bluuebunny/crossref_metadata_2025 huggingface dataset:
Production of P‐glycoprotein from the MDR1 upstream promoter is insufficient to affect the response to first‐line chemotherapy in advanced breast cancer
Authors: Raguz Selina , Randle Rebecca A. , Sharpe Eva R. , Foekens John A. , Sieuwerts Anieta M. , Meijer‐van Gelder Marion E. , Melo Junia V. , Higgins Christopher F. , Yagüe Ernesto
Published: October 2007

Multidrug resistance, the phenomenon by which cells treated with a drug become resistant to the cytotoxic effect of a variety of other structurally and functionally unrelated drugs, is often associated with the expression of P‐glycoprotein, an efflux membrane pump coded by the MDR1 (ABCB1) gene. Transcription from MDR1 can start at 2 promoters: a well‐characterized downstream promoter and an as yet uncharacterized upstream promoter (USP). We have previously determined that the USP is activated in some drug‐resistant cell lines, in primary breast tumors and in metastatic epithelial cells isolated from the lymph nodes of breast cancer patients. In this study, we report the cloning and characterization of the MDR1 USP and studied its association with chemotherapy response in breast cancer patients. Deletion analysis indicated that a nearby endogenous retroviral long terminal repeat is not responsible for promoter activation, and that the region within the first 400 nucleotides upstream from the transcription start point contained all the elements necessary for promoter activity in drug‐resistant cells. We identified an element recognized by the transcription factor NF‐IL6 (activated upon interleukin‐6 exposure) which is necessary for promoter activity in drug‐resistant cells and plays a role in the activation of the promoter in response to interleukin‐6 in breast cancer MCF‐7 cells. Although transcripts from this promoter are associated with translating polyribosomes, their low abundance makes the amount of synthesized P‐glycoprotein insufficient to affect the response to first‐line chemotherapy in patients with advanced breast cancer. © 2007 Wiley‐Liss, Inc.
Morphoregulation by acetylcholinesterase in fibroblasts and astrocytes
Authors: Anderson Alexandra A. , Ushakov Dmitry S. , Ferenczi Michael A. , Mori Ryoichi , Martin Paul , Saffell Jane L.
Published: October 2007

Acetylcholinesterase (AChE) terminates neurotransmission at cholinergic synapses by hydrolysing acetylcholine, but also has non‐enzymatic morphoregulatory effects on neurons such as stimulation of neurite outgrowth. It is widely expressed outside the nervous system, but its function in non‐neuronal cells is unclear. Here we have investigated the distribution and function of AChE in fibroblasts and astrocytes. We show that these cells express high levels of AChE protein that co‐migrates with recombinant AChE but contains little catalytic activity. Fibroblasts express transcripts encoding the synaptic AChE‐T isoform and its membrane anchoring peptide PRiMA‐I. AChE is strikingly distributed in arcs, rings and patches at the leading edge of spreading and migrating fibroblasts and astrocytes, close to the cell–substratum interface, and in neuronal growth cones. During in vivo healing of mouse skin, AChE becomes highly expressed in re‐epithelialising epidermal keratinocytes 1 day after wounding. AChE appears to be functionally important for polarised cell migration, since an AChE antibody reduces substratum adhesion of fibroblasts, and slows wound healing in vitro as effectively as a β1‐integrin antibody. Moreover, elevation of AChE expression increases fibroblast wound healing independently of catalytic activity. Interestingly, AChE surface patches precisely co‐localise with amyloid precursor protein and the extracellular matrix protein perlecan, but not focal adhesions or α‐dystroglycan, and contain a high concentration of tyrosine phosphorylated proteins in spreading cells. These findings suggest that cell surface AChE, possibly in a novel signalling complex containing APP and perlecan, contributes to a generalised mechanism for polarised membrane protrusion and migration in all adherent cells. J. Cell. Physiol. 215: 82–100, 2008. © 2007 Wiley‐Liss, Inc.
Cutting two graphs simultaneously
Authors: Patel Viresh
Published: October 2007

Consider two graphs, $G_1$ and $G_2$, on the same vertex set V, with $|V|= n$ and $G_{i}$ having $m_{i}$ edges for $i = 1,2$. We give a simple algorithm that partitions V into sets A and B such that $e_{{G}_{1}}(A,B) \geq m_{1}/2$ and $e_{G_{2}}(A,B) \geq m_{2}/2 - \Delta (G_{2})/2$. We also show, using a probabilistic method, that if $G_1$ and $G_2$ belong to certain classes of graphs, (for instance, if $G_1$ and $G_2$ both have a density of at least 2/, or if $G_1$ and $G_2$ are both regular of degree at most $(n/16) - 6$ with n sufficiently large) then we can find a partition of V into sets A and B such that $e_{G_{i}}(A,B) \geq m_{i}/2$ for $i = 1,2$. © 2007 Wiley Periodicals, Inc. J Graph Theory 57: 19–32, 2008
A case for a downwasting mountain glacier during Termination I, Verçenik valley, northeastern Turkey
Authors: Akçar N. , Yavuz V. , Ivy‐Ochs S. , Kubik P. W. , Vardar M. , Schlüchter C.
Published: October 2007

Field evidence of palaeoglacial records in the Verçenik valley in the Eastern Black Sea Mountains was examined and 19 samples for surface exposure dating with cosmogenic 10Be were collected with the aim of increasing knowledge on the amplitude and frequency of palaeoglacier advances in Anatolia. Glacial erosional features were mapped and the flow directions of the palaeoglaciers were determined. The Verçenik palaeoglacier advanced before 26.1 k ± 1.2 k yr. The Last Glacial Maximum (LGM) advance continued until 18.8 k ±1.0 k yr. The Verçenik palaeoglacier collapsed during Termination I. After 17.7 k ± 0.8 k yr there was no more ice in the main valley. The Verçenik palaeoglacier most probably then separated into five small glaciers that were restricted to the tributary valleys. Among these, the Hemşin palaeoglacier completed its recession around 15.7 k ± 0.8 k yr. On the basis of glacial erosion features, a Lateglacial glacier advance can be identified. Evidence of the Little Ice Age advance appears to be absent. The results from this valley system seem to be consistent with the first results from the adjacent Kavron valley and with the Anatolian LGM palaeoclimate, the sea surface temperature minima in the western Mediterranean, the deposition of red clay layers in the Black Sea and deposition of the Heinrich‐1 layer in the North Atlantic. Copyright © 2007 John Wiley & Sons, Ltd.
Microtextural analysis of a glacially ‘deformed’ bedrock: implications for inheritance of preferred clast orientations in diamictons
Authors: Phillips Emrys , Auton Clive
Published: October 2007

Although analysis of clast macrofabrics has been used to differentiate between different types of glacial diamictons and to determine palaeo‐ice flow directions, no account appears to have been made of preferred clast orientations inherited from the parental source material. Clast macrofabrics in tills are typically interpreted as having developed in response to an imposed subglacial deformation and as such provide a link between the sedimentary record and glacier dynamics. They rely on the assumption that any preferred clast orientation is a result of deformation/flow. The results of the micromorphological study of the Langholm Till exposed at North Corbelly near Dumfries (southwestern Scotland) clearly demonstrate that bedrock structure can influence clast orientation (macrofabric) within diamictons. In the lower part of the till, the orientation of elongate clasts preserves the geometry of the tectonic cleavage present within the underlying bedrock. The intensity of this steeply inclined, ‘inherited’ clast fabric decreases upward through the till, to be replaced by a more complex pattern of successive generations of clast microfabrics developed in response to deformation/flow. These results indicate potential limitations of applying clast macrofabric or microfabric analysis in isolation to establish till genesis or palaeo ice‐flow directions. Consequently, due account should be made of other glacial palaeo‐environmental and ice flow indicators, as well as rockhead depth and morphology in relation to the selection of fabric measurements sites. © British Geological Survey/Natural Environment Research Council copyright 2007. Reproduced with the permission of BGS/NERC. Published by John Wiley & Sons, Ltd.
Genetics of posttraumatic stress disorder: Review and recommendations for future studies
Authors: Koenen Karestan C.
Published: October 2007

Posttraumatic stress disorder (PTSD) is common and debilitating. Posttraumatic stress disorder is moderately heritable; however, the role of genetic factors in PTSD etiology has been largely neglected by trauma researchers. The goal of this study is to motivate trauma researchers to reflect on the role genetic variation may play in vulnerability and resilience following trauma exposure. Evidence from family, twin, and molecular genetic studies for genetic influences on PTSD is reviewed. Recommendations for future studies are presented with emphasis on study design and assessment issues particular to the field of trauma and PTSD. Clinical implications of PTSD genetic studies are discussed.
The relationship between childhood support and later emergence of PTSD
Authors: Lauterbach Dean , Koch Ellen I. , Porter Katherine
Published: October 2007

The authors examine the relationship between three sources of social support (maternal, paternal, and peer) and the development of posttraumatic stress disorder (PTSD). This study utilized data from the National Comorbidity Survey (NCS), a large (N = 5,877) nationally representative population survey. Persons with and without a lifetime history of PTSD and those with and without a history of trauma exposure were compared on levels of social support received prior to age 15. Persons with a history of PTSD reported that they received less maternal, paternal, and peer support as children than those without PTSD. Importantly, persons who developed PTSD after the age of 17 reported lower levels of early childhood support from their fathers.*

This NCS was supported through the following grants awarded to Ronald Kessler: R01 MH/DA46376 and R01 MH49098 (NIMH), supplement to R01 MH/DA46376, (NIDA) and 90135190 (W.T. Grant Foundation).
Considerations in treatment integrity: Implications and recommendations for PTSD research
Authors: Barber Jacques P. , Triffleman Elisa , Marmar Charles
Published: October 2007

In this article, the authors address the rationale for and uses of treatment integrity measurement in psychotherapy research, focusing on therapists' adherence and competence in trauma and posttraumatic stress disorder treatment research. The following issues are examined: (a) distinctions between adherence monitoring, performed contemporaneously with ongoing study treatments, and adherence evaluation, and the implications for outcomes analysis; (b) simultaneous measurement of adherence and competence; (c) selection of sessions for adherence/competence assessment and the need for concurrent outcome measurement, and (d) the association between therapist adherence, competence, alliance and treatment outcome. Recommendations regarding common problems in the implementation of adherence and competence measurement are made throughout. The article concludes with a summary of steps and considerations in decision‐making with regard to treatment integrity.
An asperity‐based mathematical model for the boundary lubrication of nominally flat metallic contacts
Authors: Zhang H. , Chang L.
Published: October 2007

A mathematical model is presented to study the boundary lubrication of nominally flat metallic contacts. It is developed on the basis of the Greenwood–Williamson model, incorporating key aspects of boundary lubrication in asperity contacts. Four variables are used to describe the asperity contact, including micro‐contact area, pressure, interfacial shear stress and flash temperature. Furthermore, three probability variables are used to define the interfacial state of an asperity junction that may be covered by the lubricant/additive molecules adsorbed on the surface, protected by a chemical film, or in direct contact with no boundary protection. Governing equations for the seven asperity‐level variables are derived based on first‐principle considerations of the asperity deformation, frictional heating and kinetics of boundary films. These equations are solved simultaneously to determine the asperity interfacial state and calculate the contact variables. The asperity‐level solutions are then integrated to formulate the boundary‐lubrication model at the system level with statistical descriptions of the surfaces. Results are presented and analysed including system friction behaviour, surface separation and real area of contact, and the state of boundary lubrication for various operating conditions and surface roughness. Some potential applications of the model are described. The model and the modelling concepts may provide a framework for future boundary‐lubrication analysis, incorporating research advances in contact mechanics, tribochemistry and other related fields. Copyright © 2007 John Wiley & Sons, Ltd.
Sugar‐Responsive Fluorescent Nanospheres
Authors: Zenkl Gunter , Mayr Torsten , Klimant Ingo
Published: October 2007

Sugar‐responsive polymer fluorescent nanospheres based on N‐isopropylacrylamide and phenylboronic acid were prepared by precipitation polymerization with an average size of 380 nm. The particles swell in the presence of sugar, and the rate and extent of this swelling was measured with distance‐dependent fluorescence resonance energy transfer. We present a direct link between the ratio of the intensities of the fluorophores and the particle size. Depending on the kind of sugar and the sugar concentration, different swelling kinetics and equilibrium sizes are observed. With this approach we can obtain insight into complex structure changes with simple fluorescent measurements.

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The influence of artificial aging on the microstructure, mechanical properties, corrosion, and environmental cracking susceptibility of a 7075 friction‐stir‐weld
Authors: Paglia C. S. , Jata K. V. , Buchheit R. G.
Published: October 2007

The influence of overaging to the T7451 temper on the microstructure, the mechanical properties, and the corrosion susceptibility of friction‐stir‐welded 7075 aluminum alloy was investigated by means of transmission electron microscope (TEM), SEM investigations, constant extension rate tests (CERT), alternate immersion tests, and potentiodynamic scans. The overaging that occurs during welding within the heat‐affected zones of the friction‐stir‐welded 7075‐O tempered plates promotes a slight formation of intragranular and grain boundary precipitates and increases the mechanical as well as the corrosion resistance properties as compared to the T7451 welded plates. The “double” overaging treatment, consisting of the T7451 temper and the thermal transient experienced by the heat‐affected zones of the 7075‐T7451 welded plates, increases the size of the intragranular and the grain boundary precipitates as well as the precipitate‐free zones. These facts decrease the mechanical and corrosion properties of the 7075‐T7451 weld. The T7451 thermal treatment applied after the welding of the 7075‐O plates promotes the high presence of small precipitates and reduces the size of the precipitate‐free zones. This fact increases the general corrosion resistance, but decreases the mechanical properties. Therefore, the corrosion as well as the mechanical properties are greatly correlated with minute changes in the microstructure, which can arise by short‐term heat exposure as for instance during welding. It was also found that the environmental susceptibility measured by means of CERTs may be influenced by “solution‐strengthening” corrosion mechanisms which increase the strain. This fact is present in weld microzones particularly susceptible to corrosion.
Corrosion resistance of three austenitic stainless steels for biomedical applications
Authors: Terada M. , Antunes R. A. , Padilha A. F. , Costa I.
Published: October 2007

The resistance to localized corrosion of three austenitic stainless steels (SS), specifically the ASTM F‐138 which is widely used in several biomedical applications, the DIN 1.4460 high N, and the DIN 1.4970 was investigated in this study by electrochemical techniques including potentiodynamic polarization and electrochemical impedance spectroscopy measurements in a phosphate‐buffered solution. The DIN 1.4460 high N and the DIN 1.4970 were tested in this study for the reason they do not form any ferromagnetic phases, such as delta‐ferrite or martensite, although these phases might be formed in the first type of SS. Although all the three SS tested are prone to localized attack, the DIN 1.4460 high N presented the highest corrosion resistance among the SS followed by the DIN 1.4970 and finally the ASTM F‐138. Shallower and smaller pits were formed on the DIN 1.4970 compared to the ASTM F‐138 SS.
Evaluation of NDT methods for detection of prestressing steel damage at post‐tensioned concrete structures
Authors: Mietz J. , Fischer J.
Published: October 2007

For an assessment of the risk potential of existing structures, where in the case of prestressing steel damage the load‐bearing capacity could be significantly affected, non‐destructive testing techniques which enable reliable evaluation of the condition of the prestressing steels are of utmost importance. During the demolition of a post‐tensioned concrete bridge in Berlin where damage of prestressing wires due to hydrogen‐induced stress corrosion cracking were found in former investigations, parts of the girders of the bridge superstructure could be taken out. After non‐destructive investigations by means of two testing techniques based on magnetic leakage flux measurement and one technique based on electromagnetic resonance measurement, subsequent removal of the concrete cover up to the ducts, opening the ducts and evaluation of the prestressing steels allowed a verification of the results obtained by the NDT methods. From the results it can be concluded that areas with fractures of several wires can be detected by the two techniques based on magnetic leakage flux measurement.
Physico‐Mechanical Properties and the TVOC Emission Factor of Gypsum Particleboards Manufactured with Pinus Massoniana and Eucalyptus Sp.
Authors: Kim Sumin , Kim Jin‐A. , An Jae‐Yoon , Kim Hee‐Soo , Kim Hyun‐Joong , Deng Yuhe , Feng Qian , Luo Jiayan
Published: October 2007

The effect of wood species on the TVOC emission factor and the physico‐mechanical properties of GPBs is investigated. Of the two wood species, the water absorption was higher for the GPBs made using Eucalyptus sp. than for those using Pinus massoniana. The Eucalyptus sp. GPBs pressed at room temperature, 40 and 60 °C all demonstrated higher moisture absorption than commercial GPBs. The TVOC emission factor decreased with increasing press temperature, especially for Eucalyptus sp. but remained under ‘excellent’ grade as defined by the KACA. From these results, GPB with higher content of wood particles should be considered for the replacement of wood‐based panels such as particleboard and medium density fiberboard (MDF).

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Polymeric One‐Dimensional Photonic Crystals by Continuous Coextrusion
Authors: Kazmierczak Tomasz , Song Hyunmin , Hiltner Anne , Baer Eric
Published: October 2007

It is shown that narrowband one‐dimensional photonic crystals can be fabricated from polymeric materials using laboratory scale layer‐multiplying coextrusion technology. The tuning of the photonic bandgap is demonstrated with films that selectively filter different regions of the visible electromagnetic spectrum. The layer uniformity of the photonic crystals is evaluated by comparing the measured UV‐vis transmission spectra with model simulations, and is independently confirmed with atomic force microscopy. Assemblies of alternating polystyrene and poly(methyl methacrylate) layers exhibit a narrow reflection band with close to 100% reflection in good agreement with the prediction for uniform layers. The flexibility of the process is demonstrated by the fabrication of elastomeric one‐dimensional photonic crystals. It is anticipated that this technology will enable the rapid and facile realization of new polymeric optical devices.

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Osmolarity at early culture stage affects development and expression of apoptosis related genes (bax‐α and bcl‐xl) in pre‐implantation porcine NT embryos
Authors: Hwang In‐Sun , Park Mi‐Rung , Moon Hyo‐Jin , Shim Joo‐Hyun , Kim Dong‐Hoon , Yang Byoung‐Chul , Ko Yeoung‐Gyu , Yang Boh‐Suk , Cheong Hee‐Tae , Im Gi‐Sun
Published: October 2007

This study examined whether high osmolarity of culture medium at the early culture stage affects development and expression of apoptosis related genes (Bax‐α and Bcl‐xl) of porcine nuclear transfer (NT) and in vitro fertilization (IVF) embryos. NT and IVF embryos were divided into three groups and the basic medium was PZM‐3 (260–270 mOsmol, control group). The control group of embryos was cultured in PZM‐3 for whole culture period. Other two groups of embryos were cultured in a modified PZM‐3 with 0.05 M sucrose (300–320 mOsmol, sucrose group) or increased NaCl to 138 mM (300–320 mOsmol, NaCl group) for the first 2 days, and then cultured in PZM‐3 for 4 days. NT embryos cultured in NaCl group showed a significantly higher developmental rate to the blastocyst stage with a decreased apoptosis rate compared to the control (P < 0.05). There was no difference in blastocyst formation and apoptosis incidence among the three culture treatments for IVF‐derived embryos. Bax‐α mRNA expression was significantly higher in the control than sucrose or NaCl group for both NT and IVF embryos (P < 0.05). Moreover, the relative abundance of Bax‐α/Bcl‐xl was higher in the control than the treatment groups. These results indicate that the higher osmolarity at the early embryonic stage of porcine NT and IVF embryos can improve the in vitro development with reduced apoptosis through regulating the Bax‐α/Bcl‐xl gene expression. Mol. Reprod. Dev. 75: 464–471, 2008. © 2007 Wiley‐Liss, Inc.
Clenbuterol increases muscle fiber size and GATA‐2 protein in rat skeletal muscle in utero
Authors: Downie Diane , Delday Margaret I. , Maltin Charlotte A. , Sneddon Alan A.
Published: October 2007

Certain β2‐adrenoceptor agonists, such as clenbuterol, are known to elicit a muscle‐specific anabolism or hypertrophy in both normal and catabolic muscle in a wide variety of species. However, the underlying mechanism(s) of the β2‐agonist‐induced anabolism remains unclear. This study aimed to determine the effects of clenbuterol administration in utero on skeletal muscle and to examine the underlying molecular mechanisms. Pregnant rats were fed clenbuterol (2 mg/kg diet) from Day 4 of gestation (4 dg) until weanling and fetal samples were taken from 13.5, 15.5, 17.5, and 19.5 dg and from 1d neonatal pups. Muscles were analyzed for total DNA, RNA and protein and sections examined morphologically for changes in muscle development. Western and immunohistochemical analyses were performed to identify changes in known myogenic signaling proteins. Clenbuterol increased the size of both fast and slow fibers in utero which was associated with a decreased DNA:protein ratio (28%) and an increased RNA:DNA ratio (36%). Additionally, drug treatment in utero induced a decrease in the fast:slow fiber ratio (38%). These myogenic changes were correlated with an increase in the GATA‐2 hypertrophic transcription factor at both 17.5 dg (by 250%) and 19.5 dg (by 40%) in fetuses from clenbuterol treated dams. In addition, drug treatment resulted in increased membrane association of PKC‐µ at 17.5 dg (325%) and increased PKC‐α cytosolic abundance (40%) and PKC‐θ membrane abundance at 19.5 dg (250%). These results are the first demonstration that β2‐agonists such as clenbuterol may act through upregulating the GATA‐2 transcription factor and implicate certain PKC isoforms in the drug‐induced regulation of skeletal muscle development. Mol. Reprod. Dev. 75: 785–794, 2008. © 2007 Wiley‐Liss, Inc.
Oocyte morphology and transcriptional silencing in relation to chromatin remodeling during the final phases of bovine oocyte growth
Authors: Lodde Valentina , Modina Silvia , Maddox‐Hyttel Poul , Franciosi Federica , Lauria Antonio , Luciano Alberto M.
Published: October 2007

The complexity of the events which orchestrate mammalian oocyte growth and ultimate acquisition of developmental competence is still unclear and under continuous investigation. Starting from the observation that germinal vesicle (GV) bovine oocytes exhibit different patterns of chromatin configuration (from GV0 to GV3), the present study aimed at analyzing the morphology of the nuclear and the cytoplasmic compartments and to determine the total transcriptional activity of immature oocytes sorted on the basis of their chromatin configuration. The oocyte morphology was analyzed by light microscopy (LM) on semi‐thin sections and transmission electron microscopy, and the global transcriptional activity was analyzed by H3‐Uridine incorporation and subsequent autoradiography on semi‐thin sections. LM confirmed the increase in chromatin condensation from GV0 to GV3. Ultrastructurally, the nucleolus was fibrillo granular at GV0 while the other stages displayed an electron‐dense fibrillar sphere with the remnant of a fibrillar center on the surface. Organelles were dispersed in the cytoplasm at GV0 while at GV1 and GV2 most of them were homogenously distributed in the oocyte cortex. At GV3 most organelles were found in clusters in the oocyte cortex. Typical features of completion of the oocyte growth phase, like undulation of the nuclear envelope and reduction of the size of Golgi complex were found at GV2 and GV3. Moreover, GV3 oocytes presented cortical granules that displayed varying degrees of degeneration. Autoradiographic labeling showed that oocytes with GV0 configuration exhibited high level of RNA synthesis, GV1 and GV2 stages showed a remarkable decrease of transcription, and the acquisition of GV3 configuration was associated with global repression of transcriptional activity. Our findings suggest a temporal relationship between the chromatin remodeling process and the main morpho‐functional events that characterize the final growth phase in bovine oocyte. Mol. Reprod. Dev. 75: 915–924, 2008. © 2007 Wiley‐Liss, Inc.
On the hierarchy of γ‐valid cuts in global optimization
Authors: Porembski Marcus
Published: October 2007

Concavity Cuts play an important role in concave minimization. In Porembski, J Global Optim 15 (1999), 371–404 we extended the concept underlying concavity cuts which led to the development of decomposition cuts. In numerical experiments with pure cutting plane algorithms for concave minimization, decomposition cuts have been shown to be superior to concavity cuts. However, three points remained open. First, how to derive decomposition cuts in the degenerate case. Second, how to ensure dominance of decomposition cuts over concavity cuts. Third, how to ensure the finite convergence of a pure cutting plane algorithm solely by decomposition cuts. These points will be addressed in this paper. © 2007 Wiley Periodicals, Inc. Naval Research Logistics, 2008
Blood–brain barrier permeability to manganese and to Gd‐DOTA in a rat model of transient cerebral ischaemia
Authors: Grillon Emmanuelle , Provent Peggy , Montigon Olivier , Segebarth Christoph , Rémy Chantal , Barbier Emmanuel L.
Published: October 2007

Loss of integrity of the blood–brain barrier (BBB) and brain swelling is a potentially lethal complication of reperfusion in human stroke. To assess the time course of BBB modifications, we performed angiography, diffusion‐weighted imaging, T1‐weighted (T1W) imaging and T1 mapping, and monitored acute changes after middle cerebral artery occlusion and recanalization in rats (n = 27). The animals were grouped according to the duration of occlusion: 30 min (group A, n = 8), 1 h 30 min (group B, n = 9), and 2 h 30 min (group C, n = 10). For 17 animals (four in group A, six in group B, and seven in group C), MnCl2 and dimeglumine gadoterate (Gd‐DOTA) were injected at 13 min and 34 min after recanalization, respectively. The 10 remaining animals (control groups) underwent the same acquisition protocols, but no contrast agents were injected. Cell damage was determined 1 h after recanalization on haematoxylin and eosin‐stained sections. Our results indicate that in the middle cerebral artery occlusion model in the rat, changes in BBB permeability assessed by contrast agent extravasation occur within the first hour of reperfusion, even after an occlusion period not exceeding 30 min. No differences between BBB permeability to Gd‐DOTA and Mn2+ were detected in our experimental conditions. The reduction in apparent diffusion coefficient during occlusion appears to be a good predictor of BBB modifications after reperfusion in this model. Copyright © 2007 John Wiley & Sons, Ltd.
A strategy to reduce the control packet load of MANETs with bidirectional links using DSR
Authors: Tamilarasi Muthu , Palanivelu T. G.
Published: October 2007

Dynamic source routing (DSR) is a robust protocol commonly applied to multi‐hop wireless mobile ad hoc networks (MANETs). In this paper, an algorithm is proposed for modifying the basic DSR protocol to enhance its performance by reducing the number of redundant route reply packets (RREPs). In the modified DSR (MDSR), for a source destination pair, the destination responds to the first received route request packet (RREQ) with an RREP, and the subsequently received RREQs, bearing the same request ID, are responded to only if the hop count is less than that of all the previously received RREQs. The performance of MDSR has been compared with that of the basic DSR for different network densities and for different mobility of nodes. Simulation results show that MDSR gives fewer control packets, less latency and a higher packet delivery ratio than DSR. Copyright © 2007 John Wiley & Sons, Ltd.
A geometrically exact thin membrane model—investigation of large deformations and wrinkling
Authors: Weinberg Kerstin , Neff Patrizio
Published: October 2007

We investigate a geometrically exact membrane model with respect to its capabilities in describing buckling and wrinkling. The concept is distinct from traditional ones by the introduction of an artificial viscosity related to an adjusted orthonormal frame (rotations). In this way our model is able to capture the detailed geometry of wrinkling while the balance of force equations remains elliptic throughout. The movement of rotations is given by a local evolution equation. We discuss the consistent linearization of the model and the local update of rotations. Numerical examples are presented, which demonstrate the effectiveness of the new model for predicting wrinkles in membranes undergoing large deformation. Copyright © 2007 John Wiley & Sons, Ltd.
Shape optimization of geotextile tubes for sandy beach protection
Authors: Isebe Damien , Azerad Pascal , Bouchette Frederic , Ivorra Benjamin , Mohammadi Bijan
Published: October 2007

This paper describes how to tackle new challenging coastal engineering problems related to beach erosion with a shape optimization approach. The method modifies the shape of the sea bottom in order to reduce beach erosion effects. Global optimization is shown to be necessary as the related functionals have several local minima. We describe the physical model used, the proposed protection devices against beach erosion and real case applications. Copyright © 2007 John Wiley & Sons, Ltd.
Risk of breast cancer in relation to antibiotic use
Authors: M. Tamim Hani , A. Hanley James , H. Hajeer Ali , Boivin Jean‐François , Collet Jean‐Paul
Published: October 2007

Background

There are conflicting results in the literature regarding the association between the antibiotic exposure and breast cancer risk. The aim of this study was to assess this association using a population‐based approach.

Methods

The source population was the dynamic cohort defined by membership in the Saskatchewan Prescription Drug Plan (Canada) between the years 1981 and 2000. Four matched controls were selected for each case identified by the Saskatchewan Cancer Agency, using incidence density sampling. Detailed drug exposure over a minimum of 15 years before diagnosis allowed studying the respective effects of dosage and timing of antibiotic use on breast cancer risk. Two antibiotic exposure definitions were used: the number of prescriptions and the number of units (tablets, capsules, etc.), which were further categorized into quartiles.

Results

A total of 3099 breast cancer cases and 12 396 matched controls were included. The incidence of breast cancer was higher in subjects who had more antibiotic prescriptions during the 1–15 years prior to the index date (RRs = 1.50, 1.63, 1.71 and 1.79 for the four quartiles, respectively, p‐trend = 0.0001). Similar results were found when a number of units were considered. We did not find any effect of the timing of antibiotic exposure on breast cancer risk. Similar patterns of increased risk of breast cancer were detected for the specific antibiotic classes.

Conclusions

We observed a dose‐dependent increase in breast cancer risk in association with the antibiotic exposure up to 15 years in the past. However, the lack of temporal trends and the absence of class‐specific effects suggest a non‐causal relationship. Copyright © 2007 John Wiley & Sons, Ltd.
The thermal polymerization of amino acids revisited; Synthesis and structural characterization of hyperbranched polymers from L‐lysine
Authors: Scholl Markus , Nguyen Tuan Q. , Bruchmann Bernd , Klok Harm‐Anton
Published: October 2007

This contribution reports on the synthesis of hyperbranched polylysines via thermal polymerization of L‐lysine hydrochloride. Polymerization of L‐lysine hydrochloride in the presence of one equivalent KOH at 150 °C resulted in polymers with a number‐average molecular weight of 4600 g/mol and a polydispersity of 2.6 after 48 h. The rate of polymerization could be significantly enhanced and the polymer molecular weight improved by carrying out the polymerization with 3 mol % of an amidation catalyst. Among the different catalysts that were investigated Zr(OnBu)4 was found to be the most effective. Unequivocal support for the branched architecture of the polymers was obtained from 1H NMR spectroscopy, which allowed the identification and quantification of the four different structural units that constitute the polymer, viz. Nα and Nε linked linear units, dendritic units and terminal units. The structure of the polymers was found to be relatively independent of the reaction conditions. The degree of branching and the average number of branches varied between 0.35–0.45 and 0.15–0.25, respectively. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5494–5508, 2007
Chemical modification of metallocene‐based polyolefinic elastomers by acrylic acid and its influence on physico‐mechanical properties: Effect of reaction parameters, crystallinity and pendant chain length
Authors: Biswas Anjan , Bandyopadhyay Abhijit , Singha Nikhil K. , Bhowmick Anil K.
Published: October 2007

In this investigation, solution grafting of acrylic acid (AA) in presence of benzoyl peroxide (BPO) was carried out onto metallocene‐based “poly(ethylene‐octene) elastomers” (POE) as well as “poly(ethylene‐butene) elastomers” (PBE), to impart polarity on the non‐polar rubbery matrix and also to study the effects of crystallinity and pendant chain length on the “grafting percentage” and “percent gel yield” at optimized conditions for all the POE and PBE systems. Reaction parameters were optimized on the basis of the relative proportions of graft and gel formations obtained through %weight gain, Fourier Transform infrared spectroscopy and elemental analysis. The effect of grafting at its maximum level on various physico‐mechanical properties was also thoroughly investigated by using X‐ray diffraction (XRD), differential scanning calorimetry (DSC), mechanical, dynamic mechanical (DMTA), and thermogravimetric analysis (TGA) and the properties were correlated with the structure of the modified polymers. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5529–5540, 2007
Hyperbranched copolyfluorene from a 2,4,7‐trifunctional fluorene monomer
Authors: Tsai Lin‐Ren , Chen Yun
Published: October 2007

A new hyperbranched (P1) and linear copolyfluorene (P2) were prepared from 2,4,7‐trifunctional (branching) and 2,7‐bifunctional fluorene monomer, respectively, by the Wittig reaction, followed with end‐capping by aromatic oxadiazole groups, to study the effect of hyperbranch structure. The weight‐average molecular weights (Mw) of P1 and P2, determined by gel permeation chromatography using polystyrene as standard, were 33,000 and 25,700, respectively. The polymers were readily soluble in common organic solvents and exhibited good thermal stability (Td > 400 °C). Optical properties, both in solution and film state, were investigated using absorption and photoluminescence (PL) spectra. In film state, the absorption and PL spectra peaked at 401–425 nm and 480–495 nm, respectively. The P1 showed energy funnel effect and enhanced fluorescence efficiency owing to hyperbranched structure and terminal oxadiazole groups. The HOMO and LUMO levels of P1 (P2), estimated from cyclic voltammograms, are −5.34 (−5.25) eV and −2.94 (−2.94) eV, respectively. Two‐layer polymer light‐emitting diodes devices (ITO/PEDOT/P1/Ca/Al) exhibited maximal luminance and luminous efficiency of 3630 cd/m2 and 0.78 cd/A, respectively, which are superior to its linear counterpart P2 (598 cd/m2, 0.11 cd/A). © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5541–5551, 2007
Supramolecular polymer/metal salt complexes containing quadruple hydrogen bonding units
Authors: Lee Kyung Ju , Kim Yong Woo , Koh Joo Hwan , Kim Jong Hak
Published: October 2007

A supramolecular material containing quadruple hydrogen bonding sites was prepared by reacting the amines of methyl isocytosine and the epoxy groups of poly (ethylene glycol diglycidyl ether). This supramolecular polymer was complexed with metal salt, that is potassium iodide, to produce polymer electrolytes, and their physical properties, specific interactions, and conductivity behavior were investigated. The ionic conductivity of polymer electrolytes continuously increased with increasing salt concentration up to 0.4 of salt weight fraction, presenting usually high solubility limit of salt in the supramolecular polymer. Wide angle X‐ray scattering data also presented that the metal salt was completely dissolved in the supramolecular polymer up to 0.4 of salt weight fraction. Upon the introduction of metal salt, the mechanical properties of the supramolecular polymer were significantly enhanced by around 10 times and the glass transition temperature of the polymer increased by about 50 °C, as revealed by complex melt viscosities and differential scanning calorimetry. These unusual behaviors of salt solubility and mechanical properties for supramolecular polymer/metal salt complexes were attributed to the strong, additional metal ion coordination to hydrogen bonding sites as well as ether oxygens of polymer matrix, as supported by FTIR spectroscopy. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 3181–3188, 2007
Lung disease severity, chronic inflammation, iron deficiency, and erythropoietin response in adults with cystic fibrosis
Authors: Fischer R. , Simmerlein R. , Huber R.M. , Schiffl H. , Lang S.M.
Published: October 2007

Chronic lung disorders are usually associated with a hypoxia driven increase in red cell mass. However, patients with cystic fibrosis (CF) often have normal or decreased haemoglobin levels. The present prospective observational study in cystic fibrosis patients was performed to determine which factors were involved in alterations in the hematopoetic response to corresponding arterial oxygen pressure. Sixty adult patients (age 21–51) with stable CF were included. They all had vitamin A, D, E, and K but no vitamin B12 supplementation. Twenty‐five patients were on oral Fe2+ (100 mg/day). Resting arterial blood gases, lung function, complete blood counts, parameters of iron status, CRP, sputum microbiology and serum erythropoietin were measured at recruitment and after 3 and 6 months. Patients had varying degrees of pulmonary functional impairment and 9% were hypoxemic (arterial oxygen pressure <60 mm Hg). Low‐grade systemic inflammation (CRP > 0.5 mg/dl) was present in 40% of the patients, who all had bacterial colonization. None of the patient had erythrocytosis and 12 patients had anemia. There was no significant difference in iron status between patients with or without chronic iron supplementation and erythropoietin levels were normal. During the 6 months observation period no significant changes occurred. The patients exhibited an impaired erythropoietic response to hypoxemia with normal or low hematocrit in spite of chronic lung disease which might be caused by chronic inflammation associated with CF. Linear multivariate regression analysis revealed CRP levels but neither iron substitution, nor erythropoietin levels nor lung function parameters as independent determinant of haemoglobin levels. CF may be associated with anemia of variable severity as expression of the chronic inflammation present in these patients. The therapeutic consequences are to treat the underlying inflammation rather than to supplement iron. Pediatr Pulmonol. 2007; 42:1193–1197. © 2007 Wiley‐Liss, Inc.
Dominance of CD4+ lymphocytic infiltrates with disturbed effector cell characteristics in the tumor microenvironment of prostate carcinoma
Authors: Ebelt Kathleen , Babaryka Gregor , Figel Ainhoa M. , Pohla Heike , Buchner Alexander , Stief Christian G. , Eisenmenger Wolfgang , Kirchner Thomas , Schendel Dolores J. , Noessner Elfriede
Published: October 2007

BACKGROUND

Prostate cancer is the most common cancer of men in the Western world. Despite the over‐expression of tumor‐associated antigens, like PSA or PSMA, immune activation is inefficient. The goal of this investigation was to assess in situ characteristics of prostate cancer‐infiltrating lymphocytes and to determine their activation status and effector function.

METHODS

We compared 17 carcinoma containing tissues, four benign prostatic hyperplasia tissues and eight healthy prostate tissues regarding lymphocyte subset composition, locoregional distribution, and functional status using immunohistological staining of cryopreserved tissues. For determination of lymphocyte subsets, serial sections were stained with CD3, CD4, and CD8 antibodies. Activation status and effector function were studied using CD69, interferon‐gamma (IFNγ), perforin, and CD3 zeta chain antibodies. T‐cell‐receptor repertoire (TCR) analysis was made to determine the complexity of infiltrating lymphocytes.

RESULTS

CD3+, CD4+, and CD69+ T lymphocytes were prominent in tissues derived from patients with prostate carcinoma. CD8+ lymphocytes were significantly less than CD4+ lymphocytes. IFNγ and perforin were downregulated on infiltrating lymphocytes compared to cells of healthy prostate tissue. Very few lymphocytes were detected within cancerous lesions whereas surrounding tissues showed extensive lymphocyte cluster formation. The TCR repertoire of infiltrating lymphocytes was broad and similar to that of healthy prostate tissue, giving no evidence for specific lymphocyte recruitment.

CONCLUSIONS

In the prostate cancer microenvironment, CD4+ T lymphocytes dominated while CD8+ T cells were sparse. The lymphocytes exhibited signs of disturbed effector function. Consequently, the immune response against autologous tumor cells is likely to be inefficient in controlling tumor growth. Prostate 68: 1–10, 2008. © 2007 Wiley‐Liss, Inc.
Accounting for variability in individual hierarchical clinical trial data
Authors: Tibaldi Fabián , Renard Didier , Molenberghs Geert
Published: October 2007

Meta‐analytical approaches have been extensively used to analyze medical data. In most cases, the data come from different studies or independent trials with similar characteristics. However, these methods can be applied in a broader sense. In this paper, we show how existing meta‐analytic techniques can also be used as well when dealing with parameters estimated from individual hierarchical data. Specifically, we propose to apply statistical methods that account for the variances (and possibly covariances) of such measures.

The estimated parameters together with their estimated variances can be incorporated into a general linear mixed model framework. We illustrate the methodology by using data from a first‐in‐man study and a simulated data set. The analysis was implemented with the SAS procedure MIXED and example code is offered. Copyright © 2007 John Wiley & Sons, Ltd.
Liquid chromatography/mass spectrometry analysis of PHY906, a Chinese medicine formulation for cancer therapy
Authors: Ye Min , Liu Shwu‐Huey , Jiang Zaoli , Lee Yashang , Tilton Robert , Cheng Yung‐Chi
Published: October 2007

PHY906 is a Chinese medicine formulation prepared from four medicinal herbs for adjuvant cancer chemotherapy. In this paper, liquid chromatography/electrospray ionization time‐of‐flight mass spectrometry (LC/ESI‐TOFMS) was used to clarify the chemical composition of PHY906. The aqueous extract of PHY906 was separated on a Waters Atlantis C18 column, and was eluted with acetonitrile/0.05% (v/v) formic acid. The separated compounds were identified with pure standards, or tentatively characterized by analyzing their mass spectra recorded in both negative and positive ion polarity modes. Further structural information was obtained from in‐source fragmentation. Based on the LC/MS analysis, we proposed the structures for 64 bioactive compounds, including flavonoids, triterpene saponins, and monoterpene glycosides. All the compounds identified from PHY906 were further assigned in the four individual herbs, and some of them are reported for the first time. Copyright © 2007 John Wiley & Sons, Ltd.