bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of CXCL16 and its receptor CXCR6/Bonzo promotes growth of human schwannomas
Authors: Held‐Feindt Janka , Rehmke Brigitte , Mentlein Rolf , Hattermann Kirsten , Knerlich Friederike , Hugo Heinz‐Hermann , Ludwig Andreas , Mehdorn H. Maximilian
Published: February 2008

Chemokines and their receptors play a decisive role in tumor progression and metastasis. Here, we describe the expression of the CXCL16‐CXCR6‐system in human schwannomas of different localization and in malignant peripheral nerve sheath tumors. The transmembrane chemokine CXCL16 and its receptor CXCR6/Bonzo were overexpressed on the mRNA and protein levels in all tumor samples investigated as compared with normal peripheral or 8th cranial nerve tissues. Chromogenic immunostaining and confocal laser microscopy revealed that CXCL16 and CXCR6 were localized mainly on S‐100 positive schwannoma cells. Cultured schwannoma cells responded to CXCL16‐stimulation by phosphorylation of kinases p42/44 (Erk 2/1) that could be inhibited by the MEK1/2‐inhibitor U0126 indicating an involvement of the mitogen‐activated protein kinase signal transduction pathway. As a biological response, CXCL16 increased proliferation and induced migration of schwannomas. Hence, CXCL16 appears to be a novel growth factor for schwannomas of different localization. © 2008 Wiley‐Liss, Inc.
S-adenosylmethionine inhibits lipopolysaccharide-induced gene expression via modulation of histone methylation
Authors: Ara Ainhoa Iglesias , Xia Meng , Ramani Komal , Mato José M. , Lu Shelly C.
Published: February 2008

We previously showed that S-adenosylmethionine (SAMe) and its metabolite methylthioadenosine (MTA) blocked lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNFα) expression in RAW (murine macrophage cell line) and Kupffer cells at the transcriptional level without affecting nuclear factor κ B nuclear binding. However, the exact molecular mechanism or mechanisms of the inhibitory effect were unclear. While SAMe is a methyl donor, MTA is an inhibitor of methylation. SAMe can convert to MTA spontaneously, so the effect of exogenous SAMe may be mediated by MTA. The aim of our current work is to examine whether the mechanism of SAMe and MTA's inhibitory effect on proinflammatory mediators might involve modulation of histone methylation. In RAW cells, we found that LPS induced TNFα expression by both transcriptional and posttranscriptional mechanisms. SAMe and MTA treatment inhibited the LPS-induced increase in gene transcription. Using the chromatin immunoprecipitation assay, we found that LPS increased the binding of trimethylated histone 3 lysine 4 (H3K4) to the TNFα promoter, and this was completely blocked by either SAMe or MTA pretreatment. Similar effects were observed with LPS-mediated induction of inducible nitric oxide synthase (iNOS). LPS increased the binding of histone methyltransferases Set1 and myeloid/lymphoid leukemia to these promoters, which was unaffected by SAMe or MTA. The effects of MTA in RAW cells were confirmed

in vivo

in LPS-treated mice. Exogenous SAMe is unstable and converts spontaneously to MTA, which is stable and cell-permeant. Treatment with SAMe doubled intracellular MTA and S-adenosylhomocysteine (SAH) levels. SAH also inhibited H3K4 binding to TNFα and iNOS promoters.

Conclusion:

The mechanism of SAMe's pharmacologic inhibitory effect on proinflammatory mediators is mainly mediated by MTA and SAH at the level of histone methylation.
Modest wine drinking and decreased prevalence of suspected nonalcoholic fatty liver disease
Authors: Dunn Winston , Xu Ronghui , Schwimmer Jeffrey B.
Published: February 2008

People at risk for coronary heart disease are often at risk for nonalcoholic fatty liver disease (NAFLD). The association of modest wine consumption with NAFLD has not been studied and the recommendation of wine for patients at risk for both diseases is controversial. The aim is to test the hypothesis that modest wine consumption is associated with decreased prevalence of NAFLD. We included Third National Health and Nutrition Examination Survey participants who either reported no alcohol consumption or preferentially drinking wine with total alcohol consumption up to 10 g per day. Suspected NAFLD was based on unexplained serum alanine aminotransferase (ALT) elevation over the cut point of the reference laboratory (ALT > 43) and the cut point based on the 95th percentile of healthy subjects (ALT > 30 for men; ALT > 19 for women). Multivariate analysis was adjusted for age, gender, race, neighborhood, income, education, caffeine intake, and physical activity. A total of 7,211 nondrinkers and 945 modest wine drinkers comprised the study sample. Based on the reference laboratory cut point, suspected NAFLD was observed in 3.2% of nondrinkers and 0.4% of modest wine drinkers. The adjusted odds ratio was 0.15 (95% confidence interval, 0.05-0.49). Using the healthy subject cut point, suspected NAFLD was observed in 14.3% of nondrinkers and 8.6% of wine drinkers. The adjusted odds ratio was 0.51 (95% confidence interval, 0.33-0.79).

Conclusion:

Modest wine consumption is associated with reduced prevalence of suspected NAFLD. The current study supports the safety of one glass of wine per day for cardioprotection in patients at risk for both coronary heart disease and NAFLD.
Adsorption of benzene, fluorobenzene and meta‐di‐fluorobenzene on Cu(110): A computational study
Authors: Zotti L. A. , Teobaldi G. , Palotás K. , Ji W. , Gao H.‐J. , Hofer W. A.
Published: February 2008

We modelled the adsorption of benzene, fluorobenzene and meta‐di‐fluorobenzene on Cu(110) by Density Functional Theory. We found that the adsorption configuration depends on the coverage. At high coverage, benzene assumes a tilted position, while at low coverage a horizontal slightly distorted geometry is favoured. Functionalizing the benzene ring with one or two fluorine atoms weakens the bonding to the surface. A rotation is induced, which decreases the distance of the fluorine atom from the surface. STM simulations reveal that details about both, benzene adsorption geometry and fluorine position, can be only detected at short tip‐surface distances. © Crown copyright 2008. J Comput Chem 2008
Q‐Dock: Low‐resolution flexible ligand docking with pocket‐specific threading restraints
Authors: Brylinski Michal , Skolnick Jeffrey
Published: February 2008

The rapidly growing number of theoretically predicted protein structures requires robust methods that can utilize low‐quality receptor structures as targets for ligand docking. Typically, docking accuracy falls off dramatically when apo or modeled receptors are used in docking experiments. Low‐resolution ligand docking techniques have been developed to deal with structural inaccuracies in predicted receptor models. In this spirit, we describe the development and optimization of a knowledge‐based potential implemented in Q‐Dock, a low‐resolution flexible ligand docking approach. Self‐docking experiments using crystal structures reveals satisfactory accuracy, comparable with all‐atom docking. All‐atom models reconstructed from Q‐Dock's low‐resolution models can be further refined by even a simple all‐atom energy minimization. In decoy‐docking against distorted receptor models with a root‐mean‐square deviation, RMSD, from native of ∼3 Å, Q‐Dock recovers on average 15‐20% more specific contacts and 25–35% more binding residues than all‐atom methods. To further improve docking accuracy against low‐quality protein models, we propose a pocket‐specific protein–ligand interaction potential derived from weakly homologous threading holo‐templates. The success rate of Q‐Dock employing a pocket‐specific potential is 6.3 times higher than that previously reported for the Dolores method, another low‐resolution docking approach. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008
Spontaneous segregation on a hybrid chiral surface
Authors: Szabelski Paweł
Published: February 2008

Segregation of enantiomers in two‐dimensional adsorbed layers is a process that is usually controlled by anisotropic directional interactions between adsorbed molecules. In this contribution, we propose a simple theoretical model in which the chiral segregation occurs even though the lateral interactions are neglected. In particular, we consider a solid surface composed of two domains with different patterns of active sites being mirror images of each other. The domains of opposite handedness represent crystal facets of a composite chiral material which are adjoined to form a heterochiral adsorbing surface. To explore equilibrium properties of the system, we use Canonical Ensemble Monte Carlo method for a square lattice. The influence of factors such as energetic properties of the surface and density of the adsorbed layer on the extent of separation is examined. The obtained results indicate that effective two‐dimensional separation on the hybrid chiral surface assumed in our model can be achieved only at sufficiently low adsorbate densities. The results also suggest that the segregation on the hybrid surface would be a promising method of enantiodiscrimination for those chiral molecules which do not exhibit strong lateral interactions. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008
Analysis of similarity/dissimilarity of DNA sequences based on a class of 2D graphical representation
Authors: Yao Yu‐hua , Dai Qi , Nan Xu‐Ying , He Ping‐An , Nie Zuo‐Ming , Zhou Song‐Ping , Zhang Yao‐Zhou
Published: February 2008

On the basis of a class of 2D graphical representations of DNA sequences, sensitivity analysis has been performed, showing the high‐capability of the proposed representations to take into account small modifications of the DNA sequences. And sensitivity analysis also indicates that the absolute differences of the leading eigenvalues of the L/L matrices associated with DNA increase with the increase of the number of the base mutations. Besides, we conclude that the similarity analysis method based on the correlation angles can better eliminate the effects of the lengths of DNA sequences if compared with the method using the Euclidean distances. As application, the examination of similarities/dissimilarities among the coding sequences of the first exon of β‐globin gene of different species has been performed by our method, and the reasonable results verify the validity of our method. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008
Theoretical study on the structure and formation mechanism of [C6H5Mm]− (MAg, Au; m = 1–3)
Authors: Liu Xiao‐Jing , Yang Chuan‐Lu , Zhang Xiang , Han Ke‐Li , Tang Zi‐Chao
Published: February 2008

The structures and formation mechanisms of the important intermediate phenyl‐coinage metal complexes [C6H5Mm]− (MAg, Au, m = 1–3) are investigated at B3LYP//6‐311G(d, p)/Lanl2dz level using Gaussian 03 program. The adiabatic electron affinity and vertical dissociation energy of [Mm]− and [C6H5Mm]− are calculated, which are excellently coincident with the experimental determination. The C6H5 group bonds on metal clusters through MC σ bond in the complex [C6H5Mm]−. The complexes [C6H5Mm]− (MAg, Au; m = 2–3) are generated through a stepwise reaction. The first step is a direct insertion reaction between [Mm]− (MAg, Au, m = 1–3) and C6H6, which leads to the generation of intermediate [C6H5MmH]− (m = 1–3) with the activation and cleavage of CH bond. The second step is the neutral metal atom abstracting the H atom to yield the product [C6H5Mm]−. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008
High‐energy femtosecond fiber lasers based on pulse propagation at normal dispersion
Authors: Wise F.W. , Chong A. , Renninger W.H.
Published: February 2008

The generation and stable propagation of ultrashort optical pulses tend to be limited by accumulation of excessive nonlinear phase shifts. The limitations are particularly challenging in fiber‐based devices, and as a result, short‐pulse fiber lasers have lagged behind bulk solid‐state lasers in performance. This article will review several new modes of pulse formation and propagation in fiber lasers. These modes exist with large normal cavity dispersion, and so are qualitatively distinct from the soliton‐like processes that have been exploited effectively in modern femtosecond lasers but which are also quite limiting. Self‐similar evolution can stabilize high‐energy pulses in fiber lasers, and this leads to order‐of‐magnitude increases in performance: fiber lasers that generate 10 nJ pulses of 100 fs duration are now possible. Pulse‐shaping based on spectral filtering of a phase‐modulated pulse yields similar performance, from lasers that have no intracavity dispersion control. These new modes feature highly‐chirped pulses in the laser cavity, and a theoretical framework offers the possibility of unifying our view of normal‐dispersion femtosecond lasers. Instruments based on these new pulse‐shaping mechanisms offer performance that is comparable to that of solid‐state lasers but with the major practical advantages of fiber.
Behaviour of cellular materials under impact loading
Authors: Vesenjak M. , Ren Z. , Öchsner A.
Published: February 2008

The paper describes experimental and computational testing of regular open‐cell cellular structures behaviour under impact loading. Open‐cell cellular specimens made of aluminium alloy and polymer were experimentally tested under quasi‐static and dynamic compressive loading in order to evaluate the failure conditions and the strain rate sensitivity. Additionally, specimens with viscous fillers have been tested to determine the increase of the energy absorption due to filler effects. The tests have shown that brittle behaviour of the cellular structure due to sudden rupture of intercellular walls observed in quasi‐static and dynamic tests is reduced by introduction of viscous filler, while at the same time the energy absorption is increased.

The influence of fluid filler on open‐cell cellular material behaviour under impact loading was further investigated with parametric computational simulations, where fully coupled interaction between the base material and the pore filler was considered. The explicit nonlinear finite element code LS‐DYNA was used for this purpose. Different failure criteria were evaluated to simulate the collapsing of intercellular walls and the failure mechanism of cellular structures in general.

The new computational models and presented procedures enable determination of the optimal geometric and material parameters of cellular materials with viscous fillers for individual application demands. For example, the cellular structure stiffness and impact energy absorption through controlled deformation can be easily adapted to improve the efficiency of crash absorbers.
Contact stress analysis on the X‐shape ring
Authors: Lee H.‐S. , Lee Y.‐S. , Chun B.‐S. , Kim S.‐Y. , Baek J.‐H.
Published: February 2008

A X‐ring is a loop of elastomer with X‐shaped cross‐section used as a mechanical seal or gasket. Such a X‐ring is designed to be seated in a groove and is compressed during assembly between two or more parts, creating a seal at the interface. The seal is designed to have line contact between the X‐ring and sealing faces. This allows a high local stress, able to contain high pressure, without exceeding the yield stress of the X‐ring shell body. This study aims to detect the contact stress and the deformed shape of a X–shaped ring shell under various compression conditions. For this analysis, four experiments were conducted to obtain material properties of the elastomer. The contact stress analysis is performed by applying material properties that we obtained through experiments. A contact stress analysis is carried out by finite element analysis.
Computational modelling of irregular open‐cell foam behaviour under impact loading
Authors: Borovinšek M. , Ren Z.
Published: February 2008

Cellular structures represent an important class of engineering materials. Typical representative of such structures are metallic foams, which are being increasingly used in many advanced engineering applications due to their low specific weight, appropriate mechanical properties and excellent energy absorption capacity. For optimal design of cellular structures it is necessary to develop proper computational models for use in computational simulations of their behaviour under impact loading.

The paper studies the effects of open‐cell metallic foam irregularity on deformation behaviour and impact energy absorption during impact loading by means of parametric computational simulations, using the lattice‐type modelling of open‐cell material structure. The 3D Voronoi technique is used for the reproduction of real, irregular open‐cell structure of metallic foams. The method uses as a reference a regular mesh structure and utilises an irregularity parameter to reproduce the irregularity of real open‐cell structure. A smoothing technique is introduced to assure proper stability and accuracy of explicit dynamic simulations using the produced lattice models. The effects of the smoothing technique were determined by comparative simulations of smoothed and unsmoothed lattices subjected to dynamic loading.
Lipid hydroperoxides from processed dietary oils enhance growth of hepatocarcinoma cells
Authors: Rohr‐Udilova Nataliya V. , Stolze Klaus , Sagmeister Sandra , Nohl Hans , Schulte‐Hermann Rolf , Grasl‐Kraupp Bettina
Published: February 2008

Linoleic acid, one of the major fatty acid in dietary oils, is an important source for hydroperoxides that may be formed in the presence of oxygen during food processing. Oxidized oils are absorbed in the intestine, transported as chylomicrones to the liver, and may affect unaltered hepatic cells as well as the process of hepatocarcinogenesis. We have studied the effects of linoleic acid hydroperoxides (LOOH) on growth and gene expression of cultured human hepatocellular carcinoma cells (HCC‐1.2). The addition of LOOH to the medium of HCC‐1.2 carcinoma cells caused dose‐dependent cell loss and enhanced lactate dehydrogenase (LDH)‐release. Under subtoxic conditions, LOOH induced intracellular hydrogen peroxide production, a decrease of glutathione content, elevated expression of the AP‐1 components c‐fos and c‐jun as well as of the anti‐apoptotic enzyme heme oxygenase 1 (HO‐1). Furthermore, the cells were pushed by LOOH into the cell cycle as indicated by increased proportion of cells in the S‐ or G2/M‐phase. The unoxidized linoleic acid was not active. Application of SnPPIX, a HO‐1 inhibitor, decreased the viability of HCC‐1.2 cells, indicating the protective role of HO‐1 induction. This is the first evidence that lipid hydroperoxides of dietary origin may be an important driving force for carcinogenesis in the liver.
Radical scavenging activity, anti‐bacterial and mutagenic effects of Cocoa bean Maillard Reaction products with degree of roasting
Authors: Summa Carmelina , McCourt Josephine , Cämmerer Bettina , Fiala Annette , Probst Martina , Kun Szillard , Anklam Elke , Wagner Karl‐Heinz
Published: February 2008

Raw, pre‐roasted and roasted Cocoa samples were separated into four different molecular weight fractions (> 30, 30–10, 10–5 and < 5 kDa) with ultrafiltration and tested for their antibacterial, mutagenic, as well as their radical‐scavenging effects. Radical‐scavenging effects were tested with electro paramagnetic resonance spectroscopy, anti‐mutagenicity in the Salmonella microsome assay (with and without metabolic activation), and antibacterial effects by incubating the fractions with several strains of Bifidobacteria, Enterobacter and Escherichia, and observing their growth. The radical‐scavenging activity and reducing substance concentrations increased, particularly in the 5–10‐kDa roasted fraction. Chromaticity testing elucidated that the 10–5‐kDa fraction was one of the darkest fractions. The Salmonella microsome assay showed neither mutagenic nor anti‐mutagenic effects in any of the samples at any of the different concentrations applied when using TA98, TA100 and TA102. All fractions reduced the growth of pathogenic bacteria, in particular at the highest concentration of 100 μg/mL; however, the same trends were also observed for Bifidobacteria.
Consumption of Brussels sprouts protects peripheral human lymphocytes against 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and oxidative DNA‐damage: results of a controlled human intervention trial
Authors: Hoelzl Christine , Glatt Hansruedi , Meinl Walter , Sontag Gerhard , Haidinger Gerald , Kundi Michael , Simic Tatjana , Chakraborty Asima , Bichler Julia , Ferk Franziska , Angelis Karel , Nersesyan Armen , Knasmüller Siegfried
Published: February 2008

To find out if the cancer protective effects of Brussels sprouts seen in epidemiological studies are due to protection against DNA‐damage, an intervention trial was conducted in which the impact of vegetable consumption on DNA‐stability was monitored in lymphocytes with the comet assay. After consumption of the sprouts (300 g/p/d, n = 8), a reduction of DNA‐migration (97%) induced by the heterocyclic aromatic amine 2‐amino‐1‐methyl‐6‐phenyl‐imidazo‐[4,5‐b]pyridine (PhIP) was observed whereas no effect was seen with 3‐amino‐1‐methyl‐5H‐pyrido[4,3‐b]‐indole (Trp‐P‐2). This effect protection may be due to inhibition of sulfotransferase 1A1, which plays a key role in the activation of PhIP. In addition, a decrease of the endogenous formation of oxidized bases was observed and DNA‐damage caused by hydrogen peroxide was significantly (39%) lower after the intervention. These effects could not be explained by induction of antioxidant enzymes glutathione peroxidase and superoxide dismutase, but in vitro experiments indicate that sprouts contain compounds, which act as direct scavengers of reactive oxygen species. Serum vitamin C levels were increased by 37% after sprout consumption but no correlations were seen between prevention of DNA‐damage and individual alterations of the vitamin levels. Our study shows for the first time that sprout consumption leads to inhibition of sulfotransferases in humans and to protection against PhIP and oxidative DNA‐damage.
Pathophysiologie und Diagnose der Obstipation. Therapie mit Bisacodyl, Picosulfat und Prokinetika
Authors: Müller‐Lissner Stefan
Published: February 2008

Die Obstipation verlangt wenig Diagnostik, die Rom‐Kriterien erlauben eine sichere Diagnosestellung aufgrund der Anamnese. Eine organische Colonerkrankung manifestiert sich nicht als chronische Obstipation. Eine Koloskopie ist daher entbehrlich, wenn Alarmsymptome fehlen, wiederholte Koloskopien sind unsinnig. Die häufig empfohlenen “allgemeinen Maßnahmen” sind von zweifelhafter Wirksamkeit. Ballaststoffe lohnen immer einen Versuch, sind aber kein Wundermittel und werden von einigen Patienten schlecht vertragen. Die verfügbaren Laxanzien sind wirksam und sicher. Die Auswahl richtet sich nach der Obstipationsform und der individuellen Verträglichkeit und Präferenz. Das günstigste Verhältnis von Wirkung zu Nebenwirkung haben die stimulierenden Laxanzien und das Macrogol.
Phytopharmaka als Laxanzien. Abführmittel auf pflanzlicher Basis
Authors: Melzig Matthias F.
Published: February 2008

Quellstoff‐ und Anthranoiddrogen sowie Rizinusöl bzw. daraus hergestellte Zubereitungen sind effizient wirksame Phytotherapeutika, die bei akuter und chronischer Obstipation im Sinne der “evidence‐based medicine” eingesetzt werden können. Nahezu problemlos ist die Verwendung von Quellstoff‐Laxanzien bei habitueller bzw. chronischer Obstipation auch über längere Anwendungszeiten sowie bei Kindern und Schwangeren möglich. Für die Beratungspraxis ist hier unbedingt auf die Aufnahme mit ausreichend Flüssigkeit hinzuweisen. Anthranoid‐haltige Phytotherapeutika und das Rizinusöl eignen sich vorrangig für die Therapie der akuten Obstipation, bei bestimmungsgemäßem Gebrauch und in Abstimmung mit dem behandelnden Arzt ist eine längerfristige Therapie aber möglich. Derzeit gibt es keine Hinweise auf unvertretbare Risiken durch Anwendung dieser Phytotherapeutika. Für Kinder und Schwangere bzw. Stillende sind diese Drogen bzw. Zubereitungen daraus nicht primär zu empfehlen.
Obstipation als Arzneimittel‐Nebenwirkung. Obstipation muss richtig erkannt und behandelt werden
Authors: Kopf Andreas
Published: February 2008

Ein Fünftel bis ein Viertel der Allgemeinbevölkerung und mehr als drei Viertel der Tumorkranken mit Opioid‐Dauermedikation leiden unter Obstipation. Somatische und funktionale Ursachen sind für die Entstehung von Obstipation verantwortlich. Wenn möglich sollte die Therapie von Obstipation kausal sein, häufig ist aber eine symptomatische Therapie notwendig. Neben Allgemeinmaßnahmen sind Laxanzien die wichtigste Therapieoption. Die Laxanzien werden nach ihren Wirkmechanismen klassifiziert und wurden aufgrund von Expertenmeinungen in ein Stufenschema eingruppiert, das sich in der klinischen Praxis bewährt hat. Während Lactulose das prophylaktisch wirksame Laxans der Wahl bei Nichttumorpatienten ist, ist Macrogol das Prophylaktikum der Wahl beim Tumorkranken mit Opioid‐Dauermedikation. Beim Tumorkranken mit Opioid‐Dauermedikation ist eine Laxanzientherapie zur Obstipationsprophylaxe obligat. Anwendungshinweise für ausgesuchte Laxanzien sind in Tabelle 8 zusammengefasst.
Inside out – das Kennzeichen gestresster Zellen
Authors: Grode Thomas , Kec Martina , Madry Milena , Zündorf Ilse , Dingermann Theo
Published: February 2008

Der von Peregrine Pharmaceuticals, Inc. entwickelte Antikörper Bavituximab wird derzeit in verschiedenen klinischen Studien getestet. Falls er dabei die Erwartungen erfüllt, könnte er sich zu einem Blockbuster entwickeln, zum einen in der Therapie verschiedener Tumorerkrankungen, zum anderen bei der Behandlung von Hepatitis‐C‐Patienten, die gleichzeitig mit HIV infiziert sind. Was ist das Besondere an Bavituximab?
Das Ende des therapeutischen Klonens, bevor es begann?
Authors: Winckler Thomas
Published: February 2008

Seit Jahren führen wir eine kontroverse Debatte um eine neue Technologie der biomedizinischen Forschung – das Klonen patientenspezifischer Zellen zu therapeutischen Zwecken. In letzter Zeit gibt es in diesem Forschungsfeld aufregende Neuigkeiten.
Resolution of chronic hypoxemia in pediatric sickle cell patients after treatment with hydroxyurea
Authors: Singh Sharon A. , Koumbourlis Anastassios C. , Aygun Banu
Published: February 2008

Chronic hypoxemia is a common manifestation among patients with sickle cell anemia (SCA) who develop chronic lung disease. We report the beneficial effect of hydroxyurea on chronic hypoxemia in three pediatric patients with SCA and recurrent episodes of acute chest syndrome (ACS). All three patients improved rapidly after they were treated with hydroxyurea despite having additional risk factors for hypoxemia. A prospective trial is warranted to assess whether there is a therapeutic effect from the use of hydroxyurea in pediatric SCA patients with chronic hypoxemia. Pediatr Blood Cancer 2008;50:1258–1260. © 2008 Wiley‐Liss, Inc.
Treatment of high‐risk relapsed Wilms tumor with dose‐intensive chemotherapy, marrow‐ablative chemotherapy, and autologous hematopoietic stem cell support: Experience by the Italian association of pediatric hematology and oncology
Authors: Spreafico Filippo , Bisogno Gianni , Collini Paola , Jenkner Alessandro , Gandola Lorenza , D'Angelo Paolo , Casazza Gabriella , Piva Luigi , Luksch Roberto , Perotti Daniela , Pession Andrea , Fagioli Franca , Dallorso Sandro
Published: February 2008

Background

We evaluated an intensified chemotherapy strategy in children with Wilms tumor who relapsed with high‐risk features.

Procedures

From January 2001 to June 2006, we treated 20 consecutive children with reinduction chemotherapy (using ifosfamide/carboplatin/etoposide in 15/20 cases), with (n = 15) or without (n = 5) subsequent high‐dose chemotherapy and hematopoietic stem cell support, surgery where feasible, and radiation therapy. The median time to relapse was 10 months after nephrectomy. All but two children initially received doxorubicin as first‐line therapy.

Results

All patients were assessed for outcome: 13 are currently alive, 12 of them in remission a median 25 months since their relapse, one with progressing tumor. The treatment was unsuccessful in eight children: the disease progressed during reinduction in three, and relapsed in five. There was one toxic death. All transplanted patients engrafted to a neutrophil count >0.5 × 103/µl after a median 11 days, and to an unsustained platelet count >25,000/µl after a median of 13 days. Three‐year disease‐free and overall survival rates were 56 ± 12% and 55 ± 13%, respectively. Neither recurrence within 12 months of nephrectomy nor extra‐lung recurrence negatively affected outcome. A survival advantage was demonstrated in patients without disease evidence prior to transplant.

Conclusion

A disease‐free survival rate nearing 50% is a realistic target in children with high‐risk recurrent Wilms tumor. The benefit of autologous hematopoietic stem cell transplantation for consolidation deserves to be investigated in a randomized, controlled study. Pediatr Blood Cancer 2008;51:23–28. © 2008 Wiley‐Liss, Inc.
Outcome of children less than three years old at diagnosis with non‐metastatic medulloblastoma treated with chemotherapy on the “Head Start” I and II protocols
Authors: Dhall Girish , Grodman Howard , Ji Lingyun , Sands Stephen , Gardner Sharon , Dunkel Ira J. , McCowage Geoffrey B. , Diez Blanca , Allen Jeffrey C. , Gopalan Anjali , Cornelius Albert S. , Termuhlen Amanda , Abromowitch Minnie , Sposto Richard , Finlay Jonathan L.
Published: February 2008

Purpose

To determine the survival of infants and young children with non‐metastatic medulloblastoma using intensive myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue (AuHCR).

Methods

Twenty‐one children less than 3 years old at diagnosis with non‐metastatic medulloblastoma were enrolled on two identical serial studies, “Head Start” I and “Head Start” II. After surgery, patients received five cycles of induction chemotherapy consisting of vincristine, cisplatin, cyclophosphamide and etoposide. Following induction, all patients underwent myeloablative chemotherapy using carboplatin, thiotepa and etoposide with AuHCR. Irradiation was used only at relapse.

Results

The 5‐year event‐free (EFS) and overall survival (OS) rates (±SE) for all patients, patients with gross total resection, and patients with residual tumor were 52 ± 11% and 70 ± 10%, 64 ± 13% and 79 ± 11%, and 29 ± 17% and 57 ± 19%, respectively. The 5‐year EFS and OS ( ± SE) for patients with desmoplastic and classical medulloblastoma were 67 ± 16% and 78 ± 14%, and 42 ± 14 and 67 ± 14%, respectively. There were four treatment related deaths. The majority of survivors (71%) avoided irradiation completely. Mean intellectual functioning and quality of life (QoL) for children surviving without irradiation was within average range for a majority of survivors tested.

Conclusion

This strategy of brief intensive chemotherapy for young children with non‐metastatic medulloblastoma eliminated the need for craniospinal irradiation 52% of the patients, and may preserve QoL and intellectual functioning. The excellent survival rates are somewhat dampened by high toxic mortality. Pediatr Blood Cancer 2008;50:1169–1175. © 2008 Wiley‐Liss, Inc.
Leukocyte transfusions revisited: Stem cell graft stimulation in graft failure
Authors: Taskinen Mervi , Talvensaari Kimmo , Hovi Liisa , Vettenranta Kim , Saarinen‐Pihkala Ulla M.
Published: February 2008

Background

The aim was to evaluate the role of leukocyte transfusions (LTX) in relation to graft function during prolonged neutropenia after stem cell transplantation (SCT).

Procedure

In 1989–2005, 22 SCT patients have received LTX in our unit. In all patients severe infection with profound neutropenia (<0.2 × 109/L) preceded LTX. 13/22 had multi‐organ failure or thrombotic microangiopathy. Irradiated leukocytes from pooled random donor products at 1.0 × 1010 leukocytes/m2/day for a minimum of 3 days were used. Myeloid recovery and clinical benefit were analyzed.

Results

Engraftment defined as an absolute neutrophil count (ANC) of >0.5 × 109/L on three consecutive days was observed in 15/22 (68%) patients at median of 6 (range 2–25) days after LTX, and sustained engraftment (ANC of >0.5 × 109/L for 4 weeks) in 11/22 (50%) patients. Clinical benefit was observed in 6/22 (27%) patients with a prolonged antecedent neutropenia, who still demonstrated rapid sustained engraftment after LTX. Ongoing thrombotic microangiopathy was associated with persistent graft failure.

Conclusions

LTX from random donors was associated with a rapid recovery of myeloid function in severely ill SCT patients. We speculate that allostimulation by LTX may have a role. Pediatr Blood Cancer 2008;50:1247–1252. © 2008 Wiley‐Liss, Inc.
Initial testing (stage 1) of sunitinib by the pediatric preclinical testing program
Authors: Maris John M. , Courtright Joshua , Houghton Peter J. , Morton Christopher L. , Kolb E. Anders , Lock Richard , Tajbakhsh Mayamin , Reynolds C. Patrick , Keir Stephen T. , Wu Jianrong , Smith Malcolm A.
Published: February 2008

Background

Sunitinib is an orally bioavailable, multi‐targeted tyrosine kinase inhibitor with selectivity for PDGF receptors, VEGF receptors, FLT3, and KIT.

Procedures

Sunitinib was tested at concentrations ranging from 0.1 nM to 1.0 µM against 23 cell lines from the PPTP in vitro panel. We also compared sunitinib (53.5 mg/kg) or vehicle administered for 28 days by oral gavage in 46 murine xenograft models representing 9 distinct pediatric cancer histologies.

Results

The leukemia cell line, Kasumi‐1 (gain‐of‐function KITAsn822Lys mutation) was the only line with an in vitro response to sunitinib (IC50 75.7 nM). Sunitinib significantly prolonged EFS in 19 of 35 (54%) of the solid tumor, and in 3 of 8 (38%) of the ALL xenografts analyzed. Using the PPTP time to event measure of efficacy, sunitinib had intermediate (13) and high (1) levels of activity against 14 of 34 evaluable solid tumor xenografts, including 4 of 6 rhabdomyosarcoma, 4 of 5 Ewing tumor, and 2 of 3 rhabdoid tumor xenografts. Following cessation of treatment for the 14 solid tumor xenografts without tumor events by day 28, tumor growth rate increased in most. The only regression noted to sunitinib in the solid tumor panels was a complete response in a rhabdoid tumor xenograft.

Conclusions

Sunitinib demonstrated significant tumor growth inhibition against most of the PPTP's solid tumor panels, but little activity against the neuroblastoma and ALL panel. Antitumor activity was manifested primarily as tumor growth delay, consistent with an anti‐angiogenic effect for sunitinib against many of the pediatric preclinical models evaluated. Pediatr Blood Cancer 2008;51:42–48. © 2008 Wiley‐Liss, Inc.
Oxygen permeability of biaxially oriented polypropylene films
Authors: Lin Y.J. , Dias P. , Chen H.Y. , Chum S. , Hiltner A. , Baer E.
Published: February 2008

The effect of thermal history on the oxygen permeability of biaxially oriented polypropylene (BOPP) films was investigated. Compression‐molded sheets prepared with different cooling rates were biaxially oriented at several temperatures in the range between the onset of melting and the peak melting temperature and at a strain rate similar to that encountered in a commercial film process. The stress response during stretching was found to depend on the residual crystallinity in the same way regardless of the thermal history of the compression‐molded sheet. Biaxial orientation reduced the oxygen permeability measured at 23°C; however, the reduction did not correlate with the amount of orientation as measured by birefringence or with the fraction of amorphous phase as determined by density. Rather, the decrease in permeability was attributed to reduced mobility of amorphous tie molecules. A single one‐to‐one correlation between the oxygen permeability and the intensity of the dynamic mechanical β‐relaxation was demonstrated for all the films used in the study. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
Rheological characterization of room temperature vulcanized silicone sealant: Effect of filler particle size
Authors: Xu Xiaoming , Gao Chuanhua , Zheng Qiang
Published: February 2008

The rheological properties of silicone sealant filled with different calcium carbonate (CaCO3) particles varying in size were investigated. It is found that as particle size decreases, the dynamic storage modulus (G′) and shear viscosity (η) increase; whereas, the width of linear viscoelastic region decreases. At low shear rate, a modulus plateau appears and the shear thinning behavior becomes apparent. The reasons for these can be ascribed to the enhanced particle–particle interaction and formation of filler network structure. Moreover, results dealing with the buildup of network structure monitored by kinetic recovery experiments reveal that both the rate of recovery and magnitude of rheological parameters increase with decreasing particle size. This phenomenon is consistent with the data collected from creep and recovery measurements, indicating an enhanced elasticity and network structure. Furthermore, transmission electron microscopy (TEM) observation and mechanical properties tests for cured sealant samples were also carried out to provide an evidence for the discussion further. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
Improved through‐plane electrical conductivity in a carbon‐filled thermoplastic via foaming
Authors: Motlagh G.H. , Hrymak A.N. , Thompson M.R.
Published: February 2008

Flow‐induced orientation of the conductive fillers in injection molding creates parts with anisotropic electrical conductivity where through‐plane conductivity is several orders of magnitude lower than in‐plane conductivity. This article provides insight into a novel processing method using a chemical blowing agent to manipulate carbon fiber (CF) orientation within a polymer matrix during injection molding. The study used a fractional factorial experimental design to identify the important processing factors for improving the through‐plane electrical conductivity of plates molded from a carbon‐filled cyclic olefin copolymer (COC) containing 10 vol% CF and 2 vol% carbon black. The molded COC plates were analyzed for fiber orientation, morphology, and electrical conductivity. With increasing porosity in the molded foam part, it was found that greater out‐of‐plane fiber orientation and higher electrical conductivity could be achieved. Maximum conductivity and fiber reorientation in the through‐plane direction occurred at lower injection flow rate and higher melt temperature. These process conditions correspond with foam flow during filling of the mold cavity, indicating the importance of shear stress on the effectiveness of a fiber being rotated out‐of‐plane during injection molding. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
Fibril formation of 1,3:2,4‐Di(3,4‐dimethylbenzylidene) sorbitol in polymer melts
Authors: Lipp Jonathan , Shuster Michael , Terry Ann E. , Cohen Yachin
Published: February 2008

1,3:2,4‐Di 3,4‐dimethylbenzylidene) sorbitol (DMDBS) is a known nucleator and clarifier for polypropylene (PP). It is also known that in the useful concentration range of roughly 0.2–2%, it forms nanofibrillar structures within the PP melt. The kinetics of the DMDBS solidification process within the PP melt and formation of the ensuing nanofibrillar structure are studied by in‐situ small angle X‐ray scattering (SAXS) analysis. The dynamic lag of the fibrillar structure formation kinetics and its temperature dependence indicate a nucleation and growth mechanism, controlled by the rate of nucleation. Examination of the polystyrene (PS)/DMDBS system indicate structure formation only in compounds containing 2.5% DMDBS, as evident in the rheological behavior. Light microscopy reveals that the fibrillar cross‐section in this case is larger by an order‐of‐magnitude in comparison to the structure in PP. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
Non‐covalently crosslinked hydrogels displaying a unique combination of water‐absorbing, elastic and adhesive properties
Authors: Bayramov Danir F , Singh Parminder , Cleary Gary W , Siegel Ronald A , Chalykh Anatoly E , Feldstein Mikhail M
Published: February 2008

BACKGROUND: Stringent requirements must be satisfied by biomedical adhesives, including biocompatibility, adhesion, cohesiveness and processability. The ability to change mechanical properties in response to environmental changes may also be desirable. In the present work the water‐absorbing, adhesive and mechanical properties of blends based on hydrogen bonding complexes between poly(N‐vinyl pyrrolidone), poly(ethylene glycol) (PEG) and poly[(methacrylic acid)‐co‐(ethyl acrylate)] were investigated. These blends, consisting of pharmaceutical‐grade components, exhibit pH‐sensitive swelling and dissolution, along with rubber‐like elasticity and bioadhesion.

RESULTS: Polymer blend films remained intact at pH = 5.6 but underwent dissolution at pH = 7.4, the difference being attributed to deprotonation of acidic side‐chains, with loss of hydrogen bonding and development of charge repulsion. Sol release was primarily due to PEG. Films swelled at low pH instead of dissolving, in a manner that was pH‐dependent but PEG‐independent. Films displayed elastic properties comparable to cured elastomers when mildly swollen, with modulus and ultimate strength decreasing with increasing PEG content. Dry films were nearly tack‐free, but became more adhesive with increasing water content, up to a point where the film dissolved.

CONCLUSION: Due to their biocompatibility and dissolution/mechanical properties, the bioadhesive polymer blends investigated may be suitable for numerous biomedical applications. Copyright © 2008 Society of Chemical Industry
Assessing the outdoor operating temperature of photovoltaic modules
Authors: Faiman David
Published: February 2008

By a careful study of data collected from seven varieties of photovoltaic (PV) module it is demonstrated that a simple modified form of the Hottel–Whillier–Bliss (HWB) equation, familiar from the analysis of flat‐plate solar–thermal collectors, can be employed to predict module temperatures within an accuracy comparable to the cell‐to‐cell temperature differences typically encountered within a module. Furthermore, for modules within the range of construction parameters employed in this study, the actual values of the two modified HWB constants do not appear to depend upon module type. The implication of these results for the accuracy of outdoor module characterization is discussed. Copyright © 2008 John Wiley & Sons, Ltd.
In‐situ X‐ray scattering studies of OFET interfaces
Authors: Gerlach Alexander , Sellner Stefan , Kowarik Stefan , Schreiber Frank
Published: February 2008

We review recent work in the field of organic thin films and organic‐inorganic interfaces which is relevant for device applications and particularly organic field effect transistors (OFETs). Focussing on the structural properties of these systems we discuss results obtained mostly through X‐ray scattering techniques. We address the growth behaviour and interface formation of organic thin films including roughness evolution and crystal structure. In particular, we review real‐time studies of pentacene, diindenoperylene, and PTCDA deposition on different subtrates which illustrate their specific growth kinetics. Covering different thickness regimes we show how the molecular orientation depends on the substrate and the growth conditions. Finally, we address the structural properties of organic heterostructures, i.e. metal and insulator films on organics, demonstrating how to assess and control interdiffusion and thermal stability of the capping layers. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
An empirical validation of object‐oriented class complexity metrics and their ability to predict error‐prone classes in highly iterative, or agile, software: a case study
Authors: Olague Hector M. , Etzkorn Letha H. , Messimer Sherri L. , Delugach Harry S.
Published: February 2008

Empirical studies have shown complexity metrics to be good predictors of testing effort and maintainability in traditional, imperative programming languages. Empirical validation studies have also shown that complexity is a good predictor of initial quality and reliability in object‐oriented (OO) software. To date, one of the most empirically validated OO complexity metrics is the Chidamber and Kemerer Weighted Methods in a Class (WMC). However, there are many more OO complexity metrics whose predictive power has not been as extensively explored. In this study, we explore the predictive ability of several complexity‐related metrics for OO software that have not been heavily validated. We do this by exploring their ability to measure quality in an evolutionary software process, by correlating these metrics to defect data for six versions of Rhino, an open‐source implementation of JavaScript written in Java. Using statistical techniques such as Spearman's correlation, principal component analysis, binary logistic regression models and their respective validations, we show that some lesser known complexity metrics including Michuraet al.'s standard deviation method complexity and Etzkornet al.'s average method complexity are more consistent predictors of OO quality than any variant of the Chidamber and Kemerer WMC metric. We also show that these metrics are useful in identifying fault‐prone classes in software developed using highly iterative or agile software development processes. Copyright © 2008 John Wiley & Sons, Ltd.
Reduced ACh release at neuromuscular synapses of heterozygous leaner Cav2.1‐mutant mice
Authors: Kaja Simon , Van De Ven Rob C. G. , Frants Rune R. , Ferrari Michel D. , Van Den Maagdenberg Arn M. J. M. , Plomp Jaap J.
Published: February 2008

Episodic ataxia type 2 (EA2) is an autosomal dominantly inherited neurological disorder. Patients have CACNA1A gene mutations resulting in truncation or single amino acid changes in the pore‐forming subunit of Cav2.1 (P/Q‐type) Ca2+ channels. These neuronal channels mediate synaptic neurotransmitter release. EA2 symptoms are thought to result from disturbed neurotransmission at cerebellar and neuromuscular synapses, caused by loss‐of‐function of Cav2.1 channels. Heterozygous leaner (Ln/wt) mice, carrying a Cacna1a truncation mutation, as well as heterozygous Cav2.1 null‐mutant (KO/wt) mice may model synaptic aspects of EA2. We studied Cav2.1‐mediated acetylcholine (ACh) release at their neuromuscular junctions (NMJs) ex vivo. KO/wt mice did not show any ACh release abnormalities, not even at older age. However, Ln/wt mice had ∼25% reduced spontaneous uniquantal ACh release and ∼10% reduced nerve‐stimulation evoked release, compared with wild‐type. EA2 is treated with acetazolamide (AZA), but the pharmacotherapeutic mechanism is unknown. We tested the possibility of a direct influence on (mutant) presynaptic Cav2.1 channel function by studying the acute effect of 50 μM AZA on ACh release at ex vivo NMJs of wild‐type, KO/wt, and Ln/wt mice. No changes were found in any of the release parameters. Our results indicate that Ln‐mutated Cav2.1 channels at Ln/wt NMJs are either normally inserted in the presynaptic membrane but have reduced function, or that they inhibit wild‐type channels by hampering their expression, trafficking, membrane insertion and/or function. In this respect Ln/wt NMJs may model EA2 synapses. Furthermore, AZA does not exert an acute, direct influence on the function of presynaptic (mutant) Cav2.1 channels. Synapse 62:337–344, 2008. © 2008 Wiley‐Liss, Inc.