bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermally induced modifications of the optic properties of lead zirconate titanate thin films obtained on different substrates by sol-gel synthesis
Authors: D’Elia Stefano , Castriota Marco , Policicchio Alfonso , Scaramuzza Nicola , Versace Carlo , Cazzanelli Enzo , Agostino Raffaele Giuseppe , Vena Carlo , Strangi Giuseppe , Bartolino Roberto
Published: December 2008

Lead zirconium titanate PbZr0.53Ti0.47O3 (PZT) thin films have been obtained by sol-gel synthesis, deposited on different substrates [float glass, indium tin oxide (ITO)-coated float glass, and intrinsic silicon wafer], and later subjected to different thermal treatments. The morphologic and the structural properties of both PZT thin films and substrates have been investigated by scanning electron microscope and their composition was determined by energy dispersive x-ray (EDX) analysis. Moreover, variable angle spectroscopic ellipsometry provides relevant information on the electronic and optical properties of the samples. In particular, the optical constant dispersion of PZT deposited on ITO-coated float glasses shows a small absorption resonance in the near IR region, not observed in PZT films deposited on the other substrates, so that such absorption resonance can be explained by interfacial effects between ITO and PZT layers. This hypothesis is also supported by EDX measurements, showing an interdiffusion of lead and indium ions, across the PZT-ITO interface, that can generate a peculiar charge distribution in this region.
A revised Kubelka–Munk theory for spectral simulation of phosphor-based white light-emitting diodes
Authors: Ishida Kunio , Mitsuishi Iwao , Hattori Yasushi , Nunoue Shinya
Published: December 2008

We developed a simulation method for designing the luminescence profiles of white light-emitting diodes (LEDs) with multicolor phosphor blend. By taking into account the effect of the light scattering by phosphor particles as well as the reabsorption effect by phosphor species, we found a model of white LEDs to calculate the light output as a function of various parameters such as the thickness of the resins, the concentration of phosphors, and the spatial distribution of phosphor particles. This method is widely applicable to phosphor-based white LEDs with either blue or UV excitation.
Polarimetric interferometer for nanoscale positioning applications
Authors: Xu S. , Ouedraogo K. , Chassagne L. , Topçu S. , Juncar P. , Alayli Y.
Published: December 2008

We propose and demonstrate a displacement control method at the subnanometric scale based on a Michelson interferometer combined with a polarimeter and a phase-locked loop electronic board. Step by step displacements with a step value of 5 nm are presented. A repeatability of 0.47 nm is obtained from back and forth displacements over 1 μm range. We show that a residual ellipticity of less than 10° on the polarization state leads to a positioning error of less than 1 nm. Such system could be used over millimeter range displacements in a controlled surrounding environment leading to numerous applications in nanometrology.
Low-temperature-fabricated InGaZnO4 thin film transistors on polyimide clean-room tape
Authors: Lim Wantae , Douglas E. A. , Kim S.-H. , Norton D. P. , Pearton S. J. , Ren F. , Shen H. , Chang W. H.
Published: December 2008

Amorphous (α-)InGaZnO4 thin film transistors (TFTs) were fabricated on polyimide clean-room tape at low temperature (<100 °C). The α-InGaZnO4 films with an n-type carrier concentration of ∼1016 cm−3 were deposited by rf-magnetron sputtering in a mixed ambient of Ar/O2. The bottom-gate-type TFTs showed good saturation mobility (∼5.3 cm2 V−1 s−1), drain current on-to-off ratio of approximately 105, threshold voltage of 1.1 V, and subthreshold gate-voltage swing of 0.55 V decade−1. These results were comparable to those of the same oxide TFTs that we have fabricated on either glass or polyethylene terephthalate substrates. The results demonstrate that even polyimide clean-room tape can be an appropriate substrate for inexpensive-flexible-adhesive-transparent electronic devices.
Effect of temperature on layer separation by plasma hydrogenation
Authors: Di Z. F. , Wang Y. Q. , Nastasi M. , Rossi F. , Shao L. , Thompson P. E.
Published: December 2008

We have studied hydrogen diffusion in plasma hydrogenated Si∕SiGe∕Si heterostructure at different temperatures. At low temperature, intrinsic point defects in the molecular beam epitaxy grown Si capping layer are found to compete with the buried strain SiGe layer for hydrogen trapping. The interaction of hydrogen with point defects affects the hydrogen long-range diffusion, and restricts the amount of hydrogen available for trapping by the SiGe layer. However, hydrogen trapping by the capping layer is attenuated with increasing hydrogenation temperature allowing more hydrogen to be trapped in the strain SiGe layer with subsequent surface blister formation. A potential temperature window for plasma hydrogenation induced layer separation is identified based on the combined considerations of trap-limited diffusion at low temperature and outdiffusion of H2 molecule together with the dissociation of Si–H bonds inside of H platelet at high temperature.
The Politics of Sacred Places: Palestinian Identity, Collective Memory, and Resistance in the Hassan Bek Mosque Conflict
Authors: Luz Nimrod
Published: December 2008

Geographers dealing with religion have pointed to the process of conflict and contestation involved in the production of sacred sites. This paper explores the conflict over a sacred site in the formulation of a minority identity through transformation of the place into a nexus of resistance and collective memory formation. I argue that under hegemonic secularizing states and within the context of ethnonational conflicts minority groups mobilize and articulate a dynamic meaning of sacred sites which allows an elaborate politics of identity. Further, in the context of their national struggle, members of the community emphasize different aspects of the sacred. In the context of the national struggle (and for the duration of the conflict), minority members enhance inclusive nationalistic (Palestinian in this particular case) identity; however, while in a community context they emphasize the religious (Islamic) meaning of the place. Particularly, I examine the dynamic nature of interpreting and constructing the sacred through the analysis of the restoration project of the Hassan Bek mosque by the Arab-Palestinian community of Jaffa, Israel.
Na+-mediated coupling between AMPA receptors and KNachannels shapes synaptic transmission
Authors: Nanou Evanthia , Kyriakatos Alexandros , Bhattacharjee Arin , Kaczmarek Leonard K. , Paratcha Gustavo , El Manira Abdeljabbar
Published: December 2008

Na+-activated K+(KNa) channels are expressed in neurons and are activated by Na+influx through voltage-dependent channels or ionotropic receptors, yet their function remains unclear. Here we show that KNachannels are associated with AMPA receptors and that their activation depresses synaptic responses. Synaptic activation of KNachannels by Na+transients via AMPA receptors shapes the decay of AMPA-mediated current as well as the amplitude of the synaptic potential. Thus, the coupling between KNachannels and AMPA receptors by synaptically induced Na+transients represents an inherent negative feedback mechanism that scales down the magnitude of excitatory synaptic responses.
Performance based design
Authors: Tyers Alex
Published: December 2008

This paper is about the application of professional information design practices that have grown out of research conducted by the Communication Research Institute (CRI), formerly the Communication Research Institute of Australia (CRIA), and others. In particular, it focuses on the role of testing in studio practice.

Starting in the mid 1980s, CRI undertook a number of large-scale applied projects funded by government and industry to improve the quality of communication between large organisations and the public. The research focused on discovering the best methods for designing information for public use.

The CRI research was able to draw on a substantial body of prior research in design methods (e.g. Jones 1970), document designs (e.g. Felker et al 1980) and specifically in information design (e.g. Easterby & Zwaga 1984). Moreover, a growing number of significant case histories published in this journal have provided an emerging view of professional practice in the field (e.g. Goodwin 1984, Tomaselli & Tomaselli 1984, Waller 1984)

This early work suggests the possibility of a unified set of highly productive information design methods, and was foreshadowed in the important contributions of Pat Wright (e.g. Wright 1979). The work started at CRI in the mid-1980s focused on unifying information design methods and demonstrating their productivity (Fisher and Sless 1990). By 1992, it was possible to suggest that the resulting design methods had a wide general application to information design (Sless 1992). However, it remained to demonstrate that these methods could be applied consistently across a range of information design problems and that the resultant designs could consistently perform at an acceptable level. This paper reports on that demonstration. In particular it shows through practical examples how testing and measurement of a design’s performance has become an integral part of professional information design practice.
Measuring the quality of information in medical package leaflets: harmful or helpful?
Authors: van der Waarde Karel
Published: December 2008

This article is based on a presentation given at the IIID Vision Plus 12 conference ‘Achieving measurable results’ in Schwarzenberg, Austria in 2006. The following text provides an outline of a single perspective on the circumstances in 2008. There are many stakeholders involved in the development of information about medicines, and all have different concerns which influence contents and design. A single article cannot do justice to the wide variation of perspectives.
Cure4Kids: Research challenges in the design of a website for global education and collaboration
Authors: Quintana Yuri
Published: December 2008

The Cure4Kids Website (www.Cure4Kids.org) brings the latest medical knowledge and continuing education on the treatment of pediatric catastrophic diseases to thousands of health care providers worldwide. The website offers a digital library, on-demand seminars with slides and audio in several languages, and online meeting rooms for international collaborations. In this paper, we describe the design challenges of the Cure4Kids Website as an online learning and collaboration center, including the web interface design, content organization, and usability. The solutions to these design challenges may help other web designers facing similar issues in the design of international web-based projects.
Simulation of ASDEX Upgrade Ohmic plasmas for SOLPS code validation
Authors: Chankin A.V. , Coster D.P. , Dux R. , Fuchs Ch. , Haas G. , Herrmann A. , Horton L.D. , Kallenbach A. , Kurzan B. , Müller H.W. , Pugno R. , Wischmeier M. , Wolfrum E.
Published: December 2008

SOLPS simulation of a dedicated ASDEX Upgrade Ohmic shot for scrape-off layer and divertor modelling is described. The tendency of the code to predict a colder and denser divertor plasma compared with the experiment for solutions that satisfy main boundary conditions (on the input power across the core/edge boundary, particle throughput and radiated power) and match upstream profiles is confirmed. Issues related to the role of neutral sources and sinks are discussed. In the interpretative modelling based on experimental upstream profiles, neither the neutral pressure in the divertor nor the method of fuelling was found to strongly influence the parameters at the outer target, which are primarily determined by the input power and separatrix density.
Dynamic transport study of the plasmas with transport improvement in LHD and JT-60U
Authors: Ida K. , Sakamoto Y. , Inagaki S. , Takenaga H. , Isayama A. , Matsunaga G. , Sakamoto R. , Tanaka K. , Ide S. , Fujita T. , Funaba H. , Kubo S. , Yoshinuma M. , Shimozuma T. , Takeiri Y. , Ikeda K. , Michael C. , Tokuzawa T.
Published: December 2008

Transport analysis during the transient phase of heating (a dynamic transport study) applied to the plasma with internal transport barriers (ITBs) in the Large Helical Device (LHD) heliotron and the JT-60U tokamak is described. In the dynamic transport study the time of transition from the L-mode plasma to the ITB plasma is clearly determined by the onset of flattening of the temperature profile in the core region and a spontaneous phase transition from a zero curvature ITB (hyperbolic tangent shaped ITB) or a positive curvature ITB (concaved shaped ITB) to a negative curvature ITB (convex shaped ITB) and its back-transition are observed. The flattening of the core region of the ITB transition and the back-transition between a zero curvature ITB and a convex ITB suggest the strong interaction of turbulent transport in space.
Correction for Sir James Woodham Menter. 22 August 1921 — 18 July 2006
Authors: Hirsch Peter , Pashley D. W.
Published: December 2008

Biogr. Mems Fell. R. Soc.
54
, 193–214 (2008; Published online 19 August 2008) (doi:
10.1098/rsbm.2008.0015
)

We regret that on page 209, paragraph 3, line 2, we erroneously gave the name of the contemporary Chief Scientist at the Cabinet Office as ‘John Ashcroft’. It should have been ‘John Ashworth’.
Proteomic analysis of human osteoprogenitor response to disordered nanotopography
Authors: Kantawong Fahsai , Burchmore Richard , Gadegaard Nikolaj , Oreffo Richard O. C. , Dalby Matthew J.
Published: December 2008

Previous studies have shown that microgroove-initiated contact guidance can induce bone formation in osteoprogenitor cells (OPGs) and produce changes in the cell proteome. For proteomic analysis, differential in-gel electrophoresis (DIGE) can be used as a powerful diagnostic method to provide comparable data between the proteomic profiles of cells cultured in different conditions. This study focuses on the response of OPGs to a novel nanoscale pit topography with osteoinductive properties compared with planar controls. Disordered near-square nanopits with 120 nm diameter and 100 nm depth with an average 300 nm centre-to-centre spacing (300 nm spaced pits in square pattern, but with ±50 nm disorder) were fabricated on 1×1 cm2polycaprolactone sheets. Human OPGs were seeded onto the test materials. DIGE analysis revealed changes in the expression of a number of distinct proteins, including upregulation of actin isoforms, beta-galectin1, vimentin and procollagen-proline, 2-oxoglutarate 4-dioxygenase and prolyl 4-hydroxylase. Downregulation of enolase, caldesmon, zyxin, GRASP55, Hsp70 (BiP/GRP78), RNH1, cathepsin D and Hsp27 was also observed. The differences in cell morphology and mineralization are also reported using histochemical techniques.
Hydrodynamics of sailing of the Portuguese man-of-warPhysalia physalis
Authors: Iosilevskii G. , Weihs D.
Published: December 2008

Physalia physalis, commonly known as the Portuguese man-of-war (PMW), is a peculiar looking colony of specialized polyps. The most conspicuous members of this colony are the gas-filled sail-like float and the long tentacles, budding asymmetrically beneath the float. This study addresses the sailing of the PMW, and, in particular, the hydrodynamics of its trailing tentacles, the interaction between the tentacles and the float and the actual sailing performance. This paper attempts to provide answers for two of the many open questions concerningP. physalis: why does it need a sail? and how does it harness the sail?
SMD and NMD are competitive pathways that contribute to myogenesis: effects on PAX3 and myogenin mRNAs
Authors: Gong Chenguang , Kim Yoon Ki , Woeller Collynn F. , Tang Yalan , Maquat Lynne E.
Published: December 2008

UPF1 functions in both Staufen 1 (STAU1)-mediated mRNA decay (SMD) and nonsense-mediated mRNA decay (NMD), which we show here are competitive pathways. STAU1- and UPF2-binding sites within UPF1 overlap so that STAU1 and UPF2 binding to UPF1 appear to be mutually exclusive. Furthermore, down-regulating the cellular abundance of STAU1, which inhibits SMD, increases the efficiency of NMD, whereas down-regulating the cellular abundance of UPF2, which inhibits NMD, increases the efficiency of SMD. Competition under physiological conditions is exemplified during the differentiation of C2C12 myoblasts to myotubes: The efficiency of SMD increases and the efficiency of NMD decreases, consistent with our finding that more STAU1 but less UPF2 bind UPF1 in myotubes compared with myoblasts. Moreover, an increase in the cellular level of UPF3X during myogenesis results in an increase in the efficiency of an alternative NMD pathway that, unlike classical NMD, is largely insensitive to UPF2 down-regulation. We discuss the remarkable balance between SMD and the two types of NMD in view of data indicating that PAX3 mRNA is an SMD target whose decay promotes myogenesis whereas myogenin mRNA is a classical NMD target encoding a protein required for myogenesis.
Growth hormone affects behaviour of wild brown troutSalmo truttain territorial owner–intruder conflicts
Authors: Neregård L. , Sundt‐Hansen L. , Björnsson B. Th. , Johnsson J. I.
Published: December 2008

The effects of growth hormone (GH) implants on aggression, and ability to win dyadic territorial conflicts were studied in brown troutSalmo truttaparr. Bovine GH or vehicle (C) was given to either the territory owner or the intruder in four treatment combinations: C and C, C and GH, GH and C, GH and GH (owner and intruder). GH‐treated intruders initiated significantly more conflicts compared to control intruders. Furthermore, GH treatment of either the owner or intruder tended to increase aggression of the intruder. This indicates that intruders have more scope for motivational increase, while the motivation of owners is already at a maximum. The GH treatment, however, did not affect the outcome of the conflict. It thus appears that growth enhancement increases intruder aggression without increasing the chance of winning the conflict, which may have implications for the effect of growth‐selected or growth‐enhanced farmed Atlantic salmonSalmo salaron wild populations.
No evidence of kin bias in dispersion of young‐of‐the‐year Atlantic salmon Salmo salar L. in a natural stream
Authors: Brodeur N. N. , Noël M. V. , Venter O. , Bernatchez L. , Dayanandan S. , Grant J. W. A.
Published: December 2008

Ninety‐one young‐of‐the‐year Atlantic salmon Salmo salar were captured using a non‐invasive snorkelling technique in a 38 m section of Catamaran Brook, New Brunswick, Canada, to test whether related fish settle closer to one another than unrelated fish. A maximum likelihood estimate of parentage relationships assessed by genotyping eight microsatellite loci revealed five half‐sibling families in the sample of fish. Related juvenile S. salar were not found closer to one another than unrelated fish in three analyses at two spatial scales: a comparison of the relatedness of focal fish to their nearest neighbour and to their four nearest neighbours, and a correlation of the pair‐wise relatedness and distance matrices for all fish in the sample. The lack of a kin‐biased dispersion pattern may be related to the lower density of fish or the scarcity of full‐siblings at the study site compared to laboratory conditions.
Male three‐spined sticklebacksGasterosteus aculeatusmake antibiotic nests: a novel form of parental protection?
Authors: Little T. J. , Perutz M. , Palmer M. , Crossan C. , Braithwaite V. A.
Published: December 2008

The egg nest of male three‐spined sticklebacksGasterosteus aculeatusis constructed with a glue‐like secretion that this study demonstrates has antimicrobial properties. Glue collected from reproductively active males decreased the growth rate of bacteria and opportunistic fungi, and eggs were more likely to mature and hatch after exposure to their father’s glue. This phenomenon may represent a direct physiological contribution from a male towards protecting his offspring from pathogens, and if so is a novel form of parental protection.
Soybean meal‐induced uptake block in Atlantic salmon Salmo salar distal enterocytes
Authors: UrÁn P. A. , Aydin R. , Schrama J. W. , Verreth J. A. J. , Rombout J. H. W. M.
Published: December 2008

Soybean meal‐induced enteritis was characterized by the disappearance of the supranuclear vacuoles (SNV) in the enterocytes of the distal intestine of Atlantic salmon Salmo salar. The loss of SNV was correlated with an endocytosis uptake block as shown with ferritin as a marker molecule.
Lipid classes and fatty acid compositions of muscle, liver and skull oil in deep‐sea redfish Sebastes mentella over the Reykjanes Ridge
Authors: Petursdottir H. , Gislason A. , Falk‐Petersen S.
Published: December 2008

The fatty acid profiles of neutral and polar lipids were analysed in tissues of muscle, liver and skull oil of the deep‐sea redfish Sebastes mentella caught over the Reykjanes Ridge. The fatty acid compositions of both the neutral and the polar lipid fractions were tissue specific. The high amounts of the phytoplankton‐derived fatty acids, 20:5n3 and 22:6n3, in the neutral fractions of the muscle tissues clearly distinguished the muscle lipids from liver lipids and skull oil. In the skull oil, the fatty acid profiles of the neutral lipids were characterized by extremely high amounts of the long‐chained mono‐unsaturated fatty acids, 22:1n1, 20:1n9 and 18:1n9, indicating selective enrichment of these fatty acids. Of the tissues studied here, the neutral fraction of the muscle best reflects diet, while the skull oil is believed to be unsuitable in trophic studies. Interestingly, in the muscle oil, there were high amounts of docosahexaenoic acid, 22:6n3 (23%). Docosahexaenoic acid is a unique fatty acid important in the cell membrane, and the levels found in S. mentella are similar to those found in other deep‐living fish species.
Calibration of a hand‐held haemoglobin analyser for use on fish blood
Authors: Clark T. D. , Eliason E. J. , Sandblom E. , Hinch S. G. , Farrell A. P.
Published: December 2008

The HemoCue haemoglobin analyser consistently overestimated haemoglobin concentration ([Hb]) in the blood of all fish species (sockeye salmon Oncorhynchus nerka, Chinook salmon Oncorhynchus tshawytscha, Pacific bluefin tuna Thunnus orientalis and chub mackerel Scomber japonicus) by 22–50% (9·9–36·0 g l−1) over a [Hb] range of 20–160 g l−1. The systematic nature of the overestimation, however, allowed the formulation of an accurate calibration equation that can be used to correct values of [Hb] measured by the HemoCue in field studies.
Real‐time polymerase chain reaction as a rapid and efficient alternative to estimation of picornavirus titers by tissue culture infectious dose 50% or plaque forming units
Authors: Jonsson Nina , Gullberg Maria , Lindberg A. Michael
Published: December 2008

Quantification of viral infectious units is traditionally measured by methods based on forming plaques in semisolid media (PFU) or endpoint dilution of a virus‐containing solution (TCID50), methods that are laborious, time‐consuming and take on average 3–7 days to carry out. Quantitative real‐time PCR is an established method to quantify nucleic acids at high accuracy and reproducibility, routinely used for virus detection and identification. In the present study, a procedure was developed using a two‐step real‐time PCR and the SYBR Green detection method to study whether there are correlations between TCID50/ml, PFU/ml and Ct values generated by real‐time PCR enabling rapid and efficient calculation of titer equivalents when working with viruses in the research laboratory. In addition, an external standard with known concentrations was included using in vitro transcribed viral RNA, thus allowing the calculation of the amount of RNA copies needed for various applications (i.e. per plaque or TCID50).The results show that there is a correlation between the three quantification methods covering a wide range of concentration of viruses. Furthermore, a general regression line between TCID50 and Ct values was obtained for all viruses included in the study, which enabled recording titer equivalents using real‐time PCR. Finally, by including an external standard, the amount of RNA genomes generating one TCID50 or PFU for each enterovirus serotype included was determined.
Quantification of circulating cell‐free DNA in the plasma of cancer patients during radiation therapy
Authors: Cheng Chao , Omura‐Minamisawa Motoko , Kang Yun , Hara Takamitsu , Koike Izumi , Inoue Tomio
Published: December 2008

Cell‐free plasma DNA is elevated in cancer patients and decreases in response to effective treatments. Consequently, these nucleic acids have potential as new tumor markers. In our current study, we investigated whether the plasma DNA concentrations in patients with cancer are altered during the course of radiation therapy. To first determine the origin of cell‐free plasma DNA, plasma samples from mice bearing transplanted human tumors were analyzed for human‐specific and mouse‐specific cell‐free DNA. Human‐specific DNA was detectable only in plasma from tumor‐bearing mice. However, mouse‐specific plasma DNA was significantly higher in tumor‐bearing mice than in normal mice, suggesting that cell‐free plasma DNA originated from both tumor and normal cells. We measured the total cell‐free plasma DNA levels by quantitative polymerase chain reaction in 15 cancer patients undergoing radiation therapy and compared these values with healthy control subjects. The cancer patients showed higher pretreatment plasma DNA concentrations than the healthy controls. Eleven of these patients showed a transient increase of up to eightfold in their cell‐free plasma DNA concentrations during the first or second week of radiation therapy, followed by decreasing concentrations toward the end of treatment. In two other cancer patients, the cell‐free plasma DNA concentrations only decreased over the course of the treatment. The total cell‐free plasma DNA levels in cancer patients thus show dynamic changes associated with the progression of radiation therapy. Additional prospective studies will be required to elucidate the potential clinical utility and biological implications of dynamic changes in cell‐free plasma DNA during radiation therapy. (Cancer Sci 2009; 100: 303–309)
Clinical significance of tumor markers and an emerging perspective on colorectal cancer
Authors: Yamashita Keishi , Watanabe Masahiko
Published: December 2008

Serum carcinoembryonic antigen (CEA) and CA19‐9, a carbohydrate antigen recognized by the monoclonal antibody NS19‐9, are commonly used as classical tumor markers in colorectal cancer (CRC) clinics. The roles of tumor markers include: (1) diagnostic screening (diagnostic markers); (2) prediction of prognosis after treatment (prognostic markers); and (3) judgment tools for treatment effect (surveillance markers). Tumor markers can be evaluated in serum, stools, or even in tissues depending on the clinical purpose. The American Society for Clinical Oncology recommends that CEA is the only marker of choice for monitoring the response of metastatic disease to systemic therapy at present. In the present paper, we are the first to review the clinical significance of the classical tumor markers CEA and CA19‐9 in serum, allowing for our original data, and present our view on the newly emerging biomarkers in CRC. Novel promising biomarkers for diagnostic, prognostic, and surveillance purposes are reviewed and considered, some of which are anticipated for further validation. For diagnostic markers, urine or serum might replace fecal samples in the near future. On the other hand, prognostic or predictive markers for treatment sensitivity may be identified from the molecular profiles of primary cancer tissues. Selection of patients who are sensitive to chemotherapy will reduce the number of patients who undergo harmful chemotherapy with no effectiveness. The optimal tumor markers would be generalized, easy to assess, and accurate, and such markers are eagerly anticipated to enable personalized tailored therapy for CRC patients. (Cancer Sci 2009; 100: 195–199)
Formosanin C‐induced apoptosis requires activation of caspase‐2 and change of mitochondrial membrane potential
Authors: Lee Jenq‐Chang , Su Chun‐Li , Chen Lin‐Lin , Won Shen‐Jeu
Published: December 2008

Formosanin C is a pure compound isolated from Paris formosana Hayata (Liliaceae). The antitumor efficacy of formosanin C has been observed in cultured cells and animal systems. However, the molecular mechanisms of formosanin C remain unknown. The results of the present study indicate that formosanin C induced apoptosis of HT‐29 cells characterized by exposure of phosphatidylserine, accumulation of cells at the sub‐G1 phase, fragmentation of DNA, and change of nuclear morphology in a time‐ and dose‐related manner. The apoptotic signaling cascades may proceed via proteolytic activation of caspase‐2, change of mitochondrial membrane potential (Δψm), release of cytochrome c and second mitochondria‐derived activator of caspase/direct IAP binding protein with low pI (Smac/DIABLO), activation of caspase‐9 and ‐3, and cleavage of poly(ADP‐ribose) polymerase (PARP). Increase in apoptosis‐inducing factor and endonuclease G expressions in nuclei, and increase in Bax and Bak expressions and decrease in Bcl‐XL expression on mitochondria were also observed in formosanin C‐treated HT‐29 cells. Attenuation of formosanin C‐induced change of Δψm by caspase‐2 inhibitor (Z‐VDVAC) implies that caspase‐2 acts upstream of the mitochondria. Blockage of formosanin C‐induced apoptotic process by using either permeability transition pore inhibitor (cyclosporine A) or caspase‐9 inhibitor (Z‐LEHD) demonstrates the necessity of mitochondria and caspase‐9 in formosanin C‐induced apoptosis of HT‐29 cells. Taken together, the apoptotic mechanism of formosanin C in human colorectal cancer HT‐29 cells involves activation of caspase‐2 and the dysfunction of mitochondria. (Cancer Sci 2009; 100: 503–513)
Identification of C2orf18, termed ANT2BP (ANT2‐binding protein), as one of the key molecules involved in pancreatic carcinogenesis
Authors: Kashiwaya Kotoe , Hosokawa Masayo , Eguchi Hidetoshi , Ohigashi Hiroaki , Ishikawa Osamu , Shinomura Yasuhisa , Nakamura Yusuke , Nakagawa Hidewaki
Published: December 2008

Pancreatic ductal adenocarcinoma (PDAC) shows one of the worst mortality rates among the common malignancies, and the great majority of PDAC patients are diagnosed at an advanced stage where no effective therapy is presently available. Hence, identification of novel molecular targets and development of molecular therapy for PDAC are urgently required. Through our genome‐wide gene expression profiles of microdissected PDAC cells, we here identified a novel gene C2orf18 as a molecular target for PDAC treatment. Transcriptional and immunohistochemical analysis validated its overexpression in PDAC cells and limited expression in normal adult organs. Knockdown of C2orf18 by small‐interfering RNA in PDAC cell lines resulted in induction of apoptosis and suppression of cancer cell growth, suggesting its essential role in maintaining viability of PDAC cells. We showed that C2orf18 was localized in the mitochondria and it could interact with adenine nucleotide translocase 2 (ANT2), which is involved in maintenance of the mitochondrial membrane potential and energy homeostasis, and was indicated some roles in apoptosis. These findings implicated that C2orf18, termed ANT2‐binding protein (ANT2BP), might serve as a candidate molecular target for pancreatic cancer therapy. (Cancer Sci 2009; 100: 457–464)
Review article: ‘true’ re‐infection of Helicobacter pylori after successful eradication – worldwide annual rates, risk factors and clinical implications
Authors: ZHANG Y.‐Y. , XIA H. H.‐X. , ZHUANG Z.‐H. , ZHONG J.
Published: December 2008

Background  The incidence of ‘true’ re‐infection with Helicobacter pylori after successful eradication remains uncertain.

Aim  To determine the worldwide rates, risk factors and clinical implications of ‘true’ re‐infection of Helicobacter pylori. ‘True’ re‐infection of H. pylori is defined as the situation where tests for H. pylori infection, which were negative for 12 months after eradication, become positive again at a later stage.

Results  Thirty six studies were identified through a literature search to be able to produce annual rates of ‘true’ re‐infection, and data from 33 original articles were considered reliable and adequate in the further review. Generally, the reported rates varied from 0% to 23.4% in adults and from 1.9% to 9.6% in children. Most studies from developed countries reported rates of less than 1%, whereas relatively higher rates were reported in most of the developing countries. Small sample sizes included in the studies appeared to be associated with increased re‐infection rates. Interfamilial transmission is the major cause of re‐infection, although iatrogenic re‐infection through contaminated endoscopic equipment has been reported.

Conclusion  Helicobacter pylori re‐infection is not a concern in a clinical setting, especially in the developed world; however, caution must be exercised in most developing countries.
The epidemiology of haemochromatosis: a population‐based study
Authors: CROOKS C. J. , WEST J. , SOLAYMANI‐DODARAN M. , CARD T. R.
Published: December 2008

Background  The discovery of the HFE genotype has revolutionized the diagnosis of haemochromatosis, changing the associated mortality and morbidity.

Aim  To investigate the clinical significance of a diagnosis of haemochromatosis.

Methods  In a cohort study, we identified 501 people with haemochromatosis and 4950 age‐ and gender‐matched controls from the UK General Practice Research Database between 1987 and 2002.

Results  The incidence of a diagnosis of haemochromatosis increased approximately 2‐fold over the study period and was associated with a 2.2‐fold increase in mortality [hazard ratio, 95% confidence interval (95% CI), 1.6–3.0]. There was no increase in extra hepatic malignancy, but an absolute risk excess of liver cancer of 0.89% per year. Diabetes, impotence, osteoarthritis and crystal arthritis were associated with haemochromatosis with odds ratios of 5.4 (95% CI, 4.1–7.0), 2.7(95% CI, 1.8–4.0), 1.9(95% CI, 1.5–2.4) and 2.1(95% CI, 1.4–3.1) respectively.

Conclusion  Increasing numbers of people are being diagnosed with haemochromatosis, and the mortality associated with this disease remains high. However, people are living with considerably lower levels of morbidity than previously reported. This encouragingly suggests earlier diagnoses are being made, prior to the development of complications.
Efficacy and complications of adalimumab treatment for medically‐refractory Crohn’s disease: analysis of nationwide experience in Scotland (2004–2008)
Authors: HO G. T. , MOWAT A. , POTTS L. , CAHILL A. , MOWAT C. , LEES C. W. , HARE N. C. , WILSON J. A. , BOULTON‐JONES R. , PRIEST M. , WATTS D. A. , SHAND A. G. , ARNOTT I. D. , RUSSELL R. K. , WILSON D. C. , MORRIS A. J. , SATSANGI J.
Published: December 2008

Background  Adalimumab is a second generation humanized anti‐tumour necrosis factor (TNF) monoclonal antibody with established efficacy in Crohn’s disease (CD).

Aims  To evaluate the efficacy and safety of adalimumab on a nationwide clinical setting.

Methods  We used the Scottish Society of Gastroenterology network to identify and follow up the clinical outcomes of patients with CD treated with adalimumab over a 4‐year period (2004–2008).

Results  A total of 98 patients received adalimumab ‐ 100.5 patient follow‐up years were recorded (64.3% females; median age at diagnosis of 20.7 years; 88.8% treated with 80/40 mg induction regimen. Eighty eight (89.8%) had previous infliximab with 29 (32.9%) primary nonresponders; 32 (32.6%) were corticosteroid‐dependent; 47 (47.9%) were intolerant/resistant to most immunosuppressive therapies (two or more). In all, 60% of patients were in clinical remission at 1‐year follow‐up, with 30% and 55% requiring dose escalation to weekly therapy at 1‐and 2‐year follow‐up respectively. Overall, 29 (29.6%) patients developed complications with eight nonfatal serious (8.2%) adverse events and 2 (2.0%) case fatalities (sepsis following perforation and disseminated colorectal cancer, respectively).

Conclusions  Adalimumab is efficacious in severe and refractory CD in the clinical setting, although there remain significant therapy‐ and disease‐related risks of serious complications.
B type natriuretic peptide – a diagnostic breakthrough in peri‐operative cardiac risk assessment?
Authors: Rodseth R. N.
Published: December 2008

The B‐type natriuretic peptides; B‐type natriuretic peptide and N‐terminal pro‐B‐type natriuretic peptide, are increasing being used as biomarkers for the diagnosis, management and prognostication of cardiac failure, but their application in the peri‐operative period is unclear. This review examines the current understanding of the role of B‐type natriuretic peptides in both the operative and non‐operative settings. Normal values, diagnostic thresholds, monitoring targets and significant prognostic levels are identified. Using this as a background, the role of B‐type natriuretic peptides in the prediction of peri‐operative mortality and morbidity is examined and potential confounders, such as renal failure and body mass index, which may impact significantly on the utility of the biomarkers, are discussed. Clinical recommendations with regard to its use are made and a research agenda is proposed for future peri‐operative studies.
Age‐associated difference in gene expression of paediatric acute myelomonocytic lineage leukaemia (FAB M4 and M5 subtypes) and its correlation with prognosis
Authors: Jo Aoi , Tsukimoto Ichiro , Ishii Eiichi , Asou Norio , Mitani Sachiyo , Shimada Akira , Igarashi Takashi , Hayashi Yasuhide , Ichikawa Hitoshi
Published: December 2008

Acute myeloid leukaemia, French‐American‐British M4 and M5 subtypes (AML‐M4/M5) is frequently associated with MLL gene rearrangement and its incidence is relatively high among infants. Clinically, paediatric AML‐M4/M5 has been considered as an intermediate or undefined prognostic group. In this study, we analysed gene expression of 40 paediatric AML‐M4/M5 patients excluding inv(16) and t(8;21) patients, and found striking differences among the patients in an age‐associated manner. In particular, most of the infants displayed very distinct gene expression. On the basis of this difference, we divided paediatric patients into three subgroups (A, B and C) with the average age of 0·3, 3·1 and 6·6 years old respectively. All subgroups included patients with MLL gene rearrangement as well as normal and other karyotypes. Surprisingly, gene expression signatures of MLL gene rearrangement differed substantially among these subgroups. In addition, subgroup C presented extremely poor outcome (3‐year event‐free survival 28%) whilst eight patients with MLL gene rearrangement in subgroup C had all relapsed within 18 months. These results suggest that age is an important factor contributing to the biology of AML‐M4/M5 and the sub‐grouping procedures developed in this study could be a powerful tool to identify unfavourable risk patients within paediatric AML‐M4/M5.
Effects of recombinant human LH and hCG on serum and urine LH and androgens in men
Authors: Handelsman David J. , Goebel Catrin , Idan Amanda , Jimenez Mark , Trout Graham , Kazlauskas Rymantas
Published: December 2008

Context The administration of gonadotrophins is prohibited in sport but the effect in men of recently available recombinant hCG and LH on serum and urine concentrations of gonadotrophins and androgens has not been systematically evaluated in the antidoping context.

Objective To determine the time‐course of recombinant LH (rhLH) and hCG (rhCG) on blood and urine hormone profiles in men to develop effective tests to detect rhLH and rhCG doping.

Design Two randomized controlled studies with a 2 × 2 factorial design.

Setting Academic research centre.

Participants Healthy male volunteers aged 18–45 years.

Interventions In the rhLH study, men were randomized into (i) either of two single doses of rhLH (75 IU or 225 IU), and (ii) suppression of endogenous LH and testosterone by nandrolone or no suppression. In the rhCG study, men were randomized into (i) either of two single doses of rhCG (250 or 750 µg), and (ii) suppression of endogenous LH and testosterone by nandrolone decanoate (ND) or no suppression. ND suppression comprised a single dose of 200 mg ND 3 days prior to, and in the rhCG study an additional dose 1 day after gonadotrophin injection.

Main outcome measures Serum and urine hCG, LH, T, T : LH ratio, urine epitestosterone (E) and urine T : E ratio.

Results Neither rhLH dose produced a significant increase in serum or urine LH or T or in the T : E or T : LH ratios regardless of ND‐induced suppression of endogenous LH and T. Nor did an even higher dose (750 IU) in three healthy men with unsuppressed gonadal axis. These findings were confirmed with two different commercial LH immunoassays together with adjustment for any influence of urine sediment and dilution. Both rhCG doses produced a steep, dose‐proportional increase in serum and urine hCG with increases in serum and urine T and suppression of serum and urine LH, regardless of hCG dose. Serum but not urine T was lowered by ND suppression. The T : LH ratio showed a progressive increase unrelated to rhCG dose or ND suppression, whereas both rhCG and ND suppression minimally increased T : E ratio.

Conclusions Both rhCG doses produce a striking increase in serum hCG and T with suppression of serum LH but, at single doses up to 750 IU, rhLH has no influence on serum or urine LH or T. Effective rhLH doping, which relies on a sustained increases in endogenous T, would require much higher and more frequent daily rhLH doses. Use of LH immunoassays optimized for serum to detect rhLH doping by urine LH measurement requires more standardization and validation and, at present, is unreliable. The T : LH ratio is, however, a useful screening test for hCG doping although its utility requires further evaluation.
The wideband [0.001 Hz–100 kHz] interferometry project in Central Italy
Authors: Palangio P. , Masci F. , Di Lorenzo C. , Di Persio M.
Published: December 2008

We are reporting some results and future planning of the Magnetic and Electric fields Monitoring Project. The principal purpose of the project is to create a network of observatories for monitoring the electromagnetic signals in the 0.001 Hz–100 kHz frequency bands in Central Italy. These bands include both natural and artificial signals. The technological objectives of the project are the development of new instrumentation and the know‐how transfer to the industry. These instruments were tested in the Geomagnetic Observatory of L'Aquila, the first station of the network. Here we show some examples of the developed electric and magnetic sensors. These instruments are designed for the automatic long‐term recording of the electromagnetic fields in a wide band of frequency. The preliminary results of the first operating station of the network are shown taking into account, in the signal elaboration, the single station approach. Here we are reporting some examples concerning the calculation of the ground electric resistivity profile, the evaluation of the magnetic induction vectors and the study of the magnetic sources by the eigenvectors calculation. When all the stations of the network will be in operation, the use of an innovative technique, the wideband interferometry will be proposed. Combining the simultaneous observations of the electromagnetic field measured in each station, we will be able to obtain detailed information about the investigated electromagnetic sources.
Anisotropic P‐wave attenuation measured from a multi‐azimuth surface seismic reflection survey
Authors: Clark Roger A. , Benson Philip M. , Carter Andrew J. , Moreno Carlos A. Guerrero
Published: December 2008

A system of aligned vertical fractures produces azimuthal variations in stacking velocity and amplitude variation with offset, characteristics often reported in seismic reflection data for hydrocarbon exploration. Studies of associated attenuation anisotropy have been mostly theoretical, laboratory or vertical seismic profiling based. We used an 11 common‐midpoint‐long portion of each of four marine surface‐seismic reflection profiles, intersecting each other at 45° within circa 100 m of a common location, to measure the azimuthal variation of effective attenuation, Q−1eff and stacking velocity, in a shallow interval, about 100 m thick, in which consistently orientated vertical fracturing was expected due to an underlying salt diapirism. We found qualitative and quantitative consistency between the azimuthal variation in the attenuation and stacking velocity, and published amplitude variation with offset results. The 135° azimuth line showed the least apparent attenuation (1000 Q−1eff= 16 ± 7) and the fastest stacking velocity, hence we infer it to be closest to the fracture trend: the orthogonal 45° line showed the most apparent attenuation (1000Q−1eff= 52 ± 15) and slowest stacking velocity. The variation of Q−1eff with azimuth φ is well fitted by 1000Q−1eff= 34 − 18cos[2(φ+40°)] giving a fracture direction of 140 ± 23° (±1SD, derived from ‘bootstrapping’ fits to all 114 combinations of individual common‐midpoint/azimuth measurements), compared to 134 ± 47° from published amplitude variation with offset data. The effects of short‐window spectral estimation and choices of spectral ratio bandwidth and offset ranges used in attenuation analysis, individually give uncertainties of up to ±13° in fracture direction. This magnitude of azimuthal variation can be produced by credible crack geometries (e.g., dry cracks, radius 6.5 m, aspect ratio 3 × 10−5, crack density 0.2) but we do not claim these to be the actual properties of the interval studied, because of the lack of well control (and its consequences for the choice of theoretical model and host rock physical properties) and the small number of azimuths available here.
The use of reference models from a priori data to guide 2D inversion of electrical resistivity tomography data
Authors: Catt Lucy M. L. , West L. Jared , Clark Roger A.
Published: December 2008

Clay‐rich till plains cover much of the UK. Such sites are attractive locations for landfills, since clay aquitards lower the risk of landfill leachate entering groundwater. However, such tills often contain sand and gravel bodies that can act as leachate flow routes. Such bodies may not be detected by conventional site investigation techniques such as drilling boreholes and trial pitting. A method of guided inversion, where a priori data are used to construct structural reference models for use in inverting electrical resistivity tomography data, was proposed as a tool to improve the detection of sand and gravel bodies within clay‐rich till sequences.

Following a successful 2D guided inversion synthetic modelling study, a field study was undertaken. Wenner 2D electrical resistivity tomography lines, resistivity cone penetrometry bores and electromagnetic induction ground resistivity data were collected over a site on the East Yorkshire coast, England, where sand and gravel lenses were known to exist from cliff exposures. A number of equally valid geoelectrical models were constructed using the electromagnetic and resistivity cone data. These were used as structural reference models in the inversion of the resistivity tomography data. Blind inversion using an homogenous reference model was also carried out for comparison.

It was shown for the first time that the best solution model produced by 2D inversion of one data set with a range of structural reference models could be determined by using the l2 model misfit between the solution models and associated reference models (reference misfit) as a proxy for the l2 misfit between the solution models and the synthetic model or ‘best‐guess’ geoelectrical model (true misfit). The 2D methodology developed here is applicable in clay‐rich till plains containing sand and gravel bodies throughout the UK.