological drugs with mumie (Shilagen, Abana, Cystone, Diabecon 400, EveCare, Geriforte, Lukol, Pilex, Rumalava, Tentex forte, Nefrotec, Adrenotone, Siotone, La‐Tone Gold, Andro‐Surge, Solanova Libidoplex). It was concluded that therapeutic properties of crude extracts from peat, sapropel, and mumie have similarity to the ones of fulvic and humic acids. They are antibacterial, antitoxic, antiradical, antiulcerogenic, antiarthritic, immunomodulatory, and antiinflammatory properties. Possible directions for better development of new drugs from humus matter are discussed. Drug Dev. Res. 57:140–159, 2002. © 2002 Wiley‐Liss, Inc.
Paleoindian geoarchaeology and paleoenvironments of the western Killpecker Dunes, Wyoming, U.S.A.
Authors: Mayer James H.
Published: December 2002

The Killpecker Dunes in southwestern Wyoming have long been known to contain evidence for Paleoindian occupation. This paper presents the results of geoarchaeological investigations in the western, dormant portion of the Killpecker Dunes. Five localities, including the Krmpotich Folsom and Finley Cody Complex sites, were examined in order to better understand the Paleoindian geochronology of the dune field, and to facilitate a late Quaternary paleoenvironmental reconstruction. Age control is provided by radiocarbon, optical, and artifact ages. Four late Quaternary eolian units, designated as strata 1–4, were recognized; strata 1 and 2 are relevant to the Paleoindian record. Aggradation of stratum 1 began by at least 14,690 cal yr (∼12,55014C yr B.P.), probably in the form of a sand sheet under cool, dry conditions. Redoximorphic features are ubiquitous in stratum 1, indicating a rise in the water table during the latest Pleistocene. A buried soil (Calcid) at the top of this unit indicates a period of stability between ca. 12,000 and 11,00014C yr B.P. and has the potential to yield Clovis (11,200–10,90014C yr B.P.) artifacts. Unconformably overlying stratum 1 is stratum 2, a latest Pleistocene to early Holocene sand containing Folsom (10,900–10,20014C yr B.P.) through Cody Complex (9000–850014C yr B.P.) occupations. A buried soil characterized by the accumulation of illuvial clay and sodium (Natrargid) occurs at the top of stratum 2 and probably formed in and around interdunal ponds. The association of Paleoindian material with the stratum 2 soil suggests the use of interdunal areas as natural traps for hunting extinct bison. The accumulation of soluble salts indicates increased rates of evaporation during the early Holocene, probably from an increase in summer insolation. Although conditions in the dune field during the early Holocene became increasingly dry, they were probably moister than at present. © 2003 Wiley Periodicals, Inc.
The Euro and mergers: What are the opportunities and risks?
Authors: Goldberg Stephen R. , Benet Bruce A. , Cannon David M.
Published: December 2002

Americans who want to play the M&A game on European soil should go in with their eyes wide open, warn the
authors. The differences between the U.S. and European environments are so great that even seasoned players can feel
the ground shifting unexpectedly beneath them. But to ignore the opportunities would be disastrous. ©
2003 Wiley Periodicals, Inc.
SPEs: What is their role in future mergers?
Authors: Munter Paul
Published: December 2002

Special Purpose Entities (SPEs) have been a hot news item lately. Enron abused its SPEs to hide
debt, and now Congress and the FASB have zeroed in on the issue. How have they changed the rules? What
regulations are ahead? What is the FASB likely to do? © 2003 Wiley Periodicals,
Inc.
M&A in Greater China
Authors: Tang Roger Y. W. , Metwalli Ali M.
Published: December 2002

Many articles have discussed M&A activity in the United States and Europe. But what has been happening in
one of the world's biggest potential markets—Greater China? © 2003 Wiley
Periodicals, Inc.
ICFF: A new method to incorporate implicit flexibility into an internal coordinate force field
Authors: Katritch Vsevolod , Totrov Maxim , Abagyan Ruben
Published: December 2002

We introduce a new method to accurately “project” a Cartesian force field onto an internal coordinate molecular model with fixed‐bond geometry. The algorithm automatically generates the Internal Coordinate Force Field (ICFF), which is a close approximation of the “source” Cartesian force field. The ICFF method reduces the number of free variables in a model by at least 10‐fold and facilitates the fast convergence of geometry optimizations, an advantage that is critical for many applications such as the docking of flexible ligands or conformational modeling of macromolecules. Although covalent geometry is fixed in an ICFF model, implicit flexibility is incorporated into the force field parameters in the following two ways. First, we formulate an empirical torsion energy term in ICFF as a sixfold Fourier series and develop a procedure to calculate the Fourier coefficients from the conformational energy profiles of the fully flexible Cartesian model. The ICFF torsion parameters thus represent not only torsion component of the source force field, but also bond bending, bond stretching, and “1‐4” van der Waals interactions. Second, we use a soft polynomial repulsion function for “1‐5” and “1‐6” interactions to mimic the flexibility of bonds, connecting these atoms. Also, we suggest a way to use a local part of the Cartesian force field to automatically generate fixed covalent geometries, compatible with the ICFF energy function. Here, we present an implementation of the ICFF algorithm, which employs the MMFF94s Cartesian force field as a “source.” Extensive benchmarking of ICFF with a representative set of organic molecules demonstrates that the implicit flexibility model accurately reproduces MMFF94s equilibrium conformational energy differences (RMSD ∼0.64 kcal) and, most importantly, detailed torsion energy profiles (RMSD ∼0.37 kcal). This accuracy is characteristic of the method, because all the ICFF parameters (except one scaling factor in the “1‐5,1‐6” repulsion term) are derived directly from the source Cartesian force field and do not depend on any particular molecular set. In contrast, the rigid geometry model with the MMFF94s energy function yields highly biased estimations in this test with the RMSD exceeding 1.2 kcal for the equilibrium energy comparisons and ∼3.4 kcal for the torsion energy profiles. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 254–265, 2003
Exact rotamer optimization for protein design
Authors: Gordon D. Benjamin , Hom Geoffrey K. , Mayo Stephen L. , Pierce Niles A.
Published: December 2002

Computational methods play a central role in the rational design of novel proteins. The present work describes a new hybrid exact rotamer optimization (HERO) method that builds on previous dead‐end elimination algorithms to yield dramatic performance enhancements. Measured on experimentally validated physical models, these improvements make it possible to perform previously intractable designs of entire protein core, surface, or boundary regions. Computational demonstrations include a full core design of the variable domains of the light and heavy chains of catalytic antibody 48G7 FAB with 74 residues and 10128 conformations, a full core/boundary design of the β1 domain of protein G with 25 residues and 1053 conformations, and a full surface design of the β1 domain of protein G with 27 residues and 1060 conformations. In addition, a full sequence design of the β1 domain of protein G is used to demonstrate the strong dependence of algorithm performance on the exact form of the potential function and the fidelity of the rotamer library. These results emphasize that search algorithm performance for protein design can only be meaningfully evaluated on physical models that have been subjected to experimental scrutiny. The new algorithm greatly facilitates ongoing efforts to engineer increasingly complex protein features. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 232–243, 2003
An improved method for nonbonded list generation: Rapid determination of near‐neighbor pairs
Authors: Petrella Robert J. , Andricioaei Ioan , Brooks Bernard R. , Karplus Martin
Published: December 2002

Generation of the list of near‐neighbor pairs of atoms not bonded to each other is a key feature of many programs for calculating the energy and energy derivatives for large molecules. Because this step can take a significant amount of CPU time, more efficient nonbonded list generation can speed up the energy calculations. In this article, a novel nonbonded list generation algorithm, BYCC, is introduced. It combines certain features of other algorithms and achieves more rapid nonbonded list generation; a factor of ≈2.5 for a molecule of 5000 atoms with a cutoff in the 10 Å range is obtained on Hewlett‐Packard (HP) and Alpha processors, without greatly increasing memory requirements. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 222–231, 2003