bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative effects of scaffold pore size, pore volume, and total void volume on cranial bone healing patterns using microsphere‐based scaffolds
Authors: Petrie Aronin Caren E. , Sadik Karim W. , Lay Ann L. , Rion Dave B. , Tholpady Sunil S. , Ogle Roy C. , Botchwey Edward A.
Published: April 2008

Bony craniofacial deficits resulting from injury, disease, or birth defects remain a considerable clinical challenge. In this study, microsphere‐based scaffold fabrication methods were use to study the respective effects of scaffold pore size, open pore volume, and total void volume fraction on osseous tissue infiltration and bone regeneration in a critical size rat cranial defect. To compare the healing effects of these parameters, three different scaffolds types were fabricated: solid 100 μm spheres, solid 500 μm spheres, and hollow 500 μm spheres. These constructs were implanted into surgically created rat calvarial defects. By 90‐days post op, results of micro computed tomography (CT) analysis showed that all scaffolds generated similar amounts of new bone which was significantly greater than untreated controls. Interestingly, the spatial distribution of new bone within the defect area varied by scaffold group. MicroCT and histological analysis demonstrated healing restricted to the dural side in the hollow 500 μm group, whereas the solid 500 μm group demonstrated healing along the dural side and within the center of the defect. Solid 100 μm groups demonstrated healing along the dural layer, periosteal layer, and within the center of the defect. These results suggest that pore size and closed void volume may both play important roles in scaffold degradation patterns and associated bone healing. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Surface‐dependent modulation of proliferation, bone matrix molecules, and inflammatory factors in human osteoblasts
Authors: Tonnarelli Beatrice , Manferdini Cristina , Piacentini Anna , Codeluppi Katia , Zini Nicoletta , Ghisu Sonia , Facchini Andrea , Lisignoli Gina
Published: April 2008

Surface properties affect the biological properties of cells modulating the expression of different factors. Osteoblasts contribute both to new bone formation and controlling haematopoiesis through cytokines and growth factors. We analyzed the effect of bone (calcium‐phosphate bone slides), cartilaginous (hyaluronan‐based scaffold), and plastic substrate culture on human osteoblast proliferation, bone matrix molecule, and inflammatory factor expression. Osteoblast proliferation increased to a greater extent when the cells were grown for 14 days on plastic and bone slides, whereas hyaluronan‐based scaffold (HA‐scaffold) induced only a minimal increase. Collagen type I, osteonectin, alkaline phosphatase and osteocalcin were expressed on osteoblasts grown on plastic and bone slides and down‐modulated at mRNA and protein level by HA‐scaffold. Bone slides showed the ability to increase osteopontin mRNA expression. The expression of CXCR4 and CXCL13 was upregulated by bone slides and HA‐scaffold, while CXCL12 and CXCR5 expression was down‐modulated. These data suggest a substrate‐dependent modulation of human osteoblast proliferation, bone matrix and inflammatory factor expression, which might help to understand the active role played by osteoblasts in bone microenvironment by coupling bone extracellular matrix, chemokines and the haematopoietic system. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Identification of genes regulated by nanog which is involved in ES cells pluripotency and early differentiation
Authors: Liu Na , Feng Xiaoming , Fang Zhihong , Ma Fengxia , Lu Shihong , Lu Min , Han Zhongchao
Published: April 2008

Nanog plays an important role in embryonic stem (ES) cells pluripotency and self‐renewal, yet the precise mechanism through which Nanog accomplishes this important function remains unclear. To understand comprehensive molecular mechanism by which Nanog mediates, we identified genome‐wide molecular changes upon silencing Nanog in ES cells by using microarray technology. In order to downregulate Nanog expression efficiently, four siRNAs were designed on the basis of the conserved Nanog sequence and their effects on the Nanog expression were tested. Among these four siRNAs, Nanog‐siRNA‐P1 was found to be most effective. Once Nanog was downregulated, ES cells underwent differentiation by showing morphological change and decreased proliferation rate. Microarray analysis was then used to identify the altered gene expression after Nanog was silenced. A series of differentially expressed genes due to reduced expression of Nanog was identified as Nanog‐related genes. These genes identified here could provide insights into the roles of Nanog in ES cells self‐renewal and early differentiation. J. Cell. Biochem. 104: 2348–2362, 2008. © 2008 Wiley‐Liss, Inc.
Effects of prelamin A processing inhibitors on the differentiation and activity of human osteoclasts
Authors: Zini Nicoletta , Avnet Sofia , Ghisu Sonia , Maraldi Nadir Mario , Squarzoni Stefano , Baldini Nicola , Lattanzi Giovanna
Published: April 2008

Osteoclast differentiation is a complex process involving cytoskeleton and nuclear reorganization. Osteoclasts regulate bone homeostasis and have a key role in bone degenerative processes. Osteolysis and osteoporosis characterize a subset of laminopathies, inherited disorders due to defects in lamin A/C. Laminopathies featuring bone resorption are characterized, at the molecular level, by anomalous accumulation of the unprocessed lamin A precursor, called prelamin A. To obtain a suitable cell model to study prelamin A effects on osteoclasts, prelamin A processing inhibitors FTI‐277 or AFCMe were applied to peripheral blood monocytes induced to differentiate towards the osteoclastic lineage. Previous studies have shown that treatment with FTI‐277 causes accumulation of non‐farnesylated prelamin A, while AFCMe inhibition of prelamin A maturation causes accumulation of a farnesylated form. We demonstrate that monocytes subjected to FTI‐277 treatment and mostly those subjected to AFCMe administration, differentiate towards the osteoclastic lineage more efficiently than untreated monocytes, in terms of number of multinucleated giant cells, mRNA expression of osteoclast‐related genes and TRACP 5b activity. On the other hand, the bone resorption activity of osteoclasts obtained in the presence of high prelamin A levels is lower with respect to control osteoclasts. This finding may help the understanding of the osteolytic and osteoporotic processes that characterize progeroid laminopathies. J. Cell. Biochem. 105: 34–40, 2008. © 2008 Wiley‐Liss, Inc.
Claudin‐16 reduces the aggressive behavior of human breast cancer cells
Authors: Martin Tracey A. , Harrison Gregory M. , Watkins Gareth , Jiang Wen G.
Published: April 2008

Claudin‐16 (Paracellin‐1) is a transmembrane tight junction (TJ) protein originally described as having a critical role in the re‐absorption of magnesium and calcium in the kidney. This study examined expression of Claudin‐16 in human breast cells and tissues to identify a possible link between expression and aggressiveness in cells and between Claudin‐16 levels and patient prognosis. Insertion of the Claudin‐16 gene into MDA‐MB‐231 human breast cancer cells resulted in cells that were significantly less motile and invasive in behavior, with increased adhesion to matrix. These cells also exhibited significantly increased TJ functionality and “tighter” colony morphology. Moreover, growth rates were reduced in both in vitro and in vivo assays (P < 0.002). Frozen sections from breast cancer primary tumors (matched tumor 124 and background 33) were immuno‐stained. RNA was reverse transcribed and analyzed by Q‐PCR (standardized using β‐actin, normalized with cytokeratin‐19 levels). Levels of expression of Claudin‐16 were significantly decreased in node positive tumors compared to negative (P = 0.016). Expression was significantly lower in patients with node positive tumors (P = 0.016) and in those who had died from breast cancer or had general poor prognosis (P < 0.015). Immunohistochemical staining showed decreased expression of Claudin‐16 in tumor sections (P < 0.00001). In conclusion, forced expression of Claudin‐16 in breast cancer cells resulted in a less aggressive phenotype and reduced in vivo tumor volume. Claudin‐16 expression was reduced in human breast cancer, particularly in patients with aggressive tumors and high mortality. This suggests that Claudin‐16 plays a role beyond that of an initial metastasis repressor in this cancer type. J. Cell. Biochem. 105: 41–52, 2008. © 2008 Wiley‐Liss, Inc.
On the modeling of arginine‐bound carboxylates: A case study with Pyruvate Formate‐Lyase
Authors: Čondić‐Jurkić Karmen , Perchyonok V. Tamara , Zipse Hendrik , Smith David M.
Published: April 2008

High level ab initio and density functional calculations have been employed to determine the most appropriate manner in which to truncate an arginine‐bound carboxylate motif, using the substrate mechanism of Pyruvate Formate‐Lyase as a case study. The results show that, both qualitatively and quantitatively, a neutral carboxylic acid provides a more realistic approximation to the salt bridge arrangement than does a bare anionic carboxylate substituent. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
Utilizing a library of synthetic affinity ligands for the enrichment, depletion and one‐step purification of leech proteins
Authors: Dong Dexian , Gui Yanli , Chen Dezhao , Li Rongxiu
Published: April 2008

Although the concept of affinity purification using synthetic ligands had been utilized for many years, there are few articles related to this research area, and they focus only on the affinity purification of specific protein by a defined library of synthetic ligands. This study presents the design and construction of a 700‐member library of synthetic ligands in detail. We selected 297 ligand columns from a 700‐member library of synthetic ligands to screen leech protein extract. Of the 297, 154 columns had an enrichment effect, 83 columns had a depletion effect, 36 columns had a one‐step purification effect, and 58 columns had a one‐step purification via flowthrough effect. The experimental results achieved by this large library of affinity ligands provide solid convincing data for the theory that affinity chromatography could be used for the enrichment of proteins that are present in low abundance, the depletion of high abundance proteins, and one‐step purification of special proteins. Copyright © 2008 John Wiley & Sons, Ltd.
Protein–protein recognition as a first step towards the inhibition of XIAP and Survivin anti‐apoptotic proteins
Authors: Obiol‐Pardo Cristian , Granadino‐Roldán Jose Manuel , Rubio‐Martinez Jaime
Published: April 2008

Apoptosis, also called programmed cell death, is a conserved mechanism inherent to all cells that sentences them to death when they receive the appropriate external stimuli. Inhibitor of apoptosis proteins (IAPs) are a family of regulatory proteins that suppress such cell death. XIAP is the most commonly studied member of the IAP family. It binds to and inhibits Caspases, an important family of apoptotic proteases. In addition, XIAP over‐expression has been detected in numerous types of cancer. Smac/DIABLO, a mitochondrial protein that binds to IAPs and promotes Caspase activation, has the opposite action to XIAP and can be considered a key protein in the regulation of IAPs. Survivin, the smallest IAP protein, has received a lot of attention due to its specific expression in many cancer cell lines. It has been shown to interact with Smac/DIABLO, even though the structure of this complex has not yet been reported.

We analysed the protein–protein interactions appearing in the Smac/DIABLO–XIAP and Smac/DIABLO–Survivin complexes fully, using molecular dynamics simulations. This information is a first step towards the design of Smac/DIABLO peptidomimetics that could be used as innovative therapeutic agents for the treatment of malignancy.

Our results complement the experimental interactions described for the first complex and provide a detailed description for the second. We show that Smac/DIABLO interacts in a similar way with both targets through its amino terminal residues. In addition, we identify a pharmacophore formed by eight stable protein–protein interactions for the XIAP complex and seven stable protein–protein interactions for the Survivin complex, which describe the whole contact surface.

This information is used to suggest the binding mode of embelin, the first non‐peptidic inhibitor of XIAP, and two of its derivatives. Molecular docking and molecular dynamics simulations were also carried out to describe ligand and receptor flexibility.

Finally, an MMGBSA protocol was used to obtain a more quantitative description of the binding in all the complexes studied. Copyright © 2008 John Wiley & Sons, Ltd.
Mass spectrometric studies of potent inhibitors of farnesyl protein transferase—detection of pentameric noncovalent complexes
Authors: Mirza Urooj A. , Chen Guodong , Liu Yan‐Hui , Doll Ronald J. , Girijavallabhan Viyyoor M. , Ganguly Ashit K. , Pramanik Birendra N.
Published: April 2008

Farnesyl protein transferase (FPT) inhibition is an interesting and promising approach to noncytotoxic anticancer therapy. Research in this area has resulted in several orally active compounds that are in clinical trials. Electrospray ionization (ESI) time‐of‐flight mass spectrometry (TOF‐MS) was used for the direct detection of a 95 182 Da pentameric noncovalent complex of α/β subunits of FPT containing Zn, farnesyl pyrophosphate (FPP) and SCH 66336, a compound currently undergoing phase III clinical trials as an anticancer agent. It was noted that the desalting of protein samples was an important factor in the detection of the complex. This study demonstrated that the presence of FPP in the system was necessary for the detection of the FPT–inhibitor complex. No pentameric complex was detected in the spectrum when the experiment was carried out in the absence of the FPP. An indirect approach was also applied to confirm the noncovalent binding of SCH 66336 to FPT by the use of an off‐line size exclusion chromatography followed by liquid chromatography‐electrospray ionization mass spectrometry (LC‐ESI‐MS) for the detection of the inhibitor. Copyright © 2008 John Wiley & Sons, Ltd.
Reconstructing hydrological variability in Lake Baikal during MIS 11: an application of oxygen isotope analysis of diatom silica
Authors: Mackay Anson W. , Karabanov Eugene , Leng Melanie J. , Sloane Hilary J. , Morley David W. , Panizzo Virginia N. , Khursevich Galina , Williams Douglas
Published: April 2008

In this paper we reconstruct hydrological variability in Lake Baikal during Marine Isotope Stage 11 (MIS 11) (427–362 ka BP) from oxygen isotope analysis of diatom silica. Highest δ18Odiatom values are found during MIS 11.3, highlighting the dominance of hydrological input from rivers flowing into the south and central basins of Lake Baikal, especially the Selenga River. Hydrological input from south basin rivers dominated for over 30 ka. However, there is evidence from both biogenic silica and δ18Odiatom records for an abrupt cooling event at ca. 390 ka BP. Stadial conditions at this time are coincident with an iceberg discharge event into the North Atlantic. The decline in δ18Odiatom values suggests increasing proportion of hydrological input from rivers to the north of Lake Baikal, due to greater influence of winter precipitation and snow‐melt. After a period of interstadial conditions during the early stages of MIS 11.1, biogenic silica and δ18Odiatom values decline, mirroring the slow growth in Northern Hemisphere ice sheets. Despite rigorous cleaning procedures, palaeoclimatic inferences need to be treated with caution due to contamination of the δ18Odiatom record; during stadial and glacial periods, contamination of the δ18Odiatom record is even more significant. © Natural Environment Research Council (NERC) copyright 2008. Reproduced with the permission of NERC. Published by John Wiley & Sons, Ltd.
Silicon, oxygen and carbon isotope composition of wheat (Triticum aestivum L.) phytoliths: implications for palaeoecology and archaeology
Authors: Hodson Martin J. , Parker Adrian G. , Leng Melanie J. , Sloane Hilary J.
Published: April 2008

Six mature wheat (Triticum aestivum L.) plants from one crop were collected one week before harvest, and organs were separated as follows: culm, rachis, leaf sheaths, leaf blades and inflorescence bracts. Percentage silica (% SiO2), % C, % N and δ13C were determined in these samples. Phytoliths isolated from the individual organs were subsequently analysed for δ29Si, δ30Si, and δ18O, as well as % C, % N and δ13C from occluded organic material within the phytoliths. Percentage silica was highest in the leaf sheaths and leaf blades and lower in the inflorescence bracts, culm and rachis. δ30Si and δ29Si were highly correlated, and both increased in the upper parts of the plant. It appears there are two routes for Si transport within the plant, and that heavier isotopes increase towards the end of both routes. The δ18O results indicate that the culm and the leaf blades were the sites of highest δ18O, with lower values in the rachis, leaf sheath and inflorescence. There was no correlation between the accumulation of either heavy silicon isotope (29Si and 30Si) and heavy oxygen accumulation (18O). δ13C values were typical of C3 species, and whole plant and isolated phytolith values were similar. Low % N concentrations were detected in phytoliths. © Natural Environment Research Council (NERC) copyright 2008. Reproduced with the permission of NERC. Published by John Wiley & Sons, Ltd.
Isotope offsets in marine diatom δ18O over the last 200 ka
Authors: Swann George E. A. , Leng Melanie J. , Sloane Hilary J. , Maslin Mark A.
Published: April 2008

Previous work has suggested that a species effect may be present in diatom oxygen isotope ratios (δ18Odiatom). While predominantly attributed to be a size‐related species effect, currently the precise mechanism remains unknown. Here, two size fractions of diatoms (38–75 µm and >100 µm) covering the last 200 ka are analysed for δ18O from ODP Site 882 in the North‐West Pacific Ocean. Synchronous variations of up to 13‰ occur in both size fractions. However, large isotope offsets (mean = 2.02‰) exist between the two fractions with no relationship between their magnitude and the overlying palaeoenvironmental conditions. In contrast to earlier work from the same site, no one size fraction is constantly higher or lower in δ18O relative to the other. As such, the dominant mechanism is most likely separate to the size effect previously detected. In addition, no relationship exists between the magnitude of the offsets and the species composition of the two size fractions. The presence of these isotope offsets imposes significant constraints upon the future use of δ18Odiatom in palaeoceanographic reconstructions and reiterates the need to extract and analyse only species‐ and size‐specific diatom samples. © Natural Environment Research Council (NERC) copyright 2008. Reproduced with the permission of NERC. Published by John Wiley & Sons, Ltd.
Towards an understanding of late Quaternary variations in the continental biogeochemical cycle of silicon: multi‐isotope and sediment‐flux data for Lake Rutundu, Mt Kenya, East Africa, since 38 ka BP
Authors: Street‐Perrott F. Alayne , Barker Philip A. , Leng Melanie J. , Sloane Hilary J. , Wooller Matthew J. , Ficken Katherine J. , Swain David L.
Published: April 2008

Silicon is an essential nutrient for marine diatoms, which dominate the export of organic carbon to the deep ocean. Despite the dominance of the oceanic Si budget by fluvial inputs and the role of the land biosphere in controlling Si losses from rocks and soils to rivers, few studies have considered how continental biogeochemical Si fluxes varied on an orbital timescale. We reconstruct changes in Si cycling by the catchment‐lake ecosystem of Lake Rutundu, Mt Kenya (3078 m a.s.l.), over the last ca. 38 ka, using a novel combination of lake‐sediment fluxes and stable‐isotope (δ13C, δ15N, δ18O, δ30Si) data. Under glacial conditions (38.3–14.3 ka BP), high diatom productivity was maintained by substantial losses of dissolved SiO2 and soil nutrients from a sparse, leaky, terrestrial ecosystem. During the following period of enhanced monsoon rainfall and seasonality (14.3–9.5 ka BP), rapid Si cycling by fire‐prone, mesic grassland was associated with substantial aeolian transport of opal phytoliths by smoke plumes, but greatly reduced nutrient losses in runoff. Invasion of tall, subalpine shrubs after 9.5 ka BP further enhanced landscape stability, leading to very low sediment fluxes of both phytoliths and diatoms. This case study offers new insights into processes that may have operated at biome to continental scales during the late Quaternary. © Natural Environment Research Council (NERC) copyright 2008. Reproduced with the permission of NERC. Published by John Wiley & Sons, Ltd.
Laser Materials Processing in Japan
Authors: Miyamoto Isamu
Published: April 2008

Japan is one of the most advanced countries in terms of manufacturing technologies, and the role of lasers has become increasingly important since the beginning of 21st century [1]. The Japanese laser market is expanding steadily and competing with existing manufacturing technologies. In this article, recent market trends of laser processing systems using CO2 lasers, solid state lasers and excimer lasers in Japanese market are outlined. Hot topics of successful laser‐based manufacturing technologies for largescale production are also introduced.
Process Monitoring and Control of Laser Beam Welding
Authors: Kaierle Stefan
Published: April 2008

Laser materials processing is widely used in industry today. For a long time, the statement „the best sensor is no sensor”︁was mentioned often in this field of technology. However, a change of paradigm can now be observed. ISO 9000 and other by law‐enforced regulations have led to the understanding that quality control is an essential tool in modern manufacturing and necessary in order to keep production results in deterministic boundaries.
Laser Drilling in Industrial Use
Authors: Dürr Ulrich
Published: April 2008

Laser drilling makes about 3 % of the Laser material processing market and there are many niches within this market, each with special requirements. The most important share has through hole drilling. The respective holes have diameters between 0.005 to 1.5 mm and aspect ratios (depth/diameter) from less than 1 to above 50. They have different requirements with respect to geometrical tolerances and process side effects like thermal side effects as change of metallurgy, recast, cracks, burr etc. The situation is similar for blind holes. In the following through hole drilling will be discussed.
Betulinic acid suppresses constitutive and TNFα‐induced NF‐κB activation and induces apoptosis in human prostate carcinoma PC‐3 cells
Authors: Rabi Thangaiyan , Shukla Sanjeev , Gupta Sanjay
Published: April 2008

Development of chemoresistance in androgen‐refractory prostate cancer cells is partly due to constitutive activation of Rel/NF‐κB transcription factors that regulate several cell survival and anti‐apoptotic genes. In this study we examined whether betulinic acid (BetA), a pentacyclic triterpene from the bark of white birch, is effective in inhibiting NF‐κB expression in androgen‐refractory human prostate cancer cells exhibiting high constitutive NF‐κB expression. Treatment of PC‐3 cells with BetA inhibited DNA binding and reduced nuclear levels of the NF‐κB/p65. BetA‐mediated NF‐κB inhibition involved decreased IKK activity and phosphorylation of IκBα at serine 32/36 followed by its degradation. Reporter assays revealed that NF‐κB inhibition by BetA is transcriptionally active. These effects were found to correlate with a shift in Bax/Bcl‐2 ratio and cleavage of poly(ADP)ribose polymerase more towards apoptosis. BetA also inhibited TNFα‐induced activation of NF‐κB via the IκBα pathway, thereby sensitizing the cells to TNFα‐induced apoptosis. Our studies demonstrate that BetA effectively inhibits constitutive NF‐κB activation and supports the rationale for targeting NF‐κB through combination protocols with BetA in androgen‐refractory prostate cancer. © 2008 Wiley‐Liss, Inc.
Carbonic anhydrase III promotes transformation and invasion capability in hepatoma cells through FAK signaling pathway
Authors: Dai Huei‐Yue , Hong Chih‐Chen , Liang San‐Chi , Yan Ming‐De , Lai Gi‐Ming , Cheng Ann‐Lii , Chuang Shuang‐En
Published: April 2008

Carbonic anhydrase III (CAIII) is distinguished from the other members of the CA family by low carbon dioxide hydratase activity, resistance to the CA inhibitor acetazolamide, and a predominant expression in the liver of males. In this report the effects of CAIII expression on liver cancer cells invasiveness were explored. Overexpression of CAIII in the HCC cell line SK‐Hep1 resulted in increased anchorage‐independent growth and invasiveness. And siRNA‐mediated silencing of CAIII expression decreased the invasive ability of SK‐Hep1 cells. Furthermore, CAIII transfectants showed elevated focal adhesion kinase (FAK) and Src activity. Silencing of FAK expression in CAIII transfectants led to suppression of HCC cell invasion. More importantly, the CAIII transfectants acidified the culture medium at an accelerated speed than the control cells did. Taken together, these data suggest that the CAIII‐promoted invasive ability of HCC cells may probably be mediated through, at least in part, the FAK signaling pathway via intracellular and/or extracellular acidification. © 2008 Wiley‐Liss, Inc.
Overexpression of cyclooxygenase‐2 (COX‐2) in the mouse urinary bladder induces the expression of immune‐ and cell proliferation‐related genes
Authors: Wang Xingya , Colby Jennifer K.L. , Rengel Robert C. , Fischer Susan M. , Clinton Steven K. , Klein Russell D.
Published: April 2008

The mechanisms whereby cyclooxygenase‐2 (COX‐2) overexpression may contribute to bladder carcinogenesis remain unknown. We recently developed a transgenic mouse model overexpressing COX‐2 under the control of a bovine keratin 5 (BK5) promoter causing a high incidence of transitional cell hyperplasia (TCH) in the bladder with a proportion of lesions progressing to invasive carcinoma. Microarray gene analysis was employed to determine the effects of COX‐2 overexpression on gene expression profiles in the urinary bladder. Statistical analysis revealed that 70 genes were upregulated and 60 were downregulated by twofold or more in bladders from transgenic compared to wild‐type mice. Expression Analysis Systematic Explorer (EASE) analysis revealed that genes associated with Immune/Stress Response and Cell Cycle/Proliferation biological processes were overexpressed in the transgenic mice. Relevant downregulated genes included three transforming growth factor (TGF)‐β related genes, Tgfb2, Tgfb3, and Tgfbi. The growth factor epiregulin was the most highly induced gene among those validated by qRT‐PCR in TCH of BK5.COX‐2 mouse bladders in parallel with increased staining for Ki67. Prostaglandin E2 (PGE2) directly induced the expression of epiregulin mRNA in bladders from wild‐type FVB mice ex vivo. We further determined that recombinant epiregulin increased both cell proliferation and Erk phosphorylation in UMUC‐3 bladder cancer cells. These results indicate that the response of the mouse urinary bladder to elevated COX‐2 expression includes enhanced inflammatory response and induction of cell proliferation. The growth factor epiregulin may play a role in bladder carcinogenesis and may serve as a novel target for the prevention and treatment of bladder cancer. © 2008 Wiley‐Liss, Inc.
The course of dyskinesia induction by different treatment schedules of levodopa in Parkinsonian rats: Is continuous dopaminergic stimulation necessary?
Authors: Tsironis Christos , Marselos Marios , Evangelou Angelos , Konitsiotis Spiridon
Published: April 2008

The aim of the present study was to investigate the course of levodopa induced dyskinesia (LID) development in parkinsonian rats treated with several different levodopa dosing regiments. Administration of 6.25 mg/kg levodopa once daily did not induce any dyskinesia for the first 12.5 ± 2.5 days. Then, LID gradually increased in intensity reaching an AIMs score on day 40 of 6.3 ± 0.9. Treatment with 6.25 mg/kg of levodopa qid resulted in the rapid appearance of LID with a mean latency of 2 days and an AIMs score of 19.9 ± 2.9 on day 10. Levodopa (25 mg/kg) once daily induced severe LID from the second day of treatment reaching an AIMs score of 35 ± 3.2. In summary, the worst way for delivering levodopa was through intermittent administration of high doses. The daily cumulative dose of levodopa was found more important for LID induction than the total amount of levodopa received. In contrast, the best way to administer levodopa in respect to prevention/delay of LID was “low dopaminergic stimulation” with one low daily dose, instead of trying to achieve “continuous dopaminergic stimulation” using several levodopa doses throughout the day. The benefits of this strategy offered protection against severe dyskinesia even if subsequently subjects were switched to high dose levodopa. © 2007 Movement Disorder Society
Red flags for multiple system atrophy
Authors: Köllensperger Martin , Geser Felix , Seppi Klaus , Stampfer‐Kountchev Michaela , Sawires Martin , Scherfler Christoph , Boesch Sylvia , Mueller Joerg , Koukouni Vasiliki , Quinn Niall , Pellecchia Maria Teresa , Barone Paolo , Schimke Nicole , Dodel Richard , Oertel Wolfgang , Dupont Erik , Østergaard Karen , Daniels Christine , Deuschl Günther , Gurevich Tanya , Giladi Nir , Coelho Miguel , Sampaio Cristina , Nilsson Christer , Widner Håkan , Sorbo Francesca Del , Albanese Alberto , Cardozo Adriana , Tolosa Eduardo , Abele Michael , Klockgether Thomas , Kamm Christoph , Gasser Thomas , Djaldetti Ruth , Colosimo Carlo , Meco Giuseppe , Schrag Anette , Poewe Werner , Wenning Gregor K.
Published: April 2008

The clinical diagnosis of multiple system atrophy (MSA) is fraught with difficulty and there are no pathognomonic features to discriminate the parkinsonian variant (MSA‐P) from Parkinson's disease (PD). Besides the poor response to levodopa, and the additional presence of pyramidal or cerebellar signs (ataxia) or autonomic failure as major diagnostic criteria, certain other clinical features known as “red flags” or warning signs may raise the clinical suspicion of MSA. To study the diagnostic role of these features in MSA‐P versus PD patients, a standardized red flag check list (RFCL) developed by the European MSA Study Group (EMSA‐SG) was administered to 57 patients with probable MSA‐P and 116 patients with probable PD diagnosed according to established criteria. Those red flags with a specifity over 95% were selected for further analysis. Factor analysis was applied to reduce the number of red flags. The resulting set was then applied to 17 patients with possible MSA‐P who on follow‐up fulfilled criteria of probable MSA‐P. Red flags were grouped into related categories. With two or more of six red flag categories present specificity was 98.3% and sensitivity was 84.2% in our cohort. When applying these criteria to patients with possible MSA‐P, 76.5% of them would have been correctly diagnosed as probable MSA‐P 15.9 (±7.0) months earlier than with the Consensus criteria alone. We propose a combination of two out of six red flag categories as additional diagnostic criteria for probable MSA‐P. © 2008 Movement Disorder Society.
Circadian rest‐activity rhythm is altered in Parkinson's disease patients with hallucinations
Authors: Whitehead Daisy L. , Davies Ann D.M. , Playfer Jeremy R. , Turnbull Christopher J.
Published: April 2008

The sleep‐wake cycle in Parkinson's Disease (PD) is profoundly disrupted, but less is known about circadian rhythm in PD and its relationship to other important clinical features. This study compared rest‐activity rhythms in healthy older adults and PD patients with and without hallucinations. Twenty‐nine older adults and 50 PD patients (27 with hallucinations, 23 without) were assessed using wrist‐worn actigraphy for 5 days. Disease‐related and cognitive data were also collected. PD patients demonstrated reduced amplitude of activity (F = 12.719, P < 0.01) and increased intradaily variability (F = 22.005, P < 0.001), compared to healthy older adults, independently of age, and cognitive status. Hallucinators showed lower interdaily stability (F = 7.493, P < 0.01) significantly greater activity during “night‐time” (F = 6.080, P < 0.05) and significantly reduced relative amplitude of activity (F = 5.804, P < 0.05) compared to nonhallucinators, independently of clinical factors including motor fluctuations. PD patients with hallucinations display altered rest‐activity rhythm characterized by an unpredictable circadian pattern across days, likely arising from damage to brainstem and hypothalamic sleep centers. Treatment of sleep and rest‐activity rhythm disturbance is an important target in Parkinson's Disease. © 2008 Movement Disorder Society.
Long‐term follow‐up of thalamic stimulation versus thalamotomy for tremor suppression
Authors: Schuurman P. Richard , Bosch D. Andries , Merkus Maruschka P. , Speelman Johannes D.
Published: April 2008

Thalamic stimulation and thalamotomy for treatment of tremor due to Parkinson's disease, essential tremor, and multiple sclerosis were compared in a randomized trial. The symptomatic and functional outcome was studied after 5 years of follow‐up. Sixty‐eight patients were treated (45 Parkinson's disease, 13 essential tremor, 10 multiple sclerosis) by thalamotomy (n = 34) or thalamic stimulation (n = 34). After 5 years, 48 patients were available for follow‐up. The primary outcome measure was change in functional status measured by the Frenchay Activities Index (FAI), scores ranging from 0 to 60. Secondary outcome measures were tremor severity, frequency of complications, and patients' assessment of the outcome. The mean difference in FAI scores between thalamic stimulation and thalamotomy was 4.4 (95% CI: 1.1–7.7) after 6 months, 3.3 (95% CI: −0.03–6.6) after 2 years and 4.0 (95% CI: 0.3–7.7) after 5 years in favor of stimulation. Tremor suppression was equally effective after both procedures, and stable in Parkinson patients. In ET and multiple sclerosis, a diminished effect of stimulation was observed in half of the patients. There were six stimulation equipment‐related complications, but neurological side effects of surgery were higher after thalamotomy. Subjective outcome‐assessment by the patients was more favorable in the stimulation group. © 2008 Movement Disorder Society.
Familial aggregation of Parkinson's disease: A meta‐analysis
Authors: Thacker Evan L. , Ascherio Alberto
Published: April 2008

We sought to determine the relative risk (RR) of Parkinson's disease (PD) for having a first‐degree relative with PD versus having no first‐degree relative with PD. Studies of familial aggregation of PD were identified by searching Medline and other sources. From each study, RRs were extracted or calculated based on the published data. Studies were categorized according to methodological characteristics, as well as by first‐degree relationship type and age at PD onset restrictions. Meta‐analyses and meta‐regressions were based on random effect models. Twenty‐nine studies of familial aggregation of PD were identified with results for first‐degree relatives. The best estimate of the RR of PD for having a first‐degree relative with PD was 2.9 (95% CI: 2.2, 3.8; P = 2.2 E‐14), based on the studies with the most rigorous methods. The RR for sibling pairs was 4.4 (95% CI: 3.1, 6.1; P < 1.0 E‐30), while for child‐parent pairs it was 2.7 (95% CI: 2.0, 3.7; P = 3.6 E‐10). The RR for early onset PD was 4.7 (95% CI: 3.2, 6.8; P = 6.7 E‐16), while for late onset PD it was 2.7 (95% CI: 1.9, 3.9; P = 1.8 E‐8). Inclusion of methodologically less rigorous investigations tended to increase the RR estimates. Summary RRs were clearly elevated above one for all study methods, all first‐degree relationship types, and all age at onset categories. Familial aggregation of PD is strong and unlikely to be due to chance or to deficiencies in study methodology. © 2008 Movement Disorder Society.
Multiregional brain iron deficiency in restless legs syndrome
Authors: Godau Jana , Klose Uwe , Di Santo Adriana , Schweitzer Katherine , Berg Daniela
Published: April 2008

Evidence for tissue iron deficiency in restless legs syndrome (RLS) is limited to the substantia nigra (SN). Using MRI, we assessed T2 values of various brain regions in 6 RLS patients and 19 controls and correlated them with sonographically assessed SN echogenicity. Both neuroimaging features are supposed to correlate with tissue iron content. Mean T2 values of all regions were higher in patients (2.9–7.8%), though significantly increased only in four regions; the mean T2 over all voxels was higher in patients (5.1%, P < 0.001) and correlated inversely with SN echogenicity (r = −0.61, P < 0.001). This indicates multiregional (global) brain iron deficiency in RLS and proposes SN echogenicity as a potential morphological marker for brain iron status. © 2008 Movement Disorder Society
Asymptotic behavior of vortices in axisymmetric flow without swirl
Authors: Ren Kun , Tang Tai‐Man
Published: April 2008

We investigate the confinement properties of bounded, nonnegative, compactly supported vortices of axisymmetric incompressible Euler flows without swirl. We show that along one direction of the symmetry axis, its support can grow no faster than O[(t log t)1/2]. The rate at which it approaches the symmetry axis is also estimated. Together with the result of Maffei–Marchioro on the radial growth rate of the support, it is contained in a slowly expanding tubular region. The techniques of the above‐mentioned authors, Iftimie–Lopes–Nussenzveig and Iftimie–Sideris–Gamblin, are used. Copyright © 2008 John Wiley & Sons, Ltd.
A geometrically and materially non‐linear piezoelectric three‐dimensional‐beam finite element formulation including warping effects
Authors: Butz A. , Klinkel S. , Wagner W.
Published: April 2008

This paper is concerned with a three‐dimensional piezoelectric beam formulation and its finite element implementation. The developed model considers geometrically and materially non‐linear effects. An eccentric beam formulation is derived based on the Timoshenko kinematics. The kinematic assumptions are extended by three additional warping functions of the cross section. These functions follow from torsion and piezoelectrically induced shear deformations. The presented beam formulation incorporates large displacements and finite rotations and allows the investigation of stability problems. The finite element model has two nodes with nine mechanical and five electrical degrees of freedom. It provides an accurate approximation of the electric potential, which is assumed to be linear in the direction of the beam axis and quadratic within the cross section. The mechanical degrees of freedom are three displacements, three rotations and three scaling factors for the warping functions. The latter are computed in a preprocess by solving a two‐dimensional in‐plane equilibrium condition with the finite element method. The gained warping patterns are considered within the integration through the cross section of the beam formulation. With respect to material non‐linearities, which arise in ferroelectric materials, the scalar Preisach model is embedded in the formulation. This model is a mathematical model for the general description of hysteresis phenomena. Its application to piezoelectric materials leads to a phenomenological model for ferroelectric hysteresis effects. Here, the polarization direction is assumed to be constant, which leads to unidirectional constitutive equations. Some examples demonstrate the capability of the proposed model. Copyright © 2008 John Wiley & Sons, Ltd.
Practical finite‐analytic method for solving differential equations by compact numerical schemes
Authors: Civan Faruk
Published: April 2008

Methodology for development of compact numerical schemes by the practical finite‐analytic method (PFAM) is presented for spatial and/or temporal solution of differential equations. The advantage and accuracy of this approach over the conventional numerical methods are demonstrated. In contrast to the tedious discretization schemes resulting from the original finite‐analytic solution methods, such as based on the separation of variables and Laplace transformation, the practical finite‐analytical method is proven to yield simple and convenient discretization schemes. This is accomplished by a special universal determinant construction procedure using the general multi‐variate power series solutions obtained directly from differential equations. This method allows for direct incorporation of the boundary conditions into the numerical discretization scheme in a consistent manner without requiring the use of artificial fixing methods and fictitious points, and yields effective numerical schemes which are operationally similar to the finite‐difference schemes. Consequently, the methods developed for numerical solution of the algebraic equations resulting from the finite‐difference schemes can be readily facilitated. Several applications are presented demonstrating the effect of the computational molecule, grid spacing, and boundary condition treatment on the numerical accuracy. The quality of the numerical solutions generated by the PFAM is shown to approach to the exact analytical solution at optimum grid spacing. It is concluded that the PFAM offers great potential for development of robust numerical schemes. © 2008 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2009
Synthesis of carboxymethyl potato starch and comparison of optimal reaction conditions from different sources
Authors: Bi Yinghui , Liu Mingzhu , Wu Lan , Cui Dapeng
Published: April 2008

Carboxymethyl potato starch (CMPS) was synthesized under heterogeneous reaction conditions. The influences of etherification temperature, alkalization and etherification time, sodium hydroxide to monochloroacetic acid (MCA) molar ratio (nNaOH/nMCA), theoretical degree of substitution (DSt), the ratio of isopropyl alcohol (IPA) volume to starch mass (vIPA/mst) on degree of substitution (DS) and reaction efficiency (RE) of CMPS were investigated. Compared with the previous literature data, the results had significant difference for the optimal carboxymethylation conditions of potato starch from different sources. CMPS prepared under optimal conditions showed the highest DS and RE, which were 1.36 and 0.88, respectively. Furthermore, the RE value in this work is considerably higher than that reported in the literature. The time of alkalization and etherification were also discussed independently. In addition, CMPS was characterized by Fourier transform infrared spectrophotometry and scanning electron microscopy (SEM). Copyright © 2008 John Wiley & Sons, Ltd.
Synthesis, static, and dynamic light scattering studies of soluble aromatic polyamide
Authors: Zulfiqar Sonia , Ishaq Muhammad , Ahmad Zahoor , Sarwar Muhammad Ilyas
Published: April 2008

Aromatic polyamide was synthesized via condensation polymerization of 4‐aminophenyl sulfone (APS) with isophthaloyl chloride (IPC) using N,N‐dimethyl acetamide (DMAc) as a solvent under anhydrous conditions. The purified aramid was studied by laser light scattering (LLS) in dimethyl sulfoxide (DMSO), a thermodynamically good solvent at 20°C. Static and dynamic light scattering studies permitted to determine the weight average molecular weight $\langle {M_{\rm w}}\rangle $, radius of gyration $\langle {R_{\rm g}}\rangle $, second virial coefficient A2, the hydrodynamic radius RH, and the diffusion coefficient D. Light scattering experiments were conducted at five concentrations ranging from 0.27 to 2.5 g/L. LLS measurement is also a very useful technique to study the aggregation or association in a polymer system as long as the large “clusters” are reasonably stable in time. The intensity autocorrelation function obtained on the quasi‐elastically scattered light showed a simple diffusive relaxation mode. The ratio of radius of gyration to the hydrodynamic radius, i.e. $\langle {R_{\rm g} }\rangle /\langle {R_{\rm H}}\rangle $ ∼ 1.3 indicates that the polyamide chain has coil conformation in DMSO at 20°C. Copyright © 2008 John Wiley & Sons, Ltd.
Non‐halogen fire resistant plastics for aircraft interiors
Authors: Lyon Richard E. , Emrick Todd
Published: April 2008

Strategies for developing fireproof aircraft cabin materials are reviewed in light of environmental legislation restricting the use of halogens in plastics. The important physical and chemical processes of flaming combustion in terms of their effect on the heat release rate (HRR) of a burning material are flame inhibition, fuel replacement, heat resistance, and intumescence. These fire resistance (FR) mechanisms acting simultaneously or synergistically are particularly effective at reducing HRR of a new generation of transparent plastics suitable for aircraft cabin interiors. Copyright © 2008 John Wiley & Sons, Ltd.
Progress in the development of interpenetrating polymer network hydrogels
Authors: Myung David , Waters Dale , Wiseman Meredith , Duhamel Pierre‐Emile , Noolandi Jaan , Ta Christopher N. , Frank Curtis W.
Published: April 2008

Interpenetrating polymer networks (IPNs) have been the subject of extensive study since their advent in the 1960s. Hydrogel IPN systems have garnered significant attention in the last two decades due to their usefulness in biomedical applications. Of particular interest are the mechanical enhancements observed in “double network” IPN systems which exhibit nonlinear increases in fracture properties despite being composed of otherwise weak polymers. We have built upon pioneering work in this field as well as in responsive IPN systems to develop an IPN system based on end‐linked poly‐(ethylene glycol) (PEG) and loosely crosslinked poly(acrylic acid) (PAA) with hydrogen bond‐ reinforced strain‐hardening behavior in water and high initial Young's moduli under physiologic buffer conditions through osmotically induced pre‐stress. Uniaxial tensile tests and equilibrium swelling measurements were used to study PEG/PAA IPN hydrogels having second networks prepared with varying crosslinking and photoinitiator content, pH, solids content, and comonomers. Studies involving the addition of non‐ionic comonomers and neutralization of the second network showed that template polymerization appears to be important in the formation of mechanically enhanced IPNs. Copyright © 2008 John Wiley & Sons, Ltd.
Effect of core group substituents on the monomer mesophase, photocuring, and film viscoelastic properties of mesogenic diacrylates
Authors: Suresh Kattimuttathu I. , Tamboli Jaki R. , Rao Butti S. , Verma Suraj , Unnikrishnan G.
Published: April 2008

In this paper, the influence of molecular structure variations on the mesophase behavior, photocurability, and film properties of polymerizable mesogenic diacrylates is reported. The effect of methoxy or chloro substituent on the mesophase behavior of the monomers, present at the 2‐position of the phenylene core, in comparison to the unsubstituted core, has been studied using thermal and photo‐DSC techniques. These monomers were used in combination with a chiral dopant to form cholesteric mesophases, which was subsequently crosslinked through photopolymerization. Optical microscopy and polarized optical microscopy (POM) were used to study the morphology of monomers as well as the photopolymerized films. Optical images show the influence of chiral dopant on the texture present in the films, both before and after the crosslinking. POM images show the mesophase present in the monomers and the free films. Evaluation of viscoelastic properties of the photocured films demonstrates the influence of mesogenic core substituents on the network transition temperature, modulus, and damping characteristics. Copyright © 2008 John Wiley & Sons, Ltd.